FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Lopes, CMB Rohacs, T Czirjak, G Balla, T Enyedi, P Logothetis, DE AF Lopes, CMB Rohacs, T Czirjak, G Balla, T Enyedi, P Logothetis, DE TI PIP2 hydrolysis underlies agonist-induced inhibition and regulates voltage gating of two-pore domain K+ channels SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID POTASSIUM CHANNELS; PHOSPHOLIPASE-C; GLOMERULOSA CELLS; ATP CHANNELS; BETA-GAMMA; ACTIVATION; TASK-1; RECEPTOR; PTDINS(4,5)P-2; MODULATION AB Two-pore (2-P) domain potassium channels are implicated in the control of the resting membrane potential, hormonal secretion, and the amplitude, frequency and duration of the action potential. These channels are strongly regulated by hormones and neurotransmitters. Little is known, however, about the mechanism underlying their regulation. Here we show that phosphatidylinositol 4,5-bisphosphate (PIP2) gating underlies several aspects of 2-P channel regulation. Our results demonstrate that all four 2-P channels tested, TASK1, TASK3, TREK1 and TRAAK are activated by PIP2. We show that mechanical stimulation may promote PIP2 activation of TRAAK channels. For TREK1, TASK1 and TASK3 channels, PIP2 hydrolysis underlies inhibition by several agonists. The kinetics of inhibition by the PIP2 scavenger polylysine, and the inhibition by the phosphatidylinositol 4-kinase inhibitor wortmannin correlated with the level of agonist-induced inhibition. This finding suggests that the strength of channel PIP2 interactions determines the extent of PLC-induced inhibition. Finally, we show that PIP2 hydrolysis modulates voltage dependence of TREK1 channels and the unrelated voltage-dependent KCNQ1 channels. Our results suggest that PIP2 is a common gating molecule for K+ channel families despite their distinct structures and physiological properties. C1 CUNY Mt Sinai Sch Med, Dept Physiol & Biophys, New York, NY 10029 USA. Semmelweis Univ, Dept Physiol, H-1444 Budapest, Hungary. NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Logothetis, DE (reprint author), CUNY Mt Sinai Sch Med, Dept Physiol & Biophys, Box 1218, New York, NY 10029 USA. EM enyedi@puskin.sote.hu; diomedes.logothetis@mssm.edu OI Czirjak, Gabor/0000-0002-5485-2327; Balla, Tamas/0000-0002-9077-3335 FU NHLBI NIH HHS [HL59949, R01 HL059949] NR 43 TC 108 Z9 110 U1 0 U2 6 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD APR 1 PY 2005 VL 564 IS 1 BP 117 EP 129 DI 10.1113/jphysiol.2004.081935 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 917TZ UT WOS:000228493400010 PM 15677683 ER PT J AU Sabin, JA Zatzick, DF Rivara, FP AF Sabin, JA Zatzick, DF Rivara, FP TI A role for school health personnel in supporting children and families following childhood injury SO JOURNAL OF SCHOOL HEALTH LA English DT Editorial Material ID POSTTRAUMATIC-STRESS-DISORDER; TRAUMATIC BRAIN INJURY; PHYSICAL INJURY; RISK-FACTORS; PREVENTION; PREDICTORS; ACCIDENTS; PARENTS; HEAD C1 Univ Washington, Sch Social Work, NIMH, Seattle, WA 98105 USA. Univ Washington, Dept Psychiat & Behav Sci, Seattle, WA 98104 USA. Univ Washington, Harborview Injury Prevent & Res Ctr, Dept Pediat, Seattle, WA 98104 USA. RP Sabin, JA (reprint author), Univ Washington, Sch Social Work, NIMH, 4101 15th Ave NE, Seattle, WA 98105 USA. EM sabinja@u.washington.edu; dzatzick@u.washington.edu; fpr@u.washington.edu FU NIMH NIH HHS [T32MH20010] NR 29 TC 1 Z9 1 U1 0 U2 1 PU AMER SCHOOL HEALTH ASSOC PI KENT PA PO BOX 708, KENT, OH 44240 USA SN 0022-4391 J9 J SCHOOL HEALTH JI J. Sch. Health PD APR PY 2005 VL 75 IS 4 BP 141 EP 144 PG 4 WC Education & Educational Research; Education, Scientific Disciplines; Health Care Sciences & Services; Public, Environmental & Occupational Health SC Education & Educational Research; Health Care Sciences & Services; Public, Environmental & Occupational Health GA 925DE UT WOS:000229030900005 PM 15988840 ER PT J AU Montoya, ID Schroeder, JR Preston, KL Covi, L Umbricht, A Contoreggi, C Fudala, PJ Johnson, RE Gorelick, DA AF Montoya, ID Schroeder, JR Preston, KL Covi, L Umbricht, A Contoreggi, C Fudala, PJ Johnson, RE Gorelick, DA TI Influence of psychotherapy attendance on buprenorphine treatment outcome SO JOURNAL OF SUBSTANCE ABUSE TREATMENT LA English DT Article; Proceedings Paper CT 65th Annual Meeting of the College-on-Problems-of-Drug-Dependence CY JUN 14-19, 2003 CL Bal Harbor, FL SP Coll Problems Drug Dependence DE buprenorphine; cocaine; heroin; dual dependence; psychotherapy ID METHADONE-MAINTENANCE TREATMENT; COLLABORATIVE COCAINE TREATMENT; COGNITIVE-BEHAVIORAL THERAPY; VOUCHER-BASED REINFORCEMENT; SUBSTANCE-ABUSE TREATMENT; CONTINGENCY MANAGEMENT; RANDOMIZED-TRIAL; FOLLOW-UP; DEPENDENCE; HEROIN AB We evaluated the influence of psychotherapy attendance on treatment outcome in 90 dually (cocaine and heroin) dependent outpatients who completed 70 days of a controlled clinical trial of sublingual buprenorphine (16 mg, 8 mg, or 2 mg daily, or 16 mg every other day) plus weekly individual standardized interpersonal cognitive psychotherapy. Treatment outcome was evaluated by quantitative urine benzoylecgonine (BZE) and morphine levels (log-transformed), performed three times per week. Repeated-measures linear regression was used to assess the effects of psychotherapy attendance (percent of visits kept), medication group, and study week on urine drug metabolite levels. Mean psychotherapy attendance was 71% of scheduled visits. Higher psychotherapy attendance was associated with lower urine BZE levels, and this association grew more pronounced as the study progressed (p = 0.04). The inverse relationship between psychotherapy attendance and urine morphine levels varied by medication group, being most pronounced for subjects receiving 16 mg every other day (p = 0.02). These results suggest that psychotherapy can improve the outcome of buprenorphine maintenance treatment for patients with dual (cocaine and opioid) dependence. Published by Elsevier Inc. C1 NIDA, Div Pharmacotherapie & Med Consequences Drug Abus, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDA, Clin Pharmacol & Therapeut Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIDA, Brain Imaging Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Dept Vet Affairs Med Ctr, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD 21224 USA. Reckitt Benckiser Pharmaceut Inc, Baltimore, MD 21224 USA. RP Montoya, ID (reprint author), NIDA, Div Pharmacotherapie & Med Consequences Drug Abus, NIH, Dept Hlth & Human Serv, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM imontoya@mail.nih.gov RI Preston, Kenzie/J-5830-2013 OI Preston, Kenzie/0000-0003-0603-2479 FU Intramural NIH HHS [Z99 DA999999] NR 49 TC 20 Z9 21 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0740-5472 J9 J SUBST ABUSE TREAT JI J. Subst. Abus. Treat. PD APR PY 2005 VL 28 IS 3 BP 247 EP 254 DI 10.1016/j.jsat.2005.01.004 PG 8 WC Psychology, Clinical; Substance Abuse SC Psychology; Substance Abuse GA 925ZT UT WOS:000229093100005 PM 15857725 ER PT J AU Chan, JL Ehrlich, A Lawrence, RC Moshell, AN Turner, ML Kimball, AB AF Chan, JL Ehrlich, A Lawrence, RC Moshell, AN Turner, ML Kimball, AB TI Assessing the role of race in quantitative measures of skin pigmentation and clinical assessments of photosensitivity SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID ETHNIC SKIN; ERYTHEMA; COLOR; MELANIN; REFLECTANCE; DERMATOLOGY; MEDICINE; GENOMICS; DEEP AB Background: Given the increasing demographic diversity in the United States, clarifying relationships between race, color, ethnicity, and disease processes is critical. Objectives: We sought to examine the correlation between objective measures of skin pigmentation, racial identification, and physician-diagnosed and self-reported skin phototypes. Methods: A total of 558 participants (76 nonwhite) were evaluated. A subset underwent spectrometric readings and digital photography of the upper aspect of the inner arm. Self-identified race was compared with 7 measures of pigmentation. Results: Race correlates best with physician-diagnosed skin phototype (r = 0.55, P <.01), whereas self-reported skin phototype, spectrometry, and colorimetry correlate poorly with race (r = 0.28, < 0.40, and r > -0.31, respectively, P <.01). Associations between race and subjective measures strengthen among patients with darker skin. Conclusion: Objective measures of pigmentation fail to correlate well with race, whereas race correlates moderately with physician-diagnosed skin phototype. including objective methods of analyzing skin color may reduce subjective influences of race in assessing photosensitivity and potential risk for skin cancer. C1 Stanford Univ, Med Ctr, Dept Dermatol, Stanford, CA 94305 USA. George Washington Univ, Dept Dermatol, Washington, DC 20052 USA. NIAMSD, Program Epidemiol, NIH, Bethesda, MD USA. NIAMSD, Skin Dis Branch, NIH, Bethesda, MD USA. NCI, Dermatol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Kimball, AB (reprint author), Massachusetts Gen Hosp, Dermatol Clin Studies Unit, 221 Longwood Ave,1st Floor, Boston, MA 02115 USA. EM harvardskinstudies@partners.org OI Ehrlich, Alison/0000-0002-4062-5289 NR 32 TC 18 Z9 18 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2005 VL 52 IS 4 BP 609 EP 615 DI 10.1016/j.jaad.2004.03..051 PG 7 WC Dermatology SC Dermatology GA 912WN UT WOS:000228110700007 PM 15793510 ER PT J AU Elster, EA Hale, DA Mannon, RB Cendales, LC Meiner, D Swanson, SJ Kirk, AD AF Elster, EA Hale, DA Mannon, RB Cendales, LC Meiner, D Swanson, SJ Kirk, AD TI Surgical transplant physical examination: Correlation of renal resistance index and biopsy-proven chronic allograft nephropathy SO JOURNAL OF THE AMERICAN COLLEGE OF SURGEONS LA English DT Article ID DYSFUNCTION; RECIPIENTS; SURVIVAL AB BACKGROUND: Chronic allograft nephropathy (CAN) remains the leading cause of late renal allograft loss that is minimally responsive to therapy once graft dysfunction is clinically evident. A screening test capable of identifying individuals at high risk for CAN would be a valuable adjunct to patient care, but to be cost effective, should be administered during routine evaluations by transplantation clinicians. STUDY DESIGN: We have compared the resistive index (RI) as measured by Doppler ultrasonography with subsequent biopsy findings on 91 renal allograft recipients who had a subsequent protocol-directed biopsy at least 3 months after renal transplant. All ultrasonography was performed by the transplantation surgical staff without involving the radiology department or a separate appointment time. RESULTS: Twenty-one patients had RI >= 80 (average 621 days posttransplantation). Among these individuals, the subsequent incidence of CAN was 38%. Length of time between initial assessment of increased RI and biopsy-proved CAN averaged 233 days. The remaining 70 patients with RI < 80 had an incidence of CAN of 11.4% (p = 0.018). There were minimal complications from these biopsies. Sensitivity and specificity of an elevated RI in predicting CAN were 50% and 83%, respectively. The negative predicted value of an elevated RI in determination of CAN was 89%. CONCLUSIONS: These results suggest that elevated RI is an early predictor of histologically relevant CAN, possibly a result of burgeoning vasculopathy. The technical expertise required to make this appraisal is well within the capabilities of transplantation surgeons and trainees. Early evidence of CAN may allow for a targeted change in therapy before clinically significant injury. Ultrasonography should become a routine part of a transplantation clinic evaluation. (c) 2005 by the American College of Surgeons. C1 NIDDKD, Transplantat Branch, Bethesda, MD 20892 USA. NCI, Lab Pathol, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. USN, Med Res Ctr, Radiat & Combat Injury Dept, Bethesda, MD USA. Natl Inst Diabet Digest & Kidney Dis, Transplantat Branch, Bethesda, MD 20892 USA. RP Elster, EA (reprint author), NIDDKD, Transplantat Branch, 10 Ctr Dr,Bldg 10,Rm 5-5750, Bethesda, MD 20892 USA. RI Kirk, Allan/B-6905-2012; OI Kleiner, David/0000-0003-3442-4453 NR 10 TC 9 Z9 10 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1072-7515 J9 J AM COLL SURGEONS JI J. Am. Coll. Surg. PD APR PY 2005 VL 200 IS 4 BP 552 EP 556 DI 10.1016/j.jamcollsurg.2004.12.009 PG 5 WC Surgery SC Surgery GA 912NH UT WOS:000228085200008 PM 15804469 ER PT J AU Shumway-Cook, A Patla, A Stewart, AL Ferrucci, L Ciol, MA Guralnik, JM AF Shumway-Cook, A Patla, A Stewart, AL Ferrucci, L Ciol, MA Guralnik, JM TI Assessing environmentally determined mobility disability: Self-report versus observed community mobility SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE mobility; disability; aging; environment; self-report ID PHYSICAL PERFORMANCE BATTERY; LOWER-EXTREMITY FUNCTION; MORTALITY; DEMANDS AB OBJECTIVES: To examine the test-retest reliability and concurrent validity of a new self-report measure of mobility function by comparing it with observed mobility, self-reported activity of daily living (ADL) function, and performance-based measures of gait and balance. DESIGN: Cross-sectional study involving two groups of older adults. SETTING: Community sites in Seattle, Washington, and Waterloo, Ontario, Canada. PARTICIPANTS: Fifty-four adults aged 70 and older, recruited. MEASUREMENTS: Subjects completed the Environmental Analysis of Mobility Questionnaire (EAMQ), reporting frequency of encounter and avoidance of 24 features of the physical environment, grouped into eight dimensions, on two occasions 1 week apart. Subjects were observed and videotaped during six trips into the community; frequency of encounters with environmental features within the eight dimensions was recorded. EAMQ encounter and avoidance scores were compared with observed environmental encounters, with disability in ADLs and instrumental ADLs (IADLs), and lower extremity functional measures including the Short Physical Performance Battery (SPPB) and the Berg Balance Test. RESULTS: EAMQ test-retest reliability was high for all eight dimensions (intraclass correlation coefficient range=0.81-1.0) and for summary encounter (0.98) and avoidance (0.96) scores. Observed mobility was significantly correlated (Spearman correlation = r) with EAMQ summary encounter (r=0.66) and avoidance (r=-0.58) scores. Moderate correlations were present between the EAMQ (encounter or avoidance) and observed mobility in the distance, temporal, terrain, posture, load, and density dimensions but not in the attention and ambient dimensions. EAMQ encounter/avoidance was significantly associated with ADL and IADL ability and performance on the SPPB and Berg Balance Test. CONCLUSION: Self-reported frequency of encounter and avoidance of specific environmental features appears to be a valid method for determining environmentally specific mobility disability but needs to be confirmed in a larger sample. C1 Univ Washington, Dept Rehabil Med, Seattle, WA 98195 USA. Univ Waterloo, Dept Kinesiol, Waterloo, ON N2L 3G1, Canada. Univ Calif San Francisco, Inst Hlth & Aging, San Francisco, CA 94143 USA. NIA, Baltimore Longitudinal Study Aging, Baltimore, MD 21224 USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD USA. RP Shumway-Cook, A (reprint author), Univ Washington, Dept Rehabil Med, Box 356490, Seattle, WA 98195 USA. EM ashumway@u.washington.edu NR 15 TC 40 Z9 43 U1 0 U2 9 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 BP 700 EP 704 DI 10.1111/j.1532-5415.2005.53222.x PG 5 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 909ZM UT WOS:000227899200022 PM 15817020 ER PT J AU Atkinson, HH Rosano, C Simonsick, E Williamson, J Davis, C Leng, I Rapp, S Newman, A Harris, T Cesari, M Rubin, S Yaffe, K Satterfield, S Kritchevsky, S AF Atkinson, HH Rosano, C Simonsick, E Williamson, J Davis, C Leng, I Rapp, S Newman, A Harris, T Cesari, M Rubin, S Yaffe, K Satterfield, S Kritchevsky, S TI Relationship of cognitive function, gait speed decline, and comorbidities. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Pittsburgh, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Tennessee, Memphis, TN 38163 USA. RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S6 EP S6 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900016 ER PT J AU Bartali, B Frongillo, EA Bandinelli, S Lauretani, F Semba, RD Fried, LP Ferrucci, L AF Bartali, B Frongillo, EA Bandinelli, S Lauretani, F Semba, RD Fried, LP Ferrucci, L TI Deficient nutrient intake is an essential component of frailty in older persons. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Cornell Univ, Ithaca, NY USA. ASF, Geriatr Rehabil Unit, Florence, Italy. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, Clin Res Branch, Longitudinal Studies Sect, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S177 EP S177 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900513 ER PT J AU Boyd, CM Fried, LP Xue, Q Ricks, M Guralnik, JM Bandeen-Roche, K AF Boyd, CM Fried, LP Xue, Q Ricks, M Guralnik, JM Bandeen-Roche, K TI Functional decline and recovery among hospitalized, older disabled women. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Johns Hopkins Univ, Div Geriatr Med & Gerontol, Ctr Aging & Hlth, Baltimore, MD USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S11 EP S11 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900030 ER PT J AU Cesari, M Kritchevsky, SB Nicklas, BJ Penninx, BW Holvoet, P Cummings, S Koh-Banerjee, P Harris, TB Newman, AB Pahor, M AF Cesari, M Kritchevsky, SB Nicklas, BJ Penninx, BW Holvoet, P Cummings, S Koh-Banerjee, P Harris, TB Newman, AB Pahor, M TI Lipoprotein peroxidation and onset of mobility disability - Results from the health ABC study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Wake Forest Univ, Winston Salem, NC 27109 USA. Vrije Univ Amsterdam, NL-1081 HV Amsterdam, Netherlands. Catholic Univ Louvain, B-3000 Louvain, Belgium. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Tennessee, Ctr Hlth Sci, Memphis, TN 38163 USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S82 EP S82 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900232 ER PT J AU Fisher, D Williamson, J Cesari, M Atkinson, H Fried, L Guralnik, J Kritchevsky, S AF Fisher, D Williamson, J Cesari, M Atkinson, H Fried, L Guralnik, J Kritchevsky, S TI Cognitive function and disability in elderly patients with type 2 diabetes. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Wake Forest Univ, Winston Salem, NC 27109 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, Bethesda, MD 20892 USA. RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S57 EP S57 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900162 ER PT J AU Gonzalgo, SR Gonzalgo, ML Simonsick, EM Ko, CW Ostir, GV Markides, KS AF Gonzalgo, SR Gonzalgo, ML Simonsick, EM Ko, CW Ostir, GV Markides, KS TI Disability transitions by urinary incontinence in Mexican American women. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 JHU, Baltimore, MD USA. NIA, Baltimore, MD 21224 USA. UTMB, Galveston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S84 EP S84 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900238 ER PT J AU Kritchevsky, SB Guralnik, J Dunn, AL Newman, AB Pruitt, L Wallace, K Walkup, M Hsu, F Studenski, S Katula, J Gill, TM Pahor, M AF Kritchevsky, SB Guralnik, J Dunn, AL Newman, AB Pruitt, L Wallace, K Walkup, M Hsu, F Studenski, S Katula, J Gill, TM Pahor, M TI Recruiting high-risk older adults for disability prevention research: The lifestyle interventions and independence for elders (LIFE) study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Wake Forest Sch Med, Sticht Ctr Aging, Winston Salem, NC USA. NIA, Bethesda, MD 20892 USA. Cooper Inst, Dallas, TX USA. Univ Pittsburgh, Pittsburgh, PA USA. Stanford Univ, Palo Alto, CA 94304 USA. Wake Forest Univ, Sch Med, Publ Hlth Serv, Winston Salem, NC 27109 USA. Yale Univ, Sch Med, New Haven, CT USA. RI Katula, Jeffrey/K-5905-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S175 EP S176 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900508 ER PT J AU Landi, F Cesari, M Russo, A Zamboni, V Pahor, M Ferrucci, L Bernabei, R AF Landi, F Cesari, M Russo, A Zamboni, V Pahor, M Ferrucci, L Bernabei, R TI Co-morbidity and physical function results from the ilSIRENTE Study SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Univ Cattolica Sacro Cuore, Dept Gerontol & Geriatr, I-00168 Rome, Italy. Wake Forest Univ, Sch Med, Sticht Ctr Aging, Winston Salem, NC 27109 USA. NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD 21224 USA. RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S132 EP S132 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900377 ER PT J AU Leveille, SG Bean, JF McMullen, W Guralnik, JM AF Leveille, SG Bean, JF McMullen, W Guralnik, JM TI Exploring the pathway from musculoskeletal pain to mobility difficulty in older women. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Spaulding Rehabil Hosp, Boston, MA USA. Hebrew Senior Life, Boston, MA USA. NIA, Bethesda, MD 20892 USA. RI Bean, Jonathan/F-5798-2017 OI Bean, Jonathan/0000-0001-8385-8210 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S13 EP S13 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900035 ER PT J AU Ling, SM Zhan, M Metter, EJ Ferrucci, L AF Ling, SM Zhan, M Metter, EJ Ferrucci, L TI Changes in selected proteins associated with aging: Preliminary results of the Baltimore Longitudinal Study on Aging (BLSA). SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 NIA, Intramural Res Program, Clin Res Branch, Baltimore, MD USA. RRB, NIA, IRP, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S71 EP S71 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900201 ER PT J AU Masaki, K He, Q Petrovitch, H Ross, GW Korf, E Launer, L Davis, D Blanchette, P White, L AF Masaki, K He, Q Petrovitch, H Ross, GW Korf, E Launer, L Davis, D Blanchette, P White, L TI Low hippocampal volume is an insensitive predictor of neuropathological Alzheimer's disease: The Honolulu-Asia Aging Study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Univ Hawaii, Honolulu, HI 96822 USA. Pacific Hlth Res Inst, Honolulu, HI USA. NIA, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, NL-1081 HV Amsterdam, Netherlands. Univ Kentucky, Lexington, KY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S208 EP S209 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900600 ER PT J AU Mast, BT Miles, T Ayonayon, H Harris, T Penninx, B Rosano, C Satterfield, S Simonsick, E Yaffe, K AF Mast, BT Miles, T Ayonayon, H Harris, T Penninx, B Rosano, C Satterfield, S Simonsick, E Yaffe, K TI Vascular disease and risk for incident depression in the elderly: The health, aging and body composition study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Univ Louisville, Louisville, KY 40292 USA. Univ Tennessee, Memphis, TN 38163 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Vrije Univ Amsterdam, NL-1081 HV Amsterdam, Netherlands. NIA, Bethesda, MD 20892 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S4 EP S4 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900012 ER PT J AU Newman, A Simonsick, E Naydeck, B Kritchevsky, S Nevitt, M Pahor, M Satterfield, S Brach, J Studenski, S Harris, T AF Newman, A Simonsick, E Naydeck, B Kritchevsky, S Nevitt, M Pahor, M Satterfield, S Brach, J Studenski, S Harris, T TI Long distance corridor walk predicts mortality - The health, aging and body composition (Health ABC) study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Univ Pittsburgh, Pittsburgh, PA USA. NIA, Baltimore, MD 21224 USA. WFU, Winston Salem, NC USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Tennessee, Memphis, TN 38163 USA. RI Brach, Jennifer/A-6912-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S11 EP S12 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900031 ER PT J AU Strotmeyer, ES de Rekeneire, N Schwartz, AV Resnick, HE Shorr, R Vinik, AI Harris, TB Newman, AB AF Strotmeyer, ES de Rekeneire, N Schwartz, AV Resnick, HE Shorr, R Vinik, AI Harris, TB Newman, AB TI Are traditional risk factors for neuropathy related to poor nerve function in older adults? SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Univ Pittsburgh, Pittsburgh, PA USA. NIA, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. MedStar Res Inst, Hyattsville, MD USA. Univ Tennessee, Memphis, TN 38163 USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. RI Strotmeyer, Elsa/F-3015-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S34 EP S34 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900092 ER PT J AU Whicker, B Cesari, M Pahor, M Penninx, BW Bandinelli, S Woodman, RC Guralnik, JM Ferrucci, L AF Whicker, B Cesari, M Pahor, M Penninx, BW Bandinelli, S Woodman, RC Guralnik, JM Ferrucci, L TI Anemia and cognitive function in older persons - Results from the Invecchiare in Chianti (Aging in the Chianti area, InCHIANTI) study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Vrije Univ Amsterdam, Amsterdam, Netherlands. INRCA Florence, Dept Geriatr, Florence, Italy. Ortho Biotech Prod, Bridgewater, NJ USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Bethesda, MD 20892 USA. RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S159 EP S159 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900458 ER PT J AU White, H Merriam, GR Petrie, C Landschulz, W MacLean, D Fryburg, D Taylor, A Lyles, K Blackman, MR Wei, JY Hoffman, A Clipp, E Morey, M AF White, H Merriam, GR Petrie, C Landschulz, W MacLean, D Fryburg, D Taylor, A Lyles, K Blackman, MR Wei, JY Hoffman, A Clipp, E Morey, M TI Effects of an oral growth hormone secretagogue in pre-frail older adults: An exploratory study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Duke Univ, Durham, NC USA. Univ Washington, Tacoma, WA USA. Pfizer Inc, Groton, CT USA. NIH, Bethesda, MD 20892 USA. Univ Arkansas, Little Rock, AR 72204 USA. Palo Alto VA, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S174 EP S174 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900504 ER PT J AU Whitson, H Pieper, C Horner, R Sanders, L Lyles, KW AF Whitson, H Pieper, C Horner, R Sanders, L Lyles, KW TI Fracture risk after stroke in an American cohort. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Durham VA Med Ctr, Durham, NC USA. NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S191 EP S191 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900552 ER PT J AU Williamson, JD Miller, ME Bryan, N Lazaar, R Sullivan, M Launer, L AF Williamson, JD Miller, ME Bryan, N Lazaar, R Sullivan, M Launer, L TI The action to control cardiovascular risk in diabetes: Memory in diabetes (accord-mind) - Design and organization. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 11-15, 2005 CL Orlando, FL SP Amer Geriatr Soc C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NIA, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2005 VL 53 IS 4 SU S BP S158 EP S158 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 917HE UT WOS:000228450900455 ER PT J AU Ninichuk, V Gross, O Reichel, C Khandoga, A Pawar, RD Ciubar, R Segerer, S Belemezova, E Radomska, E Luckow, B de Lema, GP Murphy, PM Gao, JL Henger, A Kretzler, M Horuk, R Weber, M Krombach, F Schlondorff, D Anders, HJ AF Ninichuk, V Gross, O Reichel, C Khandoga, A Pawar, RD Ciubar, R Segerer, S Belemezova, E Radomska, E Luckow, B de Lema, GP Murphy, PM Gao, JL Henger, A Kretzler, M Horuk, R Weber, M Krombach, F Schlondorff, D Anders, HJ TI Delayed chemokine receptor 1 blockade prolongs survival in collagen 4A3-deficient mice with Alport disease SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID REDUCES RENAL FIBROSIS; MACROPHAGES; APOPTOSIS; CELLS; CCR1; GLOMERULONEPHRITIS; INFLAMMATION; RECRUITMENT; PROGRESSION; REDUNDANCY AB Human Alport disease is caused by a lack of the alpha 3-, 4-, or 5-chain of type IV collagen (COL4A). Affected humans and COL4A3-deficient mice develop glomerulosclerosis and progressive renal fibrosis in the presence of interstitial macrophages, but their contribution to disease progression is under debate. This question was addressed by treating COL4A3-deficient mice with BX471, an antagonist of chemokine receptor 1 (CCR1) that is known to block interstitial leukocyte recruitment. Treatment with BX471 from weeks 6 to 10 of life improved survival of COL4A3-deficient mice, associated with less interstitial macrophages, apoptotic tubular epithelial cells, tubular atrophy, interstitial fibrosis, and less globally sclerotic glomeruli. BX471 reduced total renal Cll5 mRNA expression by reducing the number of interstitial CCL5-positive cells in inflammatory cell infiltrates. Intravital microscopy of the cremaster muscle in male mice identified that BX471 or lack of CCR1 impaired leukocyte adhesion to activated vascular endothelium and transendothelial leukocyte migration, whereas leukocyte rolling and interstitial migration were not affected. Furthermore, in activated murine macrophages, BX471 completely blocked CCL3-induced CCL5 production. Thus, CCR1-mediated recruitment and local activation of macrophages contribute to disease progression in COL4A3-deficient mice. These data identify CCR1 as a potential therapeutic target for Alport disease or other progressive nephropathies associated with interstitial macrophage infiltrates. C1 Univ Munich, Med Poliklin, Nephrol Ctr, D-80336 Munich, Germany. Univ Munich, Inst Surg Res, D-80336 Munich, Germany. Univ Cologne, Fac Med, Dept Internal Med 1, Cologne Gen Hosp,Merheim Med Ctr, Cologne, Germany. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. Berlex Biosci, Dept Immunol, Richmond, CA USA. RP Anders, HJ (reprint author), Univ Munich, Med Poliklin, Nephrol Ctr, Pettenkoferstr 8A, D-80336 Munich, Germany. EM hjanders@med.uni-muenchen.de NR 26 TC 62 Z9 62 U1 0 U2 0 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2005 VL 16 IS 4 BP 977 EP 985 DI 10.1681/ASN.2004100871 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 910MO UT WOS:000227935800020 PM 15716328 ER PT J AU Matsusaka, T Xin, J Niwa, S Kobayashi, K Akatsuka, A Hashizume, H Wang, QC Pastan, I Fogo, AB Ichikawa, I AF Matsusaka, T Xin, J Niwa, S Kobayashi, K Akatsuka, A Hashizume, H Wang, QC Pastan, I Fogo, AB Ichikawa, I TI Genetic engineering of glomerular sclerosis in the mouse via control of onset and severity of podocyte-specific injury SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-of-Nephrology CY NOV 12-17, 2003 CL SAN DIEGO, CA SP Amer Soc Nephrol ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; CONGENITAL NEPHROTIC SYNDROME; TRANSGENIC MICE; PUROMYCIN AMINONUCLEOSIDE; RECOMBINANT IMMUNOTOXIN; CD2-ASSOCIATED PROTEIN; EXPERIMENTAL-MODEL; EPITHELIAL-CELL; ANIMAL TOXICITY; ANTI-TAC(FV)-PE38 AB This study aimed to generate a mouse model of acquired glomerular sclerosis. A model system that allows induction of podocyte injury in a manner in which onset and severity can be controlled was designed. A transgenic mouse strain (NEP25) that expresses human CD25 selectively in podocytes was first generated. Injection of anti-Tac (Fv)-PE38 (LMB2), an immunotoxin with specific binding to human CD25, induced progressive nonselective proteinuria, ascites, and edema in NEP25 mice. Podocytes showed foot process effacement, vacuolar degeneration, detachment and downregulation of synaptopodin, WT-1, nephrin, and podocalyxin. Mesangial cells showed matrix expansion, increased collagen, mesangiolysis, and, later, sclerosis. Parietal epithelial cells showed vacuolar degeneration and proliferation, whereas endothelial cells were swollen. The severity of the glomerular injury was LMB2 dose dependent. With 1.25 ng/g body wt or more, NEP25 mice developed progressive glomerular damage and died within 2 wk. With 0.625 ng/g body wt of LMB2, NEP25 mice survived > 4 wk and developed focal segmental glomerular sclerosis. Thus, the study has established a mouse model of acquired progressive glomerular sclerosis in which onset and severity can be preprogrammed by experimental maneuvers. C1 Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA. Tokai Univ, Sch Med, Inst Med Sci, Isehara, Kanagawa 25911, Japan. Tokai Univ, Sch Med, Dept Pediat, Isehara, Kanagawa 25911, Japan. Tokai Univ, Sch Med, Ctr Excellence, Isehara, Kanagawa 25911, Japan. Tokai Univ, Sch Med, Educat & Res Support Ctr, Isehara, Kanagawa 25911, Japan. Fukushima Med Univ, Sch Med, Inst Biomed Sci, Dept Mol Genet, Fukushima, Japan. Natl Def Med Coll, Dept Pediat, Tokorozawa, Saitama, Japan. NCI, Mol Biol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Matsusaka, T (reprint author), Vanderbilt Univ, Sch Med, Dept Pediat, 1161 21st Ave S,MCN C4204, Nashville, TN 37232 USA. EM taiji.matsusaka@vanderbilt.edu FU NIDDK NIH HHS [DK37868, DK447577] NR 37 TC 143 Z9 150 U1 0 U2 1 PU AMER SOC NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2005 VL 16 IS 4 BP 1013 EP 1023 DI 10.1681/ASN.2004080720 PG 11 WC Urology & Nephrology SC Urology & Nephrology GA 910MO UT WOS:000227935800024 PM 15758046 ER PT J AU Warner, DG Olney, CA Wood, FB Hansen, L Bowden, VM AF Warner, DG Olney, CA Wood, FB Hansen, L Bowden, VM TI High school peer tutors teach MedlinePlus: a model for Hispanic outreach SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article AB Objectives: The objective was to introduce the MedlinePlus Website to the predominantly Hispanic residents of the Lower Rio Grande Valley region of Texas by partnering with a health professions magnet high school (known as Med High). Methods: Community assessment was used in the planning stages and included pre-project focus groups with students and teachers. Outreach methods included peer tutor selection, train-the-trainer sessions, school and community outreach, and pre- and posttests of MedlinePlus training sessions. Evaluation methods included Web statistics; end-of-project interviews; focus groups with students, faculty, and librarians; and end-of-project surveys of students and faculty. Results: Four peer tutors reached more than 2,000 people during the project year. Students and faculty found MedlinePlus to be a useful resource. Faculty and librarians developed new or revised teaching methods incorporating MedlinePlus. The project enhanced the role of school librarians as agents of change at Med High. The project continues on a self-sustaining basis. Conclusions: Using peer tutors is an effective way to educate high school students about health information resources and, through the students, to reach families and community members. C1 Univ Texas, Hlth Sci Ctr, Ctr S Texas Program, Harlington, TX 78550 USA. Natl Lib Med, Off Hlth Informat Program dev, Bethesda, MD 20894 USA. S Texas High Sch Hlth Prof, Mercedes, TX 78570 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. RP Warner, DG (reprint author), Univ Texas, Hlth Sci Ctr, Ctr S Texas Program, 2102 Treasure Hills Blvd, Harlington, TX 78550 USA. EM warnerd1@uthscsa.edu; olney@triad.rr.com; fredwood@mail.nih.gov; lucy.hansen@stisd.net; bozvdenv@sbcglobal.net FU NLM NIH HHS [N0-1-LM-1-3515] NR 12 TC 12 Z9 12 U1 1 U2 5 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD APR PY 2005 VL 93 IS 2 BP 243 EP 252 PG 10 WC Information Science & Library Science SC Information Science & Library Science GA 919QA UT WOS:000228631400009 PM 15858628 ER PT J AU Duncan, DT Quarells, RC Jones, DJ AF Duncan, Dustin T. Quarells, Rakale Collins Jones, Dionne J. TI Approaching health equity SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Letter C1 [Duncan, Dustin T.] Morehouse Coll, Dept Psychol, Atlanta, GA 30314 USA. [Duncan, Dustin T.] Morehouse Coll, Publ Hlth Sci Inst, Atlanta, GA USA. [Duncan, Dustin T.; Quarells, Rakale Collins] Morehouse Sch Med, Dept Community Hlth & Prevent Med, Social Epidemiol Res Ctr, Atlanta, GA 30310 USA. [Jones, Dionne J.] NIDA, Serv Res Branch, Div Epidemiol Serv & Prevent Res, NIH, Bethesda, MD 20892 USA. [Jones, Dionne J.] Univ Maryland, Univ Coll, Sch Undergrad Studies, Dept Psychol, Adelphi, MD USA. RP Duncan, DT (reprint author), Morehouse Coll, Dept Psychol, Atlanta, GA 30314 USA. EM dduncan39@hotmail.com NR 15 TC 0 Z9 0 U1 1 U2 2 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD APR PY 2005 VL 97 IS 4 BP 584 EP 585 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA V50IY UT WOS:000203403200043 PM 15868781 ER PT J AU Deans, KJ Haley, M Natanson, C Eichacker, PQ Minneci, PC AF Deans, KJ Haley, M Natanson, C Eichacker, PQ Minneci, PC TI Novel therapies for sepsis: A review SO JOURNAL OF TRAUMA-INJURY INFECTION AND CRITICAL CARE LA English DT Review DE glucocorticoids; sepsis; anti-inflammatory agent; anticoagulant agent; antithrombotic agent; steroids ID TUMOR-NECROSIS-FACTOR; FACTOR PATHWAY INHIBITOR; RANDOMIZED CONTROLLED-TRIAL; ACTIVATED PROTEIN-C; SEPTIC SHOCK; ANTITHROMBIN-III; DOUBLE-BLIND; DOSE CORTICOSTEROIDS; CORTISOL RESPONSE; ORGAN DYSFUNCTION AB Background. Over the past 30 years, efforts have been made to identify therapeutic targets in the host response to infection. Methods. A review of the randomized controlled clinical sepsis trials and meta-analyses of glucocorticoids, mediator-specific anti-inflammatory agents, and anticoagulant agents was performed. Results. The effects of glucocorticoids in sepsis appear to be dose-dependent, with high doses decreasing survival and low doses improving survival. As a class, the mediator-specific anti-inflammatory agents have a small beneficial effect on survival; however, no single agent has demonstrated significant benefit. The treatment effects of these agents appear to be related to the patient's risk of death. As a class, the anticoagulant agents do not improve survival; however, the efficacy of these agents may have been confounded by concurrent heparin therapy. Activated protein C demonstrated a beneficial effect on survival that was dependent on severity of illness. Conclusion. Trials of agents directed at altering the host's response during sepsis have had variable results, and it appears that several different factors may alter the efficacy of these agents. C1 NIH, Crit Care Med Dept, Ctr Clin, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Dept Surg, Boston, MA 02114 USA. RP Minneci, PC (reprint author), NIH, Crit Care Med Dept, Ctr Clin, Bldg 10,Room 7D43,10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. EM pminneci@mail.cc.nih.gov NR 58 TC 84 Z9 88 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-6061 J9 J TRAUMA JI J. Trauma-Injury Infect. Crit. Care PD APR PY 2005 VL 58 IS 4 BP 867 EP 874 DI 10.1097/01.TA.0000158244.69179.94 PG 8 WC Critical Care Medicine; Surgery SC General & Internal Medicine; Surgery GA 919VS UT WOS:000228646300051 PM 15824673 ER PT J AU Goncalves, LF Espinoza, J Lee, W Nien, JK Hong, JS Forgas, JS Santolaya-Forgas, J Mazor, M Romero, R AF Goncalves, LF Espinoza, J Lee, W Nien, JK Hong, JS Forgas, JS Santolaya-Forgas, J Mazor, M Romero, R TI A new approach to fetal echocardiography - Digital casts of the fetal cardiac chambers and great vessels for detection of congenital heart disease SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE congenital heart disease; fetal echocardiography; 4-dimensional ultrasonography; spatiotemporal image correlation; 3-dimensional ultrasonography; 4D; 3D ID SPATIOTEMPORAL IMAGE CORRELATION; PRENATAL-DIAGNOSIS; B-FLOW; 4-DIMENSIONAL ULTRASONOGRAPHY; INVERSION MODE; ULTRASOUND; DEFECTS; TRANSPOSITION; PREGNANCIES; MANAGEMENT AB Objective. The purpose of this study was to describe a method of 4-dimensional (4D) reconstruction of the cardiac chambers and outflow tracts using a combination of spatiotemporal image correlation, "inversion mode," and "B-flow" imaging. Methods. Spatiotemporal image correlation and the inversion mode were used in the examination of the volume data sets of 23 fetuses with congenital heart anomalies. A subset was also examined with B-flow imaging using the gradient light algorithm. Digital reconstructions from abnormal hearts were compared with a library obtained from fetuses without abnormalities. Results. Rendered images of the 4-chamber view using the inversion mode were characterized by: (1) echogenic chambers; (2) sharp delineation of chamber contours when compared with 2-dimensional (2D) images; and (3) distinct display of the myocardium, interventricular septum, interatrial septum, and mitral and tricuspid valves as anechoic structures. Ventricular septal defects, abnormal differential insertion of the atrioventricular valves, and valve atresia were well visualized with the inversion mode. The application of inversion mode or B-flow imaging to 4D rendering of the outflow tracts resulted in "digital casts" displaying the spatial relationships between the outflow tracts as well as the connections between the great arteries and ventricular chambers. The spatial relationships and communications among cardiac structures cannot be visualized with conventional 2D ultrasonography. Conclusions. The application of spatiotemporal image correlation, inversion mode, and B-flow imaging generates information about the anatomy and pathologic characteristics of the fetal heart (digital casts) that cannot be obtained with 2D fetal echocardiography. We propose that these modalities enhance the information provided by ultrasonographic interrogation of the fetal heart and will improve prenatal diagnosis. C1 Wayne State Univ, Hutzel Hosp, NICHHD, Perinatol Res Branch,Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. William Beaumont Hosp, Div Fetal Imaging, Royal Oak, MI 48072 USA. Ben Gurion Univ Negev, Dept Obstet & Gynecol, Soroka Med Ctr, IL-84105 Beer Sheva, Israel. RP Romero, R (reprint author), Wayne State Univ, Hutzel Hosp, NICHHD, Perinatol Res Branch,Dept Obstet & Gynecol, 3990 John R,Box 4, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov NR 36 TC 45 Z9 56 U1 0 U2 1 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD APR PY 2005 VL 24 IS 4 BP 415 EP 424 PG 10 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 912OJ UT WOS:000228088400003 PM 15784759 ER PT J AU Mari, G Abuhamad, AZ Cosmi, E Segata, M Altaye, M Akiyama, M AF Mari, G Abuhamad, AZ Cosmi, E Segata, M Altaye, M Akiyama, M TI Middle cerebral artery peak systolic velocity - Technique and variability SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE Doppler ultrasonography; fetal anemia; interobserver; variability; middle cerebral artery; peak systolic velocity ID RED-CELL ALLOIMMUNIZATION; FETAL ANEMIA; DOPPLER ULTRASONOGRAPHY; NONINVASIVE DIAGNOSIS; ULTRASOUND; PREDICTION; INFECTION AB Objective. Assessment of the middle cerebral artery (MCA) peak systolic velocity (PSV) can accurately diagnose fetal anemia and has decreased the number of invasive procedures, such as amniocentesis and cordocentesis. The objective of this investigation was to evaluate the intraobserver and interobserver variability as a measure of reproducibility of MCA PSV The technique of correctly sampling this vessel is described. Methods. The study population included 30 appropriate-for-gestational-age fetuses. in each fetus, MCA PSV was determined proximal to the transducer at 3 different locations: 2 mm after its origin from the internal carotid artery, at the midlength between its origin and division, and at its division. The peak systolic velocity was also determined at the contralateral MCA 2 mm after its origin. With each measurement (obtained at 2 different institutions), care was taken to ensure that the ultrasound beam was parallel to the artery for its entire length. The reliability of an angle corrector was also assessed. The intraobserver and interobserver reliabilities were determined from the appropriate version of the intraclass correlation. Results. Gestational age at study entry ranged from 14 to 37.5 weeks (median, 23.6 weeks). The proximal MCA, 2 mm after its origin from the internal carotid artery had the best intraobserver and interobserver variability in both institutions. (Intraclass correlation ranged from 0.98 to 0.99.) Conclusions. Our data indicate that fetal MCA PSV is optimally measured soon after the MCA's origin from the internal carotid artery. Given the importance of clinical decision making based on this measurement, sonographers and sonologists interested in measuring MCA PSV should test their variability after a suitable period of training. C1 Wayne State Univ, Dept Obstet, NICHHD, Perinatol Res Branch,NIH,Dept Hlth & Human Serv, Detroit, MI 48201 USA. Wayne State Univ, Dept Gynecol, NICHHD, Perinatol Res Branch,NIH,Dept Hlth & Human Serv, Detroit, MI 48201 USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. Univ Virginia, Charlottesville, VA USA. Univ Padua, I-35100 Padua, Italy. Univ Bologna, I-40126 Bologna, Italy. Kagawa Univ, Kagawa, Japan. Childrens Hosp, Ctr Biostat & Epidemiol, Cincinnati, OH 45229 USA. RP Mari, G (reprint author), Wayne State Univ, Dept Obstet & Gynecol, NICHHD, Perinatol Res Branch,NIH,Dept Hlth & Human Serv, 3990 John R,Box 4, Detroit, MI 48201 USA. EM gmari@med.wayne.edu RI Altaye, Mekibib/N-5274-2015 NR 14 TC 50 Z9 57 U1 0 U2 8 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD APR PY 2005 VL 24 IS 4 BP 425 EP 430 PG 6 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 912OJ UT WOS:000228088400004 PM 15784760 ER PT J AU Nickel, JC Wang, YL Shoskes, D Propert, K AF Nickel, JC Wang, YL Shoskes, D Propert, K CA NIH Chronic Prostatitis Collaborat TI Validation of the PRE and post massage test (PPMT) for the evaluation of the patient with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) SO JOURNAL OF UROLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Urological-Association CY MAY 21-26, 2005 CL San Antonio, TX SP Amer Urol Assoc C1 NIH, Chron Prostatitis Collaborat Res Network, 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 19106-3261 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2005 VL 173 IS 4 SU S MA 106 BP 29 EP 29 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 907AU UT WOS:000227687900107 ER PT J AU Tripp, D Nickel, JC McNaughton-Collins, M Wang, YL Landis, JR AF Tripp, D Nickel, JC McNaughton-Collins, M Wang, YL Landis, JR CA NIH Chronic Prostatitis Collaborat TI Coping with depression in Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A key to treatment of the pain? SO JOURNAL OF UROLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Urological-Association CY MAY 21-26, 2005 CL San Antonio, TX SP Amer Urol Assoc C1 NIH, Chron Prostatitis Collaborat Res Network, Bethesda, MD USA. RI Landis, J. Richard/A-9330-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2005 VL 173 IS 4 SU S MA 113 BP 31 EP 31 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA 907AU UT WOS:000227687900114 ER PT J AU Kundu, SD Grubb, RL Roehl, KA Antenor, JAV Han, M Catalona, WJ AF Kundu, SD Grubb, RL Roehl, KA Antenor, JAV Han, M Catalona, WJ TI Delays in cancer detection using 2 and 4-year screening intervals for prostate cancer screening with initial prostate specific antigen less than 2 ng/ml SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostate-specific antigen; prostatic neoplasms; mass screening; risk ID RADICAL PROSTATECTOMY; MEN; RISK AB Purpose: The American Urological Association and American Cancer Society advocate annual screening with serum prostate specific antigen (PSA) and digital rectal examination starting at age 50 years in the general population and earlier in men at high risk. Some groups have suggested that screening at 2 or 4-year intervals may be sufficient in men with initial PSA 2 ng/ml or less. We reviewed the records of men enrolled in a PSA and digital rectal examination based prostate cancer screening study to determine the extent to which the diagnosis of cancer would have been delayed using a 2 or 4-year screening interval. Materials and Methods: We evaluated 18,140 volunteers in a prostate cancer screening study in whom PSA was less than 2 ng/ml at initial screening and who were screened at 6-month to 1-year intervals for up to 8 years. We evaluated the cancers detected in these intervals to determine the possible delay in cancer diagnosis that would occur using prolonged screening intervals. We report the overall cancer detection rate, clinical and pathological tumor stage, and Gleason grade of the cancers detected. Results: Excluding 70 men in whom prostate cancer was detected at initial evaluation 2.0% had prostate cancer detected during the next 8 years (mean 21.6 cancers per 6 months, median 20, range 12 to 33). Using a hypothetical 2-year screening interval cancer detection 62% would have been delayed by 4 to 20 months. Using a hypothetical 4-year screening interval cancer detection would have been delayed in 77% of men by 4 to 44 months. Of the tumors detected 100% were clinically localized, 77% were pathologically organ confined and 29% had a Gleason score of 7 or greater. Conclusions: The 2 or 4-year PSA screening interval in men with initial serum PSA less than 2 ng/ml would result in substantial delays in prostate cancer detection. To our knowledge the extent to which these delays would affect treatment outcomes is undetermined. C1 Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. NCI, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Neurol Surg, St Louis, MO 63110 USA. RP Catalona, WJ (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Urol, 675 N St Clair St,Suite 20-150, Chicago, IL 60611 USA. EM wcatalona@nmff.org NR 18 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2005 VL 173 IS 4 BP 1116 EP 1120 DI 10.1097/01.ju.0000155460.20581.a4 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 907AS UT WOS:000227687600014 PM 15758718 ER PT J AU Mayer, R Propert, KJ Peters, KM Payne, CK Zhang, YW Burks, D Culkin, DJ Diokno, A Hanno, P Landis, JR Madigan, R Messing, EM Nickel, JC Sant, GR Warren, J Wein, AJ Kusek, JW Nyberg, LM Foster, HE AF Mayer, R Propert, KJ Peters, KM Payne, CK Zhang, YW Burks, D Culkin, DJ Diokno, A Hanno, P Landis, JR Madigan, R Messing, EM Nickel, JC Sant, GR Warren, J Wein, AJ Kusek, JW Nyberg, LM Foster, HE CA Interstitial Cystitis Grp TI A randomized controlled trial of intravesical bacillus Calmette-Guerin for treatment refractory interstitial cystitis SO JOURNAL OF UROLOGY LA English DT Article DE mycobacterium bovis; cystitis; interstitial; pain; quality of life ID DOUBLE-BLIND; PENTOSAN POLYSULFATE; CLINICAL-TRIALS; EFFICACY; PAIN AB Purpose: We compared intravesical bacillus Calmette-Guerin (BCG) to placebo instillations in patients with treatment refractory interstitial cystitis (IC). Materials and Methods: Subjects who met the National Institutes of Health-National Institute for Diabetes and Digestive and Kidney Diseases criteria for IC, and reported at least moderate pain and frequency for a minimum of 6 months before study entry, were randomized to 6 weekly double-blinded intravesical instillations of either BCG or placebo, and then followed for a total of 34 weeks. The primary outcome was a patient reported global response assessment at week 34, supplemented with medications for IC during weeks 31 to 34. Secondary outcomes included a 24-hour voiding diary, pain, urgency, validated IC symptom indexes and adverse events. The target sample size was 260 participants, designed to detect a difference in response rates between placebo and BCG of 30% and 50%, respectively. Results: A total of 265 participants were randomized and 17 (6%) patients withdrew from study. The response rates for the primary outcome were 12% for placebo and 21% for BCG (p = 0.062). Small improvements were observed for all secondary outcomes, some more so with BCG, but these differences were of borderline statistical significance. Although a large number of adverse events were reported in the BCG arm, there was no statistically significant difference between the treatment arms in overall adverse event rates. Conclusions: Although the BCG safety profile was acceptable, the response rate for the primary outcome was low. Effective medical treatment for patients with moderate to severe interstitial cystitis remains elusive. C1 Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Rochester, Rochester, NY USA. William Beaumont Hosp, Royal Oak, MI 48072 USA. Stanford Univ, Stanford, CA 94305 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Queens Univ, Kingston, ON, Canada. Sanofi Synthelabo Inc, New York, NY USA. Univ Maryland, Baltimore, MD 21201 USA. NIDDK, NIH, Bethesda, MD USA. Yale Univ, New Haven, CT USA. RP Propert, KJ (reprint author), Univ Penn, Sch Med, Dept Biostat & Epidemiol, Blockley Hall,6th Floor,423 Guardian Dr, Philadelphia, PA 19104 USA. EM kpropert@cceb.upenn.edu RI Landis, J. Richard/A-9330-2010 FU NCRR NIH HHS [M01 RR16500]; NIDDK NIH HHS [U01 DK54125, U01 DK54108, U01 DK54127, U01 DK54133, U01 DK54138, U01 DK54158] NR 18 TC 69 Z9 70 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2005 VL 173 IS 4 BP 1186 EP 1191 DI 10.1097/01.ju.0000152337.82806.e8 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 907AS UT WOS:000227687600027 PM 15758738 ER PT J AU Wood, BJ Zhang, H Durrani, A Glossop, N Ranjan, S Lindisch, D Levy, E Banovac, F Borgert, J Krueger, S Kruecker, J Viswanathan, A Cleary, K AF Wood, BJ Zhang, H Durrani, A Glossop, N Ranjan, S Lindisch, D Levy, E Banovac, F Borgert, J Krueger, S Kruecker, J Viswanathan, A Cleary, K TI Navigation with electromagnetic tracking for interventional radiology procedures: A feasibility study SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID CT; PLACEMENT; CATHETER AB PURPOSE: To assess the feasibility of the use of preprocedural imaging for guide wire, catheter, and needle navigation with electromagnetic tracking in phantom and animal models. MATERIALS AND METHODS: An image-guided intervention software system was developed based on open-source software components. Catheters, needles, and guide wires were constructed with small position and orientation sensors in the tips. A tetrahedral-shaped weak electromagnetic field generator was placed in proximity to an abdominal vascular phantom or three pigs on the angiography table. Preprocedural computed tomographic (CT) images of the phantom or pig were loaded into custom-developed tracking, registration, navigation, and rendering software. Devices were manipulated within the phantom or pig with guidance from the previously acquired CT scan and simultaneous real-time angiography. Navigation within positron emission tomography (PET) and magnetic resonance (MR) volumetric datasets was also performed. External and endovascular fiducials were used for registration in the phantom, and registration error and tracking error were estimated. RESULTS: The CT scan position of the devices within phantoms and pigs was accurately determined during angiography and biopsy procedures, with manageable error for some applications. Preprocedural CT depicted the anatomy in the region of the devices with real-time position updating and minimal registration error and tracking error (< 5 mm). PET can also be used with this system to guide percutaneous biopsies to the most metabolically active region of a tumor. CONCLUSIONS: Previously acquired CT, MR, or PET data can be accurately codisplayed during procedures with reconstructed imaging based on the position and orientation of catheters, guide wires, or needles. Multimodality interventions are feasible by allowing the real-time updated display of previously acquired functional or morphologic imaging during angiography, biopsy, and ablation. C1 Natl Inst Hlth Clin Ctr, Dept Diagnost Radiol, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Imaging Sci & Informat Syst Ctr, Washington, DC 20007 USA. Georgetown Univ, Med Ctr, Dept Radiol, Washington, DC 20007 USA. Traxtal Technol, Bellaire, TX USA. Philips Res USA, Briarcliff Manor, NY USA. Sector Tech Syst, Hamburg, Germany. RP Wood, BJ (reprint author), Natl Inst Hlth Clin Ctr, Dept Diagnost Radiol, Bldg 10,Room 1C-660, Bethesda, MD 20892 USA. EM bwood@nih.gov OI Viswanathan, Anand/0000-0003-3810-6217 FU Intramural NIH HHS [Z99 CL999999] NR 11 TC 122 Z9 126 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD APR PY 2005 VL 16 IS 4 BP 493 EP 505 DI 10.1097/01.RVI.0000148827.62296.B4 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 913SY UT WOS:000228174700009 PM 15802449 ER PT J AU Roca, AL Nash, WG Menninger, JC Murphy, WJ O'Brien, SJ AF Roca, AL Nash, WG Menninger, JC Murphy, WJ O'Brien, SJ TI Insertional polymorphisms of endogenous feline leukemia viruses SO JOURNAL OF VIROLOGY LA English DT Article ID FELV-RELATED SEQUENCES; DOMESTIC CAT; SUBGROUP-B; IMMUNODEFICIENCY VIRUS; NUCLEOTIDE-SEQUENCE; MELATONIN RECEPTOR; ENVELOPE GENE; Y-CHROMOSOME; EVOLUTION; DNA AB The number, chromosomal distribution, and insertional polymorphisms of endogenous feline leukemia viruses (enFeLVs) were determined in four domestic cats (Burmese, Egyptian Mau, Persian, and nonbreed) using fluorescent in situ hybridization and radiation hybrid mapping. Twenty-nine distinct enFeLV loci were detected across 12 of the 18 autosomes. Each cat carried enFeLV at only 9 to 16 of the loci, and many loci were heterozygous for presence of the provirus. Thus, an average of 19 autosomal copies of enFeLV were present per cat diploid genome. Only five of the autosomal enFeLV sites were present in all four cats, and at only one autosomal locus, B4q15, was enFeLV present in both homologues of all four cats. A single enFeLV occurred in the X chromosome of the Burmese cat, while three to five enFeLV proviruses occurred in each Y chromosome. The X chromosome and nine autosomal enFeLV loci were telomeric, suggesting that ectopic recombination between nonhomologous subtelomeres may contribute to enFeLV distribution. Since endogenous FeLVs may affect the infectiousness or pathogenicity of exogenous FeLVs, genomic variation in enFeLVs represents a candidate for genetic influences on FeLV leukemogenesis in cats. C1 NCI, Lab Genet Divers, Frederick, MD 21702 USA. SAIC, Lab Genom Divers, Basic Res Program, Frederick, MD USA. H&W Cytogenet Serv, Lovettsville, VA USA. Texas A&M Univ, Dept Vet Integrat Biosci, College Stn, TX USA. RP Roca, AL (reprint author), NCI, Lab Genet Divers, Bldg 560, Frederick, MD 21702 USA. EM roca@ncifcrf.gov; obrien@ncifcrf.gov FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 60 TC 15 Z9 15 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 7 BP 3979 EP 3986 DI 10.1128/JVI.79.7.3979-3986.2005 PG 8 WC Virology SC Virology GA 907UO UT WOS:000227743700009 PM 15767400 ER PT J AU Sosnovtsev, SV Belliot, G Chang, KO Onwudiwe, O Green, KY AF Sosnovtsev, SV Belliot, G Chang, KO Onwudiwe, O Green, KY TI Feline calicivirus VP2 is essential for the production of infectious virions SO JOURNAL OF VIROLOGY LA English DT Article ID HEMORRHAGIC-DISEASE VIRUS; CAPSID PROTEIN GENE; NONSTRUCTURAL POLYPROTEIN; UNTRANSLATED REGION; NUCLEOTIDE-SEQUENCE; PRECURSOR PROTEIN; NONCODING REGIONS; RNA REPLICATION; GENOMIC RNA; IDENTIFICATION AB The third open reading frame (ORF3) located at the 3' end of the genomic RNA of feline calicivirus (FCV) encodes a small (12.2-kDa) minor structural protein of 106 amino acids designated VP2. Point mutations and deletions were introduced into an infectious FCV cDNA clone in order to evaluate the functional importance of ORF3 and its encoded protein, VP2. Deletion of the entire ORF3 sequence was lethal for the virus, and evidence was found for strong selective pressure to produce the VP2 protein. Extended deletions in the 5' end and small deletions in the 3' end of ORF3, as well as the introduction of stop codons into the ORF3 sequence, were tolerated by the viral replication machinery, but infectious virus could not be recovered. Infectious virus particles could be rescued from a full-length FCV cDNA clone encoding a nonfunctionall VP2 when VP2 was provided in trans from a eukaryotic expression plasmid. Our data indicate that VP2, a protein apparently unique to the caliciviruses, is essential for productive replication that results in the synthesis and maturation of infectious virions and that the ORF3 nucleotide sequence itself overlaps a cis-acting RNA signal at the genomic 3' end. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Sosnovtsev, SV (reprint author), 50 S Dr MSC8007,Bldg 50,Room 6316, Bethesda, MD 20892 USA. EM ss2l6m@nih.gov NR 44 TC 61 Z9 65 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 7 BP 4012 EP 4024 DI 10.1128/JVI.79.7.4012-4024.2005 PG 13 WC Virology SC Virology GA 907UO UT WOS:000227743700012 PM 15767403 ER PT J AU Speirs, C van Nimwegen, E Bolton, D Zavolan, M Duvall, M Angleman, S Siegel, R Perelson, AS Lenardo, MJ AF Speirs, C van Nimwegen, E Bolton, D Zavolan, M Duvall, M Angleman, S Siegel, R Perelson, AS Lenardo, MJ TI Analysis of human immunodeficiency virus cytopathicity by using a new method for quantitating viral dynamics in cell culture SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 VPR; T-CELLS; COMBINATION THERAPY; IN-VIVO; INFECTION; APOPTOSIS; TYPE-1; PROTEIN; PATHOGENESIS; LYMPHOCYTES AB Human immunodeficiency virus (HIV) causes complex metabolic changes in infected CD4(+) T cells that lead to cell cycle arrest and cell death by necrosis. To study the viral functions responsible for deleterious effects on the host cell, we quantitated the course of HIV type I infection in tissue cultures by using How cytometry for a virally encoded marker protein, heat-stable antigen (HSA). We found that HSA appeared on the surface of the target cells in two phases: passive acquisition due to association and fusion of virions with target cells, followed by active protein expression from transcription of the integrated provirus. The latter event was necessary for decreased target cell viability. We developed a general mathematical model of viral dynamics in vitro in terms of three effective time-dependent rates: those of cell proliferation, infection, and death. Using this model we show that the predominant contribution to the depletion of viable target cells results from direct cell death rather than cell cycle blockade. This allows us to derive accurate bounds on the time-dependent death rates of infected cells. We infer that the death rate of HIV-infected cells is 80 times greater than that of uninfected cells and that the elimination of the vpr protein reduces the death rate by half. Our approach provides a general method for estimating time-dependent death rates that can be applied to study the dynamics of other viruses. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Basel, Div Bioinformat, Biozentrum, Basel, Switzerland. Los Alamos Natl Lab, Los Alamos, NM USA. RP Lenardo, MJ (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM Lenardo@nih.gov RI Siegel, Richard/C-7592-2009; OI Siegel, Richard/0000-0001-5953-9893; Angleman, Sara/0000-0002-9520-5716; van Nimwegen, Erik/0000-0001-6338-1312; Zavolan, Mihaela/0000-0002-8832-2041 FU NCRR NIH HHS [R01 RR006555, RR06555]; NIAID NIH HHS [AI28433, R01 AI028433, R37 AI028433] NR 39 TC 14 Z9 14 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 7 BP 4025 EP 4032 DI 10.1128/JVI.79.7.4025-4032.2005 PG 8 WC Virology SC Virology GA 907UO UT WOS:000227743700013 PM 15767404 ER PT J AU Rudner, L Nydegger, S Coren, LV Nagashima, K Thali, M Ott, DE AF Rudner, L Nydegger, S Coren, LV Nagashima, K Thali, M Ott, DE TI Dynamic fluorescent imaging of human immunodeficiency virus type 1 Gag in live cells by biarsenical labeling SO JOURNAL OF VIROLOGY LA English DT Article ID LATE-BUDDING DOMAINS; PLASMA-MEMBRANE; NUCLEAR EXPORT; IN-VIVO; POSTTRANSLATIONAL MODIFICATIONS; MULTIVESICULAR BODIES; PRIMARY MACROPHAGES; PARTICLE RELEASE; PROTEIN FUNCTION; HIV-1 AB Human immunodeficiency virus type 1 (HIV-1) Gag is the primary structural protein of the virus and is sufficient for particle formation. We utilized the recently developed biarsenical-labeling method to dynamically observe HIV-1 Gag within live cells by adding a tetracysteine tag (C-C-P-G-C-C) to the C terminus of Gag in both Pr55Gag expression and full-length proviral constructs. Membrane-permeable biarsenical compounds FIAsH and ReAsH covalently bond to this tetracysteine sequence and specifically fluoresce, effectively labeling Gag in the cell. Biarsenical labeling readily and specifically detected a tetracysteine-tagged HIV-1 Gag protein (Gag-TC) in HeLa, Mel JuSo, and Jurkat T cells by deconvolution fluorescence microscopy. Gag-TC was localized primarily at or near the plasma membrane in all cell types examined. Fluorescent two-color analysis of Gag-TC in HeLa cells revealed that nascent Gag was present mostly at the plasma membrane in distinct regions. Intracellular imaging of a Gag-TC myristylation mutant observed a diffuse signal throughout the cell, consistent with the role of myristylation in Gag localization to the plasma membrane. In contrast, mutation of the L-domain core sequence did not appreciably alter the localization of Gag, suggesting that the PTAP L domain functions at the site of budding rather than as a targeting signal. Taken together, our results show that Gag concentrates in specific plasma membrane areas rapidly after translation and demonstrate the utility of biarsenical labeling for visualizing the dynamic localization of Gag. C1 NCI, Basic Res Program, SAIC, Frederick Inc, Frederick, MD 21702 USA. NCI, Res Technol Program, SAIC, Frederick Inc, Frederick, MD 21702 USA. Univ Verona, Dept Mol Genet & Microbiol, Burlington, VT USA. RP Ott, DE (reprint author), NCI, Basic Res Program, SAIC, Frederick Inc, Frederick, MD 21702 USA. EM ott@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NIAID NIH HHS [R01 AI 47727, R01 AI047727, R56 AI047727] NR 73 TC 86 Z9 88 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 7 BP 4055 EP 4065 DI 10.1128/JVI.79.7.4055-4065.2005 PG 11 WC Virology SC Virology GA 907UO UT WOS:000227743700016 PM 15767407 ER PT J AU Husain, M Moss, B AF Husain, M Moss, B TI Role of receptor-mediated endocytosis in the formation of vaccinia virus extracellular enveloped particles SO JOURNAL OF VIROLOGY LA English DT Article ID INTERMEDIATE COMPARTMENT; INTRACELLULAR MOVEMENT; ENDOPLASMIC-RETICULUM; PROGENY VACCINIA; GOLGI NETWORK; CELL-SURFACE; A36R PROTEIN; MEMBRANE; GENE; GLYCOPROTEIN AB Infectious intracellular mature vaccinia virus particles are wrapped by cisternae, which may arise from trans-Golgi or early endosomal membranes, and are transported along microtubules to the plasma membrane where exocytosis occurs. We used EH21, a dominant-negative form of Eps15 that is an essential component of clathrin-coated pits, to investigate the extent and importance of endocytosis of viral envelope proteins from the cell surface. Several recombinant vaccinia viruses that inducibly or constitutively express an enhanced green fluorescent protein (GFP)-EH21 fusion protein were constructed. Expression of GFP-EH21, blocked uptake of transferrin, a marker for clathrin-mediated endocytosis, as well as association of adaptor protein-2 with clathrin-coated pits. When GFP-EH21 was expressed, there were increased amounts of viral envelope proteins, including A33, A36, B5, and F13, in the plasma membrane, and their internalization was inhibited. Wrapping of virions appeared to be qualitatively unaffected as judged by electron microscopy, a finding consistent with a primary trans-Golgi origin of the cisternae. However, GFP-EH21 expression caused a 50% reduction in released enveloped virions, decreased formation of satellite plaques, and delayed virus spread, indicating an important role for receptor-mediated endocytosis. Due to dynamic interconnection between endocytic and exocytic pathways, viral proteins recovered from the plasma membrane could be used by trans-Golgi or endosomal cisternae to form new viral envelopes. Adherence of enveloped virions to unrecycled viral proteins on the cell surface may also contribute to decreased virus release in the presence of GFP-EH21. In addition to a salvage function, the retrieval of viral proteins from the cell surface may reduce immune recognition. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, Viral Dis Lab, NIH, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. EM bmoss@nih.gov NR 42 TC 13 Z9 13 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 7 BP 4080 EP 4089 DI 10.1128/JVI.79.7.4080-4089.2005 PG 10 WC Virology SC Virology GA 907UO UT WOS:000227743700018 PM 15767409 ER PT J AU Chen, JB Dang, Q Unutmaz, D Pathak, VK Maldarelli, F Powell, D Hu, WS AF Chen, JB Dang, Q Unutmaz, D Pathak, VK Maldarelli, F Powell, D Hu, WS TI Mechanisms of nonrandom human immunodeficiency virus type 1 infection and double infection: Preference in virus entry is important but is not the sole factor SO JOURNAL OF VIROLOGY LA English DT Article ID HIV-1 INFECTION; DENDRITIC CELLS; PRIMARY PATIENT; HIGH-TITER; IN-VIVO; RECOMBINATION; CD4; CCR5; PATHOGENESIS; MEMBRANE AB We previously demonstrated that human immunodeficiency virus type 1 (HIV-1) infection is nonrandom and that double infection occurs more frequently than predicted from random events. To probe the possible mechanisms for nonrandom infection, we examined the role of HIV-1 entry pathways by using viruses pseudotyped with either CCR5-tropic HIV-1 Env or vesicular stomatitis virus G protein (VSV G). These two proteins use different receptors and entry pathways. We found that regardless of the protein used, double infection occurred more frequently than random events, indicating nonrandorn HIV-1 infection in both entry pathways. However, the frequency of double infection differed significantly, depending on the envelope protein. In primary CD4(+) T cells, double infection occurred most frequently when both viruses had CCR5-tropic HIV-1 Env and least frequently when the two viruses had different envelopes. These results indicated that the preference in virus entry was a significant but not the only factor contributing to nonrandom double infection. Furthermore, we demonstrated that the CD4 expression level in primary T cells affects their susceptibility to CCR5-tropic HIV-1 infection but not VSV G-pseudotyped HIV-1 infection. We have also examined infection with two viruses pseudotyped with CCR5- or CXCR4-tropic HIV-1 Env and have found that double infection occurred more frequently than random events. These results indicate that coreceptor usage is not a barrier to recombination between the two virus populations. In our previous study, we also demonstrated nonrandom double infection via dendritic cell (DC)-mediated HIV-1 transmission. To test our hypothesis that multiple HIV-1 virions are transmitted during DC-T-cell contact, we used two populations of DCs, each capturing one vector virus, and added both DC populations to T cells. We observed a decreased frequency of double infection compared with experiments in which DCs captured both viruses simultaneously. Therefore, these results support our hypothesis that multiple virions are transmitted from DCs to T cells during cell-mediated HIV-1 transmission. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. NCI, Data Management Serv, Frederick, MD 21702 USA. Vanderbilt Univ, Dept Microbiol & Immunol, Nashville, TN USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 535,Room 336, Frederick, MD 21702 USA. EM whu@ncifcrf.gov RI Chen, Jianbo/N-3737-2014 OI Chen, Jianbo/0000-0001-6491-6577 FU NIAID NIH HHS [R01 AI049131, R01-AI-49131] NR 35 TC 45 Z9 46 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 7 BP 4140 EP 4149 DI 10.1128/JVI.79.7.4140-4149.2005 PG 10 WC Virology SC Virology GA 907UO UT WOS:000227743700024 PM 15767415 ER PT J AU Lee, SK Nagashima, K Hu, WS AF Lee, SK Nagashima, K Hu, WS TI Cooperative effect of Gag proteins p12 and capsid during early events of murine leukemia virus replication SO JOURNAL OF VIROLOGY LA English DT Article ID ROUS-SARCOMA-VIRUS; SPLEEN NECROSIS VIRUS; SYNTHESIS IN-VIVO; NUCLEOCAPSID PROTEIN; DNA-SYNTHESIS; VIRAL-DNA; RETROVIRAL REPLICATION; ESCHERICHIA-COLI; DOMAIN; CELLS AB The Gag polyprotein of murine leukemia virus (MLV) is processed into matrix (MA), p12, capsid (CA), and nucleocapsid (NC) proteins. p12 affects early events of virus replication and contains a PPPY motif important for virus release. To probe the functions of p12 in the early steps of MLV replication, we tested whether p12 can be replaced by spleen necrosis virus (SNY) p18, human immunodeficiency virus type 1 p6, or Rous sarcoma virus p2b. Analyses revealed that all chimeras generated virions at levels similar to that of MLV gag-pol; however, none of them could support MLV vector replication, and all of them exhibited severely reduced DNA synthesis upon virus infection. Because a previously reported SNV gag-MLV pol chimera, but not the MLV hybrid with SNV p18, can support replication of an MLV vector, we hypothesized that other Gag proteins act cooperatively with p12 during the early phase of virus replication. To test this hypothesis, we generated three more MLV-based chimeras containing SNV CA, p18-CA, or p18-CA-NC. We found that the MLV chimera containing SNV p18-CA or p18-CA-NC could support MLV vector replication, but the chimera containing SNV CA could not. Furthermore, viruses derived from the MLV chimera with SNY CA could synthesize viral DNA upon infection but were blocked at a post-reverse-transcription step and generated very little two long terminal repeat circle DNA, thereby producing a phenotype similar to that of the provirus formation-defective p12 mutants. Taken together, our data indicate that when p12/p18 or CA was from different viruses, despite abundant virus production and proper Gag processing, the resulting viruses were not infectious. However, when p12/p18 and CA were from the same virus, even though they were from SNY and not MLV, the resulting viruses were infectious. Therefore, these results suggest a cooperative effect of p12 and CA during the early events of MLV replication. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. SAIC, Frederick, MD USA. RP Hu, WS (reprint author), NCI, HIV Drug Resistance Program, Bldg 535,Room 336, Frederick, MD 21702 USA. EM whu@ncifcrf.org NR 47 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 7 BP 4159 EP 4169 DI 10.1128/JVI.79.7.4159-4169.2005 PG 11 WC Virology SC Virology GA 907UO UT WOS:000227743700026 PM 15767417 ER PT J AU Vazquez, N Greenwell-Wild, T Marinos, NJ Swaim, WD Nares, S Ott, DE Schubert, U Henklein, P Orenstein, JM Sporn, MB Wahl, SM AF Vazquez, N Greenwell-Wild, T Marinos, NJ Swaim, WD Nares, S Ott, DE Schubert, U Henklein, P Orenstein, JM Sporn, MB Wahl, SM TI Human immunodeficiency virus type 1-induced macrophage gene expression includes the p21 gene, a target for viral regulation SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; CELL-CYCLE ARREST; T-CELLS; HIV-1 REPLICATION; ALVEOLAR MACROPHAGES; MISMATCH REPAIR; RHESUS MACAQUES; BINDING-PROTEIN; LIM-KINASE; INFECTION AB In contrast to CD4(+) T cells, human immunodeficiency virus type I (HIV-1) -infected macrophages typically resist cell death, support viral replication, and consequently, may facilitate HIV-1 transmission. To elucidate how the virus commandeers the macrophage's intracellular machinery for its benefit, we analyzed HIV-1-infected human macrophages for virus-induced gene transcription by using multiple parameters, including cDNA expression arrays. HIV-1 infection induced the transcriptional regulation of genes associated with host defense, signal transduction, apoptosis, and the cell cycle, among which the cyclin-dependent kinase inhibitor 1A (CDKNlA/p21) gene was the most prominent. p21 mRNA and protein expression followed a bimodal pattern which was initially evident during the early stages of infection, and maximum levels occurred concomitant with active HIV-1 replication. Mechanistically, viral protein R (Vpr) independently regulates p21 expression, consistent with the reduced viral replication and lack of p21 upregulation by a Vpr-negative virus. Moreover, the treatment of macrophages with p21 antisense oligonucleotides or small interfering RNAs reduced HTV-1 infection. In addition, the synthetic triterpenoid and peroxisome proliferator-activated receptor gamma ligand, 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), which is known to influence p21 expression, suppressed viral replication. These data implicate p21 as a pivotal macrophage facilitator of the viral life cycle. Moreover, regulators of p21, such as CDDO, may provide an interventional approach to modulate HIV-1 replication. C1 NIH, NIDCR, OIIB, Bethesda, MD 20892 USA. NIH, NIAID, Bethesda, MD 20892 USA. SAIC Frederick Inc, Basic Res Program, NCI, Frederick, MD USA. Humboldt Univ, Berlin, Germany. George Washington Univ, Washington, DC USA. Dartmouth Coll, Hanover, NH 03756 USA. RP Vazquez, N (reprint author), NIH, NIDCR, OIIB, 30 Convent Dr,Bldg 30,Rm 332,MSC 4352, Bethesda, MD 20892 USA. EM nvazquez@mail.nih.gov FU NCI NIH HHS [N01CO12400] NR 72 TC 69 Z9 69 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 7 BP 4479 EP 4491 DI 10.1128/JVI.79.7.4479-4491.2005 PG 13 WC Virology SC Virology GA 907UO UT WOS:000227743700057 PM 15767448 ER PT J AU Seaman, MS Santra, S Newberg, MH Philippon, V Manson, K Xu, L Gelman, RS Panicali, D Mascola, JR Nabel, GJ Letvin, NL AF Seaman, MS Santra, S Newberg, MH Philippon, V Manson, K Xu, L Gelman, RS Panicali, D Mascola, JR Nabel, GJ Letvin, NL TI Vaccine-elicited memory cytotoxic T lymphocytes contribute to Mamu-A*01-associated control of simian/human immunodeficiency virus 89.6P replication in rhesus monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; CLASS-I MOLECULE; DISEASE PROGRESSION; IMMUNE-RESPONSES; INFECTION; HIV-1; AIDS; PROTECTION; EPITOPES; PREVENTION AB The expression of particular major histocompatibility complex (MHC) class I alleles can influence the rate of disease progression following lentiviral infections. This effect is a presumed consequence of potent cytotoxic T-lymphocyte (CTL) responses that are restricted by these MHC class I molecules. The present studies have examined the impact of the MHC class I allele Mamu-A*01 on simian/human immunodeficiency virus 89.6P (SHIV-89.6P) infection in unvaccinated and vaccinated rhesus monkeys by exploring the contribution of dominant-epitope specific CTL in this setting. Expression of Mamu-A*01 in immunologically naive monkeys was not associated with improved control of viral replication, CD4(+) T-lymphocyte loss, or survival. In contrast, Mamu-A*01(+) monkeys that had received heterologous prime/boost immunizations prior to challenge maintained higher CD4(+) T-lymphocyte levels and better control of SHIV-89.6P replication than Mamu-A*01(-) monkeys. This protection was associated with the evolution of high-frequency anamnestic CTL responses specific for a dominant Mamu-A*01-restricted Gag epitope following infection. These data indicate that specific MHC class I alleles can confer protection in the setting of a pathogenic SHIV infection by their ability to elicit memory CTL following vaccination. C1 Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, Boston, MA 02215 USA. Dana Farber Canc Inst, Dept Biostat, Boston, MA 02115 USA. Therion Biol, Cambridge, MA USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Letvin, NL (reprint author), Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Div Viral Pathogenesis, 330 Brookline Ave,RE-113, Boston, MA 02215 USA. EM nletvin@bidmc.harvard.edu FU NIAID NIH HHS [N01AI30033, AI30033] NR 29 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 4580 EP 4588 DI 10.1128/JVI.79.8.4580-4588.2005 PG 9 WC Virology SC Virology GA 912JJ UT WOS:000228073700003 PM 15795244 ER PT J AU Snyder, GA Ford, J Torabi-Parizi, P Arthos, JA Schuck, P Colonna, M Sun, PD AF Snyder, GA Ford, J Torabi-Parizi, P Arthos, JA Schuck, P Colonna, M Sun, PD TI Characterization of DC-SIGN/R interaction with human immunodeficiency virus type 1 gp120 and ICAM molecules favors the receptor's role as an antigen-capturing rather than an adhesion receptor SO JOURNAL OF VIROLOGY LA English DT Article ID C-TYPE LECTIN; ENDOTHELIAL-CELLS; ANTIBODY 2G12; CARBOHYDRATE-RECOGNITION; SELECTIVE RECOGNITION; GLYCOPROTEIN GP120; MANNOSE RECEPTOR; EBOLA-VIRUS; T-CELLS; BINDING AB The dendritic cell (DC)-specific intercellular adhesion molecule 3 (ICAM-3)-grabbing nonintegrin binding receptor (DC-SIGN) was shown to bind human immunodeficiency virus type 1 (HIV-1) viral envelope protein gp120 and proposed to function as a Trojan horse to enhance trans-virus infection to host T cells. To better understand the mechanism by which DC-SIGN and DC-SIGNR selectively bind HIV-1 gp120, we constructed a series of deletion mutations in the repeat regions of both receptors. Different truncated receptors exist in different oligomeric forms. The carbohydrate binding domain without any repeats was monomeric, whereas the full extracellular receptors existed as tetramers. All reconstituted receptors retained their ability to bind gp120. The dissociation constant, however, differed drastically from micromolar values for the monomeric receptors to nanomolar values for the tetrameric receptors, suggesting that the repeat region of these receptors contributes to the avidity of gp120 binding. Such oligomerization may provide a mechanism for the receptor to selectively recognize pathogens containing multiple high-mannose-concentration carbohydrates. In contrast, the receptors bound to ICAMs with submicromolar affinities that are similar to those of two nonspecific cell surface glycoproteins, Fc gamma RIIb and Fc gamma RIII, and the oligomerization of DC-SIGNR resulted in no increase in binding affinity to ICAM-3. These findings suggest that DC-SIGN may not discriminate other cell surface glycoproteins from ICAM-3 binding. The pH dependence in DC-SIGN binding to gp120 showed that the receptor retained high-affinity gp120 binding at neutral pH but lost gp120 binding at pH 5, suggesting a release mechanism of HIV in the acidic endosomal compartment by DC-SIGN. Our work contradicts the function of DC-SIGN as a Trojan horse to facilitate HIV-1 infection; rather, it supports the function of DC-SIGN/R (a designation referring to both DC-SIGN and DC-SIGNR) as an antigen-capturing receptor. C1 NIAID, Immunogenet Lab, Struct Immunol Sect, NIH, Rockville, MD 20852 USA. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NIH, Off Director, Off Res Serv, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. Emory Univ, Dept Med, Atlanta, GA 30322 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO USA. RP Sun, PD (reprint author), NIAID, Immunogenet Lab, Struct Immunol Sect, NIH, Twinbrook 2,12441 Parklawn Dr, Rockville, MD 20852 USA. EM psun@nih.gov OI Schuck, Peter/0000-0002-8859-6966; Colonna, Marco/0000-0001-5222-4987 NR 32 TC 57 Z9 62 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 4589 EP 4598 DI 10.1128/JVI.79.8.4589-4598.2005 PG 10 WC Virology SC Virology GA 912JJ UT WOS:000228073700004 PM 15795245 ER PT J AU Alamgir, ASM Owens, N Lavignon, M Malik, F Evans, LH AF Alamgir, ASM Owens, N Lavignon, M Malik, F Evans, LH TI Precise identification of endogenous proviruses of NFS/N mice participating in recombination with Moloney ecotropic murine leukemia virus (MuLV) to generate polytropic MuLVs SO JOURNAL OF VIROLOGY LA English DT Article ID FOCUS-FORMING VIRUSES; LONG TERMINAL REPEAT; AKR/J MICE; THYMIC LYMPHOMAS; C-MYC; MONOCLONAL-ANTIBODIES; HETERODUPLEX ANALYSIS; NUCLEOCAPSID PROTEIN; NUCLEOTIDE-SEQUENCE; STRAND TRANSFER AB Polytropic murine leukemia viruses (MuLVs) are generated by recombination of ecotropic MuLVs with env genes of a family of endogenous proviruses in mice, resulting in viruses with an expanded host range and greater virulence. Inbred mouse strains contain numerous endogenous proviruses that are potential donors of the env gene sequences of polytropic MuLVs; however, the precise identification of those proviruses that participate in recombination has been elusive. Three different structural groups of proviruses in NFS/N mice have been described and different ecotropic MuLVs preferentially recombine with different groups of proviruses. In contrast to other ecotropic MuLVs such as Friend MuLV or Akv that recombine predominantly with a single group of proviruses, Moloney MuLV (M-MuLV) recombines with at least two distinct groups. In this study, we determined that only three endogenous proviruses, two of one group and one of another group, are major participants in recombination with M-MuLV. Furthermore, the distinction between the polytropic MuLVs generated by M-MuLV and other ecotropic MuLVs is the result of recombination with a single endogenous provirus. This provirus exhibits a frameshift mutation in the 3' region of the surface glycoprotein-encoding sequences that is excluded in recombinants with M-MuLV. The sites of recombination between the env genes of M-MuLV and endogenous proviruses were confined to a short region exhibiting maximum homology between the ecotropic and polytropic env sequences and maximum stability of predicted RNA secondary structure. These observations suggest a possible mechanism for the specificity of recombination observed for different ecotropic MuLVs. C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. RP Evans, LH (reprint author), NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, 903 S 4th St, Hamilton, MT 59840 USA. EM levans@niaid.nih.gov NR 71 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 4664 EP 4671 DI 10.1128/JVI.79.8.4664-4671.2005 PG 8 WC Virology SC Virology GA 912JJ UT WOS:000228073700011 PM 15795252 ER PT J AU Ruthel, G Demmin, GL Kallstrom, G Javid, MP Badie, SS Will, AB Nelle, T Schokman, R Nguyen, TL Carra, JH Bavari, S Aman, MJ AF Ruthel, G Demmin, GL Kallstrom, G Javid, MP Badie, SS Will, AB Nelle, T Schokman, R Nguyen, TL Carra, JH Bavari, S Aman, MJ TI Association of Ebola virus matrix protein VP40 with microtubules SO JOURNAL OF VIROLOGY LA English DT Article ID VESICULAR STOMATITIS-VIRUS; SWINE-FEVER VIRUS; SENDAI-VIRUS; BINDING PROPERTIES; VIRAL TRANSPORT; PLASMA-MEMBRANE; INFECTED-CELLS; IN-VITRO; TRANSCRIPTION; INTERACTS AB Viruses exploit a variety of cellular components to complete their life cycles, and it has become increasingly clear that use of host cell microtubules is a vital part of the infection process for many viruses. A variety of viral proteins have been identified that interact with microtubules, either directly or via a microtubule-associated motor protein. Here, we report that Ebola virus associates with microtubules via the matrix protein VP40. When transfected into mammalian cells, a fraction of VP40 colocalized with microtubule bundles and VP40 coimmunoprecipitated with tubulin. The degree of colocalization and microtubule bundling in cells was markedly intensified by truncation of the C terminus to a length of 317 amino acids. Further truncation to 308 or fewer amino acids abolished the association with microtubules. Both the full-length and the 317-amino-acid truncation mutant stabilized microtubules against depolymerization with nocodazole. Direct physical interaction between purified VP40 and tubulin proteins was demonstrated in vitro. A region of moderate homology to the tubulin binding motif of the microtubule-associated protein MAP2 was identified in VP40. Deleting this region resulted in loss of microtubule stabilization against drug-induced depolymerization. The presence of VP40-associated microtubules in cells continuously treated with nocodazole suggested that VP40 promotes tubulin polymerization. Using an in vitro polymerization assay, we demonstrated that VP40 directly enhances tubulin polymerization without any cellular mediators. These results suggest that microtubules may play an important role in the Ebola virus life cycle and potentially provide a novel target for therapeutic intervention against this highly pathogenic virus. C1 USAMRIID, Frederick, MD 21702 USA. NCI, Dev Therapeut Program, Frederick, MD 21701 USA. RP Aman, MJ (reprint author), USAMRIID, 1425 Porter St, Frederick, MD 21702 USA. EM amanm@ncifcrf.gov OI Javid, Melodi/0000-0002-8163-6881 FU PHS HHS [P41-04050] NR 58 TC 42 Z9 44 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 4709 EP 4719 DI 10.1128/JVI.79.8.4709-4719.2005 PG 11 WC Virology SC Virology GA 912JJ UT WOS:000228073700016 PM 15795257 ER PT J AU Senkevich, TG Moss, B AF Senkevich, TG Moss, B TI Vaccinia virus H2 protein is an essential component of a complex involved in virus entry and cell-cell fusion SO JOURNAL OF VIROLOGY LA English DT Article ID NEUTRALIZING MONOCLONAL-ANTIBODIES; INTRACELLULAR MATURE VIRIONS; SURFACE HEPARAN-SULFATE; ENVELOPE PROTEIN; A27L PROTEIN; IN-VITRO; MEMBRANE; IDENTIFICATION; RELEASE; FORMS AB The vaccinia virus H2R gene (VACWR 100) is conserved in all sequenced members of the poxvirus family and encodes a protein with a predicted transmembrane domain and four invariant cysteines. A recombinant vaccinia virus, in which expression of the H2 protein is stringently regulated, was unable to replicate without inducer. However, under nonpermissive conditions, all stages of virus morphogenesis appeared normal and extracellular virions were detected at the tips of actin tails. Nevertheless, virus did not spread to neighboring cells nor did syncytia form after low-pH treatment. Purified -H2 and +H2 virions from cells infected in the absence or presence of inducer, respectively, were indistinguishable in microscopic appearance and contained the same complement of major proteins, though only +H2 virions were infectious. The -H2 virions bound to cells, but their cores did not penetrate into the cytoplasm. In addition, exogenously added -H2 virions were unable to mediate the formation of syncytia after low-pH treatment. In contrast, virions lacking the A27 (p14) protein, which was previously considered to have an essential role in fusion, penetrated cells and induced extensive syncytia. The properties of H2, however, are very similar to those recently reported for the A28 protein. Moreover, coimmunoprecipitation experiments indicated an interaction between H2 and A28. Therefore, H2 and A28 are the only proteins presently known to be specifically required for vaccinia virus entry and are likely components of a fusion complex. C1 NIAID, NIH, Viral Dis Lab, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, NIH, Viral Dis Lab, 4 Ctr Dr,MSC 0445, Bethesda, MD 20892 USA. EM bmoss@nih.gov NR 46 TC 64 Z9 65 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 4744 EP 4754 DI 10.1128/JVI.79.8.4744-4754.2005 PG 11 WC Virology SC Virology GA 912JJ UT WOS:000228073700019 PM 15795260 ER PT J AU Desmezieres, E Gupta, N Vassell, R He, Y Peden, K Sirota, L Yang, ZN Wingfield, P Weiss, CD AF Desmezieres, E Gupta, N Vassell, R He, Y Peden, K Sirota, L Yang, ZN Wingfield, P Weiss, CD TI Human immunodeficiency virus (HIV) gp41 escape mutants: Cross-resistance to peptide inhibitors of HIV fusion and altered receptor activation of gp120 SO JOURNAL OF VIROLOGY LA English DT Article ID TYPE-1 ENVELOPE GLYCOPROTEIN; TRANSMEMBRANE PROTEIN GP41; MEMBRANE-FUSION; COILED-COIL; INTERHELICAL INTERACTIONS; FUNCTIONAL-ANALYSIS; ENFUVIRTIDE T-20; ATOMIC-STRUCTURE; 6-HELIX BUNDLE; DOMAIN AB Human immunodeficiency virus (HIV) infects cells by fusing with cellular membranes. Fusion occurs when the envelope glycoprotein (Env) undergoes conformational changes while binding to cellular receptors. Fusogenic changes involve assembly of two heptad repeats in the ectodomain of the gp41 transmembrane subunit to form a six-helix bundle (6HB), consisting of a trimeric N heptad repeat (N-HR) coiled-coil core with three antiparallel C heptad repeats (C-HRs) that pack in the coiled-coil grooves. Peptides corresponding to the N-and C-HRs (N and C peptides, respectively) interfere with formation of the 6HB in a dominant-negative manner and are emerging as a new class of antiretroviral therapeutics for treating HIV infection. We generated an escape mutant virus with resistance to an N peptide and show that early resistance involved two mutations, one each in the N- and C-HRs. The mutations conferred resistance not only to the selecting N peptide but also to C peptides, as well as other types of N-peptide inhibitors. Moreover, the N-HR mutation altered sensitivity to soluble CD4. Biophysical studies suggest that the 6HB with the resistance mutations is more stable than the wild-type 6HB and the 6HB formed by inhibitor binding to either wild-type or mutant C-HR. These findings provide new insights into potential mechanisms of resistance to HIV peptide fusion inhibitors and dominant-negative inhibitors in general. The results are discussed in the context of current models of Env-mediated membrane fusion. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Biostat, Bethesda, MD 20892 USA. Natl Inst Arthritis & Musculoskeletal Dis, Prot Express Lab, NIH, Bethesda, MD USA. RP Weiss, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, HFM-466,Bldg 29,Room 532,8800 Rockville Pike, Bethesda, MD 20892 USA. EM cdweiss@helix.nih.gov RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 NR 43 TC 17 Z9 18 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 4774 EP 4781 DI 10.1128/JVI.79.4.4774-4781.2005 PG 8 WC Virology SC Virology GA 912JJ UT WOS:000228073700022 PM 15795263 ER PT J AU Ou, W Silver, J AF Ou, W Silver, J TI Inhibition of murine leukemia virus envelope protein (Env) processing by intracellular expression of the Env N-terminal heptad repeat region SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MEDIATED CELL-FUSION; MEMBRANE-FUSION; COILED-COIL; TRANSDOMINANT INTERFERENCE; INFLUENZA HEMAGGLUTININ; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; VIRAL ENTRY; HIV-1 GP41 AB A conserved structural motif in the envelope proteins of several viruses consists of an N-terminal, alpha-helical, trimerization domain and a C-terminal region that refolds during fusion to bind the N-helix trimer. Interaction between the N and C regions is believed to pull viral and target membranes together in a crucial step during membrane fusion. For several viruses with type I fusion proteins, C regions pack as alpha-helices in the grooves between N-helix monomers, and exogenously added N- and C-region peptides block fusion by inhibiting the formation of the six-helix bundle. For other viruses, including influenza virus and murine leukemia virus (MLV), there is no evidence for comparably extended C-region alpha-helices, although a short, non-alpha-helical interaction structure has been reported for influenza virus. We tested candidate N-helix and C-region peptides from MLV for their ability to inhibit cell fusion but found no inhibitory activity. In contrast, intracellular expression of the MLV N-helix inhibited fusion by efficiently blocking proteolytic processing and intracellular transport of the envelope protein. The results highlight another mechanism by which the N-helix peptides can inhibit fusion. C1 NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Silver, J (reprint author), NIAID, Mol Microbiol Lab, NIH, Bldg 4,Room 336, Bethesda, MD 20892 USA. EM jsilver@nih.gov NR 45 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 4782 EP 4792 DI 10.1128/JVI.79.8.4782-4792.2005 PG 11 WC Virology SC Virology GA 912JJ UT WOS:000228073700023 PM 15795264 ER PT J AU Baxter, MK McPhillips, MG Ozato, K McBride, AA AF Baxter, MK McPhillips, MG Ozato, K McBride, AA TI The mitotic chromosome binding activity of the papillomavirus E2 protein correlates with interaction with the cellular chromosomal protein, Brd4 SO JOURNAL OF VIROLOGY LA English DT Article ID NUCLEAR ANTIGEN 1; SARCOMA-ASSOCIATED HERPESVIRUS; BOVINE PAPILLOMAVIRUS; BROMODOMAIN PROTEIN; DNA-REPLICATION; TRANSCRIPTIONAL ACTIVATION; TRANSACTIVATION DOMAIN; SACCHAROMYCES-CEREVISIAE; EPISOMAL MAINTENANCE; ONCOGENE EXPRESSION AB The papillomavirus transcriptional activator, E2, is involved in key functions of the viral life cycle. These include transcriptional regulation, viral DNA replication, and viral genome segregation. The transactivation domain of E2 is required for each of these functions. To identify the regions of the domain that mediate binding to mitotic chromosomes, a panel of mutations has been generated and their effect on various E2 functions has been analyzed. A structural model of the bovine papillomavirus type 1 (BPV1) E2 transactivation domain was generated based on its homology with the solved structure of the human papillomavirus type 16 (HPV16) domain. This model was used to identify distinct surfaces of the domain to be targeted by point mutation to further delineate the functional region of the transactivation domain responsible for mitotic chromosome association. The mutated E2 proteins were assessed for mitotic chromosome binding and, in addition, transcriptional activation and transcriptional repression activities. Mutation of amino acids R37 and 173, which are located on a surface of the domain that in HPV16 E2 is reported to mediate self-interaction, completely eliminated mitotic chromosome binding. Mitotic chromosome binding activity was found to correlate well with the ability to interact with the cellular chromosomal associated factor Brd4, which has recently been proposed to mediate the association between BPV1 E2 and mitotic chromosomes. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP McBride, AA (reprint author), NIAID, Viral Dis Lab, NIH, Bldg 4,Room 137,4 Ctr Dr,MSC 0455, Bethesda, MD 20892 USA. EM amcbride@nih.gov OI McBride, Alison/0000-0001-5607-5157 NR 64 TC 83 Z9 86 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 4806 EP 4818 DI 10.1128/JVI.79.8.4806-4818.2005 PG 13 WC Virology SC Virology GA 912JJ UT WOS:000228073700025 PM 15795266 ER PT J AU Walter, BL Wehrly, K Swanstrom, R Platt, E Kabat, D Chesebro, B AF Walter, BL Wehrly, K Swanstrom, R Platt, E Kabat, D Chesebro, B TI Role of low CD4 levels in the influence of human immunodeficiency virus type 1 envelope V2 and V2 regions on entry and spread in macrophages SO JOURNAL OF VIROLOGY LA English DT Article ID AIDS PATIENTS; HIV-1 ENTRY; MONOCYTE-MACROPHAGES; SYNCYTIUM FORMATION; GP120 GLYCOPROTEIN; RECEPTOR-BINDING; VARIABLE LOOPS; RHESUS-MONKEYS; VIRAL ENTRY; TROPISM AB Human immunodeficiency virus type 1 (HIV-1) isolates vary in their ability to infect macrophages. Previous experiments have mapped viral determinants of macrophage infectivity to the V3 hypervariable region of the HIV-1 envelope glycoprotein. In our earlier studies, V1 and V2 sequences of HIV-1 were also shown to alter the ability of virus to spread in macrophage cultures, whereas no effect was seen in lymphocyte cultures. In the present study, determinants that allowed certain HIV-1 clones to infect and spread in macrophages were primarily mapped to the V2 region and were found to act by influencing early events of viral infection. By an assay of viral entry into macrophages, it was shown that viruses with the V2 region from the Ba-L strain of HIV-1 had > 10-fold-higher entry efficiency than viruses with the V2 region derived from the NL4-3 strain. V1 region differences between these groups caused a twofold difference in entry. The known low expression of CD4 on macrophages appeared to be important in this process. In entry assays conducted with HeLa cell lines expressing various levels of CD4 and CCR5, low levels of CD4 influenced the efficiency of entry and fusion which were dependent on viral V1 and V2 envelope sequences. In contrast, no effect of V1 or V2 was seen in HeLa cells expressing high levels of CD4. Thus, the limited expression of CD4 on macrophages or other cell types could serve as a selective factor for V1 and V2 envelope sequences, and this selection could in turn influence many aspects of AIDS pathogenesis in vivo. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. Univ N Carolina, UNC Ctr AIDS Res, Chapel Hill, NC USA. Oregon Hlth & Sci Univ, Dept Biochem & Mol Biol, Portland, OR 97201 USA. RP Chesebro, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, 903 S 4th St, Hamilton, MT 59840 USA. EM behesebro@niaid.nih.gov FU NIAID NIH HHS [R01 AI044667, P30 AI050410] NR 48 TC 48 Z9 49 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 4828 EP 4837 DI 10.1128/JVI.79.8.4828-4837.2005 PG 10 WC Virology SC Virology GA 912JJ UT WOS:000228073700027 PM 15795268 ER PT J AU Kim, EY Busch, M Abel, K Fritts, L Bustamante, P Stanton, J Lu, D Wu, S Glowczwskie, J Rourke, T Bogdan, D Piatak, M Lifson, JD Desrosiers, RC Wolinsky, S Miller, CJ AF Kim, EY Busch, M Abel, K Fritts, L Bustamante, P Stanton, J Lu, D Wu, S Glowczwskie, J Rourke, T Bogdan, D Piatak, M Lifson, JD Desrosiers, RC Wolinsky, S Miller, CJ TI Retroviral recombination in vivo: Viral replication patterns and genetic structure of simian immunodeficiency virus (SIV) populations in rhesus macaques after simultaneous or sequential intravaginal inoculation with SIVmac239 Delta vpx/Delta vpr and SIVmac239 Delta nef SO JOURNAL OF VIROLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE; NEF GENE; HIV-1; INFECTION; RESPONSES; TYPE-1; RESISTANCE; DIVERSITY; SUPERINFECTION; TRANSMISSION AB To characterize the occurrence, frequency, and kinetics of retroviral recombination in vivo, we intravaginally inoculated rhesus macaques, either simultaneously or sequentially, with attenuated simian immunodeficiency virus (SIV) strains having complementary deletions in their accessory genes and various degrees of replication impairment. In monkeys inoculated simultaneously with SIVmac239 Delta vpx/Delta vpr and SIVmac239 Delta nef, recombinant wild-type (wt) virus and wild-type levels of plasma viral RNA (vRNA) were detected in blood by 2 weeks postinoculation. In monkeys inoculated first with SIVmac239 Delta vpx/Delta vpr and then with SIVmac239 Delta nef, recombination occurred but was associated with lower plasma vRNA levels than plasma vRNA levels seen for monkeys inoculated intravaginally with wt SIVmac239. In one monkey, recombination occurred 6 weeks after the challenge with SIVmac239 Delta nef when plasma SIVmac239 Delta vpx/Delta vpr RNA levels were undetectable. In monkeys inoculated first with the more highly replicating strain, SIVmac239 Delta nef, and then with SIVmac239 Delta vpx/Delta vpr, wild-type recombinant virus was not detected in blood or tissues. Instead, a virus that had repaired the deletion in the nef gene by a compensatory mutation was found in one animal. Overall, recombinant SIV was eventually found in four of six animals intravaginally inoculated with the two SIVmac239 deletion mutants. These findings show that recombination can occur readily in vivo after mucosal SIV exposure and thus contributes to the generation of viral genetic diversity and enhancement of viral fitness. C1 Univ Calif Davis, CNPRC, Sch Med, Davis, CA 95616 USA. Univ Calif Davis, Ctr Comparat Med, Sch Med, Davis, CA 95616 USA. Univ Calif Davis, Div Infect Dis, Sch Med, Davis, CA 95616 USA. Northwestern Univ, Div Infect Dis, Feinberg Sch Med, Chicago, IL 60611 USA. NCI, AIDS Vaccine Program, SAIC Fraderick Inc, Frederick, MD 21701 USA. Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. RP Miller, CJ (reprint author), Univ Calif Davis, CNPRC, Sch Med, 1 Shields Ave, Davis, CA 95616 USA. EM cjmiller@ucdavis.edu RI Wolinsky, Steven/B-2893-2012 FU NCI NIH HHS [N01CO12400]; NCRR NIH HHS [P51 RR000169]; NIAID NIH HHS [U19 AI051596] NR 32 TC 27 Z9 27 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 4886 EP 4895 DI 10.1128/JVI.79.8.4886-4895.2005 PG 10 WC Virology SC Virology GA 912JJ UT WOS:000228073700033 PM 15795274 ER PT J AU Padron, E Bowman, V Kaludov, N Govindasamy, L Levy, H Nick, P McKenna, R Muzyczka, N Chiorini, JA Baker, TS Agbandje-McKenna, M AF Padron, E Bowman, V Kaludov, N Govindasamy, L Levy, H Nick, P McKenna, R Muzyczka, N Chiorini, JA Baker, TS Agbandje-McKenna, M TI Structure of adeno-associated virus type 4 SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN GENE-THERAPY; HEPARAN-SULFATE PROTEOGLYCAN; CANINE TRANSFERRIN RECEPTOR; PARVOVIRUS CAPSID STRUCTURE; SIALIC-ACID BINDING; FELINE PARVOVIRUSES; HOST-RANGE; FUNCTIONAL IMPLICATIONS; 3-DIMENSIONAL STRUCTURE; ANGSTROM RESOLUTION AB Adeno-associated virus (AAV) is a member of the Parvoviridae, belonging to the Dependovirus genus. Currently, several distinct isolates of AAV are in development for use in human gene therapy applications due to their ability to transduce different target cells. The need to manipulate AAV capsids for specific tissue delivery has generated interest in understanding their capsid structures. The structure of AAV type 4 (AAV4), one of the most antigenically distinct serotypes, was determined to 13-angstrom resolution by cryo-electron microscopy and image reconstruction. A pseudoatomic model was built for the AAV4 capsid by use of a structure-based sequence alignment of its major capsid protein, VP3, with that of AAV2, to which AAV4 is 58% identical and constrained by its reconstructed density envelope. The model showed variations in the surface loops that may account for the, differences in receptor binding and antigenicity between AAV2 and AAV4. The AAV4 capsid surface topology also shows an unpredicted structural similarity to that of Aleutian mink disease virus and human parvovirus B19, autonomous members of the genus, despite limited sequence homology. C1 Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Powell Gene Therapy Ctr, Gainesville, FL 32610 USA. Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. Natl Inst Dent & Craniofacial Res, GTTB, NIH, Bethesda, MD USA. RP Agbandje-McKenna, M (reprint author), Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. EM mckenna@ufl.edu FU NHLBI NIH HHS [P01 HL51811, P01 HL051811]; NIAID NIH HHS [P01 AI045976]; NIGMS NIH HHS [R01 GM033050, R37 GM033050, GM33050] NR 70 TC 56 Z9 58 U1 2 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 5047 EP 5058 DI 10.1128/JVI.79.8.5047-5058.2005 PG 12 WC Virology SC Virology GA 912JJ UT WOS:000228073700049 PM 15795290 ER PT J AU Cohen, JI Krogmann, T Bontems, S Sadzot-Delvaux, C Pesnicak, L AF Cohen, JI Krogmann, T Bontems, S Sadzot-Delvaux, C Pesnicak, L TI Regions of the varicella-zoster virus open reading frame 63 latency-associated protein important for replication in vitro are also critical for efficient establishment of latency SO JOURNAL OF VIROLOGY LA English DT Article ID HERPES-SIMPLEX-VIRUS; HUMAN TRIGEMINAL GANGLIA; DORSAL-ROOT GANGLIA; VIRAL REPLICATION; GENE-EXPRESSION; KINASE; VZV; PHOSPHORYLATION; TRANSCRIPTION; LOCALIZATION AB Varicella-zoster virus (VZV) open reading frame 63 (ORF63) is one of the most abundant transcripts expressed during VZV latency in humans, and ORF63 protein has been detected in human ganglia by several laboratories. Deletion of over 90% of the ORF63 gene showed that the protein is required for efficient establishment of latency in rodents. We have constructed viruses with a series of mutations in ORF63. While prior experiments showed that transfection of cells with a plasmid expressing ORF63 but lacking the putative nuclear localization signal of the protein resulted in increased expression of the protein in the cytoplasm, we found that ORF63 protein remained in the nucleus in cells infected with a VZV ORF63 nuclear localization signal deletion mutant. This mutant was not impaired for growth in cell culture or for latency in rodents. Replacement of five serine or threonine phosphorylation sites in ORF63 with alanines resulted in a virus that was impaired for replication in vitro and for latency. A series of ORF63 carboxy-terminal mutants showed that the last 70 amino acids do not affect replication in vitro or latency in rodents; however, the last 108 amino acids are important for replication and latency. Thus, regions of ORF63 that are important for replication in vitro are also required for efficient establishment of latency. C1 NIH, Lab Clin Infect Div, Med Virol Sect, Bethesda, MD 20892 USA. Univ Liege, Lab Virol & Immunol, Liege, Belgium. RP Cohen, JI (reprint author), NIH, Lab Clin Infect Div, Med Virol Sect, Bldg 10,Room 11N228,10 Ctr Dr, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov NR 27 TC 27 Z9 31 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 5069 EP 5077 DI 10.1128/JVI.79.8.5069-5077.2005 PG 9 WC Virology SC Virology GA 912JJ UT WOS:000228073700051 PM 15795292 ER PT J AU Goldstein, S Ourmanov, I Brown, CR Plishka, R Buckler-White, A Byrum, R Hirsch, VM AF Goldstein, S Ourmanov, I Brown, CR Plishka, R Buckler-White, A Byrum, R Hirsch, VM TI Plateau levels of viremia correlate with the degree of CD4(+)-T-cell loss in simian immunodeficiency virus SIVagm-infected pigtailed macaques: Variable pathogenicity of natural SIVagm isolates SO JOURNAL OF VIROLOGY LA English DT Article ID AFRICAN-GREEN MONKEYS; VIRAL REPLICATION; SOOTY MANGABEYS; MANDRILLUS-SPHINX; TANTALUS MONKEYS; RHESUS-MONKEYS; IN-VIVO; HIGHLY DIVERGENT; HIV-1 INFECTION; AIDS VIRUSES AB Simian immunodeficiency virus from African green monkeys (SIVagm) results in asymptomatic infection in its natural host species. The virus is not inherently apathogenic, since infection of pigtailed (PT) macaques (Macaca nemestrina) with one isolate of SIVagm results in an immunodeficiency syndrome characterized by progressive CD4(+)-T-cell depletion and opportunistic infections. This virus was passaged once in a PT macaque and, thus, may not be entirely reflective of the virulence of the parental strain. The goal of the present study was to assess the pathogenicity of the PT-passaged isolate (SIVagm9063) and two primary SIVagm isolates in PT macaques, including the parental strain of the PT-passaged variant. Infection of macaques with any of the three isolates resulted in high levels of primary plasma viremia by 1 week after inoculation. Viremia was quickly controlled following infection with SIVagm155; these animals have maintained CD4(+)-T-cell subsets and remain healthy. The plateau levels among SIVagm90- and SIVagm9063-inoculated macaques varied widely from 100 to 1 million copies/ml of plasma. Three of four animals from each of these groups progressed to AIDS. Setpoint viremia and the degree of CD4(+)-T-cell loss at 6 months postinfection were not significantly different between macaques inoculated with SIVagm90 and SIVagm9063. However these parameters were significantly different in SIVagm155-inoculated macaques (P values of < 0.01). Considering all the macaques, the degree of CD4(+)-T-cell loss by 6 months postinfection correlated with the plateau levels of viremia. Thus, similar to SIVsm/mac infection of macaques and human AIDS, viral load is an excellent prognostic indicator of disease course. The inherent pathogenicity of natural SIVagm isolates varies, but such natural isolates are capable of inducing AIDS in macaques without prior macaque passage. C1 NIAID, LMM, NIH, Twinbrook Facil 2, Rockville, MD 20852 USA. Bioqual Inc, Rockville, MD USA. RP Hirsch, VM (reprint author), NIAID, LMM, NIH, Twinbrook Facil 2, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM vhirsch@niaid.nih.gov NR 61 TC 38 Z9 39 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 5153 EP 5162 DI 10.1128/JVI.79.8.5153-5162.2005 PG 10 WC Virology SC Virology GA 912JJ UT WOS:000228073700058 PM 15795299 ER PT J AU Monie, D Simmons, RP Nettles, RE Kieffer, TL Zhou, Y Zhang, HL Karmon, S Ingersoll, R Chadwick, K Zhang, H Margolick, JB Quinn, TC Ray, SC Wind-Rotolo, M Miller, M Persaud, D Siliciano, RF AF Monie, D Simmons, RP Nettles, RE Kieffer, TL Zhou, Y Zhang, HL Karmon, S Ingersoll, R Chadwick, K Zhang, H Margolick, JB Quinn, TC Ray, SC Wind-Rotolo, M Miller, M Persaud, D Siliciano, RF TI A novel assay allows genotyping of the latent reservoir for human immunodeficiency virus type 1 in the resting CD4(+) T cells of viremic patients SO JOURNAL OF VIROLOGY LA English DT Article ID ACTIVE ANTIRETROVIRAL THERAPY; BLOOD MONONUCLEAR-CELLS; HIV-INFECTED PATIENTS; IN-VITRO SELECTION; REVERSE-TRANSCRIPTASE; COMBINATION THERAPY; DRUG-RESISTANCE; GENETIC-CHARACTERIZATION; LIFELONG PERSISTENCE; PROTEASE INHIBITORS AB A latent reservoir for human immunodeficiency virus type 1 (HIV-1) consisting of integrated provirus in resting memory CD4(+) T cells prevents viral eradication in patients on highly active antiretroviral therapy (HAART). It is difficult to analyze the nature and dynamics of this reservoir in untreated patients and in patients failing therapy, because it is obscured by an excess of unintegrated viral DNA that constitutes-the majority of viral species in resting CD4(+) T cells from viremic patients. Therefore, we developed a novel culture assay that stimulates virus production from latent, integrated HIV-1 in resting CD4+ T cells in the presence of antiretroviral drugs that prevent the replication of unintegrated virus. Following activation, resting CD4(+) T cells with integrated HIV-1 DNA produced virus particles for several days, with peak production at day 5. Using this assay, HIV-1 pol sequences from the resting CD4(+) T cells of viremic patients were found to be genetically distinct from contemporaneous plasma virus. Despite the predominance of a relatively homogeneous population of drug-resistant viruses in the plasma of patients failing HAART, resting CD4(+) T cells harbored a diverse array of wild-type and archival drug-resistant viruses that were less fit than plasma virus in the context of current therapy. These results provide the first direct evidence that resting CD4(+) T cells serve as a stable reservoir for HIV-1 even in the setting of high levels of viremia. The ability to analyze archival species in viremic patients may have clinical utility in detecting drug-resistant variants not present in the plasma. C1 Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. Howard Hughes Med Inst, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. Merck Res Labs, West Point, PA USA. RP Siliciano, RF (reprint author), Johns Hopkins Univ, Sch Med, Broadway Res Bldg,Room 879,733 N Broadway St, Baltimore, MD 21205 USA. EM rsiliciano@jhmi.edu RI Ray, Stuart/B-7527-2008; OI Ray, Stuart/0000-0002-1051-7260; Simmons, Rachel/0000-0003-2498-7965 FU NIAID NIH HHS [R01 AI051178, AI43222, AI51178, K08 AI060367, R01 AI043222, R37 AI051178] NR 79 TC 33 Z9 34 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 5185 EP 5202 DI 10.1128/JVI.79.8.5185-5202.2005 PG 18 WC Virology SC Virology GA 912JJ UT WOS:000228073700061 PM 15795302 ER PT J AU Wu, XL Li, Y Crise, B Burgess, SM Munroe, DJ AF Wu, XL Li, Y Crise, B Burgess, SM Munroe, DJ TI Weak palindromic consensus sequences are a common feature found at the integration target sites of many retroviruses SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IN-VITRO; HIV-1 INTEGRATION; HUMAN GENOME; TYPE-1 CDNA; DNA; SELECTION; NUCLEOSOMES; PREFERENCES; COMPLEXES AB Integration into the host genome is one of the hallmarks of the retroviral life cycle and is catalyzed by virus-encoded integrases. While integrase has strict sequence requirements for the viral DNA ends, target site sequences have been shown to be very diverse. We carefully examined a large number of integration target site sequences from several retroviruses, including human immunodeficiency virus type 1, simian immunodeficiency virus, murine leukemia virus, and avian sarcoma-leukosis virus, and found that a statistical palindromic consensus, centered on the virus-specific duplicated target site sequence, was a common feature at integration target sites for these retroviruses. C1 NCI, Lab Mol Technol, Sci Applicat Int Corp, Frederick, MD 21701 USA. NCI, AIDS Vaccine Program, Sci Applicat Int Corp, Frederick, MD 21701 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. RP Wu, XL (reprint author), NCI, Lab Mol Technol, Sci Applicat Int Corp, 915 Toll HOuse Ave, Frederick, MD 21701 USA. EM forestwu@mail.nih.gov OI Burgess, Shawn/0000-0003-1147-0596 FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 26 TC 106 Z9 110 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 5211 EP 5214 DI 10.1128/JVI.79.8.5211-5214.2005 PG 4 WC Virology SC Virology GA 912JJ UT WOS:000228073700063 PM 15795304 ER PT J AU Wegienka, G Baird, DD AF Wegienka, G Baird, DD TI A comparison of recalled date of last menstrual period with prospectively recorded dates SO JOURNAL OF WOMENS HEALTH LA English DT Article ID PREGNANCIES; OUTCOMES; WOMEN AB Background: Women are often asked to recall the first day of their last menstrual period (LMP date) in a clinic setting (i.e., pregnancy dating, x-rays). There are no data supporting the validity of these reports. Methods: Using data from a group of 385 women ages 35 - 49 from a larger cohort study in the Washington, DC, area, we constructed menstrual segments from a prospective daily menstrual record. We then compared the first day of a menstrual segment to a woman's recalled LMP date at a subsequent study-related clinic appointment to assess the accuracy of recall. Results: More than half of the women (56%) accurately recalled their LMP date; 74% were within 1 day, and 81% were within 2 days. Women tended to underreport (25%) the length of time since their last menstrual period rather than overreport the length of time (19%). Recall accuracy did not vary significantly with education or by whether the woman usually recorded her menstrual cycle when not in the study. As one might expect, women with a shorter recall duration tended to report more accurately. Discussion: Women appear to recall their LMP dates fairly accurately, but inaccurate recall was not random. When length of recall was 3 weeks or longer, women tended to overestimate the time since LMP. This suggests that gestational age calculated from LMP date will tend to be overestimated. Most women can recall the date of their LMP reasonably well regardless of their education and whether they usually record their LMP dates. C1 Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, Detroit, MI 48202 USA. NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Wegienka, G (reprint author), Henry Ford Hlth Syst, Dept Biostat & Res Epidemiol, 1 Ford Pl, 3E, Detroit, MI 48202 USA. EM gwegien1@hfhs.org OI Baird, Donna/0000-0002-5544-2653 NR 10 TC 45 Z9 45 U1 0 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD APR PY 2005 VL 14 IS 3 BP 248 EP 252 DI 10.1089/jwh.2005.14.248 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 920XB UT WOS:000228727700007 PM 15857271 ER PT J AU Nadon, NL Mohr, D Becker, KG AF Nadon, NL Mohr, D Becker, KG TI National institute on aging microarray facility - Resources for gerontology research SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID GENE-EXPRESSION; CDNA ARRAYS AB The use of DNA microarrays allows rapid, large-scale analyses of changes in gene expression. This article introduces the National Institute on Aging Microarray Facility, developed to provide DNA microarrays to the biogerontology research community and to promote the use of this new technology. C1 NIA, Off Biol Resources & Resource Dev, Bethesda, MD 20892 USA. Johns Hopkins Univ, Microarray Facil, Baltimore, MD USA. NIA, Gene Express & Genom Unit, Ctr Gerontol Res, Baltimore, MD 21224 USA. RP Nadon, NL (reprint author), NIA, Off Biol Resources & Resource Dev, 7201 Wisconsin Ave,GW2C231, Bethesda, MD 20892 USA. EM nadonn@nia.nih.gov; beckerk@grc.nia.nih.gov OI Becker, Kevin/0000-0002-6794-6656 NR 10 TC 10 Z9 10 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2005 VL 60 IS 4 BP 413 EP 415 PG 3 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 928VX UT WOS:000229300900002 PM 15933377 ER PT J AU Smith, AL Ellison, FA McCoy, JP Chen, JC AF Smith, AL Ellison, FA McCoy, JP Chen, JC TI c-Kit expression and stem cell factor-induced hematopoietic cell proliferation are up-regulated in aged B6D2F1 mice SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID FUNCTIONAL FAILURE; PROTO-ONCOGENE; PIEBALD TRAIT; BONE-MARROW; W-LOCUS; GENOTYPE; NUMBERS; TRANSPLANTATION; SENESCENCE; PHENOTYPE AB Expression of c-Kit (CD117) and stem cell factor/c-Kit-mediated cell proliferation were tested in vitro in young and old B6D2F1 mice to study the role of c-Kit signaling in hematopoietic stem cell (HSC) senescence. Increasing age is associated with a significant increase in bone marrow (BM) cells without affecting mature blood cells. The number of c-Kit-expressing BM cells increased significantly in old mice when compared to young controls, to 201% in total BM cells, 261% in Lin(-) cells, 517% in Lin(-)CD34(+)Sca1(+) progenitor cells, and 1272% in Lin(-)CD34(-)Sca1(+) HSCs. Sorted Lin(-)Sca1(+)CD117(+) BM cells from an old mouse expanded 5-fold when cultured in vitro for 72 hours with stem cell factor at 25 ng/ml, which was significantly higher than a 2.5-fold expansion of the same cells from a young donor. HSCs and progenitor cells from B6D2F1 mice maintain extremely high proliferative potentials and do not reach proliferative arrest at old age during a normal life span. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. RP Chen, JC (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10,Clin Res Ctr Room 3-5132,10 Ctr Dr, Bethesda, MD 20892 USA. EM chenji@nhlbi.nih.gov NR 37 TC 9 Z9 9 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2005 VL 60 IS 4 BP 448 EP 456 PG 9 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 928VX UT WOS:000229300900007 PM 15933382 ER PT J AU Menon, V Wang, XL Greene, T Beck, GJ Kusek, JW Selhub, J Levey, AS Sarnak, MJ AF Menon, V Wang, XL Greene, T Beck, GJ Kusek, JW Selhub, J Levey, AS Sarnak, MJ TI Homocysteine in chronic kidney disease: Effect of low protein diet and repletion with B vitamins SO KIDNEY INTERNATIONAL LA English DT Article DE chronic kidney disease; homocysteine; vitamin supplementation; low protein diet ID STAGE RENAL-DISEASE; GLOMERULAR-FILTRATION-RATE; TOTAL PLASMA HOMOCYSTEINE; FOLIC-ACID; HEMODIALYSIS-PATIENTS; CARDIOVASCULAR-DISEASE; NUTRITIONAL-STATUS; DIALYSIS PATIENTS; VASCULAR-DISEASE; RISK-FACTOR AB Background. Data are limited on the determinants of homocysteine (tHcy) and its relationship with nutritional indices, and dietary protein intake, in the earlier stages of chronic kidney disease (CKD). Methods. Levels of tHcy were assayed at baseline (N= 804) and 1 year postrandomization (N= 678) in the Modification of Diet in Renal Disease (MDRD) Study [study A, glomerular filtration rate (GFR) 25 to 55 mL/min/1.73 m(2) and study B GFR 13 to 24 mL/min/1.73 m(2)]. Participants were randomly assigned to different blood pressure targets and protein diets and all subjects received a multivitamin supplement containing 1 mg of folic acid, 10 mg pyridoxal 5'-phosphate (PLP) and 6 mu g of vitamin B-12. Multivariable analyses were used to evaluate determinants of tHcy at baseline and 1 year. Results. The prevalence of hyperhomocysteinemia (tHcy > 15 mu mol/L) at baseline was 56% in study A and 85% in study B. Baseline tHcy was negatively correlated with measures of body fat and dietary protein intake. Folate, vitamin B-12, and GFR were the major determinants of tHcy levels. Of the patients with hyperhomocysteinemia at baseline, 49% and 24% reduced their tHcy levels at 1 year to <= 15 mu mol/L in study A and study B, respectively. There was no association between dietary protein intake and odds of developing hyperhomocysteinemia at 1 year in study A (P= 0.94) or study B (P= 0.10). Conclusion. Hyperhomocysteinemia is partly amenable to correction by vitamin supplementation in CKD stages 3 and 4. There is insufficient evidence to suggest that low tHcy is associated with poor nutritional status in the MDRD Study cohort. B vitamins and GFR, but not dietary protein, are the major determinants of tHcy in this patient population. C1 Tufts Univ New England Med Ctr, Dept Med, Div Nephrol, Boston, MA 02111 USA. Cleveland Clin Fdn, Dept Biostat & Epidemiol, Cleveland, OH 44195 USA. NIH, Bethesda, MD 20892 USA. Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA USA. RP Sarnak, MJ (reprint author), Tufts Univ New England Med Ctr, Dept Med, Div Nephrol, 750 Washington St,NEMC 391, Boston, MA 02111 USA. EM msarnak@tufts-nemc.org FU NIDDK NIH HHS [UO1 DK 35073, K23 DK02904] NR 39 TC 18 Z9 18 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 2005 VL 67 IS 4 BP 1539 EP 1546 DI 10.1111/j.1523-1755.2005.00234.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 905UR UT WOS:000227596500036 PM 15780109 ER PT J AU Balow, JE AF Balow, JE TI Nephropathy in the context of HIV infection SO KIDNEY INTERNATIONAL LA English DT Editorial Material DE HIV nephropathy; immune complex; glomerulonephritis ID ACQUIRED IMMUNODEFICIENCY SYNDROME; RENAL-DISEASE; INVOLVEMENT; HOSPITALS; SPECTRUM; VIRUS C1 NIH, Clin Res Ctr, Bethesda, MD 20892 USA. RP Balow, JE (reprint author), NIH, Clin Res Ctr, Room 5-2551, Bethesda, MD 20892 USA. EM james.e.balow@nih.gov NR 13 TC 13 Z9 13 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 2005 VL 67 IS 4 BP 1632 EP 1633 DI 10.1111/j.1523-1755.2005.00254.x PG 2 WC Urology & Nephrology SC Urology & Nephrology GA 905UR UT WOS:000227596500049 PM 15780122 ER PT J AU Hampshire, V Davis, JA AF Hampshire, V Davis, JA TI The role of the veterinary staff in mouse breeding colony management SO LAB ANIMAL LA English DT Article ID SYSTEM; MICE AB The rapid increase in the production and use of transgenic mice has been a boon for biomedical research and a challenge for the animal care and use programs responsible for providing housing and medical care to these animals. The authors suggest ways in which the veterinary staff can successfully organize and manage transgenic mouse breeding programs to reduce uncontrolled breeding and the problems associated with it. C1 US FDA, Ctr Vet Med, Rockville, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Hampshire, V (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20892 USA. EM vhampshi@cvm.fda.gov NR 9 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD APR PY 2005 VL 34 IS 4 BP 45 EP 49 DI 10.1038/laban0405-45 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 914DB UT WOS:000228204000011 PM 15806090 ER PT J AU Saika, S Ikeda, K Yamanaka, O Flanders, KC Nakajima, Y Miyamoto, T Ohnishi, Y Kao, WWY Muragaki, Y Ooshima, A AF Saika, S Ikeda, K Yamanaka, O Flanders, KC Nakajima, Y Miyamoto, T Ohnishi, Y Kao, WWY Muragaki, Y Ooshima, A TI Therapeutic effects of adenoviral gene transfer of bone morphogenic proteinalkali injury model in mice SO LABORATORY INVESTIGATION LA English DT Article DE bone morphogenic protein-7; gene therapy; adenovirus; cornea; alkali burn; wound healing; mouse ID GROWTH-FACTOR-BETA; AMNIOTIC MEMBRANE TRANSPLANTATION; EPITHELIAL-MESENCHYMAL TRANSITION; NF-KAPPA-B; TGF-BETA; MATRIX METALLOPROTEINASES; TRANSFORMING GROWTH-FACTOR-BETA-1; MYOFIBROBLAST DIFFERENTIATION; RECOMBINANT ADENOVIRUS; CELL-PROLIFERATION AB An alkali burn in the cornea is a common serious clinical problem often leading to permanent visual impairment. Since transforming growth factor-beta (TGF-beta) is involved in the response to corneal injury, we evaluated the therapeutic effects of adenoviral gene transfer of mouse bone morphogenic proten-7 (BMP-7), which has antagonistic effects on TGF-beta in tissue fibrosis. Burned cornea did not express endogenous BMP-7 mRNA and protein. Resurfacing of the burned cornea by invading conjunctival epithelium was accelerated by adenoviral introduction of BMP-7. Exogenous BMP- 7 expression also suppressed myofibroblast generation, appearance of monocytes/macrophages and expression of MCP-1, TGF-beta s, and collagen I alpha 2 chain in the affected stroma. Ectopic BMP- 7 did not suppress stromal neovascularization throughout the interval studied and also did not reduce VEGF mRNA expression at Day 10. Ectopic BMP- 7 in burned corneal tissue resulted in activation of Smad1/5/8 signaling and partial suppression of the phospho-Smad2 signal. These data suggest that overexpression of BMP- 7 is an effective strategy for treatment of ocular alkali burns. C1 Wakayama Med Univ, Dept Ophthalmol, Wakayama 6410012, Japan. Osaka City Univ, Grad Sch Med, Dept Anat, Abeno Ku, Osaka 558, Japan. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Med Ctr, Dept Ophthalmol, Cincinnati, OH 45267 USA. Wakayama Med Univ, Dept Pathol, Wakayama 6410012, Japan. RP Saika, S (reprint author), Wakayama Med Univ, Dept Ophthalmol, 811-1 Kimiidera, Wakayama 6410012, Japan. EM shizuya@wakayama-med.ac.jp FU NEI NIH HHS [EY 13755] NR 63 TC 30 Z9 32 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0023-6837 J9 LAB INVEST JI Lab. Invest. PD APR PY 2005 VL 85 IS 4 BP 474 EP 486 DI 10.1038/labinvest.3700247 PG 13 WC Medicine, Research & Experimental; Pathology SC Research & Experimental Medicine; Pathology GA 909KV UT WOS:000227859700005 PM 15696184 ER PT J AU Hebbar, V Shen, GX Hu, R Kim, BR Chen, C Korytko, PJ Crowell, JA Levine, BS Kong, ANT AF Hebbar, V Shen, GX Hu, R Kim, BR Chen, C Korytko, PJ Crowell, JA Levine, BS Kong, ANT TI Toxicogenomics of resveratrol in rat liver SO LIFE SCIENCES LA English DT Article DE resveratrol; in vivo; drug metabolizing enzymes; DNA arrays; gene expression ID TRANS-RESVERATROL; RED WINE; EPITHELIAL-CELLS; GENE-EXPRESSION; CANCER CELLS; INHIBITION; APOPTOSIS; ANTIOXIDANT; POLYPHENOLS; ENZYMES AB Resveratrol, a polyphenolic compound found in grape skin and peanuts has been shown to prevent many diseases including cardiovascular diseases and cancer. To better understand resveratrol's potential in vivo toxicity, we studied the dose response using cDNA stress arrays coupled with drug metabolizing enzymatic (DME) assays to investigate the expression of stress-responsive genes and Phase I and II detoxifying enzymes in rat livers. Male and female CD rats were treated with high doses of resveratrol (0.3, 1.0 and 3.0 gm/kg/day) for a period of 28 days. Total RNA from rat liver was reverse-transcribed using gene-specific primers and hybridized to stress-related cDNA arrays. Among female rats, Phase I DME genes were repressed at 0.3 and 1.0 gm/kg/day doses, while genes such as manganese superoxide dismutase, cytochrome P450 reductase, quinone oxidoreductase and thiosulfate sulfurtransferase demonstrated a dose-dependent increase in gene expression. The modulation of these liver genes may implicate the potential toxicity as observed among the rats at the highest dose level of resveratrol. Real-Time PCR was conducted on some of the Phase II DME genes and anti-oxidant genes to validate the cDNA array data. The gene expression from real-time PCR demonstrated good correlation with the cDNA array data. UGTIA genes were amongst the most robustly induced especially at the high doses of resveratrol. We next performed Phase I and Phase II enzymatic assays on cytochrome P450 2E1 (CYP2E1), cytochrome P450 1A1 (CYP1A1), NAD(P)H:quinone oxidoreductase (NQO1), glutathione S-transferase (GST) and UDP-glucuronosyl transferase (UGT). Induction of Phase II detoxifying enzymes was most pronounced at the highest dose of resveratrol. CYP1A1 activity demonstrated a decreasing trend among the 3 dose groups and CYP2E1 activity increased marginally among female rats over controls. In summary, at lower doses of resveratrol there are few significant changes in gene expression whereas the modulation of liver genes at the high dose of resveratrol may implicate the potential toxicity observed. (c) 2005 Elsevier Inc. All rights reserved. C1 Rutgers State Univ, Dept Pharmaceut, Ernest Mario Sch Pharm, Piscataway, NJ 08854 USA. Univ Illinois, Toxicol Res Lab, Chicago, IL 60612 USA. NCI, Rockville, MD USA. RP Kong, ANT (reprint author), Rutgers State Univ, Dept Pharmaceut, Ernest Mario Sch Pharm, 160 Frelinghuysen Rd, Piscataway, NJ 08854 USA. EM KongT@rci.rutgers.edu RI Chen, Chi/B-4618-2008 FU NCI NIH HHS [N01-CN-95132] NR 34 TC 78 Z9 81 U1 2 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 J9 LIFE SCI JI Life Sci. PD APR 1 PY 2005 VL 76 IS 20 BP 2299 EP 2314 DI 10.1016/j.lfs.2004.10.039 PG 16 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 905PG UT WOS:000227580700003 PM 15748624 ER PT J AU Wali, A Morin, PJ Hough, CD Lonardo, F Seya, T Carbone, M Pass, HI AF Wali, A Morin, PJ Hough, CD Lonardo, F Seya, T Carbone, M Pass, HI TI Identification of intelectin overexpression in malignant pleural mesothelioma by serial analysis of gene expression (SAGE) SO LUNG CANCER LA English DT Article DE intelectin; mesothelioma; SAGE; glycoprotein; lectin ID C-TYPE LECTIN; MOLECULAR-CLONING; HUMAN SERUM; CANCER; ASBESTOS; CELLS; GALECTIN-1; SURVIVAL; ANTIGEN; RATIOS AB Malignant pleural mesothelioma (MPM) is a fatal neoplasm with no acceptable curative approaches. We used serial analysis of gene expression (SAGE) to compare the gene expression pattern of a surgically resected MPM to the autologous normal mesothelium. Intelectin gene overexpression (> 139-fold) was found in the tumor. Online SAGE datasets revealed intelectin to be consistently present in mesothelioma(s), ovarian cancer, and colon cancer. Intelectin mRNA expression was found by RT-PCR in 4 of 5 resected MPM tumors, and Intelectin protein expression was confirmed by immunohistochemistry in 28 of 53 MPM tumors, and in 4 of 4 mesothelioma cell tines studied by Western blot. A marked induction in intelectin gene expression was observed among human primary mesothelial cells as a consequence of crocidolite asbestos exposure and simian virus 40 infection. Intelectin overexpression in mesothelioma could have potential screening, and therapeutic implications. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Wayne State Univ, Karmanos Canc Inst, Thorac Oncol Program, Detroit, MI 48201 USA. Wayne State Univ, John D Dingell VA Med Ctr, Detroit, MI 48201 USA. NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. Osaka Med Ctr Canc & Cardiovasc Dis, Osaka 5378511, Japan. Loyola Univ, Med Ctr, Dept Pathol, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. RP Pass, HI (reprint author), Wayne State Univ, Karmanos Canc Inst, Thorac Oncol Program, 3990 John R,Suite 2102, Detroit, MI 48201 USA. EM hpass@dmc.org RI Seya, Tsukasa/A-4336-2012 NR 30 TC 21 Z9 26 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0169-5002 J9 LUNG CANCER-J IASLC JI Lung Cancer PD APR PY 2005 VL 48 IS 1 BP 19 EP 29 DI 10.1016/j.lungcan.2004.10.011 PG 11 WC Oncology; Respiratory System SC Oncology; Respiratory System GA 916WZ UT WOS:000228418600003 PM 15777968 ER PT J AU Breuer, FA Kellman, P Griswold, MA Jakob, PM AF Breuer, FA Kellman, P Griswold, MA Jakob, PM TI Dynamic autocalibrated parallel imaging using temporal GRAPPA (TGRAPPA) SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE parallel imaging; dynamic imaging; cardiac imaging; real-time; GRAPPA; TSENSE ID SMASH AB Current parallel imaging techniques for accelerated imaging require a fully encoded reference data set to estimate the spatial coil sensitivity information needed for reconstruction. In dynamic parallel imaging a time-interleaved acquisition scheme can be used, which eliminates the need for separately acquiring additional reference data, since the signal from directly adjacent time frames can be merged to build a set of fully encoded full-resolution reference data for coil calibration. In this work, we demonstrate that a time-interleaved sampling scheme, in combination with autocalibrated GRAPPA (referred to as TGRAPPA), allows one to easily update the coil weights for the GRAPPA algorithm dynamically, thereby improving the acquisition efficiency. This method may update coil sensitivity estimates frame by frame, thereby tracking changes in relative coil sensitivities that may occur during the data acquisition. Published 2005 Wiley-Liss, Inc. C1 Univ Wurzburg, Dept Phys, D-97074 Wurzburg, Germany. NHLBI, Cardiac Energet Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Breuer, FA (reprint author), Univ Wurzburg, Dept Phys, EP 5, D-97074 Wurzburg, Germany. EM fxbreuer@physik.uni-wuerzburg.de OI Jakob, Peter/0000-0002-3481-5545 NR 11 TC 122 Z9 123 U1 3 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD APR PY 2005 VL 53 IS 4 BP 981 EP 985 DI 10.1002/mrm.20430 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 912HL UT WOS:000228068100032 PM 15799044 ER PT J AU Isenberg, JS Calzada, MJ Zhou, LG Guo, NH Lawler, J Wang, XQ Frazier, WA Roberts, DD AF Isenberg, JS Calzada, MJ Zhou, LG Guo, NH Lawler, J Wang, XQ Frazier, WA Roberts, DD TI Endogenous thrombospondin-1 is not necessary for proliferation but is pen-nissive for vascular smooth muscle cell responses to platelet-derived growth factor SO MATRIX BIOLOGY LA English DT Article DE thrombospondin-1; vascular smooth muscle cells; angiogenesis; proliferation chemotaxis ID INTEGRIN-ASSOCIATED PROTEIN; C-TERMINAL DOMAIN; FACTOR RECEPTOR-BETA; ENDOTHELIAL-CELLS; EXTRACELLULAR-MATRIX; IN-VITRO; CARCINOMA-CELLS; DNA-SYNTHESIS; TUMOR-GROWTH; ANGIOGENESIS AB We have reexamined the role of endogenous thrombospondin-1 (TSP1) in growth and motility of vascular smooth muscle cells (SMCs). Based on the ability of aortic-derived SMCs isolated from TSP1 null mice and grown in the absence of exogenous TSP1 to grow at comparable rates and to a slightly higher density than equivalent cells from wild-type mice, TSP1 is not necessary for their growth. Low concentrations of exogenous TSP1 stimulate growth of TSP1 null SMCs, but higher doses of TSP1 or its C-terminal domain are inhibitory. However, SMCs from TSP1 null mice are selectively deficient in chemotactic and proliferative responses to platelet-derived growth factor and in outgrowth in three-dimensional cultures. Recombinant portions of the N- and C-terminal domains of TSP1 stimulate SMC chemotaxis through different integrin receptors. Based on these data, the relative deficiency in SMC outgrowth during an ex vivo angiogenic response of muscle tissue from TSP1 null mice is probably due to restriction of platelet-derived growth factor dependent SMC migration and/or proliferation. © 2005 Elsevier B.V./International Society of Matrix Biology. All rights reserved. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Biochem & Mol Biophys, St Louis, MO 63110 USA. RP Isenberg, JS (reprint author), NCI, Pathol Lab, NIH, Bldg 10,Room 2A33,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. EM isenberj@mail.nih.gov RI Roberts, David/A-9699-2008 OI Roberts, David/0000-0002-2481-2981 FU NCI NIH HHS [CA92644]; NHLBI NIH HHS [HL68003, HL54390] NR 50 TC 42 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0945-053X J9 MATRIX BIOL JI Matrix Biol. PD APR PY 2005 VL 24 IS 2 BP 110 EP 123 DI 10.1016/j.matbio.2005.01.002 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 932RI UT WOS:000229570600004 PM 15890262 ER PT J AU Klabunde, CN Reeve, BB Harlan, LC Davis, WW Potosky, AL AF Klabunde, CN Reeve, BB Harlan, LC Davis, WW Potosky, AL TI Do patients consistently report comorbid conditions over time? Results from the prostate cancer outcomes study SO MEDICAL CARE LA English DT Article DE comorbidity; survey research; health status; prostate cancer ID MEDICAL RECORDS; BREAST-CANCER; QUESTIONNAIRE DATA; CHRONIC-DISEASES; WOMEN; MORTALITY; AGREEMENT; ACCURACY; RISK; AGE AB Background: Comorbidity is an important dimension of patient health status. However, limited attention has been given to assessing the reliability of patient-reported data on comorbid conditions. Objectives: We sought to evaluate the consistency of self-report of 12 comorbid conditions at 3 distinct time points and examine the sociodemographic, clinical, health status, and survey factors associated with reliability. Study Design: We undertook a longitudinal cohort analysis of survey and medical record abstract data obtained from a population-based sample of 3095 prostate cancer survivors. Methods: Consistent and inconsistent response patterns were assessed using descriptive statistics and regression modeling. Results: More than half of the cohort demonstrated consistent responses to all comorbid condition questionnaire items. Arthritis had the highest (13%) and liver disease the lowest (1%) proportion of inconsistent responses. Older age, lower income, and poorer general and mental health status were significant predictors of inconsistent responses. Subset analyses of the 4 most prevalent comorbid conditions (ie, arthritis, diabetes, hypertension, and depression) showed that respondents who reported that they were limited by, or taking prescription medicine for, the condition were more likely to provide consistent responses than those neither limited nor taking medicine. Response consistencies of 92% or better were obtained for 11 of the 12 conditions. Conclusions: Men with a relatively recent prostate cancer diagnosis are generally able to provide reliable reports of their concomitant health conditions. To increase the likelihood of obtaining reliable data, investigators should consider ascertaining condition severity and current medical management when querying subjects about comorbid conditions in surveys. C1 NCI, Appl Res Program, Hlth Serv & Econ Branch, Bethesda, MD 20892 USA. NCI, Appl Res Program, Outcomes Res Branch, Bethesda, MD 20892 USA. NCI, Stat Res & Applicat Branch, Surveillance Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Klabunde, CN (reprint author), NCI, Appl Res Program, Hlth Serv & Econ Branch, Execut Plaza N,Room 4005,6130 Execut Blvd, Bethesda, MD 20892 USA. EM ck97b@nih.gov NR 27 TC 37 Z9 37 U1 4 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 2005 VL 43 IS 4 BP 391 EP 400 DI 10.1097/01.mlr.0000156851.80900.d1 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 910EU UT WOS:000227914000010 PM 15778642 ER PT J AU Goldstein, RB Rotheram-Borus, MJ Johnson, MO Weinhardt, LS Remien, RH Lightfoot, M Catz, SL Gore-Felton, C Kirshenbaum, S Morin, SF AF Goldstein, RB Rotheram-Borus, MJ Johnson, MO Weinhardt, LS Remien, RH Lightfoot, M Catz, SL Gore-Felton, C Kirshenbaum, S Morin, SF CA NIMH Healthy Living Trial Group TI Insurance coverage, usual source of care, and receipt of clinically indicated care for comorbid conditions among adults living with human immunodeficiency virus SO MEDICAL CARE LA English DT Article DE HIV; comorbidity; antiretroviral therapy; antidepressants; Pneumocystis carinii pneumonia prophylaxis; addiction treatment ID ACTIVE ANTIRETROVIRAL THERAPY; INJECTION-DRUG USERS; HEALTH-SERVICES; HIV-INFECTION; UNITED-STATES; ASSISTANCE PROGRAMS; MENTAL-HEALTH; DEPRESSION; AIDS; ABUSE AB Background and Objectives: Associations of insurance coverage and source of care with use of human immunodeficiency virus (HIV)-related health, mental health, and substance abuse services are examined in a large, diverse, highly active antiretroviral therapy-era cohort. Methods: Adults who were infected with HIV (n = 3818) were interviewed in clinics and community agencies in Los Angeles, Milwaukee, New York, and San Francisco regarding drug use behaviors, health status, and health care utilization. Results: Most participants were insured by Medicaid. During the previous 3 months, 90% of privately insured, 87% of publicly insured, and 78% of uninsured participants had visited any provider. Publicly and privately insured participants were similar in receipt of antiretrovirals, prophylaxis against Pneumocystis carinii pneumonia, substance abuse services, and antidepressants. Uninsured participants were less likely to receive antiretrovirals but were more likely to use substance abuse services. Participants with no usual source of care were less likely to receive PCP prophylaxis. Conclusions: A lack of insurance is associated with barriers to care, but the advantage of private over public coverage appears smaller than in previous studies. PCP prophylaxis, substance abuse treatment, and antidepressants remain markedly underutilized. Educational initiatives about these treatments targeting providers and patients are indicated. C1 Univ Calif Los Angeles, Ctr Community Hlth, Inst Neuropsychiat, Los Angeles, CA USA. Univ Calif San Francisco, Ctr AIDS Prevent Studies, San Francisco, CA 94143 USA. Med Coll Wisconsin, Ctr AIDS Intervent Res, Milwaukee, WI 53226 USA. New York State Psychiat Inst & Hosp, HIV Ctr Clin & Behav Studies, New York, NY 10032 USA. Columbia Univ, New York, NY USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98121 USA. RP Goldstein, RB (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH, 5635 Fishers Lane,Room 3068,MS 9304, Bethesda, MD 20892 USA. EM goldster@mail.nih.gov OI Goldstein, Rise/0000-0002-9603-9473 FU NIMH NIH HHS [U10-MH57615, P30 MH043520, P30-MH062246, P30-MH43520, P30-MH57226, U01-MH57636, U10-MH57616, U10-MH57631] NR 55 TC 25 Z9 25 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD APR PY 2005 VL 43 IS 4 BP 401 EP 410 DI 10.1097/01.mlr.0000156850.86917.f8 PG 10 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 910EU UT WOS:000227914000011 PM 15778643 ER PT J AU Rodriguez, A Muller, DC Engelhardt, M Andres, R AF Rodriguez, A Muller, DC Engelhardt, M Andres, R TI Contribution of impaired glucose tolerance in subjects with the metabolic syndrome: Baltimore Longitudinal Study of Aging SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID AMERICAN-DIABETES-ASSOCIATION; DENSITY-LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR-DISEASE; FASTING GLUCOSE; OLDER-ADULTS; FOLLOW-UP; RISK; MORTALITY; DIAGNOSIS; MELLITUS AB Background: In addition to fasting plasma glucose (FPG), we examined the contribution of the oral glucose tolerance test (OGTT) in the prevalence of subjects with the metabolic syndrome (MS). Methods and Results: Study participants were white adults in the Baltimore Longitudinal Study of Aging who underwent a fasting 2-hour OGTT. In men between the ages of 20 to 39, 40 to 59, 60 to 79, and 80 to 95 years, the prevalence of the MS by Adult Treatment Panel (ATP) III criteria (which excludes OGTT) was 11%, 28%, 32%, and 15%, respectively; whereas in women the prevalence was 5%, 12%, 24%, and 16%, respectively. If the current ATPIII dysglycemia criteria also included a 2-hour postchallenge glucose (2hPG) of 7.8 mmol/L or higher, the prevalence of the MS increased from 25% to 33% in men and from 15% to 21% in women (P < .0001). In study participants with FPG less than 5.6 mmol/L, the prevalence of the MS increased from 16% to 23% in men and from 9% to 13% in women. In men between the ages of 20 to 39, 40 to 59, 60 to 79, and 80 to 95 years and FPG less than 5.6 mmol/L, the prevalence of the MS increased to 15%, 32%, 40%, and 29%, respectively (P < .005 for men between 40 and 95 years of age), with inclusion of an abnormal 2hPG. In women between the ages of 20 to 39, 40 to 59, 60 to 79, and 80 to 95 years and FPG less than 5.6 mmol/L, the prevalence of the MS increased to 7%, 14%, 33%, and 31%, respectively, with inclusion of an abnormal 2hPG (P < .001 for women between 60 and 95 years of age). Conclusion: The prevalence of the MS is significantly underestimated when the current ATPIII criteria of FPG 6.1 mmol/L or higher is the only determinant of dysglycemia. (c) 2005 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21224 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. NIA, Lab Clin Res, Baltimore, MD 21224 USA. RP Rodriguez, A (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Bayview Med Ctr, Baltimore, MD 21224 USA. EM arodrig5@jhmi.edu NR 30 TC 21 Z9 22 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD APR PY 2005 VL 54 IS 4 BP 542 EP 547 DI 10.1016/j.metabol.2004.11.010 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 916AE UT WOS:000228352600019 PM 15798964 ER PT J AU Carreras, E Boix, E Navarro, S Rosenberg, HF Cuchillo, CM Nogues, MV AF Carreras, E Boix, E Navarro, S Rosenberg, HF Cuchillo, CM Nogues, MV TI Surface-exposed amino acids of eosinophil cationic protein play a critical role in the inhibition of mammalian cell proliferation SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE cell proliferation inhibition; cytotoxicity; eosinophils; eosinophil cationic protein; ribonuclease ID MAJOR BASIC-PROTEIN; RIBONUCLEASE-ACTIVITY; IN-VITRO; GRANULE PROTEINS; ECP; NEUROTOXIN; INVITRO; RESIDUES; DISEASE; BINDING AB Eosinophil cationic protein (ECP) is a ribonuclease secreted from activated eosinophils that may cause tissue injure as a result of eosinophilic inflammation. ECP possesses bactericidal, antiviral and helminthotoxic activity and inhibits mammalian cell growth. The mechanism by which ECP exerts its toxicity is not known but it has been related to the ability of the protein to destabilise lipid bilayers. We have assessed the involvement of some cationic and aromatic surface exposed residues of ECP in the inhibition of proliferation of mammalian cell lines. We have constructed ECP mutants for the selected residues and assessed their ability to prevent cell growth. Trp10 and Trp35 together with the adjacent stacking residue are critical for the damaging effect of ECP on mammalian cell lines. These residues are also crucial for the membrane disruption activity of ECP. Other exposed aromatic residues packed against arginines (Arg75-Phe76 and Arg121-Tyr122) and specific cationic amino acids (Arg101and Arg104) of ECP play a secondary role in the cell growth inhibition. This may be related to the ability of the protein to bind carbohydrates such as those found on the surface of mammalian cells. C1 Univ Autonoma Barcelona, Fac Ciencies, Dept Bioquim & Biol Mol, Bellaterra 08193, Spain. NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Nogues, MV (reprint author), Univ Autonoma Barcelona, Fac Ciencies, Dept Bioquim & Biol Mol, Bellaterra 08193, Spain. EM victoria.nogues@uab.es RI Boix, Ester/B-9038-2012; Nogues, Victoria/H-6100-2015; OI Boix, Ester/0000-0003-1790-2142; Nogues, Victoria/0000-0002-7104-0961; Navarro, Susanna/0000-0001-8160-9536 NR 38 TC 40 Z9 40 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD APR PY 2005 VL 272 IS 1-2 BP 1 EP 7 DI 10.1007/s11010-005-4777-2 PG 7 WC Cell Biology SC Cell Biology GA 924JD UT WOS:000228974200001 PM 16010966 ER PT J AU Dey, M Trieselmann, B Locke, EG Lu, JF Cao, C Dar, AC Krishnamoorthy, T Dong, JS Sicheri, F Dever, TE AF Dey, M Trieselmann, B Locke, EG Lu, JF Cao, C Dar, AC Krishnamoorthy, T Dong, JS Sicheri, F Dever, TE TI PKR and GCN2 kinases and guanine nucleotide exchange factor eukaryotic translation initiation factor 2B (eIF2B) recognize overlapping surfaces on eIF2 alpha SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID DOUBLE-STRANDED-RNA; ACTIVATED PROTEIN-KINASE; ALPHA-SUBUNIT; SACCHAROMYCES-CEREVISIAE; CRYSTAL-STRUCTURE; SUBSTRATE RECOGNITION; FACTOR-II; FUNCTIONALLY SUBSTITUTE; PEPTIDE INHIBITOR; CATALYTIC SUBUNIT AB Four stress-responsive protein kinases, including GCN2 and PKR, phosphorylate eukaryotic translation initiation factor 2 alpha (eIF2 alpha) on Ser51 to regulate general and gene-specific protein synthesis. Phosphorylated eIF2 is an inhibitor of its guanine nucleotide exchange factor, eIF2B. Mutations that block translational regulation were isolated throughout the N-terminal OB-fold domain in Saccharomyces cerevisiae eIF2 alpha, including those at residues flanking Ser51 and around 20 angstrom away in the conserved motif K(79)GYID(83). Any mutation at Glu49 or Asp83 blocked translational regulation; however, only a subset of these mutations impaired Ser51 phosphorylation. Substitution of Ala for Asp83 eliminated phosphorylation by GCN2 and PKR both in vivo and in vitro, establishing the critical contributions of remote residues to kinase-substrate recognition. In contrast, mutations that blocked translational regulation but not Ser51 phosphorylation impaired the binding of eIF2B to phosphorylated eIF2 alpha. Thus, two structurally distinct effectors of eIF2 function, eIF2 alpha kinases and eIF2B, have evolved to recognize the same surface and overlapping determinants on eIF2 alpha. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Program Mol Biol & Canc, Toronto, ON, Canada. Mt Sinai Hosp, Dept Mol & Med Genet, Toronto, ON, Canada. RP Dever, TE (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, 6 Ctr Dr, Bethesda, MD 20892 USA. EM tdever@box-t.nih.gov RI Sicheri, Frank/F-8856-2013 NR 44 TC 38 Z9 41 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2005 VL 25 IS 8 BP 3063 EP 3075 DI 10.1128/MCB.25.8.3063-3075.2005 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 913GB UT WOS:000228138500017 PM 15798194 ER PT J AU Leaner, VD Donninger, H Ellis, CA Clark, GJ Birrer, MJ AF Leaner, VD Donninger, H Ellis, CA Clark, GJ Birrer, MJ TI p75-Ras-GRF1 is a c-Jun/AP-1 target protein: Its up regulation results in increased ras activity and is necessary for c-Jun-induced nonadherent growth of Rat1a cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ANCHORAGE-INDEPENDENT GROWTH; NUCLEOTIDE EXCHANGE FACTORS; R-RAS; ONCOGENIC TRANSFORMATION; TERMINAL PHOSPHORYLATION; CELLULAR-TRANSFORMATION; FAMILY GTPASES; RAT-1A CELLS; ACTIVATION; AP-1 AB The c-Jun/AP-1 transcription complex is associated with diverse cellular processes such as differentiation, proliferation, transformation, and apoptosis. These different biological endpoints are likely achieved by the regulation of specific target gene expression. We describe the identification of Ras guanine nucleotide exchange factor 1, Ras-GRF1, by microarray analysis as a c-jun/AP-1 regulated gene essential for anchorage-independent growth of immortalized rat fibroblasts. Increased Ras-GRF1 expression, in response to inducible c-Jun expression in Rat1a fibroblasts, was confirmed by both real-time PCR and Northern blot analysis. We show that c-jun/AP-1 can bind and activate the Ras-GRF1 promoter in vivo. A 75-kDa c-jun/AP-1-inducible protein, p75-Ras-GRF1, was detected, and the inhibition of its expression with antisense oligomers significantly blocked c-Jun-regulated anchorage-independent cell growth. p75-Ras-GRF1 expression occurred with a concomitant increase in activated Ras (GTP bound), and the activation of Ras was significantly inhibited by antisense Ras-GRF1 oligomers. Moreover, p75-Ras-GRF1 could be coprecipitated with a Ras dominant-negative glutathione S-transferase (GST) construct, GST-Ras15A, demonstrating an interaction between p75-Ras-GRF1 and Ras. A downstream target of Ras activation, Elk-1, had increased transcriptional activity in c-Jun-expressing cells, and this activation was inhibited by dominant-negative Ras. In addition, c-Jun overexpression resulted in an increase in phospho-AKT while phosphorylation of ERK1/2 remained largely unaffected. The inhibition of phosphatidylinositol 3-kinase (PI3K)-AKT signal transduction by Ly294002 and wortmannin significantly blocked c-jun-regulated morphological transformation, while inhibition of basal MEK-ERK activity with PD98059 and U0126 had little effect. We conclude that c-jun/AP-1 regulates endogenous p75-Ras-GRF1 expression and that c-jun/AP-1-regulated anchorage-independent cell growth requires activation of Ras-PI3KAKT signal transduction. C1 NCI, Cell & Canc Biol Dept, Ctr Canc Res, Rockville, MD 20850 USA. RP Birrer, MJ (reprint author), NCI, Cell & Canc Biol Dept, Ctr Canc Res, 9610 Med Ctr Dr,Room 300, Rockville, MD 20850 USA. EM birrerm@mail.nih.gov NR 53 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2005 VL 25 IS 8 BP 3324 EP 3337 DI 10.1128/MCB.25.8.3324-3337.2005 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 913GB UT WOS:000228138500039 PM 15798216 ER PT J AU Conze, DB Albert, L Ferrick, DA Goeddel, DV Yeh, WC Mak, T Ashwell, JD AF Conze, DB Albert, L Ferrick, DA Goeddel, DV Yeh, WC Mak, T Ashwell, JD TI Posttranscriptional downregulation of c-IAP2 by the ubiquitin protein ligase c-IAP1 in vivo SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NF-KAPPA-B; NECROSIS-FACTOR-ALPHA; GAMMA-DEFICIENT MICE; C-TERMINAL FRAGMENT; T-CELL ACTIVATION; GENE-EXPRESSION; APOPTOSIS PROTEIN-1; INHIBITOR; XIAP; TRANSCRIPTION AB Inhibitor of apoptosis proteins (IAPs) c-IAP1 and c-IAP2 were identified as part of the tumor necrosis factor receptor 2 (TNFR2) signaling complex and have been implicated as intermediaries in tumor necrosis factor alpha signaling. Like all RING domain-containing IAPs, c-IAP1 and c-IAP2 have ubiquitin protein ligase (E3) activity. To explore the function of c-IAP1 in a physiologic setting, c-IAP1-deficient mice were generated by homologous gene recombination. These animals are viable and have no obvious sensitization to proapoptotic stimuli. Cells from c-IAP1(-/-) mice do, however, express markedly elevated levels of c-IAP2 protein in the absence of increased c-IAP2 mRNA. In contrast to reports implicating c-IAPs in the activation of NF-kappa B, resting and cytokine-induced NF-kappa B activation was not impaired in c-IAP1-deficient cells. Transient transfection studies with wild-type and E3-defective c-IAP1 revealed that c-IAP2 is a direct target for c-IAP1-mediated ubiquitination and subsequent degradation, which are potentiated by the adaptor function of TRAF2. Thus, the c-IAPs represent a pair of TNFR-associated ubiquitin protein ligases in which one regulates the expression of the other by a posittranscriptional and E3-dependent mechanism. C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. Princess Margaret Hosp, Adv Med Discovery Inst, Div Cellular & Mol Biol, Toronto, ON M4X 1K9, Canada. Sagres Discovery, Davis, CA USA. Tularik Inc, San Francisco, CA USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, 9000 Rockville Pike,Bldg 37,Room 3002, Bethesda, MD 20892 USA. EM jda@pop.nci.nih.gov NR 46 TC 129 Z9 132 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2005 VL 25 IS 8 BP 3348 EP 3356 DI 10.1128/MCB.25.8.3348-3356.2005 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 913GB UT WOS:000228138500041 PM 15798218 ER PT J AU Woodworth, CD Michael, E Marker, D Allen, S Smith, L Nees, M AF Woodworth, CD Michael, E Marker, D Allen, S Smith, L Nees, M TI Inhibition of the epidermal growth factor receptor increases expression of genes that stimulate inflammation, apoptosis, and cell attachment SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID TYROSINE KINASE INHIBITOR; NF-KAPPA-B; HUMAN-PAPILLOMAVIRUS; EPITHELIAL-CELLS; CANCER-CELLS; LUNG-CANCER; TARGETED DISRUPTION; HUMAN KERATINOCYTES; EGF RECEPTOR; SOLID TUMORS AB The epidermal growth factor receptor (EGFR) is overexpressed in several types of human cancer, and inhibition of EGFR function is a promising strategy for cancer therapy. We used cDNA microarrays to examine alterations in gene expression after treatment of carcinoma cells with PD153035, a specific and reversible inhibitor of EGFR function. When human cervical carcinoma cells were grown on a collagen substrate in three-dimensional organotypic culture, untreated cells expressed high levels of EGFR RNA and invaded the underlying collagen. Blocking EGFR function decreased DNA synthesis and inhibited invasion in a dose-dependent manner. Microarray analyses identified 312 genes that were significantly increased or decreased in expression after EGFR inhibition. Many could be classified into one of four functional groups including genes that (a) stimulate inflammation and innate immunity, (b) promote cell attachment, (c) enhance apoptosis, and (d) inhibit cell cycle progression. PD153035 induced a dose-dependent activation of nuclear factor kappa B, a transcription factor that stimulates proinflammatory gene expression. Our results identify alterations in gene expression caused by EGFR inhibition and show that this response varies significantly in different cell lines. C1 Clarkson Univ, Dept Biol, Potsdam, NY 13699 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, Bethesda, MD 20892 USA. Univ Heidelberg, Dept Pediat Oncol, Heidelberg, Germany. Univ Heidelberg, Dept Hematol & Immunol, Heidelberg, Germany. RP Woodworth, CD (reprint author), Clarkson Univ, Dept Biol, Potsdam, NY 13699 USA. EM woodworth@clarkson.edu FU NCI NIH HHS [1R15CA101873-01A1] NR 57 TC 63 Z9 69 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD APR PY 2005 VL 4 IS 4 BP 650 EP 658 DI 10.1158/1535-7163.MCT-04-0238 PG 9 WC Oncology SC Oncology GA 915GR UT WOS:000228286600017 PM 15827339 ER PT J AU Kireeva, ML Hancock, B Cremona, GH Walter, W Studitsky, VM Kashlev, M AF Kireeva, ML Hancock, B Cremona, GH Walter, W Studitsky, VM Kashlev, M TI Nature of the nucleosomal barrier to RNA polymerase II SO MOLECULAR CELL LA English DT Article ID CHROMATIN-REMODELING COMPLEX; TRANSCRIPTION ELONGATION; SACCHAROMYCES-CEREVISIAE; IN-VIVO; GENETIC INTERACTIONS; STRUCTURAL BASIS; ARREST SITE; CLEAVAGE; TFIIS; DNA AB In the cell, RNA polymerase II (pol II) efficiently transcribes DNA packaged into nucleosomes, but in vitro encounters with the nucleosomes induce catalytic inactivation (arrest) of the pol II core enzyme. To determine potential mechanisms making nucleosomes transparent to transcription in vivo, we analyzed the nature of the nucleosome-induced arrest. We found that the arrests have been detected mostly at positions of strong intrinsic pause sites of DNA. The transient pausing makes pol II vulnerable to arrest, which involves backtracking of the elongation complex for a considerable distance on DNA. The histone-DNA contacts reestablished in front of pol II stabilize backtracked conformation of the polymerase. In agreement with this mechanism, blocking of backtracking prevents nucleosome-induced arrest. Transcript cleavage factor TFIIS reactivates the backtracked complexes and promotes pol II transcription through the nucleosome. Our findings establish the crucial role of elongation factors that suppress pol II pausing and backtracking for transcription in the context of chromatin. C1 NCI, Ctr Canc Res, Frederick, MD 21702 USA. Wayne State Univ, Sch Med, Detroit, MI 48201 USA. RP Kashlev, M (reprint author), NCI, Ctr Canc Res, Frederick, MD 21702 USA. EM mkashlev@mail.ncifcrf.gov RI Studitsky, Vasily/A-9382-2014 FU NIGMS NIH HHS [GM58650] NR 44 TC 120 Z9 121 U1 2 U2 12 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD APR 1 PY 2005 VL 18 IS 1 BP 97 EP 108 DI 10.1016/j.molcel.2005.02.027 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 914MG UT WOS:000228231300009 PM 15808512 ER PT J AU Sheehan, KM Calvert, VS Kay, EW Lu, YL Fishman, D Espina, V Aquino, J Speer, R Araujo, R Mills, GB Liotta, LA Petricoin, EF Wulfkuhle, JD AF Sheehan, KM Calvert, VS Kay, EW Lu, YL Fishman, D Espina, V Aquino, J Speer, R Araujo, R Mills, GB Liotta, LA Petricoin, EF Wulfkuhle, JD TI Use of reverse phase protein microarrays and reference standard development for molecular network analysis of metastatic ovarian carcinoma SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID CANCER-CELL-LINES; C-KIT; CLINICAL PROTEOMICS; PROSTATE-CANCER; BREAST-CANCER; TRASTUZUMAB HERCEPTIN; KINASE INHIBITORS; ANTICANCER DRUGS; ZD1839 IRESSA; MAP KINASE AB Cancer can be defined as a deregulation or hyperactivity in the ongoing network of intracellular and extracellular signaling events. Reverse phase protein microarray technology may offer a new opportunity to measure and profile these signaling pathways, providing data on posttranslational phosphorylation events not obtainable by gene microarray analysis. Treatment of ovarian epithelial carcinoma almost always takes place in a metastatic setting since unfortunately the disease is often not detected until later stages. Thus, in addition to elucidation of the molecular network within a tumor specimen, critical questions are to what extent do signaling changes occur upon metastasis and are there common pathway elements that arise in the metastatic microenvironment. For individualized combinatorial therapy, ideal therapeutic selection based on proteomic mapping of phosphorylation end points may require evaluation of the patient's metastatic tissue. Extending these findings to the bedside will require the development of optimized protocols and reference standards. We have developed a reference standard based on a mixture of phosphorylated peptides to begin to address this challenge. C1 US FDA, FDA NCI, Clin Prote Program,Off Cell Tissue & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, FDA NCI, Clin Prote Program,Lab Pathol,Ctr Canc Res, NCI,NIH, Bethesda, MD 20892 USA. Beaumont Hosp, Dept Pathol, Dublin 9, Ireland. Royal Coll Surgeons Ireland, Dublin 2, Ireland. Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, Houston, TX 77054 USA. NYU, Natl Ovarian Canc Early Detect Program, New York, NY 10016 USA. RP Wulfkuhle, JD (reprint author), US FDA, FDA NCI, Clin Prote Program,Off Cell Tissue & Gene Therapy, Ctr Biol Evaluat & Res, Bldg 29A-2D12,HFM 710,8800 Rockville Pike, Bethesda, MD 20892 USA. EM wulfkuhlecber@fda.gov OI Espina, Virginia/0000-0001-5080-5972 FU NCI NIH HHS [P01 CA64602, P50CA83639A] NR 79 TC 202 Z9 213 U1 2 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD APR PY 2005 VL 4 IS 4 BP 346 EP 355 DI 10.1074/mcp.T500003-MCP200 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 911DB UT WOS:000227980600002 PM 15671044 ER PT J AU Veenstra, TD Conrads, TP Hood, BL Avellino, AM Ellenbogen, RG Morrison, RS AF Veenstra, TD Conrads, TP Hood, BL Avellino, AM Ellenbogen, RG Morrison, RS TI Biomarkers: Mining the biofluid proteome SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID HUMAN SERUM PROTEOME; 2-DIMENSIONAL ELECTROPHORESIS GELS; NORMAL-PRESSURE HYDROCEPHALUS; HUMAN PLASMA PROTEOME; CEREBROSPINAL-FLUID; MASS-SPECTROMETRY; ALZHEIMERS-DISEASE; RHEUMATOID-ARTHRITIS; SYNOVIAL-FLUID; OVARIAN-CANCER AB Proteomics has brought with it the hope of identifying novel biomarkers for diseases such as cancer. This hope is built on the ability of proteomic technologies, such as mass spectrometry ( MS), to identify hundreds of proteins in complex biofluids such as plasma and serum. There are many factors that make this research very challenging beginning with the lack of standardization of sample collection and continuing through the entire analytical process. Fortunately the advances made in the characterization of biofluids using proteomic techniques have been rapid and suggest that these mainly discovery driven approaches will lead to the development of highly specific platforms for diagnosing diseases and monitoring responses to different treatments in the near future. C1 SAIC Frederick Inc, NCI, Lab Prote & Analyt Technol, Frederick, MD 21702 USA. Univ Washington, Sch Med, Dept Neurol Surg, Seattle, WA 98195 USA. RP Veenstra, TD (reprint author), SAIC Frederick Inc, NCI, Lab Prote & Analyt Technol, POB B,Bldg 469,Rm 160, Frederick, MD 21702 USA. EM veenstra@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400]; NINDS NIH HHS [NS047670, NS35533, NS42699] NR 46 TC 145 Z9 158 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD APR PY 2005 VL 4 IS 4 BP 409 EP 418 DI 10.1074/mcp.M500006-MCP200 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 911DB UT WOS:000227980600008 PM 15684407 ER PT J AU Liu, Y Ando, S Xia, XM Yao, RF Kim, M Fondell, J Yen, PM AF Liu, Y Ando, S Xia, XM Yao, RF Kim, M Fondell, J Yen, PM TI p62, a TFIIH subunit, directly interacts with thyroid hormone receptor and enhances T-3-mediated transcription SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID ESTROGEN-RECEPTOR; RESPONSIVE PROMOTERS; BASAL TRANSCRIPTION; NUCLEAR RECEPTOR; BINDING PROTEIN; RAR-ALPHA; IN-VIVO; ACTIVATION; PHOSPHORYLATION; COACTIVATOR AB Currently, little is known about the direct interactions of general transcription factors and nuclear hormone receptors. To investigate the potential role of the general transcription factor, TFIIH, in T-3-mediated transcriptional activation, we examined thyroid hormone receptor (TR) interaction with individual TFIIH subunits in a yeast-two hybrid system. Among the nine subunits of TFIIH studied, only p62 subunit interacted with TR beta in a ligand-dependent manner. Glutathione-S-transferase pulldown and in vivo coimmunoprecipitation studies also demonstrated direct TR/p62 interaction. Using chromatin immunoprecipitation assays, we showed that TFIIH subunits were corecruited on or near an endogenous thyroid hormone response element upon T 3 addition. Cotransfection studies with TSA201 cells showed that p62 increased T-3-mediated transcription, which could be further enhanced when p62 and another TFIIH subunit, p44, were cotransfected simultaneously. Taken together, these data suggest that TRs can interact directly with a subunit of TFIIH and may provide an alternative pathway for nuclear receptor communication with the general transcription machinery that circumvents coactivators. C1 Johns Hopkins Univ, Johns Hopkins Bayview Med Ctr, Dept Med, Div Endocrinol, Baltimore, MD 21224 USA. NIDDKD, Mol Regulat & Neuroendocrinol Sect, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Physiol & Biophys, Piscataway, NJ 08854 USA. RP Yen, PM (reprint author), Johns Hopkins Univ, Johns Hopkins Bayview Med Ctr, Dept Med, Div Endocrinol, 4940 Eastern Ave,Room B114, Baltimore, MD 21224 USA. EM pyen3@jhmi.edu NR 31 TC 10 Z9 10 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD APR PY 2005 VL 19 IS 4 BP 879 EP 884 DI 10.1210/me.2004-0385 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 908YN UT WOS:000227826200005 PM 15625236 ER PT J AU Sidransky, E AF Sidransky, E TI Gaucher disease and parkinsonism SO MOLECULAR GENETICS AND METABOLISM LA English DT Editorial Material ID MUTATIONS; RISK; GENE C1 NIMH, Clin Neurosci Branch, Sect Mol Neurogenet, NIH, Bethesda, MD 20892 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NIMH, Clin Neurosci Branch, Sect Mol Neurogenet, NIH, Bethesda, MD 20892 USA. EM sidranse@irp.nimh.nih.gov NR 17 TC 38 Z9 40 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 2005 VL 84 IS 4 BP 302 EP 304 DI 10.1016/j.ymgme.2004.11.007 PG 3 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 913FZ UT WOS:000228138300002 PM 15781189 ER PT J AU Fariss, MW Chan, CB Patel, M Van Houten, B Orrenius, S AF Fariss, MW Chan, CB Patel, M Van Houten, B Orrenius, S TI Defining mitochondrial targets to combat the pleiotropic effects of toxic oxidative stress SO MOLECULAR INTERVENTIONS LA English DT Review ID MANGANESE SUPEROXIDE-DISMUTASE; UNCOUPLING PROTEIN-2 GENE; CYTOCHROME-C RELEASE; STIMULATED INSULIN-SECRETION; IRON-RESPONSIVE ELEMENT; PANCREATIC BETA-CELL; SUCCINATE PROTECTS HEPATOCYTES; TUMOR-NECROSIS-FACTOR; VITAMIN-E SUCCINATE; FREE FATTY-ACIDS AB Oxidative stress and mitochondrial oxidative damage have been implicated in the etiology of numerous common diseases. The critical mitochondrial events responsible for oxidative stress-mediated cell death (toxic oxidative stress), however, have yet to be defined. Several oxidative events implicated in toxic oxidative stress include alterations in mitochondrial lipids (e.g. cardiolipin), mitochondrial DNA, and mitochondrial proteins (eg. aconitase and uncoupling protein 2). Furthermore, recent findings indicate the enrichment of mitochondrial membranes with vitamin E protects cells against the toxic effects of oxidative stress. This review briefly summarizes the role of these mitochondrial events in toxic oxidative stress, including: 1) the protective role of mitochondrial vitamin E in toxic oxidative stress, 2) the role of mitochondrial DNA in toxic oxidative stress, 3) the interaction between cardiolipin and cytochrome c in mitochondrial regulation of apoptosis, 4) the role of mitochondrial aconitase in oxidative neurodegeneration, and 5) the role of mitochondrial uncoupling protein 2 in the pathogenesis of type 2 diabetes. C1 Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Ctr Canc, Denver, CO 80262 USA. Univ Prince Edward Isl, Dept Biomed Sci, Charlottetown, PE C1A 4P3, Canada. Univ Colorado, Hlth Sci Ctr, Program Neurosci, Denver, CO 80262 USA. NIEHS, Genet Mol Lab, NIH, Res Triangle Pk, NC 27709 USA. Karolinska Inst, Inst Environm Med, Div Toxicol, SE-17177 Stockholm, Sweden. RP Fariss, MW (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Pharmaceut Sci, Denver, CO 80262 USA. EM marc.fariss@uchsc.edu; cchan@upei.ca; patel@uchsc.edu; vanhout1@niehs.nih.gov; sten.orrenius@imm.ki.se RI Chan, Catherine/C-1162-2011 FU NIEHS NIH HHS [ES05452]; NINDS NIH HHS [NS044202, NS045748] NR 137 TC 146 Z9 168 U1 0 U2 6 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 1534-0384 J9 MOL INTERV JI Mol. Interv. PD APR PY 2005 VL 5 IS 2 BP 94 EP 111 DI 10.1124/mi.5.2.7 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 917EU UT WOS:000228439800007 PM 15821158 ER PT J AU Eiden, LE AF Eiden, LE TI Fusion polypeptides that inhibit exocytosis: Fusing aptamer and cell-penetrating peptide technologies and pharmacologies SO MOLECULAR PHARMACOLOGY LA English DT Editorial Material ID PROTEIN TRANSDUCTION; DELIVERY AB Cell-penetrating peptides are amphipathic or cationic oligopeptides able to transport covalently attached cargoes across cell membranes. Peptide aptamers are polypeptide fragments of endogenous proteins that mimic and thus perturb interactions with other cellular proteins. Combining aptamer and CPP technology can generate pharmacological reagents effective in cell culture models and in vivo. C1 NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Intramural Res Program, Bethesda, MD 20892 USA. RP Eiden, LE (reprint author), NIMH, Mol Neurosci Sect, Lab Cellular & Mol Regulat, Intramural Res Program, Bldg 36,Room 2A-11,9000 Rockville Pike, Bethesda, MD 20892 USA. EM eidenl@mail.nih.gov OI Eiden, Lee/0000-0001-7524-944X NR 19 TC 5 Z9 6 U1 1 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 2005 VL 67 IS 4 BP 980 EP 982 DI 10.1142/mol.105.011429 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 908RC UT WOS:000227805800002 PM 15673600 ER PT J AU Yan, ZH Liang, ZD Tomic, M Obsil, T Stojilkovic, SS AF Yan, ZH Liang, ZD Tomic, M Obsil, T Stojilkovic, SS TI Molecular determinants of the agonist binding domain of a P2X receptor channel SO MOLECULAR PHARMACOLOGY LA English DT Article ID TRANSFER-RNA SYNTHETASE; ATP-BINDING; CRYSTAL-STRUCTURES; EXTRACELLULAR PH; PROTEIN MODELS; SWISS-MODEL; AMINO-ACIDS; RESIDUES; DESENSITIZATION; IDENTIFICATION AB P2 purinergic receptor channel receptors ( P2XRs) are a family of ligand-gated cation channels composed of two transmembrane domains, N and C termini located intracellularly, and a large extracellular loop containing the ATP binding domain. To identify regions important for binding and gating, previous experimental work was focused on mutagenesis of conserved ectodomain residues. Here, we used the known sequence and secondary structure similarities between the Lys180-Lys326 ectodomain region of P2X(4) and the class II aminoacyl-tRNA synthetases as a guide to generate a three-dimensional model of the receptor-binding site and to design mutants. The interplay between homology modeling and site-directed mutagenesis suggested that Asp280 residue of P2X(4)R coordinates ATP binding via the magnesium ion, Phe230 residue coordinates the binding of the adenine ring of ATP, and Lys190, His286, and Arg278 residues coordinate the actions of negatively charged alpha-, beta-, and gamma-phosphate groups, respectively. Until the crystal structure of the channel is solved, this model could provide a useful approach for future studies on the identification of ATP binding domain and gating of P2XRs. C1 NICHHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. Charles Univ, Fac Sci, Dept Phys & Macromol Chem, Prague, Czech Republic. RP Stojilkovic, SS (reprint author), NICHD, ERRB, Bldg 49,Room 6A-36,49 Convent Dr, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov RI Obsil, Tomas/B-7142-2012; Tomic, Melanija/C-3371-2016 OI Obsil, Tomas/0000-0003-4602-1272; NR 46 TC 50 Z9 52 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 2005 VL 67 IS 4 BP 1078 EP 1088 DI 10.1124/mol.104.010108 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 908RC UT WOS:000227805800013 PM 15632318 ER PT J AU Khan, NL Horta, W Eunson, L Graham, E Johnson, JO Chang, S Davis, M Singleton, A Wood, NW Lees, AJ AF Khan, NL Horta, W Eunson, L Graham, E Johnson, JO Chang, S Davis, M Singleton, A Wood, NW Lees, AJ TI Parkin disease in a Brazilian kindred: Manifesting heterozygotes and clinical follow-up over 10 years SO MOVEMENT DISORDERS LA English DT Article DE manifesting carriers; haploinsufficiency; isolated population ID NIGROSTRIATAL DOPAMINERGIC SYSTEM; PSEUDO-DOMINANT INHERITANCE; EARLY-ONSET PARKINSONISM; MUTATIONS; GENE; TRIPLICATION; PROGRESSION; FAMILY AB We report on a large Brazilian kindred with young-onset parkinsonism due to either a homozygous or heterozygous mutation in parkin. A total of 6 members were affected: 5 were homozygous and 1 heterozygous for a deletion in exon 4. Two other heterozygotes also had extrapyramidal signs. All affected subjects showed characteristic features of parkin disease with foot dystonia and an excellent response to levodopa complicated by motor fluctuations and dyskinesia within 3 years of therapy. Careful clinical follow-up over 10 years showed the phenotype was similar in all the homozygotes with asymmetrical limb bradykinesia and early walking difficulties. Some acceleration of disability was observed in some of the cases as they entered the third decade of illness, but dementia was absent. (c) 2004 Movement Disorder Society. C1 Royal Free Hosp, Reta Lila Weston Unit Neurol Studies, London W1T 4JF, England. Univ Coll Med Sch, London W1T 4JF, England. Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. Fed Univ Ceara, Hosp Univ Walter Cantidio, Serv Neurol, Fortaleza, Ceara, Brazil. Fed Univ Ceara, Dept Movement Disorders, Fortaleza, Ceara, Brazil. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Lees, AJ (reprint author), Royal Free Hosp, Reta Lila Weston Unit Neurol Studies, Windmeyer Bldg,46 Cleveland St, London W1T 4JF, England. EM alees@ion.ucl.ac.uk RI Singleton, Andrew/C-3010-2009; Lees, Andrew/A-6605-2009; Wood, Nicholas/C-2505-2009 OI Wood, Nicholas/0000-0002-9500-3348 FU Parkinson's UK [G-4029] NR 18 TC 22 Z9 22 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2005 VL 20 IS 4 BP 479 EP 484 DI 10.1002/mds.20335 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 918KI UT WOS:000228540300013 PM 15641013 ER PT J AU Voon, V AF Voon, V TI Reply: Repetitive behaviors in Parkinson's disease SO MOVEMENT DISORDERS LA English DT Letter C1 Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. NINDS, NIH, Bethesda, MD 20892 USA. RP Voon, V (reprint author), Toronto Western Hosp, Toronto, ON M5T 2S8, Canada. EM valerie.voon@uhn.on.ca NR 1 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2005 VL 20 IS 4 BP 509 EP 510 DI 10.1002/mds.20447 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 918KI UT WOS:000228540300022 ER PT J AU Thomas, M Ashizawa, T Jankovic, J AF Thomas, M Ashizawa, T Jankovic, J TI Reply: Huntington's disease and minocycline SO MOVEMENT DISORDERS LA English DT Letter ID MODEL C1 NIH, Bethesda, MD 20892 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Baylor Coll Med, Houston, TX 77030 USA. RP Thomas, M (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM thomasmad@ninds.nih.gov NR 8 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 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2005 VL 20 IS 4 BP 511 EP 511 DI 10.1002/mds.20430 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 918KI UT WOS:000228540300024 ER PT J AU Rouzaud, F Kadekaro, AL Abdel-Malek, ZA Hearing, VJ AF Rouzaud, F Kadekaro, AL Abdel-Malek, ZA Hearing, VJ TI MC1R and the response of melanocytes to ultraviolet radiation SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Review DE melanocortin 1 receptor (MC1R); ultraviolet radiation (UVR); alpha MSH; pigmentation; melanocyte ID STIMULATING-HORMONE-RECEPTOR; MELANOCORTIN 1 RECEPTOR; CULTURED HUMAN MELANOCYTES; AGOUTI SIGNAL PROTEIN; EARLY-ONSET OBESITY; RED HAIR; SKIN TYPE; HUMAN KERATINOCYTES; MELANOMA-CELLS; DNA-DAMAGE AB The constitutive color of our skin plays a dramatic role in our photoprotection from solar ultraviolet radiation (UVR) that reaches the Earth and in minimizing DNA damage that gives rise to skin cancer. More than 120 genes have been identified and shown to regulate pigmentation, one of the key genes being melanocortin 1 receptor (MC1R) that encodes the melanocortin I receptor (MC1R), a seven-transmembrane G protein-coupled receptor expressed on the surface of melanocytes. Modulation of MC1R function regulates melanin synthesis by melanocytes qualitatively and quantitatively. The MC1R is regulated by the physiological agonists alpha-melanocyte-stimulating hormone (alpha MSH) and adrenocorticotropic hormone (ACTH), and antagonist agouti signaling protein (ASP). Activation of the MC1R by binding of an agonist stimulates the synthesis of eumelanin primarily via activation of adenylate cyclase. The significance of cutaneous pigmentation lies in the photoprotective effect of melanin, particularly eumelanin, against sun-induced carcinogenesis. Epidermal melanocytes and keratinocytes respond to UVR by increasing their expression of alpha MSH and ACTH, which up-regulate the expression of MC1R, and consequently enhance the response of melanocytes to melanocortins. Constitutive skin pigmentation dramatically affects the incidence of skin cancer. The pigmentary phenotype characterized by red hair, fair complexion, inability to tan and tendency to freckle is an independent risk factor for all skin cancers, including melanoma. The MC1R gene is highly polymorphic in human populations, and allelic variation at this locus accounts, to a large extent, for the variation in pigmentary phenotypes and skin phototypes (SPT) in humans. Several allelic variants of the MC1R gene are associated with the red hair and fair skin (RHC) phenotype, and carrying one of these variants is thought to diminish the ability of the epidermis to respond to DNA damage elicited by UVR. The MC1R gene is considered a melanoma susceptibility gene, and its significance in determining the risk for skin cancer is of tremendous interest. (c) 2005 Elsevier B.V. All rights reserved. C1 NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Dept Dermatol, Cincinnati, OH 45267 USA. RP Hearing, VJ (reprint author), NCI, NIH, Cell Biol Lab, Bldg 37,Room 2132, Bethesda, MD 20892 USA. EM hearingv@nih.gov NR 210 TC 87 Z9 90 U1 1 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD APR 1 PY 2005 VL 571 IS 1-2 BP 133 EP 152 DI 10.1016/j.mrfmmm.2004.09.014 PG 20 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 909BH UT WOS:000227833400012 PM 15748644 ER PT J AU Chen, SN Fabricant, DS Pauli, GF Fong, HHS Farnsworth, NR AF Chen, SN Fabricant, DS Pauli, GF Fong, HHS Farnsworth, NR TI Synthesis of cimiracemate B, a phenylpropanoid found in Cimicifuga racemosa SO NATURAL PRODUCT RESEARCH LA English DT Article DE Cimicifuga racemosa; cimiracemate B; black cohosh; phenylpropanoid ID MACROPHAGE INFLAMMATORY PROTEIN-2; FUKIIC ACID-ESTERS; ISOFERULIC ACID; CHEMOCONTROLLED REDUCTION; FUKINOLIC ACID; PISCIDIC ACID; FERULIC ACID; BLACK COHOSH; RAW264.7; SIMPLEX AB The synthesis of the rare bioactive phenylpropanoid ester known as cimiracemate B (1) from black cohosh, Cimicifuga racemosa, is described. The procedure employs a coupling method using 1,1'-carbonyldiimidazole and methyltrifluoromethanesulfonate as coupling reagents in the presence of N-methylmorpholine. C1 Univ Illinois, Coll Pharm, Program Collaborat Res Pharmaceut Sci, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, NIH, Ctr Bot Dietary Supplements Res, Chicago, IL 60612 USA. RP Farnsworth, NR (reprint author), Univ Illinois, Coll Pharm, Program Collaborat Res Pharmaceut Sci, M-C 877,833 S Wood St, Chicago, IL 60612 USA. EM Norman@uic.edu OI Pauli, Guido/0000-0003-1022-4326 FU NCCIH NIH HHS [P50 AT00155] NR 23 TC 4 Z9 5 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1478-6419 J9 NAT PROD RES JI Nat. Prod. Res. PD APR PY 2005 VL 19 IS 3 BP 287 EP 290 DI 10.1080/14786410410001714650 PG 4 WC Chemistry, Applied; Chemistry, Medicinal SC Chemistry; Pharmacology & Pharmacy GA 892RZ UT WOS:000226669000012 PM 15702643 ER PT J AU Fernandez, DC Bhargava, R Hewitt, SM Levin, IW AF Fernandez, DC Bhargava, R Hewitt, SM Levin, IW TI Infrared spectroscopic imaging for histopathologic recognition SO NATURE BIOTECHNOLOGY LA English DT Article ID TISSUE MICROARRAYS; PROSTATE-CANCER; SPECIMENS; CELLS; MICROSPECTROSCOPY; ADENOCARCINOMA; PHENOTYPE AB The process of histopathology, comprising tissue staining and morphological pattern recognition, has remained largely unchanged for over 140 years(1). Although it is integral to clinical and research activities, histopathologic recognition remains a time-consuming, subjective process to which only limited statistical confidence can be assigned because of inherent operator variability(2,3). Although immunohistochemical approaches allow limited molecular detection, significant challenges remain in using them for quantitative, automated pathology. Vibrational spectroscopic approaches, by contrast, directly provide nonperturbing molecular descriptors(4), but a practical spectroscopic protocol for histopathology is lacking. Here we couple high-throughput Fourier transform infrared (FTIR) spectroscopic imaging(5) of tissue microarrays(6) with statistical pattern recognition of spectra indicative of endogenous molecular composition and demonstrate histopathologic characterization of prostatic tissue. This automated histologic segmentation is applied to routine archival tissue samples, incorporates well-defined tests of statistical significance(7) and eliminates any requirement for dyes or molecular probes. Finally, we differentiate benign from malignant prostatic epithelium by spectroscopic analyses. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Levin, IW (reprint author), NIDDKD, Chem Phys Lab, NIH, Bldg 2, Bethesda, MD 20892 USA. EM iwl@helix.nih.gov RI Exarchos, Konstantinos/B-5978-2008; OI Hewitt, Stephen/0000-0001-8283-1788; Bhargava, Rohit/0000-0001-7360-994X NR 33 TC 299 Z9 313 U1 3 U2 66 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD APR PY 2005 VL 23 IS 4 BP 469 EP 474 DI 10.1038/nbt1080 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 914AR UT WOS:000228197300031 PM 15793574 ER PT J AU Leitzmann, MF AF Leitzmann, MF TI Is there a link between macronutrient intake and prostate cancer? SO NATURE CLINICAL PRACTICE ONCOLOGY LA English DT Editorial Material DE diet; fatty acids; macronutrients; prostate cancer; starch ID RISK C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. RP Leitzmann, MF (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd EPS MSC 7232, Bethesda, MD 20892 USA. EM leitzmann@mail.nih.gov NR 5 TC 4 Z9 4 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1743-4254 J9 NAT CLIN PRACT ONCOL JI Nat. Clin. Pract. Oncol. PD APR PY 2005 VL 2 IS 4 BP 184 EP 185 DI 10.1038/ncponc0127 PG 2 WC Oncology SC Oncology GA 926JI UT WOS:000229119100005 PM 16264928 ER PT J AU Schwartz, RH AF Schwartz, RH TI Natural regulatory T cells and self-tolerance SO NATURE IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR FOXP3; RECEPTOR-ALPHA-CHAINS; CLONAL DELETION; IN-VIVO; NEGATIVE SELECTION; THYMIC EPITHELIUM; TRANSGENIC MICE; B-CELLS; EXPRESSION; THYMOCYTES AB The adaptive immune system allows individual organisms to mount defensive reactions against unanticipated pathogens by developmentally creating a diverse repertoire of clonally distributed receptors capable of recognizing a multitude of antigens and then expanding as effector cell populations those that can recognize molecules from the pathogens. To function properly, the system must deal with the problem of randomly generated receptors that can recognize self components. Most solutions to this self-tolerance problem are cell intrinsic and involve the deletion or inactivation of autoreactive cells. However, an extrinsic form of dominant tolerance has been demonstrated that takes the form of CD4(+) regulatory T cells. This perspective discusses why such a mechanism might have evolved and the problems it presents for self-non-self discrimination. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Schwartz, RH (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. EM rschwartz@niaid.nih.gov NR 59 TC 167 Z9 182 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2005 VL 6 IS 4 BP 327 EP 330 DI 10.1038/ni1184 PG 4 WC Immunology SC Immunology GA 909KY UT WOS:000227860000002 PM 15785757 ER PT J AU Belkaid, Y Rouse, BT AF Belkaid, Y Rouse, BT TI Natural regulatory T cells in infectious disease SO NATURE IMMUNOLOGY LA English DT Review ID TRANSCRIPTION FACTOR FOXP3; HUMAN-IMMUNODEFICIENCY-VIRUS; LEISHMANIA-MAJOR INFECTION; TGF-BETA; DENDRITIC CELLS; HELICOBACTER-PYLORI; IN-VITRO; RETROVIRAL INFECTION; DEPENDENT MECHANISMS; SUPPRESSIVE ACTIVITY AB This review discusses the control exerted by natural CD4(+)CD25(+) regulatory T cells ( natural T-reg cells) during infectious processes. Natural T-reg cells may limit the magnitude of effector responses, which may result in failure to adequately control infection. However, natural T-reg cells also help limit collateral tissue damage caused by vigorous antimicrobial immune responses. We describe here various situations in which the balance between natural T-reg cells and effector immune functions influences the outcome of infection and discuss how manipulating this equilibrium might be exploited therapeutically. C1 Cincinnati Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH 45229 USA. Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA. RP Belkaid, Y (reprint author), NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. EM ybelkaid@niaid.nih.gov NR 80 TC 648 Z9 696 U1 2 U2 30 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2005 VL 6 IS 4 BP 353 EP 360 DI 10.1038/ni1181 PG 8 WC Immunology SC Immunology GA 909KY UT WOS:000227860000006 PM 15785761 ER PT J AU Sun, GP Liu, XL Mercado, P Jenkinson, SR Kypriotou, M Feigenbaum, L Galera, P Bosselut, R AF Sun, GP Liu, XL Mercado, P Jenkinson, SR Kypriotou, M Feigenbaum, L Galera, P Bosselut, R TI The zinc finger protein cKrox directs CD4 lineage differentiation during intrathymic T cell positive selection SO NATURE IMMUNOLOGY LA English DT Article ID THYMOCYTE DEVELOPMENT; NEGATIVE SELECTION; GENE-EXPRESSION; TRANSGENIC MICE; C-KROX; ANTIGEN RECEPTOR; BTB DOMAIN; THYMUS; COMMITMENT; SIGNALS AB The genetic programs directing CD4 or CD8 T cell differentiation in the thymus remain poorly understood. While analyzing gene expression during intrathymic T cell selection, we found that Zfp67, encoding the zinc finger transcription factor cKrox, was upregulated during the differentiation of CD4(+) but not CD8(+) T cells. Expression of a cKrox transgene impaired CD8 T cell development and caused major histocompatibility complex class I - restricted thymocytes to differentiate into CD4(+) T cells with helper properties rather than into cytotoxic CD8(+) T cells, as normally found. CD4 lineage differentiation mediated by cKrox required its N-terminal BTB (bric-a-brac, tramtrack, broad complex) domain. These findings identify cKrox as a chief CD4 differentiation factor during positive selection. C1 NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. CHU Caen, Fac Med, Lab Biochim Tissu Conjonctif, F-14000 Caen, France. NCI, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Bosselut, R (reprint author), NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM remy@helix.nih.gov NR 50 TC 177 Z9 181 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2005 VL 6 IS 4 BP 373 EP 381 DI 10.1038/ni1183 PG 9 WC Immunology SC Immunology GA 909KY UT WOS:000227860000011 PM 15750595 ER PT J AU Salvador, JM Mittelstadt, PR Guszczynski, T Copeland, TD Yamaguchi, H Appella, E Fornace, AJ Ashwell, JD AF Salvador, JM Mittelstadt, PR Guszczynski, T Copeland, TD Yamaguchi, H Appella, E Fornace, AJ Ashwell, JD TI Alternative p38 activation pathway mediated by T cell receptor-proximal tyrosine kinases SO NATURE IMMUNOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION; PROTEIN-KINASE; MAP KINASES; PHOSPHORYLATION; JNK; AUTOPHOSPHORYLATION; PROLIFERATION; LYMPHOCYTES; ZAP-70; SYK AB Signaling-responsive MAP kinases (MAPKs) are key in mediating immune responses and are activated through the phosphorylation of a Thr-X-Tyr motif by upstream MAPK kinases. Here we show that T cells stimulated through the T cell receptor (TCR) used an alternative mechanism in which p38 was phosphorylated on Tyr323 and subsequently autophosphorylated residues Thr180 and Tyr182. This required the TCR-proximal tyrosine kinase Zap70 but not the adaptor protein LAT, which was required for activation of extracellular signal - regulated protein kinase MAPKs. TCR activation of p38 lacking Tyr323 was diminished, and blocking of p38 activity prevented p38 dual phosphorylation in normal T cells but not in B cells. Thus, phosphorylation of Tyr323 dependent on the tyrosine kinase Lck and mediated by Zap70 serves as an important mechanism for TCR activation of p38 in T cells. C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. NCI, Gene Response Sect, NIH, Bethesda, MD 20892 USA. NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. EM jda@pop.nci.nih.gov RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 35 TC 152 Z9 164 U1 1 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2005 VL 6 IS 4 BP 390 EP 395 DI 10.1038/ni1177 PG 6 WC Immunology SC Immunology GA 909KY UT WOS:000227860000013 PM 15735648 ER PT J AU Salvador, JM Mittelstadt, PR Belova, GI Fornace, AJ Ashwell, JD AF Salvador, JM Mittelstadt, PR Belova, GI Fornace, AJ Ashwell, JD TI The autoimmune suppressor Gadd45 alpha inhibits the T cell alternative p38 activation pathway SO NATURE IMMUNOLOGY LA English DT Article ID MAP KINASE ACTIVATION; IFN-GAMMA PRODUCTION; PROTEIN-KINASE; SIGNAL-TRANSDUCTION; MOLECULAR-CLONING; MICE; GADD45A; JNK; APOPTOSIS; ARREST AB The p38 MAP kinase ( MAPK) is phosphorylated and activated by upstream MAPK kinases. T cells have an alternative pathway in which T cell receptor - activated tyrosine kinase Zap70 phosphorylates p38 on Tyr323. Mice lacking Gadd45 alpha, a small p38-binding molecule, develop a lupus-like autoimmune disease. Here we show that resting T cells but not B cells from Gadd45a(-/-) mice had spontaneously increased p38 activity in the absence of 'upstream' MAPK kinase activation. The p38 from resting Gadd45a(-/-) T cells was spontaneously phosphorylated on Tyr323, and its activity was specifically inhibited by recombinant Gadd45a in vitro. Thus, constitutive activation of T cell p38 through the alternative pathway is prevented by Gadd45a, the absence of which results in p38 activation, T cell hyperproliferation and autoimmunity. C1 NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Gen Response Sect, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM jda@pop.nci.nih.gov RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 42 TC 60 Z9 64 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1529-2908 J9 NAT IMMUNOL JI Nat. Immunol. PD APR PY 2005 VL 6 IS 4 BP 396 EP 402 DI 10.1038/ni1176 PG 7 WC Immunology SC Immunology GA 909KY UT WOS:000227860000014 PM 15735649 ER PT J AU Kelsall, B AF Kelsall, B TI Getting to the guts of NOD2 SO NATURE MEDICINE LA English DT Editorial Material ID CROHNS-DISEASE; PANETH CELLS; MUTATION; SUSCEPTIBILITY; ASSOCIATION; VARIANTS; GENE AB Mutations in NOD2, encoding an intracellular bacteria-sensing protein, have been associated recently with Crohn disease. Two studies in mice investigate how these mutations may affect innate immunity to microbes in the intestine and progression of disease. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Kelsall, B (reprint author), NIAID, NIH, Bethesda, MD 20892 USA. EM bkelsall@niaid.nih.gov NR 11 TC 19 Z9 19 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2005 VL 11 IS 4 BP 383 EP 384 DI 10.1038/nm0405-383 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 913UU UT WOS:000228180500023 PM 15812518 ER PT J AU Scaffidi, P Misteli, T AF Scaffidi, P Misteli, T TI (R)eversal of the cellular phenotype in the premature aging disease Hutchinson-Gilford progeria syndrome SO NATURE MEDICINE LA English DT Article ID A-TYPE LAMINS; ANTISENSE OLIGOMERS; MORPHOLINO; MUTATIONS; MISREGULATION; DEFECTS AB Hutchinson-Gilford progeria syndrome (HGPS) is a childhood premature aging disease caused by a spontaneous point mutation in lamin A ( encoded by LMNA), one of the major architectural elements of the mammalian cell nucleus(1-4). The HGPS mutation activates an aberrant cryptic splice site in LMNA pre-mRNA, leading to synthesis of a truncated lamin A protein and concomitant reduction in wild-type lamin A(3,4). Fibroblasts from individuals with HGPS have severe morphological abnormalities in nuclear envelope structure. Here we show that the cellular disease phenotype is reversible in cells from individuals with HGPS. Introduction of wild-type lamin A protein does not rescue the cellular disease symptoms. The mutant LMNA mRNA and lamin A protein can be efficiently eliminated by correction of the aberrant splicing event using a modified oligonucleotide targeted to the activated cryptic splice site. Upon splicing correction, HGPS fibroblasts assume normal nuclear morphology, the aberrant nuclear distribution and cellular levels of lamina-associated proteins are rescued, defects in heterochromatin-specific histone modifications are corrected and proper expression of several misregulated genes is reestablished. Our results establish proof of principle for the correction of the premature aging phenotype in individuals with HGPS. C1 NCI, NIH, Bethesda, MD 20892 USA. RP Misteli, T (reprint author), NCI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM mistelit@mail.nih.gov FU NCI NIH HHS [Z01 BC010309-07] NR 22 TC 290 Z9 300 U1 4 U2 35 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2005 VL 11 IS 4 BP 440 EP 445 DI 10.1038/nm1204 PG 6 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 913UU UT WOS:000228180500037 PM 15750600 ER PT J AU Dean, M Fojo, T Bates, S AF Dean, M Fojo, T Bates, S TI Tumour stem cells and drug resistance SO NATURE REVIEWS CANCER LA English DT Review ID ACUTE MYELOID-LEUKEMIA; SIDE POPULATION CELLS; BINDING CASSETTE TRANSPORTER; INHIBITOR INCEL BIRICODAR; P-GLYCOPROTEIN INHIBITOR; IMATINIB MESYLATE STI571; SOUTHWEST-ONCOLOGY-GROUP; ADVANCED BREAST-CANCER; BLOOD-BRAIN-BARRIER; MULTIDRUG-RESISTANCE AB The contribution of tumorigenic stem cells to haematopoietic cancers has been established for some time, and cells possessing stem-cell properties have been described in several solid tumours. Although chemotherapy kills most cells in a tumour, it is believed to leave tumour stem cells behind, which might be an important mechanism of resistance. For example, the ATP-binding cassette (ABC) drug transporters have been shown to protect cancer stem cells from chemotherapeutic agents. Gaining a better insight into the mechanisms of stem-cell resistance to chemotherapy might therefore lead to new therapeutic targets and better anticancer strategies. C1 NCI, Lab Genom Divers, Frederick, MD 21702 USA. NCI, Canc Therapeut Branch, Bethesda, MD 20892 USA. RP Dean, M (reprint author), NCI, Lab Genom Divers, Frederick, MD 21702 USA. EM dean@ncifcrf.gov RI Dean, Michael/G-8172-2012 OI Dean, Michael/0000-0003-2234-0631 NR 105 TC 1864 Z9 2026 U1 53 U2 379 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD APR PY 2005 VL 5 IS 4 BP 275 EP 284 DI 10.1038/nrc1590 PG 10 WC Oncology SC Oncology GA 912PG UT WOS:000228091000013 PM 15803154 ER PT J AU Burnett, JC Henchal, EA Schmaljohn, AL Bavari, S AF Burnett, JC Henchal, EA Schmaljohn, AL Bavari, S TI The evolving field of biodefence: Therapeutic developments and diagnostics SO NATURE REVIEWS DRUG DISCOVERY LA English DT Review ID ANTHRAX LETHAL FACTOR; RICIN A-CHAIN; BOTULINUM NEUROTOXIN-B; PUBLIC-HEALTH MANAGEMENT; EBOLA-VIRUS GLYCOPROTEIN; T-CELL ACTIVATION; STAPHYLOCOCCAL-ENTEROTOXIN-B; SMALL-MOLECULE INHIBITORS; N-GLYCOSIDASE ACTIVITY; ACTIVITY IN-VITRO AB The threat of bioterrorism and the potential use of biological weapons against both military and civilian populations has become a major concern for governments around the world. For example, in 2001 anthrax-tainted letters resulted in several deaths, caused widespread public panic and exerted a heavy economic toll. If such a small-scale act of bioterrorism could have such a huge impact, then the effects of a large-scale attack would be catastrophic. This review covers recent progress in developing therapeutic countermeasures against, and diagnostics for, such agents. C1 NCI, Dev Therapeut Program, Based Drug Discovery Grp, SAIC, Frederick, MD 21702 USA. USA, Med Res Inst Infect Dis, Frederick, MD 21702 USA. RP Bavari, S (reprint author), NCI, Dev Therapeut Program, Based Drug Discovery Grp, SAIC, Frederick, MD 21702 USA. EM sina.bavari@amedd.army NR 204 TC 100 Z9 101 U1 4 U2 17 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD APR PY 2005 VL 4 IS 4 BP 281 EP 297 DI 10.1038/nrd1694 PG 17 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 912PV UT WOS:000228092600016 PM 15803193 ER PT J AU Schwartzberg, PL Finkelstein, LD Readinger, JA AF Schwartzberg, PL Finkelstein, LD Readinger, JA TI TEC-family kinases: Regulators of T-helper-cell differentiation SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID BRUTONS TYROSINE KINASE; X-LINKED AGAMMAGLOBULINEMIA; NF-KAPPA-B; PLECKSTRIN HOMOLOGY DOMAIN; IMMUNODEFICIENT XID MICE; EXCHANGE FACTOR VAV; C-THETA; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR AB The TEC-family protein tyrosine kinases ITK, RLK and TEC have been identified as key components of T-cell-receptor signalling that contribute to the regulation of phospholipase C-gamma, the mobilization of Ca2+ and the activation of mitogen-activated protein kinases. Recent data also show that TEC kinases contribute to T-cell-receptor-driven actin reorganization and cell polarization, which are required for productive T-cell activation. Functional studies have implicated TEC kinases as important mediators of pathways that control the differentiation of CD4(+) T helper cells. Here, we review studies of signalling pathways that involve TEC kinases and how these pathways might contribute to the regulation of T-helper-cell differentiation and function. C1 NHGRI, NIH, Bethesda, MD 20892 USA. RP Schwartzberg, PL (reprint author), NHGRI, NIH, 4A38-49 Convent Dr, Bethesda, MD 20892 USA. EM pams@mail.nih.gov NR 119 TC 72 Z9 74 U1 2 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD APR PY 2005 VL 5 IS 4 BP 284 EP 295 DI 10.1038/nri1591 PG 12 WC Immunology SC Immunology GA 912PX UT WOS:000228092800012 PM 15803148 ER PT J AU Rouault, TA Tong, WH AF Rouault, TA Tong, WH TI Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis SO NATURE REVIEWS MOLECULAR CELL BIOLOGY LA English DT Review ID FRATAXIN-DEFICIENT STRAIN; CYTOSOLIC FE/S PROTEINS; YEAST FRATAXIN; FRIEDREICH ATAXIA; SACCHAROMYCES-CEREVISIAE; SCAFFOLD PROTEIN; S PROTEINS; IN-VIVO; HOMOLOG; METABOLISM AB Iron-sulphur clusters are important cofactors for proteins that are involved in many cellular processes, including electron transport, enzymatic catalysis and regulation. The enzymes that catalyse the formation of iron-sulphur clusters are widely conserved from bacteria to humans. Recent studies in model systems and humans reveal that iron-sulphur proteins have important roles in mitochondrial iron homeostasis and in the pathogenesis of the human disease Friedreich ataxia. C1 NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. RP Rouault, TA (reprint author), NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. EM trou@helix.nih.gov; tongw@mail.nih.gov NR 70 TC 209 Z9 216 U1 0 U2 19 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0072 J9 NAT REV MOL CELL BIO JI Nat. Rev. Mol. Cell Biol. PD APR PY 2005 VL 6 IS 4 BP 345 EP 351 DI 10.1038/nrm1620 PG 7 WC Cell Biology SC Cell Biology GA 912EQ UT WOS:000228060400016 PM 15803140 ER PT J AU Vanderpool, CK Gottesman, S AF Vanderpool, CK Gottesman, S TI Noncoding RNAs at the membrane SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Editorial Material ID SIGNAL RECOGNITION PARTICLE; ESCHERICHIA-COLI; MESSENGER-RNA; GLUCOSE-TRANSPORTER; POSTTRANSCRIPTIONAL REGULATION; DEGRADATION; EXPRESSION; TARGETS; GENE; HFQ AB A noncoding regulatory RNA in Escherichia coli, SgrS, downregulates the message for the glucose transporter, limiting accumulation of toxic sugar phosphates. Now a new study finds that SgrS can work only when the target message is brought to the membrane by transmembrane coding regions. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. RP Vanderpool, CK (reprint author), NCI, Mol Biol Lab, Bethesda, MD 20892 USA. EM susang@helix.nih.gov NR 12 TC 13 Z9 14 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD APR PY 2005 VL 12 IS 4 BP 285 EP 286 DI 10.1038/nsmb0405-285 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 913BW UT WOS:000228126200005 PM 15809646 ER PT J AU Gandjour, J Oehler, J Mohr, A Schellinger, RD AF Gandjour, J Oehler, J Mohr, A Schellinger, RD TI Heat stroke with alpha coma. A case report SO NERVENARZT LA German DT Article DE alpha coma; heat stroke; hyperthermia; multiorgan failure; SIRS ID HEATSTROKE; SEPSIS AB We report the case of a near-fatal heat stroke in a 41-year-old patient. The comatose patient had a body core temperature of 41.5&DEG; C. The clinical course was complicated by systemic inflammatory response syndrome and multiorgan failure. The EEG showed an alpha coma that did not react to external stimuli and, in general, has a poor prognosis. The patient regained consciousness and was discharged from our intensive care unit after 16 days. In the further course cerebral toxoplasmosis developed which was treated with a combination therapy of sulfadiazine and pyrimethamine. The patient was transferred to a neurorehabilitation clinic with a moderate neurological deficit 65 days after heat stroke onset. C1 Univ Zurich Hosp, Neurointensivstat Neurochirurg Klin, CH-8091 Zurich, Switzerland. Univ Heidelberg, Abt Neuroradiol, Heidelberg, Germany. Univ Heidelberg, Neurol Klin, Heidelberg, Germany. Stadt Klinikum Karlsruhe, Neurol Klin, Karlsruhe, Germany. Univ Gottingen, Abt Neuroradiol, D-3400 Gottingen, Germany. NINDS, NIH, Bethesda, MD 20892 USA. RP Gandjour, J (reprint author), Univ Zurich Hosp, Neurointensivstat Neurochirurg Klin, Frauenklinikstr 10, CH-8091 Zurich, Switzerland. EM joubin.gandjour@usz.ch NR 10 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0028-2804 J9 NERVENARZT JI Nervenarzt PD APR PY 2005 VL 76 IS 4 BP 467 EP 470 DI 10.1007/s00115-004-1715-6 PG 6 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 924DZ UT WOS:000228960300009 PM 15127143 ER PT J AU Schaefer, M Flor, H Heinze, HJ Rotte, M AF Schaefer, M Flor, H Heinze, HJ Rotte, M TI Dynamic shifts in the organization of primary somatosensory cortex induced by bimanual spatial coupling of motor activity SO NEUROIMAGE LA English DT Article DE plasticity; somatosensory cortex; bimanual movement; gating; magnetoencephalography ID EVOKED MAGNETIC-FIELDS; PHANTOM-LIMB PAIN; FUNCTIONAL-ORGANIZATION; FINGER MOVEMENTS; SHORT-TERM; REPRESENTATION; COORDINATION; MODULATION; AREA; REORGANIZATION AB Previous work has shown that training and learning can induce powerful changes in the homuncular organization of the primary somatosensory cortex (S1). Moreover, a number of studies suggest the existence of short-term adaptation of representational maps in SI. Recently, motor activity has been shown to induce rapid modulation of somatosensory cortical maps. It is hypothesized that there is a task-related influence of motor and premotor areas upon the organization of somatosensory cortex. In order to test this hypothesis, we studied the functional organization of somatosensory cortex by examining coupling effects in a bimanual movement task. Bimanual coupling is known to be related to an activation of the premotor cortex and the supplementary motor area. The functional organization of the somatosensory cortex for known bimanual coupling effects was compared to the organization of the somatosensory cortex during the same movements but with only a small effort in coupling. Topography of the functional organization of the somatosensory cortex was assessed using neuromagnetic source imaging based on tactile stimulation of the first (D1) and fifth digit (D5). We could show that the cortical representations of D1 and D5 moved further apart during the bimanual coupling task in comparison to the same task without coupling and rest. Our data suggest that somatosensory cortical maps undergo fast and dynamic modulation as a result of a task-related influence of motor or premotor areas. (c) 2004 Elsevier Inc. All rights reserved. C1 Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. Otto Von Guericke Univ, Dept Neurol 2, D-39120 Magdeburg, Germany. Univ Heidelberg, Cent Inst Mental Hlth, Dept Clin & Cognit Neurosci, D-68159 Mannheim, Germany. RP Schaefer, M (reprint author), Natl Inst Neurol Disorders & Stroke, Human Cort Physiol Sect, NIH, Bldg 10,Room 5S-208, Bethesda, MD 20892 USA. EM schaefem@ninds.nih.gov OI Flor, Herta/0000-0003-4809-5398 NR 37 TC 14 Z9 14 U1 1 U2 2 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 1 PY 2005 VL 25 IS 2 BP 395 EP 400 DI 10.1016/j.neuroimage.2004.11.032 PG 6 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 915XI UT WOS:000228344300006 PM 15784417 ER PT J AU Holton, JL Revesz, T Bhardwaj, N Venner, K Vicart, P Goldfarb, L Clarke, C AF Holton, JL Revesz, T Bhardwaj, N Venner, K Vicart, P Goldfarb, L Clarke, C TI A novel desmin mutation associated with skeletal myopathy and heart block SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Meeting Abstract CT 106th Annual Meeting of the British-Neuropathological-Society CY JAN 12-14, 2005 CL Inst Child Hlth, London, ENGLAND SP British Neuropathol Soc HO Inst Child Hlth C1 Inst Neurol, Div Neuropathol, London WC1N 3BG, England. Inst Neurol, Dept Mol Neurosci, London WC1N 3BG, England. NINDS, Clin Neurogenet Unit, Bethesda, MD 20892 USA. UCL Natl Hosp Neurol & Neurosurg, London WC1N 3BG, England. EM j.holton@ion.ucl.ac.uk RI Holton, Janice/F-6831-2011 OI Holton, Janice/0000-0002-3882-5249 NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD APR PY 2005 VL 31 IS 2 BP 239 EP 239 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 905VA UT WOS:000227597500066 ER PT J AU Le Foll, B Sokoloff, P Stark, H Goldberg, SR AF Le Foll, B Sokoloff, P Stark, H Goldberg, SR TI Dopamine D-3 receptor ligands block nicotine-induced conditioned place preferences through a mechanism that does not involve discriminative-stimulus or antidepressant-like effects SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE conditioned place preference; dopamine D-3 receptors; nicotine; discrimination; antidepressant; D3R-deficient mice ID COCAINE-SEEKING BEHAVIOR; NUCLEUS-ACCUMBENS; D-AMPHETAMINE; DRUG DISCRIMINATION; OXIDATION CURRENTS; MESSENGER-RNA; BRAIN REWARD; RAT-BRAIN; ANTAGONIST; MICE AB Environmental stimuli previously paired with drug taking appear to play a critical role in nicotine dependence. Converging anatomical, pharmacological, and behavioral evidence implicates dopamine D-3 receptors (D(3)Rs) in the mechanisms underlying stimulus-controlled drug-seeking behavior. This study assessed the effects of BP 897, a D3R partial agonist and ST 198, a D3R antagonist, on nicotine-induced conditioned place preferences (CPPs), used as a measure of drug-seeking behavior, on food-maintained responding and on discrimination performance under a two-lever-choice nicotine discrimination procedure. BP 897 and ST 198 both blocked the expression of nicotine-induced CPP at doses selective for D3R. They had no effect on locomotor activity in the CPP apparatus and no significant effect on nicotine discrimination performance or food-maintained responding under the discrimination procedure. Involvement of antidepressant actions in the effects of BP 897 and ST 198 on CPP is unlikely, since we found no effect of D3R blockade with BP 897 or genetic depletion of D(3)Rs in a forced swimming test, used as a behavioral test for antidepressant activity. This suggests that D3R ligands reduce the motivational effects of nicotine by a mechanism distinct from those of nicotine replacement therapy and bupropion, the two currently used aids for smoking cessation in humans. These findings support the use of D3R ligands as aids for smoking cessation and indicate that their effects would be selective for those rewarding or reinforcing effects of nicotine that contribute to the maintenance of tobacco-smoking behavior, without affecting subjective responses to nicotine or producing any antidepressant-like effects. C1 NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, NIH,Dept HHS, Baltimore, MD 21224 USA. Ctr Paul Broca, INSERM, U573, Unite Neurobiol & Pharmacol Mol, Paris, France. Goethe Univ Frankfurt, Inst Pharmazeut Chem, D-6000 Frankfurt, Germany. RP Le Foll, B (reprint author), NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, NIH,Dept HHS, 5500 Nathan Shock Dr,POB 5180, Baltimore, MD 21224 USA. EM blefoll@intra.nida.nih.gov RI Stark, Holger/A-4235-2009; Le Foll, Bernard/K-2952-2014; Fachbereich14, Dekanat/C-8553-2015 OI Stark, Holger/0000-0003-0642-0180; Le Foll, Bernard/0000-0002-6406-4973; NR 70 TC 67 Z9 68 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 2005 VL 30 IS 4 BP 720 EP 730 DI 10.1038/sj.npp.1300622 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 907JY UT WOS:000227714300008 PM 15562293 ER PT J AU Cobb, NK Graham, AL Bock, BC Papandonatos, G Abrams, DB AF Cobb, NK Graham, AL Bock, BC Papandonatos, G Abrams, DB TI Initial evaluation of a real-world Internet smoking cessation system SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID TOBACCO DEPENDENCE; INTERVENTIONS; PROGRAM; RELAPSE; COMMUNICATION; PROSPECTUS; SMOKERS; FUTURE; MODEL; CARE AB To significantly reduce smoking prevalence, treatments must balance reach, efficacy, and cost. The Internet can reach millions of smokers cost-effectively. Many cessation Web sites exist, but few have been evaluated. As a result, the potential impact of the Internet on smoking prevalence remains unknown. The present study reports the results, challenges, and limitations of a preliminary, large-scale evaluation of a broadly disseminated smoking cessation Web site used worldwide (QuitNet). Consecutive registrants (N = 1,50 1) were surveyed 3 months after they registered on the Web site to assess 7-day point prevalence abstinence. Results must be interpreted cautiously because this is an uncontrolled study with a 25.6% response rate. Approximately 30% of those surveyed indicated they had already quit smoking at registration. Excluding these participants, an intention-to-treat analysis yielded 7%. point prevalence abstinence (for the responders only, abstinence was 30%). A range of plausible cessation outcomes (9.8%-13.1%) among various subgroups is presented to illustrate the strengths and limitations of conducting Web-based evaluations, and the tensions between clinical and dissemination research methods. Process-to-outcome analyses indicated that sustained use of QuitNet, especially the use of social support, was associated with more than three times greater point prevalence abstinence and more than four times greater continuous abstinence. Despite its limitations, the present study provides useful information about the potential efficacy, challenging design and methodological issues, process-to-outcome mechanisms of action, and potential public health impact of Internet-based behavior change programs for smoking cessation. C1 Brown Med Sch, Miriam Hosp, Ctr Behav & Prevent Med, Providence, RI 02903 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Brown Univ, Ctr Stat Sci, Providence, RI 02912 USA. Brown Univ, Sch Med, Ctr Alcohol & Addict Studies, Providence, RI 02912 USA. NIH, Off Behav & Social Sci, Bethesda, MD USA. RP Graham, AL (reprint author), Brown Med Sch, Miriam Hosp, Ctr Behav & Prevent Med, 1 Hoppin St,Coro Suite 500, Providence, RI 02903 USA. EM amanda_graham@brown.edu RI Papandonatos, George/J-2328-2014; OI Cobb, Nathan/0000-0003-4210-226X; Papandonatos, George/0000-0001-6770-932X FU NCI NIH HHS [1R43CA09790301A1, CA84719, P50 CA084719, R01 CA104836, R01 CA104836-01A1, R43CA09921101] NR 43 TC 133 Z9 135 U1 0 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD APR PY 2005 VL 7 IS 2 BP 207 EP 216 DI 10.1081/14622200500055319 PG 10 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 926IQ UT WOS:000229117300004 PM 16036277 ER PT J AU Garmestani, K Milenic, DE Brady, ED Plascjak, PS Brechbiel, MW AF Garmestani, K Milenic, DE Brady, ED Plascjak, PS Brechbiel, MW TI Purification of cyclotron-produced Pb-203 for labeling Herceptin SO NUCLEAR MEDICINE AND BIOLOGY LA English DT Article DE (203) Ph; SPECT Herceptin; cyclotron ID MONOCLONAL-ANTIBODY; OVARIAN-CARCINOMA; THERAPY; LIGAND; DECAY AB A simple and rapid procedure was developed for the purification of cyclotron-produced Ph-203 via the Tl-203(d,2n) Pb-203 reaction. A Pb(II) selective ion-exchange resin; with commercial name Pb Resin from Eichrom Technologies, Inc., was used to purify Pb-203 from the cyclotron-irradiated Tl target with excellent recovery of the enriched Tl target material. The Purified Pb-203 was used to radiolabel the monoclonal antibody Herceptin. The in vitro and in vivo properties of the Pb-203 radioimmunoconjugate were evaluated. (c) 2005 Elsevier Inc. All rights reserved. C1 NCI, Radiat Oncol Branch, Radioimmune & Inorgan Chem Sect, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept PET, Bethesda, MD 20892 USA. RP Brechbiel, MW (reprint author), NIH, Sect Chem, Bldg 10, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov NR 23 TC 8 Z9 8 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0969-8051 J9 NUCL MED BIOL JI Nucl. Med. Biol. PD APR PY 2005 VL 32 IS 3 BP 301 EP 305 DI 10.1016/j.nucmedbio.2004.11.004 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 921WW UT WOS:000228797300011 PM 15820766 ER PT J AU Vahratian, A Zhang, J Troendle, JF Sciscione, AC Hoffman, MK AF Vahratian, A Zhang, J Troendle, JF Sciscione, AC Hoffman, MK TI Labor progression and risk of cesarean delivery in electively induced nulliparas SO OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 24th Annual Meeting of the Society-for-Maternal-Fetal-Medicine CY FEB 02-07, 2004 CL NEW ORLEANS, LA SP Soc Maternal Fetal Med ID FOLEY CATHETER; INDUCTION; MISOPROSTOL; WOMEN; OUTCOMES; COHORT; TRIAL; TERM AB OBJECTIVE: To describe the pattern of labor progression and risk of cesarean delivery in women whose labor was electively induced. METHODS: We analyzed data on all low-risk, nulliparous women with an elective induction or spontaneous onset of labor between 37 + 0 and 40 + 6 weeks from January 2002 to March 2004 at a single institution. The median duration of labor by each centimeter of cervical dilation and the risk of cesarean delivery were computed for 143 women with preinduction cervical ripening and oxytocin induction, 286 women with oxytocin induction, and 1,771 women with a spontaneous onset of labor. An intracervical Foley catheter was used to ripen the cervix. RESULTS: Electively induced labor with cervical ripening had substantially slower latent and early active phases. After controlling for potential confounders, women who had an elective induction with cervical ripening had 3.5 times the risk of cesarean delivery during the first stage of labor (95% confidence interval 2.7-4.5), compared with those admitted in spontaneous labor. Elective induction without cervical ripening, on the other hand, was associated with a faster labor progression from 4 to 10 cm (266 compared with 358 minutes, P < .01) and did not increase the risk of cesarean delivery, compared with those in spontaneous labor. CONCLUSION: The pattern of labor progression differs substantially for women with an electively induced labor compared with those with spontaneous onset of labor. Furthermore, elective induction in nulliparous women with an unfavorable cervix has a high rate of labor arrest and a substantially increased risk of cesarean delivery. C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, Bethesda, MD 20892 USA. Drexel Univ, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Christiana Care Hlth Syst, Dept Obstet & Gynecol, Wilmington, DE USA. RP Zhang, J (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, US Dept HHS, 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA. EM zhangj@exchange.nih.gov RI Vahratian, Anjel/A-1182-2011 NR 19 TC 144 Z9 148 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2005 VL 105 IS 4 BP 698 EP 704 DI 10.1097/01.AOG.0000157436.68847.3b PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 910WK UT WOS:000227962700003 PM 15802393 ER PT J AU Meikle, SF Steiner, CA Zhang, J Lawrence, WL AF Meikle, SF Steiner, CA Zhang, J Lawrence, WL TI A national estimate of the elective primary cesarean delivery rate SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID IDENTIFY INDICATIONS AB OBJECTIVE: We describe national trends for elective primary cesarean delivery from 1994 to 2001, with attention to changes in indications. METHODS: We used data from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample. Cesarean deliveries were identified by International Classification of Diseases, 9th Revision, Clinical Modification procedure and diagnostic codes; V codes identified all types of deliveries for denominators. Twelve indications for elective primary cesarean delivery were targeted. International Classification of Diseases, 9th Revision, Clinical Modification coding changes were also evaluated. RESULTS: After excluding women who had labored and previous cesarean deliveries, elective primary cesarean deliveries rose from 19.7% of all cesarean deliveries in 1994 to 28.3% in 2001, an increase of approximately 43.6%. The use of the identified indications for elective primary cesarean delivery increased for codes representing malpresentation, antepartum bleeding, hypertension and severe hypertension, macrosomia, unengaged head, preterm gestation, and maternal soft tissue disorders. Coding for herpes, multiple gestation, other uterine scar, and congenital central nervous system remained the same. Additionally, a new 1998 code for fetal heart rate abnormalities was rapidly adopted during the study period. CONCLUSION: A national estimate of the elective primary cesarean delivery rate shows a rising trend. Additionally, coded indications for these procedures are shifting. Further examination into the use and clinical implications of indications through national surveillance for elective primary cesarean delivery is important for future obstetric practice. A revision of the terminology classification used to identify indications for cesarean delivery procedures would aid in this effort. C1 Agcy Healthcare Res & Qual, Rockville, MD 20850 USA. NICHHD, NIH, Rockville, MD USA. RP Meikle, SF (reprint author), Agcy Healthcare Res & Qual, 540 Gaither Rd, Rockville, MD 20850 USA. EM smeikle@ahrq.gov NR 15 TC 65 Z9 66 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2005 VL 105 IS 4 BP 751 EP 756 DI 10.1097/01.AOG.0000157435.67138.78 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 910WK UT WOS:000227962700011 PM 15802401 ER PT J AU Signore, C Mills, JL Cox, C Trumble, AC AF Signore, C Mills, JL Cox, C Trumble, AC TI Effects of folic acid fortification on twin gestation rates SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID NEURAL-TUBE DEFECTS; FOOD FORTIFICATION; MULTIPLE BIRTHS; UNITED-STATES; SUPPLEMENTATION; TECHNOLOGY; PREVENTION; VITAMIN; FOLATE AB OBJECTIVE: Previous studies have reported an increase in twinning of as much as 40% associated with folic acid-containing supplements, and folic acid fortification of enriched cereal grains was authorized in 1996. The purpose of this study was to investigate whether twinning rates have increased since that time. METHODS: We used United States birth and fetal death records to calculate twin gestation rates from 1990 through 2000. To eliminate the influence of fertility treatments, our analysis was limited to nulliparous women aged 16-19. We compared time trends in twin gestation rates before and after folic acid fortification in 1996. RESULTS: A total of 25,065 twin and 3,362,245 singleton pregnancies were included. Twin gestation rates were stable from January 1990 through December 1996, at 7.2 per 1,000, and then began a steady increase, averaging 2.4% (95% confidence interval 0.1-4.2%, P = .006) per year, which continued through 2000 and readied 8.2 per 1,000. This translates to 2 additional twin pregnancies per 10,000 gestations per year. Twin rates continued to increase well beyond 1998, when the maximal fortification effect on folate status had been reached. CONCLUSION: Although twin gestation rates in women not using fertility treatments increased after food fortification with folic acid, they rose by much less than the 40% rate previously reported; the observed pattern of increase in twin gestation rates is not consistent with a folic acid fortification effect. C1 NICHD, Epidemiol Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. NICHD, Biometry & Math Stat Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. NICHD, Biometry & Math Stat Branch, Comp Sci Sect,Div Epidemiol Stat & Prevent Res, NIH,US Dept HHS, Bethesda, MD 20892 USA. RP Mills, JL (reprint author), NICHD, Pediat Epidemiol Sect, DESPR, NIH, 6100 Execut Blvd,Room 7B03, Bethesda, MD 20892 USA. EM jamesmills@nih.gov NR 35 TC 13 Z9 15 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2005 VL 105 IS 4 BP 757 EP 762 DI 10.1097/01.AOG.0000154886.40318.5e PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 910WK UT WOS:000227962700012 PM 15802402 ER PT J AU Dunson, DB Bigelow, JL Colombo, B AF Dunson, DB Bigelow, JL Colombo, B TI Reduced fertilization rates in older men when cervical mucus is suboptimal SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID FERTILITY; PREGNANCY; AGE; INTERCOURSE; CONCEPTION; OVULATION; INSEMINATION; PROBABILITY AB OBJECTIVE: Cervical mucus is vital in the regulation of sperm survival and transport through the reproductive tract. The goal of this study is to assess whether the lowered fertility for men in their late 30s and early 40s is related to the nature of cervical mucus on the day of intercourse. METHODS: In a prospective study of 7 European family planning centers, 782 couples not using birth control recorded daily observations of intercourse and the nature of cervical mucus. Using data from 1,459 menstrual cycles, 342 ending in pregnancy, we estimate day-specific conception probabilities in relation to mucus and male and female age. RESULTS: On days where cervical mucus was not evident, intercourse for men in their late 30s and early 40s was 50% less likely to result in a clinical pregnancy, adjusting for intercourse timing and female age. As secretions become more conducive to sperm transport, the effect of male age diminishes steadily from 21% on days with damp secretions, to 11% on days with thick mucus, to only 4% on days with most fertile-type mucus. CONCLUSION: The effect of male age on fecundability can be minimized by timing intercourse on days with optimal secretions. C1 NIEHS, US NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Univ Padua, Dept Stat, Padua, Italy. RP Dunson, DB (reprint author), NIEHS, US NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM dunson1@niehs.nih.gov NR 25 TC 8 Z9 11 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2005 VL 105 IS 4 BP 788 EP 793 DI 10.1097/01.AOG.0000154155.20366.ee PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 910WK UT WOS:000227962700016 PM 15802406 ER PT J AU Harville, EW Hertz-Picciotto, I Schramm, M Watt-Morse, M Chantala, K Osterloh, J Parsons, PJ Rogan, W AF Harville, EW Hertz-Picciotto, I Schramm, M Watt-Morse, M Chantala, K Osterloh, J Parsons, PJ Rogan, W TI Factors influencing the difference between maternal and cord blood lead SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID SUDDEN-INFANT-DEATH; COGNITIVE-DEVELOPMENT; DIETARY CALCIUM; PREGNANT-WOMEN; MEXICO-CITY; PLASMA LEAD; EXPOSURE; BONE; LEVEL; PRESSURE AB Aims: To determine the factors that affect why some infants receive higher exposures relative to the mother's body burden than do others. Methods: A total of 159 mother-infant pairs from a cohort of women receiving prenatal care at Magee-Womens Hospital in Pittsburgh, PA from 1992 to 1995 provided blood samples at delivery for lead determination. The difference between cord and maternal blood lead concentration (PbB) and a dichotomous variable indicator of higher cord than maternal PbB, were examined as indicators of relative transfer. Women were interviewed twice during the pregnancy about lifestyle, medical history, calcium nutrition, and physical activity. Results: Higher blood pressure was associated with relatively greater cord compared with maternal PbB, as was maternal alcohol use. Sickle cell trait and higher haemoglobin were associated with a lower cord relative to maternal blood lead PbB. No association was seen with smoking, physical exertion, or calcium consumption. Conclusion: While reduction in maternal exposure will reduce fetal exposure, it may also be possible to mitigate infant lead exposure by reducing transfer from the pregnant woman. Interventions aimed at reducing blood pressure and alcohol consumption during pregnancy may be useful in this regard. C1 Univ N Carolina, Dept Epidemiol, Chapel Hill, NC 27599 USA. Univ N Carolina, Carolina Populat Ctr, Chapel Hill, NC 27599 USA. Magee Womens Hosp, Dept Obstet & Gynecol, Pittsburgh, PA USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. New York State Dept Hlth, Wadsworth Ctr, Albany, NY 12237 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Harville, EW (reprint author), Univ N Carolina, Dept Epidemiol, CB 7435, Chapel Hill, NC 27599 USA. EM ewh@unc.edu RI Parsons, Patrick/I-2985-2015; Rogan, Walter/I-6034-2012 OI Parsons, Patrick/0000-0001-9133-875X; Rogan, Walter/0000-0002-9302-0160 FU NIEHS NIH HHS [R01-ES05738] NR 64 TC 25 Z9 27 U1 1 U2 6 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD APR PY 2005 VL 62 IS 4 BP 263 EP 269 DI 10.1136/oem.2003.012492 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 907TC UT WOS:000227739900011 PM 15778260 ER PT J AU Wright, JJ Zerivitz, K Gravell, A AF Wright, JJ Zerivitz, K Gravell, A TI Current clinical trials of BAY 43-9006, Part 1 SO ONCOLOGY-NEW YORK LA English DT Editorial Material ID BRAF GENE; MUTATIONS; CARCINOMA; CANCER; RAF C1 NCI, Bethesda, MD 20892 USA. Tech Resources Int Inc, Bethesda, MD USA. Emmes Corp, Rockville, MD USA. RP Wright, JJ (reprint author), NCI, Bethesda, MD 20892 USA. NR 14 TC 8 Z9 9 U1 0 U2 0 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD APR PY 2005 VL 19 IS 4 BP 499 EP 502 PG 4 WC Oncology SC Oncology GA 052EG UT WOS:000238213600014 PM 15934518 ER PT J AU Ferrigno, L Aldigeri, R Rosmini, F Sperduto, RD Maraini, G AF Ferrigno, L Aldigeri, R Rosmini, F Sperduto, RD Maraini, G CA Italian-American Cataract Stdy Grp TI Associations between plasma levels of vitamins and cataract in the Italian-American Clinical Trial of Nutritional Supplements and Age-related Cataract (CTNS): CTNS report #2 SO OPHTHALMIC EPIDEMIOLOGY LA English DT Article DE vitamin A; vitamin E; vitamin C; glutathione reductase; age-related cataract; cataract prevalence ID POSTERIOR SUBCAPSULAR CATARACTS; OPACITIES CASE-CONTROL; LENS OPACITIES; NUTRIENT INTAKE; RISK-FACTORS; ANTIOXIDANT VITAMINS; BETA-CAROTENE; NUCLEAR; EYE; PROGRESSION AB Purpose: To investigate the association at baseline between plasma levels of selected vitamins and the presence and type of cataract in the participants in The Italian-American Trial of Nutritional Supplements and Age-related Cataract. Methods: At baseline, the participants (1020, 710 with "early cataract" and 310 with "no cataract," 55-75 years of age) received an ocular examination, photographic lens grading, and measurement of plasma levels of vitamins A, C, E, beta-carotene, and of red blood cell glutathione reductase activity. Results: In multiple logistic models adjusted for potential confounders, high vitamin C levels were associated with a protective effect on nuclear (N) [OR: 0.54; 95% CI: 0.30, 0.97] and posterior subcapsular (PSC) cataract (OR: 0.37; 95% CI: 0.15, 0.93). High vitamin E levels were associated with increased prevalence of cortical cataract (C) (OR: 1.99; 95% CI: 1.02-3.90), PSC (OR: 3.27; 95% CI: 1.34, 7.96) and of any cataract (OR: 1.86; 95% CI: 1.08, 3.18). Conclusions: In agreement with some earlier studies, we found higher plasma levels of vitamin C to be associated with reduced prevalence of N and PSC cataracts. The finding of an increased prevalence of some types of cataract with higher levels of vitamin E was unexpected, has not been previously reported, and could be due to unadjusted confounding. C1 Univ Parma, Otorino Odonto Oftalmol & Cerv Fac, Dipartimento Sci, Sect Ophthalmol, I-43100 Parma, Italy. ISS, Sorveglianza & Promoz Salut, Ctr Nazl Epidemiol, Rome, Italy. NEI, Bethesda, MD 20892 USA. RP Maraini, G (reprint author), Univ Parma, Dept Ophthalmol, Via Gramsci 14, I-43100 Parma, Italy. EM maraini@ipruniv.cc.unipr.it OI Aldigeri, Raffaella/0000-0003-2350-1222 FU NEI NIH HHS [N01-EY-5-2100] NR 33 TC 19 Z9 21 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0928-6586 J9 OPHTHAL EPIDEMIOL JI Ophthalmic Epidemiol. PD APR PY 2005 VL 12 IS 2 BP 71 EP 80 DI 10.1080/09286580590932815 PG 10 WC Ophthalmology SC Ophthalmology GA 930NL UT WOS:000229422800001 PM 16019690 ER PT J AU Milton, RC Clemons, TE Kurinij, N Sperduto, RD AF Milton, RC Clemons, TE Kurinij, N Sperduto, RD CA Age Related Eye Dis Study Res Grp TI Risk factors for the incidence of advanced age-related macular degeneration in the age-elated eye disease study (AREDS) - AREDS report no.19 SO OPHTHALMOLOGY LA English DT Article ID BLUE-MOUNTAINS-EYE; BEAVER-DAM EYE; BODY-MASS INDEX; CIGARETTE-SMOKING; POOLED FINDINGS; DIETARY-FAT; 10-YEAR INCIDENCE; CATARACT-SURGERY; BETA-CAROTENE; UNITED-STATES AB Purpose: To describe the association of demographic, behavioral, medical, and nonretinal ocular factors with the incidence of neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA) in the Age-Related Eye Disease Study (AREDS), a randomized trial of antioxidants and zinc supplementation prophylaxis for development of advanced AMD. Design: Clinic-based prospective cohort study. Participants: Of individuals with early or intermediate AMD at baseline with a median follow-up of 6.3 years, 788 were at risk of developing advanced AMD in one eye (the fellow eye had advanced AMD), and 2506 were at risk in both eyes. Methods: The incidence of neovascular AMD and CGA was assessed from stereoscopic color fundus photographs taken at baseline and at annual visits beginning at year 2. Main Outcome Measures: Neovascular AMD was defined as photocoagulation for choroidal neovascularization, or photographic documentation at the reading center of any of the following: nondrusenoid retinal pigment epithelial detachment, serous or hemorrhagic retinal detachment, hemorrhage under the retina or the retinal pigment epithelium, and subretinal fibrosis. Central geographic atrophy was defined as geographic atrophy involving the center of the macula. Results: In multivariable models, in persons at risk of advanced AMD in both eyes, while controlling for age, gender, and AREDS treatment group, the following variables were statistically significantly associated with the incidence of neovascular AMD: race (odds ratio [OR], white vs. black, 6.77; 95% confidence interval [CI], 1.24-36.9) and larger amount smoked (OR, > 10 vs. <= 10 pack-years [a pack-year is an average of 1 pack of cigarette smoked per day for a year], 1.55; 95% CI, 1.15-2.09). The following were statistically significantly associated with the incidence of CGA: less education (OR, high school graduate or less vs. college graduate, 1.75; 95% CI, 1.10-2.78), greater body mass index (BMI) (OR, obese vs. nonobese, 1.93; 95% CI, 1.25-2.65), larger amount smoked (OR, > 10 pack-years vs. <= 10 pack-years, 1.82; 95% CI, 1.25-2.65), and antacid use (OR, 0.29; 95% CI, 0.09-0.91). In persons at risk of developing advanced AMD in one eye, the incidence of neovascular AMD was associated with diabetes (OR, 1.88; 95% CI, 1.07-3.31), and the incidence of CGA was associated with use of anti inflammatory medications (OR, 0.22; 95% Cl, 0.08-0.59). Conclusions: Results suggest that, among persons with early or intermediate AMD, smoking and BMI are modifiable factors associated with progression to advanced AMD, and suggest other associations (e.g., use of antacids and anti inflammatory medications) that warrant further study. Ophthalmology 2005;112:533-539 (c) 2005 by the American Academy of Ophthalmology. C1 EMMES Corp, AREDS Coordinating Ctr, Rockville, MD 20850 USA. Univ Wisconsin, Madison, WI USA. Massachusetts Eye & Ear Infirm, Boston, MA 02114 USA. NEI, Bethesda, MD 20892 USA. RP Milton, RC (reprint author), EMMES Corp, AREDS Coordinating Ctr, 701 N Washington St,Suite 700, Rockville, MD 20850 USA. EM rmilton@emmes.com; aredspub@emmes.com NR 52 TC 314 Z9 319 U1 3 U2 20 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2005 VL 112 IS 4 BP 533 EP 539 DI 10.1016/j.ophtha.2004.10.047 PG 7 WC Ophthalmology SC Ophthalmology GA 910WF UT WOS:000227962200002 ER PT J AU Goh, PP Abqariyah, Y Pokharel, GP Ellwein, LB AF Goh, PP Abqariyah, Y Pokharel, GP Ellwein, LB TI Refractive error and visual impairment in school-age children in Gombak District, Malaysia SO OPHTHALMOLOGY LA English DT Article ID POPULATION; CHINA; PREVALENCE; MYOPIA AB Purpose: To assess the prevalence of refractive error and visual impairment in school-age children in Gombak District, a suburban area near Kuala Lumpur city. Design: Population -based, cross-sectional survey. Participants: Four thousand six hundred thirty-four children 7 to 15 years of age living in 3004 households. Methods: Random selection of geographically defined clusters was used to identify the study sample. Children in 34 clusters were enumerated through a door-to-door survey and examined in 140 schools between March and July 2003. The examination included visual acuity measurements; ocular motility evaluation; retinoscopy and autorefraction under cycloplegia; and examination of the external eye, anterior segment, media, and fundus. Main Outcome Measures: Distance visual acuity and cycloplegic refraction. Results: The examined population was 70.3% Malay, 16.5% Chinese, 8.9% Indian, and 4.3% of other ethnicity. The prevalence of uncorrected (unaided), presenting, and best-corrected visual impairment (visual acuity :<= 20/40 in the better eye) was 17.1 %, 10.1 %, and 1.4%, respectively. More than half of those in need of corrective spectacles were without them. In eyes with reduced vision, refractive error was the cause in 87.0%, amblyopia in 2.0%, other causes in 0.6%, and unexplained causes in 10.4%, mainly suspected amblyopia. Myopia (spherical equivalent of at least -0.50 diopter [D] in either eye) measured with retinoscopy was present in 9.8% of children 7 years of age, increasing to 34.4% in 15-year-olds; and in 10.0% and 32.5%, respectively, with autorefraction. Myopia was associated with older age, female gender, higher parental education, and Chinese ethnicity. Hyperopia (>= 2.00 D) with retinoscopy varied from 3.8% in 7-year-olds, 5.0% with autorefraction, to less than 1 % by age 15, with either measurement method. Hyperopia was associated with younger age and "other" ethnicity. Astigmatism (>= 0.75 D) was present in 15.7% of children with retinoscopy and in 21.3% with autorefraction. Conclusions: Visual impairment in school-age children in urban Gombak District is overwhelmingly caused by myopia, with a particularly high prevalence among children of Chinese ethnicity. Eye health education and screening may help address the unmet need for refractive correction. Ophthalmology 2005;112:678-685 (c) 2005 by the American Academy of Ophthalmology. C1 NEI, NIH, Bethesda, MD 20892 USA. Hosp Selayang, Dept Ophthalmol, Selangor, Malaysia. Clin Res Ctr & Inst Med Res, Kuala Lumpur, Malaysia. WHO, Prevent Blindness & Deafness, CH-1211 Geneva, Switzerland. RP Ellwein, LB (reprint author), NEI, NIH, 31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. EM ellweinl@nei.nih.gov RI Yahya, Abqariyah/B-5638-2017 OI Yahya, Abqariyah/0000-0001-9158-415X FU NEI NIH HHS [N01-EY-2103] NR 19 TC 140 Z9 152 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0161-6420 J9 OPHTHALMOLOGY JI Ophthalmology PD APR PY 2005 VL 112 IS 4 BP 678 EP 685 DI 10.1016/j.ophtha.2004.10.048 PG 8 WC Ophthalmology SC Ophthalmology GA 910WF UT WOS:000227962200024 PM 15808262 ER PT J AU He, MG Xu, JJ Yin, QX Ellwein, LB AF He, MG Xu, JJ Yin, QX Ellwein, LB TI Need and challenges of refractive correction in urban Chinese school children SO OPTOMETRY AND VISION SCIENCE LA English DT Article DE visual acuity; eyeglasses; ocular refraction; children; urban population; Chinese ID VISUAL IMPAIRMENT; ERROR; PREVALENCE; POPULATION; MYOPIA AB Purpose. Uncorrected refractive error is recognized as the principal cause of visual impairment in school-aged children. Although correction of refractive error is easy, safe, and effective, many children are without the necessary spectacles. Empiric research on barriers to refractive correction remains limited, precluding the formulation of effective remedial actions. The aims of this study were to characterize parental awareness and other barriers to spectacle use among children considered to be in need of refractive correction and to determine the proportion undercorrected for those already with spectacles. Methods. A population-based sample of children 5 to 15 years of age was examined in Guangzhou, China. Visual acuity was measured followed by cycloplegic refraction and best-corrected vision. Parental awareness of the child's vision difficulties, spectacle use, and frequency of vision checkups were collected by questionnaire. Associations between these variables and demographic and socioeconomic characteristics were investigated with multiple logistic regression. Results. Among the 4359 examined children, 919 (21.1 %) were found to be in need of refractive correction. Need was defined as uncorrected visual acuity <= 0.50 in both eyes correctable by at least two lines in the better eye. Parental awareness was apparent for 85% of cases; 74% had spectacles. Awareness of vision difficulties was associated with older child age, greater visual impairment, and higher parental education. The purchase of spectacles was associated with greater visual impairment; the child's age, gender, parental education, and family income were not significant factors. Undercorrection by two lines or more in the better eye was found in 30% of those already with spectacles; undercorrection was associated with greater visual impairment and less frequent refraction checkups. Conclusions. Half of the children in need of first-time or updated spectacles are without them, an unacceptably high proportion. Younger children with moderate visual impairment are at particular risk for uncorrected refractive error. Parental education and enhanced school-based screening programs may be necessary to address the unfilled need for refractive correction among school-aged children. C1 NEI, NIH, Bethesda, MD 20892 USA. Zhongshan Ophthal Ctr, Guangzhou, Peoples R China. Helen Keller Int, New York, NY USA. RP Ellwein, LB (reprint author), NEI, NIH, 31 Ctr Dr,MSC 2510, Bethesda, MD 20892 USA. EM ellweinl@nei.nih.gov OI He, Mingguang/0000-0002-6912-2810 FU NEI NIH HHS [N01-EY-2103] NR 14 TC 32 Z9 36 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-5488 J9 OPTOMETRY VISION SCI JI Optom. Vis. Sci. PD APR PY 2005 VL 82 IS 4 BP 229 EP 234 PG 6 WC Ophthalmology SC Ophthalmology GA 918UF UT WOS:000228572400002 PM 15829844 ER PT J AU Gutkind, JS AF Gutkind, JS TI Signal transduction and oral cancer: novel therapeutic opportunities? SO ORAL ONCOLOGY LA English DT Meeting Abstract CT 10th International Congress on Oral Cancer CY APR 19-24, 2005 CL Crete, GREECE C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RI Gutkind, J. Silvio/A-1053-2009 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 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD APR PY 2005 VL 1 IS 1 SU S BP 30 EP 31 DI 10.1016/S1744-7895(05)80018-5 PG 2 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 000XE UT WOS:000234494900017 ER PT J AU Gutkind, JS AF Gutkind, JS TI Genomic approaches in oral cancer: What have we learned? SO ORAL ONCOLOGY LA English DT Meeting Abstract CT 10th International Congress on Oral Cancer CY APR 19-24, 2005 CL Crete, GREECE C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. RI Gutkind, J. Silvio/A-1053-2009 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 1368-8375 J9 ORAL ONCOL JI Oral Oncol. PD APR PY 2005 VL 1 IS 1 SU S BP 59 EP 59 DI 10.1016/S1744-7895(05)80102-6 PG 1 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA 000XE UT WOS:000234494900099 ER PT J AU Yoo, BM Yeo, M Oh, TY Choi, JH Kim, WW Kim, JH Cho, SW Kim, SJ Hahm, KB AF Yoo, BM Yeo, M Oh, TY Choi, JH Kim, WW Kim, JH Cho, SW Kim, SJ Hahm, KB TI Amelioration of pancreatic fibrosis in mice with defective TGF-beta signaling SO PANCREAS LA English DT Article ID TRANSFORMING-GROWTH-FACTOR; CERULEIN-INDUCED PANCREATITIS; STELLATE CELLS; INCREASED EXPRESSION; GENE-EXPRESSION; TRANSGENIC MICE; RAT PANCREAS; GROWTH-FACTOR-BETA-1; ACTIVATION; RECEPTORS AB Objectives: Pancreatic fibrosis is a characteristic feature of chronic pancreatic injury, which is a result of the imbalance between synthesis and degradation of extracellular matrix (ECM) proteins. Transforming growth factor-beta (TGF-beta) plays a central role in biosynthesis and turnover of the ECM. In this study, we evaluated the role of TGF-beta signaling in pancreatic fibrosis induced by repetitive acute pancreatic injuries with mice of dominant-negative mutant of TGF-beta receptor II selectively in pancreas. Methods: TGF-beta signaling was inactivated by overexpressing a dominant-negative mutant form of TGF-beta type II receptor (pS(2)-dnR II) only in the pancreas under control of pS2/TFF1 promoter. Pancreatic fibrosis was induced by repeated intraperitoneal injections of 40 mu g/kg cerulein for 5 or 10 weeks. Results: Repeated administration of cerulein induced significant pancreatic fibrosis, but of which fibrosis was remarkably attenuated in pS(2)-dnR II mice compared with wild-type littermates (P < 0.01). The ameliorated fibrosis was due to the reduction of synthesis of ECM proteins such as collagen type I, fibronectin, and ICAM-1. DNA binding activity of transcriptional factors including nuclear factor (NF)-kappa B and AP-1, responsible for the induction of immediate early genes of inflammatory responses, were significantly decreased in pS(2)-dnR II mice. While TGF-beta 1 treatment in isolated pancreatic stellate cells (PSCs) stimulated the expression of alpha-SMA and fibronectin, PSCs transfected with TGF-beta dnRII showed attenuation of the ECM components. Conclusion: Conditional loss of TGF-beta signaling selectively in the pancreas led to a failure in fibrogenic responses of repeated injections of cerulein, signifying that the modulation of TGF-beta signaling could be the therapeutic target for the prevention of chronic fibrosing pancreatitis. C1 Ajou Univ, Genome Res Ctr Gastroenterol, Sch Med, Dept Gastroenterol, Suwon 442749, South Korea. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Hahm, KB (reprint author), Ajou Univ, Genome Res Ctr Gastroenterol, Sch Med, Dept Gastroenterol, 5 Wonchon Dong, Suwon 442749, South Korea. EM hahmkb@hotmail.com NR 44 TC 31 Z9 32 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0885-3177 J9 PANCREAS JI Pancreas PD APR PY 2005 VL 30 IS 3 BP E71 EP E79 DI 10.1097/01.mpa.0000157388.54016.0a PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 911MO UT WOS:000228007300022 PM 15782092 ER PT J AU Van Winkle, P Angiolillo, A Krailo, M Cheung, YK Anderson, B Davenport, V Reaman, G Cairo, MS AF Van Winkle, P Angiolillo, A Krailo, M Cheung, YK Anderson, B Davenport, V Reaman, G Cairo, MS TI Ifosfamide, carboplatin, and etoposide (ICE) reinduction chemotherapy in a large cohort of children and adolescents with recurrent/refractory sarcoma: The Children's Cancer Group (CCG) experience SO PEDIATRIC BLOOD & CANCER LA English DT Article DE refractory sarcomas; reinduction chemotherapy ID PEDIATRIC-ONCOLOGY-GROUP; COLONY-STIMULATING FACTOR; MALIGNANT SOLID TUMORS; SOFT-TISSUE SARCOMA; RELAPSED WILMS-TUMOR; HIGH-DOSE IFOSFAMIDE; GROUP PHASE-II; FRENCH-SOCIETY; INTERGROUP RHABDOMYOSARCOMA; PROGNOSTIC-FACTORS AB Background. The prognosis for children with recurrent/refractory sarcomas is poor. We determined the overall response rate (ORR) and overall survival (OS) of children with recurrent/refractory sarcomas who were given ifosfamide, carboplatin, and etoposide (ICE) in three Children's Cancer Group (CCG) phase I/II trials. Procedure. Children with recurrent/refractory sarcoma were treated with ifosfamide (1,800 mg/m(2)/day on day 0-4), carboplatin (400 mg/m(2)/day on day 0-1), etoposide (100 mg/m(2)/day on day 0-4) and either rhG-CSF (10 mug/kg/day vs. 5 mug/kg/clay, CCG-0894 71 patients), PIXY321 (500-1,000 mug/m(2)/clay CCG-0924, 14 patients), or rhG-CSF (5 mug/kg/day) and IL-6 (2.5-5 mug/kg/day, CCG-0931, 12 patients). Results. Ninety-seven patients were evaluable for tumor response, 56 male and 41 female, median age 14.1 years (range 2.82-2.5 years). Tumor types were osteosarcoma (OTS) (n=34), rhabdomyosarcoma (n 27). Ewing sarcoma (EWS) (n=21), soft tissuesarcoma-not otherwise specified (n=5), undifferentiated sarcoma (n=6), fibrosarcoma (n=2), peripheral primitive neuroectodermal tumor (n=1), and extraosseous Ewing (n=1). The ORR was 51% (27% complete response CRI). OS at 1 and 2 years was 49% and 281%, respectively. Patients with CR or partial response (PR) had significantly increased 1- and 2-year OS, 71% and 41%, respectively, (P<0.001). Rhabdomyosarcoma patients with embryonal histology had significant improvement in 1- and 2-year OS: 82% and 46%, respectively, compared with other histologies, (P<0.005). Conclusions. The ORR to ICE re-induction chemotherapy in children with recurrent/refractory sarcoma was 51%. OS of 1 and 2 years appeared significantly improved in patients who had CR or PR following ICE reinduction therapy or who had rhabdomyosarcoma with embryonal histology. Published 2004 Wiley-Liss, Inc.(dagger) C1 Childrens Oncol Grp, Arcadia, CA 91066 USA. Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Columbia Univ, New York, NY USA. NCI, CTEP, Bethesda, MD 20892 USA. RP Cairo, MS (reprint author), Childrens Oncol Grp, POB 60012, Arcadia, CA 91066 USA. EM mc1310@columbia.edu NR 45 TC 47 Z9 50 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD APR PY 2005 VL 44 IS 4 BP 338 EP 347 DI 10.1002/pbc.20227 PG 10 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 901MJ UT WOS:000227286300005 PM 15503297 ER PT J AU Nachman, SA Lindsey, JC Moye, J Stanley, KE Johnson, GM Krogstad, PA Wiznia, AA AF Nachman, SA Lindsey, JC Moye, J Stanley, KE Johnson, GM Krogstad, PA Wiznia, AA CA Pediat AIDS Clinical Trials Grp TI Growth of human immunodeficiency virus-infected children receiving highly active antiretroviral therapy SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE human immunodeficiency virus; child; growth; body height; body weight; highly active antiretroviral therapy ID RANDOMIZED CONTROLLED-TRIAL; 1-INFECTED CHILDREN; PROTEASE INHIBITORS; PROSPECTIVE COHORT; PLUS NEVIRAPINE; SOMATIC GROWTH; YOUNG-CHILDREN; RITONAVIR; HIV; WEIGHT AB Background: Weight and height growth of HIV-infected children tends to lag behind that of uninfected children of similar age. Previous reports of the effect of highly active antiretroviral therapy (HAART) on the growth of HIV-infected children have been contradictory. Methods: Age- and gender-adjusted height and weight z scores were studied for 192 HIV-infected children, 4 months to 17 years of age, who had been treated with antiretroviral therapy for at least 16 weeks. These children, in clinically and immunologically stable condition, were enrolled into one of 4 HAART regimens and evaluated for 96 weeks. Results: At baseline, these HIV-infected children were significantly shorter than uninfected children (mean 7 score, -0.57; 95% confidence interval, -0.73 to -0.41; P < 0.001). Children with greater viral loads at baseline were significantly shorter and lighter than children with smaller viral loads (both P < 0.001). Administration of HAART led to an increase in mean weight 7 scores to normal values (mean z score increase, from - 0.16 to > 0) by week 48 and an increase in mean height z scores of 72% toward normal values (mean z score increase, from -0.57 to -0.16) by week 96. Younger children gained height more rapidly (P < 0.001), and children with greater baseline viral loads gained weight more rapidly (P < 0.001). There was no evidence of differential height or weight changes in 48 weeks between children with different degrees of virologic control. Conclusions: HAART improved the average weight gain of HIV-infected children from subnormal to normal after I year and improved average height growth to nearly normal after 2 years. C1 SUNY Stony Brook, Hlth Sci Ctr, Dept Pediat, Stony Brook, NY 11794 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Dept Pediat, Charleston, SC 29425 USA. Univ Calif Los Angeles, Dept Pediat, David Geffen Sch Med, Los Angeles, CA 90024 USA. Jacobi Med Ctr, Dept Pediat, New York, NY USA. Albert Einstein Coll Med, New York, NY USA. RP Nachman, SA (reprint author), SUNY Stony Brook, Hlth Sci Ctr, Dept Pediat, Stony Brook, NY 11794 USA. EM snachman@notes.cc.sunysb.edu OI moye, john/0000-0001-9976-8586 NR 25 TC 58 Z9 59 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD APR PY 2005 VL 24 IS 4 BP 352 EP 357 DI 10.1097/01.inf.0000157095.75081.43 PG 6 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 918RU UT WOS:000228566100010 PM 15818296 ER PT J AU Kleta, R Kaskel, F Dohil, R Goodyer, P Guay-Woodford, LM Harms, E Ingelfinger, JR Koch, VH Langman, CB Leonard, MB Mannon, RB Sarwal, M Schneider, JA Skovby, F Sonies, BC Thoene, JG Trauner, DA Gahl, WA AF Kleta, R Kaskel, F Dohil, R Goodyer, P Guay-Woodford, LM Harms, E Ingelfinger, JR Koch, VH Langman, CB Leonard, MB Mannon, RB Sarwal, M Schneider, JA Skovby, F Sonies, BC Thoene, JG Trauner, DA Gahl, WA TI First NIH/office of rare diseases conference on cystinosis: Past, present, and future SO PEDIATRIC NEPHROLOGY LA English DT Article C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIH, Off Rare Dis, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Childrens Hosp Montefiore, Bronx, NY 10461 USA. Univ Calif San Diego, Div Pediat Gastroenterol & Hepatol, San Diego, CA 92103 USA. McGill Univ, Med Ctr, Dept Pediat, Montreal, PQ, Canada. Univ Alabama, Div Genet & Translat Med, Birmingham, AL USA. Univ Childrens Hosp, Munster, Germany. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Pediat Nephrol Unit, Boston, MA USA. Sao Paulo Med Sch, Hosp Clin, Inst Crianca, Pediat Nephrol Unit, Sao Paulo, Brazil. Childrens Mem Med Ctr, Chicago, IL USA. Childrens Hosp Philadelphia, Div Nephrol, Philadelphia, PA 19104 USA. NIDDK, Transplantat Branch, Bethesda, MD USA. Stanford Univ, Dept Pediat, Stanford, CA 94305 USA. Univ Calif San Diego, La Jolla, CA 92093 USA. Copenhagen Univ Hosp, Dept Clin Genet, Copenhagen, Denmark. NIH, Ultrasound Imaging Lab, Dept Rehabil Med, Bethesda, MD 20892 USA. Tulane Univ, Sch Med, Hayward Genet Ctr, New Orleans, LA 70112 USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. NIH, Sect Human Biochem Genet, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NHGRI, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1851,Bldg 10,Room 10C103, Bethesda, MD 20892 USA. EM bgahl@helix.nih.gov NR 2 TC 18 Z9 19 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD APR PY 2005 VL 20 IS 4 BP 452 EP 454 DI 10.1007/s00467-004-1777-5 PG 3 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 903RA UT WOS:000227442100003 PM 15747161 ER PT J AU Nelson, KB Dambrosia, JM Iovannisci, DM Cheng, S Grether, JK Lammer, E AF Nelson, KB Dambrosia, JM Iovannisci, DM Cheng, S Grether, JK Lammer, E TI Genetic polymorphisms and cerebral palsy in very preterm infants SO PEDIATRIC RESEARCH LA English DT Article ID RISK; INFLAMMATION; DISEASE; COAGULATION; INFECTION; CHILDREN AB In the present study, we examine whether selected genetic polymorphisms contribute to the development of cerebral palsy (CP) in very preterm infants. Subjects were 96 singleton infants with later-diagnosed CP and 119 control children, white non-Hispanic (n for CP = 74, controls = 88) or white Hispanic (CP = 22, controls = 31), born < 32 wk gestation. Presence of CP was identified through state service agencies, with review of medical records. DNA extracted from archived neonatal blood was genotyped using multi-locus polymerase chain reaction amplification and immobilized sequence-specific oligonucleotide probes. Single nucleotide polymorphisms (SNPs) showing evidence of association with development of CP were endothelial nitric oxide synthase (eNOS) A(-922)G, factor 7 (177) arg353gln and del(-323)10bp-ins, and lymphotoxin A (LTA) thr26asn. In white non-Hispanic children, beta-2 adrenergic receptor gln27glu was associated with CP risk; in Hispanic children, plasminogen activator inhibitor-1 (PAI-1) 4G(-675)5G and G11053T were associated with risk of CP. In a logistic regression considering these SNPs simultaneously in non-Hispanics, an association with CP was observed for heterozygotes of eNOS -922 (OR 3.0, Cl 1.4-6.4), F7 (OR 2.7, CI 1.1-6.5), LTA (OR 2.1, Cl 1.0-4.6), and PAI-1 (OR 3.2, CI 1.2-8.7). Factor 5, Factor 2, methylene tetrahydrofolate reductase, tumor necrosis factor-alpha, and other SNPs tested were not significantly associated with CP risk. We conclude that further study of genetic factors that may influence susceptibility to CP in very preterm infants is warranted. C1 NINDS, Bethesda, MD 20892 USA. Childrens Hosp, Oakland, CA 94609 USA. Res Ctr, Oakland, CA 94609 USA. Roche Mol Syst Inc, Dept Human Genet, Alameda, CA 94501 USA. Calif Dept Hlth Serv, Oakland, CA 94612 USA. RP Nelson, KB (reprint author), NIH, Bldg 10,Room 5S220, Bethesda, MD 20892 USA. EM knelson@helix.nih.gov FU NINDS NIH HHS [NS35573-01] NR 18 TC 62 Z9 71 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2005 VL 57 IS 4 BP 494 EP 499 DI 10.1203/01.PDR.0000156477.00386.E7 PG 6 WC Pediatrics SC Pediatrics GA 907VQ UT WOS:000227746600006 PM 15718364 ER PT J AU Moolchan, ET Robinson, ML Ernst, M Cadet, JL Pickworth, WB Heishman, SJ Schroeder, JR AF Moolchan, ET Robinson, ML Ernst, M Cadet, JL Pickworth, WB Heishman, SJ Schroeder, JR TI Safety and efficacy of the nicotine patch and gum for the treatment of adolescent tobacco addiction SO PEDIATRICS LA English DT Article DE treatment; adolescent; tobacco; nicotine patch; nicotine gum; cessation; smoking reduction ID RANDOMIZED CLINICAL-TRIAL; SMOKING-CESSATION; CIGARETTE-SMOKING; REPLACEMENT THERAPY; MAJOR DEPRESSION; HARM REDUCTION; DOUBLE-BLIND; SMOKERS; DEPENDENCE; ISSUES AB Objectives. To determine the safety and efficacy of the nicotine patch and gum for adolescents who want to quit smoking. Design. Double-blind, double-dummy, randomized, 3-arm trial with a nicotine patch ( 21 mg), nicotine gum ( 2 and 4 mg), or a placebo patch and gum; all participants received cognitive-behavioral group therapy. Setting. Inner-city, outpatient clinic on the East Coast. Subjects. Thirteen- to 17-year-old adolescents who smoked >= 10 cigarettes per day (CPD), scored >= 5 on the Fagerstrom Test of Nicotine Dependence, and were motivated to quit smoking. Intervention. Twelve weeks of nicotine patch or gum therapy with cognitive-behavioral therapy, with a follow-up visit at 6 months ( 3 months after the end of treatment). Main Outcome Measures. Safety assessed on the basis of adverse event reports for all 3 groups, prolonged abstinence, assessed through self-report and verified with exhaled carbon monoxide ( CO) levels of <= 6 ppm, in intent-to-treat analyses, and smoking reduction ( CPD and thiocyanate concentrations) among trial completers. Results. A total of 120 participants were randomized (72% white, 70% female; age: 15.2 +/- 1.33 years; smoking: 18.8 +/- 8.56 CPD; Fagerstrom Test of Nicotine Dependence score: 7.04 +/- 1.29) from 1999 to 2003. Participants started smoking at 11.2 +/- 1.98 years of age and had been smoking daily for 2.66 +/- 1.56 years; 75% had at least 1 current psychiatric diagnosis. Mean compliance across groups was higher for the patch ( mean: 78.4 - 82.8%) than for the gum ( mean: 38.5 - 50.7%). Both the patch and gum were well tolerated, and adverse events were similar to those reported in adult trials. Changes in mean saliva cotinine concentrations throughout treatment were not statistically significant. Intent-to-treat analyses of all randomized participants showed CO-confirmed prolonged abstinence rates of 18% for the active-patch group, 6.5% for the active-gum group, and 2.5% for the placebo group; the difference between the active-patch and placebo arms was statistically significant. There was no significant effect of patch versus gum or gum versus placebo on cessation outcomes. Abstinence rates at the 3-month follow-up assessment were sustained but were not significantly associated with treatment group. Mean smoking rates, but not CO or thiocyanate concentrations, decreased significantly in all 3 arms but not as a function of treatment group. Conclusions. Nicotine patch therapy combined with cognitive-behavioral intervention was effective, compared with placebo, for treatment of tobacco dependence among adolescent smokers. Decreases in the numbers of cigarettes smoked appeared to be offset by compensatory smoking. Additional study of nicotine gum, with enhanced instructional support, is needed to assess its efficacy among adolescent smokers. C1 NIDA, Teen Tobacco Addict Res Clin, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, Baltimore, MD 21224 USA. RP Moolchan, ET (reprint author), NIDA, Teen Tobacco Addict Res Clin, Clin Pharmacol & Therapeut Res Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM emoolcha@intra.nida.nih.gov NR 42 TC 60 Z9 61 U1 2 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD APR PY 2005 VL 115 IS 4 DI 10.1542/peds.2004-1894 PG 8 WC Pediatrics SC Pediatrics GA 912VL UT WOS:000228107900005 PM 15805342 ER PT J AU Nachman, S Gona, P Dankner, W Weinberg, A Yogev, R Gershon, A Rathore, M Read, JS Huang, S Elgie, C Hudgens, K Hughes, W AF Nachman, S Gona, P Dankner, W Weinberg, A Yogev, R Gershon, A Rathore, M Read, JS Huang, S Elgie, C Hudgens, K Hughes, W TI The rate of serious bacterial infections among HIV-infected children with immune reconstitution who have discontinued opportunistic infection prophylaxis SO PEDIATRICS LA English DT Article; Proceedings Paper CT 11th Conference on Retroviruses and Opportunistic Infections CY FEB 08-11, 2004 CL San Francisco, CA DE pediatric HIV; bacterial infections; immune reconstitution ID PNEUMOCYSTIS-CARINII-PNEUMONIA; IMMUNODEFICIENCY-VIRUS TYPE-1; ANTIRETROVIRAL THERAPY; EFFICACY; COUNT; AIDS; CHEMOPROPHYLAXIS; DISEASE; TRIAL; RISK AB Objective. Receipt of highly active antiretroviral therapy is associated with a decrease in the incidence of opportunistic infections (OIs) among HIV-infected adults. The goal of Pediatric AIDS Clinical Trials Group protocol 1008 was to evaluate prospectively the incidence of serious bacterial infections (SBIs) and other OIs after discontinuation of OI and/or Pneumocystis jiroveci pneumonia (PCP) prophylaxis among HIV-infected pediatric subjects who experienced immune reconstitution while receiving stable antiretroviral therapy. Methods. HIV-infected children and adolescents, 2 to 21 years of age, who had received OI and/or PCP prophylaxis for >= 6 months were enrolled if they had sustained responses (> 16 weeks before study entry) to antiretroviral therapy, with CD4(+) cell percentages of >= 20% for patients > 6 years of age or >= 25% for patients 2 to 6 years of age. Prophylaxis was discontinued at entry. To identify whether any correlation existed between functional immune reconstitution and protection from OIs, subjects were immunized with the hepatitis A virus vaccine. The association between the humoral immune response and the likelihood of developing an OI was evaluated. Results. A total of 235 HIV-infected subjects from 43 participating sites had a median follow-up period of 132 weeks, yielding 547 person-years of observation. Twenty SBIs were observed among 19 subjects, resulting in an incidence rate of 3.66 SBIs per 100 person-years (95% confidence interval: 2.24 - 5.66 SBIs per 100 person-years). Sixteen of the events were presumed bacterial pneumonia, with 4 proven SBIs. One participant experienced 2 separate pneumonia episodes, of presumed bacterial cause. Ten subjects who developed SBIs had baseline CD4(+) cell counts of >= 750 cells per mm(3), and 15 had CD4(+) cell percentages of >= 25% at the time of their SBIs. Two subjects died as a result of non - SBI-related causes. There were no statistically significant differences in changes over time in CD4(+) cell counts or CD4(+) cell percentages between subjects who experienced primary end points and those who did not. There was no evidence that baseline protease inhibitor use, gender, race/ethnicity, age, or CD4(+) cell count or percentage affected the time to development of a SBI. Conclusions. OI or PCP prophylaxis can be withdrawn safely for HIV-infected pediatric patients who experience CD4(+) cell recovery while receiving stable antiretroviral therapy. More studies are needed to assess the association between antibody responses to neoantigens and the development of SBIs. C1 SUNY Stony Brook, Dept Pediat, Stony Brook, NY 11794 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Northwestern Univ, Chicago, IL 60611 USA. Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Univ Florida, Hlth Sci Ctr, Jacksonville, FL 32209 USA. NICHHD, Bethesda, MD 20892 USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Social & Sci Syst, Silver Spring, MD USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. RP Nachman, S (reprint author), SUNY Stony Brook, Dept Pediat, HSC T11-060, Stony Brook, NY 11794 USA. EM sharon.nachman@stonybrook.edu FU NIAID NIH HHS [AI-41110]; NICHD NIH HHS [HD-33162, HD-33345] NR 25 TC 20 Z9 21 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2005 VL 115 IS 4 DI 10.1542/peds.2004-1847 PG 7 WC Pediatrics SC Pediatrics GA 912VL UT WOS:000228107900016 PM 15772172 ER PT J AU Raje, S Cornish, J Newman, AH Cao, JJ Katz, JL Eddington, ND AF Raje, S Cornish, J Newman, AH Cao, JJ Katz, JL Eddington, ND TI Pharmacodynamic assessment of the benztropine analogues AHN-1055 and AHN-2005 using intracerebral microdialysis to evaluate brain dopamine levels and pharmacokinetic/pharmacodynamic modeling SO PHARMACEUTICAL RESEARCH LA English DT Article DE benztropine; dopamine; cocaine; pharmacokinetics; pharmacodynamics ID UPTAKE INHIBITORS; IN-VIVO; EXTRACELLULAR DOPAMINE; NUCLEUS-ACCUMBENS; COCAINE; TRANSPORTER; RAT; LIGANDS; POTENT AB Purpose. The benztropine (BZT) analogues bind with high affinity to the dopamine transporter (DAT) and demonstrate a behavioral and pharmacokinetic profile unlike that of cocaine. The development of a predictive pharmacokinetic/pharmacodynamic (PK/PD) model to characterize the concentration-effect relationship between the BZT analogues and brain dopamine (DA) levels is an important step in the evaluation of these compounds as potential cocaine abuse pharmacotherapies. Hence, the objective of this study was to mathematically characterize the PD of BZT analogues and cocaine, using appropriate PK/PD models. Methods. Dialysis probes were stereotaxically implanted into the nucleus accumbens of Sprague-Dawley rats ( 275 - 300 g). Extracellular fluid (ECF) DA levels were measured after intravenous administration of the BZT analogues AHN-1055 and AHN-2005, as well as cocaine using high performance liquid chromatography-electrochemical detection (HPLC-ECD). PD models were used to describe the relationship between the BZT analogues or cocaine and brain microdialysate DA, and suitability was based on standard goodness-of-fit criteria. Results. The BZT analogues produced a sustained increase in brain microdialysate DA levels in comparison to cocaine. The time of maximum concentration (T-max) for brain microdialysate DA was 2 h for AHN-1055 and 1 h for AHN-2005 compared to a Tmax of 10 min for cocaine. The duration of brain microdialysate DA elevation was similar to 12 - 24 h for the BZTs in comparison to 1 h for cocaine. An indirect model with inhibition of loss of response and a sigmoid E-max model best described the PK/PD for the BZT analogues and cocaine, respectively. The 50% of maximum inhibition (IC50) of the loss of DA was lower for AHN-2005 ( 226 +/- 27.5 ng/ml) compared to AHN-1055 ( 321 +/- 19.7 ng/ml). In addition, the EC50 for cocaine was 215 +/- 11.2 ng/ml. Conclusions. The slow onset and long duration of BZT analogue - induced DA elevation may avoid the reinforcing effects and craving of cocaine. Further, the developed models will be useful in characterizing the PK/PD of other analogues and aid in the assessment of the therapeutic efficacy of the BZT analogues as substitute medications for cocaine abuse. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, Baltimore, MD 21201 USA. NIDA, Psychobiol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIDA, Med Chem Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Eddington, ND (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Pharmacokinet Biopharmaceut Lab, Baltimore, MD 21201 USA. EM neddingt@rx.umaryland.edu OI Katz, Jonathan/0000-0002-1068-1159 NR 25 TC 25 Z9 25 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD APR PY 2005 VL 22 IS 4 BP 603 EP 612 DI 10.1007/s11095-005-2496-8 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 919TV UT WOS:000228641400010 PM 15846468 ER PT J AU Winhusen, T Somoza, E Haffer, JM Moore, E Ussery, T Kropp, F Singal, B Elkashef, A Mojsiak, J AF Winhusen, T Somoza, E Haffer, JM Moore, E Ussery, T Kropp, F Singal, B Elkashef, A Mojsiak, J TI Metyrapone and cocaine: A double-blind, placebo-controlled drug interaction study SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article DE cocaine; metyrapone; cortisol; cardiovascular effects; subjective effects ID GROWTH-HORMONE; CORTISOL; STRESS; GLUCOCORTICOIDS; CORTICOSTERONE; REINSTATEMENT; VULNERABILITY; PROLACTIN; SECRETION; HUMANS AB Pre-clinical research suggests that suppression of adrenocorticosteroid synthesis might decrease susceptibility to stress-induced relapse. Metyrapone effectively suppresses cortisol synthesis and thus might have promise as a cocaine dependence treatment. The present inpatient study evaluated the interaction of metyrapone and cocaine to assess the safety of conducting an outpatient trial. Twelve nontreatment-seeking cocaine-dependent individuals completed this double-blind, placebo-controlled, crossover study with two factors: medication (750 mg of metyrapone vs. placebo) and infusion (40 mg of cocaine vs. saline). Safety measures included vital signs, adverse events, and electrocardiogram. Efficacy measures included visual analog scale (VAS) ratings of craving and drug effect. Neuroendocrine measures included cortisol and ACTH. As predicted, metyrapone was well tolerated and did not exacerbate cocaine's physiological effects. Also as predicted, metyrapone did not significantly alter cocaine's subjective effects. The results of the present study suggest that metyrapone at the dose studied can likely be used safely in an outpatient study with active cocaine users. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Cincinnati, Coll Med, Dept Psychiat, Cincinnati, OH 45220 USA. Dept Vet Affairs Med Ctr, Cincinnati, OH 45220 USA. Natl Inst Drug Abuse, Med Dev Div, Bethesda, MD 20892 USA. RP Winhusen, T (reprint author), Univ Cincinnati, Coll Med, Dept Psychiat, 3210 Jefferson Ave, Cincinnati, OH 45220 USA. EM winhusen@mdru.uc.edu OI Winhusen, Theresa/0000-0002-3364-0739 FU NIDA NIH HHS [N01-DA-9-8095] NR 23 TC 7 Z9 7 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD APR PY 2005 VL 80 IS 4 BP 631 EP 638 DI 10.1016/j.pbb.2005.01.017 PG 8 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 920GT UT WOS:000228678100012 PM 15820533 ER PT J AU Wobus, AM Boheler, KR AF Wobus, AM Boheler, KR TI Embryonic stem cells: Prospects for developmental biology and cell therapy SO PHYSIOLOGICAL REVIEWS LA English DT Review ID IN-VITRO DIFFERENTIATION; PRIMORDIAL GERM-CELLS; GREEN FLUORESCENT PROTEIN; INSULIN-PRODUCING CELLS; DOUBLE-STRANDED-RNA; HEPATOCYTE-LIKE CELLS; EARLY MOUSE DEVELOPMENT; NEURAL PRECURSOR CELLS; GENE-EXPRESSION LEVELS; ZINC-FINGER GENE AB Stem cells represent natural units of embryonic development and tissue regeneration. Embryonic stem (ES) cells, in particular, possess a nearly unlimited self-renewal capacity and developmental potential to differentiate into virtually any cell type of an organism. Mouse ES cells, which are established as permanent cell lines from early embryos, can be regarded as a versatile biological system that has led to major advances in cell and developmental biology. Human ES cell lines, which have recently been derived, may additionally serve as an unlimited source of cells for regenerative medicine. Before therapeutic applications can be realized, important problems must be resolved. Ethical issues surround the derivation of human ES cells from in vitro fertilized blastocysts. Current techniques for directed differentiation into somatic cell populations remain inefficient and yield heterogeneous cell populations. Transplanted ES cell progeny may not function normally in organs, might retain tumorigenic potential, and could be rejected immunologically. The number of human ES cell lines available for research may also be insufficient to adequately determine their therapeutic potential. Recent molecular and cellular advances with mouse ES cells, however, portend the successful use of these cells in therapeutics. This review therefore focuses both on mouse and human ES cells with respect to in vitro propagation and differentiation as well as their use in basic cell and developmental biology and toxicology and presents prospects for human ES cells in tissue regeneration and transplantation. C1 IPK Gatersleben, In Vitro Differentiat Grp, D-06466 Gatersleben, Germany. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Wobus, AM (reprint author), IPK Gatersleben, In Vitro Differentiat Grp, Corrensstr 3, D-06466 Gatersleben, Germany. EM wobusam@ipk-gatersleben.de; bohelerk@grc.nia.nih.gov NR 419 TC 429 Z9 471 U1 19 U2 99 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD APR PY 2005 VL 85 IS 2 BP 635 EP 678 DI 10.1152/physrev.00054.2003 PG 44 WC Physiology SC Physiology GA 909IX UT WOS:000227854700005 PM 15788707 ER PT J AU Parekh, AB Putney, JW AF Parekh, AB Putney, JW TI Store-operated calcium channels SO PHYSIOLOGICAL REVIEWS LA English DT Review ID CAPACITATIVE CA2+ ENTRY; BASOPHILIC LEUKEMIA-CELLS; PROTEIN-KINASE-C; CURRENT I-CRAC; SMOOTH-MUSCLE-CELLS; PANCREATIC ACINAR-CELLS; INOSITOL 1,4,5-TRISPHOSPHATE RECEPTORS; JURKAT T-LYMPHOCYTES; ADRENAL CHROMAFFIN CELLS; POLYCYCLIC AROMATIC-HYDROCARBONS AB In electrically nonexcitable cells, Ca2+ influx is essential for regulating a host of kinetically distinct processes involving exocytosis, enzyme control, gene regulation, cell growth and proliferation, and apoptosis. The major Ca2+ entry pathway in these cells is the store-operated one, in which the emptying of intracellular Ca2+ stores activates Ca2+ influx (store-operated Ca2+ entry, or capacitative Ca2+ entry). Several biophysically distinct store-operated currents have been reported, but the best characterized is the Ca2+ release-activated Ca2+ current, I-CRAC. Although it was initially considered to function only in nonexcitable cells, growing evidence now points towards a central role for I-CRAC-like currents in excitable cells too. In spite of intense research, the signal that relays the store Ca2+ content to CRAC channels in the plasma membrane, as well as the molecular identity of the Ca2+ sensor within the stores, remains elusive. Resolution of these issues would be greatly helped by the identification of the CRAC channel gene. In some systems, evidence suggests that store- operated channels might be related to TRP homologs, although no consensus has yet been reached. Better understood are mechanisms that inactivate store- operated entry and hence control the overall duration of Ca2+ entry. Recent work has revealed a central role for mitochondria in the regulation of I-CRAC, and this is particularly prominent under physiological conditions. I-CRAC therefore represents a dynamic interplay between endoplasmic reticulum, mitochondria, and plasma membrane. In this review, we describe the key electrophysiological features of I-CRAC and other store-operated Ca2+ currents and how they are regulated, and we consider recent advances that have shed insight into the molecular mechanisms involved in this ubiquitous and vital Ca2+ entry pathway. C1 Univ Oxford, Dept Physiol, Oxford OX1 3PT, England. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Parekh, AB (reprint author), Univ Oxford, Dept Physiol, Parks Rd, Oxford OX1 3PT, England. EM anant.parekh@physiol.ox.ac.uk NR 416 TC 1299 Z9 1351 U1 10 U2 119 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0031-9333 J9 PHYSIOL REV JI Physiol. Rev. PD APR PY 2005 VL 85 IS 2 BP 757 EP 810 DI 10.1152/physrev.00057.2003 PG 54 WC Physiology SC Physiology GA 909IX UT WOS:000227854700008 PM 15788710 ER PT J AU Chen, KG Szakacs, G Annereau, JP Rouzaud, F Liang, XJ Valencia, JC Nagineni, CN Hooks, JJ Hearing, VJ Gottesman, MM AF Chen, KG Szakacs, G Annereau, JP Rouzaud, F Liang, XJ Valencia, JC Nagineni, CN Hooks, JJ Hearing, VJ Gottesman, MM TI Principal expression of two mRNA isoforms (ABCB5 alpha and ABCB5 beta) of the ATP-binding cassette transporter gene ABCB5 in melanoma cells and melanocytes SO PIGMENT CELL RESEARCH LA English DT Article DE ATP-binding cassette transporter; ABCB5; melanoma; melanocytes ID MULTIDRUG-RESISTANCE GENE; PRODUCT P-GLYCOPROTEIN; MELANOSOMAL PROTEINS; CANCER; TISSUES; SUPERFAMILY; PATTERNS; DISEASE; SISTER; TIME AB ATP-binding cassette (ABC) transporters play a pivotal role in physiology and pathology. We identified and cloned two novel mRNA isoforms (ABCB 5 alpha and ABCB 5 beta) of the ABC transporter ABCB 5 in human melanoma cells. The deduced ABCB 5 alpha protein appears to be an altered splice variant containing only a putative ABC, whereas the ABCB 5 beta isoform shares approximately 70% similarity with ABCB1 (MDR1) and has a deduced topological arrangement similar to that of the whole carboxyl terminal half of the ABCB1 gene product, P-glycoprotein, including an intact ABC. Northern blot, real-time PCR, and conventional RT-PCR were used to verify the expression profiles of ABCB 5 alpha/beta. We found that the melanomas included among the NCI-60 panel of cell lines preferentially expressed both ABCB 5 alpha and ABCB 5 beta. However, ABCB 5 alpha/beta expression was undetectable in two amelanotic melanomas (M14 and LOX-IMVI). The expression profile of ABCB 5 alpha/beta in all of the other melanomas of the panel was confirmed both by RT-PCR and by sequencing. Neither ABCB 5 alpha nor ABCB 5 beta expression was found in normal tissues such as liver, spleen, thymus, kidney, lung, colon, small intestines or placenta. ABCB 5 alpha/beta mRNAs were also expressed in normal melanocytes and in retinal pigment epithelial cells, suggesting that ABCB 5 alpha/beta expression is pigment cell-specific and might be involved in melanogenesis. Our findings indicate that expression of ABCB 5 alpha/beta might possibly provide two novel molecular markers for differential diagnosis of melanomas and constitute potential molecular targets for therapy of melanomas. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI Szakacs, Gergely/A-2580-2009; Chen, Kevin/D-6769-2011 OI Szakacs, Gergely/0000-0002-9311-7827; Chen, Kevin/0000-0003-2983-6330 FU Intramural NIH HHS [Z99 NS999999] NR 29 TC 46 Z9 47 U1 1 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD APR PY 2005 VL 18 IS 2 BP 102 EP 112 DI 10.1111/j.1600-0749.2005.00214.x PG 11 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 904XX UT WOS:000227533000006 PM 15760339 ER PT J AU Jeong, SY Rose, A Joseph, J Dass, M Meier, I AF Jeong, SY Rose, A Joseph, J Dass, M Meier, I TI Plant-specific mitotic targeting of RanGAP requires a functional WPP domain SO PLANT JOURNAL LA English DT Article DE RanGAP; Ran cycle; nuclear envelope; mitosis; cell plate; plant ID GTPASE-ACTIVATING PROTEIN; XENOPUS EGG EXTRACTS; NUCLEAR-PORE COMPLEX; CELL PLATE FORMATION; RNA1 GENE-PRODUCT; IMPORTIN-BETA; BINDING-PROTEIN; ENVELOPE; CYTOKINESIS; ARABIDOPSIS AB The small GTPase Ran is involved in nucleocytoplasmic transport, spindle formation, nuclear envelope (NE) formation, and cell-cycle control. In vertebrates, these functions are controlled by a three-dimensional gradient of Ran-GTP to Ran-GDP, established by the spatial separation of Ran GTPase-activating protein (RanGAP) and the Ran guanine nucleotide exchange factor RCC1. While this spatial separation is established by the NE during interphase, it is orchestrated during mitosis by association of RCC1 with the chromosomes and RanGAP with the spindle and kinetochores. SUMOylation of vertebrate RanGAP1 is required for NE, spindle, and centromere association. Arabidopsis RanGAP1 (AtRanGAP1) lacks the SUMOylated C-terminal domain of vertebrate RanGAP, but contains a plant-specific N-terminal domain (WPP domain), which is necessary and sufficient for its targeting to the NE in interphase. Here we show that the human and plant RanGAP-targeting domains are kingdom specific. AtRanGAP1 has a mitotic trafficking pattern uniquely different from that of vertebrate RanGAP, which includes targeting to the outward-growing rim of the cell plate. The WPP domain is necessary and sufficient for this targeting. Point mutations in conserved residues of the WPP domain also abolish targeting to the nuclear rim and the cell plate, suggesting that the same mechanism is involved in both targeting events. These results indicate that plant and animal RanGAPs undergo different migration patterns during cell division, which require their kingdom-specific targeting domains. C1 Ohio State Univ, Ctr Plant Biotechnol, Columbus, OH 43210 USA. Ohio State Univ, Dept Plant Cellular & Mol Biol, Columbus, OH 43210 USA. Natl Inst Child Hlth & Dev, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Meier, I (reprint author), Ohio State Univ, Ctr Plant Biotechnol, Columbus, OH 43210 USA. EM meier.56@osu.edu OI Dasso, Mary/0000-0002-5410-1371 FU Intramural NIH HHS [Z01 HD008740-06] NR 42 TC 34 Z9 39 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0960-7412 J9 PLANT J JI Plant J. PD APR PY 2005 VL 42 IS 2 BP 270 EP 282 DI 10.1111/j.1365.313X.2005.02368.x PG 13 WC Plant Sciences SC Plant Sciences GA 919UX UT WOS:000228644200012 PM 15807788 ER PT J AU Foster, J Ganatra, M Kamal, I Ware, J Makarova, K Ivanova, N Bhattacharyya, A Kapatral, V Kumar, S Posfai, J Vincze, T Ingram, J Moran, L Lapidus, A Omelchenko, M Kyrpides, N Ghedin, E Wang, S Goltsman, E Joukov, V Ostrovskaya, O Tsukerman, K Mazur, M Comb, D Koonin, E Slatko, B AF Foster, J Ganatra, M Kamal, I Ware, J Makarova, K Ivanova, N Bhattacharyya, A Kapatral, V Kumar, S Posfai, J Vincze, T Ingram, J Moran, L Lapidus, A Omelchenko, M Kyrpides, N Ghedin, E Wang, S Goltsman, E Joukov, V Ostrovskaya, O Tsukerman, K Mazur, M Comb, D Koonin, E Slatko, B TI The Wolbachia genome of Brugia malayi: Endosymbiont evolution within a human pathogenic nematode SO PLOS BIOLOGY LA English DT Review ID HUMAN FILARIAL PARASITE; NUCLEAR-MAGNETIC-RESONANCE; KERATITIS RIVER-BLINDNESS; ONCHOCERCA-VOLVULUS; PHYLOGENETIC ANALYSIS; BACTERIAL ENDOSYMBIONTS; DIROFILARIA-IMMITIS; SURFACE PROTEIN; IN-VITRO; CYTOPLASMIC INCOMPATIBILITY AB Complete genome DNA sequence and analysis is presented for Wolbachia, the obligate alpha-proteobacterial endosymbiont required for fertility and survival of the human filarial parasitic nematode Brugia malayi. Although, quantitatively, the genome is even more degraded than those of closely related Rickettsia species, Wolbachia has retained more intact metabolic pathways. The ability to provide riboflavin, flavin adenine dinucleotide, heme, and nucleotides is likely to be Wolbachia's principal contribution to the mutualistic relationship, whereas the host nematode likely supplies amino acids required for Wolbachia growth. Genome comparison of the Wolbachia endosymbiont of B. malayi (wBm) with the Wolbachia endosymbiont of Drosophila melanogaster (wMel) shows that they share similar metabolic trends, although their genomes show a high degree of genome shuffling. In contrast to wMel, wBm contains no prophage and has a reduced level of repeated DNA. Both Wolbachia have lost a considerable number of membrane biogenesis genes that apparently make them unable to synthesize lipid A, the usual component of proteobacterial membranes. However, differences in their peptidoglycan structures may reflect the mutualistic lifestyle of wBm in contrast to the parasitic lifestyle of wMel. The smaller genome size of wBm, relative to wMel, may reflect the loss of genes required for infecting host cells and avoiding host defense systems. Analysis of this first sequenced endosymbiont genome from a filarial nematode provides insight into endosymbiont evolution and additionally provides new potential targets for elimination of cutaneous and lymphatic human filarial disease. C1 New England Biolabs Inc, Mol Parasitol Div, Beverly, MA 01915 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD USA. Integrated Genom, Chicago, IL USA. Inst Genom Res, Rockville, MD USA. RP New England Biolabs Inc, Mol Parasitol Div, 32 Tozer Rd, Beverly, MA 01915 USA. EM dnaseq@neb.com RI Kamal, Ibrahim/J-2033-2012; Kyrpides, Nikos/A-6305-2014; Lapidus, Alla/I-4348-2013 OI Kamal, Ibrahim/0000-0002-6026-5794; Kyrpides, Nikos/0000-0002-6131-0462; Lapidus, Alla/0000-0003-0427-8731 NR 182 TC 280 Z9 487 U1 11 U2 60 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD APR PY 2005 VL 3 IS 4 BP 599 EP 614 AR e121 DI 10.1371/journal.pbio.0030121 PG 16 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 915EF UT WOS:000228279900008 PM 15780005 ER PT J AU Winitsky, SO Gopal, TV Hassanzadeh, S Takahashi, H Gryder, D Rogawski, MA Takeda, K Yu, ZX Xu, YH Epstein, ND AF Winitsky, SO Gopal, TV Hassanzadeh, S Takahashi, H Gryder, D Rogawski, MA Takeda, K Yu, ZX Xu, YH Epstein, ND TI Adult murine skeletal muscle contains cells that can differentiate into beating cardiomyocytes in vitro SO PLOS BIOLOGY LA English DT Article ID CARDIAC STEM-CELLS; SATELLITE CELLS; INFARCTED MYOCARDIUM; CALCIUM CURRENTS; PROGENITOR CELLS; ATRIAL MYOCYTES; FUSION; HEART; CONTRACTION; RAT AB It has long been held as scientific fact that soon after birth, cardiomyocytes cease dividing, thus explaining the limited restoration of cardiac function after a heart attack. Recent demonstrations of cardiac myocyte differentiation observed in vitro or after in vivo transplantation of adult stem cells from blood, fat, skeletal muscle, or heart have challenged this view. Analysis of these studies has been complicated by the large disparity in the magnitude of effects seen by different groups and obscured by the recently appreciated process of in vivo stem-cell fusion. We now show a novel population of nonsatellite cells in adult murine skeletal muscle that progress under standard primary cell-culture conditions to autonomously beating cardiomyocytes. Their differentiation into beating cardiomyocytes is characterized here by video microscopy, confocal-detected calcium transients, electron microscopy, immunofluorescent cardiac-specific markers, and single-cell patch recordings of cardiac action potentials. Within 2 d after tail-vein injection of these marked cells into a mouse model of acute infarction, the marked cells are visible in the heart. By 6 d they begin to differentiate without fusing to recipient cardiac cells. Three months later, the tagged cells are visible as striated heart muscle restricted to the region of the cardiac infarct. C1 NHLBI, Mol Physiol Sect, Mol Cardiol Lab, Bethesda, MD 20892 USA. NINDS, Epilepsy Res Sect, Bethesda, MD 20892 USA. NHLBI, Mol Cardiol Lab, Bethesda, MD 20892 USA. NHLBI, Pathol Sect, Bethesda, MD 20892 USA. NHLBI, Electron Microscopy Core Facil, Bethesda, MD 20892 USA. RP Epstein, ND (reprint author), NHLBI, Mol Physiol Sect, Mol Cardiol Lab, Bldg 10, Bethesda, MD 20892 USA. EM Epsteinn@mail.nih.gov RI Rogawski, Michael/B-6353-2009 OI Rogawski, Michael/0000-0002-3296-8193 NR 42 TC 72 Z9 77 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD APR PY 2005 VL 3 IS 4 BP 662 EP 671 AR e87 DI 10.1371/journal.pbio.0030087 PG 10 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 915EF UT WOS:000228279900013 PM 15757365 ER PT J AU Rutten, LJF Meissner, HI Breen, N Vernon, SW Rimer, BK AF Rutten, LJF Meissner, HI Breen, N Vernon, SW Rimer, BK TI Factors associated with men's use of prostate-specific antigen screening: evidence from Health Information National Trends Survey SO PREVENTIVE MEDICINE LA English DT Article DE prostate-specific antigen test; prostate cancer screening; informed decision making; shared decision making; communication ID SHARED DECISION-MAKING; PATIENTS SELF-REPORTS; SERVICES-TASK-FORCE; COLORECTAL-CANCER; INTERVIEW SURVEY; PHYSICIAN RECOMMENDATION; INFORMED DECISIONS; MAMMOGRAPHY USE; PRIMARY-CARE; COMMUNICATION AB Background. Rapid uptake of prostate-specific antigen (PSA) testing has occurred in the United States despite inconclusive evidence regarding mortality benefit. Methods. We examined data (n = 927) from the 2003 Health Information National Trends Survey to assess prevalence of self-reported PSA use and its association with patients' decision making. Results. Over half (55.2%) the sample reported ever having had a PSA test. Men aged 65-74 (OR = 2.53, 1.49-4.31), with some college (OR = 2.41, 1.22-4.77) or college degrees (OR = 5.01, 2.53-9.90) were more likely to have had PSA tests, while men without health insurance (OR = 0.32, 0.12-0.88) or a usual source of care (OR = 0.35, 0.22-0.54) were less likely. In a model including healthcare provider communication and information seeking, men who reported that providers involved them in decisions (OR = 1.76, 1.02-3.03) and recommended PSA (OR = 236.3, 70.5-791.4) were more likely to have had the tests. Men aged 65-74 (OR = 2.30, 1.33-4.00), with college degrees (OR = 2.91, 1.45-5.82), and greater information attention/seeking (OR = 1.23, 1.07-1.40) were more likely to report PSA recommendations, while those without usual care were less likely (OR = 0.37, 0.22-0.64). Men without usual care (OR = 0.38, 0.20-0.71) and Hispanic men (OR = 0.40, 0.19-0.85) were less likely to report that healthcare providers involved them in healthcare decisions. Conclusions. Results emphasize the relevance of patient decision making and the importance of healthcare providers in PSA testing. (C) 2004 The Institute For Cancer Prevention and Elsevier Inc. All rights reserved. C1 NCI, Div Canc Prevent, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. NCI, Div Canc Control & Populat Sci, Hlth Commun & Informat Res Branch, Bethesda, MD 20892 USA. NCI, Appl Canc Screening Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Hlth Serv & Econ Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Texas, Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX 77225 USA. Univ N Carolina, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. RP Rutten, LJF (reprint author), NCI, Div Canc Prevent, Canc Prevent Fellowship Program, 6130 Execut Blvd,4051A MSC 7365, Bethesda, MD 20892 USA. EM finneyl@mail.nih.gov NR 56 TC 48 Z9 49 U1 2 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-7435 J9 PREV MED JI Prev. Med. PD APR PY 2005 VL 40 IS 4 BP 461 EP 468 DI 10.1016/j.ypmed.2004.07.011 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 883SQ UT WOS:000226036400011 ER PT J AU Esposito, D Gillette, WK Miller, DA Taylor, TE Frank, PH Hu, RQ Bekisz, J Hernandez, J Cregg, JM Zoon, KC Hartley, JL AF Esposito, D Gillette, WK Miller, DA Taylor, TE Frank, PH Hu, RQ Bekisz, J Hernandez, J Cregg, JM Zoon, KC Hartley, JL TI Gateway cloning is compatible with protein secretion from Pichia pastoris SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE Pichia pastoris; gateway cloning secretion; interferon ID LYMPHOBLASTOID INTERFERON-ALPHA; SITE-SPECIFIC RECOMBINATION; COMPONENTS; EXPRESSION; BINDING; YEAST AB Secretion of a recombinant protein from the yeast Pichia pastoris requires the presence of a signal peptide at the amino terminus. Maintaining the full amino acid sequence of the signal peptide is thought to be important for proper signal processing and protein secretion. We show that at least for one protein, a synthetic human interferon, the presence of a Gateway recombination site within the signal peptide is fully compatible with high levels of protein secretion. The amino termini of the secreted interferon proteins cloned with Gateway and cloned with restriction enzymes and ligase are identical, and the proteins were highly active in biological assays. Compatibility with Gateway cloning simplifies construction of plasmids directing secretion of recombinant proteins from P. pastoris. (c) 2005 Elsevier Inc. All rights reserved. C1 SAIC Frederick Inc, Natl Canc Inst, Protein Express Lab, Frederick, MD 21702 USA. NIAID, NIH, Bethesda, MD 20892 USA. Keck Grad Inst Appl Life Sci, Claremont, CA 91711 USA. RP Hartley, JL (reprint author), SAIC Frederick Inc, Natl Canc Inst, Protein Express Lab, POB B, Frederick, MD 21702 USA. EM hartley@ncifcrf.gov NR 10 TC 7 Z9 8 U1 1 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD APR PY 2005 VL 40 IS 2 BP 424 EP 428 DI 10.1016/j.pep.2004.12.006 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 909VU UT WOS:000227889600025 PM 15766886 ER PT J AU Wang, GS Peterkofsky, A Keifer, PA Li, X AF Wang, GS Peterkofsky, A Keifer, PA Li, X TI NMR characterization of the Escherichia coli nitrogen regulatory protein IIA(Ntr) in solution and interaction with its partner protein, NPr SO PROTEIN SCIENCE LA English DT Article DE NMR; translational diffusion coefficient; heteronuclear NOE; residual dipolar coupling; IIA(Ntr); NPr; Escherichia coli; structure-based functional discovery ID SUGAR PHOSPHOTRANSFERASE SYSTEM; SIGNAL-TRANSDUCING PROTEIN; PHOSPHORYL TRANSFER COMPLEX; N-TERMINAL DOMAIN; ENZYME I; CHEMICAL-SHIFT; PHOSPHOENOLPYRUVATE; IIA(GLUCOSE); SPECTROSCOPY; C-13 AB The solution form of IIA(Ntr) from Escherichia coli and its interaction with its partner protein, NPr, were characterized by nuclear magnetic resonance (NMR) spectroscopy. The diffusion coefficient of the protein (1.13 x 10(-6) cm/sec) falls between that of HPr (similar to 9 kDa) and the N-terminal domain of E. coli enzyme I (similar to 30 kDa), indicating that the functional form of IIA(Ntr) is a monomer (similar to 18 kDa) in solution. Thus, the dimeric structure of the protein found in the crystal is an artifact of crystal packing. The residual dipolar coupling data of IIA(Ntr) (covering residues 11-155) measured in the absence and presence of a 4% polyethyleneglycol-hexanol liquid crystal alignment medium fit well to the coordinates of both molecule A and molecule B of the dimeric crystal structure, indicating that the 3D structures in solution and in the crystal are indeed similar for that protein region. However, only molecule A possesses an N-terminal helix identical to that derived from chemical shifts of IIA(Ntr) in solution. Further, the N-15 heteronuclear nuclear Overhauser effect (NOE) data also support molecule A as the representative structure in solution, with the terminal residues 1-8 and 158-163 more mobile. Chemical shift mapping identified the surface on IIA(Ntr) for NPr binding. Residues Gly61, Asp115, Ser125, Thr156, and nearby regions of IIA(Ntr) are more perturbed and participate in interaction with NPr. The active-site His73 of IIA(Ntr) for phosphoryl transfer was found in the N delta 1-H tautomeric state. This work lays the foundation for future structure and function studies of the signal transducing proteins from this nitrogen pathway. C1 Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198 USA. NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wang, GS (reprint author), Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, 986805 Nebraska Med Ctr, Omaha, NE 68198 USA. EM gwang@unmc.edu NR 47 TC 15 Z9 15 U1 0 U2 1 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD APR PY 2005 VL 14 IS 4 BP 1082 EP 1090 DI 10.1110/ps.041232805 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 907SS UT WOS:000227738900027 PM 15741344 ER PT J AU Davies, MA Compton-Toth, BA Hufeisen, SJ Meltzer, HY Roth, BL AF Davies, MA Compton-Toth, BA Hufeisen, SJ Meltzer, HY Roth, BL TI The highly efficacious actions of N-desmethylclozapine at muscarinic receptors are unique and not a common property of either typical or atypical antipsychotic drugs: is M-1 agonism a pre-requisite for mimicking clozapine's actions? SO PSYCHOPHARMACOLOGY LA English DT Article DE clozapine; atypical antipsychotic; N-desmethylclozapine; muscarinic ID PROTEIN-COUPLED RECEPTORS; HAMSTER OVARY CELLS; OPEN CLINICAL-TRIAL; CHOLINERGIC RECEPTORS; INTRACELLULAR CALCIUM; SEROTONIN RECEPTOR; COGNITIVE FUNCTION; IN-VITRO; SCHIZOPHRENIA; ANTAGONIST AB Rationale: Recent studies have suggested that the salutary actions of clozapine in schizophrenia may be due to selective activation of M-1 muscarinic receptors by clozapine and/or its major active metabolite N-desmethyl-clozapine. Objective: We systematically tested this hypothesis by screening a large number of psychoactive compounds.. including, many atypical antipsychotic drugs, for agonist activity at cloned, human M-1, M-3 and M-5 muscarinic receptors. Results: Only three of the 14 atypical antipsychotic drugs we tested were found to possess partial agonist actions at M, muscarinic receptors (fluperlapine, JL13, clozapine). A few additional miscellaneous compounds had a modest degree of M-1 agonist actions. Only carbachol and N-desmethylclozapine had appreciable M-3 muscarinic agonism at M-3 muscarinic receptors, although several were M-5 partial agonists including MK-212, N-desmethylelozapine and xanomeline. Conclusion: Although M-1 muscarinic receptor-selective partial agonists have shown promise in some preclinical antipsychotic drug models, these studies indicate that it is unlikely that the salutary actions of clozapine and similar atypical antipsychotic drugs are mediated solely by M-1 muscarinic receptor activation. It is possible, however, that the M-1 agonism of N-desmethylclozapine contributes to the uniquely beneficial actions of clozapine. Thus, these results are consistent with the notion that a balanced degree of activity at multiple biogenic amine receptors, including M-1 muscarinic agonism, is responsible for the uniquely beneficial actions of clozapine. C1 Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Pharmacol, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, NIMH, Psychoact Drug Screening Program, Cleveland, OH 44106 USA. RP Roth, BL (reprint author), Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. EM bryan.roth@case.edu RI Roth, Bryan/F-3928-2010; Meltzer, Herbert/E-8131-2013 FU NIMH NIH HHS [R01MH57635, K02MH01366] NR 68 TC 83 Z9 85 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD APR PY 2005 VL 178 IS 4 BP 451 EP 460 DI 10.1007/s00213-004-2017-1 PG 10 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 915IV UT WOS:000228298800010 PM 15765260 ER PT J AU Le Foll, B Goldberg, SR AF Le Foll, B Goldberg, SR TI Nicotine induces conditioned place preferences over a large range of doses in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE conditioned place preference; reward; biased procedure; unbiased procedure; nicotine; rats; tobacco smoking; CB1; dopamine D-3 receptor; rimonabant; BP.897; SR141716 ID VENTRAL TEGMENTAL AREA; DOPAMINE D-3 RECEPTOR; SQUIRREL-MONKEYS; BEHAVIOR; COCAINE; REWARD; BLOCKADE; ANTAGONIST; INJECTIONS; ADDICTION AB Rationale: Conditioned place preference (CPP) procedures provide one measure of potential rewarding effects of abused drugs. Many attempts to induce CPP with nicotine have been unsuccessful. Objectives: To assess the influence of nicotine dose and stimulus assignment procedure on development of nicotine-induced CPP. Methods: Initial preferences for one side of a two-compartment apparatus were first determined in Sprague-Dawley rats. In subsequent conditioning trials, the compartment paired with nicotine was the initially preferred side for half of the rats, and the initially nonpreferred side for the other half. Rats received either an injection of nicotine (0.01-2 mg/kg SC) before being placed in one compartment (three trials) or saline before being placed in the other compartment (three trials). Control rats had saline injections associated with both compartments. A final test trial with no injection assessed final place preference. Results: Significant CPP were induced by 0.1-1.4 mg/kg doses of nicotine. Nicotine-induced CPP were only apparent when nicotine was paired with the intially non-preferred side. Moreover, a very high dose of nicotine (2 mg/kg) induced conditioned place aversion when paired with the initially preferred side of the apparatus. Conclusions: Nicotine induced significant CPP across a wide range of doses, in accordance with its role as the primary addictive component of tobacco. Small preferences for one side of the apparatus played a major role in the development of nicotine-induced CPP. These findings suggest that biased procedures may be more Suitable than unbiased procedures for evaluation of rewarding effects of nicotine using CPP paradigms. C1 Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. RP Le Foll, B (reprint author), Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Dept Hlth & Human Serv,NIH, 5500 Nathan Shock Drive, Baltimore, MD 21224 USA. EM sgoldber@intra.nida.nih.gov RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 NR 70 TC 131 Z9 131 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD APR PY 2005 VL 178 IS 4 BP 481 EP 492 DI 10.1007/s00213-004-2015-5 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 915IV UT WOS:000228298800013 PM 15765262 ER PT J AU Herin, DV Liu, SJ Urich, T Rice, KC Cunningham, KA AF Herin, DV Liu, SJ Urich, T Rice, KC Cunningham, KA TI Role of the serotonin 5-HT2A receptor in the hyperlocomotive and hyperthermic effects of (+)-3,4-methylenedioxymethamphetamine SO PSYCHOPHARMACOLOGY LA English DT Article DE MDMA; hyperactivity; hyperthennia; M100907 ID VENTRAL TEGMENTAL AREA; LOCOMOTOR-ACTIVITY; 3,4-METHYLENEDIOXYMETHAMPHETAMINE ECSTASY; NUCLEUS-ACCUMBENS; AMBIENT-TEMPERATURE; MDMA; RAT; DOPAMINE; ANTAGONIST; MDL-100,907 AB Rationale: Contradictory evidence exists regarding the role of the 5-HT2A receptor (5-HT2AR) in hyperactivity and hyperthermia elicited by the substituted amphetamine (+)-3,4-methylenedioxymethamphetamine. Objectives: The present studies examined the ability of the selective 5-HT2AR antagonist M 100907 to block hyperactivity and hyperthermia produced across the (+)-MDMA dose-effect curve. Methods: Male rats were pretreated with M100907 (0, 0.25, 0.5, 1, and 2 mg/kg) followed by treatment with (+)-MDMA (0-12 mg/kg); activity was recorded for 90 min followed by determination of rectal temperature. Additionally, we investigated the ability of M100907 (0 and 0.5 mg/kg) to reverse hyperthermia elicited by (+)-MDMA (12 rng/kg). Results: The first study demonstrated that M 100907 attenuated hyperactivity in the periphery of the monitor and eliminated rearing induced by (+)-MDMA (3 rng/kg) with no effect on basal activity. In two subsequent studies, (+)-MDMA (0-12 mg/kg) dose-dependently increased peripheral activity and rearing and produced hyperthermia. Pretreatment with M100907 decreased peripheral activity evoked by (+)-MDMA, right-shifted the dose-effect curve for rearing, and blocked (+)-MDMA-induced hyperthermia, while having no effect when administered alone. A final study demonstrated the ability of M100907 (0.5 mg/kg) to reverse hyperthermia produced by (+)-MDMA (12 rng/kg). Conclusions: These results suggest that the 5-HT2AR contributes to the generation of peripheral hyperactivity and rearing and, especially. the hyperthermia evoked by (+)-MDMA and that 5-HT2AR antagonists should be further investigated as treatments for the psychological and hyperthermic effects of (+/-)-MDMA. C1 NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Cunningham, KA (reprint author), Univ Texas, Med Branch, Dept Pharmacol & Toxicol, Addict Res Ctr, Galveston, TX 77555 USA. EM kcunning@utmb.edu RI Cunningham, Kathryn/O-2718-2013 FU NIDA NIH HHS [F31 DA015272-03, DA 00260, DA 07287, DA 13595, DA 15272, F31 DA015272, F31 DA015272-01, F31 DA015272-02] NR 45 TC 43 Z9 43 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD APR PY 2005 VL 178 IS 4 BP 505 EP 513 DI 10.1007/s00213-004-2030-4 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 915IV UT WOS:000228298800016 PM 15765263 ER PT J AU Choyke, PL AF Choyke, PL TI Science to practice - Contrast agents for imaging tumor angiogenesis: Is bigger better? SO RADIOLOGY LA English DT Editorial Material C1 NCI, Mol Imaging Program, Bethesda, MD 20892 USA. RP Choyke, PL (reprint author), NCI, Mol Imaging Program, Bldg 10,Rm B3B69, Bethesda, MD 20892 USA. EM pchoyke@nih.gov NR 4 TC 19 Z9 20 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2005 VL 235 IS 1 BP 1 EP 2 DI 10.1148/radiol.2351041773 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 910SN UT WOS:000227952600001 PM 15798159 ER PT J AU Ben-Aharon, I Brown, PR Etkovitz, N Eddy, EM Shalgi, R AF Ben-Aharon, I Brown, PR Etkovitz, N Eddy, EM Shalgi, R TI The expression of calpain 1 and calpain 2 in spermatogenic cells and spermatozoa of the mouse SO REPRODUCTION LA English DT Article ID CALCIUM-DEPENDENT PROTEASE; PROTO-ONCOGENE PRODUCT; ACROSOME REACTION; SPERM CAPACITATION; MU-CALPAIN; RAT TESTIS; CALPASTATIN; INVOLVEMENT; PROTEINS; SYSTEM AB There is some evidence suggesting that Ca2+ is involved in processes that occur during the development and function of spermatozoa. Calcium-dependent proteins, such as calmodulin, are expressed during mammalian spermatogenesis further suggesting that Ca2+ takes part in its regulation. However, the precise roles of Ca2+ in spermatogenesis remain to be elucidated. Calpains are a family of Ca2+-dependent cysteine proteases whose members are expressed ubiquitously or in a tissue-specific manner. Calpain has been demonstrated to mediate specific Ca2+-dependent processes including cell fusion, mitosis and meiosis. We herein followed the expression pattern of calpain's ubiquitous isoforms, 1 and 2, throughout spermatogenesis at the RNA and protein levels by RT-PCR and Western blotting analysis. Both RNA and protein studies revealed that these isoforms are expressed in all spermatogenic cells. The expression of calpain 1 levels is slightly higher in spermatocytes entering the meiotic phase. Both calpain isoforms are also expressed in mouse spermatozoa and are localized to the acrosomal cap. Inducing capacitated spermatozoa to undergo the acrosome reaction in the presence of a selective calpain inhibitor significantly reduced the acrosome reaction rate in a dose-dependent manner. Thus, calpain, a pluripotential protease with numerous substrates, may serve as an effector in more than one pathway in the complex process of spermatogenesis and in the events preceding fertilization, such as the acrosome reaction. C1 Tel Aviv Univ, Sackler Sch Med, Dept Cell & Dev Biol, IL-69978 Tel Aviv, Israel. Natl Inst Environm Hlth Sci, Gamete Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC USA. Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel. RP Shalgi, R (reprint author), Tel Aviv Univ, Sackler Sch Med, Dept Cell & Dev Biol, IL-69978 Tel Aviv, Israel. EM shalgir@post.tau.ac.il NR 49 TC 16 Z9 16 U1 0 U2 0 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1470-1626 J9 REPRODUCTION JI Reproduction PD APR PY 2005 VL 129 IS 4 BP 435 EP 442 DI 10.1530/rep.1.00255 PG 8 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 921RD UT WOS:000228781400006 PM 15798018 ER PT J AU Soler-Garcia, AA Maitra, R Kumar, V Ise, T Nagata, S Beers, R Bera, TK Pastan, I AF Soler-Garcia, AA Maitra, R Kumar, V Ise, T Nagata, S Beers, R Bera, TK Pastan, I TI The PATE gene is expressed in the accessory tissues of the human male genital tract and encodes a secreted sperm-associated protein SO REPRODUCTION LA English DT Article ID SULFATED GLYCOPROTEIN-1 PROSAPOSIN; EQUATORIAL SEGMENT; PHOSPHOLIPASE A(2); SEMINAL-VESICLE; HUMAN SPERMATOZOA; PLASMA-MEMBRANE; NORMAL PROSTATE; SERTOLI CELLS; HOUSE MOUSE; MOTILITY AB The PATE gene is expressed in prostate and testis. To determine if PATE is expressed in other accessory tissues of the male genital tract, RT-PCR of the epididymis and seminal vesicle was performed. PATE mRNA was highly expressed in the epididymis and seminal vesicle. In situ hybridization of the testis showed PATE mRNA is strongly expressed in the spermatogonia. The PATE gene encodes a 14-kDa protein with a predicted signal sequence and a cleavage site between residues G21 and S22. To determine if PATE is a secreted protein, 293T cells were transfected with a pcDNA-PATE-myc-His plasmid and protein immunoprecipitated with anti-myc monoclonal antibody. Western blot analysis showed the presence of PATE-myc-His protein was in the medium and the cell lysate. Confocal microscopy demonstrated that PATE-myc-His protein is found in the endoplasmic reticulum. The polyclonal antibody SOL-1 was generated by immunization of rabbits with recombinant PATE protein expressed and purified from Escherichia coli. Western blots were performed on extracts of prostate, testis, seminal vesicle and ejaculated spermatozoa, but PATE protein was only detected in the spermatozoa. Immunostaining of sperm smears revealed that PATE is located in a band-like pattern in the sperm head. Our data indicate that PATE is made by various sexual accessory tissues and secreted into the semen where it becomes associated with sperm, suggesting that PATE is a novel sperm-associated protein with a possible role in mammalian sperm maturation. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Div Nephrol, Med Genet Res Ctr, Washington, DC 20010 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM pastini@mail.nih.gov NR 55 TC 13 Z9 13 U1 0 U2 0 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1470-1626 J9 REPRODUCTION JI Reproduction PD APR PY 2005 VL 129 IS 4 BP 515 EP 524 DI 10.1053/rep.1.00576 PG 10 WC Developmental Biology; Reproductive Biology SC Developmental Biology; Reproductive Biology GA 921RD UT WOS:000228781400015 PM 15798027 ER PT J AU Nagashima, N Hisasue, M Nishigaki, K Miyazawa, T Kano, R Hasegawa, A AF Nagashima, N Hisasue, M Nishigaki, K Miyazawa, T Kano, R Hasegawa, A TI In vitro selective suppression of feline myeloid colony formation is attributable to molecularly cloned strain of feline leukemia virus with unique long terminal repeat SO RESEARCH IN VETERINARY SCIENCE LA English DT Article DE AML; bone marrow; FeLV; LTR; MDS ID CATS; CELLS AB Molecularly cloned feline leukemia virus (FeLV)-clone 33 (C-33), derived from a cat with acute myelocytic leukemia (AML), was examined to assess its relation to the pathogenesis of AML and myelodysplastic syndrome (MDS). To evaluate in vitro pathogenicity of FeLV C-33, bone marrow colony-forming assay was performed on marrow cells infected with FeLV C-33 or an FeLV subgroup A strain (61E, a molecularly cloned strain with minimal pathogenicity). The myeloid colony-forming activity of feline bone marrow mononuclear cells infected with FeLV C-33 was significantly lower than that of cells infected with 61E. This suggests that FeLV C-33 has myeloid lineage-specific pathogenicity for cats, and that FeLV C-33 infection is useful as an experimental model for investigating pathogenesis of MDS and AML. (C) 2004 Elsevier Ltd. All rights reserved. C1 Azabu Univ, Sch Vet Med, Lab Vet Internal Med 2, Sagamihara, Kanagawa 2298501, Japan. Nihon Univ, Sch Vet Med, Dept Pathobiol, Fujisawa, Kanagawa 2528510, Japan. NCI, Basic Res Lab, Frederick, MD 21702 USA. Japan Sci & Technol Agcy, PRESTO, Host & Def, Kawaguchi, Saitama 3320012, Japan. Obihiro Univ Agr & Vet Med, Dept Vet Publ Hlth, Obihiro, Hokkaido 0808555, Japan. RP Hisasue, M (reprint author), Azabu Univ, Sch Vet Med, Lab Vet Internal Med 2, 1-17-71,Fuchinobe, Sagamihara, Kanagawa 2298501, Japan. EM hisasue@azabu-u.ac.jp NR 15 TC 4 Z9 4 U1 1 U2 1 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0034-5288 J9 RES VET SCI JI Res. Vet. Sci. PD APR PY 2005 VL 78 IS 2 BP 151 EP 154 DI 10.1016/j.rvsc.2004.07.003 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 897LL UT WOS:000227005500008 PM 15563922 ER PT J AU Ordonez, AE Bobb, A Greenstein, D Baker, N Sporn, A Lenane, M Malaspina, D Rapoport, JL Gogtay, N AF Ordonez, AE Bobb, A Greenstein, D Baker, N Sporn, A Lenane, M Malaspina, D Rapoport, JL Gogtay, N TI Lack of evidence for elevated obstetric complications in childhood onset schizophrenia SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 20th International Congress on Schizophernia Research CY APR 02-06, 2005 CL Savannah, GA C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 3 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD APR PY 2005 VL 31 IS 2 BP 234 EP 235 PG 2 WC Psychiatry SC Psychiatry GA 914PY UT WOS:000228241200145 ER PT J AU Roberts, B Schooler, C AF Roberts, B Schooler, C TI Context and schizophreic cognitive processing SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 20th International Congress on Schizophernia Research CY APR 02-06, 2005 CL Savannah, GA C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD APR PY 2005 VL 31 IS 2 BP 373 EP 373 PG 1 WC Psychiatry SC Psychiatry GA 914PY UT WOS:000228241201197 ER PT J AU Gogtay, N Ordonez, AE Herman, DH Gied, JN Hayashi, KM Greenstein, D Vaitiuzis, C Nugent, TF Clasen, L Thompson, PM Rapoport, JL AF Gogtay, N Ordonez, AE Herman, DH Gied, JN Hayashi, KM Greenstein, D Vaitiuzis, C Nugent, TF Clasen, L Thompson, PM Rapoport, JL TI Dynamic mapping of cortical brain development in pediatric bipolar illness SO SCHIZOPHRENIA BULLETIN LA English DT Meeting Abstract CT 20th International Congress on Schizophernia Research CY APR 02-06, 2005 CL Savannah, GA C1 NIMH, Bethesda, MD 20892 USA. RI Gogtay, Nitin/A-3035-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD APR PY 2005 VL 31 IS 2 BP 390 EP 390 PG 1 WC Psychiatry SC Psychiatry GA 914PY UT WOS:000228241201245 ER PT J AU Paul, BM Elvevag, B Bokat, CE Weinberger, DR Goldberg, TE AF Paul, BM Elvevag, B Bokat, CE Weinberger, DR Goldberg, TE TI Levels of processing effects on recognition memory in patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE episodic memory; encoding; recognition; schizophrenia ID NEUROPSYCHOLOGICAL FUNCTION; CONSCIOUS RECOLLECTION; ENCODING ORIENTATION; ALZHEIMERS-DISEASE; THOUGHT-DISORDER; EPISODIC MEMORY; MATCHED TASKS; DSM-III; IMPAIRMENT; RECALL AB This study sought to characterize the performance of patients with schizophrenia, as compared with healthy participants, on a memory task that required encoding of items to different depths. Participants included 21 individuals with schizophrenia and 26 healthy controls. During the encoding phase of the study, participants processed successively presented words in two ways: perceptually (by making a decision as to whether the letter "a" was present in the word) or semantically (by making a living/ nonliving decision for each word). During the recognition phase of the study, participants were presented with a list of words containing items that had been presented during the encoding phase (during either the letter decision task or the semantic decision task), as well as items that had not been seen before (foils). Though patients with schizophrenia performed more poorly overall on the recognition task, recognition was facilitated by semantic encoding to an equivalent degree in both groups. In other words, while significant main effects were present for group and encoding, no group x encoding condition was present. This result is consistent with previous findings of a lack of qualitative differences in performance on learning and memory tasks between patients with schizophrenia and healthy controls. It also suggests that strategies that place constraints on the encoding processes used by patients may help improve the efficiency with which they learn and remember information. (C) 2004 Elsevier B.V. All rights reserved. C1 NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. RP Goldberg, TE (reprint author), NIMH, Clin Brain Disorders Branch, 10 Ctr Dr,MSC 1379, Bethesda, MD 20892 USA. EM goldbert@intra.nimh.nih.gov NR 61 TC 19 Z9 19 U1 3 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD APR 1 PY 2005 VL 74 IS 1 BP 101 EP 110 DI 10.1016/j.schres.2004.05.019 PG 10 WC Psychiatry SC Psychiatry GA 900BP UT WOS:000227190700011 PM 15694759 ER PT J AU Fauci, AS Zerhouni, EA AF Fauci, AS Zerhouni, EA TI NIH response to open letter SO SCIENCE LA English DT Letter C1 NIAID, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. RP Fauci, AS (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM afauci@niaid.nih.gov NR 1 TC 6 Z9 6 U1 0 U2 1 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 1 PY 2005 VL 308 IS 5718 BP 49 EP 49 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 914IQ UT WOS:000228221500015 PM 15802584 ER PT J AU Glick, AB Yuspa, SH AF Glick, AB Yuspa, SH TI Tissue homeostasis and the control of the neoplastic phenotype in epithelial cancers SO SEMINARS IN CANCER BIOLOGY LA English DT Review DE tumor suppression; skin; Keratinocytes; junctional complexes; Notch1; TGF beta ID GROWTH-FACTOR-BETA; KINASE-C-DELTA; TUMOR PROMOTER 12-O-TETRADECANOYLPHORBOL-13-ACETATE; MOUSE SKIN CARCINOGENESIS; MAMMARY-CARCINOMA CELLS; TERMINAL DIFFERENTIATION; STEM-CELLS; ALPHA-6-BETA-4 INTEGRIN; TRANSGENIC MICE; EPIDERMAL-CELLS AB Neoplastic cells at various stages of tumor progression may remain dormant for many years. The suppression of the neoplastic phenotype and tumor outgrowth depends on close contact of neoplastic cells with surrounding normal cells. This review examines the nature of these contacts primarily in models for skin cancer induction. Junctional complexes, membrane associated growth factors and their receptors, and paracrine mechanisms likely contribute to this state of tumor cell dormancy. Understanding these mechanisms will be important in primary cancer prevention and for counteracting recurrences in cancer survivors. Published by Elsevier Ltd. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, 37 Convent Dr,MSC-4255,Bldg 37,Room 4068A1, Bethesda, MD 20892 USA. EM yuspas@mail.nih.gov NR 82 TC 28 Z9 31 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-579X J9 SEMIN CANCER BIOL JI Semin. Cancer Biol. PD APR PY 2005 VL 15 IS 2 BP 75 EP 83 DI 10.1016/j.semcancer.2004.08.008 PG 9 WC Oncology SC Oncology GA 893JQ UT WOS:000226715500002 PM 15652452 ER PT J AU Jacobson, KA Mamedova, L Joshi, BV Besada, P Costanzi, S AF Jacobson, KA Mamedova, L Joshi, BV Besada, P Costanzi, S TI Molecular recognition at adenine nucleotide (P2) receptors in platelets SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Article DE G protein-coupled receptors; P2Y receptors; agonist; antagonist; mutant ID HUMAN P2Y(1) RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; BIOLOGICAL-ACTIVITY; P2X(1) RECEPTORS; 2,2'-PYRIDYLISATOGEN TOSYLATE; P-2Y-PURINOCEPTOR AGONISTS; SELECTIVE ANTAGONISTS; ANTITHROMBOTIC DRUGS; ACTIVE METABOLITE; IN-VIVO AB Transmembrane signaling through P2Y receptors for extracellular nucleotides controls a diverse array of cellular processes, including thrombosis. Selective agonists and antagonists of the two P2Y receptors present on the platelet surface-the G(q)-coupled P2Y(1) subtype and the G(i)-coupled P2Y(12) subtype-are now known. High-affinity antagonists of each have been developed from nucleotide structures. The (N)-methanocarba bisphosphate derivatives MRS2279 and MRS2500 are potent and selective P2Y, receptor antagonists. The carbocyclic nucleoside AZD6140 is an uncharged, orally active P2Y(12) receptor antagonist of nM affinity. Another nucleotide receptor on the platelet surface, the P2X(1) receptor, the activation of which may also be proaggregatory, especially under conditions of high shear stress, has high-affinity ligands, although high selectivity has not yet been achieved. Although α,β-methylene-adenosine triphosphate (ATP) is the classic agonist for the P2X(1) receptor, where it causes rapid desensitization, the agonist BzATP is among the most potent in activating this subtype. The aromatic sulfonates NF279 and NF449 are potent antagonists of the P2X(1) receptor. The structures of the two platelet P2Y receptors have been modeled, based on a rhodopsin template, to explain the basis for nucleotide recognition within the putative transmembrane binding sites. The P2Y(1) receptor model, especially, has been exploited in the design and optimization of antagonists targeted to interact selectively with that subtype. C1 NIDDK, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDK, Bioorgan Chem Lab, Mol Recognit Sect, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Besada Pereira, Pedro/E-6051-2012; Costanzi, Stefano/G-8990-2013; OI Jacobson, Kenneth/0000-0001-8104-1493; Besada Pereira, Pedro/0000-0002-9985-9063; Costanzi, Stefano/0000-0003-3183-7332 FU Intramural NIH HHS [Z01 DK031116-20] NR 69 TC 14 Z9 15 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD APR PY 2005 VL 31 IS 2 BP 205 EP 216 DI 10.1055/s-2005-869526 PG 12 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 923HP UT WOS:000228901300010 PM 15852224 ER PT J AU Shaw, JW Horrace, WC Vogel, RJ AF Shaw, JW Horrace, WC Vogel, RJ TI The determinants of life expectancy: An analysis of the OECD health data SO SOUTHERN ECONOMIC JOURNAL LA English DT Article ID MODERATE ALCOHOL-CONSUMPTION; MEDICAL EXPENDITURES; SOCIAL-SECURITY; RISK-FACTORS; TESTS; MORTALITY; DISEASE; SPECIFICATION; PATTERNS; CANCER AB This study considers an aggregate life expectancy production function for a sample of developed countries. We find that pharmaceutical consumption has a positive effect on life expectancy at middle and advanced ages but is sensitive to the age distribution of a given country. Thus, ignoring age distribution in a regression of life expectancy on pharmaceutical consumption creates an omitted-variable bias in the pharmaceutical coefficient. We find that doubling annual pharmaceutical expenditures adds about one year of life expectancy for males at age 40 and slightly less than a year of life expectancy for females at age 65. We also present results for lifestyle inputs into the production of life expectancy. For example, decreasing tobacco consumption by about two cigarettes per day or increasing fruit and vegetable consumption by 30% (one-third pound per day) increases life expectancy approximately one year for 40-year-old females. C1 NCI, Tobacco Control Res Branch, Behav Res Program, Bethesda, MD 20892 USA. Syracuse Univ, Dept Econ, Syracuse, NY 13244 USA. Univ Arizona, Coll Pharm, Ctr Hlth Outcomes & PharmacoEcon Res, Tucson, AZ 85721 USA. RP Horrace, WC (reprint author), NCI, Tobacco Control Res Branch, Behav Res Program, Bethesda, MD 20892 USA. EM shawjim@mail.nih.gov; whorrace@maxwell.syr.edu; vogel@pharmacy.arizona.edu RI Horrace, William/I-6279-2015 OI Horrace, William/0000-0003-1325-5320 NR 58 TC 28 Z9 30 U1 4 U2 7 PU UNIV NORTH CAROLINA PI CHAPEL HILL PA SOUTHERN ECONOMIC JOURNAL, CHAPEL HILL, NC 27514 USA SN 0038-4038 J9 SOUTH ECON J JI South. Econ. J. PD APR PY 2005 VL 71 IS 4 BP 768 EP 783 PG 16 WC Economics SC Business & Economics GA 917CL UT WOS:000228433500006 ER PT J AU Leong, PA Heymann, JB Jensen, GJ AF Leong, PA Heymann, JB Jensen, GJ TI Peach: A simple perl-based system for distributed computation and its application to cryo-EM data processing - Ways & means SO STRUCTURE LA English DT Article ID ELECTRON-MICROSCOPY; RESOLUTION; CRYSTALLOGRAPHY; CRYSTALS; IMAGE AB A simple distributed processing system named "Peach" was developed to meet the rising computational demands of modern structural biology (and other) laboratories without additional expense by using existing hardware resources more efficiently. A central server distributes jobs to idle workstations in such a way that each computer is used maximally, but without disturbing intermittent interactive users. As compared to other distributed systems, Peach is simple, easy to install, easy to administer, easy to use, scalable, and robust. While it was designed to queue and distribute large numbers of small tasks to participating computers, it can also be used to send single jobs automatically to the fastest currently available computer and/or survey the activity of an entire laboratory's computers. Tests of robustness and scalability are reported, as are three specific electron cryomicroscopy applications where Peach enabled projects that would not otherwise have been feasible without an expensive, dedicated cluster. C1 CALTECH, Div Biol, Pasadena, CA 91125 USA. CALTECH, Dept Appl Phys, Pasadena, CA 91125 USA. NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. RP Jensen, GJ (reprint author), CALTECH, Div Biol, 1200 E Calif Blvd, Pasadena, CA 91125 USA. EM jensen@caltech.edu RI Heymann, Bernard/F-6825-2011 FU NIGMS NIH HHS [P01 GM66521] NR 18 TC 8 Z9 8 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD APR PY 2005 VL 13 IS 4 BP 505 EP 511 DI 10.1016/j.str.2005.01.015 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 920JT UT WOS:000228685900005 PM 15837189 ER PT J AU Zheng, WJ Brooks, BR Doniach, S Thirumalai, D AF Zheng, WJ Brooks, BR Doniach, S Thirumalai, D TI Network of dynamically important residues in the open/closed transition in polymerases is strongly conserved SO STRUCTURE LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; NORMAL-MODE ANALYSIS; TERNARY COMPLEXES; LARGE FRAGMENT; AMINO-ACID; DNA; MOTIONS; PROTEINS; BETA; FIDELITY AB The open/closed transition in polymerases is a crucial event in DNA replication and transcription. We hypothesize that the residues that transmit the signal for the open/closed transition are also strongly conserved. To identify the dynamically relevant residues, we use an elastic network model of polymerases and probe the residue-specific response to a local perturbation. In a variety of DNA/RNA polymerases, a network of residues spanning the fingers and palm domains is involved in the open/closed transition. The similarity in the network of residues responsible for large-scale domain movements supports the notion of a common induced-fit mechanism in the polymerase families for the formation of a closed ternary complex. Multiple sequence alignment shows that many of these residues are also strongly conserved. Residues with the largest sensitivity to local perturbations include those that are not so obviously involved in the polymerase catalysis. Our results suggest that mutations of the mechanical "hot spots" can compromise the efficiency of the enzyme. C1 NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Phys, Stanford, CA 94305 USA. Stanford Univ, Dept Appl Phys, Stanford, CA 94305 USA. Stanford Univ, Adv Mat Lab, Stanford, CA 94305 USA. Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA. RP Zheng, WJ (reprint author), NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. EM zhengwj@helix.nih.gov; thirum@glue.umd.edu OI Zheng, Wenjun/0000-0002-6236-9765 NR 26 TC 78 Z9 78 U1 0 U2 13 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0969-2126 J9 STRUCTURE JI Structure PD APR PY 2005 VL 13 IS 4 BP 565 EP 577 DI 10.1016/j.str.2005.01.017 PG 13 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 920JT UT WOS:000228685900011 PM 15837195 ER PT J AU Chambers, DA Pearson, JL Lubell, K Brandon, S O'Brien, K Zinn, J AF Chambers, DA Pearson, JL Lubell, K Brandon, S O'Brien, K Zinn, J TI The science of public messages for suicide prevention: A workshop summary SO SUICIDE AND LIFE-THREATENING BEHAVIOR LA English DT Editorial Material ID HELP-SEEKING; RISK AB There is minimal guidance for efforts to create effective public messages that increase awareness that suicide is preventable. To address this need, several agencies in the U.S. Department of Health and Human Services and the Annenberg Foundation convened a workshop consisting of suicide prevention advocates and persons with expertise in public health evaluation, suicide contagion, decision-making, and marketing. "Logic models" were used to define intended messages and audiences, assumed mechanisms of change, and outcomes. This summary describes some of the challenges and opportunities identified by workshop participants in evaluating public awareness campaigns in suicide prevention, technical assistance needs, and a proposed research agenda. C1 NIMH, Disseminat & Implement Program, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Chambers, DA (reprint author), NIMH, Disseminat & Implement Program, 6001 Execut Blvd,Rm 7133,MSC 9631, Bethesda, MD 20892 USA. EM dchamber@mail.nih.gov NR 14 TC 18 Z9 18 U1 2 U2 6 PU GUILFORD PUBLICATIONS INC PI NEW YORK PA 72 SPRING STREET, NEW YORK, NY 10012 USA SN 0363-0234 J9 SUICIDE LIFE-THREAT JI Suicide Life-Threat. Behav. PD APR PY 2005 VL 35 IS 2 BP 134 EP 145 DI 10.1521/suli.35.2.134.62871 PG 12 WC Psychiatry; Psychology, Multidisciplinary SC Psychiatry; Psychology GA 924AD UT WOS:000228949900003 PM 15843331 ER PT J AU Ikemoto, S Donahue, KM AF Ikemoto, S Donahue, KM TI A five-minute, but not a fifteen-minute, conditioning trial duration induces conditioned place preference for cocaine administration into the olfactory tubercle SO SYNAPSE LA English DT Article DE reinforcement; reward; olfactory tubercle ID AMPHETAMINE; INJECTIONS AB The establishment of conditioned place preference (CPP) with intracranial injections requires specific injection sites, drug doses, and conditioning trial durations. We examined the role of conditioning trial duration in CPP with cocaine injections into the medial olfactory tubercle. Only those rats that had spent 5 min in the compartments showed CPP for cocaine, while rats that had been removed immediately or spent 15 min following cocaine injections did not show CPP. Effective conditioning trial durations for CPP induced by intracranial cocaine injections are apparently much shorter than those typically used for intracranial injections of other drugs of abuse. C1 NIDA, Behav Neurosci Branch, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Branch, NIH, Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sikemoto@intra.nida.nih.gov OI Ikemoto, Satoshi/0000-0002-0732-7386 NR 7 TC 10 Z9 11 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD APR PY 2005 VL 56 IS 1 BP 57 EP 59 DI 10.1002/syn.20124 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 902RF UT WOS:000227373500008 PM 15700283 ER PT J AU Antalis, TM Bugge, TH Lawrence, DA Netzel-Arnett, S Schwartz, BS Strickland, DK AF Antalis, TM Bugge, TH Lawrence, DA Netzel-Arnett, S Schwartz, BS Strickland, DK TI Amalfi to Washington D. C. - Twenty years of plasminogen activator research SO THROMBOSIS AND HAEMOSTASIS LA English DT Editorial Material C1 Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Branch, NIH, Bethesda, MD 20852 USA. Univ Maryland, Sch Med, Dept Surg, Rockville, MD USA. Univ Maryland, Sch Med, Dept Physiol, Rockville, MD USA. Univ Illinois, Coll Med, Dept Biochem, Urbana, IL 61801 USA. Univ Illinois, Coll Med, Dept Med, Urbana, IL 61801 USA. RP Bugge, TH (reprint author), Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Branch, NIH, 30 Convent Dr, Bethesda, MD 20852 USA. EM thomas.bugge@nih.gov FU NCI NIH HHS [R01 CA098369, P30 CA134274] NR 7 TC 0 Z9 0 U1 0 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 BP 625 EP 626 DI 10.1160/TH05-02-0110 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000001 PM 15841304 ER PT J AU Curino, A Patel, V Nielsen, BS Iskander, A Ensley, J Yoo, G Holsinger, FC Myers, J El-Nagaar, A Kellman, R Shillitoe, E Molinolo, A Gutkind, S Bugge, T AF Curino, A Patel, V Nielsen, BS Iskander, A Ensley, J Yoo, G Holsinger, FC Myers, J El-Nagaar, A Kellman, R Shillitoe, E Molinolo, A Gutkind, S Bugge, T TI Detection of plasminogen activators in human cancer by laser capture microdissection combined with zymography SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Mol Carcinogenesis Unit, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. Rigshosp, Finsen Lab, DK-2100 Copenhagen, Denmark. Wayne State Univ, Univ Hlth Ctr 5E, Dept Otolaryngol Head & Neck Surg, Detroit, MI 48201 USA. Wayne State Univ, Univ Hlth Ctr 5E, Karmanos Canc Ctr, Dept Internal Med, Detroit, MI 48201 USA. Univ Texas, MD Anderson Canc Ctr, Dept Head & Neck Surg, Houston, TX 77030 USA. SUNY Syracuse, Coll Med, Dept Microbiol & Immunol, Syracuse, NY 13210 USA. RI Gutkind, J. Silvio/A-1053-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 119 BP A31 EP A31 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000148 ER PT J AU Curino, A Engelholm, L Yamada, S Holmbeck, K Lund, L Molinolo, A Behrendt, N Nielsen, BS Bugge, TH AF Curino, A Engelholm, L Yamada, S Holmbeck, K Lund, L Molinolo, A Behrendt, N Nielsen, BS Bugge, TH TI Intracellular collagen degradation mediated by uPARAP/Endo180 is a major pathway of extracellular matrix turnover during malignancy SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Mol Carcinogenesis Unit, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Matrix Metalloproteinase Unit, NIH, Bethesda, MD 20892 USA. Rigshosp, Finsen Lab, DK-2100 Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 2 U2 4 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 011 BP A4 EP A4 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000041 ER PT J AU Hobson, JP Liu, L Leppla, SH Bugge, TH AF Hobson, JP Liu, L Leppla, SH Bugge, TH TI A simple, sensitive, and versatile assay for imaging specific cell surface proteolytic activity on living cells SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 Natl Inst Dental & Craniofacial Res, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD 20892 USA. NIAID, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 118 BP A31 EP A31 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000147 ER PT J AU Hobson, JP Netzel-Arnett, S Szabo, R Rehault, SM Church, FC Strickland, DK Lawrence, DA Antalis, TM Bugge, TH AF Hobson, JP Netzel-Arnett, S Szabo, R Rehault, SM Church, FC Strickland, DK Lawrence, DA Antalis, TM Bugge, TH TI DESC1, a member of a large new subfamily of type II transmembrane serine proteases, forms serpin inhibitory complexes SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodelling Unit, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Physiol, Rockville, MD 20855 USA. Univ Maryland, Sch Med, Dept Surg, Rockville, MD 20855 USA. Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 059 BP A16 EP A16 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000089 ER PT J AU Jogi, A Pass, J Hoyer-Hansen, G Liu, S Bugge, TH Leppla, SH Dano, K Romer, J AF Jogi, A Pass, J Hoyer-Hansen, G Liu, S Bugge, TH Leppla, SH Dano, K Romer, J TI Antibody directed against mouse uPAR rescues mouse cells exposed to a lethal dose of cell surface uPA-dependent anthrax toxin SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 Rigshosp, Finsen Lab, DK-2100 Copenhagen, Denmark. NIAID, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 121 BP A32 EP A32 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000150 ER PT J AU List, K Szabo, R Wertz, PW Segre, J Behrendt, N Bugge, TH AF List, K Szabo, R Wertz, PW Segre, J Behrendt, N Bugge, TH TI Matriptase as a key regulator of epidermal barrier acquisition and proteolytic processing of the skin-specific polyprotein, profilaggrin SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD 20892 USA. Finsen Lab, DK-2100 Copenhagen, Denmark. Univ Iowa, Coll Dent, Dows Inst, Iowa City, IA 52242 USA. NHGRI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 062 BP A17 EP A17 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000092 ER PT J AU List, K Szabo, R Molinolo, A Sriuranpong, V Redeye, V Murdock, T Burke, B Nielsen, BS Gutkind, JS Bugge, TH AF List, K Szabo, R Molinolo, A Sriuranpong, V Redeye, V Murdock, T Burke, B Nielsen, BS Gutkind, JS Bugge, TH TI The pro-uPA activator matriptase causes multistage carcinogenesis via pathways mechanistically dependent or independent of ras activation SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Mol Carcinogenesis Unit, Bethesda, MD 20892 USA. Finsen Lab, DK-2100 Copenhagen, Denmark. RI Gutkind, J. Silvio/A-1053-2009 NR 0 TC 0 Z9 0 U1 1 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 036 BP A10 EP A10 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000066 ER PT J AU Liu, S Redeye, V Kuremsky, JG Kuhnen, MM Leppla, SH Bugge, TH AF Liu, S Redeye, V Kuremsky, JG Kuhnen, MM Leppla, SH Bugge, TH TI Efficient tumor targeting by an anthrax toxin that requires both uPA and MMP proteolysis for cytotoxicity SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 NIAID, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 123 BP A32 EP A32 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000152 ER PT J AU Minor, KH Schar, CR Blouse, GE Shore, JD Lawrence, DA Schuck, P Peterson, CB AF Minor, KH Schar, CR Blouse, GE Shore, JD Lawrence, DA Schuck, P Peterson, CB TI An ordered mechanism for assembly of complexes of vitronectin and plasminogen activator inhibitor-I: sedimentation velocity analysis of higher order complexes in the analytical ultracentrifuge SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 Univ Tennessee, Dept Biochem Cellular & Mol Biol, Knoxville, TN USA. Univ Tennessee, Ctr Excellence Struct Biol, Knoxville, TN USA. Wayne State Univ, Dept Pathol, Henry Ford Hlth Syst, Detroit, MI USA. Wayne State Univ, Dept Pharmacol, Detroit, MI 48201 USA. Barbara Ann Karmanos Canc Inst, Detroit, MI USA. Univ Maryland, Sch Med, Dept Surg, Rockville, MD USA. Univ Maryland, Sch Med, Dept Physiol, Rockville, MD USA. Protein Biophys Resource, Div Bioengn & Phys Sci, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 028 BP A8 EP A8 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000058 ER PT J AU Moutsopoulos, NM Greenwell-Wild, T Jin, W Lei, KJ Ma, G Swaim, W Wahl, SM AF Moutsopoulos, NM Greenwell-Wild, T Jin, W Lei, KJ Ma, G Swaim, W Wahl, SM TI SLPI blocks plasminogen-dependent proteolysis through annexin II SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 NIDCR, OIIB, NIH, Bethesda, MD 20892 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 035 BP A10 EP A10 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000065 ER PT J AU Netzel-Arnett, S Bugge, TH Hess, RA Antalis, TM AF Netzel-Arnett, S Bugge, TH Hess, RA Antalis, TM TI On the biological function of testisin: a GPI-anchored serine protease SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 Univ Maryland, Sch Med, Dept Physiol & Surg, Rockville, MD USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. Univ Illinois, Dept Vet Biosci, Urbana, IL 61801 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 015 BP A5 EP A5 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000045 ER PT J AU Pang, PT Woo, N Lu, B AF Pang, PT Woo, N Lu, B TI Bi-directional control of long-term hippocampal plasticity by tPA/plasmin-mediated extracellular cleavage of proBDNF SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 NICHD, Sect Neural Dev & Plast, LCSN, NIH, Bethesda, MD 20892 USA. RI Lu, Bai/A-4018-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 001 BP A2 EP A2 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000031 ER PT J AU Rono, B Romer, J Leppla, SH Liu, S Bugge, TH Kristjansen, PEG AF Rono, B Romer, J Leppla, SH Liu, S Bugge, TH Kristjansen, PEG TI Significant anti-tumor efficacy after systemic administration of urokinase activation dependent anthrax toxin SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 Univ Copenhagen, Inst Mol Pathol, Expt Oncol Lab, Copenhagen, Denmark. Rigshosp, Finsen Lab, DK-2100 Copenhagen, Denmark. Microbial Pathogenesis Sect, NIH, Bethesda, MD USA. Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 044 BP A12 EP A12 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000074 ER PT J AU Szabo, R Netzel-Arnett, S Hobson, JP Antalis, TM Bugge, TH AF Szabo, R Netzel-Arnett, S Hobson, JP Antalis, TM Bugge, TH TI Matriptase-3 is a novel, evolutionarily conserved matriptase/MT-SP1 homologue that encodes a functional type II transmembrane serine protease with conserved expression in mice and humans SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Rockville, MD 20855 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 064 BP A17 EP A17 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000094 ER PT J AU Szabova, L Yamada, SS Birkedal-Hansen, H Holmbeck, K AF Szabova, L Yamada, SS Birkedal-Hansen, H Holmbeck, K TI Expression pattern of four membrane-type matrix metalloproteinases in the normal and diseased mouse mammary gland SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, Matrix Metalloproteinase Unit, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 065 BP A18 EP A18 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000095 ER PT J AU Wagenaar-Miller, RA Netzel-Arnett, S Hobson, JP Antalis, TM Bugge, TH AF Wagenaar-Miller, RA Netzel-Arnett, S Hobson, JP Antalis, TM Bugge, TH TI Functional characterization of DESC3; a novel type II transmembrane serine protease SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Rockville, MD 20855 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 060 BP A16 EP A16 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000090 ER PT J AU Wagenaar-Miller, RA Engelholm, LH Kuhnen, M Kahan, S Yamada, S Nielsen, BS Behrendt, N Bugge, TH Holmbeck, K AF Wagenaar-Miller, RA Engelholm, LH Kuhnen, M Kahan, S Yamada, S Nielsen, BS Behrendt, N Bugge, TH Holmbeck, K TI A critical role of uPARAP/Endo180-dependent intracellular collagen turnover in mouse postnatal development SO THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract CT 10th Interenational Workshop on Molecular and Cellular Biology of Plasminogen Activation CY APR 09-13, 2005 CL Washington, DC C1 NIDCR, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD 20892 USA. NIDCR, Matrix Metalloproteinase Unit, NIH, Bethesda, MD 20892 USA. Rigshosp, Finsen Lab, DK-2100 Copenhagen, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD APR PY 2005 VL 93 IS 4 MA 021 BP A7 EP A7 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 916NS UT WOS:000228393000051 ER PT J AU Wolff, J AF Wolff, J TI What is the role of pendrin? SO THYROID LA English DT Editorial Material ID PORCINE THYROID-CELLS; APICAL IODIDE EFFLUX; TRANSPORT; GLAND; MEMBRANE; GENE; RADIOIODIDE; PERCHLORATE; SYMPORTER; PROTEIN C1 NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Wolff, J (reprint author), NIDDKD, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. EM janw@bdg8.niddk.nih.gov NR 28 TC 23 Z9 23 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD APR PY 2005 VL 15 IS 4 BP 346 EP 348 DI 10.1089/thy.2005.15.346 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 926SQ UT WOS:000229143400009 PM 15876157 ER PT J AU Spong, CY AF Spong, CY TI Maternal thyroid disorders and preterm birth: Another piece of the puzzle? SO THYROID LA English DT Editorial Material C1 NICHD, Pregnancy & Perinatol Branch, Bethesda, MD 20892 USA. RP Spong, CY (reprint author), NICHD, Pregnancy & Perinatol Branch, 6100 Execut Blvd,Rm 4B03,MSC 7510, Bethesda, MD 20892 USA. EM spongc@mail.nih.gov NR 3 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD APR PY 2005 VL 15 IS 4 BP 349 EP 350 DI 10.1089/thy.2005.15.349 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 926SQ UT WOS:000229143400010 PM 15876158 ER PT J AU Liu, J Waalkes, MP AF Liu, J Waalkes, MP TI Focal adhesion kinase as a potential target in arsenic toxicity SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material DE thyroxine; triiodothyronine; rat; Oatp2; biliary clearance; thyroid stimulating hormone; hepatic transporters ID CANCER C1 NCI, Comparat Carcinogenesis Lab, NIEHS, Res Triangle Pk, NC 27709 USA. RP Liu, J (reprint author), NCI, Comparat Carcinogenesis Lab, NIEHS, 111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM Liu6@niehs.nih.gov NR 13 TC 6 Z9 6 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 2005 VL 84 IS 2 BP 212 EP 213 DI 10.1093/toxsci/kfi111 PG 2 WC Toxicology SC Toxicology GA 911AQ UT WOS:000227973900002 PM 15834968 ER PT J AU Karrow, NA McCay, JA Brown, RD Musgrove, DL Guo, TL Germolec, DR White, KL AF Karrow, NA McCay, JA Brown, RD Musgrove, DL Guo, TL Germolec, DR White, KL TI Oral exposure to atrazine modulates cell-mediated immune function and decreases host resistance to the B16F10 tumor model in female B6C3F1 mice SO TOXICOLOGY LA English DT Article DE atrazine; immunomodulation; B6C3F1 mice; cell-mediated immunity; B16F10 melanoma ID SPRAGUE-DAWLEY RATS; HERBICIDE ATRAZINE; STRESS-RESPONSE; PARAMETERS; CORTISOL; ETHANOL AB Atrazine (ATZ) is used throughout North America to control annual broadleaf weeds and grasses in various crops including; corn, sorghum, and sugar cane. Unfortunately, contamination of surface and ground water has occurred as a result of ATZ's chemical and physical properties, and its widespread use throughout the U.S. Midwest. A study of ATZ's immunomodulatory properties was conducted using female B6C3F1 mice and a panel of immune assays and host resistance models designed to evaluate cell-mediated and antibody-mediated immunity. Mice were administered ATZ by gavage (0, 24,250, and 500 mg/kg/day) for 14 days then evaluated for immune responsiveness. ATZ treatment significantly increased the number of splenic CD8(+) T cells, cytotoxic T cell and mixed leukocyte responses, and dose-dependently reduced host resistance to B 161710 melanoma. Thymus and spleen weights, total spleen cell numbers and fixed macrophage function was also reduced in mice that were exposed to ATZ. These results demonstrate that oral ATZ exposure is sufficient to alter cell-mediated immune function and disease resistance in female B6C3F1 mice. (C) 2004 Published by Elsevier Ireland Ltd. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NIEHS, Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP White, KL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Med Coll Virginia Campus, Richmond, VA 23298 USA. EM kwhite@hsc.vcu.edu FU NIEHS NIH HHS [ES55387] NR 41 TC 33 Z9 36 U1 2 U2 4 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 1 PY 2005 VL 209 IS 1 BP 15 EP 28 DI 10.1016/j.tox.2004.12.002 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 904ON UT WOS:000227507700002 PM 15725510 ER PT J AU Kleinman, S Glynn, SA Busch, M Todd, D Powell, L Pietrelli, L Nemo, G Schreiber, G Bianco, C Katz, L AF Kleinman, S Glynn, SA Busch, M Todd, D Powell, L Pietrelli, L Nemo, G Schreiber, G Bianco, C Katz, L CA NHLBI Retrovirus Epidemiology Stud TI The 2003 West Nile virus United States epidemic: the America's Blood Centers experience SO TRANSFUSION LA English DT Article ID INFECTIONS; MINIPOOL; DONORS AB BACKGROUND: A detailed assessment of West Nile virus (WNV) yield is needed to evaluate the effectiveness of the WNV nucleic acid amplification technology (NAT) screening implemented in 2003. STUDY DESIGN AND METHODS: WNV NAT screening and donation data were compiled from members of America's Blood Centers, which collect nearly 50 percent of the US blood supply. WNV RNA screening was performed with either the Gen-Probe/Chiron Procleix transcription-mediated amplification assay or the Roche TaqScreen polymerase chain reaction. Results of alternate NAT and WNV immunoglobulin M (IgM) antibody assays conducted on index and follow-up samples were obtained from test manufacturers. Presumed WNV positivity was based on NAT repeat reactivity of the individual index donation whereas confirmatory status was based on additional IgM testing of the index donation and NAT and serology testing of follow-up samples. RESULTS: From July through October 2003, 2.5 million donations were screened for WNV RNA. Of 877 NAT-reactive donations (screening positivity rate of 3.5 per 10,000 units), 430 (49%) were confirmed positive, whereas 68 (8%) lacking follow-up data remained presumed positive. The sensitivity and positive predictive value of a presumed viremic result relative to final confirmatory status were 92 and 99 percent, respectively. WNV activity was highest in the central plains with prevalence per 10,000 peaking August 1 to 15 in Colorado (67.7) and South Dakota (77.5) and August 16 to 31 in Wyoming (74.1) and North Dakota (102.0). CONCLUSIONS: WNV screening interdicted many viremic units, thereby reducing transfusion-transmitted infections. This study demonstrates that a national collaborative effort facilitates timely surveillance of blood donor infectious disease prevalence rates. C1 WESTAT Corp, Rockville, MD 20850 USA. Univ British Columbia, Victoria, BC, Canada. Blood Syst Inc, Scottsdale, AZ USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Gen Probe Inc, San Diego, CA USA. Roche Mol Syst, Pleasanton, CA USA. NHLBI, Div Blood Dis & Resources, Blood Resources Branch, Bethesda, MD 20892 USA. Amer Blood Ctr, Washington, DC USA. Mississippi Valley Reg Blood Ctr, Davenport, IA USA. RP Glynn, SA (reprint author), WESTAT Corp, WB280,1441 W Montgomery Ave, Rockville, MD 20850 USA. FU NHLBI NIH HHS [N01-HB-9708097081, N01-HB-47114, N01-HB-97078, N01-HB-97082, N01-HB-97079, N01-HB-97077] NR 13 TC 51 Z9 53 U1 0 U2 2 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2005 VL 45 IS 4 BP 469 EP 479 DI 10.1111/j.0041-1132.2005.04315.x PG 11 WC Hematology SC Hematology GA 908GV UT WOS:000227776400005 PM 15819665 ER PT J AU Lin, LL Hanson, CV Alter, HJ Jauvin, V Bernard, KA Murthy, KK Metzel, P Corash, L AF Lin, LL Hanson, CV Alter, HJ Jauvin, V Bernard, KA Murthy, KK Metzel, P Corash, L TI Inactivation of viruses in platelet concentrates by photochemical treatment with amotosalen and long-wavelength ultraviolet light SO TRANSFUSION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HEPATITIS-B-VIRUS; WEST-NILE VIRUS; ACUTE-RESPIRATORY-SYNDROME; BLOOD-TRANSFUSION; PARVOVIRUS B19; NON-A; PATHOGEN INACTIVATION; CDNA CLONE; TRANSMISSION AB BACKGROUND: Viral contamination of platelet (PLT) concentrates can result in transfusion-transmitted diseases. A photochemical treatment (PCT) process with amotosalen-HCl and long-wavelength ultraviolet light (UVA), which cross-links nucleic acids, was developed to inactivate viruses and other pathogens in PLT concentrates. STUDY DESIGN AND METHODS: High titers of pathogenic or blood-borne viruses, representing 10 different families, were added to single-donor PLT concentrates containing 3.0 x 10(11) to 6.0 x 10(11) PLTs in approximately 300 mL of 35 percent plasma and 65 percent PLT additive solution (InterSol). After PCT with 150 mu mol per L amotosalen and 3 J per cm(2) UVA, residual viral infectivity was assayed by sensitive cell culture or animal systems. RESULTS: Enveloped viruses were uniformly sensitive to inactivation by PCT whereas nonenveloped viruses demonstrated variable inactivation. Log reduction of enveloped viruses for cell-free HIV-1 was > 6.2; for cell-associated HIV-1, > 6.1; for clinical isolate HIV-1, > 3.4; for clinical isolate HIV-2, > 2.5; for HBV, > 5.5; for HCV, > 4.5; for DHBV, > 6.2; for BVDV, > 6.0; for HTLV-I, 4.2; for HTLV-II, 4.6; for CMV, > 5.9; for WNV, > 5.5; for SARS-HCoV, > 5.8; and for vaccinia virus, > 4.7. Log reduction of nonenveloped viruses for human adenovirus 5 was > 5.2; for parvovirus B19, 3.5-> 5.0; for bluetongue virus, 5.6-5.9; for feline conjunctivitis virus, 1.7-2.4; and for simian adenovirus 15, 0.7-2.3. CONCLUSION: PCT inactivates a broad spectrum of pathogenic, blood-borne viruses. Inactivation of viruses in PLT concentrates with amotosalen and UVA offers the potential to prospectively prevent the majority of PLT transfusion-associated viral diseases. C1 Cerus Corp, Concord, CA 94520 USA. Calif Dept Hlth Serv, Viral & Rickettsial Dis Lab, Richmond, CA USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. Victor Segalen Univ, Virol Lab, Bordeaux, France. Wadsworth Ctr, New York State Dept Hlth, ArbLabArbovirus Labs, Albany, NY USA. SW Fdn Biomed Res, Dept Virol & Immunol, San Antonio, TX 78284 USA. Baxter Healthcare Corp, Transfus Therapies, Round Lake, IL 60073 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. RP Lin, LL (reprint author), Cerus Corp, 2411 Stanwell Dr, Concord, CA 94520 USA. EM lily_lin@cerus.com NR 57 TC 100 Z9 101 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2005 VL 45 IS 4 BP 580 EP 590 DI 10.1111/j.0041-1132.2005.04316.x PG 11 WC Hematology SC Hematology GA 908GV UT WOS:000227776400020 PM 15819680 ER PT J AU Wu, GG Yu, Q Su, YQ Deng, ZH Liang, YL Wei, TL Zhao, TM AF Wu, GG Yu, Q Su, YQ Deng, ZH Liang, YL Wei, TL Zhao, TM TI Novel ABO blood group allele with a 767T > C substitution in three generations of a Chinese family SO TRANSFUSION LA English DT Letter C1 Shenzhen Inst Transfus Med, Shenzhen, Peoples R China. NIH, Bethesda, MD 20892 USA. RP Wu, GG (reprint author), Shenzhen Inst Transfus Med, Shenzhen, Peoples R China. NR 2 TC 5 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2005 VL 45 IS 4 BP 645 EP 646 DI 10.1111/j.0041-1132.2005.00456.x PG 2 WC Hematology SC Hematology GA 908GV UT WOS:000227776400030 PM 15819691 ER PT J AU Bassett, CL Nickerson, ML Farrell, RE Artlip, TS El Ghaouth, A Wilson, CL Wisniewski, ME AF Bassett, CL Nickerson, ML Farrell, RE Artlip, TS El Ghaouth, A Wilson, CL Wisniewski, ME TI Characterization of an S-locus receptor protein kinase-like gene from peach SO TREE PHYSIOLOGY LA English DT Article DE photoperiod; salicylic acid; signal transduction; UV-C light ID BRASSICA SELF-INCOMPATIBILITY; ARABIDOPSIS-THALIANA; UV-C; SIGNAL-TRANSDUCTION; OLERACEA; LIGAND; PHOSPHORYLATION; EXPRESSION; INDUCTION; GROWTH AB A receptor-like protein kinase gene (Ppsrkl1) was isolated from a peach (Prunus persica (L.) Batsch.) bark cDNA library prepared with RNAs isolated from bark collected in December (cold acclimated). Sequence analysis indicated that this gene is related to the S-locus family of receptor protein kinases (SRKs) and that it shares greatest homology with ZMPK1 from maize and At4g32300 from Arabidopsis, both of which are intron-less genes. In bark tissues, Ppsrkl1 is induced by water deficit treatment, repressed by short-day photoperiods and showed no response to cold treatment. The Ppsrkl1 mRNA also increased in roots in response to water deficit. In fruit, Ppsrkl1 shows no response up to 6 It after wounding, but at 12 and 24 h after wounding, Ppsrkl1 mRNA shows an abrupt decline. This decline was prevented by the addition of salicylic acid to the wound site. The Ppsrkl1 mRNA rapidly decreased in fruit after 10-min exposure to UV-C radiation, followed by a return to normal levels within 1.5 h. Taken together, these experiments indicate that Ppsrkl1 is negatively regulated by light and positively influenced by salicylic acid treatment in fruit and water stress in bark and roots. C1 USDA ARS, Appalachian Fruit Res Stn, Kearneysville, WV 25430 USA. NCI, Immunol Lab, Frederick, MD 21702 USA. Penn State Univ, Dept Biol, York, PA 17403 USA. RIM Informat, Nouakchott, Mauritania. RP Bassett, CL (reprint author), USDA ARS, Appalachian Fruit Res Stn, 45 Wiltshire Rd, Kearneysville, WV 25430 USA. EM cbassett@afrs.ars.usda.gov NR 45 TC 9 Z9 10 U1 1 U2 5 PU HERON PUBLISHING PI VICTORIA PA 202, 3994 SHELBOURNE ST, VICTORIA, BC V8N 3E2, CANADA SN 0829-318X J9 TREE PHYSIOL JI Tree Physiol. PD APR PY 2005 VL 25 IS 4 BP 403 EP 411 PG 9 WC Forestry SC Forestry GA 911XX UT WOS:000228041200003 PM 15687089 ER PT J AU Agnati, LF Fuxe, K Ferre, S AF Agnati, LF Fuxe, K Ferre, S TI How receptor mosaics decode transmitter signals. Possible relevance of cooperativity SO TRENDS IN BIOCHEMICAL SCIENCES LA English DT Editorial Material ID CENTRAL-NERVOUS-SYSTEM; CAVEOLIN-SCAFFOLDING DOMAIN; DOPAMINE-RECEPTOR; NUCLEUS-ACCUMBENS; BINDING-SITES; NEGATIVE COOPERATIVITY; PHOSPHATASE-1 CASCADE; BASAL GANGLIA; RAT-BRAIN; IN-VIVO AB It has been demonstrated that receptor-receptor interactions between G-protein-coupled receptors (GPCRs) occur at the plasma-membrane level. It has also been shown that clustering of GPCRs in aggregates or receptor mosaics (RMs) results in the reciprocal modulation of their binding and decoding characteristics. It is hypothesized that cooperativity plays an important part in the decoding of signals processed by RMs of GPCIRs. Thus, the binding of the ligand at one receptor alters the likelihood of the same ligand binding at the next site, in the case of RMs, formed by identical receptors and/or by iso-receptors (receptors that bind the same ligand). C1 Dept Biomed Sci, I-41100 Modena, Italy. Karolinska Inst, Dept Neurosci, S-17177 Stockholm, Sweden. NIDA, Behav Neurosci Branch, IRP, NIH,DHHS, Baltimore, MD 21224 USA. RP Agnati, LF (reprint author), Dept Biomed Sci, I-41100 Modena, Italy. EM luigiagnati@tin.it RI Ferre, Sergi/K-6115-2014; OI Ferre, Sergi/0000-0002-1747-1779; Fuxe, Kjell/0000-0001-8491-4288 NR 51 TC 47 Z9 48 U1 0 U2 5 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0968-0004 J9 TRENDS BIOCHEM SCI JI Trends Biochem.Sci. PD APR PY 2005 VL 30 IS 4 BP 188 EP 193 DI 10.1016/j.tibs.2005.02.010 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 919HK UT WOS:000228608800007 PM 15817395 ER PT J AU McLeod, CJ Pagel, I Sack, MN AF McLeod, CJ Pagel, I Sack, MN TI The mitochondrial biogenesis regulatory program in cardiac adaptation to ischemia - A putative target for therapeutic intervention SO TRENDS IN CARDIOVASCULAR MEDICINE LA English DT Review ID PROLIFERATOR-ACTIVATED RECEPTOR; K-ATP CHANNEL; MYOCARDIAL-ISCHEMIA; SKELETAL-MUSCLE; GENE-EXPRESSION; TRANSGENIC MICE; HIGH-ALTITUDE; NITRIC-OXIDE; ROSIGLITAZONE; REPERFUSION AB The resurgence of mitochondrial biology research stems from the realization that the distinct regulation of mitochondria to meet diverse homeostatic demands is driven by exquisite biochemical and molecular control mechanisms. This program termed mitochondrial biogenesis is integral to orchestrating mitochondrial function and appears to exhibit adaptive remodeling following biomechanical and oxidative stress. The major bioenergetic function of mitochondria partitions the final utilization of oxygen between oxidative phosphorylation and reactive oxygen species. As disruption in oxidative phosphorylation and excessive reactive oxygen species contribute to cardiac ischemia-reperfusion injury, we hypothesize that the mitochondrial biogenesis regulatory program is an explicit target for cardiac therapeutic interventions. The objectives of this review are to (a) define the advances in understanding the mitochondrial biogenesis regulatory program integrated to its control of mitochondrial bioenergetics and oxygen utilization, (b) reveal how this program is modulated by chronic hypoxia and ischemic preconditioning, and (c) examine the therapeutic potential of modulating the regulation of mitochondrial biogenesis as a strategy to attenuate ischemia-reperfusion injury. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Sack, MN (reprint author), NHLBI, NIH, Bldg 10,CRC,Room 5-3150,10 Ctr Dr, Bethesda, MD 20892 USA. EM sackm@nhlbi.nih.gov NR 50 TC 58 Z9 60 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1050-1738 J9 TRENDS CARDIOVAS MED JI Trends Cardiovasc. Med. PD APR PY 2005 VL 15 IS 3 BP 118 EP 123 AR PII S1050-1738(05)00055-1 DI 10.1016/j.tcm.2005.05.001 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 960OR UT WOS:000231603500007 PM 16039972 ER PT J AU Stojilkovic, SS AF Stojilkovic, SS TI Ca2+-regulated exocytosis and SNARE function SO TRENDS IN ENDOCRINOLOGY AND METABOLISM LA English DT Review ID DEPENDENT PHOSPHORYLATION; REGULATED EXOCYTOSIS; PROTEIN; FUSION; CELLS AB Secretory vesicles formed at the trans-Golgi network of neuroendocrine and endocrine cells must undergo several steps, such as translocation, docking and priming, before they are ready to fuse with the plasma membrane and deliver their cargo into the extracellular space. This process is called regulated exocytosis and is controlled by Ca2+ (using synaptotagmin) and mediated by SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) proteins. Recent studies from three leading laboratories reveal novel details about the mechanism by which Ca2+ and SNAREs regulate this complex process. These findings highlight the roles of both SNAP25 (synaptosome-associated protein of 25kD), one of the SNARE proteins, and CAPS (Ca2+-dependent activator protein for secretion), a Ca2+-sensor protein, in vesicle priming, depriming and fusion. C1 NICHHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Stojilkovic, SS (reprint author), NICHHD, Sect Cellular Signaling, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. EM stankos@helix.nih.gov NR 13 TC 51 Z9 53 U1 1 U2 7 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1043-2760 J9 TRENDS ENDOCRIN MET JI Trends Endocrinol. Metab. PD APR PY 2005 VL 16 IS 3 BP 81 EP 83 DI 10.1016/j.tem.2005.02.002 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 918AG UT WOS:000228509900002 PM 15808803 ER PT J AU Diaz, M Lawrence, C AF Diaz, M Lawrence, C TI An update on the role of translesion synthesis DNA polyrnerases in Ig hypermutation SO TRENDS IN IMMUNOLOGY LA English DT Review ID CLASS-SWITCH RECOMBINATION; MISMATCH REPAIR PROTEIN; IMMUNOGLOBULIN VARIABLE GENES; AFFECT SOMATIC HYPERMUTATION; ACTIVATION-INDUCED DEAMINASE; EXPRESSING ANTISENSE RNA; A-T MUTATOR; POLYMERASE-ZETA; ANTIBODY DIVERSIFICATION; MICE DEFICIENT AB (S)everal years have passed since the discovery of activation-induced cytosine deaminase (AID), the molecule responsible for triggering hypermutation of Ig genes. We now know that AID deaminates cytosines in the DNA encoding the variable portion of the Ig receptor, although an additional role in deaminating a regulatory mRNA transcript has not been ruled out. A major question that remains unanswered is how AID, a cytosine deaminase, causes mutations at both G:C and A:T base pairs. Mounting evidence suggests the involvement of a group of error-prone DNA polymerases known to bypass DNA lesions: the translesion synthesis (TLS) DNA polymerases. In this Review, we discuss the evidence for a role of TLS DNA polymerases in Ig hypermutation and argue that a major remaining challenge in our understanding of this mechanism is the recruitment of TLS DNA polymerases to the Ig locus following AID-mediated cytosine deamination. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. Univ Rochester, Sch Med & Dent, Dept Biochem & Biophys, Rochester, NY 14642 USA. RP Diaz, M (reprint author), NIEHS, Mol Genet Lab, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM diaz@niehs.nih.gov NR 67 TC 45 Z9 46 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4906 J9 TRENDS IMMUNOL JI Trends Immunol. PD APR PY 2005 VL 26 IS 4 BP 215 EP 220 DI 10.1016/j.it.2005.02.008 PG 6 WC Immunology SC Immunology GA 918AB UT WOS:000228509400007 PM 15797512 ER PT J AU Hinton, DM AF Hinton, DM TI Molecular gymnastics: distortion of an RNA polymerase sigma factor SO TRENDS IN MICROBIOLOGY LA English DT Review ID BACTERIOPHAGE-T4 ASIA PROTEIN; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; T4 ASIA; TRANSCRIPTION INITIATION; ANGSTROM RESOLUTION; BINDING-PROTEIN; ACTIVATOR MOTA; OPEN COMPLEX; PROMOTER AB A recent structure obtained by nuclear magnetic resonance (NMR) spectroscopy shows that the binding of a small phage factor to the sigma(70) subunit of Escherichia coli RNA polymerase induces an unprecedented remodeling of a region of sigma(70), converting a DNA-binding helix-turn-helix into a continuous pseudohelix. This conformational change suggests how the phage factor can function both as an inhibitor and co-activator of transcription. C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hinton, DM (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. EM dhinton@helix.nih.gov NR 25 TC 5 Z9 5 U1 0 U2 3 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD APR PY 2005 VL 13 IS 4 BP 140 EP 143 DI 10.1016/j.tim.2005.02.005 PG 4 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 919HE UT WOS:000228608200002 PM 15817381 ER PT J AU Karten, YJG Olariu, A Cameron, HA AF Karten, YJG Olariu, A Cameron, HA TI Stress in early life inhibits neurogenesis in adulthood SO TRENDS IN NEUROSCIENCES LA English DT Article ID NEONATAL MATERNAL SEPARATION; DENTATE GYRUS; GLUCOCORTICOID-RECEPTOR; PSYCHOSOCIAL STRESS; CELL-PROLIFERATION; ADRENAL-STEROIDS; RATS; DEPRESSION; HIPPOCAMPUS; ACTIVATION AB Both structure and function of the hippocampus are altered by stress: by increasing levels of corticosteroids, stress causes atrophy of CA3 pyramidal cell dendrites, inhibits adult neurogenesis in the dentate gyrus, and impairs hippocampus-dependent learning. A recent study shows that adverse experience limited to early life, specifically removal of rat pups from their mother for three hours each day, decreases production of new granule neurons in adulthood through a corticosteroid-dependent mechanism. This finding suggests that stress in early life could permanently impair hippocampus-dependent learning and memory and increase susceptibility to depression by inhibiting adult neurogenesis in the hippocampus. C1 NIMH, Unit Neuroplastic 35 3C915, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Cameron, HA (reprint author), NIMH, Unit Neuroplastic 35 3C915, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM heathercameron@mail.nih.gov RI Cameron, Heather/E-6221-2011 OI Cameron, Heather/0000-0002-3245-5777 NR 23 TC 53 Z9 62 U1 1 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0166-2236 J9 TRENDS NEUROSCI JI Trends Neurosci. PD APR PY 2005 VL 28 IS 4 BP 171 EP 172 DI 10.1016/j.tins.2005.01.009 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 917ZP UT WOS:000228508200002 PM 15808349 ER PT J AU Monteith, GR Bird, GSJ AF Monteith, GR Bird, GSJ TI Techniques: High-throughput measurement of intracellular Ca2+ - back to basics SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Review ID IMAGING PLATE READER; PROTEIN-COUPLED RECEPTORS; VANILLOID RECEPTOR; FLUORESCENT INDICATORS; FUNCTIONAL ASSAYS; SCREENING ASSAYS; DRUG DISCOVERY; TRPC3 CHANNELS; ION-CHANNEL; CALCIUM AB High-throughput screening techniques continue to provide important tools to the pharmaceutical industry for the efficient identification of drug leads. However, high-throughput techniques are now being exploited to address a variety of pharmacological and cellular signaling research questions, including the regulation and role of intracellular Ca2+ in a plethora of biological systems. Although an awareness of specific assay conditions is crucial for reliable and reproducible measurements of intracellular free Ca2+ whichever system of study is used, the complex temporal nature of Ca2+ signals has posed some unique limitations for its measurement in high-throughput mode. Progress in high-throughput design has overcome many of these limitations and will complement other technical approaches to understanding the underlying regulation and role of intracellular Ca2+. C1 Univ Queensland, Sch Pharm, Brisbane, Qld 4072, Australia. NIEHS, DHHS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Monteith, GR (reprint author), Univ Queensland, Sch Pharm, St Lucia Campus, Brisbane, Qld 4072, Australia. EM G.Monteith@pharmacy.uq.edu.au RI Monteith, Gregory/B-1626-2008 OI Monteith, Gregory/0000-0002-4345-530X NR 50 TC 32 Z9 34 U1 0 U2 4 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD APR PY 2005 VL 26 IS 4 BP 218 EP 223 DI 10.1016/j.tips.2005.02.002 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 919HI UT WOS:000228608600010 PM 15808347 ER PT J AU Mari, G AF Mari, G TI Middle cerebral artery peak systolic velocity for the diagnosis of fetal anemia: the untold story SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Editorial Material ID RED-CELL ALLOIMMUNIZATION; PROSPECTIVE MULTICENTER TRIAL; DOPPLER ULTRASONOGRAPHY; NONINVASIVE DIAGNOSIS; RHESUS-ISOIMMUNIZATION; RH ISOIMMUNIZATION; PREDICTION; MANAGEMENT; PREGNANCY; TRANSFUSION C1 Wayne State Univ, Dept Obstet & Gynecol, NICHD, Perinatol Res Branch,NIH,DHHS, Detroit, MI USA. RP Mari, G (reprint author), Wayne State Univ, Dept Obstet & Gynecol, NICHD, Perinatol Res Branch,NIH,DHHS, Detroit, MI USA. EM gmari@med.wayne.edu NR 61 TC 29 Z9 39 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD APR PY 2005 VL 25 IS 4 BP 323 EP 330 DI 10.1002/uog.1882 PG 8 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 918BB UT WOS:000228512200002 PM 15789353 ER PT J AU Espinoza, J Goncalves, LF Romero, R Nien, JK Stites, S Kim, YM Hassan, S Gomez, R Yoon, BH Chaiworapongsa, T Lee, W Mazor, M AF Espinoza, J Goncalves, LF Romero, R Nien, JK Stites, S Kim, YM Hassan, S Gomez, R Yoon, BH Chaiworapongsa, T Lee, W Mazor, M TI The prevalence and clinical significance of amniotic fluid 'sludge' in patients with preterm labor and intact membranes SO ULTRASOUND IN OBSTETRICS & GYNECOLOGY LA English DT Article DE amniotic fluid 'sludge'; chorioamnionitis; intrauterine inflammation; microbial invasion of the amniotic cavity; preterm delivery; preterm labor; ultrasound ID FREE-FLOATING PARTICLES; CERVICAL-MUCUS PLUG; BLOOD-CELL COUNT; INTRAUTERINE INFECTION; PREMATURE RUPTURE; ANTIBACTERIAL PROPERTIES; UREAPLASMA-UREALYTICUM; MICROBIAL INVASION; INTRAAMNIOTIC INFECTION; ALPHA-FETOPROTEIN AB Objective To determine the prevalence and clinical significance of amniotic fluid (AF) 'sludge' observed during transvaginal ultrasound examination of the cervix in patients with preterm labor and intact membranes, and in those with uncomplicated pregnancies. Methods This retrospective study included patients with preterm labor and intact membranes (n = 84) and those with uncomplicated term pregnancies (n = 298). The outcome variables included the occurrence of documented microbial invasion of the amniotic cavity (MIAC), histological chorioamnionitis, examination-to-delivery interval, admission to the neonatal intensive care unit (NICU), a composite neonatal morbidity, perinatal death, and delivery within 48 h, 7 days, and < 35 weeks and < 32 weeks. Statistical analysis included Chi-square test, stepwise logistic regression analysis and survival analysis. Results The prevalence of AF 'sludge' was 1% (3/298) in patients with uncomplicated term pregnancies and 22.6% (19/84) in those with preterm labor and intact membranes. Among patients with preterm labor and intact membranes: (1) cervical length <= 15 mm was present in 58.3% (49/84) of the patients; (2) the prevalence of MIAC and histological chorioamnionitis was 12.1% (7/58) and 32.9% (25/76), respectively; (3) the rate of spontaneous preterm delivery within 48 h, 7 days, and < 32 weeks and < 35 weeks of gestation was 13.6% (8/59), 28.8% (17/59), 39.5% (17/43) and 50.8% (30/59), respectively; (4) patients with AF 'sludge' bad a higher frequency of positive A], cultures [33.3% (6/18) vs. 2.5% (1/40), P = 0.003] and histological chorioamnionitis [77.8% (14/18) vs. 19% (11/58), P < 0.001] than those without AF 'sludge'; (5) a higher proportion of neonates born to patients with AF 'sludge' was admitted to the NICU 164.3% (9/14) vs. 12.9% (8/62), P < 0.01], had a composite neonatal morbidity [36.8% (7/19) vs. 13.8% (9/65), P = 0.04] and died in the perinatal period [36.8% (7/19) vs. 4.6% (3/65), P = 0.001] than those born to women without 'sludge'; (6) a higher proportion of patients with AF 'sludge' had spontaneous delivery within 48 h [42.9% (6/14) vs. 4.4% (2/45), P = 0.001], within 7 days [71.4% (10/14) vs. 15.6% (7/45), P < 0.001], < 32 weeks [75% (9/12) vs. 25.8% (8/31), P = 0.005] and < 35 weeks [92.9% (13/14) vs. 37.8% (17/45), P < 0.001] than those without AF 'sludge'; and (7) patients with AF 'sludge' bad a shorter examination-to-delivery interval than those without AF 'sludge' [AF 'sludge' median, 1 (IQR, 1-5) days vs. no AF 'sludge' median, 33 (IQR, 18-58) days; P < 0.001]. Conclusion The presence of AF 'sludge' in patients with preterm labor and intact membranes is a risk factor for MIAC, histological chorioamnionitis and impending preterm delivery. Copyright (c) 2005 ISUOG. C1 NICHD, Perinatol Res Branch, DHHS, NIH, Detroit, MI 48201 USA. Wayne State Univ, Hutzel Hosp, Dept Obstet & Gynecol, Detroit, MI USA. Wayne State Univ, Hutzel Hosp, Dept Pathol, Detroit, MI USA. Pontificia Univ Catolica Chile, Hosp Dr Sotero del Rio, Dept Obstet & Gynecol, CEDIP, Puente Alto, Chile. Seoul Natl Univ, Dept Obstet & Gynecol, Seoul, South Korea. William Beaumont Hosp, Dept Obstet & Gynecol, Royal Oak, MI 48072 USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, DHHS, NIH, 4707 St Antoine Blvd, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov RI Yoon, Bo Hyun/H-6344-2011 NR 57 TC 41 Z9 42 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0960-7692 J9 ULTRASOUND OBST GYN JI Ultrasound Obstet. Gynecol. PD APR PY 2005 VL 25 IS 4 BP 346 EP 352 DI 10.1002/uog.1871 PG 7 WC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Obstetrics & Gynecology; Radiology, Nuclear Medicine & Medical Imaging GA 918BB UT WOS:000228512200006 PM 15789375 ER PT J AU Dudko, OK Szabo, A AF Dudko, OK Szabo, A TI Time-dependent rate coefficients for diffusion-influenced reactions with centrosymmetric potentials SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID RECOMBINATION AB Simple closed-form expressions are presented for the time-dependent rate coefficients of diffusion-influenced reactions in the presence of spherically symmetric potentials. For diffusion-controlled contact reactions, our expression reproduces the first two terms in both the short- and long-time expansions of the rate coefficient. At intermediate times, agreement with numerical results for the Debye-Muckel potential is found to be within a few percent for a wide range of parameters. For diffusion-influenced contact reactions (described by the radiation boundary condition), the agreement is even better. When the reactivity depends on the distance between the reactants (e.g., exponentially), our analytic result is less accurate, because it reproduces the two terms in the long-time expansion only to the linear order of the reciprocal of the diffusion coefficient. Our results should prove useful in the analysis of experimental data for diffusion-influenced reactions with centrosymmetric interaction potentials. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Ctr Informat Technol, Div Computat Biosci, Math & Stat Comp Lab, Bethesda, MD 20892 USA. RP Szabo, A (reprint author), NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM attilas@nih.gov RI Szabo, Attila/H-3867-2012 NR 13 TC 9 Z9 9 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD MAR 31 PY 2005 VL 109 IS 12 BP 5891 EP 5894 DI 10.1021/jp044433q PG 4 WC Chemistry, Physical SC Chemistry GA 911HS UT WOS:000227993800076 PM 16851641 ER PT J AU Goldhar, AS Vonderhaar, BK Trott, JF Hovey, RC AF Goldhar, AS Vonderhaar, BK Trott, JF Hovey, RC TI Prolactin-induced expression of vascular endothelial growth factor via Egr-1 SO MOLECULAR AND CELLULAR ENDOCRINOLOGY LA English DT Article DE angiogenesis; prolactin; mammary gland; lymphoma ID BREAST-CANCER CELLS; PERMEABILITY FACTOR EXPRESSION; BETA-CASEIN GENE; TUMOR ANGIOGENESIS; FACTOR VEGF; MAMMARY-GLAND; TRANSCRIPTION FACTOR; PITUITARY-TUMORS; EPITHELIAL-CELLS; UP-REGULATION AB Angiogenesis is a dynamic process regulated by both local and systemic factors. Among these is vascular endothelial growth factor (VEGF), a potent effector of angiogenesis and vascular permeability. Previously we showed that VEGF is temporally and spatially regulated in the mouse mammary gland during development and lactation. Given the functions of prolactin (PRL) during these stages and the supporting role of the vasculature, we investigated the regulation of VEGF by PRL. Treatment of HC11 mouse mammary epithelial and Nb2 rat lymphoma cells with PRL induced VEGF expression. Deletion and mutation analysis identified a GC-rich region in the proximal region of the VEGF promoter that constitutively bound Sp1 and PRL-induced Egr-1. These sites conferred PRL-responsiveness leading to increased VEGF transcription. The induction of VEGF by PRL was PRL receptor-, Jak2- and MAP kinase kinase-dependent. Our results indicate that PRL induces VEGF expression through Egr-1, and implicates VEGF as an intermediary of PRL-regulated angiogenesis. Published by Elsevier Ireland Ltd. C1 Univ Vermont, Dept Anim Sci, Lactat & Mammary Gland Biol Grp, Burlington, VT 05405 USA. NCI, Mammary Biol & Tumorigenesis Lab, NIH, Bethesda, MD 20892 USA. RP Hovey, RC (reprint author), Univ Vermont, Dept Anim Sci, Lactat & Mammary Gland Biol Grp, Room 221,Terrill Hall, Burlington, VT 05405 USA. EM russell.hovey@uvm.edu NR 68 TC 51 Z9 54 U1 1 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0303-7207 J9 MOL CELL ENDOCRINOL JI Mol. Cell. Endocrinol. PD MAR 31 PY 2005 VL 232 IS 1-2 BP 9 EP 19 DI 10.1016/j.mce.2005.01.005 PG 11 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 908AC UT WOS:000227758500002 PM 15737464 ER PT J AU Steiner, FA Hong, JA Fischette, MR Beer, DG Guo, ZS Chen, GA Weiser, TS Kassis, ES Nguyen, DM Lee, S Trepel, JB Schrump, DS AF Steiner, FA Hong, JA Fischette, MR Beer, DG Guo, ZS Chen, GA Weiser, TS Kassis, ES Nguyen, DM Lee, S Trepel, JB Schrump, DS TI Sequential 5-Aza 2 '-deoxycytidine/depsipeptide FK228 treatment induces tissue factor pathway inhibitor 2 (TFPI-2) expression in cancer cells SO ONCOGENE LA English DT Article DE TFPI-2; 5-aza 2 '-deoxycytidine; depsipeptide FK228; lung cancer; esophageal cancer ID HISTONE DEACETYLASE INHIBITORS; SERINE-PROTEASE INHIBITOR; HUMAN GLIOMA-CELLS; FACTOR VIIA; DNA METHYLATION; IN-VITRO; DEMETHYLASE ACTIVITY; CARCINOMA-CELLS; UP-REGULATION; GENE AB cDNA arrays were used to examine gene induction in CALU-6 and H460 lung cancer cells mediated by sequential 5-aza 2-deoxycytidine (DAC)/depsipeptide FK228 (DP) exposure in order to identify translational end points for clinical trials evaluating these agents. In both cell lines, sequential DAC/DP treatment induced expression of tissue factor pathway inhibitor-2 (TFPI-2), an inhibitor of Factor VII: tissue factor signal transduetion known to diminish the malignant phenotype of cancer cells. TFPI-2 expression was diminished or absent in 16 of 32 cell lines established from thoracic malignancies. Sequential DAC/DP treatment induced TFPI-2 in cancer cells deficient for TFPI-2 expression in the basal state. Promoter methylation coincided with loss of TFPI-2 expression in a number of cancer tines. TFPI-2 promoter methylation was observed in one of five pulmonary adenocarcinomas, and seven of seven esophageal adenocarcinomas, but not corresponding normal tissues. DP enhanced acetylation of TFPI-2-associated histones in CALU-6 cells. DP or PDBU, alone, induced TFPI-2 expression in cancer cells deficient for TFPI-2 expression in the absence of promoter methylation. In these cells, DP-mediated TFPI-2 induction was abrogated by calphostin. Induction of TFPI-2 by distinct, yet cooperative mechanisms involving chromatin remodeling and PKC signaling strengthens the preclinical rationale for sequential administration of DNA demethylating agents and HDAC inhibitors in cancer patients. Furthermore, induction of TFPI-2 may be a useful surrogate marker of treatment response in individuals receiving sequential DAC/DP infusions. C1 NCI, Thorac Oncol Sect, Surg Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Univ Michigan, Ctr Med, Thorac Surg Sect, Ann Arbor, MI USA. NCI, Med Oncol Clin Res Unit, Ctr Canc Res, NIH, Bethesda, MD USA. RP Schrump, DS (reprint author), NCI, Thorac Oncol Sect, Surg Branch, Ctr Canc Res,NIH, Bldg 10,Room 4-3942,10 Ctr Dr MSC1201, Bethesda, MD 20892 USA. EM david_schrump@nih.gov NR 75 TC 36 Z9 44 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 31 PY 2005 VL 24 IS 14 BP 2386 EP 2397 DI 10.1038/sj.onc.1208376 PG 12 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 909RC UT WOS:000227877400011 PM 15735751 ER PT J AU Kiyatkin, EA Brown, PL AF Kiyatkin, EA Brown, PL TI Brain and body temperature homeostasis during sodium pentobarbital anesthesia with and without body wanning in rats SO PHYSIOLOGY & BEHAVIOR LA English DT Article DE barbiturates; general anesthesia; thermorecording; brain metabolism; heat production; heat loss ID HYPERTHERMIA; MONKEY; BLOOD; CELLS AB High-speed, multi-site thermorecording offers the ability to follow the dynamics of heat production and flow in an organism. This approach was used to study brain-body temperature homeostasis during the development of general anesthesia induced by sodium pentobarbital (50 mg/ kg, ip) in rats. Animals were chronically implanted with thermocouple probes in two brain areas, the abdominal cavity, and subcutaneously, and temperatures were measured during anesthesia both with and without (control) body warming. In control conditions, temperature in all sites rapidly and strongly decreased (from 36-37 degrees C to 32-33 degrees C, or 3.5-4.5 degrees C below baselines). Relative to body core, brain hypothermia was greater (by 0.3-0.4 degrees C) and skin hypothermia was less (by similar to 0.7 degrees C). If the body was kept warm with a heating pad, brain hypothermia was three-fold weaker (similar to 1.2 degrees C), but the brain-body difference was significantly augmented (similar to 0.6 degrees C). These results suggest that pentobarbital-induced inhibition of brain metabolic activity is a major factor behind brain hypothermia and global body hypothermia during general anesthesia. These data also indicate that body warming is unable to fully compensate for anesthesia-induced brain hypothermia and enhances the negative brain-body temperature differentials typical of anesthesia. Since temperature strongly affects various underlying parameters of neuronal activity, these findings are important for electrophysiological studies performed in anesthetized animal preparations. (c) Published by Elsevier Inc. C1 NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. RP Kiyatkin, EA (reprint author), NIDA, Cellular Neurobiol Branch, Intramural Res Program, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ekiyatki@intra.nida.nih.gov NR 32 TC 49 Z9 49 U1 0 U2 4 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 MAR 31 PY 2005 VL 84 IS 4 BP 563 EP 570 DI 10.1016/j.physbeh.2005.02.002 PG 8 WC Psychology, Biological; Behavioral Sciences SC Psychology; Behavioral Sciences GA 919AB UT WOS:000228589600008 PM 15811391 ER PT J AU Miles, AP McClellan, HA Rausch, KM Zhu, DM Whitmore, MD Singh, S Martin, LB Wu, YM Giersing, BK Stowers, AW Long, CA Saul, A AF Miles, AP McClellan, HA Rausch, KM Zhu, DM Whitmore, MD Singh, S Martin, LB Wu, YM Giersing, BK Stowers, AW Long, CA Saul, A TI Montanide((R)) ISA 720 vaccines: quality control of emulsions, stability of formulated antigens, and comparative immunogenicity of vaccine formulations SO VACCINE LA English DT Article DE Montanide ISA 720; adjuvant; vaccine recombinant protein ID PLASMODIUM-FALCIPARUM MALARIA; PHASE-I TRIAL; ADJUVANT; SPF66; EFFICACY; SAFETY; OIL; VOLUNTEERS AB Montanide (R) ISA 720 is an experimental adjuvant, formulated as water-in-oil emulsions, that induces high antibody titers in several animal species. It has been used in human vaccine trials with malaria and HIV vaccines. The heightened response is likely due, in part, to the formation of a depot at the injection site. However, post-formulation modifications were seen with seven proteins tested during storage of ISA 720 formulations at 37 degrees C for 1 week and two proteins stored longer at 4 degrees C. Potency studies in mice. in which the stored vaccines were diluted into placebo emulsions for appropriate dosing, indicated that this instability could lead to loss of immunogenicity in the post-injection depot, limiting the allowable storage time of preformed vaccines. We describe point-of-injection formulation for ISA 720 vaccines that meets the requirement for in vitro stability. For preformed vaccines, addition of glycine or glycylglycine prevented antigen modification on storage at 37 degrees C, providing a potential way of stabilizing antigen/ISA 720 formulations for in vitro storage and the post-injection depot. Published by Elsevier Ltd. C1 NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. RP Miles, AP (reprint author), NIAID, Malaria Vaccine Dev Branch, NIH, 5640 Fishers Lane,Twinbrook 1 Room 1118, Rockville, MD 20852 USA. EM amiles@niaid.nih.gov RI Saul, Allan/I-6968-2013; Martin, Laura/N-1789-2013 OI Saul, Allan/0000-0003-0665-4091; Martin, Laura/0000-0002-4431-4381 NR 23 TC 48 Z9 48 U1 1 U2 4 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 MAR 31 PY 2005 VL 23 IS 19 BP 2530 EP 2539 DI 10.1016/j.vaccine.2004.08.049 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 909ZI UT WOS:000227898800015 PM 15752840 ER PT J AU Floel, A Buyx, A Breitenstein, C Lohmann, H Knecht, S AF Floel, A Buyx, A Breitenstein, C Lohmann, H Knecht, S TI Hemispheric lateralization of spatial attention in right- and left-hemispheric language dominance SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE functional Doppler ultrasonography; word generation; landmark task; handedness; right-shift theory ID TRANSCRANIAL DOPPLER SONOGRAPHY; LINE BISECTION JUDGMENTS; CEREBRAL BLOOD-FLOW; CROSSED APHASIA; CORTICAL ORGANIZATION; HEMISPATIAL NEGLECT; FMRI; REPRODUCIBILITY; LOCALIZATION; VARIABILITY AB Hemispheric lateralization of the neural systems supporting language and spatial attention most commonly dissociate in healthy individuals. However, the reverse pattern with association of language and attention within the right hemispheres has also been observed. We investigated in 75 healthy volunteers (37 right-handed, 38 left-handed) if language and spatial attention may associate not only in individuals with an atypical pattern of language lateralization, but also in subjects showing the standard, i.e. left-hemispheric dominance for language. Hemispheric lateralization of cerebral perfusion was determined with functional transcranial Doppler ultrasonography during a visuospatial attention, and a word generation task. We found that language and visuospatial attention associated within the left hemisphere in five subjects and within the right hemisphere in eight subjects. We conclude that all combinations of cerebral lateralization for language and attention may exist in the healthy brain. (C) 2004 Elsevier B.V. All rights reserved. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. Univ Munster, Dept Neurol, D-4400 Munster, Germany. RP Floel, A (reprint author), NINDS, Human Cort Physiol Sect, NIH, 10 Ctr Dr,Bldg 10, Bethesda, MD 20892 USA. EM floela@ninds.nih.gov RI Floel, Agnes/A-9426-2017; OI Knecht, Stefan/0000-0003-1056-9228 NR 38 TC 52 Z9 53 U1 3 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD MAR 30 PY 2005 VL 158 IS 2 BP 269 EP 275 DI 10.1016/j.bbr.2004.09.016 PG 7 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 901RX UT WOS:000227300700009 PM 15698893 ER PT J AU Tanji, K Suzuki, K Delorme, A Shamoto, H Nakasato, N AF Tanji, K Suzuki, K Delorme, A Shamoto, H Nakasato, N TI High-frequency gamma-band activity in the basal temporal cortex during picture-naming and lexical-decision tasks SO JOURNAL OF NEUROSCIENCE LA English DT Article DE gamma; language; visual word form area; fusiform gyrus; ERSP; kanji; fMRI; oscillatory activity; LFP; ECoG; naming ID WORD FORM AREA; VISUAL-CORTEX; OSCILLATORY RESPONSES; SYNCHRONIZATION; ALEXIA; EEG; PERCEPTION; LESION; KANJI; REPRESENTATION AB gamma-Band activity (GBA) in electroencephalograms (EEGs) has been shown to reflect various cognitive processes. GBA has typically been recorded in the 30-60 Hz range in scalp EEGs. Recently, task-related "high GBA" (HGBA) with frequencies up to 100 Hz has been observed in studies with invasive electrocorticograms (ECoGs). In the present study, we recorded ECoGs from the bilateral basal temporal cortices in a patient with epilepsy and evaluated the task-related HGBA (most prominently in the 80-120 Hz range) accompanying picture-naming and lexical-decision tasks. We examined picture naming using two categories (line drawings of animals and tools). The lexical-decision task was performed using words and pseudowords of two distinct Japanese writing forms, kanji (morphograms) and kana (syllabograms). Task-related HGBA was observed bilaterally during the naming task. Recordings from some electrodes revealed significant differences in HGBA between animal and tool pictures. In contrast to the naming task, there was apparent left dominance in the lexical-decision task. Furthermore, significant differences in HGBA were observed between the Japanese kanji and kana words and between the kanji words and kanji pseudowords. A number of differences in the HGBA observed in the recordings from the basal temporal area were consistent with previous findings from neuroimaging and patient studies and suggest that HGBA is a good correlate of visual cognitive functions. C1 Tohoku Univ, Grad Sch Int Cultural Studies, Sendai, Miyagi 9808576, Japan. Tohoku Univ, Dept Behav Neurol & Cognit Neurosci, Sendai, Miyagi 9808576, Japan. Salk Inst Biol Studies, Computat Neurobiol Lab, La Jolla, CA 92037 USA. Kohnan Hosp, Dept Neurosurg, Sendai, Miyagi 9828523, Japan. RP Tanji, K (reprint author), NIMH, Lab Neuropsychol, Bldg 49,Room 1B-80, Bethesda, MD 20892 USA. EM tanjik@mail.nih.gov RI Delorme, Arnaud/F-8917-2011 NR 42 TC 75 Z9 78 U1 1 U2 9 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 MAR 30 PY 2005 VL 25 IS 13 BP 3287 EP 3293 DI 10.1523/JNEUROSCI.4948-04.2005 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 911WU UT WOS:000228038200005 PM 15800183 ER PT J AU Zheng, G Tian, X AF Zheng, G Tian, X TI The impact of diagnostic error on testing genetic association in case-control studies SO STATISTICS IN MEDICINE LA English DT Article DE case-control study; diagnostic error; power; sample size; sensitivity-specificity; trend test ID TREND TESTS; SAMPLE-SIZE; DISEASE; VALIDATION; MARKERS; SCORES; POWER AB In case-control studies, subjects in the case group may be recruited from suspected patients who are diagnosed positively with disease. While many statistical methods have been developed for measurement error or misclassification of exposure variables in epidemiological studies, no studies have been reported on the effect of errors in diagnosing disease on testing genetic association in case-control studies. We study the impact of using the original Cochran-Armitage trend test assuming no diagnostic error when, in fact, cases and controls may be clinically diagnosed by an imperfect gold standard or a reference test. The type I error, sample size and asymptotic power of trend tests are examined under a family of genetic models in the presence of diagnostic error. The empirical powers of the trend tests are also compared by simulation studies under various genetic models. Published in 2004 by John Wiley I Sons, Ltd. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Zheng, G (reprint author), NHLBI, Off Biostat Res, Room 8223,6701 Rockledge Dr,MSC 7938, Bethesda, MD 20892 USA. EM zhengg@nhlbi.nih.gov NR 17 TC 25 Z9 26 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 MAR 30 PY 2005 VL 24 IS 6 BP 869 EP 882 DI 10.1002/sim.1976 PG 14 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 908GK UT WOS:000227775300003 PM 15568195 ER PT J AU Lee-Huang, S Maiorov, V Huang, PL Ng, A Lee, HC Chang, YT Kallenbach, N Huang, PL Chen, HC AF Lee-Huang, S Maiorov, V Huang, PL Ng, A Lee, HC Chang, YT Kallenbach, N Huang, PL Chen, HC TI Structural and functional modeling of human lysozyme reveals a unique nonapeptide, HL9, with anti-HIV activity SO BIOCHEMISTRY LA English DT Article ID SITE CLEFT; PEPTIDES; PROTEINS; CELLS; INFECTION; DEFENSE; ASSAY; GENE AB We previously reported that lysozyme accounts for anti-HIV activity associated with the beta-core fraction of human chorionic gonadotropin [Lee-Huang, S., Huang, P. L., Sun, Y., Kuna, H. F., Blithe, D. L. W Chen, H. C. (1999) Proc Natl Acad Sci U S A 96, 2678-81]. To define the structural and sequence requirements for anti-HIV activity, we carried out peptide fragmentation and activity mapping of human lysozyme. We identified two peptides that consist of 18 and 9 amino acids of human lysozyme (HL18 and HL9), corresponding to residues 98-115 and 107-115. HLI 8 and HL9 are potent inhibitors of HIV-1 infection and replication with EC50S of 50 to 55 nM, comparable to intact lysozyme. Scrambling the sequence or substitution of key arginine or tryptophan residues results in loss of antiviral activity. HL9, with the sequence RAWVAWRNR, is the smallest peptide we identified with full anti-HIV activity. It forms a pocket with its basic residues on the surface of the molecule. HL9 exists as an alpha-helix in native human lysozyme, in a region of the protein distinct from the muramidase catalytic site. Monte Carlo peptide folding energy minimizing simulation modeling and CD studies indicate that helical propensity does not correlate with antiviral activity. HL9 blocks HIV-1 viral entrance and replication, and modulates gene expression of HIV-infected cells, affecting pathways involved in survival, stres;s, TGF beta, p53, NF kappa B, protein kinase C and hedgehog signaling. C1 NYU, Sch Med, Dept Biochem, New York, NY 10016 USA. Amer Biosci, Boston, MA 02114 USA. NYU, Dept Chem, New York, NY 10003 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. NICHHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Lee-Huang, S (reprint author), NYU, Sch Med, Dept Biochem, 550 1St Ave, New York, NY 10016 USA. RI Chang, Young-Tae/B-2780-2010 OI Chang, Young-Tae/0000-0002-1927-3688 FU NCCIH NIH HHS [R01 AT001383, R01 AT001383-01A2, R01 AT001383-02, R01 AT001383-03, R01-AT01383]; NIAID NIH HHS [R01 AI031343-03, R01 AI031343, R01 AI031343-03S1, R01 AI031343-06] NR 28 TC 50 Z9 52 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 29 PY 2005 VL 44 IS 12 BP 4648 EP 4655 DI 10.1021/bi0477081 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 909EH UT WOS:000227842500005 PM 15779891 ER PT J AU Pelzer, T Loza, PAA Hu, K Bayer, B Dienesch, C Calvillo, L Couse, JF Korach, KS Neyses, L Ertl, G AF Pelzer, T Loza, PAA Hu, K Bayer, B Dienesch, C Calvillo, L Couse, JF Korach, KS Neyses, L Ertl, G TI Increased mortality and aggravation of heart failure in estrogen receptor-beta knockout mice after myocardial infarction SO CIRCULATION LA English DT Article DE receptors; myocardial infarction; heart failure; hormones ID VASCULAR INJURY RESPONSE; REPRODUCTIVE PHENOTYPES; CARDIOVASCULAR-DISEASE; POSTMENOPAUSAL WOMEN; HORMONE-THERAPY; PLUS PROGESTIN; FOLLOW-UP; 17-BETA-ESTRADIOL; REPLACEMENT; ALPHA AB Background - Lower mortality rates among women with chronic heart failure than among men may depend in part on the action of female sex hormones, especially estrogens. The biological effects of estrogens are mediated by 2 distinct estrogen receptor (ER) subtypes (ER alpha and ER beta). The present study was undertaken to determine the role of ER beta in the development of chronic heart failure after experimental myocardial infarction (MI). Methods and Results - Female ER beta null mice (BERKOChapel Hill) and wild-type littermates (WT) were ovariectomized, given 17 beta-estradiol, and subjected to chronic anterior MI (MI; BERKO n = 31, WT n = 30) or sham operation ( sham; BERKO n = 14, WT n = 14). At 8 weeks after MI, both genotypes revealed left ventricular remodeling and impaired contractile function at similar average infarct size (BERKO-MI 32.9 +/- 5% versus WT-MI 33.0 +/- 4%); however, BERKO mice showed increased mortality ( BERKO-MI 42% versus WT-MI 23%), increased body weight and fluid retention ( P < 0.01), higher ventricular pro-ANP expression ( BERKO-MI 27.9-fold versus sham, WT-MI 5.2-fold versus sham; BERKO-MI versus WT-MI P < 0.001), higher atrial natriuretic peptide serum levels, and increased phospholamban expression ( P < 0.05) compared with WT mice. Conclusions - Systemic deletion of ER beta in female mice increases mortality, aggravates clinical and biochemical markers of heart failure, and contributes to impaired expression of Ca2+-handling proteins in chronic heart failure after MI. Further studies are required to delineate the relative importance of cardiac and vascular effects of ER beta and the role of ER alpha in the development of heart failure. C1 Univ Wurzburg, Dept Med, D-97080 Wurzburg, Germany. Univ Milan, Hosp San Raffaele, I-20122 Milan, Italy. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. Univ Manchester, Div Cardiol, Manchester, Lancs, England. RP Pelzer, T (reprint author), Univ Wurzburg, Dept Med, Josef Schneider Str 2, D-97080 Wurzburg, Germany. EM pelzer_t@klinik.uni-wuerzburg.de OI Korach, Kenneth/0000-0002-7765-418X NR 38 TC 81 Z9 84 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD MAR 29 PY 2005 VL 111 IS 12 BP 1492 EP 1498 DI 10.1161/01.CIR.0000159262.18512.46 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 911EH UT WOS:000227984800007 PM 15781739 ER PT J AU Chodankar, R Kwang, S Sangiorgi, F Hong, H Yen, HY Deng, CX Pike, MC Shuler, CF Maxson, R Dubeau, L AF Chodankar, R Kwang, S Sangiorgi, F Hong, H Yen, HY Deng, CX Pike, MC Shuler, CF Maxson, R Dubeau, L TI Cell-nonautonomous induction of ovarian and uterine serous cystadenomas in mice lacking a functional Brca1 in ovarian granulosa cells SO CURRENT BIOLOGY LA English DT Article ID PROPHYLACTIC OOPHORECTOMY SPECIMENS; EPITHELIAL TUMORS; CANCER RISK; BREAST; MUTATION; WOMEN; RECEPTOR AB Women with germline mutations in BRCA1 have a 40% risk of developing ovarian cancer by age 70 [1] and are also predisposed to cancers of the fallopian tubes [2-4]. Given that ovulatory activity is a strong risk factor for sporadic ovarian cancer [5], we hypothesized that reduced BRCA1 expression might predispose to gynecological cancers indirectly, by influencing ovarian granulosa cells. These cells secrete sex steroids that control the ovulatory cycle and influence the growth of ovarian epithelial tumors [6, 7]. Granulosa cells also secrete mullerian inhibiting substance (MIS), a hormone that inhibits both the formation of female reproductive organs in male embryos [8] and the proliferation of ovarian epithelial tumor cells [9, 10]. We tested this hypothesis by using the Cre-lox system to inactivate the Brca1 gene in mouse ovarian granulosa cells. A truncated form of the Fsh receptor promoter [11] served as the Cre driver. Here, we show that indeed, inactivation of the Brca1 gene in granulosa cells led to the development of cystic tumors in the ovaries and uterine horns. These tumors carried normal Brca1 alleles, supporting the view that Brca1 may influence tumor development indirectly, possibly through an effector secreted by granulosa cells. C1 Univ So Calif, Dept Pathol, Los Angeles, CA 90033 USA. Univ So Calif, Dept Biochem, Los Angeles, CA 90033 USA. Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ So Calif, Norris Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Univ So Calif, Ctr Craniofacial Mol Biol, Los Angeles, CA 90033 USA. NIDDKD, Genet & Dev & Dis Branch, Bethesda, MD 20892 USA. RP Dubeau, L (reprint author), Univ So Calif, Dept Pathol, Los Angeles, CA 90033 USA. EM ldubeau@usc.edu RI deng, chuxia/N-6713-2016 NR 22 TC 44 Z9 46 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 29 PY 2005 VL 15 IS 6 BP 561 EP 565 DI 10.1016/j.cub.2005.01.052 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 914EQ UT WOS:000228208400026 PM 15797026 ER PT J AU Fung, HC Evans, J Evans, W Duckworth, J Pittman, A de Silva, R Myers, A Hardy, J AF Fung, HC Evans, J Evans, W Duckworth, J Pittman, A de Silva, R Myers, A Hardy, J TI The architecture of the tau haplotype block in different ethnicities SO NEUROSCIENCE LETTERS LA English DT Article DE tau; MAPT gene; populations genetics; FTDP-17; progressive supranuclear palsy; linkage disequilibrium ID PROGRESSIVE SUPRANUCLEAR PALSY; SUBACUTE SCLEROSING-PANENCEPHALITIS; NEURODEGENERATIVE DISEASES; ASSOCIATION; GUAM; GENE AB We have assessed the pattern of the extended haplotype block over the tau gene which covers a region of similar to 2 Mb in different ethnicities. This analysis shows that the pattern of linkage disequilibrium over the tau region is shared by different ethnic groups indicating that haplotype structure in human is ancient. We discuss this observation in terms of the establishment of the haplotype structure and the possible impact of the tau haplotype on neurodegeneration in humans. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Natl Inst Aging, Neurogenet Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. UCL, Reta Lila Weston Inst Neurol Studies, London W1T 4JF, England. Chang Gung Univ, Chang Gung Mem Hosp, Dept Neurol 2, Taipei 10591, Taiwan. Chang Gung Univ, Coll Med, Taipei 10591, Taiwan. RP Fung, HC (reprint author), Natl Inst Aging, Neurogenet Lab, Natl Inst Hlth, 35 Convent Dr,Bldg 35,Room 1A1008, Bethesda, MD 20892 USA. EM fungp@mail.nih.gov RI de Silva, Rohan/C-1734-2008; Myers, Amanda/B-1796-2010; Hardy, John/C-2451-2009; Pittman, Alan/D-6231-2012 OI de Silva, Rohan/0000-0002-5052-5775; Myers, Amanda/0000-0002-3100-9396; NR 16 TC 10 Z9 10 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 29 PY 2005 VL 377 IS 2 BP 81 EP 84 DI 10.1016/j.neulet.2004.11.072 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 907WW UT WOS:000227749800002 PM 15740841 ER PT J AU Margulies, EH Vinson, JP Miller, W Jaffe, DB Lindblad-Toh, K Chang, JL Green, ED Lander, ES Mullikin, JC Clamp, M AF Margulies, EH Vinson, JP Miller, W Jaffe, DB Lindblad-Toh, K Chang, JL Green, ED Lander, ES Mullikin, JC Clamp, M CA NISC Comparative Sequencing Progra TI An initial strategy for the systematic identification of functional elements in the human genome by low-redundancy comparative sequencing SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE comparative genomics; genome sequencing; genome analysis; phylogenetics; mammalian evolution ID ALIGNMENTS; EVOLUTION; INSIGHTS; GENES; RATES; MODEL AB With the recent completion of a high-quality sequence of the human genome, the challenge is now to understand the functional elements that it encodes. Comparative genomic analysis offers a powerful approach for finding such elements by identifying sequences that have been highly conserved during evolution. Here, we propose an initial strategy for detecting such regions by generating low-redundancy sequence from a collection of 16 eutherian mammals, beyond the 7 for which genome sequence data are already available. We show that such sequence can be accurately aligned to the human genome and used to identify most of the highly conserved regions. Although not a long-term substitute for generating high-quality genomic sequences from many mammalian species, this strategy represents a practical initial approach for rapidly annotating the most evolutionarily conserved sequences in the human genome, providing a key resource for the systematic study of human genome function. C1 MIT, Broad Inst, Cambridge, MA 02141 USA. NHGRI, Genome Technol Branch, Bethesda, MD 20892 USA. NHGRI, NISC, Bethesda, MD 20892 USA. Harvard Univ, Cambridge, MA 02141 USA. Penn State Univ, Dept Comp Sci & Engn, University Pk, PA 16802 USA. RP Mullikin, JC (reprint author), MIT, Broad Inst, Cambridge, MA 02141 USA. EM mullikin@mail.nih.gov; mclamp@broad.mit.edu NR 24 TC 82 Z9 88 U1 1 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 29 PY 2005 VL 102 IS 13 BP 4795 EP 4800 DI 10.1073/pnas.0409882102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 912JM UT WOS:000228074000026 PM 15778292 ER PT J AU Morra, M Barrington, RA Abadia-Molina, AC Okamoto, S Julien, A Gullo, C Kalsy, A Edwards, MJ Chen, G Spolski, R Leonard, WJ Huber, BT Borrow, P Biron, CA Satoskar, AR Carroll, MC Terhorst, C AF Morra, M Barrington, RA Abadia-Molina, AC Okamoto, S Julien, A Gullo, C Kalsy, A Edwards, MJ Chen, G Spolski, R Leonard, WJ Huber, BT Borrow, P Biron, CA Satoskar, AR Carroll, MC Terhorst, C TI Defective B cell responses in the absence of SH2D1A SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Epstein-Barr virus; germinal center; immunoglobulin; SLAM/CD150 ID LINKED LYMPHOPROLIFERATIVE-DISEASE; COMMON VARIABLE IMMUNODEFICIENCY; INOSITOL PHOSPHATASE; IMMUNE RECEPTORS; MICE DEFICIENT; ENCODING GENE; SLAM FAMILY; SAP; EXPRESSION; MEMORY AB More than half of patients with X-linked lympho-proliferative disease, which is caused by a defect in the intracellular adapter protein SH2D1A, suffer from an extreme susceptibility to Epstein-Barr virus. One-third of these patients, however, develop dysgammaglobulenemia without an episode of severe mononucleosis. Here we show that in SH2D1A(-/-) mice, both primary and secondary responses of all Ig subclasses are severely impaired in response to specific antigens. Because germinal centers were absent in SH2D1A(-/-) mice upon primary immunization, and because SH2D1A was detectable in wt germinal center B cells, we examined whether SH2D1A(-/-) B cell functions were impaired. Using the adoptive cotransfer of B lymphocytes from hapten-primed SH2D1A(-/-) mice with CD4(+) T cells from primed wt mice into irradiated wt mice provided evidence that signal transduction events controlled by SH2D1A are essential for B cell activities resulting in antigen specific IgG production. Defects in naive SH2D1A(-/-) B cells became evident upon cotransfer with non-primed wt CD4(+) cells into Rag2(-/-) recipients. Thus, both defective T and B cells exist in the absence of SH2D1A, which may explain the progressive dysgammaglobulinemia in a subset of X-linked lympho-proliferative disease patients without involvement of Epstein-Barr virus. C1 Harvard Univ, Sch Med, Div Immunol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Harvard Univ, CBR, Inst Biomed Res, Boston, MA 02215 USA. Harvard Univ, Dept Pathol, Boston, MA 02215 USA. Edward Jenner Inst Vaccine Res, Newbury RG20 7NN, Berks, England. Tufts Univ, Sch Med, Dept Pathol, Boston, MA 02111 USA. NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA. Ohio State Univ, Dept Microbiol, Columbus, OH 43210 USA. RP Morra, M (reprint author), Harvard Univ, Sch Med, Div Immunol, Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. EM mmorra@bidmc.harvard.edu; terhorst@bidmc.harvard.edu FU NIAID NIH HHS [P01 AI035714, AI-35714] NR 40 TC 51 Z9 56 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 MAR 29 PY 2005 VL 102 IS 13 BP 4819 EP 4823 DI 10.1073/pnas.0408681102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 912JM UT WOS:000228074000030 PM 15774582 ER PT J AU Styner, M Lieberman, JA McClure, RK Weinberger, DR Jones, DW Gerig, G AF Styner, M Lieberman, JA McClure, RK Weinberger, DR Jones, DW Gerig, G TI Morphometric analysis of lateral ventricles in schizophrenia and healthy controls regarding genetic and disease-specific factors SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE brain morphometry; shape analysis; twin study; MRI ID MONOZYGOTIC TWINS DISCORDANT; STATISTICAL SHAPE-ANALYSIS; CORPUS-CALLOSUM; OBSTETRIC COMPLICATIONS; MEDIAL MODELS; BRAIN; MORPHOLOGY; SIZE; CLASSIFICATION; VARIABILITY AB The structural variability of lateral ventricles is poorly understood notwithstanding that enlarged size has been identified as an unspecific marker for psychiatric illness, including schizophrenia. This paper explores the effects of heritability and genetic risk for schizophrenia reflected in ventricular size and structure. We examined ventricular size and shape in the MRI studies of monozygotic (MZ) twin pairs discordant for schizophrenia (DS), healthy MZ twin pairs, healthy dizygotic twin pairs, and healthy nonrelated subject pairs. Heritability and effect due to disease were analyzed in two tests. First, heritability was examined by ventricle similarity between pairs of co-twins. Results show that co-twin ventricle shape similarity decreases with decreasing genetic identity, an effect not seen in the volume analysis. Co-twin shape similarity of healthy MZ twins did not differ from DS MZ twins. Second, the disease effect was examined through the ventricular differences of DS subjects to a template shape representing healthy subjects. Affected DS twins showed shape differences from healthy subjects on the left and right sides. Interestingly, unaffected DS twins also showed significant shape differences from healthy subjects for both sides. Volume comparisons did not show differences between these groups. Locality of shape difference suggests that the ventricular shape of the anterior and posterior regions is under genetic influence in both healthy controls and schizophrenia patients. Affected and unaffected groups demonstrate main shape differences, compared with healthy controls, only in the posterior region. Our results suggest that genetics have a stronger influence on the shape of lateral ventricles than do the disease-related changes in schizophrenia. C1 Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Dept Psychiat, Chapel Hill, NC 27599 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. Univ Bern, ME Muller Res Ctr Orthopaed Surg, Inst Surg Technol & Biomech, CH-3014 Bern, Switzerland. RP Styner, M (reprint author), Univ N Carolina, Dept Comp Sci, Chapel Hill, NC 27599 USA. EM martin_styner@ieee.org OI Styner, Martin/0000-0002-8747-5118; Gerig, Guido/0000-0002-9547-6233 FU NCI NIH HHS [CA47982, P01 CA047982]; NIMH NIH HHS [P50 MH064065]; PHS HHS [156001393A1] NR 41 TC 104 Z9 105 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 MAR 29 PY 2005 VL 102 IS 13 BP 4872 EP 4877 DI 10.1073/pnas.0501117102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 912JM UT WOS:000228074000039 PM 15772166 ER PT J AU Murphy, E Jacobson, S Franchini, G Taylor, GP Hanchard, B Morgan, O Lairmore, M AF Murphy, E Jacobson, S Franchini, G Taylor, GP Hanchard, B Morgan, O Lairmore, M TI International Retrovirology Association brings together scientists and clinicians to bridge discoveries about human T-lymphotropic viruses from the laboratory to clinical trials SO RETROVIROLOGY LA English DT Editorial Material ID HTLV-I; MYELOPATHY AB Human T-lymphotropic virus type 1 (HTLV-1) and HTLV-2 were among the first human retroviruses discovered in the early 1980' s. The International Retrovirology Association is an organized effort that fostered the efforts of scientists and clinicians to form interdisciplinary groups to study this group of retroviruses and their related diseases. The Association promotes excellent science, patient education, and fosters the training of young scientists to promote "bench-to-bedside" research. The International Conference on Human Retrovirology: HTLV and Related Viruses sponsored by the Association supports clinicians and researchers in the exchange of research findings and stimulation of new research directions. This years conference will be held from June 22 to 25, in Montego Bay, Jamaica http:// www. htlvconference. org. jm/. Since its inception in 1988, these conferences have provided a highly interactive forum for the global community of HTLV scientists. This is of particular importance as HTLV research enters its third decade and a new generation of scientists takes over this important work. Many of the scientists attending the meeting will be from developing countries where HTLV is endemic, consistent with the history of international collaborations that have characterized HTLV research. The International Conference on Human Retrovirology provides a unique opportunity for researchers of all disciplines interested in HTLV infections to meet their peers and to address the questions facing clinicians and scientists who study retroviruses, like HTLV. C1 Ohio State Univ, Dept Vet Biosci, Ctr Retrovirus Res, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. Univ Calif San Francisco, Lab Med Epidemiol Biostat, San Francisco, CA 94143 USA. Natl Inst Immunol & Neurol Dis, Viral Immunol Sect, NIH, Bethesda, MD USA. NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci & Technol, London, England. Univ W Indies, Dept Pathol & Med Sci, Kingston 7, Jamaica. RP Lairmore, M (reprint author), Ohio State Univ, Dept Vet Biosci, Ctr Retrovirus Res, Columbus, OH 43210 USA. EM murphy@itsa.ucsf.edu; jacobsons@ninds.nih.gov; franchig@mail.nih.gov; g.p.taylor@imperial.ac.uk; barrie.hanchard@uwimona.edu.jm; owen.morgan@uwimona.edu.jm; lairmore.1@osu.edu NR 15 TC 1 Z9 1 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 MAR 29 PY 2005 VL 2 AR 22 DI 10.1186/1742-4690-2-22 PG 5 WC Virology SC Virology GA 032RJ UT WOS:000236791800001 PM 15796774 ER PT J AU Hurst, SA Hull, SC DuVal, G Danis, M AF Hurst, SA Hull, SC DuVal, G Danis, M TI Physicians' responses to resource constraints SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HEALTH-CARE; REIMBURSEMENT RULES; COST-CONTROL; DOCTORS; ATTITUDES; ETHICS; PRIORITIZATION; ALLOCATION; DILEMMAS; MEDICINE AB Background: A common dilemma that confronts physicians in clinical practice is the allocation of scarce resources. Yet the strategies used by physicians in actual situations of resource constraint have not been studied. This study explores the strategies and rationales reported by physicians in situations of resource constraints encountered in practice. Methods: A national survey of US internists, oncologists, and intensive care specialists was performed by computer-assisted telephone interviews. As part of this survey, we asked physicians to tell us about a recent ethical dilemma encountered in practice. A subset of respondents reported difficulties regarding resource allocation. Transcripts of open-ended responses were coded for content based on consensus. Results: Of the 600 physicians originally identified, 537 were eligible and 344 participated (response rate, 64%). Internists do not make allocation decisions alone but rather engage in negotiation in their resolution. Furthermore, these decisions are not made as dichotomous choices. Rather they often involve alternative solutions in the face of complexities of both the health care system and situations where limited resources must be allocated. justice is not commonly the justification for rationing. Conclusion: Physicians' experiences in situations of resource constraints appear to be more complex than the normative literature on health care rationing assumes. In addition, reasoning about justice in health care seems to play only a small part in clinical decision making. Bridging this gap could be an important step in fostering fair allocation of resources in difficult cases. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Univ Toronto, Joint Ctr Bioeth, Toronto, ON, Canada. RP Hurst, SA (reprint author), Ctr Med Univ Geneva, Unite Rech & Enseignement Bioeth, Villa Thury 8,Rue Michel Servet 1, CH-1211 Geneva, Switzerland. EM samia.hurst@medecine.unige.ch RI Hurst, Samia/A-9661-2008 OI Hurst, Samia/0000-0002-1980-5226 NR 31 TC 28 Z9 29 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 28 PY 2005 VL 165 IS 6 BP 639 EP 644 DI 10.1001/archinte.165.6.639 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 909WW UT WOS:000227892400006 PM 15795339 ER PT J AU Chen, DT Rosenstein, DL Muthappan, P Hilsenbeck, SG Miller, FG Emanuel, EJ Wendler, D AF Chen, DT Rosenstein, DL Muthappan, P Hilsenbeck, SG Miller, FG Emanuel, EJ Wendler, D TI Research with stored biological samples - What do research participants want? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID GENETIC RESEARCH; INFORMED CONSENT; POPULATION; TISSUE; EXPERIENCE; DEBATE AB Background: There is widespread disagreement about the type of consent needed for research with stored biological samples. Many believe consent for each future use is required to respect individuals. Others worry this approach may block important research. Methods: We analyzed 1670 consent forms signed by research participants at the Warren G. Magnuson Clinical Center, National Institutes of Health, between January 1, 2000, and May 31, 2002, that offer options for future research with participants' biological samples. The research participants were healthy volunteers, family members of affected individuals, and individuals with a broad range of medical conditions enrolled in clinical research studies with and without the prospect of direct medical benefit. Results: Overall, 87.1% of research participants given the option chose to authorize future research on any medical condition. More than 85% permitted unlimited future research with their stored biological samples regardless of sex, age, geographic location, or whether the individual was affected by the disease being studied or a healthy volunteer. Only 6.7% of those given the option to refuse all future research did so. Although African Americans were less likely to permit future research, 75.0% of African Americans still authorized unlimited future research with their samples. Conclusions: Most research participants authorize the unlimited future research use of their biological samples when given the opportunity to do so. These findings suggest that providing research participants with a simple binary choice to authorize or refuse all future research might allow individuals to control use of their samples, simplify consent forms, and allow important research to proceed. C1 NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIMH, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Breast Ctr, Houston, TX 77030 USA. RP Wendler, D (reprint author), NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 14 TC 72 Z9 73 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 28 PY 2005 VL 165 IS 6 BP 652 EP 655 DI 10.1001/archinte.165.6.652 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 909WW UT WOS:000227892400008 PM 15795341 ER PT J AU Zhang, HL Huang, ZH Zhu, Y Liang, ZQ Han, R Wang, XX Chase, TN Qin, ZH AF Zhang, HL Huang, ZH Zhu, Y Liang, ZQ Han, R Wang, XX Chase, TN Qin, ZH TI Neuroprotective effects of prostaglandin A(1) in animal models of focal ischemia SO BRAIN RESEARCH LA English DT Article DE prostaglandin A(1); middle cerebral artery occlusion; ischemia; reperfusion; neuroprotection ID NF-KAPPA-B; HEAT-SHOCK PROTEINS; CEREBRAL-ISCHEMIA; CYCLOPENTENONE PROSTAGLANDINS; BRAIN ISCHEMIA; RAT STRIATUM; CELL-DEATH; APOPTOSIS; RESPONSES; RECEPTOR AB The present study evaluated the neuroprotective potential of prostaglandin A(1) (PGA(1)) in rodent models of focal cerebral ischemia. PGA(1) 33 nmol reduced infarction volume by about 43% (P < 0.05) when administered intracerebroventricularly before and after transient ischemia in mice. PGA(1) 16.5-66 nmol diminished infarction volume by 18% to 27% (P < 0.01) when administered immediately following permanent ischemia in rats. PGA(1) treatment also significantly ameliorated motor dysfunction after brain ischemia. These results suggest that PGA(1) protects neurons from ischemic injury. (c) 2005 Elsevier B.V. All rights reserved. C1 Soochow Univ, Sch Med, Dept Pharmacol, Suzhou 215007, Peoples R China. NINDS, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Qin, ZH (reprint author), Soochow Univ, Sch Med, Dept Pharmacol, 48 Ren Ming Rd, Suzhou 215007, Peoples R China. EM qinzh5555@peoplepc.com NR 24 TC 14 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 28 PY 2005 VL 1039 IS 1-2 BP 203 EP 206 DI 10.1016/j.brainres.2005.01.046 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 914AF UT WOS:000228196100024 PM 15781063 ER PT J AU Panousis, C Rayzman, VM Johns, TG Renner, C Liu, Z Cartwright, G Lee, FT Wang, D Gan, H Cao, D Kypridis, A Smyth, FE Brechbiel, MW Burgess, AW Old, LJ Scott, AM AF Panousis, C Rayzman, VM Johns, TG Renner, C Liu, Z Cartwright, G Lee, FT Wang, D Gan, H Cao, D Kypridis, A Smyth, FE Brechbiel, MW Burgess, AW Old, LJ Scott, AM TI Engineering and characterisation of chimeric monoclonal antibody 806 (ch806) for targeted immunotherapy of tumours expressing de2-7 EGFR or amplified EGFR SO BRITISH JOURNAL OF CANCER LA English DT Article DE EGFR; chimeric antibody; immunotherapy; EGFRvIII ID GROWTH-FACTOR-RECEPTOR; CONFERS ENHANCED TUMORIGENICITY; TYROSINE KINASE; PHASE-I; HUMAN GLIOBLASTOMAS; THERAPEUTIC TARGET; MALIGNANT GLIOMAS; CANCER-THERAPY; BREAST-CANCER; ABX-EGF AB We report the generation of a chimeric monoclonal antibody (ch806) with specificity for an epitope on the epidermal growth factor receptor (EGFR) that is different from that targeted by all other anti-EGFR therapies. Ch806 antibody is reactive to both de2-7 and overexpressed wild-type (wt) EGFR but not native EGFR expressed in normal tissues at physiological levels. Ch806 was stably expressed in CHO (DHFR -/-) cells and purified for subsequent characterisation and validated for use in preliminary immunotherapy investigations. Ch806 retained the antigen binding specificity and affinity of the murine parental antibody. Furthermore, ch806 displayed enhanced antibody-dependent cellular cytotoxicity against target cells expressing the 806 antigen in the presence of human effector cells. Ch806 was successfully radiolabelled with both iodine-125 and indium-111 without loss of antigen binding affinity or specificity. The radioimmunoconjugates were stable in the presence of human serum at 37 degrees C for up to 9 days and displayed a terminal half-life (T-1/2 beta) of approximately 78 h in nude mice. Biodistribution studies undertaken in BALB/c nude mice bearing de2-7 EGFR-expressing or amplified EGFR-expressing xenografts revealed that I-125-labelled ch806 failed to display any significant tumour retention. However, specific and prolonged tumour localisation of In-111-labelled ch806 was demonstrated with uptake of 31% ID g(-1) and a tumour to blood ratio of 5:1 observed at 7 days postinjection. In vivo therapy studies with ch806 demonstrated significant antitumour effects on established de2-7 EGFR xenografts in BALB/c nude mice compared to control, and both murine 806 and the anti-EGFR 528 antibodies. These results support a potential therapeutic role of ch806 in the treatment of suitable EGFR-expressing tumours, and warrants further investigation of the potential of ch806 as a therapeutic agent. C1 Austin Hosp, Ludwig Inst Canc Res, Melbourne Tumour Biol Branch, Heidelberg, Vic 3084, Australia. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Ludwig Inst Canc Res, New York, NY 10021 USA. RP Scott, AM (reprint author), Austin Hosp, Ludwig Inst Canc Res, Melbourne Tumour Biol Branch, Level 1,Harold Stokes Bldg,145-163 Studley Rd, Heidelberg, Vic 3084, Australia. EM andrew.scott@ludwig.edu.au RI Johns, Terrance/C-2441-2008 OI Johns, Terrance/0000-0002-8874-4543 NR 55 TC 23 Z9 25 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 28 PY 2005 VL 92 IS 6 BP 1069 EP 1077 DI 10.1038/sj.bjc.6602470 PG 9 WC Oncology SC Oncology GA 908ZA UT WOS:000227827500015 PM 15770208 ER PT J AU Honda, A Al-Awar, OS Hay, JC Donaldson, JG AF Honda, A Al-Awar, OS Hay, JC Donaldson, JG TI Targeting of Arf-1 to the early golgi by membrin, an ER-Golgi SNARE SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GUANINE-NUCLEOTIDE-EXCHANGE; ADP-RIBOSYLATION FACTOR; ENDOPLASMIC-RETICULUM; RECYCLING PATHWAY; PLASMA-MEMBRANE; COAT PROTEINS; LIVING CELLS; COPI COAT; COMPLEX; TRANSPORT AB Arf and Rab family GTPases regulate membrane traffic in cells, yet little is known about how they are targeted to distinct organelles. To identify sequences in Arf-1 necessary for Golgi targeting, we examined the localization of chimeras between Arf-1 and Arf-6. Here, we identify a 16-amino acid sequence in Arf-1 that specifies Golgi targeting and contains a motif ( MXXE) that is important for Arf-1 binding to membrin, an ER-Golgi SNARE protein. The MXXE motif is conserved in all Arfs known to localize to the Golgi and enables Arf-1 to localize to the early Golgi. Arf-1 lacking these 16 aa can still localize to the late Golgi where it displays a more rapid Golgi-cytosol cycle than wildtype Arf-1. These studies suggest that membrin recruits Arf-1 to the early Golgi and reveal distinct kinetic cycles for Arf-1 at early and late Golgi determined by different sets of Arf regulators and effectors. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Montana, Div Biol Sci, Missoula, MT 59812 USA. RP Donaldson, JG (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM jdonalds@helix.nih.gov NR 57 TC 54 Z9 55 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 MAR 28 PY 2005 VL 168 IS 7 BP 1039 EP 1051 DI 10.1083/jcb.200409138 PG 13 WC Cell Biology SC Cell Biology GA 913WV UT WOS:000228187200008 PM 15781476 ER PT J AU Liu, W Duden, R Phair, RD Lippincott-Schwartz, J AF Liu, W Duden, R Phair, RD Lippincott-Schwartz, J TI ArfGAP1 dynamics and its role in COPI coat assembly on Golgi membranes of living cells SO JOURNAL OF CELL BIOLOGY LA English DT Article ID GTPASE-ACTIVATING PROTEIN; ADP-RIBOSYLATION FACTOR; ARF-GAP; NONCATALYTIC DOMAIN; VESICLE FORMATION; KDEL RECEPTOR; BETA-COP; IN-VIVO; TRANSPORT; COMPLEX AB Secretory protein trafficking relies on the COPI coat, which by assembling into a lattice on Golgi membranes concentrates cargo at specific sites and deforms the membranes at these sites into coated buds and carriers. The GTPase-activating protein ( GAP) responsible for catalyzing Arf1 GTP hydrolysis is an important part of this system, but the mechanism whereby ArfGAP is recruited to the coat, its stability within the coat, and its role in maintenance of the coat are unclear. Here, we use FRAP to monitor the membrane turnover of GFP-tagged versions of ArfGAP1, Arf1, and coatomer in living cells. ArfGAP1 underwent fast cytosol/Golgi exchange with similar to 40% of the exchange dependent on engagement of ArfGAP1 with coatomer and Arf1, and affected by secretory cargo load. Permanent activation of Arf1 resulted in ArfGAP1 being trapped on the Golgi in a coatomer-dependent manner. These data suggest that ArfGAP1, coatomer and Arf1 play interdependent roles in the assembly-disassembly cycle of the COPI coat in vivo. C1 NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Bioinformat Serv, Rockville, MD 20851 USA. Univ London, Sch Biol Sci, London WC1E 7HU, England. RP Lippincott-Schwartz, J (reprint author), NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM jlippin@helix.nih.gov RI Duden, Rainer/C-8917-2011 NR 43 TC 56 Z9 57 U1 0 U2 2 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 MAR 28 PY 2005 VL 168 IS 7 BP 1053 EP 1063 DI 10.1083/jcb.200410142 PG 11 WC Cell Biology SC Cell Biology GA 913WV UT WOS:000228187200009 PM 15795316 ER PT J AU Ju, EM Choi, KC Hong, SH Lee, CH Kim, BC Kim, SJ Kim, IH Park, SH AF Ju, EM Choi, KC Hong, SH Lee, CH Kim, BC Kim, SJ Kim, IH Park, SH TI Apoptosis of mink lung epithelial cells by co-treatment of low-dose staurosporine and transforming growth factor-beta 1 depends on the enhanced TGF-beta signaling and requires the decreased phosphorylation of PKB/Akt SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE apoptosis.; staurosporine; TGF-beta 1; mink lung epithelial cell; Akt ID WEHI-231 B-LYMPHOCYTES; PROTEIN-KINASES; MEDIATED APOPTOSIS; ACTIVATION; UCN-01; INHIBITION; MECHANISM; CASPASE; PATHWAY; DEATH AB We demonstrate how co-treatment of low-dose staurosporine (STS) and TGF-beta1, which alone have little effect on cell death, markedly induces apoptosis in Mv1Lu mink lung epithelial cells, but not in its clonal variant RIB cells lacking functional TGF-beta signaling. This process was associated with mitochondria-dependent apoptosis and the enhanced TGF-beta/Smad signaling in MvI Lu cells. When RIB cells were infected with adenovirus carrying wild-type ALK5, a functional TGF-beta type I receptor gene, the apoptotic cell death was significantly restored in these cells following co-treatment of low-dose STS and TGF-beta1. Treatment of MvlLu cells with both low-dose STS and TGF-beta1 decreased the activity of phospho-Akt, which is involved in cell survival signal. In addition, pre-treatments of P13 kinase inhibitors, LY294002 and wortmannin, further increased the apoptosis of MvlLu cells induced by co-treatment of low-dose STS and TGF-beta1. And overexpression of constitutively active Akt (myr-Akt) using adenoviral expression system inhibited the apoptotic cell death of MvILu cells by about 50% upon co-treatment of low-dose STS and TGF-beta1. These results suggest that cotreatment of low-dose STS and TGF-beta1 induces apoptosis of mink lung epithelial cells by enhancing TGF-beta signaling and in part suppressing cytoprotective signaling. (C) 2005 Elsevier Inc. All rights reserved. C1 Natl Canc Ctr, Res Inst, Goyang 411769, Gyeonggi, South Korea. Inha Univ, Coll Med, Dept Pathol, Inchon 400712, South Korea. Kangweon Natl Univ, Coll Nat Sci, Div Life Sci, Chunchon, Kangwon, South Korea. NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD 20892 USA. RP Kim, IH (reprint author), Natl Canc Ctr, Res Inst, Goyang 411769, Gyeonggi, South Korea. EM ihkim@ncc.re.kr; parksh@inha.ac.kr NR 56 TC 7 Z9 7 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 25 PY 2005 VL 328 IS 4 BP 1170 EP 1181 DI 10.1016/j.bbrc.2005.01.078 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 900RW UT WOS:000227233000050 PM 15708000 ER PT J AU Ghosh, A Cheung, YY Mansfield, BC Chou, JY AF Ghosh, A Cheung, YY Mansfield, BC Chou, JY TI Brain contains a functional glucose-6-phosphatase complex capable of endogenous glucose production SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GLYCOGEN-STORAGE-DISEASE; PHOSPHOHISTIDINE-ENZYME INTERMEDIATE; SUBUNIT-RELATED PROTEIN; MICROSOMAL GLUCOSE-6-PHOSPHATASE; MURINE GLUCOSE-6-PHOSPHATASE; TRANSMEMBRANE TOPOLOGY; GENE; TRANSPORTER; ASTROCYTES; IDENTIFICATION AB Glucose is absolutely essential for the survival and function of the brain. In our current understanding, there is no endogenous glucose production in the brain, and it is totally dependent upon blood glucose. This glucose is generated between meals by the hydrolysis of glucose-6-phosphate (Glc-6-P) in the liver and the kidney. Recently, we reported a ubiquitously expressed Glc-6-P hydrolase, glucose-6-phosphatase-beta (Glc-6-Pase-beta), that can couple with the Glc-6-P transporter to hydrolyze Glc-6-P to glucose in the terminal stages of glycogenolysis and gluconeogenesis. Here we show that astrocytes, the main reservoir of brain glycogen, express both the Glc-6-Pase-beta and Glc-6-P transporter activities and that these activities can couple to form an active Glc-6-Pase complex, suggesting that astrocytes may provide an endogenous source of brain glucose. C1 NICHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Chou, JY (reprint author), NICHD, Sect Cellular Differentiat, Heritable Disorders Branch, NIH, Bldg 10,Rm 9S241,9000 Rockville Pike, Bethesda, MD 20892 USA. EM chouja@mail.nih.gov OI Mansfield, Brian/0000-0002-8533-2789 NR 45 TC 40 Z9 44 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 MAR 25 PY 2005 VL 280 IS 12 BP 11114 EP 11119 DI 10.1074/jbc.M410894200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 908BI UT WOS:000227761800030 PM 15661744 ER PT J AU Kaldis, P AF Kaldis, P TI The N-terminal peptide of the Kaposi's sarcoma-associated herpesvirus (KSHV)-cyclin determines substrate specificity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYCLIN-DEPENDENT-KINASE; CDK-ACTIVATING KINASE; VIRUS-ENCODED CYCLIN; STRUCTURAL BASIS; POTENTIAL MEDIATOR; CRYSTAL-STRUCTURE; IN-VIVO; INHIBITOR; PHOSPHORYLATION; P27(KIP1) AB Cyclin- dependent kinases ( Cdks) are activated by cyclin binding and phosphorylation by the Cdk- activating kinase ( CAK). Activation of Cdk6 by the D- type cyclins requires phosphorylation of Cdk6 by CAK on threonine 177. In contrast, Cdk6 is activated by the Kaposi's sarcomaassociated herpesvirus ( KSHV)- cyclin in the absence and presence of CAK phosphorylation. The activity of Cdk6 (.) KSHV- cyclin complexes was investigated here by analyzing mutants of the KSHV- cyclin and Cdk6 in vitro as well as in U2OS cells. Deletion of the N terminus of the KSHV- cyclin affects the substrate specificity indicating that the N terminus is required for phosphorylation of histone H1 but not for other substrates. Mutation of residues in the region 180 - 200 of the KSHVcyclin decreases the binding affinity to Cdk6 in U2OS cells but increases the activity of Cdk6 (.) KSHV- cyclin complexes in vitro indicating that low affinity binding of cyclins to the Cdk subunit might favor increased on- or off- rates of Cdk substrates. Expression of high levels of p16(INK4a) in cells leads to the formation of a heterotrimeric complex composed of Cdk6 (.) KSHV- cyclin, and p16(INK4a). Some of the Cdk6 (.) KSHV- cyclin (.) p16 complexes were found to be active indicating that there might be different modes of p16 binding to Cdk6 (.) cyclin complexes. C1 NCI, NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. RP Kaldis, P (reprint author), NCI, NCI, Mouse Canc Genet Program, Frederick, MD 21702 USA. EM kaldis@ncifcrf.gov RI Kaldis, Philipp/G-2714-2010 OI Kaldis, Philipp/0000-0002-7247-7591 NR 72 TC 6 Z9 6 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 MAR 25 PY 2005 VL 280 IS 12 BP 11165 EP 11174 DI 10.1074/jbc.M408887200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 908BI UT WOS:000227761800037 PM 15664993 ER PT J AU Sidhu, G Li, W Laryngakis, N Bishai, E Balla, T Southwick, F AF Sidhu, G Li, W Laryngakis, N Bishai, E Balla, T Southwick, F TI Phosphoinositide 3-kinase is required for intracellular Listeria monocytogenes actin-based motility and filopod formation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ARP2/3 COMPLEX; IN-VITRO; CYTOSKELETON; PI(3,4,5)P-3; PHAGOCYTOSIS; CHEMOTAXIS; CALCIUM; BINDING; PROTEIN; ROLES AB Motile nonmuscle cells concentrate phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P-3) and phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P-2) in areas of new actin filament assembly. There is great interest in assessing the in vivo functional significance of these phosphoinositides, and we have used Listeria monocytogenes to explore the contribution of PtdIns( 3,4,5) P3 and PtdIns( 4,5) P2 to its actin-based motility. In Listeria-infected PtK2 cells Akt-pleckstrin homology (PH)-green fluorescent protein (GFP) and phospholipase C delta(PLC delta)-PH-GFP both first concentrate at the front of motile Listeria, subsequently surrounding the bacterium and then concentrating in the actin filament tail. Surprisingly, Listeria ActA mutant strains lacking the putative phosphoinositide binding site are also able to concentrate these probes. Reduction of available PtdIns( 3,4,5)P-3 by expression of Akt-PH-GFP and available PtdIns(4,5)P-2 by expression of PLC delta-PH-GFP both significantly slow Listeria actin-based movement. Treatment of cells with the PI 3-kinase inhibitor, LY294002, dissociates Akt-PH but not PLC delta-PH, from the bacterial surface and cell membranes, and results in near complete inhibition of Listeria actin-based motility and filopod formation. Removal of LY294002 results in rapid and full recovery of Akt-PH localization, Listeria actin-based motility, and filopod formation. These findings suggest that PtdIns(4,5)P-2 is concentrated at the surface of Listeria and serves as the substrate for PtdIns(3,4,5)P-3 production, indicating a central role for PI 3-kinases in Listeria intracellular actin-based motility and filopod formation. C1 Univ Florida, Coll Med, Div Infect Dis, Dept Med, Gainesville, FL 32610 USA. NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20982 USA. RP Southwick, F (reprint author), Univ Florida, Coll Med, Div Infect Dis, Dept Med, Box 100277, Gainesville, FL 32610 USA. EM southfs@med.mac.ufl.edu OI Balla, Tamas/0000-0002-9077-3335 FU NIAID NIH HHS [R01 AI034276, R01AI-23262, R01AI34276] NR 26 TC 14 Z9 14 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 25 PY 2005 VL 280 IS 12 BP 11379 EP 11386 DI 10.1074/jbc.M414533200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 908BI UT WOS:000227761800060 PM 15642729 ER PT J AU Appelbaum, L Anzulovich, A Baler, R Gothilf, Y AF Appelbaum, L Anzulovich, A Baler, R Gothilf, Y TI Homeobox-clock protein interaction in zebrafish SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SEROTONIN-N-ACETYLTRANSFERASE; EUKARYOTIC CIRCADIAN SYSTEMS; E-BOX; PINEAL-GLAND; MELATONIN SYNTHESIS; GENE; TRANSCRIPTION; CRX; EXPRESSION; PROMOTER AB In non-mammalian vertebrates, the pineal gland is photoreceptive and contains an intrinsic circadian oscillator that drives rhythmic production and secretion of melatonin. These features require an accurate spatiotemporal expression of an array of specific genes in the pineal gland. Among these is the arylalkylamine N-acetyltransferase, a key enzyme in the melatonin production pathway. In zebrafish, pineal specificity of zfaanat2 is determined by a region designated the pineal-restrictive downstream module (PRDM), which contains three photoreceptor conserved elements (PCEs) and an E-box, elements that are generally associated with photoreceptor-specific and rhythmic expression, respectively. Here, by using in vivo and in vitro approaches, it was found that the PCEs and E-box of the PRDM mediate a synergistic effect of the photoreceptor-specific homeobox OTX5 and rhythmically expressed clock protein heterodimer, BMAL/CLOCK, on zfaanat2 expression. Furthermore, the distance between the PCEs and the E-box was found to be critical for PRDM function, suggesting a possible physical feature of this synergistic interaction. OTX5-BMAL/CLOCK may act through this mechanism to simultaneously control pineal-specific and rhythmic expression of zfaanat2 and possibly also other pineal and retinal genes. C1 Tel Aviv Univ, Dept Zool, George S Wise Fac Life Sci, IL-69978 Tel Aviv, Israel. Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. NIMH, Unit Temporal Gene Express, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Gothilf, Y (reprint author), Tel Aviv Univ, Dept Zool, George S Wise Fac Life Sci, IL-69978 Tel Aviv, Israel. EM yoavg@tauex.tau.ac.il NR 49 TC 42 Z9 43 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 MAR 25 PY 2005 VL 280 IS 12 BP 11544 EP 11551 DI 10.1074/jbc.M412935200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 908BI UT WOS:000227761800080 PM 15657039 ER PT J AU Tang, C Williams, DC Ghirlando, R Clore, GM AF Tang, C Williams, DC Ghirlando, R Clore, GM TI Solution structure of enzyme IIA(Chitobiose) from the N,N '-diacetylchitobiose branch of the Escherichia coli phosphotransferase system SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHORYL TRANSFER COMPLEX; PHOSPHOCARRIER PROTEIN HPR; MANNITOL TRANSPORTER IIMANNITOL; RESIDUAL DIPOLAR COUPLINGS; SIGNAL-TRANSDUCING PROTEIN; NMR STRUCTURE REFINEMENT; N-TERMINAL DOMAIN; CRYSTAL-STRUCTURE; BACILLUS-SUBTILIS; COILED COILS AB The solution structure of trimeric Escherichia coli enzyme IIA(Chb) (34 kDa), a component of the N,N'-diacetylchitobiose/lactose branch of the phosphotransferase signal transduction system, has been determined by NMR spectroscopy. Backbone residual dipolar couplings were used to provide long range orientational restraints, and long range (vertical bar i - j vertical bar >= 5 residues) nuclear Overhauser enhancement restraints were derived exclusively from samples in which at least one subunit was N-15/C-13/H-2/(Val-Leu-Ile)-methyl-protonated. Each subunit consists of a three-helix bundle. Hydrophobic residues lining helix 3 of each subunit are largely responsible for the formation of a parallel coiled-coil trimer. The active site histidines (His-89 from each subunit) are located in three symmetrically placed deep crevices located at the interface of two adjacent subunits (A and C, C and B, and B and A). Partially shielded from bulk solvent, structural modeling suggests that phosphorylated His-89 is stabilized by electrostatic interactions with the side chains of His-93 from the same subunit and Gln-91 from the adjacent subunit. Comparison with the x-ray structure of Lactobacillus lactis IIA(Lac) reveals some substantial structural differences, particularly in regard to helix 3, which exhibits a 40 degrees kink in IIA(Lac) versus a 7 degrees bend in IIAChb. This is associated with the presence of an unusually large (230-angstrom(3)) buried hydrophobic cavity at the trimer interface in IIALac that is reduced to only 45 angstrom(3) in IIA(Chb). C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5,Rm B1-301, Bethesda, MD 20892 USA. EM mariusc@intra.niddk.nih.gov RI Clore, G. Marius/A-3511-2008; Ghirlando, Rodolfo/A-8880-2009 OI Clore, G. Marius/0000-0003-3809-1027; NR 75 TC 10 Z9 10 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 MAR 25 PY 2005 VL 280 IS 12 BP 11770 EP 11780 DI 10.1074/jbc.M414300200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 908BI UT WOS:000227761800106 PM 15654077 ER PT J AU Moroz, OV Murzin, AG Makarova, KS Koonin, EV Wilson, KS Galperin, MY AF Moroz, OV Murzin, AG Makarova, KS Koonin, EV Wilson, KS Galperin, MY TI Dimeric dUTPases, HisE, and MazG belong to a new superfamily of all-alpha NTP pyrophosphohydrolases with potential "house-cleaning" functions SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE histidine biosynthesis; non-canonical nucleotides; mutagenesis; gene silencing; oxidative damage ID PROTEIN SECONDARY STRUCTURE; NUCLEOSIDE TRIPHOSPHATE PYROPHOSPHOHYDROLASE; GENE-EXPRESSION; ESCHERICHIA-COLI; STRUCTURE PREDICTION; CRYSTAL-STRUCTURE; LEISHMANIA-MAJOR; TRYPANOSOMA-CRUZI; NUDIX HYDROLASES; DNA METHYLATION AB Structure-guided analysis of the new dimeric dUTPase family revealed its sequence relationship to the phage T4 dCTPase, phosphoribosyl-ATP pyrophosphatase HisE, NTP pyrophosphatase MazG, and several uncharacterized protein families, including the human protein XTP3TPA (RS21-C6), which is overexpressed in embryonic and cancer cells. Comparison with the recently determined structure of a MazG-like protein from Sulfolobus solfataricus supported the unification of these enzymes in one superfamily of all-alpha NTP pyrophosphatases, suggesting that dimeric dUTPases evolved from a tetrameric MazG-like ancestor by gene duplication. Analysis of the structure of the Sulfolobus MazG points to 2-hydroxyadenosine (isoguanosine) triphosphate, a product of oxidative damage of ATP, as the most likely substrate. We predict that uncharacterized members of this superfamily perform "house-cleaning" functions by hydrolyzing abnormal NTPs and are functionally analogous to the structurally unrelated hydrolases of the Nudix superfamily. We outline probable tertiary and quaternary structures of the all-alpha NTP pyrophosphatase superfamily members. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ York, Dept Chem, York Struct Biol Lab, York YO10 5YW, N Yorkshire, England. MRC, Ctr Prot Engn, Cambridge CB2 2QH, England. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Murzin, AG (reprint author), Univ York, Dept Chem, York Struct Biol Lab, York YO10 5YW, N Yorkshire, England. EM agm@mrc-lmb.cam.ac.uk; galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 70 TC 52 Z9 56 U1 1 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 MAR 25 PY 2005 VL 347 IS 2 BP 243 EP 255 DI 10.1016/j.jmb.2005.01.030 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905JS UT WOS:000227565000002 PM 15740738 ER PT J AU Sakatani, T Kaneda, A Iacobuzio-Donahue, CA Carter, MG Witzel, SD Okano, H Ko, MSH Ohlsson, R Longo, DL Feinberg, AP AF Sakatani, T Kaneda, A Iacobuzio-Donahue, CA Carter, MG Witzel, SD Okano, H Ko, MSH Ohlsson, R Longo, DL Feinberg, AP TI Loss of imprinting of Igf2 alters intestinal maturation and tumorigenesis in mice SO SCIENCE LA English DT Article ID COLORECTAL-CANCER; CELL-DIFFERENTIATION; STEM-CELL; GROWTH; GENE; MARKER; MOUSE; EXPRESSION; NEOPLASIA; DELETION AB Loss of imprinting (LOI) of the insulin-like growth factor II gene (IGF2) is an epigenetic alteration that results in a modest increase in IGF2 expression, and it is present in the normal colonic mucosa of about 30% of patients with colorectal cancer. To investigate its role in intestinal tumorigenesis, we created a mouse model of lgf2 LOI by crossing female H19(+/-) mice with mate Apc(+/min) mice. Mice with LOI developed twice as many intestinal tumors as did control littermates. Notably, these mice also showed a shift toward a less differentiated normal intestinal epithelium, reflected by an increase in crypt length and increased staining with progenitor,cell markers. A similar shift in differentiation was seen in the normal colonic mucosa of humans with LOI. Thus, altered maturation of nonneoplastic tissue may be one mechanism. by which epigenetic changes affect cancer risk. C1 Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. Keio Univ, Sch Med, Dept Physiol, Tokyo 1608582, Japan. Uppsala Univ, Dept Genet & Dev, S-75236 Uppsala, Sweden. RP Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. EM afeinberg@jhu.edu RI Carter, Mark/B-5089-2010; Ko, Minoru/B-7969-2009; Hidokano, Hideyuki/J-5973-2013 OI Ko, Minoru/0000-0002-3530-3015; FU NCI NIH HHS [K08CA106610, R01CA65145] NR 28 TC 213 Z9 228 U1 0 U2 8 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 EI 1095-9203 J9 SCIENCE JI Science PD MAR 25 PY 2005 VL 307 IS 5717 BP 1976 EP 1978 DI 10.1126/science.1108080 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 910UI UT WOS:000227957300061 PM 15731405 ER PT J AU Tchilibon, S Joshi, BV Kim, SK Duong, HT Gao, ZG Jacobson, KA AF Tchilibon, S Joshi, BV Kim, SK Duong, HT Gao, ZG Jacobson, KA TI (N)-Methanocarba 2,N-6-disubstituted adenine nucleosides as highly potent and selective A(3) adenosine receptor agonists SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID A3 ADENOSINE; A(2B) RECEPTOR; IB-MECA; LIGANDS; DERIVATIVES; ACTIVATION; ANALOGS; CELLS; INHIBITION; BINDING AB A series of ring-constrained (N)-methanocarba-5 '-uronamide 2,N-6-disubstituted adenine nucleosides have been synthesized via Mitsunobu condensation of the nucleobase precursor with a pseudosugar ring containing a 5 '-ester functionality. Following appropriate functionalization of the adenine ring, the ester group was converted to the 5 '-N-methylamide. The compounds, mainly 2-chloro-substituted derivatives, were tested in both binding and functional assays at human adenosine receptors (ARs), and many were found to be highly potent and selective A(3)AR agonists. Selected compounds were compared in binding to the rat A(3)AR to assess their viability for testing in rat disease models. The N-6-(3-chlorobenzyl) and N-6-(3-bromobenzyl) analogues displayed K-i values at the human A(3)AR of 0.29 and 0.38 nM, respectively. Other subnanomolar affinities were observed for the following N-6 derivatives: 2,5-dichlorobenzyl, 5-iodo-2-methoxybenzyl, trans-2-phenyl-1-cyclopropyl, and 2,2-diphenylethyl. Selectivity for the human A3AR in comparison to the A(3)AR was the following (fold): the N-6-(2,2-diphenylethyl) analogue 34 (1900), the N-6-(2,5-dimethoxybenzyl) analogue 26 (1200), the N-6-(2,5-dichlorobenzyl) and N-6-(2-phenyl-1-cyclopropyl) analogues 20 and 33 (1000), and the N-6-(3-substituted benzyl) analogues 17, 18, 28, and 29 (700-900). Typically, even greater selectivity ratios were obtained in comparison with the A(2A) and A(2B)ARs. The (N)-methanocarba-5 '-uronamide analogues were full agonists at the A(3)AR, as indicated by the inhibition of forskolin-stimluated adenylate cyclase at a concentration of 10 mu M. The N-6-(2,2-diphenylethyl) derivative was an A(3)AR agonist in the (N)-methanocarba-5 '-uronamide series, although it was an antagonist in the ribose series. Thus, many of the previously known groups that enhance A(3)AR affinity in the 9-riboside series, including those that reduce intrinsic efficacy, may be adapted to the (N)-methanocarba nucleoside series of full agonists. C1 NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Jacobson, KA (reprint author), NIDDKD, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20] NR 61 TC 73 Z9 74 U1 0 U2 4 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 MAR 24 PY 2005 VL 48 IS 6 BP 1745 EP 1758 DI 10.1021/jm049580r PG 14 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 907WR UT WOS:000227749300014 PM 15771421 ER PT J AU Janssen, PAJ Lewi, PJ Arnold, E Daeyaert, F de Jonge, M Heeres, J Koymans, L Vinkers, M Guillemont, J Pasquier, E Kukla, M Ludovici, D Andries, K de Bethune, MP Pauwels, R Das, K Clark, AD Frenkel, YV Hughes, SH Medaer, B De Knaep, F Bohets, H De Clerck, F Lampo, A Williams, P Stoffels, P AF Janssen, PAJ Lewi, PJ Arnold, E Daeyaert, F de Jonge, M Heeres, J Koymans, L Vinkers, M Guillemont, J Pasquier, E Kukla, M Ludovici, D Andries, K de Bethune, MP Pauwels, R Das, K Clark, AD Frenkel, YV Hughes, SH Medaer, B De Knaep, F Bohets, H De Clerck, F Lampo, A Williams, P Stoffels, P TI In search of a novel anti-HIV drug: Multidisciplinary coordination in the discovery of 4-[[4-[[4-[(1E)-2-cyanoethenyl]-2,6dimethylphenyl] amino]-2-pyrimidinyl]amino]-benzonitrile (R278474, rilpivirine) SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; REVERSE-TRANSCRIPTASE; NONNUCLEOSIDE INHIBITORS; WILD-TYPE; ANGSTROM RESOLUTION; EFAVIRENZ DMP-266; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; BINDING MODES; RESISTANCE AB Ideally, an anti-HIV drug should (1) be highly active against wild-type and mutant HIV without allowing breakthrough; (2) have high oral bioavailability and long elimination half-life, allowing once-daily oral treatment at low doses; (3) have minimal adverse effects; and (4) be easy to synthesize and formulate. R278474, a new diarylpyrimidine (DAPY) non-nucleoside reverse transcriptase inhibitor (NNRTI), appears to meet these criteria and to be suitable for high compliance oral treatment of HIV-1 infection. The discovery of R278474 was the result of a coordinated multidisciplinary effort involving medicinal chemists, virologists, crystallographers, molecular modelers, toxicologists, analytical chemists, pharmacists, and many others. C1 Janssen Pharmaceut, B-2350 Vosselaar, Belgium. Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. Johnson & Johnson Pharmaceut Res & Dev, Med Chem, Janssen Cilag France, F-27106 Val De Reuil, France. Johnson & Johnson Pharmaceut Res & Dev, Drug Discovery, Spring House, PA 19477 USA. Tibotec, B-2800 Mechelen, Belgium. NCI, Frederick, MD 21702 USA. Johnson & Johnson Pharmaceut Res & Dev, Drug Evaluat, B-2340 Beerse, Belgium. Johnson & Johnson Pharmaceut Res & Dev, Drug Dev, B-2340 Beerse, Belgium. Johnson & Johnson Pharmaceut Res & Dev, Drug Evaluat, High Wycombe HP144GT, Bucks, England. RP Lewi, PJ (reprint author), Janssen Pharmaceut, B-2350 Vosselaar, Belgium. EM plewi@prdbe.jnj.com RI de Jonge, Marc/B-3391-2010 OI de Jonge, Marc/0000-0003-3225-8172 NR 57 TC 208 Z9 221 U1 2 U2 24 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 MAR 24 PY 2005 VL 48 IS 6 BP 1901 EP 1909 DI 10.1021/jm040840e PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 907WR UT WOS:000227749300027 PM 15771434 ER PT J AU Campiani, G Fattorusso, C Butini, S Gaeta, A Agnusdei, M Gemma, S Persico, M Catalanotti, B Savini, L Nacci, V Novellino, E Holloway, HW Greig, NH Belinskaya, T Fedorko, JM Saxena, A AF Campiani, G Fattorusso, C Butini, S Gaeta, A Agnusdei, M Gemma, S Persico, M Catalanotti, B Savini, L Nacci, V Novellino, E Holloway, HW Greig, NH Belinskaya, T Fedorko, JM Saxena, A TI Development of molecular probes for the identification of extra interaction sites in the mid-gorge and peripheral sites of butyrylcholinesterase (BuChE). Rational design of novel, selective, and highly potent BuChE inhibitors SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ALZHEIMERS-DISEASE; ACETYLCHOLINESTERASE; CHOLINESTERASES; SIMULATIONS; BINDING AB Tacrine heterobivalent ligands were designed as novel and reversible inhibitors of cholinesterases. On the basis of the investigation of the active site gorge topology of butyrylcholinesterase (BuChE) and acetylcholinesterase (AChE) and by using flexible docking procedures, molecular modeling studies formulated the hypothesis of extra interaction sites in the active gorge of hBuChE, namely, a mid-gorge interaction site and a peripheral interaction site. The design strategy led to novel BuChE inhibitors, balancing potency and selectivity. Among the compounds identified, the heterobivalent ligand 4m, containing an amide nitrogen and a sulfur atom at the 8-membered tether level, is one of the most potent and selective BuChE inhibitors described to date. The novel inhibitors, bearing postulated key features, validated the hypothesis of the presence of extra interaction sites within the hBuChE active site gorge. C1 Univ Siena, Dipartimento Farmacochim Tecnol, I-53100 Siena, Italy. Univ Siena, European Res Ctr Drug Discovery & Dev NatSynDrugs, I-53100 Siena, Italy. Univ Naples Federico II, Dipartimento Chim Sostanze Nat, Naples, Italy. Univ Naples Federico II, Dipartimento Chim Farmaceut & Tossicol, I-80131 Naples, Italy. NIA, Drug Design & Dev Sect, Intramural Res Program, Baltimore, MD 21224 USA. Walter Reed Army Inst Res, Div Biochem, Silver Spring, MD 20910 USA. RP Campiani, G (reprint author), Univ Siena, Dipartimento Farmacochim Tecnol, Via Aldo Moro, I-53100 Siena, Italy. EM campiani@unisi.it RI Gemma, Sandra/D-3568-2009; Persico, Marco/L-8448-2014; butini, stefania/D-9954-2015; fattorusso, caterina/F-7113-2015; Catalanotti, Bruno/D-4025-2016 OI Gemma, Sandra/0000-0002-8313-2417; Persico, Marco/0000-0003-0010-0338; fattorusso, caterina/0000-0003-3330-4281; Catalanotti, Bruno/0000-0002-7532-6959 NR 21 TC 60 Z9 60 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-2623 J9 J MED CHEM JI J. Med. Chem. PD MAR 24 PY 2005 VL 48 IS 6 BP 1919 EP 1929 DI 10.1021/jm049510k PG 11 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 907WR UT WOS:000227749300029 PM 15771436 ER PT J AU Klauda, JB Brooks, BR MacKerell, AD Venable, RM Pastor, RW AF Klauda, JB Brooks, BR MacKerell, AD Venable, RM Pastor, RW TI An ab initio study on the torsional surface of alkanes and its effect on molecular simulations of alkanes and a DPPC bilayer SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; DYNAMICS SIMULATIONS; N-ALKANES; CONFORMATIONAL ENERGIES; FORCE-FIELD; HYDROCARBON CHAINS; LIPID BILAYERS; RESP MODEL; PHASE; EQUILIBRIUM AB Energies of 119 conformations of normal alkanes from butane to heptane were calculated at approximately the CCSD(T)/cc-pVQZ level. Energies of gauche (g) conformers relative to trans (t) decrease as chain length increases. In what is termed the "positive pentane effect", adjacent gauche conformers of the same sign are stabilized compared to nonadjacent conformers; e.g., for hexane the energies of tgt, tgg, and gtg are 0.600, 0.930, and 1.18 kcal/mol, respectively. Torsional terms in the CHARMM27 (C27) force field were fit to the calculated QM energies to yield a revised potential, C27r. Molecular dynamics simulations of normal alkanes (heptane, decane, tridecane, and pentadecane) with C27r yield higher populations of gauche states, increased transition rates, and improved agreement with experiment as compared to C27. In addition, C27r simulations of a hydrated DPPC lipid bilayer yield improved agreement with the experimental NMR deuterium order parameters for the aliphatic chain ends. C1 FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20852 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. NIH, Biophys Chem Lab, Bethesda, MD 20892 USA. RP Pastor, RW (reprint author), FDA, Ctr Biol Evaluat & Res, Biophys Lab, 1401 Rockville Pike, Rockville, MD 20852 USA. EM pastor@cber.fda.gov RI Klauda, Jeffery/A-4345-2008; OI MacKerell, Alex/0000-0001-8287-6804 FU NIGMS NIH HHS [GM51501] NR 52 TC 218 Z9 221 U1 4 U2 50 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 MAR 24 PY 2005 VL 109 IS 11 BP 5300 EP 5311 DI 10.1021/jp0468096 PG 12 WC Chemistry, Physical SC Chemistry GA 907RB UT WOS:000227734500067 PM 16863197 ER PT J AU Sonntag, KC Simantov, R Isacson, O AF Sonntag, KC Simantov, R Isacson, O TI Stem cells may reshape the prospect of Parkinson's disease therapy SO MOLECULAR BRAIN RESEARCH LA English DT Review DE embryonic stem (ES) cells; Parkinson's disease; neurogenesis; transplantation; cell replacement; ES cell differentiation; dopaminergic ID MIDBRAIN DOPAMINERGIC-NEURONS; TYROSINE-HYDROXYLASE GENE; ORPHAN NUCLEAR RECEPTOR; VENTRAL MESENCEPHALIC XENOGRAFTS; MAMMALIAN SUBSTANTIA-NIGRA; CENTRAL-NERVOUS-SYSTEM; RAT MODEL; IN-VITRO; ADULT-RAT; NEUROTROPHIC FACTOR AB The concept of cell replacement to compensate for cell loss and restore functionality has entered several disease entities including neurodegenerative disorders. Recent clinical studies have shown that transplantation of fetal dopaminergic (DA) cells into the brain of Parkinson's disease (PD) patients can reduce disease-associated motor deficits. However, the use of fetal tissue is associated with practical and ethical problems including low efficiency, variability in the clinical outcome and controversy regarding the use of fetuses as donor. An alternative cell resource could be embryonic stem (ES) cells, which can be cultivated in unlimited amounts and which have the potential to differentiate into mature DA cells. Several differentiation protocols have been developed, and some progress has been made in understanding the mechanisms underlying DA specification in ES cell development, but the "holy grail" in this paradigm, which is the production of sufficient amounts of the "right" therapeutic DA cell, has not yet been accomplished. To achieve this goal, several criteria on the transplanted DA cells need to be fulfilled, mainly addressing cell survival, accurate integration in the brain circuitry, normal function, no tumor formation, and no immunogenicity. Here, we summarize the current state of ES cell-derived DA neurogenesis and discuss the aspects involved in generating an optimal cell source for cell replacement in PD. (C) 2004 Elsevier B.V. All rights reserved. C1 Harvard Univ, Sch Med, McLean Hosp, Neuroregenerat Labs, Belmont, MA 02478 USA. Harvard Univ, Sch Med, McLean Hosp, Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA. Weizmann Inst Sci, Dept Mol Genet, IL-76100 Rehovot, Israel. RP Sonntag, KC (reprint author), Harvard Univ, Sch Med, McLean Hosp, Neuroregenerat Labs, MRC 102,115 Mill St, Belmont, MA 02478 USA. EM kai.sonntag@mclean.harvard.edu NR 166 TC 46 Z9 50 U1 4 U2 32 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 MAR 24 PY 2005 VL 134 IS 1 BP 34 EP 51 DI 10.1016/j.molbrainres.2004.09.002 PG 18 WC Neurosciences SC Neurosciences & Neurology GA 915RG UT WOS:000228321100005 ER PT J AU Blackinton, J Ahmad, R Miller, DW van der Brug, MP Canet-Aviles, RM Hague, SM Kaleem, M Cookson, MR AF Blackinton, J Ahmad, R Miller, DW van der Brug, MP Canet-Aviles, RM Hague, SM Kaleem, M Cookson, MR TI Effects of DJ-1 mutations and polymorphisms on protein stability and subcellular localization SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Parkinson's disease; proteasome; mitochondria; oxidative stress ID ONSET PARKINSONS-DISEASE; L166P; GENES; FORMS AB Mutations in the DJ-1 gene are associated with recessive, early onset Parkinson's disease (PD). We reported previously that one of the point mutations, L166P, destabilizes the protein and thus produces an effective knockout of the gene. Here, we have expanded this analysis to include a series of mutations and polymorphisms identified throughout the gene. The M261 point mutation was also unstable, although the effect was not as dramatic as With L166P. Protein levels were rescued in part, but not completely, by proteasome inhibition. Other variants, such as R98Q, were generally stable. We noted that M261 and L166P are both in helical regions near the dimer interface. However, M261 retains the ability to dimerize. We also examined the subcellular localization of DJ-1 and found that most mutations were similar to the wildtype (wt) protein in that a few cells showed mitochondrial staining. However, in all cases, the proportion of cells with mitochondrial DJ-1 staining was increased in oxidative conditions, suggesting that oxidation promotes the mitochondrial localization of DJ-1. Published by Elsevier B.V. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. RP Cookson, MR (reprint author), NIA, Neurogenet Lab, NIH, Bldg 10 Room 6C103,MSC1589 9000 Rockville Pike, Bethesda, MD 20892 USA. EM Cookson@mail.nih.gov NR 21 TC 51 Z9 51 U1 0 U2 4 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 MAR 24 PY 2005 VL 134 IS 1 BP 76 EP 83 DI 10.1016/j.molbrainres.2004.09.004 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 915RG UT WOS:000228321100009 ER PT J AU Peng, GS Li, GR Tzeng, NS Chen, PS Chuang, DM Hsu, YD Yang, SF Hong, JS AF Peng, GS Li, GR Tzeng, NS Chen, PS Chuang, DM Hsu, YD Yang, SF Hong, JS TI Valproate pretreatment protects dopaminergic neurons from LPS-induced neurotoxicity in rat primary midbrain cultures: role of microglia SO MOLECULAR BRAIN RESEARCH LA English DT Article DE Parkinson's disease; valproic acid; microglia; neuroprotection; anti-inflammation ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; HISTONE DEACETYLASE INHIBITION; NECROSIS-FACTOR-ALPHA; NITRIC-OXIDE; INTRANIGRAL INJECTION; SODIUM VALPROATE; MOOD STABILIZER; REVERSIBLE PARKINSONISM; MESENCEPHALIC NEURONS; DIFFERENT MECHANISMS AB Parkinson's disease is a neurodegenerative disorder characterized by progressive degeneration of dopaminergic (DA) neurons in the substantia nigra. Accumulating evidence supports the notion that neuroinflamniation is involved in the pathogenesis of this disease. Valproate (VPA) has long been used for the treatment of seizures and bipolar mood disorder. In vivo and in vitro studies have demonstrated that VPA has neuroprotective and neurotrophic actions. In this study, using primary neuron-glia cultures from rat midbrain, we demonstrated that VPA is a potent neuroprotective agent against lipopolysaccharide (LPS)-induced neurotoxicity. Results showed that pretreatment with 0.6 MM VPA for 48 h robustly attenuated LPS-induced degeneration of dopaminergic neurons as determined by [H-3] dopamine uptake and counting of the number of TH-ir neurons. The neuroprotective effect of VPA was concentration-dependent and was mediated, at least in part, through a decrease in levels of pro-inflammatory factors released from activated microglia. Specifically, LPS-induced increase in the release of TNFa, NO, and intracellular reactive oxygen species was markedly reduced in cultures pretreated with VPA. These anti-inflammatory effects of VPA were time and concentration-dependent correlated with a decrease in the number of microglia. Thus, our results demonstrate that protracted VPA pretreatment protects dopaminergic neurons from LPS-induced neurotoxicity through a reduction in levels of released proinflammatory factors, and further suggest that these anti-inflammatory effects may be contributed by VPA-induced reduction of microglia cell number. Taken together, our study reinforces the view that VPA may have utility in treating Parkinson's disease. (C) 2004 Elsevier B.V. All rights reserved. C1 NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. Natl Def Med Ctr, Tri Serv Gen Hosp, Dept Neurol, Taipei, Taiwan. Natl Def Med Ctr, Tri Serv Gen Hosp, Dept Psychiat, Taipei, Taiwan. Natl Cheng Kung Univ, Med Coll & Hosp, Dept Psychiat, Tainan 70101, Taiwan. NIMH, Mol Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Hong, JS (reprint author), NIEHS, Lab Pharmacol & Chem, POB 12233, Res Triangle Pk, NC 27709 USA. EM hong3@niehs.nih.gov NR 51 TC 105 Z9 107 U1 1 U2 3 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 MAR 24 PY 2005 VL 134 IS 1 BP 162 EP 169 DI 10.1016/j.molbrainres.2004.10.021 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 915RG UT WOS:000228321100017 ER PT J AU Harris, TG Burk, RD Palefsky, JM Massad, LS Bang, JY Anastos, K Minkoff, H Hall, CB Bacon, MC Levine, AM Watts, DH Silverberg, MJ Xue, XN Melnick, SL Strickler, HD AF Harris, TG Burk, RD Palefsky, JM Massad, LS Bang, JY Anastos, K Minkoff, H Hall, CB Bacon, MC Levine, AM Watts, DH Silverberg, MJ Xue, XN Melnick, SL Strickler, HD TI Incidence of cervical squamous intraepithelial lesions associated with HIV serostatus, CD4 cell counts, and human papillomavirus test results SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article; Proceedings Paper CT 8th International Conference on Malignancies in AIDS and Othe Immunodeficiencies CY APR 29-30, 2004 CL Bethesda, MA ID HIGH-RISK HPV; CYTOLOGIC ABNORMALITIES; INFECTED WOMEN; NEOPLASIA; CANCER; MANAGEMENT; REGRESSION; SMEARS AB Context Recent cervical cancer screening guidelines state that the interval between screenings can be safely extended to 3 years in healthy women 30 years or older who have normal cytology results and have negative test results for oncogenic human papillomavirus (HPV) DNA. Objective To determine the incidence of squamous intraepithelial lesions (SILs) in HIV-seropositive women with normal cytology results, by baseline HPV DNA results. Design, Setting, and Patients Participants were HIV-seropositive (n=855; mean age, 36 years) and HIV-seronegative (n=343; mean age, 34 years) US women with normal baseline cervical cytology who were enrolled in the Women's Interagency HIV Study (WIHS), a large, multi-institutional prospective cohort study. Since their recruitment during 1994-1995, WIHS participants have been followed up semi-annually with repeated Pap smears for a median of 7 years. Main Outcome Measure The cumulative incidence of any SIL and high-grade SIL or cancer (HSIL+) was estimated according to baseline HPV DNA results, stratified by HIV serostatus and CD4 T-cell count. Results Development of any SIL in women with negative HPV results (both oncogenic and nononcogenic) at 2 years was as follows: in HIV-seropositive women with CD4 counts less than 200/mu L, 9% (95% Cl, 1%-18%); with CD4 counts between 200/mu L and 500/mu L, 9% (95% Cl, 4%-13%); and with CD4 counts greater than 500/ mu L, 4% (95% Cl, 1%-7%). The Cis for these estimates overlapped with those for HIV-seronegative women with normal baseline cytology who were HPV-negative (3%; 95% Cl, 1%-5%), indicating that at 2 years, there were no large absolute differences in the cumulative incidence of any SIL between groups. Furthermore, no HPV-negative participants in any group developed HSIL+ lesions within 3 years. Multivariate Cox models showed that on a relative scale, the incidence of any SIL among HIV-seropositive women with CD4 counts greater than 500/mu L (hazard ratio [HR], 1.2; 95% Cl, 0.5-3.0), but not those with CD4 counts less than or equal to 500/mu L (HR, 2.9; 95% C1, 1.2-7.1), was similar to that in HIV-seronegative women. Conclusion The similar low cumulative incidence of any SIL among HIV-seronegative and HIV-seropositive women with CD4 counts greater than 500/mu L and who had normal cervical cytology and HPV-negative test results suggests that similar cervical cancer screening practices may be applicable to both groups, although this strategy warrants evaluation in an appropriate clinical trial. C1 Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, Bronx, NY 10461 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. So Illinois Univ, Sch Med, Springfield, IL USA. Maimonides Hosp, Brooklyn, NY 11219 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Univ So Calif, Los Angeles, CA USA. NICHHD, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. RP Harris, TG (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Populat Hlth, 1300 Morris Pk Ave,Belfer 1308A, Bronx, NY 10461 USA. EM tharris@aecom.yu.edu FU NCI NIH HHS [R01-CA-085178]; NCRR NIH HHS [M01-RR-00083, M01-RR-0007, M01-RR-00079]; NIAID NIH HHS [U01-AI-31834, U01-AI-34989, U01-AI-34993, U01-AI-34994, U01-AI-35004, U01-AI-42590]; OID CDC HHS [U01-CH-32632] NR 24 TC 90 Z9 92 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 23 PY 2005 VL 293 IS 12 BP 1471 EP 1476 DI 10.1001/jama.293.12.1471 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 908KA UT WOS:000227784700026 PM 15784870 ER PT J AU Pluta, RM Dejam, A Grimes, G Gladwin, MT Oldfield, EH AF Pluta, RM Dejam, A Grimes, G Gladwin, MT Oldfield, EH TI Nitrite infusions to prevent delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID INTRAVENTRICULAR SODIUM-NITROPRUSSIDE; OXIDE SYNTHASE ACTIVITY; CEREBROSPINAL-FLUID; BLOOD-FLOW; INTRAVENOUS NITROGLYCERIN; ENDOTHELIAL DYSFUNCTION; S-NITROSOHEMOGLOBIN; HYPOXIC CONDITIONS; GUANYLATE-CYCLASE; ANEURYSM-SURGERY AB Context Delayed cerebral vasospasm causes permanent neurological deficits or death in at least 15% of patients following otherwise successful treatment for ruptured intracranial aneurysm. Decreased bioavailability of nitric oxide has been associated with the development of cerebral vasospasm. Objective To determine whether infusions of nitrite will prevent delayed cerebral vasospasm. Design, Setting, and Subjects A total of 14 anesthetized cynomolgus monkeys had an autologous blood clot placed around the right middle cerebral artery. Cerebral arteriography was performed before clot placement and on days 7 and 14 to assess vasospasm. The study was conducted from August 2003 to February 2004. Interventions A 90-mg sodium nitrite intravenous solution infused over 24 hours plus a 45-mg sodium nitrite bolus daily (n=31); a 180-mg sodium nitrite intravenous solution infused over 24 hours (n=3); or a control saline solution infusion (n=8). Each was infused continuously for 14 days. Main Outcome Measures Nitrite, S-nitrosothiol, and methemoglobin levels in blood and cerebrospinal fluid and degree of arteriographic vasospasm. Results In control monkeys, mean (SD) cerebrospinal fluid nitrite levels decreased from 3.1 (1.5) mu mol/L to 0.4 (0.1) mu mol/L at day 7 and to 0.4 (0.4) mu mol/L at day 14 (P=.03). All 8 control monkeys developed significant vasospasm of the right middle cerebral artery which was complicated by stroke and death in I animal. Sodium nitrite infusions increased the nitrite and methemoglobin levels (<2.1% of total hemoglobin) in the blood and cerebrospinal fluid without evoking systemic hypotension. Nitrite infusion prevented development of vasospasm (no animals developed significant vasospasm; mean [SD] reduction in right middle cerebral artery area on day 7 after subarachnoid hemorrhage of 8% [9%] in nitrite-treated monkeys vs 47% [5%] in saline-treated controls; P<.001). There was a negative correlation between the concentration of nitrite in cerebrospinal fluid and the degree of cerebral vasospasm (P<.001). Pharmacological effects of nitrite infusion were also associated with the formation of S-nitrosothiol in cerebrospinal fluid. There was no clinical or pathological evidence of nitrite toxicity. Conclusion Subacute sodium nitrite infusions prevented delayed cerebral vasospasm in a primate model of subarachnoid hemorrhage. C1 NINDS, Surg Neurol Branch, Bethesda, MD 20892 USA. NIDDKD, Biol Chem Lab, Bethesda, MD 20892 USA. NHLBI, Dept Pharm, Ctr Clin, Vasc Therapeut Sect,Cardiovasc Branch, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, 10 Ctr Dr,Room 5D37, Bethesda, MD 20892 USA. EM rysiek@ninds.nih.gov NR 79 TC 163 Z9 166 U1 1 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 MAR 23 PY 2005 VL 293 IS 12 BP 1477 EP 1484 DI 10.1001/jama.293.12.1477 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 908KA UT WOS:000227784700027 PM 15784871 ER PT J AU Lim, GP Calon, F Morihara, T Yang, FS Teter, B Ubeda, O Salem, N Frautschy, SA Cole, GM AF Lim, GP Calon, F Morihara, T Yang, FS Teter, B Ubeda, O Salem, N Frautschy, SA Cole, GM TI A diet enriched with the omega-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model SO JOURNAL OF NEUROSCIENCE LA English DT Article DE DHA; polyunsaturated fatty acid; A beta; APP; secretase; Alzheimer ID N-3 FATTY-ACIDS; ALPHA-SECRETASE CLEAVAGE; RETINOID-X-RECEPTOR; PRECURSOR PROTEIN; TRANSGENIC MICE; OXIDATIVE STRESS; PLAQUE-FORMATION; DISINTEGRIN METALLOPROTEASE; DOCOSAPENTAENOIC ACID; LIPID-PEROXIDATION AB Epidemiological studies suggest that increased intake of the omega-3 ( n-3) polyunsaturated fatty acid (PUFA) docosahexaenoic acid (DHA) is associated with reduced risk of Alzheimer's disease (AD). DHA levels are lower in serum and brains of AD patients, which could result from low dietary intake and/or PUFA oxidation. Because effects of DHA on Alzheimer pathogenesis, particularly on amyloidosis, are unknown, we used the APPsw (Tg2576) transgenic mouse model to evaluate the impact of dietary DHA on amyloid precursor protein (APP) processing and amyloid burden. Aged animals (17-19 months old) were placed in one of three groups until 22.5 months of age: control (0.09% DHA), low-DHA (0%), or high-DHA (0.6%) chow. beta-Amyloid (A beta) ELISA of the detergent-insoluble extract of cortical homogenates showed that DHA-enriched diets significantly reduced total A beta by > 70% when compared with low-DHA or control chow diets. Dietary DHA also decreased A beta 42 levels below those seen with control chow. Image analysis of brain sections with an antibody against A beta (amino acids 1-13) revealed that overall plaque burden was significantly reduced by 40.3%, with the largest reductions (40-50%) in the hippocampus and parietal cortex. DHA modulated APP processing by decreasing both alpha- and beta-APP C-terminal fragment products and full-length APP. BACE1 (beta-secretase activity of the beta-site APP-cleaving enzyme), ApoE (apolipoprotein E), and transthyretin gene expression were unchanged with the high-DHA diet. Together, these results suggest that dietary DHA could be protective against beta-amyloid production, accumulation, and potential downstream toxicity. C1 Vet Affairs Healthcare Syst, North Hills, CA 91343 USA. Geriatr Res Educ Clin Ctr, North Hills, CA 91343 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Neurol, Los Angeles, CA 90095 USA. NIAAA, Sect Nutrit Neurosci, Lab Membrane Biochem & Biophys, Div Intramural Clin & Biol Res,NIH, Rockville, MD 20852 USA. RP Cole, GM (reprint author), Greater Los Angeles Vet Affairs Healthcare Syst, Geriatr Res Educ & Clin Ctr, 11E,16111 Plummer St, Sepulveda, CA 91343 USA. EM gmcole@ucla.edu FU NCCIH NIH HHS [R01 AT003008]; NIA NIH HHS [AG13471, AG16793, P50 AG016570] NR 68 TC 375 Z9 394 U1 3 U2 70 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 MAR 23 PY 2005 VL 25 IS 12 BP 3032 EP 3040 DI 10.1523/JNEUROSCI.4225-04.2005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 909JP UT WOS:000227856500004 PM 15788759 ER PT J AU Arimondo, PB Laco, GS Thomas, CJ Halby, L Pez, D Schmitt, P Boutorine, A Garestier, T Pommier, Y Hecht, SM Sun, JS Bailly, C AF Arimondo, PB Laco, GS Thomas, CJ Halby, L Pez, D Schmitt, P Boutorine, A Garestier, T Pommier, Y Hecht, SM Sun, JS Bailly, C TI Activation of camptothecin derivatives by conjugation to triple helix-forming oligonucleotides SO BIOCHEMISTRY LA English DT Article ID HUMAN TOPOISOMERASE-I; MEDIATED DNA CLEAVAGE; CELL-LINE; SEQUENCE; INHIBITION; MECHANISM; COMPLEX; SITE; RESISTANT; ANALOGS AB Topoisomerase I (topo I) is a ubiquitous DNA-cleaving enzyme and an important therapeutic target in cancer chemotherapy. Camptothecins (CPTs) reversibly trap topo I in covalent complex with DNA but exhibit limited sequence preference. The utilization of conjugates such as triplex-forming oligonucleotides (TFOs) to target a medicinal agent (like CPT) to a specific genetic sequence and orientation within the DNA has been accomplished successfully. In this study, different attachment points of the TFO to CPT (including positions 7, 9, 10, and 12) were investigated and our findings confirmed and extended previous conclusions. Interestingly, the conjugates induced specific DNA cleavage by topo I at the triplex site even when poorly active or inactive CPT derivatives were used. This suggests that the positioning of the drug in the cleavage complex by the sequence-specific DNA ligand is able to stabilize the ternary complex, even when important interactions between topo I and CPT are disrupted. Finally, certain TFO-CPT conjugates were able to induce sequence-specific DNA cleavage with the topo I mutants R364H and N722S that are resistant to camptothecin. The TFO-CPT conjugates are thus valuable tools to study the interactions involved in the formation of the ternary complex and also to enlarge the family of compounds that poison topo I. The fact that an inactive CPT analogue can act as a topo I poison when appropriately coupled to a TFO provides a new perspective at the level of drug design. C1 Museum Natl Hist Nat, UMR5153 CNRS, Biophys Lab, INSERM UR565, F-75231 Paris, France. NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Virginia, Dept Chem, Charlottesville, VA 22901 USA. Univ Virginia, Dept Biol, Charlottesville, VA 22901 USA. Urogene SA, F-91000 Evry, France. INSERM, U524, F-59045 Lille, France. RP Arimondo, PB (reprint author), Museum Natl Hist Nat, UMR5153 CNRS, Biophys Lab, INSERM UR565, USM0503,43 Rue Cuvier, F-75231 Paris, France. EM arimondo@mnhn.fr RI Boutorine, Alexandre/C-2577-2017 OI Boutorine, Alexandre/0000-0003-4931-9250 FU NCI NIH HHS [CA78415] NR 31 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 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 22 PY 2005 VL 44 IS 11 BP 4171 EP 4180 DI 10.1021/bi048031k PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 907RZ UT WOS:000227736900004 PM 15766244 ER PT J AU Niu, SL Mitchell, DC Litman, BJ AF Niu, SL Mitchell, DC Litman, BJ TI Trans fatty acid derived phospholipids show increased membrane cholesterol and reduced receptor activation as compared to their cis analogs SO BIOCHEMISTRY LA English DT Article ID CORONARY-HEART-DISEASE; OUTER SEGMENT MEMBRANES; RAT-LIVER MITOCHONDRIA; OCTADECENOIC ACIDS; MOLECULAR ORDER; DISK MEMBRANES; SERUM-LIPIDS; RHODOPSIN; PHOSPHATIDYLCHOLINE; LIPOPROTEINS AB The consumption of trans fatty acid (TFA) is linked to the elevation of LDL cholesterol and is considered to be a major health risk factor for coronary heart disease. Despite several decades of extensive research on this subject, the underlying mechanism of how TFA modulates serum cholesterol levels remains elusive. In this study, we examined the molecular interaction of TFA-derived phospholipid with cholesterol and the membrane receptor rhodopsin in model membranes. Rhodopsin is a prototypical member of the G-protein coupled receptor family. It has a well-characterized structure and function and serves as a model membrane receptor in this study. Phospholipid-cholesterol affinity was quantified by measuring cholesterol partition coefficients. Phospholipid-receptor interactions were probed by measuring the level of rhodopsin activation. Our study shows that phospholipid derived from TFA had a higher membrane cholesterol affinity than their cis analogues. TFA phospholipid membranes also exhibited a higher acyl chain packing order, which was indicated by the lower acyl chain packing free volume as determined by DPH fluorescence and the higher transition temperature for rhodopsin thermal denaturation. The level of rhodopsin activation was diminished in TFA phospholipids. Since membrane cholesterol level and membrane receptors are involved in the regulation of cholesterol homeostasis, the combination of higher cholesterol content and reduced receptor activation associated with the presence of TFA-phospholipid could be factors contributing to the elevation of LDL cholesterol. C1 NIAAA, Sect Fluorescence Studies, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. RP Niu, SL (reprint author), NIAAA, Sect Fluorescence Studies, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. EM sniu@niaaa.nih.gov; litman@helix.nih.gov FU NIAAA NIH HHS [Z01 AA000080-12] NR 54 TC 46 Z9 48 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 22 PY 2005 VL 44 IS 11 BP 4458 EP 4465 DI 10.1021/bi048319+ PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 907RZ UT WOS:000227736900036 PM 15766276 ER PT J AU Wang, TJ Evans, JC Meigs, JB Rifai, N Fox, CS D'Agostino, RB Levy, D Vasan, RS AF Wang, TJ Evans, JC Meigs, JB Rifai, N Fox, CS D'Agostino, RB Levy, D Vasan, RS TI Low-grade albuminuria and the risks of hypertension and blood pressure progression SO CIRCULATION LA English DT Article DE blood pressure; risk factors; hypertension; epidemiology ID INSULIN-RESISTANCE SYNDROME; CLINICALLY HEALTHY-SUBJECTS; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; ENDOTHELIAL DYSFUNCTION; CHOLESTEROL LEVELS; DIABETES-MELLITUS; HEART-DISEASE; MICROALBUMINURIA; EXCRETION AB Background-It has been postulated that glomerular hyperfiltration and endothelial dysfunction are early features of essential hypertension that may antedate blood pressure elevation. Microalbuminuria, a marker of glomerular hyperfiltration and endothelial dysfunction, has been described in individuals with established hypertension, but its role as a biomarker of preclinical stages of this disease has not been investigated prospectively. Methods and Results-We examined the association between urinary albumin excretion and the risks of hypertension and blood pressure progression in 1499 nonhypertensive individuals (58% women) without diabetes. During a mean follow-up of 2.9 years, 230 participants (15%) developed hypertension and 499 (33%) progressed to a higher blood pressure category (defined by the sixth report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure). In multivariable logistic regressions that adjusted for known risk factors, the urine albumin-creatinine ratio (UACR) was a significant predictor of incident hypertension (adjusted OR 1.20, 95% CI 1.01 to 1.44, per 1-SD increment in log UACR). Compared with those in the lowest UACR quartile, participants in the highest quartile (men: >6.66 mg/g; women: >15.24 mg/g) had an approximate to 2-fold risk of developing hypertension (adjusted OR 1.93, P=0.006) and 1.5-fold risk of blood pressure progression (adjusted OR 1.45, P=0.03). Conclusions-Urinary albumin excretion predicts blood pressure progression in nondiabetic, nonhypertensive individuals incrementally over established risk factors and at levels well below the conventional threshold for microalbuminuria. UACR may be a useful biomarker for identifying individuals most likely to develop hypertension. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Gen Med, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Ctr Cardiovasc Dis Prevent, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Endocrinol Hypertens & Diabet, Boston, MA USA. Boston Univ, Dept Math, Stat & Consulting Unit, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Boston Med Ctr, Prevent Med Sect, Boston, MA 02118 USA. Boston Univ, Sch Med, Boston Med Ctr, Cardiol Sect, Boston, MA 02118 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayte Ave,2, Framingham, MA 01702 USA. EM vasan@bu.edu OI Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2K24-HL-04334, K23-HL-074077, N01-HC-25195] NR 47 TC 143 Z9 157 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 22 PY 2005 VL 111 IS 11 BP 1370 EP 1376 DI 10.1161/01.CIR.0000158434.69180.2D PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 908RB UT WOS:000227805700004 PM 15738353 ER PT J AU Lupu, VD Saini, N Balish, M AF Lupu, VD Saini, N Balish, M TI CNS myelomatosis SO NEUROLOGY LA English DT Editorial Material C1 Natl Inst Neurol Disorders & Stroke, EMG Sect, NIH, Bethesda, MD 20892 USA. RP Lupu, VD (reprint author), Natl Inst Neurol Disorders & Stroke, EMG Sect, NIH, Bldg 10,Room 5C101,10 Ctr Dr MSC 1404, Bethesda, MD 20892 USA. EM lupuv@ninds.nih.gov NR 2 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 22 PY 2005 VL 64 IS 6 BP 1007 EP 1007 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 908RH UT WOS:000227806600015 PM 15781817 ER PT J AU Meschia, JF Brott, TG Brown, RD Kissela, BM Hardy, JA Brown, WM Rich, SS AF Meschia, JF Brott, TG Brown, RD Kissela, BM Hardy, JA Brown, WM Rich, SS CA Siblings Ischemic Stroke Study Inv TI Correlation of proband and sibling stroke latency: The SWISS Study SO NEUROLOGY LA English DT Article ID ISCHEMIC-STROKE; POPULATION; DISEASE AB The authors found a correlation between the age at which probands experience an incident stroke and the age at which their siblings experience an incident stroke (r = 0.68; p < 0.0001). Proband-sibling incident stroke latency correlations were observed in analyses restricted to siblings concordant for smoking (r = 0.68; p < 0.0001), diabetes (r = 0.73; p < 0.0001), and hypertension (r = 0.63; p < 0.0001). In the authors' cohort of affected sibling pairs, inherited factors were important determinants of incident ischemic stroke latency. C1 Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA. Mayo Clin, Dept Neurol, Rochester, MN USA. Univ Cincinnati, Dept Neurol, Cincinnati, OH USA. NIA, Bethesda, MD 20892 USA. Wake Forest Univ, Dept Biostat, Sch Med, Winston Salem, NC 27109 USA. RP Meschia, JF (reprint author), Mayo Clin, Dept Neurol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM Meschia.James@mayo.edu RI Hardy, John/C-2451-2009; OI Kissela, Brett/0000-0002-9773-4013 FU NINDS NIH HHS [R01 NS39987, R01 NS039987] NR 7 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 22 PY 2005 VL 64 IS 6 BP 1061 EP 1063 PG 3 WC Clinical Neurology SC Neurosciences & Neurology GA 908RH UT WOS:000227806600026 PM 15781828 ER PT J AU Su, HP Garman, SC Allison, TJ Fogg, C Moss, B Garboczi, DN AF Su, HP Garman, SC Allison, TJ Fogg, C Moss, B Garboczi, DN TI The 1.51-angstrom structure of the poxvirus L1 protein, a target of potent neutralizing antibodies SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE myristoylation; virion protein; x-ray structure ID OUTER-MEMBRANE PROTEINS; VACCINIA VIRUS; NONHUMAN-PRIMATES; SMALLPOX; SOFTWARE AB Although eradicated from nature more than two decades ago, the threat of smallpox has reemerged because of concerns over its use as a biological weapon. We present the structure of the poxvirus L1 protein, a molecule that is conserved throughout the poxvirus family and is nearly identical in vaccinia virus and in variola virus, which causes smallpox. L1 is a myristoylated envelope protein that is a potent target for neutralizing antibodies and an important component of current experimental vaccines. The L1 structure reveals a hydrophobic cavity located adjacent to its N terminus. The cavity would be capable of shielding the myristate moiety, which is essential for virion assembly. The structure of L1 is a step in the elucidation of molecular mechanisms common to all poxviruses that may stimulate the design of safer vaccines and new antipoxvirus drugs. C1 NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Dept Biochem & Mol Biol, Amherst, MA 01003 USA. RP Garboczi, DN (reprint author), NIAID, Struct Biol Sect, Immunogenet Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM dgarboczi@niaid.nih.gov NR 30 TC 31 Z9 32 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 22 PY 2005 VL 102 IS 12 BP 4240 EP 4245 DI 10.1073/pnas.0501103102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 909IY UT WOS:000227854800006 PM 15761054 ER PT J AU Poulin, B Sekiya, F Rhee, SG AF Poulin, B Sekiya, F Rhee, SG TI Intramolecular interaction between phosphorylated tyrosine-783 and the C-terminal Src homology 2 domain activates phospholipase C-gamma 1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE affinity chromatography; platelet-derived growth factor ID GROWTH-FACTOR RECEPTOR; SH2 DOMAINS; C-GAMMA-1; GAMMA; STIMULATION; ASSOCIATION; EXPRESSION; MECHANISM; RESIDUES; AFFINITY AB Phospholipase C-gamma 1 (PLC-gamma 1) contains two tandem Src homology 2 (SH2) domains. The NH2-terminal SH2 domain has been known to mediate the binding of PLC-gamma 1 to receptor protein tyrosine kinases, which then activate PLC-gamma 1 via phosphorylation at Y783. We now show that the phosphorylated Y783 residue (pY783) associates with the COOH-terminal SH2 domain [SH2(C)] within the same molecule of PLC-gamma 1. The specificity of this intramolecular interaction is demonstrated in several ways. The mutation of SH2(C), but not of the NH2-terminal SH2 domain, exposes pY783 and makes it available for binding by anti-pY783 antibodies, for intermolecular association with a GST fusion protein containing the tandem SH2 domains of PLC-gamma 1 and for dephosphorylation by phosphatases. The intramolecular interaction between pY783 and SH2(C) induces a rearrangement of surface charge such that PLC-gamma 1 molecules phosphorylated at Y783 are retained more strongly by heparin resins than are unphosphorylated molecules. Finally, the intramolecular interaction of pY783 with SH2(C) results in activation of phospholipase activity. Our results thus clarify the molecular mechanism of PLC-gamma 1 activation, revealing the specific function of pY783 and the distinct roles of the two SH2 domains in this process. C1 NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Rhee, SG (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 10, Bethesda, MD 20892 USA. EM sgrhee@nih.gov NR 25 TC 62 Z9 63 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 22 PY 2005 VL 102 IS 12 BP 4276 EP 4281 DI 10.1073/pnas.0409590102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 909IY UT WOS:000227854800012 PM 15764700 ER PT J AU Svenningsen, SL Costantino, N Court, DL Adhya, S AF Svenningsen, SL Costantino, N Court, DL Adhya, S TI On the role of Cro in lambda prophage induction SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Cl protein; genetic switch; transcription ID BACTERIOPHAGE-LAMBDA; GENE-REGULATION; RIGHT OPERATOR; CI REPRESSOR; PROTEIN; COOPERATIVITY; TRANSCRIPTION; BINDING; DIMERS; SWITCH AB The lysogenic state of bacteriophage lambda is exceptionally stable yet the prophage is readily induced in response to DNA damage. This delicate epigenetic switch is believed to be regulated by two proteins; the lysogenic maintenance promoting protein Cl and the early lytic protein Cro. First, we confirm, in the native configuration, the previous observation that the DNA loop mediated by oligomerization of Cl bound to two distinct operator regions (O-L and O-R), increases repression of the early lytic promoters and is important for stable maintenance of lysogeny. Second, we show that the presence of the cro gene might be unimportant for the lysogenic to lytic switch during induction of the lambda prophage. We revisit the idea that Cro's primary role in induction is instead to mediate weak repression of the early lytic promoters. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NCI, Frederick, MD 21702 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, 37 Convent Dr,Room 5138, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov RI Svenningsen, Sine/M-7925-2014 OI Svenningsen, Sine/0000-0001-7322-2681 NR 31 TC 59 Z9 59 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 MAR 22 PY 2005 VL 102 IS 12 BP 4465 EP 4469 DI 10.1073/pnas.0409839102 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 909IY UT WOS:000227854800045 PM 15728734 ER PT J AU Kobiler, O Rokney, A Friedman, N Court, DL Stavans, J Oppenheim, AB AF Kobiler, O Rokney, A Friedman, N Court, DL Stavans, J Oppenheim, AB TI Quantitative kinetic analysis of the bacteriophage lambda genetic network SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gene regulation; lysogeny; lysis; green fluorescent protein ID ESCHERICHIA-COLI; REPRESSOR SYNTHESIS; CII; ANTITERMINATION; EXPRESSION; MUTATIONS; INFECTION; PROTEINS; PROMOTER; VIRUSES AB The lysis-lysogeny decision of bacteriophage A has been a paradigm for a developmental genetic network, which is composed of interlocked positive and negative feedback loops. This genetic network is capable of responding to environmental signals and to the number of infecting phages. An interplay between Cl and Cro functions suggested a bistable switch model for the lysis-lysogeny decision. Here, we present a real-time picture of the execution of lytic and lysogenic pathways with unprecedented temporal resolution. We monitor, in vivo, both the level and function of the CII and Q gene regulators. These activators are cotranscribed yet control opposite developmental pathways. Conditions that favor the lysogenic response show severe delay and down-regulation of Q activity, in both CII-dependent and CII-independent ways. Whereas CII activity correlates with its protein level, Q shows a pronounced threshold before its function is observed. Our quantitative analyses suggest that by regulating CII and CIII, Cro plays a key role in the ability of the A genetic network to sense the difference between one and more than one phage particles infecting a cell. Thus, our results provide an improved framework to explain the longstanding puzzle of the decision process. C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Genet & Biotechnol, IL-91120 Jerusalem, Israel. Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel. NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Oppenheim, AB (reprint author), Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Mol Genet & Biotechnol, IL-91120 Jerusalem, Israel. EM oppenhea@mail.nih.gov RI Kobiler, Oren/J-2268-2012 OI Kobiler, Oren/0000-0001-9914-3770 NR 32 TC 63 Z9 64 U1 0 U2 11 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 MAR 22 PY 2005 VL 102 IS 12 BP 4470 EP 4475 DI 10.1073/pnas.0500670102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 909IY UT WOS:000227854800046 PM 15728384 ER PT J AU Anderson, LK Royer, SM Page, SL McKim, KS Lai, A Liily, MA Hawley, RS AF Anderson, LK Royer, SM Page, SL McKim, KS Lai, A Liily, MA Hawley, RS TI Juxtaposition of C(2)M and the transverse filament protein C(3)G within the central region of Drosophila synaptonemal complex SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE meiosis recombination; chromosome; immunogold; electron microscopy ID MEIOTIC CHROMOSOMES; C-ELEGANS; RECOMBINATION NODULES; MOLECULAR-BIOLOGY; SYNAPSIS; MELANOGASTER; RAT; PROPHASE; ABSENCE; CELLS AB The synaptonemal complex (SC) is intimately involved in the process of meiotic recombination in most organisms, but its exact role remains enigmatic. One reason for this uncertainty is that the overall structure of the SC is evolutionarily conserved, but many SC proteins are not. Two putative SC proteins have been identified in Drosophila: C(3)G and C(2)M. Mutations in either gene cause defects in SC structure and meiotic recombination. Although neither gene is well conserved at the amino acid level, the predicted secondary structure of C(3)G is similar to that of transverse-filament proteins, and C(2)M is a distantly related member of the alpha-kleisin family that includes Rec8, a meiosis-specific cohesin protein. Here, we use immunogold labeling of SCs in Drosophila ovaries to localize C(3)G and C(2)M at the EM level. We show that both C(3)G and C(2)M are components of the SC, that the orientation of C(3)G within the SC is similar to other transverse-filament proteins, and that the N terminus of C(2)M is located in the central region adjacent to the lateral elements (LEs). Based on our data and the known phenotypes of C(2)M and C(3)G mutants, we propose a model of SC structure in which C(2)M links C(3)G to the LEs. C1 Stowers Inst Med Res, Kansas City, MO 64110 USA. Colorado State Univ, Dept Biol, Ft Collins, CO 80523 USA. Rutgers State Univ, Waksman Inst, Piscataway, NJ 08854 USA. Rutgers State Univ, Dept Genet, Piscataway, NJ 08854 USA. NICHHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. RP Hawley, RS (reprint author), Stowers Inst Med Res, Kansas City, MO 64110 USA. EM rsh@stowers-institute.org RI Page, Scott/B-4984-2009; OI Lilly, Mary/0000-0003-1564-619X FU NIGMS NIH HHS [R01 GM051444, GM051444] NR 38 TC 53 Z9 56 U1 1 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 22 PY 2005 VL 102 IS 12 BP 4482 EP 4487 DI 10.1073/pnas.0500172102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 909IY UT WOS:000227854800048 PM 15767569 ER PT J AU Betts, MR Exley, B Price, DA Bansal, A Camacho, ZT Teaberry, V West, SM Ambrozak, DR Tomaras, G Roederer, M Kilby, JM Tartaglia, J Belshe, R Gao, F Douek, DC Weinhold, KJ Koup, RA Goepfert, P Ferrari, G AF Betts, MR Exley, B Price, DA Bansal, A Camacho, ZT Teaberry, V West, SM Ambrozak, DR Tomaras, G Roederer, M Kilby, JM Tartaglia, J Belshe, R Gao, F Douek, DC Weinhold, KJ Koup, RA Goepfert, P Ferrari, G TI Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE acute infection; correlate of protection; multiparameter flow cytometry ID VIRUS TYPE-1 INFECTION; SIMIAN IMMUNODEFICIENCY; ANTIRETROVIRAL THERAPY; LYMPHOCYTE RESPONSE; VIRAL ESCAPE; REPLICATION; TRANSMISSION; VOLUNTEERS; ANTIBODIES; MACAQUES AB Worldwide HIV-1 vaccine efforts are guided by the principle that HIV-specific T cell responses may provide protection from infection or delay overt disease. However, no clear correlates of T cell-mediated immune protection have been identified. Here, we examine in a HLA-B27(+) HIV seronegative vaccinee persistent HIVspecific vaccine-induced anti-Gag CD4(+) and CD8(+) T cell responses. Although these responses exhibited those characteristics (multi-functionality, appropriate memory phenotype, and targeting of epitopes associated with long-term nonprogression) predicted to correlate with protection from infection, the subject became HIV infected. After HIV infection, the vaccine-induced CD8(+) T cells expanded, but both CD4(+) and CD8(+) T cell responses acquired the functional and phenotypic patterns characteristic of chronic HIV infection. The virus quickly escaped the vaccine-induced T cell response, and the subject progressed more rapidly than expected for someone expressing the HLA-B27 allele. These data suggest that control of HIV by vaccine-elicited HIV-specific T cell responses may be difficult, even when the T cell response has those characteristics predicted to provide optimal protection. C1 Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Human Immunol Sect, NIH, Bethesda, MD 20892 USA. NIAID, ImmunoTechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Alabama Birmingham, Birmingham, AL 35294 USA. Duke Univ, Med Ctr, Human Vaccine Inst, Durham, NC 27710 USA. R&D Aventis Pasteur, N York, ON M2R 3T4, Canada. St Louis Univ Hosp, Dept Med, St Louis, MO 63119 USA. RP Ferrari, G (reprint author), Duke Univ, Med Ctr, Dept Surg, SORF Bldg,La Salle St Extens, Durham, NC 27710 USA. EM gflmp@duke.edu RI Roederer, Mario/G-1887-2011; Price, David/C-7876-2013; Ferrari, Guido/A-6088-2015; Tomaras, Georgia/J-5041-2016; OI Price, David/0000-0001-9416-2737; Kilby, J. Michael/0000-0003-3222-1003 FU Medical Research Council [G108/441]; NIAID NIH HHS [T32 AI007392, 3P30-AI28662, 5R01-AI50483, 5T32 AI07392, 5U01-AI46725, R01 AI049126, R01 AI050483, R01-AI49126, U01 AI041530, U01 AI046725, U01-AI41530] NR 36 TC 112 Z9 117 U1 1 U2 3 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 22 PY 2005 VL 102 IS 12 BP 4512 EP 4517 DI 10.1073/pnas.0408773102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 909IY UT WOS:000227854800053 PM 15753288 ER PT J AU Zhang, N Inan, S Cowan, A Sun, RH Wang, JM Rogers, TJ Caterina, M Oppenheim, JJ AF Zhang, N Inan, S Cowan, A Sun, RH Wang, JM Rogers, TJ Caterina, M Oppenheim, JJ TI A proinflarnmatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE CCR1; chemokine receptor; inflammation; pain ID RECEPTOR CCR1; MICE LACKING; HETEROLOGOUS DESENSITIZATION; SIGNALING PATHWAY; OPIOID RECEPTORS; PAIN; HYPERALGESIA; VR1; CHEMOTAXIS; ACTIVATION AB Pain, a critical component of host defense, is one hallmark of the inflammatory response. We therefore hypothesized that pain might be exacerbated by proinflammatory chemokines. To test this hypothesis, CCR1 was cotransfected into human embryonic kidney (HEK)293 cells together with transient receptor potential vanilloid 1 (TRPV1), a cation channel required for certain types of thermal hyperalgesia. In these cells, capsaicin and anandamide induced Ca2+ influx mediated by TRPV1. When CCR1:TRPV1/HEK293 cells were pretreated with CCL3, the sensitivity of TIRPV1, as indicated by the Ca2+ influx, was increased approximate to 3-fold. RT-PCR analysis showed that a spectrum of chemokine and cytokine receptors is expressed in rat dorsal root ganglia (DRG). Immunohistochemical staining of DRG showed that CCR1 is coexpressed with TRPV1 in >85% of small-diameter neurons. CCR1 on DRG neurons was functional, as demonstrated by CCL3-induced Ca2+ ion influx and PKC activation. Pretreatment with CCL3 enhanced the response of DRG neurons to capsaicin or anandamide. This sensitization was inhibited by pertussis toxin, U73122, or chelerythrine chloride, inhibitors of Gi-protein, phospholipase C, and protein kinase C, respectively. Intraplantar injection of mice with CCL3 decreased their hot-plate response latency. That a proinflammatory chemokine, by interacting with its receptor on small-diameter neurons, sensitizes TRPV1 reveals a previously undescribed mechanism of receptor cross-sensitization that may contribute to hyperalgesia during inflammation. C1 NCI, Mol Immunoregulat Lab, Intramural Res Support Program, Div Basic Sci,NIH, Frederick, MD 21702 USA. Johns Hopkins Univ, Sch Med, Dept Biol Chem, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. Temple Univ, Sch Med, Ctr Subst Abuse Res, Fels Inst Canc Res & Mol Biol,Dept Pharmacol, Philadelphia, PA 19122 USA. RP Oppenheim, JJ (reprint author), NCI, Mol Immunoregulat Lab, Intramural Res Support Program, Div Basic Sci,NIH, Frederick, MD 21702 USA. EM oppenhei@ncifcrf.gov FU NIDA NIH HHS [DA14230, DA-06650, DA-13429, DA-16544, P30 DA013429, R01 DA006650, R01 DA014230, R01 DA016544, T32 DA007237, T32DA07237] NR 24 TC 139 Z9 152 U1 2 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 MAR 22 PY 2005 VL 102 IS 12 BP 4536 EP 4541 DI 10.1073/pnas.0406030102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 909IY UT WOS:000227854800057 PM 15764707 ER PT J AU Meunier, JC Engle, RE Faulk, K Zhao, M Bartosch, B Alter, H Emerson, SU Cosset, FL Purcell, RH Bukh, J AF Meunier, JC Engle, RE Faulk, K Zhao, M Bartosch, B Alter, H Emerson, SU Cosset, FL Purcell, RH Bukh, J TI Evidence for cross-genotype neutralization of hepatitis C virus pseudo-particles and enhancement of infectivity by apolipoprotein C1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE neutralizing antibodies; high-density lipoproteins ID ANTIBODY-RESPONSE; CHIMPANZEES; SEQUENCE; GLYCOPROTEIN; PERSISTENCE; COMPLEXES; DISEASE; CLONE; ENTRY; HCV AB The lack of a cell culture system to support hepatitis C virus (HCV) replication has hampered studies of this frequent cause of chronic liver disease. However, pseudotyped retroviral particles (pp) bearing the HCV envelope glycoproteins have provided a different approach to HCV studies. We used genotype la pp to detect neutralizing antibodies (NtAb) in eight chimpanzees and four humans infected with la strains, and developed pp of genotypes 2a, 3a, 4a, 5a, and 6a to study cross-reactivity. NtAb was detected in one of four chimpanzees and none of three humans with acute resolving infection, suggesting that NtAb is not required for HCV clearance. NtAb were detected at high titer in two of four chimpanzees and, in Patient H, all with persistent infection; responses paralleled humoral responses to envelope 1 and 2 proteins and, in some cases, correlate also with antibodies to the hypervariable region 1, previously thought to be the primary site of neutralization. NtAb raised during 1 a infections could neutralize HCVpp of genotypes 4a, 5a, and 6a but had only limited reactivity against 2a and 3a. The detection of high-titer NtAb with cross-genotype reactivity has important implications for the development of active and passive immune-prophylaxis strategies against HCV. Finally, we found that HCVpp infectivity was enhanced by human or chimpanzee sera; apolipoprotein C1 alone or as a component of high-density lipoproteins caused this enhancement. Future studies of the in vivo role of apolipoprotein C1 might provide additional insights into the infection process of HCV. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Res Technol Branch, NIH, Rockville, MD 20852 USA. Ecole Normale Super Lyon, Lab Vectorol Retrovirale & Therapie Gen, F-69364 Lyon, France. NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Bukh, J (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM jbukh@niaid.nih.gov NR 29 TC 172 Z9 186 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 MAR 22 PY 2005 VL 102 IS 12 BP 4560 EP 4565 DI 10.1073/pnas.0501275102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 909IY UT WOS:000227854800061 PM 15767578 ER PT J AU Zhang, RX Liu, B Lao, LX Qiao, JT Ruda, MA AF Zhang, RX Liu, B Lao, LX Qiao, JT Ruda, MA TI Spinal preprodynorphin mRNA expression in neonatal rats following peripheral inflammation SO BRAIN RESEARCH LA English DT Article DE neonates; complete Freund's adjuvant; hyperalgesia; spinal dorsal horn; preprodynorphin mRNA; rats ID ANTINOCICEPTIVE TOLERANCE; PAIN; HYPERALGESIA AB Spinal nociceptive neural circuits undergo considerable changes during the postnatal period. This study showed that neonatal rats exhibited earlier upregulation and faster recovery of spinal preprodynorphin (PPD) mRNA than did the adults during complete Freund's adjuvant (CFA)-induced peripheral inflammation. These data suggest that the central nervous systems of neonates and adults respond differently to peripheral noxious inputs, a fact that should be considered when selecting pain treatment strategies for neonate populations. (c) 2005 Elsevier B.V All rights reserved. C1 Univ Maryland, Sch Med, Ctr Integrat Med, Baltimore, MD 21201 USA. Shanxi Med Univ, Dept Neurobiol, Shanxi 030001, Peoples R China. NIDCR, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD 20892 USA. RP Zhang, RX (reprint author), James Kernan Hosp, Ctr Integrat Med, 3rd Floor,2200 Kernan Dr, Baltimore, MD 21207 USA. EM Rzhan001@umaryland.edu RI Lao, Lixing/I-7979-2013; OI Lao, Lixing/0000-0003-0198-9714 NR 17 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 21 PY 2005 VL 1038 IS 2 BP 238 EP 242 DI 10.1016/j.brainres.2005.01.039 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 914AB UT WOS:000228195700013 PM 15757640 ER PT J AU Fannin, RD Auman, JT Bruno, ME Sieber, SO Ward, SM Tucker, CJ Merrick, BA Paules, RS AF Fannin, RD Auman, JT Bruno, ME Sieber, SO Ward, SM Tucker, CJ Merrick, BA Paules, RS TI Differential gene expression profiling in whole blood during acute systemic inflammation in lipopolysaccharide-treated rats SO PHYSIOLOGICAL GENOMICS LA English DT Article DE microarray; toxicogenomics; methods ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA; BACTERIAL LIPOPOLYSACCHARIDE; MICROARRAY ANALYSIS; HUMAN NEUTROPHIL; INNATE IMMUNITY; PROTEIN-KINASE; MACROPHAGES; CELLS; CYTOCHROME-P450 AB Microarrays have been used to evaluate the expression of thousands of genes in various tissues. However, few studies have investigated the change in gene expression profiles in one of the most easily accessible tissues, whole blood. We utilized an acute inflammation model to investigate the possibility of using a cDNA microarray to measure the gene expression profile in the cells of whole blood. Blood was collected from male Sprague-Dawley rats at 2 and 6 h after treatment with 5 mg/kg (ip) LPS. Hematology showed marked neutrophilia accompanied by lymphopenia at both time points. TNF-alpha and IL-6 levels were markedly elevated at 2 h, indicating acute inflammation, but by 6 h the levels had declined. Total RNA was isolated from whole blood and hybridized to the National Institute of Environmental Health Sciences Rat Chip v. 3.0. LPS treatment caused 226 and 180 genes to be differentially expressed at 2 and 6 h, respectively. Many of the differentially expressed genes are involved in inflammation and the acute phase response, but differential expression was also noted in genes involved in the cytoskeleton, cell adhesion, oxidative respiration, and transcription. Real-time RT-PCR confirmed the differential regulation of a representative subset of genes. Principal component analysis of gene expression discriminated between the acute inflammatory response apparent at 2 h and the observed recovery underway at 6 h. These studies indicate that, in whole blood, changes in gene expression profiles can be detected that are reflective of inflammation, despite the adaptive shifts in leukocyte populations that accompany such inflammatory processes. C1 NIEHS, Natl Ctr Toxicogenom, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Fannin, RD (reprint author), NIEHS, Natl Ctr Toxicogenom, NIH, D2-04,POB 12233, Res Triangle Pk, NC 27709 USA. EM fannin@niehs.nih.gov NR 52 TC 22 Z9 25 U1 1 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1094-8341 J9 PHYSIOL GENOMICS JI Physiol. Genomics PD MAR 21 PY 2005 VL 21 IS 1 BP 92 EP 104 DI 10.1152/physiolgenomics.00190.2004 PG 13 WC Cell Biology; Genetics & Heredity; Physiology SC Cell Biology; Genetics & Heredity; Physiology GA 916LW UT WOS:000228387500008 PM 15781589 ER PT J AU Zeng, G Aldridge, ME Wang, Y Pantuck, AJ Wang, AY Liu, YX Han, Y Yuan, YH Robbins, PF Dubinett, SM DeKernion, JB Belldegrun, AS AF Zeng, G Aldridge, ME Wang, Y Pantuck, AJ Wang, AY Liu, YX Han, Y Yuan, YH Robbins, PF Dubinett, SM DeKernion, JB Belldegrun, AS TI Dominant B cell epitope from NY-ESO-1 recognized by sera from a wide spectrum of cancer patients: Implications as a potential biomarker SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE SEREX; tumor antigen; immunotherapy; tumor biomarker; cancer vaccine ID HUMAN TUMOR-ANTIGENS; IMMUNE-RESPONSES; ANTIBODY; PROTEIN; IMMUNOTHERAPY; EXPRESSION; IDENTIFICATION; TARGETS; LAGE-1; PANEL AB Monitoring the spontaneous antibody (Ab) response against a panel of relevant tumor-associated antigens (TAA) in cancer patients may provide useful information regarding the clinical status of cancer. However, current Ab detection approaches require the purification of recombinant proteins, which is often difficult to achieve. In order to bypass the purification of recombinant proteins, we identified a dominant B-cell epitope from a shared tumor antigen NY-ESO-1. A synthetic peptide of the epitope, ESO:1-40, was as sensitive as the recombinant protein for detecting Ab against NY-ESO-1 in most patients. NY-ESO-1 specific Ab present in the sera of patients with melanoma, prostate cancer, nonsmall cell lung cancer, esophageal cancer, gastric cancer and hepatocellular carcinoma reacted with the dominant peptide at a similar frequency as the recombinant protein. To our knowledge, ESO: 1-40 is the first peptide epitope recognized by sera from a wide spectrum of cancer patients but not healthy donors. This simple and straightforward approach may allow the investigation of the clinical significance of spontaneous Ab responses against multiple TAA and their correlation with the clinical course of malignant diseases in the future. (C) 2004 Wiley-Liss, Inc. C1 Univ Calif Los Angeles, David Geffen sCh Med, Hlth Sci Ctr, Dept Urol, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, David Geffen sCh Med, Hlth Sci Ctr, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Med, Div Pulm & Crit Care Med, Los Angeles, CA 90095 USA. Peking Univ, Med Ctr, Beijing Canc Hosp, Beijing 100871, Peoples R China. Natl Canc Inst, Surg Branch, Bethesda, MD USA. RP Zeng, G (reprint author), Univ Calif Los Angeles, David Geffen sCh Med, Hlth Sci Ctr, Dept Urol, Box 951738,66-118, Los Angeles, CA 90095 USA. EM gzeng@tnednet.ucla.edu NR 26 TC 25 Z9 27 U1 0 U2 2 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 MAR 20 PY 2005 VL 114 IS 2 BP 268 EP 273 DI 10.1002/ijc.20716 PG 6 WC Oncology SC Oncology GA 893QL UT WOS:000226734200016 PM 15540228 ER PT J AU Ghadimi, BM Grade, M Difilippantonio, MJ Varma, S Simon, R Montagna, C Fuzesi, L Langer, C Becker, H Liersch, T Ried, T AF Ghadimi, BM Grade, M Difilippantonio, MJ Varma, S Simon, R Montagna, C Fuzesi, L Langer, C Becker, H Liersch, T Ried, T TI Effectiveness of gene expression profiling for response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID THYMIDYLATE SYNTHASE EXPRESSION; DISEASE-FREE SURVIVAL; COLORECTAL-CANCER; MOLECULAR MARKERS; TUMOR RESPONSE; NEOADJUVANT RADIOCHEMOTHERAPY; CONCURRENT CHEMORADIOTHERAPY; HISTOPATHOLOGIC RESPONSE; COLON-CANCER; DUKES-B AB Purpose There is a wide spectrum of tumor responsiveness of rectal adenocarcinomas to preoperative chemoradiotherapy ranging from complete response to complete resistance. This study aimed to investigate whether parallel gene expression profiling of the primary tumor can contribute to stratification of patients into groups of responders or nonresponders. Patients and Methods Pretherapeutic biopsies from 30 locally advanced rectal carcinomas were analyzed for gene expression signatures using microarrays. All patients were participants of a phase III clinical trial (CAO/ARO/AlO-94, German Rectal Cancer Trial) and were randomized to receive a preoperative combined-modality therapy including fluorouracil and radiation. Class comparison was used to identify a set of genes that were differentially expressed between responders and nonresponders as measured by T level downsizing and histopathologic tumor regression grading. Results In an initial set of 23 patients, responders and nonresponclers showed significantly different expression levels for 54 genes (P < .001). The ability to predict response to therapy using gene expression profiles was rigorously evaluated using leave-one-out cross-validation. Tumor behavior was correctly predicted in 83% of patients (P = .02). Sensitivity (correct prediction of response) was 78%, and specificity (correct prediction of nonresponse) was 86%, with a positive and negative predictive value of 78% and 86%, respectively. Conclusion Our results suggest that pretherapeutic gene expression profiling may assist in response prediction of rectal adenocarcinomas to preoperative chemoradiotherapy. The implementation of gene expression profiles for treatment stratification and clinical management of cancer patients requires validation in large, independent studies, which are now warranted. C1 NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Biomet Res Branch, NIH, Bethesda, MD 20892 USA. Univ Gottingen, Med Ctr, Dept Gen Surg, D-3400 Gottingen, Germany. Univ Gottingen, Med Ctr, Dept Pathol, D-3400 Gottingen, Germany. RP Ried, T (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, Bldg 50,Rm 1408,50 S Dr, Bethesda, MD 20892 USA. EM riedt@mail.nih.gov RI Varma, Sudhir/N-8763-2014 OI Varma, Sudhir/0000-0002-4096-4782 FU Intramural NIH HHS [Z99 CA999999] NR 59 TC 221 Z9 232 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2005 VL 23 IS 9 BP 1826 EP 1838 DI 10.1200/JCO.2005.00.406 PG 13 WC Oncology SC Oncology GA 911SK UT WOS:000228024800008 PM 15774776 ER PT J AU Grem, JL Morrison, G Guo, XD Agnew, E Takimoto, CH Thomas, R Szabo, E Grochow, L Grollman, F Hamilton, JM Neckers, L Wilson, RH AF Grem, JL Morrison, G Guo, XD Agnew, E Takimoto, CH Thomas, R Szabo, E Grochow, L Grollman, F Hamilton, JM Neckers, L Wilson, RH TI Phase I and pharmacologic study of 17-(allylamino)-17-demethoxygeldanamycin in adult patients with solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID PROTEIN 90 HSP90; ANTITUMOR AGENT; BENZOQUINONE ANSAMYCINS; MOLECULAR CHAPERONE; HSP90-BINDING AGENT; TISSUE DISTRIBUTION; GELDANAMYCIN; RECEPTOR; ASSOCIATION; DEGRADATION AB Purpose To determine the clinical toxicities of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) given as a 1-hour infusion daily for 5 days every 3 weeks. Patients and Methods Nineteen patients received 17-AAG over six dose levels (10 to 56 mg/m(2)) using an accelerated titration scheme. Drug levels of 17-AAG were determined by high-performance liquid chromatography. Biologic effects of 17-AAG were monitored by changes in the content of target proteins by immunoblot analysis of lysates prepared from peripheral-blood mononuclear cells. Results Toxicity was acceptable at doses up to 28 mg/m(2). The cohort was expanded to three patients at 40 mg/m(2) because a second occurrence of grade 2 hepatic transaminitis occurred. Two of six assessable patients who received 56 mg/m(2) had reversible, grade 3 hepatic transaminitis. Five additional patients were enrolled at 40 mg/m(2); none had dose-limiting toxicity. The maximum plasma concentrations (C-max) of 17-AAG at 40 and 56 Mg/M2 were 1,724 and 2,046 ng/mL, respectively; the average plasma exposures (AUC) were 2,809 and 6,708 hours(.)ng/mL, respectively. Less than 3% of the daily dose was excreted into the urine. Clearance did not correlate with body-surface area. Possible biologic activity was suggested by apparent increased protein content of either glucose-related 78 kd protein or heat shock protein 70 with 14 Mg/M2 and decreased protein content of either Lck or Baf1 with >= 28 mg/m(2) of 17-AAG. Conclusion 17-AAG 40 mg/m(2) (median dose, 70 mg) was well tolerated when given daily for 5 days every 3 weeks. C1 NCI, Ctr Canc Res, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Progran, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Grem, JL (reprint author), Nebraska Med Ctr 987680, Omaha, NE 68198 USA. EM jgrem@unmc.edu NR 39 TC 200 Z9 209 U1 0 U2 5 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 MAR 20 PY 2005 VL 23 IS 9 BP 1885 EP 1893 DI 10.1200/JCO.2005.12.085 PG 9 WC Oncology SC Oncology GA 911SK UT WOS:000228024800014 PM 15774780 ER PT J AU Sargent, DJ Conley, BA Allegro, C Collette, L AF Sargent, DJ Conley, BA Allegro, C Collette, L TI Clinical trial designs for predictive marker validation in cancer treatment trials SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID THYMIDYLATE SYNTHASE EXPRESSION; METASTATIC COLORECTAL-CANCER; FLUOROURACIL-BASED CHEMOTHERAPY; BREAST-CANCER; ADJUVANT CHEMOTHERAPY; PROGNOSTIC-FACTORS; PLUS IRINOTECAN; TUMOR-MARKERS; QUANTITATION; LEUCOVORIN AB Current staging and risk-stratification methods in oncology, while helpful, fail to adequately predict malignancy aggressiveness and/or response to specific treatment. Increased knowledge of cancer biology is generating promising marker candidates for more accurate diagnosis, prognosis assessment, and therapeutic targeting. To apply these exciting results to maximize patient benefit, a disciplined application of well-designed clinical trials for assessing the utility of markers should be used. In this article, we first review the major issues to consider when designing a clinical trial assessing the usefulness of a predictive marker. We then present two classes of clinical trial designs: the Marker by Treatment Interaction Design and the Marker-Based Strategy Design. In the first design, we assume that the marker splits the population into groups in which the efficacy of a particular treatment will differ. This design can be viewed as a classical randomized clinical trial with upfront stratification for the marker. In the second design, after the marker status is known, each patient is randomly assigned either to have therapy determined by their marker status or to receive therapy independent of marker status. The predictive value of the marker is assessed by comparing the outcome of all patients in the marker-based arm to that of all of the patients in the non-marker-based arm. We present detailed sample size calculations for a specific clinical scenario. We discuss the advantages and disadvantages of the two trial designs and their appropriateness to specific clinical situations to assist investigators seeking to design rigorous, marker-based clinical trials. C1 Mayo Clin, Rochester, MN 55905 USA. Natl Canc Inst, Ctr Canc Res, Med Oncol Clin Res Unit, Bethesda, MD USA. Network Med Commun & Res, Atlanta, GA USA. European Org Res Treatment Canc, Ctr Data, Brussels, Belgium. RP Sargent, DJ (reprint author), Mayo Clin, Kahler 1A,200 1st St SW, Rochester, MN 55905 USA. EM sargent.daniel@mayo.edu OI Sargent, Daniel/0000-0002-2684-4741 NR 21 TC 280 Z9 289 U1 1 U2 7 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 MAR 20 PY 2005 VL 23 IS 9 BP 2020 EP 2027 DI 10.1200/JCO.2005.01.112 PG 8 WC Oncology SC Oncology GA 911SK UT WOS:000228024800030 PM 15774793 ER PT J AU Figg, WD Retter, A Steinberg, SM Dahut, WL AF Figg, WD Retter, A Steinberg, SM Dahut, WL TI Inhibition of angiogenesis: Thalidomide or low-molecular-weight heparin? Response SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Ctr Canc Res, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 1 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 20 PY 2005 VL 23 IS 9 BP 2113 EP 2114 DI 10.1200/JCO.2005.05.296 PG 2 WC Oncology SC Oncology GA 911SK UT WOS:000228024800050 ER PT J AU Carrington, JL AF Carrington, JL TI Aging bone and cartilage: cross-cutting issues SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Review DE aging; cartilage; bone; osteoarthritis; osteoporosis; osteopenia; apoptosis; stem cells ID GLYCATION END-PRODUCTS; AGE-RELATED-CHANGES; HUMAN ARTICULAR-CARTILAGE; GROWTH-FACTOR-I; CHONDROCYTE APOPTOSIS; LIFE-SPAN; OXIDATIVE STRESS; EXTRACELLULAR-MATRIX; CALORIC RESTRICTION; CELLULAR SENESCENCE AB Aging is a major risk factor for osteoarthritis and osteoporosis. Yet, these are not necessary outcomes of aging, and the relationship between age-related changes in bone and cartilage and development of disease is not clear. There are some well-described cellular changes associated with aging in multiple tissues that appear to be fundamental to the decline in function of cartilage and bone. A better understanding of age-related changes in cells and tissues is necessary to mitigate or, hopefully, avoid loss of bone and cartilage with aging. In addition, a better understanding of the dynamics of tissue maintenance in vivo is critical to developing tissue replacement and repair therapies. The role of stem cells in this process, and why tissues are not well maintained with advancing age, are frontiers for future aging research. Published by Elsevier Inc. C1 NIA, Dept Hlth & Human Serv, Biol Aging Program, NIH, Bethesda, MD 20892 USA. RP Carrington, JL (reprint author), NIA, Dept Hlth & Human Serv, Biol Aging Program, NIH, Bethesda, MD 20892 USA. EM carringtonj@nia.nih.gov NR 90 TC 50 Z9 54 U1 0 U2 8 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 MAR 18 PY 2005 VL 328 IS 3 BP 700 EP 708 DI 10.1016/j.bbrc.2004.12.041 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 899JK UT WOS:000227140500008 PM 15694404 ER PT J AU Ray, R Choi, M Zhang, ZJ Silverman, GA Askew, D Mukherjee, AB AF Ray, R Choi, M Zhang, ZJ Silverman, GA Askew, D Mukherjee, AB TI Uteroglobin suppresses SCCA gene expression associated with allergic asthma SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CARCINOMA ANTIGEN GENE; SERINE PROTEINASES; SERPIN; CONTAINS; 18Q21.3; DISEASE; LOCUS AB Uteroglobin (UG), the founding member of the Secreto-globin superfamily, is a potent anti-inflammatory protein constitutively expressed at a high level in the airway epithelia of all mammals. We previously reported that the lungs of UG-knock-out (UG-KO) mice express elevated levels of Th2 cytokines (e. g. interleukin (IL)- 4 and IL-13), which are augmented by allergen sensitization and challenge leading to exaggerated airway inflammation. Notably, these responses are suppressed by recombinant UG treatment (Mandal, A. K., Zhang, Z., Ray, R., Choi, M. S., Chowdhury, B., Pattabiraman, N., and Mukherjee, A. B. (2004) J. Exp. Med. 199, 1317-1330). Recent reports indicate that human orthologs of murine squamous cell carcinoma antigen-2 (SCCA-2/serpinb3a), a serine protease-inhibitor, are overexpressed in the airways of asthmatic patients. We report here that compared with wild type littermates, UG-KO mouse lungs express markedly elevated levels of SCCA- 2 mRNA and protein, which are augmented by allergen-challenge. Most importantly, these effects are abrogated by recombinant UG treatment. We further demonstrate that treatment of cultured human bronchial epithelial cells with IL-4 or IL-13 stimulates phosphorylation of STAT-1 and STAT-6 leading to SCCA- 1 (SERPINB3) and SCCA- 2 (SERPINB4) gene expression. We propose that: (i) IL-4- and IL-13- stimulated SCCA gene expression is mediated via STAT-1 and STAT-6 activation, and (ii) by suppressing the production, and most likely by interfering with the signaling of these cytokines, UG inhibits SCCA gene expression associated with airway inflammation in asthma. C1 NICHD, Sect Dev Genet, Heritable Dis Branch, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Dept Pediat, Pittsburgh, PA 15213 USA. RP Mukherjee, AB (reprint author), NICHD, Sect Dev Genet, Heritable Dis Branch, NIH, Bethesda, MD 20892 USA. EM mukherja@exchange.nih.gov NR 18 TC 15 Z9 15 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 MAR 18 PY 2005 VL 280 IS 11 BP 9761 EP 9764 DI 10.1074/jbc.C400581200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905HQ UT WOS:000227559600002 PM 15677460 ER PT J AU Jiang, Y Bhattacharjee, H Zhou, TQ Rosen, BP Ambudkar, SV Sauna, ZE AF Jiang, Y Bhattacharjee, H Zhou, TQ Rosen, BP Ambudkar, SV Sauna, ZE TI Nonequivalence of the nucleotide binding domains of the ArsA ATPase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ANION-TRANSLOCATING ATPASE; P-GLYCOPROTEIN; CATALYTIC SUBUNIT; PUMP; METALLOACTIVATION; HYDROLYSIS; SITE; MUTAGENESIS; MECHANISM; TURNOVER AB The arsRDABC operon of Escherichia coli plasmid R773 encodes the ArsAB pump that catalyzes extrusion of the metalloids As(III) and Sb(III), conferring metalloid resistance. The catalytic subunit, ArsA, is an ATPase with two homologous halves, A1 and A2, connected by a short linker. Each half contains a nucleotide binding domain. The overall rate of ATP hydrolysis is slow in the absence of metalloid and is accelerated by metalloid binding. The results of photolabeling of ArsA with the ATP analogue 8-azidoadenosine 5'-[alpha-P-32]-triphosphate at 4 degrees C indicate that metalloid stimulation correlates with a > 10-fold increase in affinity for nucleotide. To investigate the relative contributions of the two nucleotide binding domains to catalysis, a thrombin site was introduced in the linker. This allowed discrimination between incorporation of labeled nucleotides into the two halves of ArsA. The results indicate that both the A1 and A2 nucleotide binding domains bind and hydrolyze trinucleotide, even in the absence of metalloid. Sb( III) increases the affinity of the A1 nucleotide binding domain to a greater extent than the A2 nucleotide binding domain. The ATP analogue labeled with P-32 at the gamma position was used to measure hydrolysis of trinucleotide at 37 degrees C. Under these catalytic conditions, both nucleotide binding domains hydrolyze ATP, but hydrolysis in A1 is stimulated to a greater degree by Sb(III) than A2. These results suggest that the two homologous halves of the ArsA may be functionally nonequivalent. C1 Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, Detroit, MI 48201 USA. NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Wayne State Univ, Sch Med, Dept Biochem & Mol Biol, 540 E Canfield Ave, Detroit, MI 48201 USA. EM brosen@med.wayne.edu RI Ambudkar, Suresh/B-5964-2008; Zhou, Tongqing/A-6880-2010 OI Zhou, Tongqing/0000-0002-3935-4637 FU NIGMS NIH HHS [GM55425] NR 27 TC 7 Z9 7 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 18 PY 2005 VL 280 IS 11 BP 9921 EP 9926 DI 10.1074/jbc.M413391200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905HQ UT WOS:000227559600023 PM 15637064 ER PT J AU Ribeiro, CMP Paradiso, AM Carew, MA Shears, SB Boucher, RC AF Ribeiro, CMP Paradiso, AM Carew, MA Shears, SB Boucher, RC TI Cystic fibrosis airway epithelial Ca-i(2+) signaling SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CAPACITATIVE CALCIUM-ENTRY; TRANSMEMBRANE CONDUCTANCE REGULATOR; ENDOPLASMIC-RETICULUM; CHLORIDE CONDUCTANCE; ACTIVATION; CELLS; 3,4,5,6-TETRAKISPHOSPHATE; CLEARANCE; DISEASE; MICE AB In cystic fibrosis (CF) airways, abnormal epithelial ion transport likely initiates mucus stasis, resulting in persistent airway infections and chronic inflammation. Mucus clearance is regulated, in part, by activation of apical membrane receptors coupled to intracellular calcium (Ca-i(2+)) mobilization. We have shown that Ca-i(2+) signals resulting from apical purinoceptor (P2Y(2)-R) activation are increased in CF compared with normal human airway epithelia. The present study addressed the mechanism for the larger apical P2Y(2)-R-dependent Ca-i(2+) signals in CF human airway epithelia. We show that the increased Ca-i(2+) mobilization in CF was not specific to P2Y(2)-Rs because it was mimicked by apical bradykinin receptor activation, and it did not result from a greater number of P2Y(2)-R or a more efficient coupling between P2Y(2)-Rs and phospholipase C-generated inositol 1,4,5-trisphosphate. Rather, the larger apical P2Y(2)-R activation-promoted Ca-i(2+) signals in CF epithelia resulted from an increased density and Ca2+ storage capacity of apically confined endoplasmic reticulum (ER) Ca2+ stores. To address whether the ER upregulation resulted from ER retention of misfolded Delta F508 CFTR or was an acquired response to chronic luminal airway infection/inflammation, three approaches were used. First, ER density was studied in normal and CF sweat duct human epithelia expressing high levels of Delta F508 CFTR, and it was found to be the same in normal and CF epithelia. Second, apical ER density was morphometrically analyzed in airway epithelia from normal subjects, Delta F508 homozygous CF patients, and a disease control, primary ciliary dyskinesia; it was found to be greater in both CF and primary ciliary dyskinesia. Third, apical ER density and P2Y(2)-R activation-mobilized Ca-i(2+), which were investigated in airway epithelia in a long term culture in the absence of luminal infection, were similar in normal and CF epithelia. To directly test whether luminal infection/inflammation triggers an up-regulation of the apically confined ER Ca2+ stores, normal airway epithelia were chronically exposed to supernatant from mucopurulent material from CF airways. Supernatant treatment expanded the apically confined ER, resulting in larger apical P2Y(2)-R activation-dependent Ca-i(2+) responses, which reproduced the increased Ca-i(2+) signals observed in CF epithelia. In conclusion, the mechanism for the larger Ca-i(2+) signals elicited by apical P2Y(2)-R activation in CF airway epithelia is an expansion of the apical ER Ca2+ stores triggered by chronic luminal airway infection/inflammation. Greater ER-derived Ca-i(2+) signals may provide a compensatory mechanism to restore, at least acutely, mucus clearance in CF airways. C1 Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. NIEHS, Inositide Signaling Sect, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. RP Ribeiro, CMP (reprint author), Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. EM carla_ribeiro@med.unc.edu RI Ribeiro, Carla Maria/A-6955-2009 FU NHLBI NIH HHS [HL34322, HL60280] NR 34 TC 76 Z9 77 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 18 PY 2005 VL 280 IS 11 BP 10202 EP 10209 DI 10.1074/jbc.M410317200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905HQ UT WOS:000227559600058 PM 15647273 ER PT J AU Jeong, SJ Pise-Masison, CA Radonovich, MF Park, HU Brady, JN AF Jeong, SJ Pise-Masison, CA Radonovich, MF Park, HU Brady, JN TI A novel NF-kappa B pathway involving IKK beta and p65/Re1A ser-536 phosphorylation results in p53 inhibition in the absence of 1NF-kappa B transcriptional activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CELL LEUKEMIA-VIRUS; NECROSIS-FACTOR-ALPHA; TYPE-1 TAX PROTEIN; DEPENDENT GENE-EXPRESSION; I ASSOCIATED MYELOPATHY; CASEIN KINASE-II; P65 SUBUNIT; TRANSACTIVATION DOMAIN; ADAPTER FUNCTION; T-CELLS AB Nuclear factor kappa B (NF-kappa B) plays an important role in regulating cellular transformation and apoptosis. The human T-cell lymphotropic virus type I protein, Tax, which is critical for viral transformation, modulates the transcription of several cellular genes through activation of NF-kappa B. We have demonstrated previously that Tax inhibits p53 activity through the p65/RelA subunit of NF-kappa B. We now present evidence that suggests that the upstream kinase IKK beta plays an important role in Tax-induced p53 inhibition through phosphorylation of p65/RelA at Ser-536. First, mouse embryo fibroblast (MEF) IKK beta-/- cells did not support Tax-mediated p53 inhibition, whereas MEFs lacking IKK alpha allowed Tax inhibition of p53. Second, transfection of IKK beta wild type (WT), but not a kinase-dead mutant, into IKK beta-/- cells rescued p53 inhibition by Tax. Third, the IKK beta-specific inhibitor SC-514 decreased the ability of Tax to inhibit p53. Fourth, we show that phosphorylation of p65/RelA at Ser-536 is important for Tax inhibition of p53 using MEF p65/RelA-/- cells transfected with p65/RelA WT or mutant plasmids. Moreover, Tax induced p65/RelA Ser536 phosphorylation in WT or IKK alpha-/- cells but failed to induce the phosphorylation of p65/RelA Ser-536 in IKK beta-/- cells, suggesting a link between IKK beta and p65/RelA phosphorylation. Consistent with this observation, blocking IKK beta kinase activity by SC-514 decreases the phosphorylation of p65/RelA at Ser-536 in the presence of Tax in human T-cell lymphotropic virus type I-transformed cells. Finally, the ability of Tax to inhibit p53 is distinguished from the NF-kappa B transcription activation pathway. Our work, therefore, describes a novel Tax-NF-kappa B p65/RelA pathway that functions to inhibit p53 but does not require NF-kappa B transcription activity. C1 NCI, Tumor Virus Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Brady, JN (reprint author), NCI, Tumor Virus Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM bradyj@exchange.nih.gov NR 63 TC 58 Z9 61 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 MAR 18 PY 2005 VL 280 IS 11 BP 10326 EP 10332 DI 10.1074/jbc.M412643200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905HQ UT WOS:000227559600072 PM 15611068 ER PT J AU Park, JB Levine, M AF Park, JB Levine, M TI Cloning, sequencing, and characterization of alternatively spliced glutaredoxin 1 cDNA and its genomic gene - Chromosomal localization, mRNA stability, and origin of pseudogenes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID RIBONUCLEOSIDE-DIPHOSPHATE REDUCTASE; PROTEIN DISULFIDE-ISOMERASE; HYDROGEN DONOR SYSTEM; THIOLTRANSFERASE GLUTAREDOXIN; HUMAN NEUTROPHILS; S-THIOLATION; GLUTATHIONE; PURIFICATION; ACTIVATION; EXPRESSION AB Alternatively spliced human glutaredoxin (Grx1(as)) cDNA was isolated from a neutrophil cDNA library, using a P-32-labeled human glutaredoxin (Grx1) cDNA probe under non-stringent conditions. The sequence of Grx1as cDNA indicated that the open reading frame of the gene was identical to the open reading frame of the previously reported first human glutaredoxin ( Grx1) cDNA, but the 3'- untranslated region of Grx1as was not homologous to Grx1 cDNA. Northern blot and RT-PCR analyses showed Grx1as mRNA was expressed in normal human neutrophils and transformed cells including U937, HL-60, THP, and Jurkat cells. Cloning and sequencing of the genomic gene corresponding to Grx1as cDNA showed that two different glutaredoxin cDNAs ( Grx1as and Grx1) were generated from the same genomic gene via alternative splicing. Origination of Grx1as and Grx1 from the same gene was confirmed by chromosomal localization of the Grx1as gene to chromosome 5q13, the same location where the Grx1 gene was localized previously. During screening of the Grx1(as) genomic gene, two additional glutaredoxin pseudogenes were also isolated. Surprisingly, these pseudogenes contained 3'-untranslated regions that were nearly identical to the 3'-untranslated regions of Grx1(as), not Grx1, cDNA. Because 3'-untranslated regions may be important in stabilizing mRNAs, the effect of the two 3'-untranslated regions of Grx1 and Grx1(as) on mRNA stability was investigated using luciferase reporter vectors with the 3'-untranslated regions. Luciferase activity was 2.6-fold greater in cells transfected with the reporter vector containing the 3'-untranslated region of Grx1as cDNA compared with the 3'-untranslated region of Grx1 cDNA. These data indicate that Grx1as cDNA is an alternatively spliced human Grx1 cDNA and that the Grx1(as) 3'-untranslated region may have a role in stabilizing mRNA. C1 NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bethesda, MD 20892 USA. USDA ARS, Beltsville Human Nutr Res Ctr, Phytonutrients Lab, Beltsville, MD 20770 USA. RP Levine, M (reprint author), NIDDK, Mol & Clin Nutr Sect, Digest Dis Branch, NIH, Bldg 10,Rm 4D52,MSC 1372, Bethesda, MD 20892 USA. EM markL@mail.nih.gov FU NIDDK NIH HHS [Z01 DK 54506] NR 30 TC 5 Z9 5 U1 1 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 18 PY 2005 VL 280 IS 11 BP 10427 EP 10434 DI 10.1074/jbc.M412450200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905HQ UT WOS:000227559600084 PM 15637068 ER PT J AU Zheng, WP Schwarzer, D LeBeau, A Weller, JL Klein, DC Cole, PA AF Zheng, WP Schwarzer, D LeBeau, A Weller, JL Klein, DC Cole, PA TI Cellular stability of serotonin N-acetyltransferase conferred by phosphonodifluoromethylene alanine (Pfa) substitution for Ser-205 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXPRESSED PROTEIN LIGATION; TYROSINE PHOSPHORYLATION; CRYSTAL-STRUCTURE; MELATONIN SYNTHESIS; CHEMICAL LIGATION; PHOSPHOSERINE; KINASE; INHIBITION; ENZYME; SEMISYNTHESIS AB Large changes in the activity of serotonin N-acetyltransferase (arylalkylamine N-acetyltransferase, AANAT) in the pineal gland control the rhythmic production of the timekeeping hormone melatonin. The activity of AANAT reflects changes in the amount and activation state of the AANAT protein, both of which increase at night. The molecular basis of this regulation is now becoming known, and recent data indicate that this involves phosphorylation- dependent binding to the 14-3-3 protein at two sites, one of which, Ser-205, is located several residues from the C terminus. In this study, we determined whether substitution of this residue with a non-hydrolyzable the phosphoserine/phosphothreonine mimetic would promote binding to the 14-3-3 protein and enhance cellular stability. To accomplish this, a C-terminal AANAT peptide containing the phosphonodifluoromethylene alanine at Ser-205 was synthesized and fused to bacterially expressed AANAT(30-199) using expressed protein ligation. The resulting semisynthetic protein has enhanced affinity for the expressed 14-3-3 protein and exhibits greater cellular stability in microinjection experiments, as compared with the unmodified AANAT. Enhanced 14-3-3 binding was also observed using humanized ovine AANAT, which has a different C-terminal sequence (Gly-Cys) than the ovine enzyme (Asp-Arg), indicating that that characteristic is not unique to the ovine enzyme. These studies provide the first evidence that substitution of Ser-205 with the stable phosphomimetic amino acid phosphonodifluoromethylene alanine enhances binding to 14-3-3 and the cellular stability of AANAT and are consistent with the view that Ser-205 phosphorylation plays a critical role in the regulation of AANAT activity and melatonin production. C1 Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. NICHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Cole, PA (reprint author), Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA. EM pcole@jhmi.edu OI Schwarzer, Dirk/0000-0002-7477-3319 NR 40 TC 30 Z9 31 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 MAR 18 PY 2005 VL 280 IS 11 BP 10462 EP 10467 DI 10.1074/jbc.M412283200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905HQ UT WOS:000227559600088 PM 15632116 ER PT J AU Zhu, GZ Fujii, K Belkina, N Liu, Y James, M Herrero, J Shaw, S AF Zhu, GZ Fujii, K Belkina, N Liu, Y James, M Herrero, J Shaw, S TI Exceptional disfavor for proline at the P+1 position among AGC and CAMK kinases establishes reciprocal specificity between them and the proline-directed kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; STRUCTURAL BASIS; SUBSTRATE RECOGNITION; PHOSPHORYLASE-KINASE; PEPTIDE SPECIFICITY; CRYSTAL-STRUCTURE; DETERMINANTS; ACTIVATION; COMPLEX; MOTIFS AB To precisely regulate critical signaling pathways, two kinases that phosphorylate distinct sites on the same protein substrate must have mutually exclusive specificity. Evolution could assure this by designing families of kinase such as basophilic kinases and proline-directed kinase with distinct peptide specificity; their reciprocal peptide specificity would have to be very complete, since recruitment of substrate allows phosphorylation of even rather poor phosphorylation sites in a protein. Here we report a powerful evolutionary strategy that assures distinct substrates for basophilic kinases (PKA, PKG and PKC (AGC) and calmodulin-dependent protein kinase (CAMK)) and proline-directed kinase, namely by the presence or absence of proline at the P+1 position in substrates. Analysis of degenerate and non-degenerate peptides by in vitro kinase assays reveals that proline at the P+1 position in substrates functions as a "veto" residue in substrate recognition by AGC and CAMK kinases. Furthermore, analysis of reported substrates of two typical basophilic kinases, protein kinase C and protein kinase A, shows the lowest occurrence of proline at the P+1 position. Analysis of crystal structures and sequence conservation provides a molecular basis for this disfavor and illustrate its generality. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. AxCell Biosci, Newtown, PA 18940 USA. RP Shaw, S (reprint author), NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. EM sshaw@nih.gov NR 35 TC 33 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 MAR 18 PY 2005 VL 280 IS 11 BP 10743 EP 10748 DI 10.1074/jbc.M413159200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905HQ UT WOS:000227559600120 PM 15647260 ER PT J AU Liu, XF Yuan, H Fu, BJ Disbrow, GL Apolinario, T Tomaic, V Kelley, ML Baker, CC Huibregtse, J Schlegel, R AF Liu, XF Yuan, H Fu, BJ Disbrow, GL Apolinario, T Tomaic, V Kelley, ML Baker, CC Huibregtse, J Schlegel, R TI The E6AP ubiquitin ligase is required for transactivation of the hTERT promoter by the human papillomavirus E6 oncoprotein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TELOMERASE REVERSE-TRANSCRIPTASE; CALCIUM-INDUCED DIFFERENTIATION; TUMOR-SUPPRESSOR PROTEIN; HUMAN EPITHELIAL-CELLS; TYPE-16 E6; C-MYC; CATALYTIC SUBUNIT; HUMAN KERATINOCYTES; MUTATIONAL ANALYSIS; ANGELMAN-SYNDROME AB Most human cancer cells display increased telomerase activity that appears to be critical for continued cell proliferation and tumor formation. The E6 protein of malignancy-associated human papillomaviruses increases cellular telomerase in primary human keratinocytes at least partly via transcriptional activation of the telomerase catalytic subunit, hTERT. In the present study, we investigated whether E6AP, a ubiquitin ligase well known for binding and mediating some of the activities of the E6 oncoprotein, participated in the transactivation of the hTERT promoter. Our results demonstrate that E6 mutants that fail to bind E6AP are also defective for increasing telomerase activity and transactivating the hTERT promoter. More importantly, E6AP knock-out mouse cells and small interfering RNA techniques demonstrated that E6AP was required for hTERT promoter transactivation in both mouse and human cells. Neither E6 nor E6AP bound to the hTERT promoter or activated the promoter in the absence of the partner protein. With all transactivation-competent E6 proteins, induction of the hTERT promoter was dependent upon E box elements in the core promoter. It appears, therefore, that E6-mediated activation of the hTERT promoter requires a complex of E6-E6AP to engage the hTERT promoter and that activation is dependent upon Myc binding sites in the promoter. The recruitment of a cellular ubiquitin ligase to the hTERT promoter during E6-mediated transcriptional activation suggests a role for the local ubiquitination (and potential degradation) of promoter-associated regulatory proteins, including the Myc protein. C1 Georgetown Univ, Dept Pathol & Oncol, Sch Med, Washington, DC 20057 USA. NCI, Cellular Oncol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Texas, Inst Cellular & Mol Biol, Sect Mol Genet & Microbiol, Austin, TX 78712 USA. RP Schlegel, R (reprint author), Georgetown Univ, Med Ctr, Dept Pathol, 3900 Reservoir Rd,NW, Washington, DC 20057 USA. EM schleger@georgetown.edu RI Yuan, Hang/E-8670-2010 FU NCI NIH HHS [R01CA106440, R01CA53371] NR 87 TC 66 Z9 74 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 MAR 18 PY 2005 VL 280 IS 11 BP 10807 EP 10816 DI 10.1074/jbc.M410343200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905HQ UT WOS:000227559600128 PM 15655249 ER PT J AU Panchal, RG Halverson, KM Ribot, W Lane, D Kenny, T Abshire, TG Ezzell, JW Hoover, TA Powell, B Little, S Kasianowicz, JJ Bavari, S AF Panchal, RG Halverson, KM Ribot, W Lane, D Kenny, T Abshire, TG Ezzell, JW Hoover, TA Powell, B Little, S Kasianowicz, JJ Bavari, S TI Purified Bacillus anthracis lethal toxin complex formed in Vitro and during infection exhibits functional and biological activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTECTIVE ANTIGEN COMPONENT; PROTEIN-KINASE KINASE; PLANAR LIPID-BILAYERS; PROTEOLYTIC INACTIVATION; MAMMALIAN-CELLS; FACTOR CLEAVES; EDEMA FACTOR; N-TERMINUS; MEMBRANE; CHANNEL AB Anthrax protective antigen (PA, 83 kDa), a pore-forming protein, upon protease activation to 63 kDa (PA(63)), translocates lethal factor (LF) and edema factor (EF) from endosomes into the cytosol of the cell. The relatively small size of the heptameric PA(63) pore (similar to 12 angstrom) raises questions as to how large molecules such as LF and EF can move through the pore. In addition, the reported high binding affinity between PA and EF/LF suggests that EF/LF may not dissociate but remain complexed with activated PA(63). In this study, we found that purified (PA(63))(7)-LF complex exhibited biological and functional activities similar to the free LF. Purified LF complexed with PA(63) heptamer was able to cleave both a synthetic peptide substrate and endogenous mitogen-activated protein kinase kinase substrates and kill susceptible macrophage cells. Electrophysiological studies of the complex showed strong rectification of the ionic current at positive voltages, an effect similar to that observed if LF is added to the channels formed by heptameric PA(63) pore. Complexes of (PA(63))(7)-LF found in the plasma of infected animals showed functional activity. Identifying active complex in the blood of infected animals has important implications for therapeutic design, especially those directed against PA and LF. Our studies suggest that the individual toxin components and the complex must be considered as critical targets for anthrax therapeutics. C1 USAMRIID, Frederick, MD 21702 USA. NCI SAIC Frederick, NIH, Dev Therapeut Program, Target Struct Based Drug Discovery Grp, Frederick, MD 21702 USA. NIST, Gaithersburg, MD 20899 USA. RP Panchal, RG (reprint author), USAMRIID, 1425 Porter St, Frederick, MD 21702 USA. EM rekha.panchal@amedd.army.mil; sina.bavari@amedd.army.mil NR 37 TC 39 Z9 41 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 MAR 18 PY 2005 VL 280 IS 11 BP 10834 EP 10839 DI 10.1074/jbc.M412210200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 905HQ UT WOS:000227559600131 PM 15644338 ER PT J AU Koshiji, M To, KKW Hammer, S Kumamoto, K Harris, AL Modrich, P Huang, LE AF Koshiji, M To, KKW Hammer, S Kumamoto, K Harris, AL Modrich, P Huang, LE TI HIF-1 alpha induces genetic instability by transcriptionally downregulating MutS alpha expression SO MOLECULAR CELL LA English DT Article ID DNA MISMATCH REPAIR; HYPOXIA-INDUCIBLE FACTOR; NONPOLYPOSIS COLORECTAL-CANCER; CELL-CYCLE ARREST; PROMOTER REGION; FACTOR 1-ALPHA; TARGET GENES; TUMOR-CELLS; P53; HEREDITARY AB Hypoxia promotes genetic instability by undefined mechanisms. The transcription factor HIF-1 alpha is crucial for the cellular response to hypoxia and is frequently overexpressed in human cancers, resulting in the activation of genes essential for cell survival. Here, we demonstrate that HIF-1 alpha is responsible for genetic instability at the nucleotide level by inhibiting MSH2 and MSH6, thereby decreasing levels of the MSH2-MSH6 complex, MutS alpha, which recognizes base mismatches. HIF-1 alpha displaces the transcriptional activator Myc from Sp1 binding to repress MutS alpha expression in a p53-dependent manner; Sp1 serves as a molecular switch by recruiting HIF-1 alpha to the gene promoter under hypoxia. Furthermore, in human sporadic colon cancers, HIF-1 alpha overexpression is statistically associated with the loss of MSH2 expression, especially when p53 is immunochemically undetectable. These findings indicate that the regulation of DNA repair is an integral part of the hypoxic response, providing molecular insights into the mechanisms underlying hypoxia-induced genetic instability. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. John Radcliffe Hosp, Weatherall Inst Mol Med, Mol Oncol Lab, Canc Res UK, Oxford OX3 9DS, England. Duke Univ, Ctr Med, Howard Hughes Med Inst, Durham, NC 27710 USA. Duke Univ, Dept Biochem, Durham, NC 27710 USA. RP Huang, LE (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. EM huange@mail.nih.gov RI To, Kenneth /M-4500-2013 OI To, Kenneth /0000-0003-2755-0283 FU NIGMS NIH HHS [GM45190] NR 56 TC 202 Z9 210 U1 1 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR 18 PY 2005 VL 17 IS 6 BP 793 EP 803 DI 10.1016/j.molcel.2005.02.015 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 910EF UT WOS:000227912400008 PM 15780936 ER PT J AU Fan, HY Trotter, KW Archer, TK Kingston, RE AF Fan, HY Trotter, KW Archer, TK Kingston, RE TI Swapping function of two chromatin remodeling complexes SO MOLECULAR CELL LA English DT Article ID IN-VIVO; NUCLEAR RECEPTORS; HISTONE OCTAMER; NUCLEOSOME; TRANSCRIPTION; ISWI; SWI/SNF; BRG1; RECONSTITUTION; DISRUPTION AB SWI/SNF- and ISWI-based complexes have distinct yet overlapping chromatin-remodeling activities in vitro and perform different roles in vivo. This leads to the hypothesis that the distinct remodeling functions of these complexes are specifically required for distinct biological tasks. By creating and characterizing chimeric proteins of BRG1 and SNF2h, the motor proteins of human SWI/SNF- and ISWI-based complexes, respectively, we found that a region that includes the ATPase domain specifies the outcome of the remodeling reaction in vitro. A chimeric protein based on BRG1 but containing the SNF2h ATPase domain formed an intact SWI/SNF complex that remodeled like SNF2h. This altered-function complex was active for remodeling and could stimulate expression from some, but not all, SWI/SNF responsive promoters in vivo. Thus, we were able to separate domains of BRG1 responsible for function from those responsible for SWI/SNF complex formation and demonstrate that remodeling functions are not interchangeable in vivo. C1 Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Archer, TK (reprint author), Massachusetts Gen Hosp, Dept Mol Biol, Boston, MA 02114 USA. EM archer1@niehs.nih.gov; kingston@frodo.mgh.harvard.edu NR 34 TC 51 Z9 51 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1097-2765 J9 MOL CELL JI Mol. Cell PD MAR 18 PY 2005 VL 17 IS 6 BP 805 EP 815 DI 10.1016/j.molcel.2005.02.024 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 910EF UT WOS:000227912400009 PM 15780937 ER PT J AU Yuspa, SH Epstein, EH AF Yuspa, SH Epstein, EH TI An anchor for tumor cell invasion SO SCIENCE LA English DT Editorial Material ID DYSTROPHIC EPIDERMOLYSIS-BULLOSA; TRANSFORMING-GROWTH-FACTOR; COLLAGEN VII; CARCINOMA C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94108 USA. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. EM sy12j@nih.gov; epsteine@derm.ucsf.edu NR 10 TC 7 Z9 8 U1 0 U2 2 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 MAR 18 PY 2005 VL 307 IS 5716 BP 1727 EP 1728 DI 10.1126/science.1110346 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 909TP UT WOS:000227883900029 PM 15774745 ER PT J AU Feder, N AF Feder, N TI NIH must tell whole truth about conflicts of interest SO NATURE LA English DT Letter C1 NIH, Bethesda, MD 20817 USA. RP Feder, N (reprint author), NIH, 2 Democracy Plaza, Bethesda, MD 20817 USA. NR 1 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 0028-0836 J9 NATURE JI Nature PD MAR 17 PY 2005 VL 434 IS 7031 BP 271 EP 271 DI 10.1038/434271a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 907KG UT WOS:000227715100014 PM 15772624 ER PT J AU Ross, MT Grafham, DV Coffey, AJ Scherer, S McLay, K Muzny, D Platzer, M Howell, GR Burrows, C Bird, CP Frankish, A Lovell, FL Howe, KL Ashurst, JL Fulton, RS Sudbrak, R Wen, GP Jones, MC Hurles, ME Andrews, TD Scott, CE Searle, S Ramser, J Whittaker, A Deadman, R Carter, NP Hunt, SE Chen, R Cree, A Gunaratne, P Havlak, P Hodgson, A Metzker, ML Richards, S Scott, G Steffen, D Sodergren, E Wheeler, DA Worley, KC Ainscough, R Ambrose, KD Ansari-Lari, MA Aradhya, S Ashwell, RIS Babbage, AK Bagguley, CL Ballabio, A Banerjee, R Barker, GE Barlow, KF Barrett, IP Bates, KN Beare, DM Beasley, H Beasley, O Beck, A Bethel, G Blechschmidt, K Brady, N Bray-Allen, S Bridgeman, AM Brown, AJ Brown, MJ Bonnin, D Bruford, EA Buhay, C Burch, P Burford, D Burgess, J Burrill, W Burton, J Bye, JM Carder, C Carrel, L Chako, J Chapman, JC Chavez, D Chen, E Chen, G Chen, Y Chen, ZJ Chinault, C Ciccodicola, A Clark, SY Clarke, G Clee, CM Clegg, S Clerc-Blankenburg, K Clifford, K Cobley, V Cole, CG Conquer, JS Corby, N Connor, RE David, R Davies, J Davis, C Davis, J Delgado, O DeShazo, D Dhami, P Ding, Y Dinh, H Dodsworth, S Draper, H Dugan-Rocha, S Dunham, A Dunn, M Durbin, KJ Dutta, I Eades, T Ellwood, M Emery-Cohen, A Errington, H Evans, KL Faulkner, L Francis, F Frankland, J Fraser, AE Galgoczy, P Gilbert, J Gill, R Glockner, G Gregory, SG Gribble, S Griffiths, C Grocock, R Gu, YH Gwilliam, R Hamilton, C Hart, EA Hawes, A Heath, PD Heitmann, K Hennig, S Hernandez, J Hinzmann, B Ho, S Hoffs, M Howden, PJ Huckle, EJ Hume, J Hunt, PJ Hunt, AR Isherwood, J Jacob, L Johnson, D Jones, S de Jong, PJ Joseph, SS Keenan, S Kelly, S Kershaw, JK Khan, Z Kioschis, P Klages, S Knights, AJ Kosiura, A Kovar-Smith, C Laird, GK Langford, C Lawlor, S Leversha, M Lewis, L Liu, W Lloyd, C Lloyd, DM Loulseged, H Loveland, JE Lovell, JD Lozado, R Lu, J Lyne, R Ma, J Maheshwari, M Matthews, LH McDowall, J McLaren, S McMurray, A Meidl, P Meitinger, T Milne, S Miner, G Mistry, SL Morgan, M Morris, S Muller, I Mullikin, JC Nguyen, N Nordsiek, G Nyakatura, G O'Dell, CN Okwuonu, G Palmer, S Pandian, R Parker, D Parrish, J Pasternak, S Patel, D Pearce, AV Pearson, DM Pelan, SE Perez, L Porter, KM Ramsey, Y Reichwald, K Rhodes, S Ridler, KA Schlessinger, D Schueler, MG Sehra, HK Shaw-Smith, C Shen, H Sheridan, EM Shownkeen, R Skuce, CD Smith, ML Sotheran, EC Steingruber, HE Steward, CA Storey, R Swann, RM Swarbreck, D Tabor, PE Taudien, S Taylor, T Teague, B Thomas, K Thorpe, A Timms, K Tracey, A Trevanion, S Tromans, AC d'Urso, M Verduzco, D Villasana, D Waldron, L Wall, M Wang, QY Warren, J Warry, GL Wei, XH West, A Whitehead, SL Whiteley, MN Wilkinson, JE Willey, DL Williams, G Williams, L Williamson, A Williamson, H Wilming, L Woodmansey, RL Wray, PW Yen, J Zhang, JK Zhou, JL Zoghbi, H Zorilla, S Buck, D Reinhardt, R Poustka, A Rosenthal, A Lehrach, H Meindl, A Minx, PJ Hillier, LW Willard, HF Wilson, RK Waterston, RH Rice, CM Vaudin, M Coulson, A Nelson, DL Weinstock, G Sulston, JE Durbin, R Hubbard, T Gibbs, RA Beck, S Rogers, J Bentley, DR AF Ross, MT Grafham, DV Coffey, AJ Scherer, S McLay, K Muzny, D Platzer, M Howell, GR Burrows, C Bird, CP Frankish, A Lovell, FL Howe, KL Ashurst, JL Fulton, RS Sudbrak, R Wen, GP Jones, MC Hurles, ME Andrews, TD Scott, CE Searle, S Ramser, J Whittaker, A Deadman, R Carter, NP Hunt, SE Chen, R Cree, A Gunaratne, P Havlak, P Hodgson, A Metzker, ML Richards, S Scott, G Steffen, D Sodergren, E Wheeler, DA Worley, KC Ainscough, R Ambrose, KD Ansari-Lari, MA Aradhya, S Ashwell, RIS Babbage, AK Bagguley, CL Ballabio, A Banerjee, R Barker, GE Barlow, KF Barrett, IP Bates, KN Beare, DM Beasley, H Beasley, O Beck, A Bethel, G Blechschmidt, K Brady, N Bray-Allen, S Bridgeman, AM Brown, AJ Brown, MJ Bonnin, D Bruford, EA Buhay, C Burch, P Burford, D Burgess, J Burrill, W Burton, J Bye, JM Carder, C Carrel, L Chako, J Chapman, JC Chavez, D Chen, E Chen, G Chen, Y Chen, ZJ Chinault, C Ciccodicola, A Clark, SY Clarke, G Clee, CM Clegg, S Clerc-Blankenburg, K Clifford, K Cobley, V Cole, CG Conquer, JS Corby, N Connor, RE David, R Davies, J Davis, C Davis, J Delgado, O DeShazo, D Dhami, P Ding, Y Dinh, H Dodsworth, S Draper, H Dugan-Rocha, S Dunham, A Dunn, M Durbin, KJ Dutta, I Eades, T Ellwood, M Emery-Cohen, A Errington, H Evans, KL Faulkner, L Francis, F Frankland, J Fraser, AE Galgoczy, P Gilbert, J Gill, R Glockner, G Gregory, SG Gribble, S Griffiths, C Grocock, R Gu, YH Gwilliam, R Hamilton, C Hart, EA Hawes, A Heath, PD Heitmann, K Hennig, S Hernandez, J Hinzmann, B Ho, S Hoffs, M Howden, PJ Huckle, EJ Hume, J Hunt, PJ Hunt, AR Isherwood, J Jacob, L Johnson, D Jones, S de Jong, PJ Joseph, SS Keenan, S Kelly, S Kershaw, JK Khan, Z Kioschis, P Klages, S Knights, AJ Kosiura, A Kovar-Smith, C Laird, GK Langford, C Lawlor, S Leversha, M Lewis, L Liu, W Lloyd, C Lloyd, DM Loulseged, H Loveland, JE Lovell, JD Lozado, R Lu, J Lyne, R Ma, J Maheshwari, M Matthews, LH McDowall, J McLaren, S McMurray, A Meidl, P Meitinger, T Milne, S Miner, G Mistry, SL Morgan, M Morris, S Muller, I Mullikin, JC Nguyen, N Nordsiek, G Nyakatura, G O'Dell, CN Okwuonu, G Palmer, S Pandian, R Parker, D Parrish, J Pasternak, S Patel, D Pearce, AV Pearson, DM Pelan, SE Perez, L Porter, KM Ramsey, Y Reichwald, K Rhodes, S Ridler, KA Schlessinger, D Schueler, MG Sehra, HK Shaw-Smith, C Shen, H Sheridan, EM Shownkeen, R Skuce, CD Smith, ML Sotheran, EC Steingruber, HE Steward, CA Storey, R Swann, RM Swarbreck, D Tabor, PE Taudien, S Taylor, T Teague, B Thomas, K Thorpe, A Timms, K Tracey, A Trevanion, S Tromans, AC d'Urso, M Verduzco, D Villasana, D Waldron, L Wall, M Wang, QY Warren, J Warry, GL Wei, XH West, A Whitehead, SL Whiteley, MN Wilkinson, JE Willey, DL Williams, G Williams, L Williamson, A Williamson, H Wilming, L Woodmansey, RL Wray, PW Yen, J Zhang, JK Zhou, JL Zoghbi, H Zorilla, S Buck, D Reinhardt, R Poustka, A Rosenthal, A Lehrach, H Meindl, A Minx, PJ Hillier, LW Willard, HF Wilson, RK Waterston, RH Rice, CM Vaudin, M Coulson, A Nelson, DL Weinstock, G Sulston, JE Durbin, R Hubbard, T Gibbs, RA Beck, S Rogers, J Bentley, DR TI The DNA sequence of the human X chromosome SO NATURE LA English DT Article ID LINKED MENTAL-RETARDATION; MAMMALIAN Y-CHROMOSOME; HUMAN GENOME SEQUENCE; INACTIVATION CENTER; REPEAT HYPOTHESIS; GENE FAMILY; EVOLUTION; MUTATIONS; REGION; RNA AB The human X chromosome has a unique biology that was shaped by its evolution as the sex chromosome shared by males and females. We have determined 99.3% of the euchromatic sequence of the X chromosome. Our analysis illustrates the autosomal origin of the mammalian sex chromosomes, the stepwise process that led to the progressive loss of recombination between X and Y, and the extent of subsequent degradation of the Y chromosome. LINE1 repeat elements cover one-third of the X chromosome, with a distribution that is consistent with their proposed role as way stations in the process of X-chromosome inactivation. We found 1,098 genes in the sequence, of which 99 encode proteins expressed in testis and in various tumour types. A disproportionately high number of mendelian diseases are documented for the X chromosome. Of this number, 168 have been explained by mutations in 113 X-linked genes, which in many cases were characterized with the aid of the DNA sequence. C1 Wellcome Trust Sanger Inst, Cambridge CB10 1SA, England. Baylor Coll Med, Human Genome Sequencing Ctr, Dept Mol & Human Genet, Houston, TX 77030 USA. Inst Mol Biotechnol, D-07745 Jena, Germany. Washington Univ, Genome Sequencing Ctr, St Louis, MO 63108 USA. Max Planck Inst Mol Genet, D-14195 Berlin, Germany. Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany. Univ Munich, D-80336 Munich, Germany. UCL, Galton Lab, HUGO Gen Nomenclature Comm, Dept Biol, London NW1 2HE, England. Penn State Coll Med, Dept Biochem & Mol Biol, Hershey, PA 17033 USA. PE Appl Biosyst, Adv Ctr Genet Technol, Foster City, CA 94404 USA. European Bioinformat Inst, Cambridge CB10 1SD, England. Inst Genet & Biophys, I-80100 Naples, Italy. Univ Edinburgh, Western Gen Hosp, Med Genet Sect, Edinburgh EH4 2XU, Midlothian, Scotland. Univ Paris 05, INSERM, U567,Inst Cochin, Lab Genet & Physiopathol Retards Mentaux, F-75014 Paris, France. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. Deutsch Krebsforschungszentrum, D-69120 Heidelberg, Germany. GSF, Natl Res Ctr Environm Hlth, Inst Human Genet, D-85764 Neuherberg, Germany. RZPD Resource Ctr Genome Res, D-14059 Berlin, Germany. NHGRI, NIH, Bethesda, MD 20892 USA. NIA, Genet Lab, Baltimore, MD 21224 USA. Duke Univ, Inst Genome Sci & Policy, Durham, NC 27708 USA. RP Ross, MT (reprint author), Wellcome Trust Sanger Inst, Wellcome Trust Genome Campus, Cambridge CB10 1SA, England. EM mtr@sanger.ac.uk RI Hubbard, Tim/C-2567-2008; Frankish, Adam/G-6545-2011; Evans, Kathryn /I-5910-2012; Johnson, David/A-3907-2011; Norouzi, Neil/H-2530-2012; Glockner, Gernot/A-7800-2010; Meitinger, Thomas/O-1318-2015; Francis, Fiona/B-5854-2016; OI Hubbard, Tim/0000-0002-1767-9318; Trevanion, Stephen/0000-0002-4862-3333; Durbin, Richard/0000-0002-9130-1006; Keenan, Stephen/0000-0002-9141-7690; Johnson, David/0000-0003-0887-3343; Glockner, Gernot/0000-0002-9061-1061; Wilming, Laurens/0000-0002-4154-7358; Gilbert, James/0000-0001-8079-3159; Andrews, Dan/0000-0003-3922-6376; Hunt, Adrienne/0000-0002-1227-0310; Hunt, Sarah/0000-0002-8350-1235; Delgado, Oliver/0000-0003-2547-5857; Bruford, Elspeth/0000-0002-8380-5247; Howe, Kevin/0000-0002-1751-9226; BALLABIO, Andrea/0000-0003-1381-4604; Davidson, Claire/0000-0002-4910-8202 FU NHGRI NIH HHS [U54 HG003273] NR 67 TC 553 Z9 1302 U1 7 U2 74 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 17 PY 2005 VL 434 IS 7031 BP 325 EP 337 DI 10.1038/nature03440 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 907KG UT WOS:000227715100040 PM 15772651 ER PT J AU Lindberg, DAB Humphreys, BL AF Lindberg, DAB Humphreys, BL TI 2015 - The future of medical libraries SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NIH, Natl Lib Med, Bethesda, MD 20892 USA. RP Lindberg, DAB (reprint author), NIH, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. NR 3 TC 28 Z9 31 U1 0 U2 10 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 MAR 17 PY 2005 VL 352 IS 11 BP 1067 EP + DI 10.1056/NEJMp048190 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 906PU UT WOS:000227655000002 PM 15784661 ER PT J AU Solomon, SD McMurray, JJV Pfeffer, MA Wittes, J Fowler, R Finn, P Anderson, WF Zauber, A Hawk, E Bertagnolli, M AF Solomon, SD McMurray, JJV Pfeffer, MA Wittes, J Fowler, R Finn, P Anderson, WF Zauber, A Hawk, E Bertagnolli, M CA APC Study Investigators TI Cardiovascular risk associated with celecoxib in a clinical trial for colorectal adenoma prevention SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SELECTIVE CYCLOOXYGENASE-2 INHIBITORS; ACUTE MYOCARDIAL-INFARCTION; RANDOMIZED CONTROLLED-TRIAL; GASTROINTESTINAL TOXICITY; RHEUMATOID-ARTHRITIS; THROMBOTIC EVENTS; ARACHIDONIC-ACID; COX-2 INHIBITION; ROFECOXIB AB BACKGROUND: Selective cyclooxygenase-2 (COX-2) inhibitors have come under scrutiny because of reports suggesting an increased cardiovascular risk associated with their use. Experimental research suggesting that these drugs may contribute to a prothrombotic state provides support for this concern. METHODS: We reviewed all potentially serious cardiovascular events among 2035 patients with a history of colorectal neoplasia who were enrolled in a trial comparing two doses of celecoxib (200 mg or 400 mg twice daily) with placebo for the prevention of colorectal adenomas. All deaths were categorized as cardiovascular or noncardiovascular, and nonfatal cardiovascular events were categorized in a blinded fashion according to a prespecified scheme. RESULTS: For all patients except those who died, 2.8 to 3.1 years of follow-up data were available. A composite cardiovascular end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure was reached in 7 of 679 patients in the placebo group (1.0 percent), as compared with 16 of 685 patients receiving 200 mg of celecoxib twice daily (2.3 percent; hazard ratio, 2.3; 95 percent confidence interval, 0.9 to 5.5) and with 23 of 671 patients receiving 400 mg of celecoxib twice daily (3.4 percent; hazard ratio, 3.4; 95 percent confidence interval, 1.4 to 7.8). Similar trends were observed for other composite end points. On the basis of these observations, the data and safety monitoring board recommended early discontinuation of the study drug. CONCLUSIONS: Celecoxib use was associated with a dose-related increase in the composite end point of death from cardiovascular causes, myocardial infarction, stroke, or heart failure. In light of recent reports of cardiovascular harm associated with treatment with other agents in this class, these data provide further evidence that the use of COX-2 inhibitors may increase the risk of serious cardiovascular events. C1 Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div, Boston, MA 02115 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Surg, Boston, MA 02115 USA. Univ Glasgow, Western Infirm, Glasgow G11 6NT, Lanark, Scotland. Stat Collaborat, Washington, DC USA. NCI, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Solomon, SD (reprint author), Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med,Cardiovasc Div, 75 Francis St, Boston, MA 02115 USA. EM ssolomon@rics.bwh.harvard.edu RI Solomon, Scott/I-5789-2013; OI mcmurray, john/0000-0002-6317-3975 NR 38 TC 1283 Z9 1344 U1 5 U2 31 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 MAR 17 PY 2005 VL 352 IS 11 BP 1071 EP 1080 DI 10.1056/NEJMoa050405 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 906PU UT WOS:000227655000004 PM 15713944 ER PT J AU Sharifi, N Mofrad, PS AF Sharifi, N Mofrad, PS TI Vascular events after acute infection or vaccination SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. Georgetown Univ Hosp, Washington, DC 20010 USA. RP Sharifi, N (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 17 PY 2005 VL 352 IS 11 BP 1152 EP 1152 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 906PU UT WOS:000227655000025 ER PT J AU Weber, HO Ludwig, RL Morrison, D Kotlyarov, A Gaestel, M Vousden, KH AF Weber, HO Ludwig, RL Morrison, D Kotlyarov, A Gaestel, M Vousden, KH TI HDM2 phosphorylation by MAPKAP kinase 2 SO ONCOGENE LA English DT Article DE HDM2; MAPKAP kinase 2; p53; phosphorylation ID CELL-CYCLE ARREST; UBIQUITIN-PROTEIN LIGASE; RING-FINGER DOMAIN; NUCLEAR EXPORT; P53 STABILITY; ONCOPROTEIN MDM2; UV-RADIATION; DNA-DAMAGE; DEGRADATION; PATHWAY AB p53 stability is regulated by HDM2, a RING domain protein that acts as an E3 ligase to ubiquitinate p53 and target its degradation. Phosphorylation of HDM2 on serine 166 by AKT has been shown to enhance HDM2 activity and promote the degradation of p53. Here, we show that MAPKAP kinase 2 ( MK2) can phosphorylate HDM2 on serine 157 and 166 in vitro. Treatment of cells with anisomycin, which activates MK2, also results in phosphorylation of HDM2 on serine 157 and 166 in vivo. Mutation of the MK2 phosphorylation sites in HDM2 to aspartic acid renders HDM2 slightly more active in the degradation of p53, and mouse cells deficient for MK2 show reduced Mdm2 phosphorylation and elevated levels of p53 protein. Together, our results suggest that MK2 may act to dampen the extent and duration of the p53 response. C1 Beatson Inst Canc Res, Glasgow G61 1BD, Lanark, Scotland. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. Hannover Med Sch, Inst Biochem Physiol Chem, D-30625 Hannover, Germany. RP Vousden, KH (reprint author), Beatson Inst Canc Res, Garscube Estate, Glasgow G61 1BD, Lanark, Scotland. EM k.vousden@beatson.gla.ac.uk OI Gaestel, Matthias/0000-0002-4944-4652 NR 49 TC 41 Z9 43 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 17 PY 2005 VL 24 IS 12 BP 1965 EP 1972 DI 10.1038/sj.onc.1208389 PG 8 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 906YU UT WOS:000227681900001 PM 15688025 ER PT J AU Diamond, JS AF Diamond, JS TI Deriving the glutamate clearance time course from transporter currents in CA1 hippocampal astrocytes: Transmitter uptake gets faster during development SO JOURNAL OF NEUROSCIENCE LA English DT Article DE diffusion; spillover; hippocampus; transporter; uptake; synaptic ID SYNAPTICALLY RELEASED GLUTAMATE; D-ASPARTATE RECEPTORS; NMDA RECEPTORS; RAT-BRAIN; SYNAPSES; DIFFUSION; ACTIVATION; SPILLOVER; SUBTYPES; NEUROTRANSMITTER AB At many excitatory synapses, the neurotransmitter glutamate diffuses beyond the synaptic cleft to activate extrasynaptic targets. The extent and impact of such transmitter "spillover" on the processing capacity of neuronal networks are unclear, in part because it remains unknown how far transmitter diffuses from its point of release before being removed from the extracellular space by high-affinity glutamate transporters. Synaptically activated, transporter-mediated currents (STCs) recorded in hippocampal astrocytes provide an experimental measure of glutamate uptake, but the time course of the STC may be shaped, or "filtered," by other factors and therefore not represent a direct indication of clearance rate. Here, STCs were recorded from astrocytes in rat hippocampal slices under conditions in which uptake capacity was reduced and the STC decay reflected a slowed rate of glutamate clearance. The temporal characteristics of the filtering mechanisms were extracted from these responses, and the glutamate clearance time course in control conditions was derived. The results indicate that glutamate can be cleared from the extrasynaptic space within 1 ms. Clearance is fastest in adult neuropil, corresponding to a developmental increase in glial transporter expression. Synaptically released glutamate is taken up at the same rate as glutamate released via flash photolysis, indicating that the spatial location of transporters relative to the site of glutamate release does not affect the time course of clearance. Slower clearance in young animals would permit glutamate to diffuse greater distances, indicating a particularly important role for extrasynaptic receptors early in development. C1 NINDS, Synapt Physiol Unit, NIH, Bethesda, MD 20892 USA. RP Diamond, JS (reprint author), NINDS, Synapt Physiol Unit, NIH, Bldg 35,Room 3C-1000,35 Convent Dr, Bethesda, MD 20892 USA. EM diamondj@ninds.nih.gov RI Diamond, Jeffrey/C-1835-2015 OI Diamond, Jeffrey/0000-0002-1770-2629 NR 45 TC 84 Z9 86 U1 1 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 MAR 16 PY 2005 VL 25 IS 11 BP 2906 EP 2916 DI 10.1523/JNEUROSCI.5125-04.2005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 906WD UT WOS:000227674300014 PM 15772350 ER PT J AU Engels, EA Goedert, JJ AF Engels, EA Goedert, JJ TI Human immunodeficiency virus/acquired immunodeficiency syndrome and cancer: Past, present, and future SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID ACTIVE ANTIRETROVIRAL THERAPY; EPSTEIN-BARR-VIRUS; SWISS HIV COHORT; KAPOSIS-SARCOMA; DNA-SEQUENCES; AIDS; RISK; INFECTION; LYMPHOMA; PEOPLE C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS, Bethesda, MD 20892 USA. RP Goedert, JJ (reprint author), NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS, 6120 Execut Blvd,EPS 8012, Bethesda, MD 20892 USA. EM goedertj@mail.nih.gov NR 19 TC 33 Z9 34 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 16 PY 2005 VL 97 IS 6 BP 407 EP 409 DI 10.1093/jnci/dji085 PG 3 WC Oncology SC Oncology GA 907IR UT WOS:000227710600002 PM 15769998 ER PT J AU Andriole, GL Levin, DL Crawford, ED Gelmann, ER Pinsky, PF Chia, D Kramer, BS Reding, D Church, TR Grubb, RL Izmirlian, G Ragard, LR Clapp, JD Prorok, PC Gohagan, JK AF Andriole, GL Levin, DL Crawford, ED Gelmann, ER Pinsky, PF Chia, D Kramer, BS Reding, D Church, TR Grubb, RL Izmirlian, G Ragard, LR Clapp, JD Prorok, PC Gohagan, JK CA PLCO Project Team TI Prostate cancer screening in the prostate, lung, colorectal and Ovarian (PLCO) Cancer Screening Trial: Findings from the initial screening round of a randomized trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID DIGITAL RECTAL EXAMINATION; WHITE MEN; ANTIGEN; UPDATE; NG/ML; BLACK AB Background: The benefit of screening for prostate cancer using prostate-specific antigen (PSA) testing and digital rectal examination (DRE) is uncertain and is under evaluation in a randomized prospective trial, the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. Although the final results are several years away, the initial round of screening is complete. We describe the population enrolled in the PLCO trial, their baseline PSA and DRE screening results, and diagnostic follow-up results during the first year of follow-up. Methods: A total of 38350 men were randomly assigned to the screening arm of the PLCO trial from November 1993 through June 2001. Men were advised to seek diagnostic follow-up from their primary care provider if their DRE was suspicious for cancer and/or if their serum PSA level was higher than 4 ng/mL. PLCO trial staff obtained records related to diagnostic follow-up. Results: Compliance with both screening tests was high (more than 89%). At screening, 7.5% of men had a positive DRE (i.e., suspicious for cancer) and 7.9% had a PSA level higher than 4 ng/mL. Of the men with positive screening tests, 74.2% underwent additional diagnostic testing, and 31.5% underwent a prostatic biopsy within 1 year. Overall, 1.4% of the men in the screening arm were diagnosed with prostate cancer, the majority of whom had clinically localized cancer. These compliance, biopsy, and cancer detection rates appear to be representative of contemporary practice patterns. Conclusion: The PLCO trial is evaluating PSA- and DRE-based screening for prostate cancer in a clinically valid manner. Whether such screening will result in a reduction of prostate cancer mortality cannot be answered until the randomized comparison is completed. C1 Washington Univ, Sch Med, Div Urol Surg, St Louis, MO 63110 USA. NCI, Early Detect Res Grp, Div Canc Prevent,NIH, Bethesda, MD 20892 USA. NCI, Biometry Res Grp, NIH, Bethesda, MD 20892 USA. Univ Colorado, Denver, CO 80202 USA. Georgetown Univ, Lombardi Canc Ctr, Washington, DC USA. Univ Calif Los Angeles, Immunogenet Ctr, Los Angeles, CA USA. NIH, Off Dis Prevent, Bethesda, MD 20892 USA. Marshfield Med Res & Educ Fdn, Marshfield, WI USA. Univ Minnesota, Minneapolis, MN USA. NCI, Urol Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Westat Corp, Rockville, MD USA. Informat Management Serv Inc, Rockville, MD USA. RP Andriole, GL (reprint author), Washington Univ, Sch Med, Div Urol Surg, 4960 Childrens Pl,Campus Box 8242, St Louis, MO 63110 USA. EM andrioleg@insnotes.wustl.edu OI Church, Timothy R./0000-0003-3292-5035 NR 18 TC 135 Z9 142 U1 0 U2 3 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 MAR 16 PY 2005 VL 97 IS 6 BP 433 EP 438 DI 10.1093/jnci/dji065 PG 6 WC Oncology SC Oncology GA 907IR UT WOS:000227710600009 PM 15770007 ER PT J AU Taplin, SH Barlow, WE Ulcickas-Yood, M Westbrook, EO Geiger, AM Bischoff, K Ichikawa, L AF Taplin, SH Barlow, WE Ulcickas-Yood, M Westbrook, EO Geiger, AM Bischoff, K Ichikawa, L TI Breast cancer screening comes full circle SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter ID STAGE C1 NCI, Appl Res Program, Rockville, MD 20852 USA. Univ Washington, Seattle, WA 98195 USA. Grp Hlth Cooperat Puget Sound, Seattle, WA USA. Henry Ford Hlth Syst, Detroit, MI USA. Kaiser Permanente So Calif, Pasadena, CA USA. Kaiser Permanente Colorado, Denver, CO USA. RP Taplin, SH (reprint author), NCI, Appl Res Program, 6310 Execut Blvd, Rockville, MD 20852 USA. EM Taplins@mail.nih.gov NR 7 TC 0 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAR 16 PY 2005 VL 97 IS 6 BP 461 EP 461 DI 10.1093/jnci/dji061 PG 1 WC Oncology SC Oncology GA 907IR UT WOS:000227710600013 PM 15770012 ER PT J AU Kim, JA Park, S Kim, K Rhee, SG Kang, SW AF Kim, JA Park, S Kim, K Rhee, SG Kang, SW TI Activity assay of mammalian 2-cys peroxiredoxins using yeast thioredoxin reductase system SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE 2-cys peroxiredoxin; yeast thioredoxin; yeast thioredoxin reductase; thioredoxin peroxidase ID CYSTEINE-SULFINIC ACID; NECROSIS-FACTOR-ALPHA; OXIDATIVE STRESS; ESCHERICHIA-COLI; SITE CYSTEINE; IN-VIVO; C-MYC; SELENOCYSTEINE; EXPRESSION; OVEREXPRESSION AB 2-Cys peroxiredoxin (Prx) is a novel cellular peroxidase that reduces peroxides in the presence of thioredoxin. thioredoxin reductase, and nicotinamide adenine dinucleotide phosphate (NADPH) and that functions in H2O2-mediated signal transduction. Recent studies have shown that 2-cys Prx can be inactivated by cysteine overoxidation in conditions of oxidative stress. Therefore, peroxidase activity, rather than the protein level, of 2-cys Prx is the more important measure to predict its cellular function. Here, we introduce a modified activity assay method for mammalian 2-cys Prx based on yeast nonselenium thioredoxin reductase. Yeast thioredoxin reductase is expressed in Escherichia coli cells and purified at high yield (40 mg/L of culture broth) as an active flavoprotein by combined diethyl aminoethyl (DEAE) and phenyl hydrophobic chromatogaphy. The optimal concentrations of yeast thioredoxin and thioredoxin reductase required to achieve maximum mammalian 2-cys Prx activity are 3.0 and 1.5 mu M, respectively. This modified assay method is useful for measuring 2-cys Prx activity in cell lysates and can also be adapted for a 96-well plate reader for high-throughput screening of chemical compounds that target 2-cys Prx. (c) 2004 Elsevier Inc. All rights reserved. C1 Ewha Womans Univ, Ctr Cell Signaling Res, Seoul, South Korea. Ewha Womans Univ, Div Mol Life Sci, Seoul, South Korea. Chonnam Natl Univ, Coll Home Econ, Dept Food & Nutr, Kwangju, South Korea. NHLBI, Lab Cell Signaling, NIH, Bethesda, MD 20892 USA. RP Kang, SW (reprint author), Ewha Womans Univ, Ctr Cell Signaling Res, Seoul, South Korea. EM kangsw@ewha.ac.kr NR 41 TC 36 Z9 38 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAR 15 PY 2005 VL 338 IS 2 BP 216 EP 223 DI 10.1016/j.ab.2004.12.008 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 907XG UT WOS:000227750900006 PM 15745741 ER PT J AU Vasan, RS Sullivan, LM Wilson, PWF Sempos, CT Sundstrom, J Kannel, WB Levy, D D'Agostino, RB AF Vasan, RS Sullivan, LM Wilson, PWF Sempos, CT Sundstrom, J Kannel, WB Levy, D D'Agostino, RB TI Relative importance of borderline and elevated levels of coronary heart disease risk factors SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID BLOOD-PRESSURE; CARDIOVASCULAR-DISEASE; ATTRIBUTABLE FRACTIONS; SERUM-CHOLESTEROL; TASK-FORCE; PREVENTION; POPULATION; PREDICTION; MORTALITY; SMOKING AB Background: Clinical trials indicate that a sizable proportion of adults have multiple borderline coronary risk factors and may benefit from treatment. Objective: To estimate the relative and absolute contributions of borderline and elevated risk factors to the population burden of coronary heart disease (CHD) events. Design: A prospective cohort study and a national crosssectional survey. Setting: The Framingham Study and the Third National Health and Nutrition Examination Survey (NHANES III). Participants: White non-Hispanic persons in the Framingham Study and in NHANES III who were between 35 to 74 years of age and had no CHD. Measurements: Occurrence of first CHD events according to 5 major CHD risk factors: blood pressure, low-density lipoprotein and high-density lipoprotein cholesterol levels, glucose intolerance, and smoking. Three categories - optimal, borderline, and elevated-were defined for each risk factor per national guide-lines. Sex-specific 10-year CHD event rates from the Framingham Study were applied to numbers of at-risk individuals estimated from NHANES III and the 2000 U.S. Census. Results: Twenty-six percent of men and 41% of women had at least 1 borderline risk factor in NHANES III. According to estimates, more than 90% of CHD events will occur in individuals with at least 1 elevated risk factor, and approximately 8% will occur in people with only borderline levels of multiple risk factors. Absolute 10-year CHD risk exceeded 10% in men older than age 45 years who had 1 elevated risk factor and 4 or more borderline risk factors and in those who had at least 2 elevated risk factors. In women, absolute CHD risk exceeded 10% only in those older than age 55 years who had at least 3 elevated risk factors. Limitations: The generalizability of the findings to persons of other ethnic backgrounds is unknown. Conclusions: Borderline CHD risk factors alone account for a small proportion of CHD events. C1 Framingham Heart Dis Epidemiol Study, Framingham, MA 01702 USA. Med Univ S Carolina, Charleston, SC 29425 USA. SUNY Buffalo, Buffalo, NY 14260 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Boston, MA 02215 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, 73 Mt Wayne Ave,Suite 2, Framingham, MA 01702 USA. EM vasan@bu.edu RI Sundstrom, Johan/A-6286-2009; OI Sundstrom, Johan/0000-0003-2247-8454; Ramachandran, Vasan/0000-0001-7357-5970; Sullivan, Lisa/0000-0003-0726-7149 NR 36 TC 96 Z9 104 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD MAR 15 PY 2005 VL 142 IS 6 BP 393 EP 402 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 906DQ UT WOS:000227621100001 PM 15767617 ER PT J AU Yanik, T Donaldson, RP AF Yanik, T Donaldson, RP TI A protective association between catalase and isocitrate lyase in peroxisomes SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE catalase; isocitrate lyase; glyoxysomes; hydrogen peroxidase (H2O2); protein oxidation ID CASTOR-BEAN ENDOSPERM; GLYOXYSOMAL MEMBRANES; HYDROGEN-PEROXIDE; MALATE SYNTHASE; PROTEINS; PURIFICATION; COTYLEDONS; CDNA; ACID; BIOSYNTHESIS AB Glyoxysomes are specialized peroxisomes in germinating seeds, which catalyze many reactions that convert fatty acids into carbohydrates thus generating H2O2. They are characterized by the presence of catalase (CAT, E.C. 1.11.1.6) in their matrix which protects cells from oxidative stress. Here, we investigated the possibility that a protein can be protected from oxidative damage by its association with CAT. We purified peroxisomal CAT from germinating castor beans by ion exchange, gel filtration, and hydroxylapatite chromatography. Gel filtration of the matrix proteins, cross-linking, and co-immunoprecipitation studies indicate that CAT associates with a glyoxysomal matrix protein, isocitrate lyase (ICL, E.C. 4.1.3.1). In addition, we found that H2O2 inactivates ICL and degrades its product, glyoxylate, when CAT is inactive. ICL and its product appear to be sensitive to oxidative damage; thus, association of CAT with ICL would afford protection from H2O2. (C) 2004 Elsevier Inc. All rights reserved. C1 George Washington Univ, Dept Biol Sci, Washington, DC 20052 USA. RP Donaldson, RP (reprint author), NICHHD, NIH, Cellular Neurobiol Sect, Bethesda, MD 20892 USA. EM robdon@gwu.edu NR 39 TC 15 Z9 16 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD MAR 15 PY 2005 VL 435 IS 2 BP 243 EP 252 DI 10.1016/j.abb.2004.12.017 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 901IJ UT WOS:000227275900001 PM 15708367 ER PT J AU Espinoza, HM Ganga, M Vadlamudi, U Martin, DM Brooks, BP Semina, EV Murray, JC Amendt, BA AF Espinoza, HM Ganga, M Vadlamudi, U Martin, DM Brooks, BP Semina, EV Murray, JC Amendt, BA TI Protein kinase c phosphorylation modulates N- and C-terminal regulatory activities of the PTTX2 homeodomain protein SO BIOCHEMISTRY LA English DT Article ID LEFT-RIGHT ASYMMETRY; IMMUNODEFICIENCY-VIRUS TYPE-1; AXENFELD-RIEGER-SYNDROME; HOMEOBOX GENE; CRANIOFACIAL DEVELOPMENT; BRANCHIAL ARCH; TOOTH MORPHOGENESIS; SIGNAL-TRANSDUCTION; EXPRESSION PATTERN; DLX2 EXPRESSION AB PKC phosphorylation regulates PITX2 DNA binding and transcriptional activity. Mutation of individual PKC sites demonstrates the functional regulation of PITX2 through phosphorylation. Immunoprecipitation of PITX2 and a PITX2 PKC mutant protein reveal specific in vivo phosphorylation by PKC in transfected cells. The transcriptional activity of PITX2 is negatively regulated by N-terminal phosphorylation and positively regulated by C-terminal phosphorylation. We demonstrate a mechanism of increased PITX2 transcriptional activation through protein interactions facilitated by phosphorylation of the PITX2 C-terminal tail. Phosphorylation of the PITX2 C terminus enhances the interaction with cellular factors. In corroboration with the PITX2 PKC functional studies, a newly identified C-terminal PITX2 mutation associated with Axenfeld-Rieger syndrome (ARS) demonstrates reduced phosphorylation. This mutation (PITX2 Delta T1261) creates a frameshift mutation in codon 227 resulting in 11 novel amino acids downstream followed by premature truncation of the protein, Three PKC sites in the C-terminal tail and OAR domain are deleted, which results in decreased transcriptional activation. PITX2 Delta T1261 is unable to interact with a cellular factor to synergistically activate transcription and demonstrates the first link of ARS with defective PITX2 protein interactions. Gene expression profiling of homozygous Pitx2 mutant mouse tissue reveals decreased Dlx2 expression as a potential molecular basis for developmental defects associated with ARS patients. Overall, phosphorylation imparts another level of regulation to the activity of the PITX2 homeodomain protein during, development. C1 Univ Tulsa, Dept Biol Sci, Tulsa, OK 74104 USA. Univ Michigan, Med Ctr, Dept Pediat & Human Genet, Ann Arbor, MI 48109 USA. NEI, NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Dept Med Genet, Milwaukee, WI 53226 USA. Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA. RP Texas A&M Univ Syst, Dept Environm & Genet Med, Hlth Sci Ctr, Inst Biosci & Technol, 2121 W Holcombe Blvd, Houston, TX 77030 USA. EM bamendt@ibt.tamhsc.edu FU NEI NIH HHS [EY12384]; NIDCR NIH HHS [DE13941] NR 68 TC 17 Z9 18 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 MAR 15 PY 2005 VL 44 IS 10 BP 3942 EP 3954 DI 10.1021/bi048362x PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 906GR UT WOS:000227629300029 PM 15751970 ER PT J AU Antignani, A Youle, RJ AF Antignani, A Youle, RJ TI A chimeric protein induces tumor cell apoptosis by delivering the human Bcl-2 family BH3-only protein bad SO BIOCHEMISTRY LA English DT Article ID COLONY-STIMULATING FACTOR; ACUTE MYELOID-LEUKEMIA; DEATH AGONIST BAD; CYTOCHROME-C; FACTOR-RECEPTOR; FUSION TOXIN; MITOCHONDRIAL APOPTOSIS; GM-CSF; SURVIVAL; PHOSPHORYLATION AB Deregulation of PI3K/Akt and Raf/Mek/Erk signal transduction cascades is one of the principal causes of neoplastic transformation. The inactivation of the proapoptotic protein Bad, upon phosphorylation by different kinases of these two pathways, may play an important role in different human malignancies. Therefore, we have expressed and purified a new chimeric protein, hGM-CSF-Bad, linking the human cyranulocyte-macrophage colony-stimulating factor to the N-terminus of the proapoptotic protein human Bad, to deliver Bad into tumor cells and induce apoptosis. Indeed. the human GM-CSF receptor is a good target because it is overexpressed on many leukemias and solid tumors and is not detectable on stern cells. We found that the chimeric protein binds the human GM-CSF receptor, is endocytosed, and appears to reach the cytosol via retrograde ER transport. After entering cells, the protein is able to induce apoptosis of human leukemia cells and human colon and gastric carcinoma cell lines (IC50 values as low as 1 mu M). We conclude that GM-CSF-Bad can overcome the inappropriate survival stimuli in transformed cells and restore the apoptotic pathway. The completely human sequence and the elevated selectivity for cancer cells could prevent immunogenicity and the nonspecific toxicity of targeted toxins in future clinical application of this fusion protein. C1 NINDS, Biochem Sect, SNB, NIH, Bethesda, MD 20892 USA. RP Youle, RJ (reprint author), NINDS, Biochem Sect, SNB, NIH, Bldg 35,Room 2C917,35 Convent Dr 2C917,MSC3704, Bethesda, MD 20892 USA. EM youler@ninds.nih.gov NR 56 TC 8 Z9 8 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 MAR 15 PY 2005 VL 44 IS 10 BP 4074 EP 4082 DI 10.1021/bi0477687 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 906GR UT WOS:000227629300043 PM 15751984 ER PT J AU Ferrucci, L Corsi, A Lauretani, F Bandinelli, S Bartali, B Taub, DD Guralnik, JM Longo, DL AF Ferrucci, L Corsi, A Lauretani, F Bandinelli, S Bartali, B Taub, DD Guralnik, JM Longo, DL TI The origins of age-related proinflammatory state SO BLOOD LA English DT Article ID C-REACTIVE PROTEIN; CARDIOVASCULAR RISK-FACTORS; INFLAMMATORY MARKERS; CYTOKINE PRODUCTION; MONONUCLEAR-CELLS; FOLLOW-UP; DISEASE; INTERLEUKIN-6; WOMEN; ASSOCIATIONS AB We hypothesized that the rising levels of inflammatory markers, with aging is explained by cardiovascular risk factors and morbidity becoming progressively more prevalent in older persons. information on inflammatory markers, cardiovascular risk factors, and diseases was collected in 595 men and 748 women sampled from the general population (age, 20-102 years). In both men and women, older age was associated with higher levels of interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1ra), IL-18, C-reactive protein (CRIP), and fibrinogen, while soluble IL-6 receptor (sIL-6r) increased significantly with age only in men. Adjusting for cardiovascular risk factors and morbidity, the age regression coefficients became substantially smaller in models predicting IL-6, IL-1ra, IL-18, and fibrinogen and larger in the model predicting sIL6r. Adjustment for cardiovascular morbidity substantially reduced the effect of age on CRP in men but not in women. Findings were confirmed in a subgroup of 51 men and 45 women with low risk profile and no cardiovascular morbidity. Part of the "proinflammatory state" in older persons is related to the high prevalence of cardiovascular risk factor and morbidity. (c) 2005 by The American Society of Hematology. C1 NIA, Intramural Res Program, Baltimore, MD 21224 USA. Italian Natl Inst Res & Care Aging, Lab Clin Epidemiol, Florence, Italy. Cornell Univ, Div Nutr Sci, Ithaca, NY USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, ASTRA Unit,Harbor Hosp, 5th Floor,3001 S Hannover St, Baltimore, MD USA. EM ferruccilu@grc.nia.nih.gov RI Lauretani, Fulvio/K-5115-2016 OI Lauretani, Fulvio/0000-0002-5287-9972 FU PHS HHS [821336, 916413] NR 37 TC 339 Z9 345 U1 1 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2005 VL 105 IS 6 BP 2294 EP 2299 DI 10.1182/blood-2004-07-2599 PG 6 WC Hematology SC Hematology GA 906HD UT WOS:000227630500019 PM 15572589 ER PT J AU Ly, H Calado, RT Allard, P Baerlocher, GM Lansdorp, PM Young, NS Parslow, TG AF Ly, H Calado, RT Allard, P Baerlocher, GM Lansdorp, PM Young, NS Parslow, TG TI Functional characterization of telomerase RNA variants found in patients with hematologic disorders SO BLOOD LA English DT Article ID BODY-SPECIFIC LOCALIZATION; BOX H/ACA SCARNAS; DYSKERATOSIS-CONGENITA; APLASTIC-ANEMIA; MAMMALIAN TELOMERASE; REVERSE-TRANSCRIPTASE; MOUSE TELOMERASE; FLOW-CYTOMETRY; STEM-LOOP; MUTATIONS AB Human telomerase uses a specific cellular RNA, called hTERC, as the template to synthesize telomere repeats at chromosome ends. Approximately 10% to 15% of patients with aplastic anemia or other bone marrow failure syndromes are carriers of hTERC sequence variants whose functional significance, in most cases, is unknown. We screened 10 reported and 2 newly discovered hTERC variants from such patients and found that 10 of these negatively affected telomerase enzymatic function when they were used to reconstitute telomerase enzymatic function in human cells. Most functional deficits were due to perturbations of hTERC secondary structure and correlated well with the degrees of telomere shortening and reduced telomerase activity observed in peripheral blood lymphocytes of the representative patients. We also found no evidence of dominant-negative activity in any of the mutants. Therefore, loss of telomerase activity and of telomere maintenance resulting from inherited hTERC mutations may limit marrow stem cell renewal and predispose some patients to bone marrow failure. (c) 2005 by The American Society of Hematology. C1 Emory Univ, Dept Pathol & Lab Med, Atlanta, GA 30322 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. British Columbia Canc Agcy, Terry Fox Lab, Vancouver, BC V5Z 1L3, Canada. RP Ly, H (reprint author), Emory Univ, Dept Pathol & Lab Med, Whitehead Biomed REs Bldg,615 Michael St,Rm 175, Atlanta, GA 30322 USA. EM hly@emory.edu RI Calado, Rodrigo/G-2619-2011 FU NIAID NIH HHS [AI36636, AI40317] NR 35 TC 61 Z9 66 U1 2 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 MAR 15 PY 2005 VL 105 IS 6 BP 2332 EP 2339 DI 10.1182/blood-2004-09-3659 PG 8 WC Hematology SC Hematology GA 906HD UT WOS:000227630500024 PM 15550482 ER PT J AU Sugaya, M Watanabe, T Yang, A Starost, MF Kobayashi, H Atkins, AM Borris, DL Hanan, EA Schimel, D Bryant, MA Roberts, N Skobe, M Staskus, KA Kaldis, P Blauvelt, A AF Sugaya, M Watanabe, T Yang, A Starost, MF Kobayashi, H Atkins, AM Borris, DL Hanan, EA Schimel, D Bryant, MA Roberts, N Skobe, M Staskus, KA Kaldis, P Blauvelt, A TI Lymphatic dysfunction in transgenic mice expressing KSHV k-cyclin under the control of the VEGFR-3 promoter SO BLOOD LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; MAGNETIC RESONANCE LYMPHANGIOGRAPHY; GROWTH-FACTOR RECEPTOR-3; KAPOSIS-SARCOMA; SPINDLE CELLS; HUMAN-HERPESVIRUS-8 HHV-8; NUCLEOTIDE-SEQUENCE; ENDOTHELIAL-CELLS; GENE-EXPRESSION; DNA-SEQUENCES AB Kaposi sarcoma-associated herpesvirus (KSHV) infects endothelial cells within KS tumors, and these cells express the KSHV latent-cycle gene k-cyclin (kCYC) as well as vascular endothelial growth factor receptor 3 (VEGFR-3), a marker for lymphatic endothelium. To further understand KSHV-mediated pathogenesis, we generated transgenic mice expressing kCYC under the control of the VEGFR-3 promoter. kCYC mRNA and functional protein expression within tissue correlated with VEGFR-3 expression and were most abundantly detected within lung tissue. Clinically, most transgenic mice died within 6 months of age secondary to progressive accumulation of chylous pleural fluid. In skin, edema was detected by magnetic resonance imaging and mice demonstrated persistent erythema of the ears following trauma. Histologically, erythematous skin showed extravasation of erythrocytes and accumulation of erythrocytes within lymphatic lumens. In addition, lymphatic drainage of injected contrast dyes was markedly impaired in transgenic mice. Karyomegaly, a feature observed in kCYC-expressing cells in vitro, was detected in many tissues, and selectively occurred within lymphatic endothelial cells expressing kCYC mRNA by in situ hybridization. In summary, kCYC expression within VEGFR-3(+) cells of mice causes marked impairment of lymphatic function. kCYC may contribute to the development of certain clinical and histologic features of KS, including localized edema and retention of extravasated erythrocytes within KS tumors. (c) 2005 by The American Society of Hematology. C1 NCI, Dermatol Branch, Off Res Serv, Div Vet Resources,Metab Branch, Bethesda, MD 20892 USA. NINDS, Mouse Imaging Facil, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Derald H Ruttenberg Canc Ctr, New York, NY USA. Univ Minnesota, Sch Med, Dept Microbiol, Minneapolis, MN 55455 USA. NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. RP Blauvelt, A (reprint author), 3710 SW US Vet Hosp Rd,Mail Code R&D 55, Portland, OR 97239 USA. EM blauvela@ohsu.edu RI Kaldis, Philipp/G-2714-2010 OI Kaldis, Philipp/0000-0002-7247-7591 FU Intramural NIH HHS NR 47 TC 27 Z9 27 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 MAR 15 PY 2005 VL 105 IS 6 BP 2356 EP 2363 DI 10.1182/blood-2004-08-3364 PG 8 WC Hematology SC Hematology GA 906HD UT WOS:000227630500028 PM 15536152 ER PT J AU Herbeuval, JP Boasso, A Grivel, JC Hardy, AW Anderson, SA Dolan, MJ Chougnet, C Lifson, JD Shearer, GM AF Herbeuval, JP Boasso, A Grivel, JC Hardy, AW Anderson, SA Dolan, MJ Chougnet, C Lifson, JD Shearer, GM TI TNF-related apoptosis-inducing ligand (TRAIL) in HIV-1-infected patients and its in vitro production by antigen-presenting cells SO BLOOD LA English DT Article ID TUMOR-NECROSIS-FACTOR; IMMUNODEFICIENCY-VIRUS TYPE-1; CD4(+) T-CELLS; HUMAN LYMPHOID-TISSUE; DENDRITIC CELLS; HIV-INFECTION; SIGNALING PATHWAY; CANCER-CELLS; INDUCTION; MONOCYTES AB There is now considerable in vitro evidence that tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is involved in HIV-1 pathogenesis by inducing CD4(+) T-cell death characteristic of AIDS. Therefore, we have tested levels of TRAIL in plasma samples from 107 HIV-1-infected and 53 uninfected controls as well as in longitudinal plasma samples from patients who started antiretroviral therapy (ART). TRAIL was elevated in plasma of HIV-1-infected patients compared with uninfected individuals, and patients receiving ART showed decreased plasma TRAIL levels that correlated with reduction in viral load. In vitro exposure to infectious and noninfectious HIV-1 induced TRAIL in monocytes and marginally in dendritic cells (DCs) but not in macrophages or T cells. Interestingly, the HIV-1 entry inhibitor, soluble CD4, blocked HIV-1-induced production of TRAIL. Furthermore, production and gene expression of TRAIL by monocytes were regulated by type I interferon via signal transducer and activator of transcription-1 (STAT1)/STAT2 signaling molecule. Ex vivo HIV-1 infection of human tonsil lymphoid tissue also resulted in increased TRAIL production. We demonstrate here that plasma TRAIL is elevated in HIV-1-infected patients and is decreased by ART therapy. The high production of TRAIL by antigen-presenting cells may contribute to the death of CD4(+) T cells during progression to AIDS. (c) 2005 by The American Society of Hematology. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Henry M Jackson Fdn & Infect Dis Serv, Wilford Hall USAF Med Ctr, Lackland AFB, TX USA. Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH 45229 USA. NCI, AIDS Vaccine Program, Sci Applicat Int Corp, Frederick, MD 21701 USA. RP Shearer, GM (reprint author), NCI, Expt Immunol Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gene_shearer@nih.gov OI Boasso, Adriano/0000-0001-9673-6319 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 43 TC 98 Z9 102 U1 0 U2 7 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2005 VL 105 IS 6 BP 2458 EP 2464 DI 10.1182/blood-2004-08-3058 PG 7 WC Hematology SC Hematology GA 906HD UT WOS:000227630500043 PM 15585654 ER PT J AU Seggewiss, R Lore, K Greiner, E Magnusson, MK Price, DA Douek, DC Dunbar, CE Wiestner, A AF Seggewiss, R Lore, K Greiner, E Magnusson, MK Price, DA Douek, DC Dunbar, CE Wiestner, A TI Imatinib inhibits T-cell receptor-mediated T-cell proliferation and activation in a dose-dependent manner SO BLOOD LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; STEM-CELL; TYROSINE KINASE; RHEUMATOID-ARTHRITIS; LYMPHOCYTE RESPONSES; HEALTHY-INDIVIDUALS; ANTIGEN RECEPTOR; DENDRITIC CELLS; VIRUS INFECTION AB The tyrosine kinase inhibitor imatinib (imatinib, ST1571, Glivec, and Gleevec) is increasingly used in patients undergoing allogeneic transplantation for leukemia. However, little is known regarding its potential immunoregulatory effects. Here, we investigate the effect of imatinib on T-cell receptor (TCR)-mediated activation of human T cells. Following stimulation with the anti-CD3 antibody 12F6, proliferation of activated T cells was almost completely inhibited by 10 mu M imatinib. Furthermore, antigen-triggered expansion of CD8(+) T cells in response to immunodominant cytomegalovirus (CMV) and Epstein-Barr virus (EBV) peptides was significantly reduced. Up-regulation of the activation markers CD25 and CD69 in response to TCR cross-linking was suppressed by imatinib at a mean inhibitory concentration 50% (IC50) of 5.4 mu M and 7.3 mu M, respectively; interleukin 2 (IL-2) production was also impaired. Analysis of the TCR-induced signaling cascade showed that imatinib substantially reduced tyrosine phosphorylation of ZAP70 and LAT in response to activation through the TCR. Sequence comparisons of all 90 tyrosine kinase genes in the human genome for homology in the adenosine triphosphate (ATP) binding pocket identified LCK, which is required for ZAP70 activation, as a likely target for imatinib. The IC50 for LCK inhibition by imatinib was 0.6 mu M to 0.8 mu M in an in vitro tyrosine kinase assay. In summary, imatinib can interfere with T-cell activation in vitro, and its impact on the frequency of opportunistic infections and graft-versus-host or graft-versus-leukemia reactions after transplantation should be investigated in clinical trials. (c) 2005 by The American Society of Hematology. C1 NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH,DHHS,Immunol Lab, Bethesda, MD 20892 USA. NIAID, Human Immunol Sect, Vaccine Res Ctr, Lab Med Chem,NIDDK,NIH,DHHS, Bethesda, MD 20892 USA. Landspitali Univ Hosp, Dept Hematol, Reykjavik, Iceland. Landspitali Univ Hosp, Dept Genet, Reykjavik, Iceland. Landspitali Univ Hosp, Dept Mol Med, Reykjavik, Iceland. RP Dunbar, CE (reprint author), NHLBI, Mol Hematopoiesis Sect, Hematol Branch, NIH,DHHS,Immunol Lab, Bldg 10,CRC,Rm 4-5140,10 Ctr Dr,MSC 1202, Bethesda, MD 20892 USA. EM dunbarc@nhlbi.nih.gov RI Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 NR 46 TC 163 Z9 173 U1 0 U2 9 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 MAR 15 PY 2005 VL 105 IS 6 BP 2473 EP 2479 DI 10.1182/blood-2004-07-2527 PG 7 WC Hematology SC Hematology GA 906HD UT WOS:000227630500045 PM 15572591 ER PT J AU Saccardi, R Mancardi, GL Solari, A Bosi, A Bruzzi, P Di Bartolomeo, P Donelli, A Filippi, M Guerrasio, A Gualandi, F La Nasa, G Murialdo, A Pagliai, F Papineschi, F Scappini, B Marmont, AM AF Saccardi, R Mancardi, GL Solari, A Bosi, A Bruzzi, P Di Bartolomeo, P Donelli, A Filippi, M Guerrasio, A Gualandi, F La Nasa, G Murialdo, A Pagliai, F Papineschi, F Scappini, B Marmont, AM CA Italian GITMO-Neuro Intergroup TI Autologous HSCT for severe progressive multiple sclerosis in a multicenter trial: impact on disease activity and quality of life SO BLOOD LA English DT Article ID STEM-CELL TRANSPLANTATION; DOSE IMMUNOSUPPRESSIVE THERAPY; BONE-MARROW-TRANSPLANTATION; AUTOIMMUNE-DISEASE; MRI; PATIENT; MITOXANTRONE; LEUKEMIA; MS AB Hematopoietic stem cell transplantation (HSCT) has been proposed for the treatment of severe multiple sclerosis (MS). In a phase 2 multicenter study we selected 19 non-primary progressive MS patients showing high disease activity on the basis of both brain magnetic resonance imaging (MRI) and sustained clinical deterioration despite conventional treatments. After stem cell mobilization with cyclophosphamide (CY) and filgrastim, patients were conditioned with BCNU (1,3-bis(2-chloroethyl)-1-nitrosourea), cytosine arabinoside, etoposide, and melphalan (BEAM) followed by antithymocyte globulin (ATG). Unmanipulated peripheral blood stem cells (PBSCs) were then infused. No maintenance treatment was administered with a median follow-up of 36 months (range, 12 to 72 months). All patients showed clinical stabilization or improvement; 3 subsequently deteriorated, 1 beyond the baseline. No MRI active lesions were detected after the HSCT except in 1 patient who showed a new lesion at 4.5 years. Infections were limited and restricted to 3 months after HSCT. Health-related quality of life was assessed through the 54-item MS quality of life (MSQOL-54) questionnaire, showing a statistically significant improvement in both composite scores and in most of the individual domains. HSCT is able to induce a prolonged clinical stabilization in severe progressive MS patients, resulting in both sustained treatment-free periods and quality of life improvement. (c) 2005 by The American Society of Hematology C1 Univ Florence, Bone Marrow Transplantat Unit, Careggi Hosp, I-50121 Florence, Italy. Univ Genoa, Dept Neurol Sci Ophthalmol & Genet, Ctr Excellence Biomed Res, I-16126 Genoa, Italy. Ist Nazl Neurol Carlo Besta, Milan, Italy. Natl Canc Inst, Unit Clin Epidemiol & Trials, Genoa, Italy. S Spirito Hosp, Bone Marrow Transplantat Unit, Pescara, Italy. Policlin Modena, Dept Hematol & Oncol, Modena, Italy. S Raffaele Hosp, Inst Sci, Neuroimaging Res Unit, Dept Neurosci, Milan, Italy. S Luigi Hosp, Internal Med & Heamtol Dept, Orbassano, Italy. San Martino Hosp, Bone Marrow Transplantat Unit, Genoa, Italy. Binaghi Hosp, Bone Marrow Transplantat Unit, Cagliari, Italy. Santa Chiara Hosp, Dept Haematol, Pisa, Italy. RP Saccardi, R (reprint author), Polcilin Careggi, Bone Marrow Transplant Unit, UO Ematol, Viale Morgagni 85, I-50134 Florence, Italy. EM r.saccardi@dac.unifi.it RI mancardi, giovanni luigi/K-8656-2016; OI mancardi, giovanni luigi/0000-0001-8427-118X; Bruzzi, Paolo/0000-0002-7874-2077; La Nasa, Giorgio/0000-0002-8247-583X NR 38 TC 93 Z9 102 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 MAR 15 PY 2005 VL 105 IS 6 BP 2601 EP 2607 DI 10.1182/blood-2004-08-3205 PG 7 WC Hematology SC Hematology GA 906HD UT WOS:000227630500062 PM 15546956 ER PT J AU Borlongan, CV Sumaya, IC Moss, DE AF Borlongan, CV Sumaya, IC Moss, DE TI Methanesulfonyl fluoride, an acetylcholinesterase inhibitor, attenuates simple learning and memory deficits in ischemic rats SO BRAIN RESEARCH LA English DT Article DE acute stroke; animal model cerebral infarct; learning and memory; vascular cognitive impairment; cholinergic system; neuroprotection ID MIDDLE CEREBRAL-ARTERY; ENHANCES ONE-TRIAL; CHOLINESTERASE-INHIBITORS; NEUROTROPHIC FACTOR; OBJECT RECOGNITION; PASSIVE-AVOIDANCE; MONGOLIAN GERBILS; BRAIN METABOLISM; BASAL FOREBRAIN; WORKING-MEMORY AB Methanesulfonyl fluoride (MSF), a highly selective CNS inhibitor of acetylcholinesterase, has been recently demonstrated to promote improvement in cognitive performance in patients with senile dementia of Alzheimer type. Because a similar cognitive impairment may accompany stroke, we investigated in the present study whether treatment with MSF could produce beneficial effects in adult rats subjected to an experimental stroke model. Sprague-Dawley rats received transient 60 min intraluminal occlusion of the right middle cerebral artery (MCAo) and were given i.p. injections of either MSF (1 mg/kg at 24 and 48 h post-MCAo and 0.3 mg/kg thereafter every other day) or the vehicle, peanut oil, for 4 weeks. Behavioral tests and biochemical assays were performed at 28 days post-surgery. MSF treatment produced about 90% inhibition of acetylcholinesterase in the brain. Ischemic animals that received the vehicle displayed significant elevated body swing biased activity (84.8 +/- 10%) and significantly prolonged acquisition (398 +/- 62 s) and shortened retention (79 +/- 26 s) of the passive avoidance task. Interestingly, while the ischemic animals that received the MSF exhibited elevated body swing biased activity (87.7 +/- 8%), they performed significantly better in the passive avoidance task (255 +/- 36 s and 145 +/- 18 s in acquisition and retention) than the vehicle-treated animals. Moreover, whereas brains from both groups of animals revealed similar extent and degree of cerebral infarction, the MSF-treated ischemic animals showed more intense immunoreactivity, as well as a significantly higher number (10-15% increase) of septal choline acetyltransferase-positive cells than the vehicle-treated ischemic animals. These results show that MSF, possibly by preserving a functional cholinergic system, attenuated stroke-induced deficits in a simple learning and memory task. Published by Elsevier B.V. C1 Natl Inst Drug Abuse, Res Program, NIH, Baltimore, MD 21224 USA. Univ Texas, Dept Psychol, El Paso, TX 79968 USA. RP Borlongan, CV (reprint author), Dept Neurol, 1120 15th St, Augusta, GA 30912 USA. EM cborlongan@mail.mcg.edu OI Borlongan, Cesar/0000-0002-2966-9782 NR 52 TC 18 Z9 19 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 15 PY 2005 VL 1038 IS 1 BP 50 EP 58 DI 10.1016/j.brainres.2005.01.028 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 914TP UT WOS:000228251000006 PM 15748872 ER PT J AU Sherman, ME Wang, SS Carreon, J Devesa, SS AF Sherman, ME Wang, SS Carreon, J Devesa, SS TI Mortality trends for cervical squamous and adenocarcinoma in the United States - Relation to incidence and survival SO CANCER LA English DT Article DE cervix; epidemiology; carcinoma; adenocarcinoma; squamous; mortality; survival; incidence ID HUMAN-PAPILLOMAVIRUS; UNDETERMINED SIGNIFICANCE; PAPANICOLAOU TEST; UTERINE CERVIX; CELL CARCINOMA; FOLLOW-UP; IN-SITU; CANCER; CYTOLOGY; WOMEN AB BACKGROUND. in the United States, detection of squamous carcinoma in situ (CIS) by screening has led to reduced rates for invasive squarnous carcinoma and lower mortalitv. Adenocarcinorna in situ (AIS) rates also have increased, but invasive cervical adenocarcinorna rates have not declined similarly. To make inferences about the effectiveness of screening, the authors assessed mortality trends for squamous and adenocarcinorna in relation to incidence of these rumors, incidence of their precursors and survival. METHODS. Using data from the Surveillance, Epidemiology, and End Results program (SEER), the authors tabulated incidence per 105 woman-years for invasive carcinomas (1976-2000) and for CIS and AIS (1976-1995) by age (< 50 vears, greater than or equal to 50 vears) and race (whites, blacks). Cumulative relative survival rates were tabulated for 1976-1995 and mortality rates were estimated for 1986-2000. RESULTS. Among all groups, CIS rates approximately doubled whereas rates for invasive squamous carcinoma declined. Among younger whites, mortality declined from.1.12 to 0.93, and for older whites, mortality decreased from 5.02 to 3.82. Among younger blacks, mortality for squamous carcinoma decreased from 2.69 to 1.96. Among older blacks, the mortality rates declined from 14.88 to 9.15. Although AIS rates have increased dramatically among whites (all ages) and younger blacks, adenocarcinorna incidence and mortalitv rates have not changed greatly. Survival for patients did not change greatly within these age-race groups. CONCLUSIONS. The authors concluded that increases in CIS seemed disproportionately large compared with improvements in mortality rates for squamous carcinoma. Despite increased reporting of AIS, declines in mortality for cervical adenocarcinoma have not been demonstrated conclusively. However, future analyses are required to evaluate these trends more cornpletelv. Cancer 2005;103:12513-64. Published 2005 by the American Cancer Society. C1 NCI, Div Canc Epidemiol & Genet, NIH, Rockville, MD 20892 USA. RP Sherman, ME (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd, Rockville, MD 20892 USA. EM shermanm@mail.nih.gov NR 33 TC 92 Z9 94 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2005 VL 103 IS 6 BP 1258 EP 1264 DI 10.1002/cncr.20877 PG 7 WC Oncology SC Oncology GA 903LO UT WOS:000227427600021 PM 15693030 ER PT J AU Suy, S Mitchell, JB Samuni, A Mueller, S Kasid, U AF Suy, S Mitchell, JB Samuni, A Mueller, S Kasid, U TI Nitroxide tempo, a small molecule, induces apoptosis in prostate carcinoma cells and suppresses tumor growth in athymic mice SO CANCER LA English DT Article DE nitroxide tempo; prostate carcinoma; apoptosis; caspases; cell cycle and cell proliferation; antitumor effect; in vitro chemosensitization ID PRO-OXIDATIVE ACTIVITY; BREAST-CANCER CELLS; DEATH; INHIBITION; DAMAGE; SUPEROXIDE; EXPRESSION; LNCAP AB BACKGROUND. in previous studies, nitroxide tempo (2, 2, 6, 6-tetramethyl-piperidine-l-oxyl), a small molecule, induced cell death in cancer cells. The current study examined the antineoplastic properties of tempo in the human hormonedependent/hormone-independent prostate carcinoma models (LNCaP, DU-145, and PC-3). METHODS. The apoptotic effects of tempo were examined by the flow cytometric analysis of cells labeled with fluorescein isothiocyanate-conjugated annexin-V, and by electron microscopy. Enzymatic assays were performed to measure the activities of 2 cysteine proteases, i.e., caspase-9 and caspase-3, in tempo-treated cells. The effects of tempo on cell proliferation and on cell cycle distribution profiles were measured by the flow cytometric assay using immuno fluorescent staining of incorporated 5'-bromo-2'-deoxyuridine (BrdU) coupled with 7 - amino- actinomycin D (7-AAD) staining of total DNA. The number of proliferating cells was also determined independently by enzyme-linked immunosorbent assay using chemiluminescent detection of incorporated BrdU. Subcutaneous growth of human prostate carcinoma in athymic mice was monitored after intraturnoral administration of tempo into tumor-bearing mice. In addition, cell viability assays were performed to compare the cytotoxic effect of a combination of doxorubicin or mitoxantrone and tempo with single agents. RESULTS. Tempo treatment of prostate carcinoma cells caused a significant increase in the number of apoptotic cells compared with control groups (tempo, 2.5 mNI, 24 hours: DIJ-145, approximately 3.4-fold; PC-3, approximately 6-7-fold; tempo 1 mM, 24 hours: LNCaP, approximately 12-fold). Tempo-induced loss of cell viability was blocked partially or completely after pretreatment of cells with actinomycin-D or cvcloheximide, suggesting a de novo macromolecule synthesisdependent mechanism of cell death. Electron microscopy revealed aggregation and marginalization of chromatin in the nuclei of a large number of tempo-treated lLNCaP cells. Tempo treatment of LNCaP cells resulted in enhanced activities of caspase-9 (tempo, 5 mM, 15 hours: approximately 2-fold) and caspase-3 (tempo, 2.5 mM, 24 hours: approximately 12-fold). Tempo treatment also led to an enhanced number of cells in G2/M phase of the cell cycle (tempo, 5.0 mM, 24 flours: DU-145, approximately 1.6-fold; PC-3, approximately 1.5-fold; LNCaP, approximately 5.3-fold), and decreased BrdU incorporation indicative of a decline in the number of proliferating cells (tempo, 2.5 mM, 24 or 48 hours; DU-145, approxiinatelv 2-3-fold; PC-3, approximately 1.2-fold; LNCaP, approximately 5-10-fold). Administration of tempo into LNCaP tumor-bearing mice resulted in a significant inhibition of tumor growth (percent initial tumor volume [Day 30, n = 4]: vehicle, 845.35 +/- 272.83; tempo, 9.72 +/- 9.72; tempo vs. vehicle, P < 0.02). In hormonerefractorv prostate carcinoma cells, a combination of relatively low doses of tempo and doxorubicin or mitoxantrone caused enhanced cytotoxicity as compared with single agents. C1 Georgetown Univ, Med Ctr, Dept Radiat Med Biochem & Mol Biol, Washington, DC 20007 USA. NCI, Div Radiat Biol, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Dept Oncol, Lombardi Canc Ctr, Washington, DC 20007 USA. RP Kasid, U (reprint author), Georgetown Univ, Med Ctr, Dept Radiat Med Biochem & Mol Biol, E208,Res Bldg,3900 Reservoir Rd NW, Washington, DC 20007 USA. EM kasidu@georgetown.edu RI Messier, Claude/A-2322-2008 OI Messier, Claude/0000-0002-4791-1763 FU NCI NIH HHS [CA68322, CA58984, CA74175] NR 39 TC 32 Z9 34 U1 1 U2 15 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD MAR 15 PY 2005 VL 103 IS 6 BP 1302 EP 1313 DI 10.1002/cncr.20898 PG 12 WC Oncology SC Oncology GA 903LO UT WOS:000227427600026 PM 15685617 ER PT J AU Li, ZJ Jaboin, J Dennis, PA Thiele, CJ AF Li, ZJ Jaboin, J Dennis, PA Thiele, CJ TI Genetic and pharmacologic identification of Akt as a mediator of brain-derived neurotrophic factor/Tr kappa B rescue of neuroblastoma cells from chemotherapy-induced cell death SO CANCER RESEARCH LA English DT Article ID ETHER LIPID ANALOGS; SERINE/THREONINE KINASE; INDUCED APOPTOSIS; UP-REGULATION; CANCER-CELLS; ACTIVATION; SURVIVAL; EXPRESSION; AKT/PKB; RESISTANCE AB Patients whose neuroblastoma tumors express high levels of brain-derived neurotrophic factor (BDNF) and TrkB have an unfavorable prognosis. Our previous studies indicated that BDNF activation of the TrkB signal transduction pathway blocked the cytotoxic effects of chemotherapeutic drugs via the phosphatidylinositol 3-kinase pathway. Akt is an important downstream target of phosphatidylinositol 3-kinase and functions to regulate cell survival, proliferation, and protein synthesis. In this study, we examined whether Akt is required and sufficient to mediate BDNF/TrkB protection of neuroblastoma cells from chemotherapy. Transient transfection of a constitutively active Akt (Akt-Myr) into TrkB-expressing SY5Y cells (TB8 cells) increases Akt activation and attenuates the cell death induced by chemotherapeutic reagents in the absence of BDNF. Furthermore, expression of a dominant-negative Akt (Akt-K179A) blocks the ability of BDNF to rescue TB8 cells from chemotherapy-induced cell death. Pharmacologic inhibition of Akt, with PIA6, a phosphatidylinositol ether lipid analogue (PIA), blocks BDNF-induced phosphorylation of Akt and the downstream target of Akt. PIA6 sensitizes neuroblastoma cells to chemotherapy and attenuates BDNF protection of neuroblastoma cells from chemotherapy-induced cell death. These results indicate that Akt is a key signaling component by which BDNF activation of the TrkB signal transduction pathway protects neuroblastoma cells from chemotherapy-induced cell death. This study raises the possibility that novel pharmacologic inhibitors of Akt may enhance the effectiveness of chemotherapeutic agents in the treatment of neuroblastoma tumors. C1 NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. China Med Univ, Affiliated Hosp 2, Shenyang, Peoples R China. RP Thiele, CJ (reprint author), NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, NIH, 10 Ctr Dr,MSC-1928,Bldg 10,CRC 1-3940, Bethesda, MD 20892 USA. EM ct47a@nih.gov NR 20 TC 48 Z9 50 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 MAR 15 PY 2005 VL 65 IS 6 BP 2070 EP 2075 DI 10.1158/0008-5472.CAN-04-3606 PG 6 WC Oncology SC Oncology GA 905VW UT WOS:000227600000005 PM 15781614 ER PT J AU Purow, BW Haque, RM Noel, MW Su, Q Burdick, MJ Lee, J Sundaresan, T Pastorino, S Park, JK Mikolaenko, I Maric, D Eberhart, CG Fine, HA AF Purow, BW Haque, RM Noel, MW Su, Q Burdick, MJ Lee, J Sundaresan, T Pastorino, S Park, JK Mikolaenko, I Maric, D Eberhart, CG Fine, HA TI Expression of Notch-1 and its ligands, Delta-like-1 and Jagged-1, is critical for glioma cell survival and proliferation SO CANCER RESEARCH LA English DT Article ID INTRACELLULAR DOMAIN; NUCLEAR-LOCALIZATION; ALAGILLE-SYNDROME; ONCOGENIC RAS; CANCER CELLS; TRANSFORMATION; EZRIN; DIFFERENTIATION; ACTIVATION; INHIBITION AB The Notch family of proteins plays an integral role in determining cell fates, such as proliferation, differentiation, and apoptosis. We show that Notch-1 and its ligands, Delta-like-1 and Jagged-1, are overexpressed in many glioma cell lines and primary human gliomas. Immunohistochemistry of a primary human glioma tissue array shows the presence in the nucleus of the Notch-1 intracellular domain, indicating Notch-1 activation in situ. Down-regulation of Notch-1, Delta-like- 1, or Jagged-1 by RNA interference induces apoptosis and inhibits proliferation in multiple glioma cell lines. In addition, pretreatment of glioma cells with Notch-1 or Delta-like-1 small interfering RNA significantly prolongs survival in a murine orthotopic brain tumor model. These results show, for the first time, the dependence of cancer cells on a single Notch ligand; they also suggest a potential Notch juxtacrine/autocrine loop in gliomas. Notch-1 and its ligands may present novel therapeutic targets in the treatment of glioma. C1 NINDS, Neurooncol Branch, NCI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD USA. RP Fine, HA (reprint author), NINDS, Neurooncol Branch, NCI, NIH, Room 225,Bldg 82,Bloch Bldg,9030 Old Georgetown R, Bethesda, MD 20892 USA. EM hfine@mail.nih.gov NR 42 TC 323 Z9 366 U1 0 U2 11 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 MAR 15 PY 2005 VL 65 IS 6 BP 2353 EP 2363 DI 10.1158/0008-5472.CAN-04-1890 PG 11 WC Oncology SC Oncology GA 905VW UT WOS:000227600000041 PM 15781650 ER PT J AU Wan, XL Mendoza, A Khanna, C Helman, LJ AF Wan, XL Mendoza, A Khanna, C Helman, LJ TI Rapamycin inhibits ezrin-mediated metastatic behavior in a murine model of osteosarcoma SO CANCER RESEARCH LA English DT Article ID P70 S6 KINASE; MAMMALIAN TARGET; SIGNALING PATHWAY; PLASMA-MEMBRANE; GROWTH-FACTOR; ERM PROTEINS; CELL; PHOSPHORYLATION; FAMILY; CYTOSKELETON AB Osteosarcoma is the most frequent primary malignant tumor of bone with a high propensity for metastasis. We have previously showed that ezrin expression is necessary for metastatic behavior in a murine model of osteosarcoma (K7M2). In this study, we found that a mechanism of ezrin-related metastatic behavior is linked to an Akt-dependent mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 kinase (S6K1)/eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) pathway. Suppression of ezrin expression either by antisense transfection or by small interfering RNAs or disruption of ezrin function by transfection of a dominant-negative ezrin-T567A mutant led to decreased expression and decreased phosphorylation of both S6K1 and 4E-BP1. Proteosomal inhibition by MG132 reversed antisense-mediated decrease of S6K1 and 4E-BP1 protein expression, but failed to affect the effect of ezrin on phosphorylation of S6K1 and 4E-BP1. Blockade of the mTOR pathway with rapamycin or its analog, cell cycle inhibitor-779 led to significant inhibition of experimental lung metastasis in vivo. These results suggest that blocking the mTOR/S6K1/4E-BP1 pathway may be an appropriate target for strategies to reduce tumor cell metastasis. C1 NCI, Mol Oncol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Helman, LJ (reprint author), NCI, Mol Oncol Sect, Pediat Oncol Branch, NIH, Bldg 10,Room 1,W 3750, Bethesda, MD 20892 USA. EM helmanl@nih.gov NR 33 TC 138 Z9 164 U1 1 U2 7 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 MAR 15 PY 2005 VL 65 IS 6 BP 2406 EP 2411 DI 10.1158/0008-5472.CAN-04-3135 PG 6 WC Oncology SC Oncology GA 905VW UT WOS:000227600000047 PM 15781656 ER PT J AU Li, HJ Kantoff, PW Giovannucci, E Leitzmann, MF Gaziano, JN Stampfer, MJ Ma, J AF Li, HJ Kantoff, PW Giovannucci, E Leitzmann, MF Gaziano, JN Stampfer, MJ Ma, J TI Manganese superoxide dismutase polymorphism, prediagnostic antioxidant status, and risk of clinical significant prostate cancer SO CANCER RESEARCH LA English DT Article ID MITOCHONDRIAL TARGETING SEQUENCE; BETA-CAROTENE SUPPLEMENTATION; BASE-LINE CHARACTERISTICS; BREAST-CANCER; SELENIUM SUPPLEMENTATION; GENETIC POLYMORPHISMS; MNSOD POLYMORPHISM; PHYSICIANS HEALTH; ALPHA-TOCOPHEROL; PREVENTION TRIAL AB Oxidative stress may enhance prostatic carcinogenesis. A polymorphism [valine (V) -> alanine (A)] of manganese superoxide dismutase (MnSOD), the primary antioxidant enzyme in mitochondria, has been recently associated with prostate cancer. We examined the relationship between prostate cancer and the MnSOD polymorphism and its interactions with baseline plasma antioxidant levels (selenium, lycopene, and alpha-tocopherol) and beta-carotene treatment among 567 cases and 764 controls nested in the prospective Physicians' Health Study. We found little overall association between MnSOD polymorphism and prostate cancer risk; however, this polymorphism significantly modified risk of prostate cancer associated with prediagnostic plasma antioxidants (P-interaction <= 0.05). Among men with the AA genotype, high selenium level (4th versus 1st quartile) was associated with a relative risk (RR) of 0.3 [95% confidence interval (CI), 0.2-0.7] for total prostate cancer; for clinically aggressive prostate cancer, the RR was 0.2 (95% CI, 0.1-0.5). In contrast, among men with the VV/VA genotype, the RRs were 0.6 (0.4-1.0) and 0.7 (0.4-1.2) for total and clinically aggressive prostate cancer. These patterns were similar for lycopene and alpha-tocopherol and were particularly strong when these antioxidants and selenium were combined; men with the AA genotype had a 10-fold gradient in risk for aggressive prostate cancer across quartiles of antioxidant status. Men with AA genotype who were randomly assigned to beta-carotene treatment (versus placebo) had a RR of 0.6 (95% CI, 0.2-0.9; P-interaction = 0.03) for fatal prostate cancer, but no significant association was observed in men with the VV/VA genotype. Both endogenous and exogenous antioxidants play an important and interdependent role in preventing clinically significant prostate cancer. C1 Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Prevent Med, Boston, MA 02115 USA. Dana Farber Canc Inst, Dept Med Oncol, Div Solid Tumor Oncol, Lank Ctr Genitourinary Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Massachusetts Vet Epidemiol Res & Informat Ctr, Vet Adm Boston Healthcare Syst, Boston, MA USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Li, HJ (reprint author), Brigham & Womens Hosp, Dept Med, Channing Lab, Room 452,181 Longwood Ave, Boston, MA 02115 USA. EM haojie.li@channing.harvard.edu FU NCI NIH HHS [CA42182, CA58684, CA90598, R01 CA097193] NR 34 TC 145 Z9 152 U1 0 U2 5 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 MAR 15 PY 2005 VL 65 IS 6 BP 2498 EP 2504 DI 10.1158/0008-5472.CAN-04-3535 PG 7 WC Oncology SC Oncology GA 905VW UT WOS:000227600000058 PM 15781667 ER PT J AU Bild, DE Detrano, R Peterson, D Guerci, A Liu, K Shahar, E Ouyang, P Jackson, S Saad, MF AF Bild, DE Detrano, R Peterson, D Guerci, A Liu, K Shahar, E Ouyang, P Jackson, S Saad, MF TI Ethnic differences in coronary calcification - The multi-ethnic study of atherosclerosis (MESA) SO CIRCULATION LA English DT Article DE epidemiology; atherosclerosis; coronary disease; calcium ID BEAM COMPUTED-TOMOGRAPHY; ARTERY RISK DEVELOPMENT; YOUNG-ADULTS CARDIA; RACIAL-DIFFERENCES; AFRICAN-AMERICANS; WHITE SUBJECTS; CALCIUM; PREVALENCE; CT; QUANTIFICATION AB Background - There is substantial evidence that coronary calcification, a marker for the presence and quantity of coronary atherosclerosis, is higher in US whites than blacks; however, there have been no large population-based studies comparing coronary calcification among US ethnic groups. Methods and Results - Using computed tomography, we measured coronary calcification in 6814 white, black, Hispanic, and Chinese men and women aged 45 to 84 years with no clinical cardiovascular disease who participated in the Multi-Ethnic Study of Atherosclerosis (MESA). The prevalence of coronary calcification (Agatston score > 0) in these 4 ethnic groups was 70.4%, 52.1%, 56.5%, and 59.2%, respectively, in men (P < 0.001) and 44.6%, 36.5%, 34.9%, and 41.9%, respectively, (P < 0.001) in women. After adjustment for age, education, lipids, body mass index, smoking, diabetes, hypertension, treatment for hypercholesterolemia, gender, and scanning center, compared with whites, the relative risks for having coronary calcification were 0.78 (95% CI 0.74 to 0.82) in blacks, 0.85 (95% CI 0.79 to 0.91) in Hispanics, and 0.92 (95% CI 0.85 to 0.99) in Chinese. After similar adjustments, the amount of coronary calcification among those with an Agatston score > 0 was greatest among whites, followed by Chinese (77% that of whites; 95% CI 62% to 96%), Hispanics (74%; 95% CI 61% to 90%), and blacks (69%; 95% CI 59% to 80%). Conclusions - We observed ethnic differences in the presence and quantity of coronary calcification that were not explained by coronary risk factors. Identification of the mechanism underlying these differences would further our understanding of the pathophysiology of coronary calcification and its clinical significance. Data on the predictive value of coronary calcium in different ethnic groups are needed. C1 NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Harbor UCLA Res & Educ Inst, Torrance, CA USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. St Francis Hosp, Roslyn, NY USA. Northwestern Univ, Dept Prevent Med, Chicago, IL USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN 55455 USA. Johns Hopkins Univ, Sch Med, Div Cardiol, Baltimore, MD USA. Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. RP Bild, DE (reprint author), NHLBI, Div Epidemiol & Clin Applicat, 6701 Rockledge Dr,MSC 7438, Bethesda, MD 20892 USA. EM bildd@nh1bi.nih.gov FU NHLBI NIH HHS [N01-HC-95163, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95162, N01-HC-95164, N01-HC-95165, N01-HC-95166] NR 37 TC 357 Z9 373 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 15 PY 2005 VL 111 IS 10 BP 1313 EP 1320 DI 10.1161/01.CIR.0000157730.94423.4B PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 906CB UT WOS:000227617000018 PM 15769774 ER PT J AU Yang, SH Mechanic, LE Yang, P Landi, MT Bowman, ED Wampfler, J Meerzaman, D Hong, KM Mann, F Dracheva, T Fukuoka, J Travis, W Caporaso, NE Harris, CC Jen, A AF Yang, SH Mechanic, LE Yang, P Landi, MT Bowman, ED Wampfler, J Meerzaman, D Hong, KM Mann, F Dracheva, T Fukuoka, J Travis, W Caporaso, NE Harris, CC Jen, A TI Mutations in the tyrosine kinase domain of the epidermal growth factor receptor in non-small cell lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID GEFITINIB; INHIBITOR; THERAPY; IRESSA; ZD1839; TRIAL AB We evaluated somatic genetic alterations in the kinase domain of the EGFR gene in the tumors of 219 non-small cell lung cancer patients of primarily Caucasian and African American origins. We identified 26 patients (12%) whose tumors had a mutation in the EGFR gene, and 11 (5%) patients carried novel genomic variations consistent with germ-line polymorphisms. All but one mutation were identified in Caucasian patients affected with adenocarcinoma. EGFR mutations were more frequent in women and in nonsmokers, but a significant portion of the affected patients were men (12 of 26) and current or past smokers accounted for half of the patients affected (13 of 26). Screening subjects with EGFR mutations may identify patients whose tumors could respond to targeted therapy using tyrosine kinase inhibitors. C1 NCI, Lab Populat Genet, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Human Carcinogenesis Lab, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. RP Jen, A (reprint author), NCI, Lab Populat Genet, Div Canc Epidemiol & Genet, Room D702,41 Lib Dr, Bethesda, MD 20892 USA. EM jenj@mail.nih.gov FU NCI NIH HHS [CA 80127, CA 84354] NR 17 TC 99 Z9 103 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 MAR 15 PY 2005 VL 11 IS 6 BP 2106 EP 2110 DI 10.1158/1078-0432.CCR-04-1853 PG 5 WC Oncology SC Oncology GA 908EK UT WOS:000227770000002 PM 15788655 ER PT J AU Kudo-Saito, C Schlom, J Hodge, JW AF Kudo-Saito, C Schlom, J Hodge, JW TI Induction of an antigen cascade by diversified subcutaneous/intratumoral vaccination is associated with antitumor responses SO CLINICAL CANCER RESEARCH LA English DT Article ID COSTIMULATORY MOLECULES; IMMUNE-RESPONSES; TUMOR REJECTION; MAMMARY ADENOCARCINOMA; SELF-ANTIGEN; EPITOPE; CELLS; GENE; IMMUNOTHERAPY; THERAPY AB Purpose: Cancer vaccines targeting tumor-associated antigens are being investigated for the therapy of tumors. Numerous strategies, including the direct intratumoral (i.t.) vaccination route, have been examined. For tumors expressing carcinoembryonic antigen (CEA) as a model tumor-associated antigen, we previously designed poxviral vectors that contain the transgenes for CEA and a triad of T-cell costimulatory molecules, B7-1, intercellular adhesion molecule-1, (ICAM-1), and leukocyte function associated antigen-3 (LFA-3) (CEA/TRICOM). Two types of poxvirus vectors were developed: replication-competent recombinant vaccinia and replication-defective recombinant fowlpox. We have shown previously that a vaccine regimen composed of priming mice s.c. with recombinant vaccinia-CEA/TRICOM and boosting i.t. with recombinant fowlpox-CEA/TRICOM was superior to priming and boosting vaccinations using the conventional s.c. route in inducing T-cell responses specific for CEA. These studies also showed that CEA was needed to be present both in the vaccine and in the tumor for therapeutic effects. Experimental Design: To determine specific immune responses associated with vaccination-mediated tumor regression, CEA-transgenic mice bearing CEA(+) tumors were vaccinated with the CEA/TRICOM s.c./i.t. regimen, and T-cell immune responses were assessed. Results: In CEX+ tumor-bearing mice vaccinated with the CEA/TRICOM s.c./i.t. regimen, T-cell responses could be detected not only to CEA encoded in vaccine vectors but also to other antigens expressed on the tumor itself: wild-type p53 and an endogenous retroviral epitope of gp70. Moreover, the magnitude of CD8+ T-cell immune responses to gp70 was far greater than that induced to CEA or p53. Finally, the predominant T-cell population infiltrating the regressing CEA(+) tumor after therapy was specific for gp70. Conclusion: These studies show that the breadth and magnitude of antitumor immune cascades to multiple antigens could be critical in the therapy of established tumors. C1 NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Point Mugu Nawc, CA 93042 USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bldg 10,Room 8B07, Point Mugu Nawc, CA 93042 USA. EM js141c@nih.gov RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 NR 31 TC 52 Z9 53 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR 15 PY 2005 VL 11 IS 6 BP 2416 EP 2426 DI 10.1158/1078-0432.CCR-04-1380 PG 11 WC Oncology SC Oncology GA 908EK UT WOS:000227770000040 PM 15788693 ER PT J AU Mildvan, D Spritzler, J Grossberg, SE Fahey, JL Johnston, DM Schock, BR Kagan, J AF Mildvan, D Spritzler, J Grossberg, SE Fahey, JL Johnston, DM Schock, BR Kagan, J TI Serum neopterin, an immune activation marker, independently predicts disease progression in advanced HIV-1 infection SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; TUMOR-NECROSIS-FACTOR; AIDS CLINICAL-TRIALS; ANTIRETROVIRAL THERAPY; PROGNOSTIC VALUE; SURROGATE MARKERS; ZIDOVUDINE RESISTANCE; PLASMA MARKERS; RNA LEVELS; CYTOKINES AB Background. CD4(+) T lymphocyte ( CD4) counts and plasma human immunodeficiency virus ( HIV) type 1 RNA concentrations predict clinical outcome in HIV-1 infection. Our objective was to assess the independent prognostic value for disease progression of soluble markers of immune system activation. Methods. This retrospective marker- validation study utilized previously obtained clinical and laboratory data, including CD4(+) cell counts, and made use of stored frozen serum samples to assay for levels of beta(2)- microglobulin, neopterin, endogenous interferon, triglycerides, interleukin- 6, soluble tumor necrosis factor-alpha receptor II, and HIV-1 RNA, and to determine HIV genotypic reverse- transcriptase inhibitor resistance. The 152 patients who participated in this study represented a subsample of participants in AIDS Clinical Trials Group ( ACTG) 116B/ 117, a randomized trial that demonstrated the clinical benefit of didanosine over zidovudine monotherapy in persons with advanced HIV-1 infection. Marker data were analyzed in relation to protocol-defined clinical disease progression, using Cox proportional hazards models. Results. The median duration of follow-up was 344 days. Elevated baseline values for neopterin (P =.0009), endogenous interferon (P =.00039) and interleukin-6 (P =.0007) were each associated with greater subsequent risk of clinical disease progression. In a head-to-head comparison that was adjusted for CD4(+) cell count (P= .0165) and HIV-1 RNA level (P =.1220), we found that elevated values for neopterin (P = .0002) and, to a lesser extent, endogenous inferon (P= .0053) were the strongest predictors of increased risk of clinical disease progression 6 months later. Conclusions. Soluble markers of immune activation add prognostic information to CD4 counts and viral load for risk of disease progression in advanced HIV-1 infection. The robust performance of neopterin, an in-expensive and reliably measured serum marker, supports its potential suitability for patient monitoring, particularly in resource-limited settings. C1 Beth Israel Med Ctr, New York, NY 10003 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. LabCorp, Res Triangle Pk, NC USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. NIAID, Div Aids, Bethesda, MD 20892 USA. RP Mildvan, D (reprint author), Beth Israel Med Ctr, 1st Ave & 16th St, New York, NY 10003 USA. EM mildvan@ix.netcom.com FU NIAID NIH HHS [AI36086, AI-46370, AI-38858, AI-38855] NR 40 TC 40 Z9 42 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2005 VL 40 IS 6 BP 853 EP 858 DI 10.1086/427877 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JP UT WOS:000227492800013 PM 15736019 ER PT J AU Hershow, RC O'Driscoll, PT Handelsman, E Pitt, J Hillyer, G Serchuck, L Lu, M Chen, KT Yawetz, S Pacheco, S Davenny, K Adeniyi-Jones, S Thomas, DL AF Hershow, RC O'Driscoll, PT Handelsman, E Pitt, J Hillyer, G Serchuck, L Lu, M Chen, KT Yawetz, S Pacheco, S Davenny, K Adeniyi-Jones, S Thomas, DL TI Hepatitis C virus coinfection and HIV load, CD4(+) cell percentage, and clinical progression to AIDS or death among HIV-infected women: Women and infants transmission study SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; DISEASE PROGRESSION; ANTIRETROVIRAL THERAPY; DRUG-USERS; SURVIVAL; TYPE-1; RNA; HEMOPHILIACS; METAANALYSIS; LYMPHOCYTES AB Background. Despite previous study, it remains unclear whether hepatitis C virus ( HCV) coinfection affects the progression of human immunodeficiency virus (HIV) type 1 infection. The Women and Infants Transmission Study provided an opportunity to assess this issue. Methods. Longitudinal data on 652 HIV-1-infected women enrolled in the study before the availability of highly active antiretroviral therapy ( HAART; 1989 - 1995) were analyzed. Random effects models were used to determine whether HCV coinfection was associated with different CD4(+) cell percentages and HIV-1 RNA levels over time, and Cox proportional hazards models were used to compare the rates of clinical progression to acquired immunodeficiency syndrome (AIDS) or death. Results. Of 652 women, 190 (29%) were HCV infected. During follow- up, 19% of women were exposed to HAART. After controlling for indicators of disease progression ( CD4(+) cell percentages and HIV-1 RNA levels determined closest to the time of delivery in pregnant women), ongoing drug use, receipt of antiretroviral therapy, and other important covariates, no differences were detected in the HIV-1 RNA levels, but the CD4+ cell percentages were slightly higher in HCV-infected women than in HCV- uninfected women. During follow- up, 48 women had progression to a first clinical AIDS- defining illness ( ADI), and 26 died with no documented antecedent ADI. In multivariable analyses, HCV- infected participants did not have faster progression to a first class C AIDS- defining event or death ( relative hazard, 0.75; 95% confidence interval, 0.37 - 1.53). Conclusions. In this cohort, the rate of clinical progression of HIV-1 infection was not greater for HCV-infected women. C1 Univ Illinois, Chicago Sch Publ Hlth, Chicago, IL 60612 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. Clin Trials & Surveys, Baltimore, MD USA. NICHHD, Bethesda, MD 20892 USA. NIDA, Bethesda, MD 20892 USA. NIAID, Bethesda, MD USA. Suny Downstate Med Ctr, New York, NY USA. Columbia Univ, Coll Phys & Surg, New York, NY USA. Brigham & Womens Hosp, Div Infect Dis, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Puerto Rico, San Juan, PR 00936 USA. RP Hershow, RC (reprint author), Univ Illinois, Chicago Sch Publ Hlth, Rm 987,1603 W Taylor St, Chicago, IL 60612 USA. EM rchersho@uic.edu FU NCRR NIH HHS [RR00645, RR00188]; NIAID NIH HHS [N01 AI 85339, U01 AI 34858, U01 AI 34841, 1 U01 AI 50274-01]; NICHD NIH HHS [U01 HD 36117, U01 HD 41983]; NIDA NIH HHS [9U01 DA 15054, U01 DA 15053] NR 36 TC 24 Z9 28 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2005 VL 40 IS 6 BP 859 EP 867 DI 10.1086/428121 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JP UT WOS:000227492800014 PM 15736020 ER PT J AU Siddiqui, AR Jooma, RA Smego, RA AF Siddiqui, AR Jooma, RA Smego, RA TI Nosocomial outbreak of hepatitis E infection in Pakistan with possible parenteral transmission SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID E VIRUS; BLOOD-TRANSFUSION; ANTIBODIES C1 Aga Khan Univ, Karachi, Pakistan. Jinnah Postgrad Med Ctr, Karachi, Pakistan. RP Smego, RA (reprint author), NIAID, Lab Immunogenet, NIH, Twinbrook 2,Rm 236,MSC 8180,12441 Parklawn Dr, Rockville, MD 20852 USA. EM rsmego@niaid.nih.gov NR 9 TC 11 Z9 11 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2005 VL 40 IS 6 BP 908 EP 909 DI 10.1086/428357 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904JP UT WOS:000227492800028 PM 15736034 ER PT J AU Benson, CA Kaplan, JE Masur, H Pau, A Holmes, KK AF Benson, CA Kaplan, JE Masur, H Pau, A Holmes, KK TI Treating opportunistic infections among HIV-infected adults and adolescents: Recommendations from CDC, the national institutes of health, and the HIV medicine association/infectious diseases society of America SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; PNEUMOCYSTIS-CARINII-PNEUMONIA; MYCOBACTERIUM-AVIUM COMPLEX; ACTIVE ANTIRETROVIRAL THERAPY; HEPATITIS-C VIRUS; HERPES-SIMPLEX-VIRUS; HUMAN-PAPILLOMAVIRUS INFECTION; CENTRAL-NERVOUS-SYSTEM; MOTHER-TO-CHILD; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY AB The CDC, National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America have developed guidelines for treatment of opportunistic infections (OIs) among adults and adolescents infected with human immunodeficiency virus (HIV). These guidelines are intended for clinicians and other health-care providers who care for HIV-infected adults and adolescents, including pregnant women; they complement companion guidelines for treatment of OIs among HIV-infected children and previously published guidelines for prevention of OIs in these populations. They include evidence-based guidelines for treatment of 28 OIs caused by protozoa, bacteria, fungi, and viruses, including certain OIs endemic in other parts of the world but that might be observed in patients in the United States. Each OI section includes information on epidemiology, clinical manifestations, diagnosis, treatment recommendations, monitoring and adverse events, management of treatment failure, prevention of recurrence, and special considerations in pregnancy. Tables address drugs and doses, drug toxicities, drug interactions, adjustment of drug doses in persons with reduced renal function, and data about use of drugs in pregnant women. C1 Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NIH, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. RP Benson, CA (reprint author), Univ Calif San Diego, Antrivral Res Ctr, 150 W Washington St,Ste 100, San Diego, CA 92103 USA. EM cbenson@ucsd.edu NR 683 TC 21 Z9 23 U1 2 U2 5 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 MAR 15 PY 2005 VL 40 SU 3 BP S131 EP S235 DI 10.1086/427906 PG 105 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 904VP UT WOS:000227526500001 ER PT J AU Herrera, L Ottolenghi, C Garcia-Ortiz, JE Pellegrini, M Manini, F Ko, MSH Nagaraja, R Forabosco, A Schlessinger, D AF Herrera, L Ottolenghi, C Garcia-Ortiz, JE Pellegrini, M Manini, F Ko, MSH Nagaraja, R Forabosco, A Schlessinger, D TI Mouse ovary developmental RNA and protein markers from gene expression profiling SO DEVELOPMENTAL BIOLOGY LA English DT Article DE microarray; ovary; primordial follicles; development ID HUMAN ENDOGENOUS RETROVIRUS; TRANSCRIPTION FACTOR FOXL2; LONG TERMINAL REPEAT; TRANSGENIC MICE; MAMMALIAN OVARY; RAT OVARY; GERM-LINE; GONADAL DIFFERENTIATION; FOLLICULAR DEVELOPMENT; CELL DIFFERENTIATION AB To identify, genes involved in morphogenetic events during mouse ovary development, we started with microarray analyses of whole organ RNA. Transcripts for 60% of the 15,000 gene NIA panel were detected, and about 2000 were differentially expressed in nascent newborn compared to adult ovary. Highly differentially expressed transcripts included noncoding RNAs and newly detected genes involved in transcription regulation and signal transduction. The phased pattern of newborn Mouse ovary differentiation allowed LIS to (1) extend information on activity and stage specificity of cell type-specific genes; and (2) generate a list of candidate genes involved in primordial follicle formation, including podocalyxin (Podxl), PDGFR-beta, and a follistatin-domain-encoding gene Flstl. Oocyte-specific transcripts included many (e.g., Deltex2, Bicd2, and Zfp37) enriched in growing oocytes, as well as a novel family of untranslated RNA's (RLTR10) that is selectively expressed in early stage follicles. The results indicate that global expression profiling of whole organ RNA provides sensitive first-line information about ovarian histogenesis for which no in vitro cell models are currently available. Published by Elsevier Inc. C1 NIA, Gerontol Res Ctr, Genet Lab, Baltimore, MD 21224 USA. Univ Modena, Dept Mother & Child, Policlin, I-41100 Modena, Italy. RP Schlessinger, D (reprint author), NIA, Gerontol Res Ctr, Genet Lab, Suite 3000,333 Cassell Dr, Baltimore, MD 21224 USA. EM schlessingierd@grc.nia.nih.gov RI Ko, Minoru/B-7969-2009; Pellegrini, Massimo/P-6359-2016 OI Ko, Minoru/0000-0002-3530-3015; Pellegrini, Massimo/0000-0002-0091-0077 NR 97 TC 36 Z9 37 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD MAR 15 PY 2005 VL 279 IS 2 BP 271 EP 290 DI 10.1016/j.ydbio.2004.11.029 PG 20 WC Developmental Biology SC Developmental Biology GA 904HR UT WOS:000227487200001 PM 15733658 ER PT J AU Kadiiska, MB Gladen, BC Baird, DD Germolec, D Graham, LB Parker, CE Nyska, A Wachsman, JT Ames, BN Basu, S Brot, N FitzGerald, GA Floyd, RA George, M Heinecke, JW Hatch, GE Hensley, K Lawson, JA Marnett, LJ Morrow, JD Murray, DM Plastaras, J Roberts, LJ Rokach, J Shigenaga, MK Sohal, RS Sun, J Tice, RR Van Thiel, DH Wellner, D Walter, PB Tomer, KB Mason, RP Barrett, JC AF Kadiiska, MB Gladen, BC Baird, DD Germolec, D Graham, LB Parker, CE Nyska, A Wachsman, JT Ames, BN Basu, S Brot, N FitzGerald, GA Floyd, RA George, M Heinecke, JW Hatch, GE Hensley, K Lawson, JA Marnett, LJ Morrow, JD Murray, DM Plastaras, J Roberts, LJ Rokach, J Shigenaga, MK Sohal, RS Sun, J Tice, RR Van Thiel, DH Wellner, D Walter, PB Tomer, KB Mason, RP Barrett, JC TI Biomarkers of oxidative stress study II. Are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning? SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE CCl4; rat; plasma; urine; lipid hydroperoxides; TBARS; MDA; isoprostanes; protein carbonyls; methionine sulfoxidation; tyrosine products; 8-OhdG; M(1)G; DNA strand breaks; free radicals ID PERFORMANCE LIQUID-CHROMATOGRAPHY; THIOBARBITURIC ACID-REACTIVITY; LOW-DENSITY-LIPOPROTEIN; FREE-RADICAL DAMAGE; CARBON-TETRACHLORIDE; IN-VIVO; MASS-SPECTROMETRY; AMINO-ACIDS; METHIONINE SULFOXIDE; BIOLOGICAL-MATERIALS AB Oxidation products of lipids, proteins, and DNA in the blood, plasma, and urine of rats were measured as part of a comprehensive, multilaboratory validation study searching for noninvasive biomarkers of oxidative stress. This article is the second report of the nationwide Biomarkers of Oxidative Stress Study using acute CCl4 poisoning as a rodent model for oxidative stress. The time-dependent (2, 7, and 16 h) and dose-dependent (120 and 1200 mg/kg ip) effects Of CCl4 on concentrations of lipid hydroperoxides, TBARS, malondialdehyde (MDA), isoprostanes, protein carbonyls, methionine sulfoxidation, tyrosine products, 8-hydroxy-2'-deoxyguano sine (8-OHdG), leukocyte DNA-MDA adducts, and DNA-strand breaks were investigated to determine whether the oxidative effects Of CCl4 would result in increased generation of these oxidation products. Plasma concentrations of MDA and isoprostanes (both measured by GG MS) and urinary concentrations of isoprostanes (measured with an immunoassay or LC/MS/MS) were increased in both low-dose and high-dose CCl4-treated rats at more than one time point. The other urinary markers (MDA and 8-OHdG) showed significant elevations with treatment Under three of the four conditions tested. It is concluded that measurements of MDA and isoprostanes in plasma and urine as well as 8-OHdG ill Urine are potential candidates for general biomarkers of oxidative stress. All other products were not changed by CCl4 or showed fewer significant effects. Published by Elsevier Inc. C1 NIEHS, US Dept HHS, NIH, Res Triangle Pk, NC 27709 USA. Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. Uppsala Univ, Fac Med, SE-75105 Uppsala, Sweden. Cornell Univ, Weill Med Coll, Hosp Special Surg, New York, NY 10029 USA. Univ Penn, Ctr Expt Therapeut, Philadelphia, PA 19104 USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. US EPA, Res Triangle Pk, NC 27711 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37240 USA. Vanderbilt Univ, Sch Med, Dept Med Pharmacol, Nashville, TN 37240 USA. OXIS Int Inc, Portland, OR 97217 USA. Florida Inst Technol, Melbourne, FL 32901 USA. Univ So Calif, Dept Mol Pharmacol & Toxicol, Los Angeles, CA 90089 USA. Integrated Lab Syst Inc, Res Triangle Pk, NC 27709 USA. Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA. RP Kadiiska, MB (reprint author), NIEHS, US Dept HHS, NIH, POB 12233,MD F0-02, Res Triangle Pk, NC 27709 USA. EM Kadiiska@niehs.nih.gov RI Walter, Patrick/A-4117-2011; FitzGerald, Garret/A-4222-2010; Tomer, Kenneth/E-8018-2013; OI Baird, Donna/0000-0002-5544-2653 NR 78 TC 396 Z9 409 U1 4 U2 42 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD MAR 15 PY 2005 VL 38 IS 6 BP 698 EP 710 DI 10.1016/j.freeradbiomed.2004.09.017 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 904MN UT WOS:000227502500002 PM 15721980 ER PT J AU Kadiiska, MB Gladen, BC Baird, DD Graham, LB Parker, CE Ames, BN Basu, S FitzGeraldd, GA Lawson, JA Marnett, LJ Morrow, JD Murray, DM Plastaras, J Roberts, LJ Rokach, J Shigenaga, MK Sun, J Walter, PB Tomer, KB Barrett, JC Mason, RP AF Kadiiska, MB Gladen, BC Baird, DD Graham, LB Parker, CE Ames, BN Basu, S FitzGeraldd, GA Lawson, JA Marnett, LJ Morrow, JD Murray, DM Plastaras, J Roberts, LJ Rokach, J Shigenaga, MK Sun, J Walter, PB Tomer, KB Barrett, JC Mason, RP TI Biomarkers of oxidative stress study III. Effects of the nonsteroidal anti-inflammatory agents indomethacin and meclofenamic acid on measurements of oxidative products of lipids in CCl4 poisoning SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE CCl4; indomethacin; meclofenamic acid; rat; plasma; urine; MDA; isoprostanes; free radicals ID URINARY 8-EPI-PROSTAGLANDIN F2-ALPHA; IN-VIVO; OXIDANT STRESS; CYCLOOXYGENASE INHIBITION; DEPENDENT FORMATION; ENDOTHELIAL-CELLS; MASS-SPECTROMETRY; BIOLOGICAL-FLUIDS; F-2 ALPHA; QUANTIFICATION AB Plasma and urinary levels of malondialdehyde-like products (MDA) and isoprostanes were identified as markers of in vivo lipid peroxidation in an animal model of CCl4 poisoning. We sought to determine the extent to which the formation of these oxidation products is influenced by inhibition of the cyclooxygenase enzymes which catalytically generate proinflammatory lipid peroxidation products known as prostaglandins and thromboxane. In the present studies, after induction of oxidant stress in rats With CCl4, lipid peroxidation products measured in plasma and Urine demonstrate that isoprostanes and MDA can be partially inhibited by cyclooxygenase inhibitors, albeit to different extents. The lowering of isoprostane and MDA formation, however, may not to doe primarily to the diminution of catalytic generation of isoprostanes or MDA by the cyclooxygenases but, rather, may be the result of the suppression of nonenzymatic lipid peroxidation. This is suggested since 8,12-iso-iPF(2 alpha)-V1 is also reduced by indomethacin, yet, unlike other isoprostanes and MDA, it is not generated catalytically by the cyclooxygenase. Thus, although the two cyclooxygenase inhibitors we tested have statistically significant effects on the measurements of both isoprostanes and MDA in this Study, the results provide evidence that these lipid-degradation products primarily constitute markers of oxidative stress. Published by Elsevier Inc. C1 NIEHS, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. Childrens Hosp, Oakland Res Inst, Oakland, CA 94609 USA. Uppsala Univ, Fac Med, Uppsala, Sweden. Univ Penn, Ctr Expt Therapeut, Philadelphia, PA 19104 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37240 USA. Vanderbilt Univ, Dept Med & Pharmacol, Nashville, TN 37240 USA. Oxis Int Inc, Portland, OR 97217 USA. Florida Inst Technol, Melbourne, FL 32901 USA. RP Kadiiska, MB (reprint author), NIEHS, NIH, US Dept HHS, POB 12233,MD F0-02, Res Triangle Pk, NC 27709 USA. EM Kadiiska@niehs.nih.gov RI Walter, Patrick/A-4117-2011; Tomer, Kenneth/E-8018-2013; OI Baird, Donna/0000-0002-5544-2653 NR 43 TC 108 Z9 112 U1 1 U2 6 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 MAR 15 PY 2005 VL 38 IS 6 BP 711 EP 718 DI 10.1016/freeradbiomed.2004.10.024 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 904MN UT WOS:000227502500003 PM 15721981 ER PT J AU Stuart, JA Bourque, BM de Souza-Pinto, NC Bohr, VA AF Stuart, JA Bourque, BM de Souza-Pinto, NC Bohr, VA TI No evidence of mitochondrial respiratory dysfunction in OGG1-null mice deficient in removal of 8-oxodeoxyguanine from mitochondrial DNA SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE free radicals; mitochondria; Ogg1(-/-); oxygen consumption ID OXIDATIVE DAMAGE; RNA-POLYMERASE; TRANSCRIPTION ELONGATION; LIPID-PEROXIDATION; REPERFUSION INJURY; COMPLEX ACTIVITY; BASE DAMAGE; AGE; ACCUMULATION; REPAIR AB Accumulation of high levels of mutagenic oxidative mitochondrial DNA (mtDNA) lesions like 8-oxodeoxyguanine (8-oxodG) is thought to be involved in the development of mitochondrial dysfunction in aging and in disorders associated with aging. Mice null for oxoguanine DNA glycosylase (OGG1) are deficient in 8-oxodG removal and accumulate 8-oxodG in mtDNA to levels 20-fold higher than in wild-type mice (N.C. Souza-Pinto et al., 200 1, Cancer Res. 61, 5378-5381). We have used these animals to investigate the effects on mitochondrial function of accumulating this particular oxidative base modification. Despite the presence of high levels of 8-oxodG, mitochondria isolated from livers and hearts of Oggl(-/-) mice were functionally normal. No differences were detected in maximal (chemically uncoupled) respiration rates, ADP phosphorylating respiration rates, or nonphosphorylating rates with glutamate/malate or with succinate/rotenone. Similarly, maximal activities of respiratory complexes I and IV from liver and heart were not different between wild-type and Oggl(-/-) mice. In addition, there was no indication of increased oxidative stress in mitochondria from Qggl(-/-) mice, as measured by mitochondrial protein carbonyl content. We conclude, therefore, that highly elevated levels of 8-oxodG in mtDNA do not cause mitochondrial respiratory dysfunction in mice. Published by Elsevier Inc. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21236 USA. Brock Univ, Dept Biol, St Catharines, ON L2S 3A1, Canada. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21236 USA. EM vbohr@nih.gov RI Souza-Pinto, Nadja/C-3462-2013 OI Souza-Pinto, Nadja/0000-0003-4206-964X NR 39 TC 54 Z9 57 U1 0 U2 3 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 MAR 15 PY 2005 VL 38 IS 6 BP 737 EP 745 DI 10.1016/j.freeradbiomed.2004.12.003 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 904MN UT WOS:000227502500006 PM 15721984 ER PT J AU Citrin, D Ning, H Guion, P Li, G Susil, RC Miller, RW Lessard, E Pouliot, J Huchen, X Capala, J Coleman, CN Camphausen, K Menard, C AF Citrin, D Ning, H Guion, P Li, G Susil, RC Miller, RW Lessard, E Pouliot, J Huchen, X Capala, J Coleman, CN Camphausen, K Menard, C TI Inverse treatment planning based on MRI for HDR prostate brachytherapy SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE brachytherapy; high dose rate; inverse planning; MRI; prostate ID MAGNETIC-RESONANCE-SPECTROSCOPY; IMAGING-GUIDED BRACHYTHERAPY; DOSE-RATE BRACHYTHERAPY; INTEROBSERVER VARIABILITY; NEUROVASCULAR BUNDLES; RADIATION-THERAPY; ERECTILE DYSFUNCTION; ENDORECTAL MR; CANCER; CT AB Purpose: To develop and optimize a technique for inverse treatment planning based solely on magnetic resonance imaging (MRI) during high-dose-rate brachytherapy for prostate cancer. Methods and Materials: Phantom studies were performed to verify the spatial integrity of treatment planning based on MRI. Data were evaluated from 10 patients with clinically localized prostate cancer who had undergone two high-dose-rate prostate brachytherapy boosts under MRI guidance before and after pelvic radiotherapy. Treatment planning MRI scans were systematically evaluated to derive a class solution for inverse planning constraints that would reproducibly result in acceptable target and normal tissue dosimetry. Results: We verified the spatial integrity of MRI for treatment planning. MRI anatomic evaluation revealed no significant displacement of the prostate in the left lateral decubitus position, a mean distance of 14.47 mm from the prostatic apex to the penile bulb, and clear demarcation of the neurovascular bundles on postcontrast imaging. Derivation of a class solution for inverse planning constraints resulted in a mean target volume receiving 100% of the prescribed dose of 95.69%, while maintaining a rectal volume receiving 75% of the prescribed dose of < 5% (mean 1.36%) and urethral volume receiving 125% of the prescribed dose of < 2% (mean 0.54%). Conclusion: Systematic evaluation of image spatial integrity, delineation uncertainty, and inverse planning constraints-in our procedure reduced uncertainty in planning and treatment. (c) 2005 Elsevier Inc. C1 NCI, Radiat Oncol Branch, CCR, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21205 USA. Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA. RP Citrin, D (reprint author), NCI, Radiat Oncol Branch, CCR, NIH,Dept Hlth & Human Serv, Bldg 10,Rm B3B69,9000 Rockville Pike, Bethesda, MD 20892 USA. EM citrind@mail.nih.gov OI Li, Guang/0000-0002-9022-2883 NR 45 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2005 VL 61 IS 4 BP 1267 EP 1275 DI 10.1016/j.ijrobp.2004.11.024 PG 9 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 905XI UT WOS:000227604200036 PM 15752909 ER PT J AU Andersson, J Boasso, A Nilsson, J Zhang, R Shire, NJ Lindback, S Shearer, GM Chougnet, CA AF Andersson, J Boasso, A Nilsson, J Zhang, R Shire, NJ Lindback, S Shearer, GM Chougnet, CA TI Cutting edge: The prevalence of regulatory T cells lymphoid tissue is correlated with viral load HIV-infected patients SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INDOLEAMINE 2,3-DIOXYGENASE; PERIPHERAL-BLOOD; DENDRITIC CELLS; IN-VITRO; CD4(+); RESPONSES; LYMPHOCYTES; EXPANSION; INDUCTION AB Inadequate local cell-mediated immunity appears crucial for the establishment of chronic HIV infection. Accumulation of regulatory T cells (T-reg) at the site of HIV replication, the lymphoid organs, may influence the outcome of HIV infection. Our data provide the first evidence that chronic HIV infection changes T-reg tissue distribution. Several molecules characteristics of T-reg (FoxP3, CTLA-4, glucocorticoid-induced TNFR family-related receptor, and CD25) were expressed more in tonsils of untreated patients compared with antiretroviral-treated patients. Importantly, most FoxP3(+) cells expressed CTLA-4, but not CD69. Furthermore, a direct correlation between FoxP3 Levels and viral load was evident. In contrast, FoxP3 expression was decreased in circulating T cells from untreated patients, but normalized after initiation of treatment. Functional markers of T-reg activity (indoleamine 2,3-dioxygenase, TGF-beta, and CD80) were markedly increased in the tonsils of untreated patients. Our data could provide a new basis for immune-based therapies that counteract in vivo T-reg and thereby reinforce appropriate antiviral immunity. C1 Childrens Hosp, Med Ctr, Dept Mol Immunol, Cincinnati, OH 45229 USA. Karolinska Univ Hosp, Karolinska Inst, Ctr Infect Med, Dept Med, Stockholm, Sweden. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Div Digest Dis, Cincinnati, OH 45267 USA. RP Chougnet, CA (reprint author), Childrens Hosp, Med Ctr, Dept Mol Immunol, 333 Burnet Ave,MLC 7021, Cincinnati, OH 45229 USA. EM Claire.Chougnet@cchmc.org NR 27 TC 254 Z9 268 U1 2 U2 10 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2005 VL 174 IS 6 BP 3143 EP 3147 PG 5 WC Immunology SC Immunology GA 904PT UT WOS:000227510900002 PM 15749840 ER PT J AU Di Giacinto, C Marinaro, M Sanchez, M Strober, W Boirivant, M AF Di Giacinto, C Marinaro, M Sanchez, M Strober, W Boirivant, M TI Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; CD4(+)CD25(-) T-CELLS; ULCERATIVE-COLITIS; ESCHERICHIA-COLI; MICE; RATS; MESALAZINE; PREVENTION; INDUCTION; MECHANISM AB Recent studies of murine models of mucosal inflammation suggest that, whereas some kinds of bacterial microflora are inducers of disease, others, known as probiotics, prevent disease. In the present study, we analyzed the regulatory cytokine and cell response to probiotic (VSL#3) administration in the context of the Th1 T cell colitis induced by trinitrobenzene sulfonic acid treatment of SJL/J mice. Daily administration of probiotics for 3 wk to mice during a remission period between a first and second course of colitis induced by trinitrobenzene sulfonic acid, resulted in a milder form of recurrent colitis than observed in mice administered PBS during this same period. This protective effect was attributable to effects on the lamina propria mononuclear cell (LPMC) population, because it could be transferred by LPMC from probiotic-treated mice to naive mice. Probiotic administration was associated with an early increase in the production of IL-10 and an increased number of regulatory CD4(+) T cells bearing surface TGF-beta in the form of latency-associated protein (LAP) (LAP(+) T cells). The latter were dependent on the IL-10 production because administration of anti-IL-10R mAb blocked their appearance. Finally, the LAP(+) T cells were essential to the protective effect of probiotics because administration of anti-IL-10R or anti-TGF-beta at the initiation of recurrent colitis induction or depletion of LAP(+) T cells from LPMC abolished the latter's capacity to transfer protection to naive recipients. These studies show that probiotic (VSL#3) administration during a remission period ameliorates the severity of recurrent colitis by inducing an immunoregulatory response involving TGF-beta-bearing regulatory cells. C1 Ist Super Sanita, Dept Infect Parasit & Immune Medicated Dis, Immune Medicated Dis Sect, I-00161 Rome, Italy. Ist Super Sanita, Dept Cell Biol & Neurosci, I-00161 Rome, Italy. NIAID, Mucosal Immun Sect, NIH, Bethesda, MD 20892 USA. RP Boirivant, M (reprint author), Ist Super Sanita, Dept Infect Parasit & Immune Medicated Dis, Immune Medicated Dis Sect, Viale Regina Elena 299, I-00161 Rome, Italy. EM monboir@iss.it RI BOIRIVANT, MONICA/B-9977-2016 NR 31 TC 270 Z9 282 U1 0 U2 11 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 2005 VL 174 IS 6 BP 3237 EP 3246 PG 10 WC Immunology SC Immunology GA 904PT UT WOS:000227510900016 PM 15749854 ER PT J AU Haeryfar, SMM DiPaolo, RJ Tscharke, DC Bennink, JR Yewdell, JW AF Haeryfar, SMM DiPaolo, RJ Tscharke, DC Bennink, JR Yewdell, JW TI Regulatory T cells suppress CD8(+) T cell responses induced by direct priming and cross-priming and moderate immunodominance disparities SO JOURNAL OF IMMUNOLOGY LA English DT Article ID VERSUS-HOST-DISEASE; LYMPHOCYTE RESPONSES; DENDRITIC CELLS; TYPE-1 RESPONSES; TUMOR-IMMUNITY; IN-VIVO; VIRUS; ANTIGEN; EPITOPES; RECEPTOR AB Little is known regarding the participation of CD4(+)CD25(+) regulatory T cells (T-reg) in T-CD8(+) responses. In this study, we show that T-reg depletion via treatment with anti-CD25 mAb (PC61) significantly enhances T-CD8(+) responses to influenza A virus, vaccinia virus, and SV40-transformed cells induced by either direct priming or cross-priming. PC61 did not enhance T-CD8(+) responses in CD4-deficient mice, providing the initial demonstration that PC61 acts on a subset of T-CD4(+), and not on other cells that express either CD25 or a fortuitously cross-reactive Ag. We further show that T-reg selectively suppress responses to the most immunodominant T-CD8(+) determinants in the three systems examined. Therefore, T-reg influence T-CD8 immunodominance hierarchies by moderating disparities in responses to different determinants. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Bennink, JR (reprint author), NIAID, Viral Dis Lab, NIH, Room 211,4 Ctr Dr,Mail Stop 0440, Bethesda, MD 20892 USA. EM jbennink@nih.gov RI yewdell, jyewdell@nih.gov/A-1702-2012; Tscharke, David/C-9133-2009 OI Tscharke, David/0000-0001-6825-9172 NR 48 TC 87 Z9 87 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 MAR 15 PY 2005 VL 174 IS 6 BP 3344 EP 3351 PG 8 WC Immunology SC Immunology GA 904PT UT WOS:000227510900028 PM 15749866 ER PT J AU Roura-Mir, C Catalfamo, M Cheng, TY Marqusee, E Besra, GS Jaraquemada, D Moody, DB AF Roura-Mir, C Catalfamo, M Cheng, TY Marqusee, E Besra, GS Jaraquemada, D Moody, DB TI CD1a and CD1c activate intrathyroidal T cells during graves' disease and Hashimoto's thyroiditis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NKT CELLS; ENDOPLASMIC-RETICULUM; DENDRITIC CELLS; RECOGNITION; ANTIGEN; GLYCOLIPIDS; LYMPHOCYTES; EXPRESSION; MOUSE; AUTOIMMUNITY AB Molecular studies have shown that CD1 proteins present self and foreign lipid Ags to T cells, but the possible roles of CD1 in human autoimmune diseases in vivo are not known, especially for the group 1 CD1 isoforms (CD1a, CD1b, and CD1c). To investigate the hypothesis that CD1-restricted T cells might be activated and home to target tissues involved in Hashimoto's thyroiditis and Graves' disease, we performed ex vivo analysis of lymphocytes from peripheral blood and autoinflammatory lesions of thyroid tissue. Immunofluorescence analysis identified two types of CD1-expressing APCs in inflamed thyroid tissues. CD1a, CD1b, and CD1c were expressed on CD83(+) dendritic cells, and CD1c was expressed on an abundant population of CD20(+)IgD(+)CD23(-)CD38(-) B cells that selectively localized to the mantle zone of lymphoid follicles within the thyroid gland. CD1c-restricted, glycolipid-specific T cells could not be detected in the peripheral blood, but were present in polyclonal lymphocyte populations isolated from affected thyroid glands. In addition, polyclonal thyroid-derived lymphocytes and short-term T cell lines were found to recognize and lyse targets in a CD1a- or CD1c-dependent manner. The targeting of CD1-restricted T cells and large numbers of CD1-expressing APCs to the thyroid gland during the early stages of autoimmune thyroiditis suggests a possible effector function of CD1-restricted T cells in tissue destruction and point to a new model of organ-specific autoinumme disease involving lipid Ag presentation. C1 Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Div Endocrinol Diabet & Hypertens, Thyroid Sect, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Endocrinol Diabet & Hypertens, Thyroid Sect, Boston, MA 02115 USA. Harvard Univ, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England. Univ Autonoma Barcelona, Inst Biotechnol & Biomed, Cellular Immunol Lab, E-08193 Barcelona, Spain. RP Moody, DB (reprint author), Brigham & Womens Hosp, Dept Med, Div Rheumatol Immunol & Allergy, Smith Bldg,Room 514,1 Jimmy Fund Way, Boston, MA 02115 USA. EM bmoody@rics.bwh.harvard.edu RI Roura-Mir, Carme/D-4538-2013; OI Roura-Mir, Carme/0000-0003-0514-337X; Besra, Gurdyal/0000-0002-5605-0395 FU NIAID NIH HHS [AI50216]; NIAMS NIH HHS [AR48632] NR 43 TC 33 Z9 33 U1 1 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 MAR 15 PY 2005 VL 174 IS 6 BP 3773 EP 3780 PG 8 WC Immunology SC Immunology GA 904PT UT WOS:000227510900080 PM 15749918 ER PT J AU Gamain, B Trimnell, AR Scheidig, C Scherf, A Miller, LH Smith, JD AF Gamain, B Trimnell, AR Scheidig, C Scherf, A Miller, LH Smith, JD TI Identification of multiple chondroitin sulfate A (CSA)-binding domains in the var2CSA gene transcribed in CSA-binding parasites SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID FALCIPARUM-INFECTED ERYTHROCYTES; PLASMODIUM-FALCIPARUM; FUNCTIONAL SPECIALIZATION; MALARIA; ADHESION; FAMILY; PLACENTA; RECEPTOR; SURFACE; CD36 AB Malaria in pregnancy is a serious complication associated with parasitized erythrocyte (PE) sequestration in the placenta. Recent work suggests that var genes could play an important role in PE binding to chondroitin sulfate A (CSA), a primary placental adherence receptor. Here, we confirm that var2CSA is transcriptionally up-regulated in CSA-binding parasites and define CSA-binding domains in var2CSA. The identification of multiple binding domains in var2CSA strengthens the evidence for their involvement in malaria during pregnancy and may have applications for the development of a vaccine against malaria in pregnancy. C1 Inst Pasteur, URA 2581, Unite Biol Interact Hote Parasite, F-75724 Paris 15, France. Seattle Biomed Res Inst, Seattle, WA 98109 USA. Univ Washington, Dept Pathobiol, Seattle, WA 98195 USA. NIAID, Lab Mol & Vector Res, NIH, Bethesda, MD 20892 USA. RP Gamain, B (reprint author), Inst Pasteur, URA 2581, Unite Biol Interact Hote Parasite, 25 Rue Docteur Roux, F-75724 Paris 15, France. EM bgamain@pasteur.fr RI Scherf, Artur/A-9674-2014 FU NIAID NIH HHS [R01 AI47953-01A1] NR 15 TC 104 Z9 105 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 MAR 15 PY 2005 VL 191 IS 6 BP 1010 EP 1013 DI 10.1086/428137 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 902UH UT WOS:000227381600026 PM 15717280 ER PT J AU Babu, S Blauvelt, CP Kumaraswami, V Nutman, TB AF Babu, S Blauvelt, CP Kumaraswami, V Nutman, TB TI Chemokine receptors of T cells and of B cells in lymphatic filarial infection: A role for CCR9 in pathogenesis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID BLOOD MONONUCLEAR-CELLS; BANCROFTIAN FILARIASIS; DISEASE; EXPRESSION; LYMPHOCYTES; MICE AB We examined the expression of chemokine receptors on the surfaces of T cells and B cells from 27 individuals either with lymphatic filarial disease (lymphedema), with the asymptomatic or subclinical form of filarial infection, or without filarial infection. Individuals with lymphedema exhibited increased percentages of CCR9-expressing T cells and CCR9-expressing B cells and decreased percentages of both CXCR1-and-CXCR3-expressing T cells and CXCR1-and-CXCR3-expressing B cells, compared with asymptomatic or uninfected individuals. A significant correlation was found between the grade of lymphedema and the percentage of CCR9-expressing T cells and CCR9-expressing B cells. The percentages of CCR9-expressing T cells and CCR9-expressing B cells from patients with lymphedema was significantly up-regulated in response to live, infective-stage larvae of Brugia malayi but not to microfilariae of this parasite. Finally, individuals with lymphedema had significantly higher concentrations of interleukin-8, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, monocyte chemotactic protein 1, thymus-and-activation-regulated chemokine, and interferon-inducible protein 10 in their serum than did uninfected individuals. These results suggest that chemokine receptors (particularly CCR9) are involved in the pathogenesis of lymphatic filarial disease and that trafficking of particular cellular subsets may influence clinical outcome. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. TB Res Ctr, Madras, Tamil Nadu, India. RP Babu, S (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Rm 4-B1-05, Bethesda, MD 20892 USA. EM sbabu@niaid.nih.gov NR 23 TC 14 Z9 16 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 MAR 15 PY 2005 VL 191 IS 6 BP 1018 EP 1026 DI 10.1086/427658 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 902UH UT WOS:000227381600028 PM 15717282 ER PT J AU Ren-Patterson, RF Cochran, LW Holmes, A Sherrill, S Huang, SJ Tolliver, T Lesch, KP Lu, B Murphy, DL AF Ren-Patterson, RF Cochran, LW Holmes, A Sherrill, S Huang, SJ Tolliver, T Lesch, KP Lu, B Murphy, DL TI Loss of brain-derived neurotrophic factor gene allele exacerbates brain monoamine deficiencies and increases stress abnormalities of serotonin transporter knockout mice SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE neurotrophins; serotonin transporter; serotonin; knockout; stress; gene interaction; behaviors; nociception ID FACTOR BDNF GENE; ADULT-RAT; 5-HT1A RECEPTOR; NERVOUS-SYSTEM; MESSENGER-RNA; MUTANT MICE; NEURONAL DIFFERENTIATION; SOMATOSTATIN NEURONS; TARGETED DISRUPTION; SYNAPTIC PLASTICITY AB To study the neurochemical and behavioral effects of altered brain-derived neurotrophic factor (BDNF) expression on a brain serotonin system with diminished serotonin transport capability, a double-mutant mouse model was developed by interbreeding serotonin transporter (SERT) knockout mice with BDNF heterozygous knockout mice (BDNF +/-), producing SERT -/- X BDNF +/- (sb) mice. Prior evidence implicates serotonin and SERT in anxiety and stress responses. Some studies have shown that BDNF supports serotonergic neuronal development, leading to our hypothesis that reduced BDNF availability during development might exaggerate the consequences of absent SERT function. In the present study, brain serotonin and 5-hydroxyindol acetic acid concentrations in male sb mice were significantly reduced in the hippocampus and hypothalamus compared with wildtype control SIB mice, BDNF-deficient Sb mice, and serotonin transporter knockout sB mice. The sb mice had significantly increased anxiety-like behaviors compared with SIB, Sb, and sB mice as measured on the elevated plus maze test. These sb mice also had significantly greater increases in plasma adrenocorticotrophic hormone than mice with other genotypes after a stressful stimulus. Analysis of neuronal morphology showed that hypothalamic and hippocampal neurons exhibited 25-30% reductions in dendrites in sb mice compared with SB control mice. These findings support the hypothesis that genetic changes in BDNF expression interact with serotonin and other circuits that modulate anxiety and stress-related behaviors. Thus, this double-mutant mouse model should prove valuable in studying other gene X gene consequences for brain plasticity as well as in evaluating epistatic interactions of BDNF and serotonin transporter gene polymorphisms in neuropsychiatric disorders. (C) 2005 Wiley-Liss, Inc. C1 NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. NIAAA, Sect Behav Sci & Genet, NIH, Bethesda, MD USA. Univ Wurzburg, Psychiat & Psychotherapy Dept, Wurzburg, Germany. NICHHD, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Ren-Patterson, RF (reprint author), NIMH, Clin Sci Lab, NIH, Bldg 10,Room 3D41, Bethesda, MD 20892 USA. EM renpatr@intra.nimh.nih.gov RI Lu, Bai/A-4018-2012; Lesch, Klaus-Peter/J-4906-2013 OI Lesch, Klaus-Peter/0000-0001-8348-153X NR 98 TC 89 Z9 92 U1 1 U2 3 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 MAR 15 PY 2005 VL 79 IS 6 BP 756 EP 771 DI 10.1002/jnr.20410 PG 16 WC Neurosciences SC Neurosciences & Neurology GA 902NV UT WOS:000227364700004 PM 15672416 ER PT J AU Schaefer, M Heinze, HJ Rotte, M AF Schaefer, M Heinze, HJ Rotte, M TI Viewing touch improves tactile sensory threshold SO NEUROREPORT LA English DT Article DE cross-modal; multisensory; perception; somatosensory cortex; touch; vision ID SOMATOSENSORY CORTEX; SPATIAL-RESOLUTION; VISION; PERCEPTION; ENHANCEMENT; HUMANS; HAND AB Previous research on multisensory integration has demonstrated that viewing the stimulated body part enhances discrimination ability. Participants in this experiment watched a video showing a hand being touched by a stick and a second video showing the stick touching the space beneath the hand. Sensory thresholds of the index fingers were tested with von Frey filaments. We found significant enhancements of the sensory threshold after showing the video with the touched hand but not after showing the video with no touch of the hand. This enhancement was specific for the index finger shown in the video. The results link the visuotactile enhancement of this study to the observation of touch rather than to the simple depiction of the body part. (c) 2005 Lippincott Williams P Wilkins. C1 NINDS, NIH, Human Cort Physiol Sect, Bethesda, MD 20892 USA. Otto Von Guericke Univ, Dept Neurol 2, D-39120 Magdeburg, Germany. RP Schaefer, M (reprint author), NINDS, NIH, Human Cort Physiol Sect, Bethesda, MD 20892 USA. EM schaefem@ninds.nih.gov NR 25 TC 23 Z9 24 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 15 PY 2005 VL 16 IS 4 BP 367 EP 370 DI 10.1097/00001756-200503150-00012 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 910XA UT WOS:000227964300012 PM 15729139 ER PT J AU Ma, BY Pan, YP Gunasekaran, K Venkataraghavan, RB Levine, AJ Nussinov, R AF Ma, BY Pan, YP Gunasekaran, K Venkataraghavan, RB Levine, AJ Nussinov, R TI Comparison of the protein-protein interfaces in the p53-DNA crystal structures: Towards elucidation of the biological interface SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE p53 dimeric interface; p53 tetramer; hot spots; cancer; gene regulation ID P53 TUMOR-SUPPRESSOR; DNA-BINDING; CORE DOMAIN; TRANSCRIPTIONAL ACTIVATION; OLIGOMERIZATION DOMAIN; MUTATIONS; DYNAMICS; RESOLUTION; TETRAMER; TERMINUS AB p53, the tumor suppressor protein, functions as a dimer of dimers. However, how the tetramer binds to the DNA is still an open question. In the crystal structure, three copies of the p53 monomers (containing chains A, B, and C) were crystallized with the DNA-consensus element. Although the structure provides crucial data on the p53-DNA contacts, the active oligomeric state is unclear because the two dimeric (A-B and B-C) interfaces present in the crystal cannot both exist in the tetramer. Here, we address the question of which of these two dimeric interfaces may be more biologically relevant. We analyze the sequence and structural properties of the p53-p53 dimeric interfaces and carry out extensive molecular dynamics simulations of the crystal structures of the human and mouse p53 dimers. We find that the A-B interface residues are more conserved than those of the B-C. Molecular dynamics simulations show that the A-B interface can provide a stable DNA-binding motif in the dimeric state, unlike B-C. Our results indicate that the interface between chains A-B in the p53-DNA complex constitutes a better candidate for a stable biological interface, whereas the B-C interface is more likely to be due to crystal packing. Thus, they have significant implications toward our understanding of DNA binding by p53 as well as p53-mediated interactions with other proteins. C1 NCI, Basic Res Program, SAIC Frederick Inc, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Inst Adv Study, Princeton, NJ 08540 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Ma, BY (reprint author), NCI, Basic Res Program, SAIC Frederick Inc, Lab Expt & Computat Biol, Frederick, MD 21702 USA. EM mab@ncifcrf.gov; alevine@ias.edu; ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01 CO-12400, N01CO12400] NR 36 TC 22 Z9 22 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 MAR 15 PY 2005 VL 102 IS 11 BP 3988 EP 3993 DI 10.1073/pnas.0500215102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 907PT UT WOS:000227731000020 PM 15738397 ER PT J AU Gupta, L Kumar, S Han, YS Pimenta, PFP Barillas-Mury, C AF Gupta, L Kumar, S Han, YS Pimenta, PFP Barillas-Mury, C TI Midgut epithelial responses of different mosquito-Plasmodium combinations: The actin cone zipper repair mechanism in Aedes aegypti SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Anopheles stephensi; malaria; ookinete; invasion; Plasmodium berghei ID TIME BOMB MODEL; ANOPHELES-STEPHENSI; OOKINETE INVASION; NITRIC-OXIDE; CELLS; GALLINACEUM; BERGHEI; GAMBIAE; PHASE AB In vivo responses of midgut epithelial cells to ookinete invasion of three different vector-parasite combinations, Aedes aegypti-Plasmodium gallinaceum, Anopheles stephensi-Plasmodium berghei, and A. stephensi-P. gallinaceum, were directly compared by using enzymatic markers and immunofluorescence stainings. Our studies indicate that, in A. aegypti and A. stephensi ookinetes traverse the midgut via an intracellular route and inflict irreversible damage to the invaded cells. These two mosquito species differ, however, in their mechanisms of epithelial repair. A. stephensi detaches damaged cells by an actin-mediated budding-off mechanism when invaded by either A berghei or P. gallinaceum. In A. aegypti, the midgut epithelium is repaired by a unique actin cone zipper mechanism that involves the formation of a cone-shaped actin aggregate at the base of the cell that closes sequentially, expelling the cellular contents into the midgut lumen as it brings together healthy neighboring cells. Invasion of A. stephensi by A berghei induced expression of nitric oxide synthase and peroxidase activities, which mediate tyrosine nitration. These enzymes and nitrotyrosine, however, were not induced in the other two vector-parasite combinations examined. These studies indicate that the epithelial responses of different mosquito-parasite combinations are not universal. The implications of these observations to validate animal experimental systems that reflect the biology of natural vectors of human malarias are discussed. C1 Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. NIAID, Mosquito Immun & Vector Competence Unit, Lab Malaria & Vector Res, NIH, Rockville, MD 20857 USA. Fundacao Oswaldo Cruz, Ctr Pesquisas Rene Rachou, Lab Med Entomol, BR-30190002 Belo Horizonte, MG, Brazil. RP Barillas-Mury, C (reprint author), Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. EM cbarillas@niaid.nih.gov FU NIAID NIH HHS [R01 AI045573] NR 22 TC 41 Z9 44 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 MAR 15 PY 2005 VL 102 IS 11 BP 4010 EP 4015 DI 10.1073/pnas.0409642102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 907PT UT WOS:000227731000024 PM 15753303 ER PT J AU Barro, M Patton, JT AF Barro, M Patton, JT TI Rotavirus nonstructural protein 1 subverts innate immune response by inducing degradation of IFN regulatory factor 3 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE innate immunity; antiviral state; double-stranded RNA virus; reovirus ID RESPIRATORY SYNCYTIAL VIRUS; IRF-3 TRANSCRIPTION FACTOR; DOUBLE-STRANDED-RNA; INFLUENZA-A; EXPRESSION; NSP1; ACTIVATION; INFECTION; INDUCTION; VACCINE AB IFN regulatory factor 3 (IRF3), a constitutively expressed protein localizing largely to the cytoplasm, is a primary effector of the innate immune response. Infection can trigger the phosphorylation, dimerization, and nuclear translocation of IRF3, where the factor stimulates the expression and release of IFN. In this study, we determined that the rotavirus gene 5 product, nonstructural protein 1 (NSP1), interacts with IRF3 in the infected cell. To understand the importance of the interaction, we compared IRF3 activation by rotaviruses expressing wild-type and C-truncated forms of NSP1. The analysis showed that IRF3 underwent dimerization and nuclear translocation and stimulated IFN promoter activity in infected cells expressing truncated NSP1. In contrast, infected cells expressing wild-type NSP1 were characterized by the rapid degradation of IRF3 during the replication cycle, severe decreases in IRF3 dimerization and nuclear translocation, and lack of IFN promoter activity. The implication of these results, that wild-type NSP1 is an antagonist of the IFN-signaling pathway, was confirmed in transient expression assays, which showed that wild-type NSP1, but not the C-truncated protein, induced the degradation of IRF3 fusion proteins. Related experiments indicated that NSP1 mediates IRF3 degradation through a proteasome-dependent pathway. The critical role of NSP1 in promoting cell-to-cell spread of rotavirus was demonstrated by using gene 5-specific short interfering RNAs in plaque assays. Although several viruses have been described that subvert the innate immune response by preventing IRF3 activation, rotavirus is identified as one that accomplishes this task by inducing the degradation of IRF3. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Patton, JT (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM jpatton@niaid.nih.gov RI Patton, John/P-1390-2014 NR 27 TC 140 Z9 150 U1 0 U2 6 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 15 PY 2005 VL 102 IS 11 BP 4114 EP 4119 DI 10.1073/pnas.0408376102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 907PT UT WOS:000227731000042 PM 15741273 ER PT J AU Whitesides, TE Horton, WC Hutton, WC Hodges, L AF Whitesides, TE Horton, WC Hutton, WC Hodges, L TI Spondylolytic spondylolisthesis - A study of pelvic and lumbosacral parameters of possible etiologic effect in two genetically and geographically distinct groups with high occurrence SO SPINE LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Scoliosis-Research-Society CY SEP 19-22, 2001 CL CLEVELAND, OH SP Scoliosis Res Soc DE spondylolisthesis; spondylolysis; occurrence rate; etiology; lumbar index; pelvic incidence; sacral table angle ID ISTHMIC SPONDYLOLISTHESIS; LUMBAR SPONDYLOLISTHESIS; NEURAL ARCH; ADOLESCENT; FRACTURES; ALIGNMENT; LORDOSIS; SACRUM; MODEL; SLIP AB Study Design. An anatomic and radiographic study of archeological skeletal remains from two genetically and geographically distinct groups with high occurrence rates of spondylolytic spondylolisthesis was done. Specimens were Aleut (27% known occurrence rate, n = 48) and Arikara Plains Indians (9% occurrence, n = 250+ of 1,062). Objective. To evaluate three radiographic parameters highly correlated with spondylolisthesis (pelvic incidence [PI], sacral table angle [STA], and lumbar index [LI]) in genetically homogeneous populations to determine which may be etiologic or most predictive for lysis. Summary of Background Data. LI has been known to vary with the percentage of slip in lytic spondylolisthesis. Recent clinical studies have shown that PI is also significantly higher in high-grade slips, and a possible etiologic effect has been ascribed to this association. STA has also been shown to vary between normals, those with only lysis, and those with lysis and slip. The etiologic significance of STA is unknown. Methods. Radiographic and direct morphologic measurement of PI, LI, and STA was done on L5 and reassembled sacra and ilia. Statistical analysis of these three parameters among all groups was done. Results. 1) There is a genetically determined difference in the upper sacral tilt (STA) that may be etiologic. 2) Genetically homogeneous groups with a lower STA in normal specimens have an increased occurrence rate of spondylolysis. 3) When there has been pars lysis, changes in the STA occur as well as deformity more caudal in the sacrum. 4) These changes are likely related to remodeling with epiphyseal growth related to changed axial stresses secondary to pars lysis. 5) PI is not a primary etiologic factor in the process. Conclusions. The STA in the normal population for each genetic group varies and relates significantly to the occurrence rate and is thus probably etiologic. STA is more highly associated with the occurrence of pars defect than is PI. Upper sacral deformities appear due to the growth plate response to the changed pressure gradients across the epiphyseal plate rather than interosseous remodeling of the ilium and acetabular area. Thus, changes in PI would be secondary. C1 Emory Univ, Sch Med, Dept Orthopaed, Emory Spine Ctr, Atlanta, GA USA. Vet Affairs Med Ctr, Decatur, GA 30033 USA. NIH, Washington, DC USA. RP Whitesides, TE (reprint author), 958 Calvert Lane NE, Atlanta, GA 30319 USA. EM twhitesides@comcast.net NR 37 TC 28 Z9 28 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD MAR 15 PY 2005 VL 30 IS 6 SU S BP S12 EP S21 DI 10.1097/01.brs.0000155574.33693.60 PG 10 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 908BX UT WOS:000227763300005 PM 15767879 ER PT J AU Chen, BSE Cook, RJ Lawless, JF Zhan, M AF Chen, BSE Cook, RJ Lawless, JF Zhan, M TI Statistical methods for multivariate interval-censored recurrent events SO STATISTICS IN MEDICINE LA English DT Article DE generalized estimating equation; interval-censoring; multi-type recurrent events; random effects ID OVERDISPERSED POISSON REGRESSION; ADJUSTED SURVIVAL-TIME; POINT-PROCESSES; MODELS; DISTRIBUTIONS; CANCER; COUNTS; TESTS AB Multi-type recurrent event data arise when two or more different kinds of events may occur repeatedly over a period of observation. The scientific objectives in such settings are often to describe features of the marginal processes and to study the association between the different types of events. Interval-censored multi-type recurrent event data arise when the precise event times are unobserved, but intervals are available during which the events are known to have occurred. This type of data is common in studies of patients with advanced cancer, for example, where the events may represent the development of different types of metastatic lesions which are only detectable by conducting bone scans of the entire skeleton. In this setting it is of interest to characterize the incidence of the various types of bone lesions, to estimate the impact of treatment and other covariate effects on the development of new lesions, and to understand the relationship between the processes generating the bone lesions. We develop joint models for multi-type interval -censored recurrent events which accommodate dependencies between different types of events and enable one to examine the covariate effects via regression. However, since the marginal likelihood resulting from the multivariate random effect model is intractable, we describe a Gibbs sampling algorithm to facilitate model fitting and inference. We use generalized estimating equations for estimation and inference based on marginal models. The finite sample properties of the marginal approach are studied via simulation. The estimates of both the regression coefficients and the variance-covariance parameters are shown to have negligible bias and 95 per cent confidence intervals based on the asymptotic variance formula are shown to have excellent empirical coverage probabilities in all of the settings considered. The application of these methods to data from a trial of women with advanced breast cancer provides insight into the clinical course of bone metastases in this population. Copyright (C) 2004 John Wiley Sons, Ltd. C1 NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. RP Chen, BSE (reprint author), NCI, Biostat Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd, Rockville, MD 20852 USA. EM cheneric@mail.nih.gov OI Chen, Bingshu/0000-0001-6139-0696 NR 30 TC 21 Z9 22 U1 2 U2 13 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 MAR 15 PY 2005 VL 24 IS 5 BP 671 EP 691 DI 10.1002/sim.1936 PG 21 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 900NX UT WOS:000227222700001 PM 15558580 ER PT J AU O'Sullivan, GJ Kinsella, A Sibley, DR Tighe, O Croke, DT Waddington, JL AF O'Sullivan, GJ Kinsella, A Sibley, DR Tighe, O Croke, DT Waddington, JL TI Ethological resolution of behavioural topography and D-1-like versus D-2-like agonist responses in congenic D-5 dopamine receptor mutants: Identification of D-5 : D-2-like interactions SO SYNAPSE LA English DT Article DE dopamine receptor subtypes; D-5 knockout mice; ethogram; grooming behaviour; seizures ID TARGETED GENE DELETION; PHOSPHOINOSITIDE HYDROLYSIS; SUBTHALAMIC NUCLEUS; ADENYLYL-CYCLASE; GROOMING SYNTAX; MONKEY BRAIN; D5 RECEPTORS; MICE LACKING; RAT-BRAIN; KNOCKOUT AB The phenotypic ethogram of congenic dopamine D-5 receptor "knockout" mice was evaluated. Each individual topography of behaviour within the natural repertoire was assessed over the extended course of initial exploration of and subsequent habituation to the environment, and following challenge with a series of D-1-like agonists. Over initial exploration, D-5-null mice evidenced a modest reduction in locomotion and a modest increase in sifting. Subsequent habituation revealed additional phenotypic effects, primarily overall reduction in grooming and delayed habituation of rearing. Among D-1-like agonists, A 68930 stimulates both adenylyl cyclase and a putative D-1-like receptor coupled to stimulation of phospholipase C-mediated phosphoinositide hydrolysis; conversely, SK&F 83959 stimulates phosphoinositide hydrolysis but not adenylyl cyclase while SK&F 83822 stimulates adenylyl cyclase but not phosphoinositide hydrolysis. Though programmed grooming syntax and episodic seizure activity induced by A 68930 and SK&F 83822 were unaltered, grooming induced by SK&F 83959 was reduced in D-5 mutants. Stereotyped, ponderous locomotion induced by the D-2-like agonist RU 24213 was enhanced in D-5 mutants. Phenotypic and pharmacological characterisation of congenic D-5-null mice at an ethological level identifies novel functional roles for the D-5 receptor in mediating discrete topographies of behaviour relating to exploration, sequential motor coordination, and how these processes change over the course of interaction with and habituation to the environment. Additionally, they indicate the involvement of phosphoinositide hydrolysis and D-5:D-2-like interactions in regulating these processes. Published 2005 Wiley-Liss, Inc.(dagger) C1 Royal Coll Surgeons Ireland, Dept Clin Pharmacol, Dublin 2, Ireland. Royal Coll Surgeons Ireland, Inst Biopharmaceut Sci, Dublin 2, Ireland. Dublin Inst Technol, Sch Math, Dublin 8, Ireland. Natl Inst Neurol Disorders & Stroke, NIH, Mol Neuropharmacol Sect, Bethesda, MD 20892 USA. Royal Coll Surgeons Ireland, Dept Biochem, Dublin 2, Ireland. RP Waddington, JL (reprint author), Royal Coll Surgeons Ireland, Dept Clin Pharmacol, St Stephens Green, Dublin 2, Ireland. EM jwadding@rcsi.ie FU NIMH NIH HHS [N01MH30003] NR 49 TC 25 Z9 26 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD MAR 15 PY 2005 VL 55 IS 4 BP 201 EP 211 DI 10.1002/syn.20107 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 899CT UT WOS:000227123200001 PM 15668951 ER PT J AU Bortner, CD AF Bortner, CD TI Apoptotic volume decrease and nitric oxide SO TOXICOLOGY LA English DT Article DE apoptosis; programmed cell death; apoptotic volume decrease (AVD); cell shrinkage; regulatory volume decrease (RVD); ions ID VASCULAR SMOOTH-MUSCLE; RECEPTOR-MEDIATED APOPTOSIS; CEREBELLAR GRANULE CELLS; FAS-INDUCED APOPTOSIS; ASCITES TUMOR-CELLS; JURKAT T-CELLS; ACTIN CYTOSKELETON; DEATH-RECEPTOR; MEMBRANE DEPOLARIZATION; CASPASE ACTIVATION AB Apoptosis is a physiological cell death process whose well-defined characteristics distinguish it from more accidental cell death processes. The loss of cell volume, or cell shrinkage, recently termed apoptotic volume decrease (AVD), is considered a hallmark of the apoptotic process. The activation and/or repression of the AVD process has been shown to be quite complex during apoptosis, with the involvement of multiple ionic transport mechanisms acting in both a cell type and stimulus specific manner. Similarly, the role of nitric oxide (NO) during apoptosis has also been shown to be just as complex, specifically in its ability to either induce and/or prevent apoptosis. This review examines current evidence for a link between AVD and NO and how they may interact during the programmed cell death process. Published by Elsevier Ireland Ltd. C1 NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, Res Triangle Pk, NC 27709 USA. RP Bortner, CD (reprint author), NIEHS, Lab Signal Transduct, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM bortner@niehs.nih.gov NR 70 TC 7 Z9 7 U1 1 U2 1 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 MAR 15 PY 2005 VL 208 IS 2 BP 213 EP 221 DI 10.1016/j.tox.2004.11.024 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 899PM UT WOS:000227156900004 PM 15691586 ER PT J AU Liu, J Waalkes, MP AF Liu, J Waalkes, MP TI Nitric oxide and chemically induced hepatotoxicity: beneficial effects of the liver-selective nitric oxide donor, V-PYRRO/NO SO TOXICOLOGY LA English DT Article DE nitric oxide; hepatotoxicity; NO donor; V-PYRRO/NO; hepatoprotection; iNOS; eNOS ID NECROSIS-FACTOR-ALPHA; ACETAMINOPHEN-INDUCED HEPATOTOXICITY; SYNTHASE-DEFICIENT MICE; REPERFUSION INJURY; ISCHEMIA-REPERFUSION; CARBON-TETRACHLORIDE; INDUCED APOPTOSIS; URSODEOXYCHOLIC ACID; HEPATOCYTE APOPTOSIS; PORTAL-HYPERTENSION AB Nitric oxide (NO) is endogenously produced by the enzyme NO synthase in the cell or pharmacologically delivered to tissues as NO prodrugs. This simple molecule is a potent biological mediator in a myriad of physiological and pathological events. The liver plays a central role in metabolism and immune processes, and is a major target organ influenced by NO. NO production in the liver is usually increased in response to acute insult with hepatotoxicants, and may be decreased during chronic liver diseases. The induction of NO production could be envisioned as an early adaptive response, which may become a mediator of tissue damage when in excess. In this regard, inhibition of endogenous NO synthase has been shown to be beneficial in some cases and detrimental in others. The creation of eNOS and iNOS knockout animals has advanced our understanding of NO function in hepatic response to toxic insults. Knocking endogenous NO production can be beneficial in response to certain toxicants; however, in general it weakens the body's defense mechanisms against toxic insults. A variety of pharmacological NO prodrugs have been developed, and, when used appropriately, most of them have demonstrated beneficial effects in the liver in a variety of pathological settings. In this review, we discuss the relationship between NO and hepatotoxicity, and the beneficial effects of NO donors on the liver, using the liver-selective NO donor, V-PYRRO/NO, as an example to demonstrate that pharmacologically delivered NO could have therapeutic benefits for liver disorders. Published by Elsevier Ireland Ltd. C1 NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Liu, J (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Comparat Carcinogenesis Lab, NIH, Mail Drop F0-09, Res Triangle Pk, NC 27709 USA. EM liu6@niehs.nih.gov NR 69 TC 31 Z9 33 U1 0 U2 3 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 MAR 15 PY 2005 VL 208 IS 2 BP 289 EP 297 DI 10.1016/j.tox.2004.11.017 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 899PM UT WOS:000227156900010 PM 15691592 ER PT J AU Hudson, TS Stoner, GD Morse, MA Young, H Mallery, SR AF Hudson, TS Stoner, GD Morse, MA Young, H Mallery, SR TI Comparison of phenethyl and 6-phenylhexyl isothiocyanate-induced toxicity in rat esophageal cell lines with and without glutathione depletion SO TOXICOLOGY LETTERS LA English DT Article DE PEITC; PHITC; GSH; cytotoxicity ID N-NITROSOMETHYLBENZYLAMINE; ANTICARCINOGENIC ISOTHIOCYANATES; PHENYLHEXYL ISOTHIOCYANATE; BENZYL ISOTHIOCYANATE; CANCER PREVENTION; EPITHELIAL-CELLS; DNA METHYLATION; METABOLISM; CARCINOGENESIS; TUMORIGENESIS AB Phenethyl isothiocyanate (PEITC) and its synthetic homolog, 6-phenylhexyl isothiocyanate (PHITC), are both potent inhibitors of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK)-induced lung mice tumorigenesis. However, unlike PEITC, PHITC enhanced N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis. These findings imply that due to its unique chemical properties, PHITC's effects on esophageal cells are procarcinogenic rather than chemopreventive. Relative to PEITC, PHITC is more lipophilic and less reactive, which could result in higher PHITC intracellular levels. Due to ITCs' inherently high level of thiol reactivity, increased intracellular levels of PHITC have the potential to deplete intracellular glutathione (GSH) reserves. Since GSH is a primary intracellular antioxidant and cytoprotective enzyme cofactor, preservation of intracellular GSH status is crucial for cytoprotection. Despite the recognized importance of isothiocyanate structure with the potential for toxicity, no studies have yet investigated the association between the primary intracellular free thiol, GSH, and isothiocyanate-induced toxicity in this target cell population. The present study investigated whether PEITC and PHITC display unique cytotoxic profiles in cultured rat esophageal cells, and also monitored the effects of ITC challenge on cellular GSH status. A final series of experiments investigated the converse i.e., affects of modulation of intracellular GSH status on ITC-mediated toxicity. Dose-response curves revealed that PEITC was significantly more toxic in turnorigenic and non-tumorigenic cells relative to PHITC. The ITC-GSH interaction studies demonstrated comparable GSH levels following either PEITC or PHITC challenge, and also showed that GSH depletion did not augment ITC-mediated cellular toxicity. While our data demonstrate structure related differences in ITC-mediated cytotoxicities, these differences do not appear to be directly attributable to cellular GSH pools. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Ohio State Univ, Coll Dent, Dept Oral & Maxillofacial Surg & Pathol, Columbus, OH 43210 USA. NCI, Div Canc Prevent, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Coll Med & Publ Hlth, Div Hematol & Oncol, Columbus, OH 43210 USA. Charles River Co, Springborn Labs Inc, Spencerville, OH 45887 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Div Epidemiol & Biostat, Washington, DC 20037 USA. RP Mallery, SR (reprint author), Ohio State Univ, Coll Dent, Dept Oral & Maxillofacial Surg & Pathol, Rm 2191B,305 W 12th Ave, Columbus, OH 43210 USA. EM mallery.1@osu.edu FU NCI NIH HHS [P30CA1658, P01CA46535] NR 43 TC 3 Z9 4 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD MAR 15 PY 2005 VL 155 IS 3 BP 427 EP 436 DI 10.1016/j.toxlet.2004.11.012 PG 10 WC Toxicology SC Toxicology GA 892JE UT WOS:000226645800011 PM 15649627 ER PT J AU Leitzmann, MF Tsai, CJ Stampfer, MJ Willett, WC Giovannucci, E AF Leitzmann, MF Tsai, CJ Stampfer, MJ Willett, WC Giovannucci, E TI Thiazide diuretics and the risk of gallbladder disease requiring surgery in women SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ACUTE CHOLECYSTITIS; QUESTIONNAIRE; CONSUMPTION; GALLSTONES; SERUM AB Background: Previous studies have suggested that thiazide diuretic use increases the risk of cholecystitis. Methods: We prospectively examined the association between thiazide use and cholecystectomy, a surrogate for symptomatic cholelithiasis, in a cohort of 81351 US women who were aged 30 to 55 years in 1980 and followed up to 2000. Regular use of thiazide diuretics was assessed at baseline by asking the participants to report whether they currently took "any of the following medications in most weeks" and listing "thiazide diuretics (eg, Diuril and Hydrodiuril)" among other drugs. Respondents were also requested to report the duration of thiazide diuretic use. Assessment of thiazide diuretic use was updated in 1982, 1988, 1994, 1996, and 1998. Cox regression was used to adjust simultaneously for other potential risk factors for cholecystectomy. Results: During follow-up, 8607 women reported undergoing a cholecystectomy. A modest positive relation between the use of thiazide diuretics and cholecystectomy was observed. Compared with never users of thiazide diuretics, the multivariate relative risk of cholecystectomy for past users was 1.16 (95% confidence interval,1.08-1.24) and the multivariate relative risk for current users was 1.39 (95% confidence interval, 1.29-1.50). Conclusions: These findings are compatible with the hypothesis that the use of thiazide diuretics increases the risk of symptomatic cholecystitis. However, we cannot rule out the possibility that our results are in part explained by unconsidered factors related to the indication for antihypertensive therapy or by differences in medical surveillance between users and nonusers of thiazide diuretics. C1 NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Univ Iowa Hosp & Clin, Ctr Digest Dis, Iowa City, IA 52242 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, Brigham & Womens Hosp, Channing Lab,Dept Med, Boston, MA 02115 USA. RP Leitzmann, MF (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, DHHS, EPS MSC 7232,6120 Execut Blvd, Bethesda, MD 20892 USA. EM leitzmann@.mail.nih.gov FU NCI NIH HHS [CA 87969, 5T32 CA 09001-26]; NIDDK NIH HHS [DK 46200] NR 22 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 14 PY 2005 VL 165 IS 5 BP 567 EP 573 DI 10.1001/archinte.165.5.567 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 906FD UT WOS:000227625000013 PM 15767534 ER PT J AU Mulligan, K Zackin, R Clark, RA Alston-Smith, B Liu, T Sattler, FR Delvers, TB Currier, JS AF Mulligan, K Zackin, R Clark, RA Alston-Smith, B Liu, T Sattler, FR Delvers, TB Currier, JS CA AIDS Clinical Trials Grp 329 Study Natl Inst Allergy Infect Dis TI Effect of nandrolone decanoate therapy on weight and lean body mass in HIV-infected women with weight loss - A randomized, double-blind, placebo-controlled, multicenter trial SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; AIDS WASTING SYNDROME; RESISTANCE EXERCISE; TESTOSTERONE LEVELS; MEGESTROL-ACETATE; MEN; SURVIVAL; ERA; ENDOCRINE AB Background: Weight loss is associated with accelerated mortality and disease progression in patients with human immunodeficiency virus (HIV) infection. Although studies have examined a variety of anabolic therapies in HIV-infected men, the safety and efficacy of such treatments in women have not been adequately studied. Methods: In this randomized, double-blind, placebo-controlled, multicenter, phase I/II study, 38 HIV-infected women with documented weight loss of 5% or greater in the preceding year or a body mass index of less than 20 kg/m(2) were randomized to receive nandrolone decanoate (100 mg) or an equivalent volume of placebo every other week by intramuscular injection. Subjects received blinded treatment for 12 weeks, followed by open-label therapy for 12 weeks. Lean body mass and fat (bioelectrical impedance analysis) and weight were measured at baseline and at weeks 6, 12, 18, and 24. Biochemical assessments of safety (hematologic analyses, liver function tests, and sex hormone measurements) were performed at these same time points. Clinical signs and symptoms were monitored biweekly. Results: Subjects randomized to receive nandrolone had significant increases in weight and lean body mass during blinded treatment (4.6 kg [9.0%] and 3.5 kg [8.6%], respectively; P <.001 vs baseline and placebo in each case). Fat mass did not change statistically significantly in either group. Although there were no statistically significant differences between groups in biochemical measures, the number of grade 3 or greater toxicities, or reports of virilizing effects, a full assessment of safety cannot be made in a trial of this size. Conclusion: Nandrolone decanoate therapy may prove to be generally safe and beneficial in reversing weight loss and lean tissue loss in women with HIV infection and other chronic catabolic diseases. C1 San Francisco Gen Hosp, Div Endocrinol, San Francisco, CA 94110 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Harvard Univ, Sch Publ Hlth, Stat & Data Anal Ctr, Boston, MA 02115 USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ So Calif, Kech Sch Med, Dept Med, Div Infect Dis, Los Angeles, CA 90089 USA. Organon Pharmaceut USA Inc, Roseland, NJ USA. Univ Calif Los Angeles, Dept Med, Div Infect Dis, Los Angeles, CA 90024 USA. RP Mulligan, K (reprint author), San Francisco Gen Hosp, Div Endocrinol, 1001 Potrero Ave,Bldg 30,Room 3501K, San Francisco, CA 94110 USA. FU NCRR NIH HHS [5M01 RR 00083]; NIAID NIH HHS [AI 38855, AI 27663] NR 35 TC 21 Z9 21 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAR 14 PY 2005 VL 165 IS 5 BP 578 EP 585 DI 10.1001/archinte.165.5.578 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 906FD UT WOS:000227625000015 PM 15767536 ER PT J AU Li, Y Brewer, D Burke, RE Ascoli, GA AF Li, Y Brewer, D Burke, RE Ascoli, GA TI Developmental changes in spinal motoneuron dendrites in neonatal mice SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE dendrite growth; quantitative morphology; dendrite reconstruction ID IDENTIFIED ALPHA-MOTONEURONS; TERM SYNAPTIC DEPRESSION; HIND-LIMB MOTONEURONS; IN-VITRO; GENIOGLOSSAL MOTONEURONS; POSTNATAL-DEVELOPMENT; ELECTROTONIC ARCHITECTURE; PHRENIC MOTONEURONS; INTRINSIC MUSCLES; GAMMA-MOTONEURONS AB We examined the age-dependent morphological changes of lumbar spinal motoneurons (MNs) in neonatal Swiss-Webster mice during the first 2 weeks of postnatal life. Neurons labeled by intracellular injection of biocytin in hemisected lumbosacral spinal cords in vitro were reconstructed from serial sections. Digitized data were compared for young (P3; postnatal days 2-4; n = 9) and older animals (P11; postnatal days 10-13; n = 8). As expected, measures of dendritic size (e.g., stem branch diameter, total surface area, maximum distance to tips, and lateral tree spread) were all significantly greater for P11 than for P3 mice. In contrast, the number of dendrites per MN and parameters related to tree topology (e.g., terminations per tree and maximum branch order), although slightly greater for P11 animals, were not significantly different between the two ages. Dendrite growth appeared to be proportional throughout the tree because the ratios between average terminal and internal branch lengths were similar for the two groups. Furthermore, this elongation was proportional to enlargement of overall spinal cord dimensions. A variety of other morphometric measures showed no significant difference between age groups. The relative constancy of MN dendritic topology up to P13 was surprising, given the striking maturation in motor function during this time period. Published 2005 Wiley-Liss, Inc. C1 NINDS, Lab Neural Control, NIH, Bethesda, MD 20892 USA. George Mason Univ, Krasnow Inst Adv Study, Fairfax, VA 22039 USA. George Mason Univ, Dept Psychol, Fairfax, VA 22039 USA. RP Burke, RE (reprint author), NINDS, Lab Neural Control, NIH, Bldg 35,Rm 3C1016, Bethesda, MD 20892 USA. EM reburke@helix.nih.gov FU NINDS NIH HHS [R01 NS39600] NR 70 TC 29 Z9 29 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9967 J9 J COMP NEUROL JI J. Comp. Neurol. PD MAR 14 PY 2005 VL 483 IS 3 BP 304 EP 317 DI 10.1002/cne.20438 PG 14 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 893RD UT WOS:000226736000005 PM 15682391 ER PT J AU Abashkin, YG Burt, SK AF Abashkin, YG Burt, SK TI Theoretical prediction of the catalytic properties for substituted salen-manganese compounds. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NCI, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. EM abashkin@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 585-INOR BP U1052 EP U1052 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177707583 ER PT J AU Amero, SA AF Amero, SA TI Peer review of bioimaging and bioengineering grant applications at the National Institutes of Health (NIH). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIH, Bioengn Sci & Technol IRG, Ctr Sci Review, Bethesda, MD 20892 USA. EM ameros@csr.nih.gov NR 0 TC 0 Z9 0 U1 4 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 058-PHYS BP U711 EP U711 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066603058 ER PT J AU Barchi, JJ AF Barchi, JJ TI Carbohydrate nanoscience: A new realm for biochemical and therapeutic applications SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Natl Canc Inst, Med Chem Lab, Ft Detrick, MD 21702 USA. EM barchi@helix.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 005-CARB BP U254 EP U254 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177701424 ER PT J AU Barry, CE AF Barry, CE TI Why does multidrug chemotherapy still allow the emergence of drug resistance during tuberculosis treatment? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIAID, TB Res Sect, NIH, Rockville, MD 20852 USA. EM clifton_barry@nih.gov RI Barry, III, Clifton/H-3839-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 314-MEDI BP U164 EP U164 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600313 ER PT J AU Besada, P Mamedova, L Thomas, CJ Costanzi, S Jacobson, KA AF Besada, P Mamedova, L Thomas, CJ Costanzi, S Jacobson, KA TI Design and synthesis of new bicyclic diketopiperazines as scaffolds for receptor probes of structurally diverse functionality. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIDDK, NIH, Bethesda, MD 20892 USA. EM pedrop@intra.niddk.nih.gov RI Jacobson, Kenneth/A-1530-2009; Besada Pereira, Pedro/E-6051-2012 OI Jacobson, Kenneth/0000-0001-8104-1493; Besada Pereira, Pedro/0000-0002-9985-9063 NR 0 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 553-MEDI BP U214 EP U214 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600583 ER PT J AU Betz, JM AF Betz, JM TI Chemistry and biomedical research on dietary supplements SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. EM betzj@od.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 036-AGFD BP U32 EP U33 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177700051 ER PT J AU Burnett, CA Xie, JW Quijano, J Hunter, F Sun, HH Bur, M Li, KCP Danthi, SN AF Burnett, CA Xie, JW Quijano, J Hunter, F Sun, HH Bur, M Li, KCP Danthi, SN TI Integrin alpha(v)beta(3)-targeted optical imaging probes. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Ctr Clin, NIH, Mol Imaging Lab, Bethesda, MD 20892 USA. RI Danthi, Simhan/B-7639-2014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 159-MEDI BP U136 EP U136 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600158 ER PT J AU Campbell, JM Stein, SE Blank, PS Epstein, J Vestal, ML Yergey, AL AF Campbell, JM Stein, SE Blank, PS Epstein, J Vestal, ML Yergey, AL TI Fundamentals of peptide fragmentation as a function of laser fluence in a MALDI TOF-TOF mass spectrometer. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIST, Phys & Chem Properties Div, Gaithersburg, MD USA. Appl Biosyst Inc, R&D, Framingham, MA 02144 USA. NICHHD, NIH, Sect Metab Anal & Mass Spectrometry, LCMB, Bethesda, MD 20892 USA. EM campbejn@appliedbiosystems.com; aly@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 371-ANYL BP U148 EP U148 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177700702 ER PT J AU Caughey, B AF Caughey, B TI Chemistry of prions: Mad cow disease and its relatives. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIAID, Rocky Mt Labs, Persistent Viral Dis Lab, NIH, Hamilton, MT 59840 USA. EM bcaughey@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 1328-CHED BP U557 EP U557 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177703745 ER PT J AU Christoph, GW Hofrichter, J Eaton, WA AF Christoph, GW Hofrichter, J Eaton, WA TI Rate of forming sickle fiber domains depends on 80th power of protein concentration. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM garrott@helix.nih.gov; eaton@helix.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 594-PHYS BP U794 EP U794 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066603592 ER PT J AU Dancey, JE AF Dancey, JE TI Inhibitors of protein kinase signaling pathways: Emerging targets and agents. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NCI, Investigat Drug Branch, Canc Therapy Evaluat Program, Rockville, MD 20852 USA. EM danceyj@ctep.nci.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 306-MEDI BP U163 EP U163 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600305 ER PT J AU del Sol Jimenez, M Jun, JH Dougherty, JM Hanson, P AF del Sol Jimenez, M Jun, JH Dougherty, JM Hanson, P TI Synthetic routes to diverse S-heterocyclic libraries. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Univ Kansas, Dept Chem, Lawrence, KS 66045 USA. NIH, Ctr Excellence Combinatorial Methodol & Lib Dev, Dept Chem, Bethesda, MD USA. EM msjimenz@ku.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 206-orgn BP U357 EP U357 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066601311 ER PT J AU DeRosa, F Citro, ML Keefer, LK Hrabie, JA AF DeRosa, F Citro, ML Keefer, LK Hrabie, JA TI Nitric oxide-releasing polymeric materials derived in part from acrylonitrile monomer. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NCI, Frederick Canc Res & Dev Ctr, Chem Sect, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. EM derosa@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 247-orgn BP U363 EP U363 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066601352 ER PT J AU Dubois, M Zemb, T Zimmerberg, JJ Lizunov, V Meister, A Perez, E Verbavatz, JM AF Dubois, M Zemb, T Zimmerberg, JJ Lizunov, V Meister, A Perez, E Verbavatz, JM TI Shape control through molecular segregation in giant surfactant aggregates. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 CEA Saclay, LIONS, DRECAM, SCM, F-91191 Gif Sur Yvette, France. NIH, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. Russian Acad Sci, AN Frumkin Electrochem Inst, Moscow 117901, Russia. CEA Saclay, Dept Biol Cellulaire & Morphol, Serv Biophys Fonct, Gif Sur Yvette, France. CNRS, IMRCP, UMR 5623, F-75700 Paris, France. EM dubois@drecam.cea.fr RI ZEMB, Thomas/E-5958-2010 NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 234-COLL BP U668 EP U668 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177704393 ER PT J AU Geho, D Wulfkuhle, J Calvert, V Liotta, L Petricoin, E AF Geho, D Wulfkuhle, J Calvert, V Liotta, L Petricoin, E TI Use of phosphoproteomic molecular network analysis for nanoparticle toxicity assessment. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NCI, Dept Pathol, Ctr Canc Res, Bethesda, MD 20892 USA. EM gehod@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 018-IEC BP U912 EP U912 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177706462 ER PT J AU Gnanakaran, S Nussinov, R Garcia, AE AF Gnanakaran, S Nussinov, R Garcia, AE TI Structural and thermodynamic characteristics of oligomeric intermediates involved in amyloid formation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Los Alamos Natl Lab, Theoret Biol & Biophys Grp, Los Alamos, NM 87545 USA. NCI, FCRDC, SAIC, Basic Res Program,Lab Expt & Computat Biol, Bethesda, MD 20892 USA. EM gnana@lanl.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 213-PHYS BP U734 EP U734 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066603212 ER PT J AU Guerra, J Herpel, R Vedantham, P Georg, GI Mitscher, LA Flynn, DL Hanson, P AF Guerra, J Herpel, R Vedantham, P Georg, GI Mitscher, LA Flynn, DL Hanson, P TI Romp strategies to high-load electrophile scavengers. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Univ Kansas, Dept Chem, Lawrence, KS 66045 USA. Univ Kansas, Dept Med Chem, Lawrence, KS 66045 USA. NIH, Dept Chem, Ctr Excellence Combinatorial Methodol & Lib Dev, KU CMLD, Bethesda, MD USA. EM jguerra@ku.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 192-ORGN BP U355 EP U355 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066601297 ER PT J AU Hara, T Hayashi, R Yamaguchi, H Appella, E Kodama, H Appella, DH AF Hara, T Hayashi, R Yamaguchi, H Appella, E Kodama, H Appella, DH TI Synthesis of peptoidsipeptide-peptoid hybrids containing a phosphonic acid moiety in the side-chain. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. Saga Univ, Dept Chem, Fac Sci & Engn, Saga, Japan. Northwestern Univ, Dept Chem, Evanston, IL 60208 USA. EM harato@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 835-ORGN BP U562 EP U562 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066602346 ER PT J AU Hassan, SA Hummer, G Sok-Lee, Y AF Hassan, SA Hummer, G Sok-Lee, Y TI Effects of electric fields on water-mediated proton transport. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIH, Ctr Mol Modeling, DHHS, Bethesda, MD 20892 USA. EM mago@helix.nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 357-COMP BP U811 EP U811 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177705677 ER PT J AU Hassan, SA AF Hassan, SA TI Intermolecular potentials of mean force of amino acid side chain interactions in aqueous medium. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 DHHS, Ctr Mol Modeling, NIH, Bethesda, MD 20892 USA. EM mago@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 017-COMP BP U758 EP U758 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177705344 ER PT J AU Horkay, F Basser, PJ Hecht, AM Geissler, E AF Horkay, F Basser, PJ Hecht, AM Geissler, E TI Comparison between the effect of calcium ions on the osmotic properties of synthetic and biopolymer gels. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Univ Grenoble 1, CNRS, UMR 5588, Spectrometrie Phys Lab, Grenoble, France. EM horkay@helix.nih.gov RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 547-POLY BP U987 EP U987 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066604543 ER PT J AU Horkay, F Horkayne-Szakaly, I Basser, PJ AF Horkay, F Horkayne-Szakaly, I Basser, PJ TI Measurement of the osmotic properties of biological tissue samples. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. EM horkay@helix.nih.gov RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 372-BIOT BP U238 EP U238 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177701354 ER PT J AU Hsu, JT Tomanee, P Ito, Y AF Hsu, JT Tomanee, P Ito, Y TI Scale-up of protein, RNA and plasmid DNA fractionation using centrifugal precipitation chromatography with convoluted tubing. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Lehigh Univ, Dept Chem Engn, Bethlehem, PA 18015 USA. NHLBI, Lab Biophys Chem, NIH, Bethesda, MD 20892 USA. EM jth0@lehigh.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 207-BIOT BP U210 EP U210 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177701194 ER PT J AU Inami, K Nims, RW Srinivasan, A Citron, ML Saavedra, JE Cederbaum, A Keefer, LK AF Inami, K Nims, RW Srinivasan, A Citron, ML Saavedra, JE Cederbaum, A Keefer, LK TI Metabolism of a liver-selective nitric oxide-releasing agent, V-PYRRO/NO, by human microsomal cytochromes P450. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NCI, Chem Sect, Lab Comparat Carcinogenesis, Frederick, MD 21702 USA. SAIC Frederick Inc, Basic Res Program, Frederick, MD USA. EM inami@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 192-MEDI BP U143 EP U143 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600191 ER PT J AU Ioanoviciu, AS Antony, S Kohlhagen, G Pommier, Y Staker, B Stewart, L Cushman, M AF Ioanoviciu, AS Antony, S Kohlhagen, G Pommier, Y Staker, B Stewart, L Cushman, M TI New indenoisoquinolinium salts, N-6-desalkylindenoisoquinolines, and 5,11-diketoindenoisoquinolines: Design and synthesis of topoisomerase I inhibitors as anticancer agents. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, Sch Pharm & Pharmacal Sci, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, Sch Pharm & Pharmacal Sci, W Lafayette, IN 47907 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. EM aioanovi@purdue.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 503-MEDI BP U205 EP U205 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600533 ER PT J AU Ioanoviciu, AS Antony, S Kohlhagen, G Pommier, Y Staker, B Stewart, L Cushman, M AF Ioanoviciu, AS Antony, S Kohlhagen, G Pommier, Y Staker, B Stewart, L Cushman, M TI New indenoisoquinolinium salts, N6-desalkylindenoisoquinolines, and 5,11-diketoindenoisoquinolines: Design and synthesis of topoisomerase I inhibitors as anticancer agents. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, Sch Pharm & Pharmacal Sci, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, Sch Pharm & Pharmacal Sci, W Lafayette, IN 47907 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. EM aioanovi@purdue.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 503-MEDI BP U199 EP U199 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600502 ER PT J AU Jeong, LS Kim, MJ Kim, AY Lee, JA Jacobson, KA Gao, ZG Kim, SK Chun, MW AF Jeong, LS Kim, MJ Kim, AY Lee, JA Jacobson, KA Gao, ZG Kim, SK Chun, MW TI Synthesis and binding affinity of 3'-ureidoadenosine analogues at the A3 adenosine receptor. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Ewha Womans Univ, Coll Pharm, Lab Med Chem, Seoul, South Korea. NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. EM lakjeong@mm.ewha.ac.kr RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 082-MEDI BP U120 EP U121 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600081 ER PT J AU Karki, R Oishi, S Shi, ZD Kang, SU Lee, K Wei, CQ Worthy, KM Bindu, L Fisher, RJ Burke, TR Nicklaus, MC AF Karki, R Oishi, S Shi, ZD Kang, SU Lee, K Wei, CQ Worthy, KM Bindu, L Fisher, RJ Burke, TR Nicklaus, MC TI Protein-ligand binding free energy estimation using linear interaction energy method: Application to GRB2 SH2 domain binding ligands. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. SAIC Frederick, Prot Chem Lab, Frederick, MD USA. EM rajeshri@helix.nih.gov RI Fisher, Robert/B-1431-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 126-MEDI BP U129 EP U129 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600125 ER PT J AU Karki, RG Nicklaus, MC AF Karki, RG Nicklaus, MC TI Conformational study of small molecules in crystallographically determined structures SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NCI, Med Chem Lab, NIH, Frederick, MD 21702 USA. EM rajeshri@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 199-COMP BP U786 EP U786 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177705522 ER PT J AU Kasianowicz, JJ Stanford, V Misakian, M Henrickson, SE Panchal, RG Halverson, KM Bavari, S Nguyen, T Gussio, R MacGillivray, D Losche, M Shenoy, DK AF Kasianowicz, JJ Stanford, V Misakian, M Henrickson, SE Panchal, RG Halverson, KM Bavari, S Nguyen, T Gussio, R MacGillivray, D Losche, M Shenoy, DK TI Elucidating structure-function relationships of transmembrane nanopore toxins: Mechanisms of action and new applications. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIST, EEL, Gaithersburg, MD 20899 USA. NCI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. EM john.kasianowicz@nist.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 101-COLL BP U645 EP U645 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177704262 ER PT J AU Kim, HY AF Kim, HY TI Mass spectrometry in membrane-related research. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIAAA, Sect Mass Spectrometry, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. EM hykim@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 387-ANYL BP U151 EP U151 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177700718 ER PT J AU Kim, P Zhang, YM Shenoy, G Nguyen, OA Rock, CO Dowd, CS Barry, CE AF Kim, P Zhang, YM Shenoy, G Nguyen, OA Rock, CO Dowd, CS Barry, CE TI Synthesis of C5 vinyl analogues of thiolactomycin and their antitubercular properties: Olefination vs. deformylation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIAID, TB Res Sect, NIH, Rockville, MD 20852 USA. St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38101 USA. EM pkim@niaid.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 049-ORGN BP U331 EP U331 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066601154 ER PT J AU Kim, SK Gao, ZG Duong, HT Jeong, LS Jacobson, KA AF Kim, SK Gao, ZG Duong, HT Jeong, LS Jacobson, KA TI Molecular recognition of 3 '-modified adenosine neoligands to the human A3 adenosine receptor and its neoceptor. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Coll Pharm, Lab Med Chem, Seoul, South Korea. EM SooKyungK@intra.niddk.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 079-MEDI BP U120 EP U120 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600078 ER PT J AU Kong, L Showalter, BM Saavedra, JE Buzard, GS Keefer, LK AF Kong, L Showalter, BM Saavedra, JE Buzard, GS Keefer, LK TI Deamidation of peptides in aerobic nitric oxide solution. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NCI, Lab Comparat Carcinogenesis, Chem Sect, Frederick, MD 21702 USA. SAIC Frederick Inc, NCI, Frederick, MD USA. EM kongl@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 552-MEDI BP U213 EP U214 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600582 ER PT J AU Kong, YL Grembecka, J Edler, MC Hamel, E Mooberry, SL Sabat, M Brown, ML AF Kong, YL Grembecka, J Edler, MC Hamel, E Mooberry, SL Sabat, M Brown, ML TI Structure based design, synthesis and evaluation of boronic acid bioisosteres of combretastatin A-4. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Univ Virginia, Dept Chem, Charlottesville, VA 22904 USA. Univ Virginia, Charlottesville, VA 22903 USA. NCI, Div Canc Treatment & Diagnost, Dev Therapeut Program, Frederick Canc Res & Dev Ctr, Bethesda, MD 20892 USA. NCI, Dev Therapeut Program, Div Canc Treatment & Diagnost, Frederick Canc Res & Dev Ctr, Bethesda, MD 20892 USA. EM yk4n@virginia.edu; mlb2v@virginia.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 429-MEDI BP U186 EP U186 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600428 ER PT J AU Kuczera, K Jas, GS Houndonougbo, Y AF Kuczera, K Jas, GS Houndonougbo, Y TI Molecular dynamics simulations of phospholamban: Effects of membrane, phosphorylation and aggregation. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Univ Kansas, Dept Chem, Lawrence, KS 66045 USA. Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM kkuczera@ku.edu NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 111-COMP BP U772 EP U772 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177705435 ER PT J AU Laughon, BE AF Laughon, BE TI Development of new tuberculosis drug candidates. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIAID, Therapeut Res Program, Div AIDS, NIH, Bethesda, MD 20892 USA. EM blaughon@niaid.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 311-MEDI BP U164 EP U164 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600310 ER PT J AU Li, XF Hassan, SA Mehler, EL AF Li, XF Hassan, SA Mehler, EL TI Long dynamics simulations of proteins using atomistic force fields and a continuum representation of solvent effects. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Cornell Univ, Weill Med Coll, New York, NY 10021 USA. NIH, DHHS, Bethesda, MD USA. EM elm2020@med.cornell.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 087-COMP BP U768 EP U768 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177705411 ER PT J AU Madiraju, C Raccor, BS Shin, Y Balachandran, R Edler, MC Hamel, E Giuliano, KA Vogt, A Curran, DP Day, BW AF Madiraju, C Raccor, BS Shin, Y Balachandran, R Edler, MC Hamel, E Giuliano, KA Vogt, A Curran, DP Day, BW TI Synthesis, biological evaluation and structure-activity relationship analysis of (-)-dictyostatin-1 and analogues. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. NCI, Screening Technol Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15260 USA. EM chmst41@pitt.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 432-MEDI BP U186 EP U186 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600431 ER PT J AU Nicklaus, MC Sitzmann, M Ihlenfeldt, WD AF Nicklaus, MC Sitzmann, M Ihlenfeldt, WD TI New web services of public small-molecule databases, tools, and identifiers. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NCI, Med Chem Lab, CCR, NIH,DHHS, Frederick, MD 21702 USA. EM mn1@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 111-CINF BP U613 EP U613 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177704110 ER PT J AU Nussinov, R AF Nussinov, R TI Modeling amyloid conformations. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NCI, FCRDC, Lab Expt & Computat Biol, Basic Res Program,SAIC, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 560-PHYS BP U788 EP U788 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066603558 ER PT J AU Petrache, HI Zemb, T Parsegian, VA AF Petrache, HI Zemb, T Parsegian, VA TI Specific salt adsorption, screening of dispersion forces and swelling of zwitterionic bilayers induced by addition salt. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIH, Lab Phys & Struct Biol, Bethesda, MD 20892 USA. CEA Saclay, LIONS, DRECAM, SCM, Gif Sur Yvette, France. EM horia@helix.nih.gov NR 0 TC 1 Z9 1 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 242-COLL BP U669 EP U669 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177704401 ER PT J AU Pozsgay, V Kubler-Kielb, J Fekete, A Hoogerhout, P Coxon, B AF Pozsgay, V Kubler-Kielb, J Fekete, A Hoogerhout, P Coxon, B TI Chemical approaches to bacterial carbohydrate antigens SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NICHHD, NIH, Bethesda, MD 20892 USA. EM pozsgayv@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 011-CARB BP U255 EP U255 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177701430 ER PT J AU Reimer, JA Paravastu, A AF Reimer, JA Paravastu, A TI Optical pumping in bulk GaAs. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Univ Calif Berkeley, Dept Chem Engn, Berkeley, CA 94720 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM reimer@socrates.cchem.berkeley.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 118-PHYS BP U720 EP U720 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066603118 ER PT J AU Silveira, JR Caughey, B AF Silveira, JR Caughey, B TI Most infectious prion protein oligomer. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIAID, Rocky Mt Lab, Lab Persistent Viral Dis, Hamilton, MT 59840 USA. EM jsilveira@nih.gov; bcaughey@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 155-PHYS BP U726 EP U726 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066603155 ER PT J AU Soubias, HCGO Luckett, KM Polozov, IV Wong, KKY Yeliseev, AA Gawrisch, K AF Soubias, HCGO Luckett, KM Polozov, IV Wong, KKY Yeliseev, AA Gawrisch, K TI NMR studies on single lipid bilayers supported in cylindrical aluminum oxide nanopores: Reconstitution of GPCR. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. EM gawrisch@helix.nih.gov RI Yeliseev, Alexei/B-3143-2009; Gaede, Holly/B-7392-2015 OI Gaede, Holly/0000-0003-4444-4394 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 156-COLL BP U654 EP U654 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177704317 ER PT J AU Stan, G Brooks, BR Thirumalai, D Lorimer, GH AF Stan, G Brooks, BR Thirumalai, D Lorimer, GH TI Computational studies of chaperonin-mediated protein folding. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NHLBI, Lab Computat BIol, NIH, Bethesda, MD 20892 USA. Univ Maryland, Inst Phys Sci & Technol, College Pk, MD 20742 USA. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. EM gstan@helix.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 090-COMP BP U768 EP U768 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177705414 ER PT J AU Tabor, DC AF Tabor, DC TI Programs for preparing future researchers SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Natl Ctr Minor Hlth & Hlth Dispar, NIH, Bethesda, MD 20892 USA. EM tabord@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 030-CHED BP U347 EP U348 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177702056 ER PT J AU Tinkle, SS AF Tinkle, SS TI Skin exposure to nanoparticles. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIEHS, Div Extamural Res & Training, NIH, Res Triangle Pk, NC 27709 USA. EM tinkle@niehs.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 016-IEC BP U911 EP U911 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177706460 ER PT J AU Tycko, R Hummer, G AF Tycko, R Hummer, G TI Molecular dynamics simulations of amyloid fibrils. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM buchete@nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 259-PHYS BP U742 EP U742 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066603258 ER PT J AU Varghese, B Paulos, CM Breur, GJ Widmer, WR Low, PS AF Varghese, B Paulos, CM Breur, GJ Widmer, WR Low, PS TI Folate-targeted immunotherapy to activated macrophages in rheumatoid arthritis SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. EM varghesb@purdue.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 236-MEDI BP U150 EP U151 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600235 ER PT J AU Wang, JH Cheung, AP Yang, C Wang, EP Fang, KX Thurston, DE Liu, PS AF Wang, JH Cheung, AP Yang, C Wang, EP Fang, KX Thurston, DE Liu, PS TI Determination of antitumor agent SJG-136 in human serum by HPLC with tandem mass spectrometric detection (HPLC-MS/MS) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 SRI Int, Dept Analyt Chem, Menlo Pk, CA 94025 USA. Univ London, Sch Pharm, London WC1E 7HU, England. NCI, DCTD, Pharmaceut Resources Branch, Bethesda, MD 20892 USA. EM jennie.wang@sri.com; liup@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 186-ANYL BP U119 EP U119 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177700519 ER PT J AU Wickner, RB Ross, ED Pierce, MM Bax, A Minton, AP Baxa, U Terry, M Edskes, HK AF Wickner, RB Ross, ED Pierce, MM Bax, A Minton, AP Baxa, U Terry, M Edskes, HK TI Sequence - Independence of the prion domain of Ure2p. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. NIH, Phys Chem Lab, Bethesda, MD 20892 USA. NIAMS, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. EM wickner@helix.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 152-PHYS BP U725 EP U725 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066603152 ER PT J AU Willis, PG Horti, AG Mukhin, AG Pavlova, OA Chefer, SI AF Willis, PG Horti, AG Mukhin, AG Pavlova, OA Chefer, SI TI Synthesis and testing of a new series of cannabinoid ligands for positron emission tomography (pet). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Natl Inst Drug Abuse, Intramural Res Program, Neuroimaging Res Branch, NIH, Baltimore, MD 21206 USA. Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21218 USA. EM pwillis@intra.nida.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 026-MEDI BP U109 EP U109 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600025 ER PT J AU Xiao, XS Antony, S Pommier, Y Cushman, M AF Xiao, XS Antony, S Pommier, Y Cushman, M TI On the binding of indeno[1,2-C]isoquinolines in the DNA-topoisomerase I cleavage complex. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. EM xsxiao@pharmacy.purdue.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 504-MEDI BP U206 EP U206 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600534 ER PT J AU Xiao, XS Antony, S Pommier, Y Cushman, M AF Xiao, XS Antony, S Pommier, Y Cushman, M TI On the binding of indeno[1,2-C]isoquinolines in the DNA-topoisomerase I cleavage complex. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Purdue Univ, Dept Med Chem & Mol Pharmacol, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. EM xsxiao@pharmacy.purdue.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 504-MEDI BP U200 EP U200 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066600503 ER PT J AU Zhang, M AF Zhang, M TI Synthesis and applications of oligomeric sulfide and sulfonium salts derived from ROM polymerization. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Univ Kansas, CMLD, NIH, Ctr Excellence Combinatorial Methodol & Lib Dev, Lawrence, KS 66047 USA. Univ Kansas, Dept Chem, Lawrence, KS 66047 USA. EM mizhang@ku.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 194-ORGN BP U355 EP U355 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066601299 ER PT J AU Gentry, PR Covington, TR Lawrence, G McDonald, T Snow, ET Germolec, D Moser, G Yager, MW Clewell, HJ AF Gentry, PR Covington, TR Lawrence, G McDonald, T Snow, ET Germolec, D Moser, G Yager, MW Clewell, HJ TI Comparison of tissue dosimetry in the mouse following chronic exposure to arsenic compounds SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID DISPOSITION; MICE; ACID AB Several chronic bioassays have been conducted in multiple strains of mice in which various concentrations of arsenate or arsenite were administered in the drinking water without a tumorigenic effect. However, one study (Ng et al., 1999) reported a significant increase in tumor incidence in C57Bl/6J mice exposed to arsenic in their drinking water throughout their lifetime, with no tumors reported in controls. A physiologically based pharmacokinetic model for arsenic in the mouse has previously been developed (Gentry et al., 2004) to investigate potential differences in tissue dosimetry of arsenic species across various strains of mice. Initial results indicated no significant differences in blood, liver, or urine dosimetry in B6C3F1 and C57Bl/6 mice for acute or subchronic exposure. The current work was conducted to compare model-predicted estimates of tissue dosimetry to additional kinetic information from the (C57Bl/6 x CBA)F1 and TgAc mouse. The results from the current modeling indicate that the pharmacokinetic parameters derived based on information in the B6C3F1 mouse adequately describe the measured concentrations in the blood/plasma, liver, and urine of both the (C57Bl/6 x CBA)F1 and TgAc mouse, providing further support that the differences in response observed in the chronic bioassays are not related to strain-specific differences in pharmacokinetics. One significant finding was that no increases in skin or lung concentrations of arsenic species in the (C57Bl/6 x CBA)F1 strain were observed following administration of low concentrations (0.2 or 2 mg/L) of arsenate in the drinking water, even though differences in response in the skin were reported. These data suggest that pharmacodynamic changes may be observed following exposure to arsenic compounds without an observable change in tissue dosimetry. These results provided further indirect support for the existence of inducible arsenic efflux in these tissues. C1 ENVIRON Int Corp, Ruston, LA 71270 USA. Deakin Univ, Burwood, Australia. NIEHS, Res Triangle Pk, NC 27709 USA. Integrated Lab Syst Inc, Res Triangle Pk, NC USA. EPRI, Palo Alto, CA USA. RP Gentry, PR (reprint author), ENVIRON Int Corp, 602 E Georgia Ave, Ruston, LA 71270 USA. EM rgentry@environcorp.com NR 15 TC 6 Z9 6 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD MAR 12 PY 2005 VL 68 IS 5 BP 329 EP 351 DI 10.1080/15287390590900813 PG 23 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 893NG UT WOS:000226725900003 PM 15799626 ER PT J AU Timsit, YE Miller, SLH Mohney, RP O'Bryan, JP AF Timsit, YE Miller, SLH Mohney, RP O'Bryan, JP TI The U-box ligase carboxyl-terminus of Hsc 70-interacting protein ubiquitylates Epsin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE endocytosis; ubiquitylation; trafficking; UIMs ID FACETS DEUBIQUITINATING ENZYME; HEAT-SHOCK PROTEINS; E3 UBIQUITIN LIGASE; CLATHRIN-MEDIATED ENDOCYTOSIS; FAT-FACETS; COATED VESICLES; INTERACTING MOTIFS; UNCOATING PROTEIN; BINDING DOMAINS; IN-VIVO AB Epsin is an endocytic adaptor protein involved in the regulation of clathrin-dependent endocytosis. We and others have demonstrated. that Epsin is ubiquitylated in cells and requires its ubiquitin interacting motifs (UIMs) for this modification. To further elucidate the mechanism of Epsin ubiquitylation, we initiated studies to identify the E3 ligase(s) that modifies Epsin. In this study, we discovered that the U-box ubiquitin ligase carboxyl-terminus of Hsc70 interacting protein (CHIP) ubiquitylated Epsin. Using an in vitro ubiquitylation assay, we demonstrate that CHIP specifically ubiquitylated Epsin in a UIM-dependent manner, Furthermore, overexpression of CHIP in cells increased Epsin ubiquitylation also in a UIM-dependent manner. Together, these data provide evidence that CHIP functions to ubiquitylate the endocytic protein Epsin. Published by Elsevier Inc. C1 NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Sch Med, Dept Biomed Engn, Chapel Hill, NC 27599 USA. RP O'Bryan, JP (reprint author), NIEHS, Lab Signal Transduct, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM obryan@niehs.nih.gov NR 57 TC 11 Z9 12 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 11 PY 2005 VL 328 IS 2 BP 550 EP 559 DI 10.1016/j.bbrc.2005.01.022 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 898KM UT WOS:000227075700027 PM 15694383 ER PT J AU Grissom, SF Lobenhofer, EK Tucker, CJ AF Grissom, SF Lobenhofer, EK Tucker, CJ TI A qualitative assessment of direct-labeled cDNA products prior to microarray analysis SO BMC GENOMICS LA English DT Article ID GENE-EXPRESSION PATTERNS; RNA AB Background: The success of the microarray process in determining differential gene expression of thousands of genes is dependent upon the quality and integrity of the starting RNA, this being particularly true of direct labeling via a reverse transcription procedure. Furthermore, an RNA of reasonable quality still may not yield reliable hybridization data if the labeling efficiency was poor. Results: Here we present a novel assay for assessing the quality of directly labeled fluorescent cDNA prior to microarray hybridization utilizing the Agilent 2100 Bioanalyzer, which employs microfluidic technology for the analysis of nucleic acids and proteins. Using varying amounts of RNase to simulate RNA degradation, we show the strength of this un-advertised assay in determining the relative amounts of cDNA obtained from a direct labeling reaction. Conclusion: Utilization of this method in the lab will help to prevent the costly mistake of hybridizing poor quality direct labeled products to expensive arrays. C1 Natl Inst Environm Hlth Sci, Intramural Microarray Grp, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Gene Regulat Grp, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Icoria Inc, Paradigm Array Labs, Res Triangle Pk, NC 27709 USA. RP Tucker, CJ (reprint author), Natl Inst Environm Hlth Sci, Intramural Microarray Grp, Res Triangle Pk, NC 27709 USA. EM grissom2@niehs.nih.gov; elobenhofer@icoria.com; tucker1@niehs.nih.gov NR 14 TC 6 Z9 6 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD MAR 11 PY 2005 VL 6 AR 36 DI 10.1186/1471-2164-6-36 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 913OY UT WOS:000228163900001 PM 15762992 ER PT J AU Resnick, MA AF Resnick, MA TI Reduced replication: A call to ARMS SO CELL LA English DT Editorial Material ID COMMON FRAGILE SITES; SACCHAROMYCES-CEREVISIAE; REARRANGEMENTS; REPAIR; BREAKS AB In this issue of Cell, Lemoine et al. (2005) monitor chromosome instability in yeast cells with reduced levels of an essential replicative DNA polymerase. The authors identify a hotspot for chromosome aberrations reminiscent of fragile sites in human cells. This hotspot is composed of inverted Ty elements, which lead to a double-strand break under conditions of limited replication. C1 NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Resnick, MA (reprint author), NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD MAR 11 PY 2005 VL 120 IS 5 BP 569 EP 570 DI 10.1016/j.cell.2005.02.028 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 908EY UT WOS:000227771400001 PM 15766518 ER PT J AU Moreau, B Straube, S Fisher, RJ Putney, JW Parekh, AB AF Moreau, B Straube, S Fisher, RJ Putney, JW Parekh, AB TI Ca2+-calmodulin-dependent facilitation and Ca2+ inactivation of Ca2+ release-activated Ca2+ channel SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CURRENT I-CRAC; INOSITOL TRISPHOSPHATE RECEPTORS; CALCIUM-DEPENDENT INACTIVATION; BASOPHILIC LEUKEMIA-CELLS; T-LYMPHOCYTES; FEEDBACK INHIBITION; INFLUX PATHWAY; ACINAR-CELLS; RBL-1 CELLS; CALMODULIN AB In non-excitable cells, one major route for Ca2+ influx is through store-operated Ca2+ channels in the plasma membrane. These channels are activated by the emptying of intracellular Ca2+ stores, and in some cell types store-operated influx occurs through Ca2+ release-activated Ca2+ (CRAC) channels. Here, we report that intracellular Ca2+ modulates CRAC channel activity through both positive and negative feedback steps in RBL-1 cells. Under conditions in which cytoplasmic Ca2+ concentration can fluctuate freely, we find that store-operated Ca2+ entry is impaired either following overexpression of a dominant negative calmodulin mutant or following whole-cell dialysis with a calmodulin inhibitory peptide. The peptide had no inhibitory effect when intracellular Ca2+ was buffered strongly at low levels. Hence, Ca2+-calmodulin is not required for the activation of CRAC channels per se but is an important regulator under physiological conditions. We also find that the plasma membrane Ca2+ ATPase is the dominant Ca2+ efflux pathway in these cells. Although the activity of the Ca2+ pump is regulated by calmodulin, the store-operated Ca2+ entry is more sensitive to inhibition by the calmodulin mutant than by Ca2+ extrusion. Hence, these two plasmalemmal Ca2+ transport systems may differ in their sensitivities to endogenous calmodulin. Following the activation of Ca2+ entry, the rise in intracellular Ca2+ subsequently feeds back to further inhibit Ca2+ influx. This slow inactivation can be activated by a relatively brief Ca2+ influx (30-60 s); it reverses slowly and is not altered by overexpression of the calmodulin mutant. Hence, the same messenger, intracellular Ca2+, can both facilitate and inactivate Ca2+ entry through store-operated CRAC channels and through different mechanisms. C1 Univ Oxford, Dept Physiol, Lab Cellular & Mol Signalling, Oxford OX1 3PT, England. RP Parekh, AB (reprint author), NIEHS, Calcium Regulat Sect, Dept Hlth & Human Serv, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM anant.parekh@physiol.ox.ac.uk RI Straube, Sebastian/E-1937-2016 OI Straube, Sebastian/0000-0001-7862-0398 FU Medical Research Council [G0200218] NR 42 TC 27 Z9 29 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 11 PY 2005 VL 280 IS 10 BP 8776 EP 8783 DI 10.1074/jbc.M409619200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903VG UT WOS:000227453100020 PM 15611075 ER PT J AU Knodler, LA Finlay, BB Steele-Mortimer, O AF Knodler, LA Finlay, BB Steele-Mortimer, O TI The Salmonella effector protein SopB protects epithelial cells from apoptosis by sustained activation of Akt SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENTERICA SEROTYPE TYPHIMURIUM; MONOCYTE-DERIVED MACROPHAGES; III SECRETION SYSTEM; PATHOGENICITY ISLAND; HOST-CELL; SEROVAR TYPHIMURIUM; CULTURED MACROPHAGES; INFECTED MACROPHAGES; POLYAMINE DEPLETION; ACTIN CYTOSKELETON AB Invasion of epithelial cells by Salmonella enterica is mediated by bacterial "effector" proteins that are delivered into the host cell by a type III secretion system. Although primarily known for their roles in actin rearrangements and membrane ruffling, translocated effectors also affect host cell processes that are not directly associated with invasion. Here, we show that SopB/SigD, an effector with phosphoinositide phosphatase activity, has anti-apoptotic activity in Salmonella-infected epithelial cells. Salmonella induced the sustained activation of Akt/protein kinase B, a pro-survival kinase, in a SopB-dependent manner. Failure to activate Akt resulted in increased levels of apoptosis after infection with a sopB deletion mutant (DeltasopB). Furthermore, cells infected with wild type bacteria, but not the DeltasopB strain, were protected from camptothecin-induced cleavage of caspase-3 and subsequent apoptosis. The antiapoptotic activity of SopB was dependent on its phosphatase activity, because a catalytically inactive mutant was unable to protect cells from the effects of camptothecin. Finally, small interfering RNA was used to demonstrate the essential role of Akt in SopB-mediated protection against apoptosis. These results provide new insights into the mechanisms of apoptosis and highlight how bacterial effectors can intercept signaling pathways to manipulate host responses. C1 NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. Univ British Columbia, Michael Smith Labs, Vancouver, BC V6T 1Z4, Canada. RP Steele-Mortimer, O (reprint author), NIAID, Rocky Mt Labs, Intracellular Parasites Lab, NIH, Hamilton, MT 59840 USA. EM omortimer@niaid.nih.gov NR 60 TC 127 Z9 131 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 MAR 11 PY 2005 VL 280 IS 10 BP 9058 EP 9064 DI 10.1074/jbc.M412588200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903VG UT WOS:000227453100054 PM 15642738 ER PT J AU Cabib, E Duran, A AF Cabib, E Duran, A TI Synthase III-dependent chitin is bound to different acceptors depending on location on the cell wall of budding yeast SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ONE-STEP PURIFICATION; SACCHAROMYCES-CEREVISIAE; LITHIUM CHLORIDE-N,N-DIMETHYLACETAMIDE; SEPTATION APPARATUS; CYCLE; MORPHOGENESIS; ARCHITECTURE; SYSTEM; CHROMATOGRAPHY; CYTOKINESIS AB In yeast, chitin is laid down at three locations: a ring at the mother-bud neck, the primary septum and, after cytokinesis, the cell wall of the daughter cell. Some of the chitin is free and the remainder attached to similar to( 1 3) glucan or beta(1-6) glucan. We recently reported that the chitin ring contributes to the prevention of growth at the mother-bud neck and hypothesized that this inhibition is achieved by a preferential binding of chitin to beta(1-3) glucan at that site. Here, we devised a novel strategy for the analysis of chitin cross-links in [C-14] glucosamine-labeled cell walls, involving solubilization in water of alkali-treated walls by carboxymethylation. Intact cell walls or their digestion products with similar to( 1 3) glucanase or similar to(1-6) glucanase were carboxymethylated and fractionated on size columns, and the percentage of chitin bound to different polysaccharides was calculated. Chitin dispersed in the wall was labeled in maturing unbudded cells and that of the ring in early budding cells. The former was mostly attached to beta( 1 6) glucan and the latter to beta( 1 - 3) glucan. This confirmed our hypothesis and indicated that the cell has mechanisms to attach chitin, a water-insoluble substance, synthesized here through chitin synthase III, to different acceptors, depending on location. In contrast, most of the chitin synthase II-dependent chitin of the primary septum was free, with the remainder linked to beta(1-3) glucan. C1 NIDDK, Lab Biochem & Genet, Dept Hllth & Human Serv, NIH, Rockville, MD 20852 USA. Univ Salamanca, Inst Microbiol Bioquim, CSIC, Salamanca 37007, Spain. RP NIDDK, Lab Biochem & Genet, Dept Hllth & Human Serv, NIH, Rockville, MD 20852 USA. EM enricoc@bdg10.niddk.nih.gov NR 38 TC 29 Z9 30 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 11 PY 2005 VL 280 IS 10 BP 9170 EP 9179 DI 10.1074/jbc.M414005200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903VG UT WOS:000227453100066 PM 15637060 ER PT J AU Gong, X Yu, L Xia, D Yu, CA AF Gong, X Yu, L Xia, D Yu, CA TI Evidence for electron equilibrium between the two hemes b(L) in the dimeric cytochrome bc(1) complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BOVINE HEART-MITOCHONDRIA; IRON-SULFUR PROTEIN; RHODOBACTER-SPHAEROIDES; SUPEROXIDE FORMATION; CRYSTAL-STRUCTURE; Q(O) SITE; Q-CYCLE; CHEMILUMINESCENCE; INHIBITION; GENERATION AB Structural analysis of the dimeric mitochondrial cytochrome bc(1) complex suggests that electron transfer between inter-monomer hemes b(L)-b(L) may occur during bc(1) catalysis. Such electron transfer may be facilitated by the aromatic pairs present between the two b(L) hemes in the two symmetry-related monomers. To test this hypothesis, R. sphaeroides mutants expressing His(6)- tagged bc1 complexes with mutations at three aromatic residues (Phe-195, Tyr-199, and Phe-203), located between two bL hemes, were generated and characterized. All three mutants grew photosynthetically at a rate comparable to that of wild-type cells. The bc(1) complexes prepared from mutants F195A, Y199A, and F203A have, respectively, 78%, 100%, and 100% of ubiquinol-cytochrome c reductase activity found in the wild- type complex. Replacing the Phe-195 of cytochrome b with Tyr, His, or Trp results in mutant complexes ( F195Y, F195H, or F195W) having the same ubiquinol-cytochrome c reductase activity as the wild- type. These results indicate that the aromatic group at position195 of cytochrome b is involved in electron transfer reactions of the bc1 complex. The rate of superoxide anion ( O-2.) generation, measured by the chemiluminescence of 2-methyl-6-( pmethoxyphenyl)3,7- dihydroimidazo[ 1,2-alpha] pyrazin-3-one hydrochloride- O2. adduct during oxidation of ubiquinol, is 3 times higher in the F195A complex than in the wild- type or mutant complexes Y199A or F203A. This supports the idea that the interruption of electron transfer between the two bL hemes enhances electron leakage to oxygen and thus decreases the ubiquinol-cytochrome c reductase activity. C1 Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA. NIH, Cell Biol Lab, Ctr Canc Inst, Bethesda, MD 20892 USA. RP Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA. EM cayuq@okstate.edu FU NIGMS NIH HHS [GM30721] NR 40 TC 42 Z9 44 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 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 11 PY 2005 VL 280 IS 10 BP 9251 EP 9257 DI 10.1074/jbc.M409994200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903VG UT WOS:000227453100075 PM 15615714 ER PT J AU Puertollano, R AF Puertollano, R TI Interactions of Tom1L1 with the multivesicular body sorting machinery SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID GROWTH-FACTOR RECEPTOR; TRANS-GOLGI NETWORK; EARLY ENDOSOMES; GAMMA-ADAPTIN; MEMBRANE ASSOCIATION; SIGNALING PATHWAYS; UBIQUITIN-BINDING; EGF RECEPTOR; VHS DOMAINS; GAT DOMAIN AB Tom1L1 ( Tom1-like1) and related proteins Tom1 ((T) under bar arget (o) under barf (M) under bar yb1) and Tom1L2 ( Tom1- like2) constitute a new protein family characterized by the presence of a VHS ((V) under bar ps27p/ (H) under bar rs/(S) under bar tam) domain in the N- terminal portion followed by a GAT ((G) under bar GA (a) under bar nd (T) under bar om) domain. Recently it was demonstrated that the GAT domain of both Tom1 and Tom1L1 binds ubiquitin, suggesting that these proteins might participate in the sorting of ubiquitinated proteins into multivesicular bodies ( MVBs). Here we report a novel interaction between Tom1L1 and members of the MVB sorting machinery. Specifically, we found that the VHS domain of Tom1L1 interacts with Hrs ( (H) under bar epatocyte growth factor-(r) under bar egulated tyrosine kinase (s) under bar ubstrate), whereas a PTAP motif, located between the VHS and GAT domain of Tom1L1, is responsible for binding to TSG101 ((t) under bar umor (s) under bar usceptibility gene 101). Myc epitopetagged Tom1L1 showed a cytosolic distribution but was recruited to endosomes following Hrs expression. In addition, Tom1L1 possesses several tyrosine motifs at the C-terminal region that mediate interactions with members of the Src family kinases and other signaling proteins such as Grb2 and p85. We showed that a fraction of Fyn kinase localizes at endosomes and that this distribution becomes more evident after epidermal growth factor internalization. Moreover, expression of a constitutive active form of Fyn also promoted the recruitment of Tom1L1 to enlarged endosomes. Taken together, we propose that Tom1L1 could act as an intermediary between signaling and degradative pathways. C1 NHLBI, Lab Cell Signaling, NIH, Rockville, MD 20852 USA. RP Puertollano, R (reprint author), NHLBI, Lab Cell Signaling, NIH, Bldg 50,Rm 3537, Rockville, MD 20852 USA. EM puertolr@mail.nih.gov NR 62 TC 44 Z9 46 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 MAR 11 PY 2005 VL 280 IS 10 BP 9258 EP 9264 DI 10.1074/jbc.M412481200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903VG UT WOS:000227453100076 PM 15611048 ER PT J AU Mori, T O'Keefe, BR Sowder, RC Bringans, S Gardella, R Berg, S Cochran, P Turpin, JA Buckheit, RW McMahon, JB Boyd, MR AF Mori, T O'Keefe, BR Sowder, RC Bringans, S Gardella, R Berg, S Cochran, P Turpin, JA Buckheit, RW McMahon, JB Boyd, MR TI Isolation and characterization of griffithsin, a novel HIV-inactivating protein, from the red alga Griffithsia sp. SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; CYANOVIRIN-N BINDS; NATURAL-PRODUCTS; DC-SIGN; CULTURED CYANOBACTERIUM; ENVELOPE GLYCOPROTEIN; GP120; POTENT; SURFACE; INFECTIVITY AB Griffithsin (GRFT), a novel anti-HIV protein, was isolated from an aqueous extract of the red alga Griffithsia sp. The 121-amino acid sequence of GRFT has been determined, and biologically active GRFT was subsequently produced by expression of a corresponding DNA sequence in Escherichia coli. Both native and recombinant GRFT displayed potent antiviral activity against laboratory strains and primary isolates of T- and M-tropic HIV-1 with EC50 values ranging from 0.043 to 0.63 nM. GRFT also aborted cell-to-cell fusion and transmission of HIV-1 infection at similar concentrations. High concentrations (e. g. 783 nM) of GRFT were not lethal to any tested host cell types. GRFT blocked CD4-dependent glycoprotein (gp) 120 binding to receptor-expressing cells and bound to viral coat glycoproteins (gp120, gp41, and gp160) in a glycosylation-dependent manner. GRFT preferentially inhibited gp120 binding of the monoclonal antibody (mAb) 2G12, which recognizes a carbohydrate-dependent motif, and the (mAb) 48d, which binds to CD4-induced epitope. In addition, GRFT moderately interfered with the binding of gp120 to sCD4. Further data showed that the binding of GRFT to soluble gp120 was inhibited by the monosaccharides glucose, mannose, and N-acetylglucosamine but not by galactose, xylose, fucose, N-acetylgalactosamine, or sialic acid-containing glycoproteins. Taken together these data suggest that GRFT is a new type of lectin that binds to various viral glycoproteins in a monosaccharide-dependent manner. GRFT could be a potential candidate microbicide to prevent the sexual transmission of HIV and AIDS. C1 NCI, Mol Targets Dev Program, Ctr Canc Res, Frederick, MD 21702 USA. SAIC Fredercik, Basic Res Program, Frederick, MD 21702 USA. SAIC Fredercik, AIDS Vaccine Program, Frederick, MD 21702 USA. So Res Inst, Retrovirus Res Lab, Frederick, MD 21702 USA. RP Mori, T (reprint author), NCI, Mol Targets Dev Program, Ctr Canc Res, Bldg 562,Rm 201, Frederick, MD 21702 USA. EM mori@ncifcrf.gov; okeefe@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 50 TC 171 Z9 180 U1 1 U2 23 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 MAR 11 PY 2005 VL 280 IS 10 BP 9345 EP 9353 DI 10.1074/jbc.M411122200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903VG UT WOS:000227453100087 PM 15613479 ER PT J AU Kim, DJ Murray, IA Burns, AM Gonzalez, FJ Perdew, GH Peters, JM AF Kim, DJ Murray, IA Burns, AM Gonzalez, FJ Perdew, GH Peters, JM TI Peroxisome proliferator-activated receptor-beta/delta inhibits epidermal cell proliferation by down-regulation of kinase activity SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FATTY-ACID OXIDATION; C-ALPHA; TARGETED DISRUPTION; GENE-EXPRESSION; BREAST-CANCER; MUSCLE-CELLS; PPAR-DELTA; CYCLIN-E; DIFFERENTIATION; INFLAMMATION AB Recent work has shown that peroxisome proliferator-activated receptor beta(PPARbeta) attenuates cell proliferation and skin carcinogenesis, and this is due in part to regulation of ubiquitin C expression. In these studies, the role of PPARbeta in modulating ubiquitin-dependent protein kinase Calpha (PKCalpha) levels and phosphorylation signaling pathways was evaluated. Intracellular phosphorylation analysis showed that phosphorylated PKCalpha and other kinases were lower in wild-type mouse skin treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) as compared with PPARbeta-null mouse skin. No differences in expression levels of other PKC isoforms present in skin were observed. Lower ubiquitination of PKCalpha was found in TPA-treated PPARbeta-null skin as compared with wild-type, and inhibition of ubiquitin-dependent proteasome degradation prevented TPA-induced down-regulation of PKCalpha. The activity of PKCalpha and downstream signaling kinases is enhanced, and expression of cyclooxygenase-2 (COX-2) is significantly greater, in PPARbeta-null mouse skin in response to TPA compared with wild-type mouse skin. Inhibition of PKCalpha or COX-2 reduced cell proliferation in TPA-treated PPARbeta-null keratinocytes in a dose-dependent manner, whereas it only slightly influenced cell proliferation in wild-type keratinocytes. Combined, these studies provide strong evidence that PPAR beta attenuates cell proliferation by modulating PKCalpha/Raf1/MEK/ERK activity that may be due in part to reduced ubiquitin-dependent turnover of PKCalpha. C1 Penn State Univ, Dept Vet Sci, University Pk, PA 16802 USA. Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. Penn State Univ, Huck Inst Life Sci, Grad Program Mol Toxicol, University Pk, PA 16802 USA. NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. RP Peters, JM (reprint author), Penn State Univ, Dept Vet Sci, 312 Life Sci Bldg, University Pk, PA 16802 USA. EM jmp21@psu.edu RI Peters, Jeffrey/D-8847-2011 FU NCI NIH HHS [CA97999, CA89607]; NIEHS NIH HHS [ES04869] NR 58 TC 78 Z9 78 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 MAR 11 PY 2005 VL 280 IS 10 BP 9519 EP 9527 DI 10.1074/jbc.M413808200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903VG UT WOS:000227453100106 PM 15632134 ER PT J AU Ulmer, TS Bax, A Cole, NB Nussbaum, RL AF Ulmer, TS Bax, A Cole, NB Nussbaum, RL TI Structure and dynamics of micelle-bound human alpha-synuclein SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MULTIDIMENSIONAL NMR EXPERIMENTS; MODEL-FREE APPROACH; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; DIPOLAR COUPLINGS; CHEMICAL-SHIFTS; STRUCTURE REFINEMENT; SECONDARY STRUCTURE; GLOBULAR-PROTEINS; LEWY BODIES AB Misfolding of the protein alpha-synuclein (aS), which associates with presynaptic vesicles, has been implicated in the molecular chain of events leading to Parkinson's disease. Here, the structure and dynamics of micelle- bound aS are reported. Val(3)-Val(37) and Lys(45)Thr(92) form curved alpha-helices, connected by a well ordered, extended linker in an unexpected anti-parallel arrangement, followed by another short extended region (Gly(93)-Lys(97)), overlapping the recently identified chaperone- mediated autophagy recognition motif and a highly mobile tail (Asp(98)-Ala(140)). Helix curvature is significantly less than predicted based on the native micelle shape, indicating a deformation of the micelle by aS. Structural and dynamic parameters show a reduced helical content for Ala(30)-Val37. A dynamic variation in interhelical distance on the microsecond timescale is complemented by enhanced sub-nanosecond timescale dynamics, particularly in the remarkably glycine-rich segments of the helices. These unusually rich dynamics may serve to mitigate the effect of aS binding on membrane fluidity. The well ordered conformation of the helix- helix connector indicates a defined interaction with lipidic surfaces, suggesting that, when bound to larger diameter synaptic vesicles, it can act as a switch between this structure and a previously proposed uninterrupted helix. C1 NHGRI, Lab Chem Phys, NIDDK, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. RP Ulmer, TS (reprint author), NHGRI, Lab Chem Phys, NIDDK, NIH, Bethesda, MD 20892 USA. EM tobias.ulmer@nih.gov NR 70 TC 361 Z9 366 U1 6 U2 64 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 MAR 11 PY 2005 VL 280 IS 10 BP 9595 EP 9603 DI 10.1074/jbc.M411805200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903VG UT WOS:000227453100114 PM 15615727 ER PT J AU Cole, NB Murphy, DD Lebowitz, J Di Noto, L Levine, RL Nussbaum, RL AF Cole, NB Murphy, DD Lebowitz, J Di Noto, L Levine, RL Nussbaum, RL TI Metal-catalyzed oxidation of alpha-synuclein - Helping to define the relationship between oligomers, protofibrils, and filaments SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID MULTIPLE SYSTEM ATROPHY; ATOMIC-FORCE MICROSCOPY; AMINO-ACID-RESIDUES; PARKINSONS-DISEASE; LEWY BODIES; IN-VITRO; ALZHEIMERS-DISEASE; LIPID-PEROXIDATION; CROSS-LINKING; INHIBITS FIBRILLATION AB Oxidative stress is implicated in a number of neuro-degenerative diseases and is associated with the selective loss of dopaminergic neurons of the substantia nigra in Parkinson's disease. The role of alpha-synuclein as a potential target of intracellular oxidants has been demonstrated by the identification of posttranslational modifications of synuclein within intracellular aggregates that accumulate in Parkinson's disease brains, as well as the ability of a number of oxidative insults to induce synuclein oligomerization. The relationship between these relatively small soluble oligomers, potentially neurotoxic synuclein protofibrils, and synuclein filaments remains unclear. We have found that metal-catalyzed oxidation of alpha-synuclein inhibited formation of synuclein filaments with a concomitant accumulation of beta sheet-rich oligomers that may represent synuclein protofibrils. Similar results with a number of oxidative and enzymatic treatments suggest that the covalent association of synuclein into higher molecular mass oligomers/ protofibrils represents an alternate pathway from filament formation and renders synuclein less prone to proteasomal degradation. C1 NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA. NINDS, NIH, Div Extramural Activities, Bethesda, MD 20892 USA. NIH, Off Res Serv, Div Bioengn & Phys Sci, Bethesda, MD 20892 USA. NHLBI, NIH, Biochem Lab, Bethesda, MD 20892 USA. RP Cole, NB (reprint author), NHGRI, NIH, Genet Dis Res Branch, 49 Convent Dr,Rm 4B67, Bethesda, MD 20892 USA. EM ncole@mail.nih.gov RI Levine, Rodney/D-9885-2011 NR 103 TC 81 Z9 84 U1 0 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAR 11 PY 2005 VL 280 IS 10 BP 9678 EP 9690 DI 10.1074/jbc.M409946200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903VG UT WOS:000227453100125 PM 15615715 ER PT J AU Ortega, J Heymann, JB Kajava, AV Ustrell, V Rechsteiner, M Steven, AC AF Ortega, J Heymann, JB Kajava, AV Ustrell, V Rechsteiner, M Steven, AC TI The axial channel of the 20 S proteasome opens upon binding of the PA200 activator SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE proteasome activator; allostery; cryo-electron microscopy; image reconstruction ID 20S PROTEASOME; ANTIGEN PRESENTATION; ANGSTROM RESOLUTION; STRAND BREAKS; PROTEIN; TRANSLOCATION; ACIDOPHILUM; PROTEOLYSIS; MICROSCOPY; TRANSPORT AB Proteasomes consist of a proteolytic core called the 20 S particle and ancillary factors that regulate its activity in various ways. PA200 has been identified as a large (200 kDa) nuclear protein that stimulates proteasomal hydrolysis of peptides. To characterize its interaction with the 20 S core, we have visualized PA200-20 S complexes by electron microscopy. Monomers of PA200 bind to one or both ends of the 20 S core. Reconstructed in three dimensions to 23 Angstrom resolution from cryo-electron micrographs of the singly bound complex, PA200 has an asymmetric dome-like structure with major and minor lobes. Taking into account previous bioinformatic analysis, it is likely to represent an irregular folding of an a-helical solenoid composed of HEAT-like repeats. PA200 makes contact with all alpha-subunits except alpha7, and this interaction induces an opening of the axial channel through the alpha-ring. Thus, the activation mechanism of PA200 is expressed via its allosteric effects on the 20 S core particle, perhaps facilitating release of digestion products or the entrance of substrates. Published by Elsevier Ltd. C1 NIAMSD, Struct Biol Lab, NIH, Bethesda, MD 20892 USA. McMaster Univ, Hlth Sci Ctr, Dept Biochem, Hamilton, ON L8N 3Z5, Canada. CNRS, Ctr Rech Biochim Macromol, FRE 2593, F-34293 Montpellier, France. Univ Utah, Dept Biochem, Salt Lake City, UT 84132 USA. RP Steven, AC (reprint author), NIAMSD, Struct Biol Lab, NIH, Bldg 50,Room 1517,50 S Dr,MSC 8025, Bethesda, MD 20892 USA. EM Alasdair_Steven@nih.gov RI Heymann, Bernard/F-6825-2011; Kajava, Andrey/E-1107-2014; OI Kajava, Andrey/0000-0002-2342-6886; Heymann, Bernard/0000-0002-8872-5326 FU Canadian Institutes of Health Research [64342] NR 37 TC 54 Z9 55 U1 0 U2 3 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 MAR 11 PY 2005 VL 346 IS 5 BP 1221 EP 1227 DI 10.1016/j.jmb.2004.12.049 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903YQ UT WOS:000227462000004 PM 15713476 ER PT J AU Hawkins, CA de Alba, E Tjandra, N AF Hawkins, CA de Alba, E Tjandra, N TI Solution structure of human saposin C in a detergent environment SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE saposin C; nuclear magnetic resonance; detergent micelles; membrane interactions; protein structure ID N-15 NMR RELAXATION; MAGNETIC-RESONANCE RELAXATION; RESIDUAL DIPOLAR COUPLINGS; LIQUID-CRYSTALLINE MEDIUM; MODEL-FREE APPROACH; ROTATIONAL DIFFUSION; ACTIVATOR PROTEINS; MEMBRANE-PROTEINS; MACROMOLECULES; MICELLES AB Saposin C is a lysosomal, membrane-binding protein that acts as an activator for the hydrolysis of glucosylceramide by the enzyme glucocerebrosidase. We used high-resolution NMR to determine the three-dimensional solution structure of saposin C in the presence of the detergent sodium dodecyl sulfate (SDS). This structure provides the first representation of membrane bound saposin C at the atomic level. In the presence of SDS, the protein adopts an open conformation with an exposed hydrophobic pocket. In contrast, the previously reported NMR structure of saposin C in the absence of SDS is compact and contains a hydrophobic core that is not exposed to the solvent. NMR data indicate that the SDS molecules interact with the hydrophobic pocket. The structure of saposin C in the presence of SDS is very similar to a monomer in the saposin B homodimer structure. Their comparison reveals possible similarity in the type of protein/lipid interaction as well as structural components differentiating their quaternary structures and functional specificity. Published by Elsevier Ltd. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Tjandra, N (reprint author), NHLBI, Biophys Chem Lab, NIH, 50 Ctr Dr, Bethesda, MD 20892 USA. EM nico@helix.nih.gov NR 47 TC 46 Z9 46 U1 0 U2 0 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 MAR 11 PY 2005 VL 346 IS 5 BP 1381 EP 1392 DI 10.1016/j.jmb.2004.12.045 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903YQ UT WOS:000227462000016 PM 15713488 ER PT J AU Zivotofsky, AZ AF Zivotofsky, AZ TI A dissociation between perception and action in open-loop smooth-pursuit ocular tracking of the Duncker Illusion SO NEUROSCIENCE LETTERS LA English DT Article DE induced motion; smooth pursuit; human; oculomotor ID RESIST VISUAL ILLUSIONS/; ILLUSORY STIMULUS MOTION; EYE-MOVEMENTS; REMEMBERED TARGETS; PERCEIVED MOTION; RESPONSES; SACCADES; LATENCY; MONKEY; GAZE AB The visual system serves two distinct functions. The information acquired by it is used to both create a percept of the external world and to guide motor actions. In recent years there has been considerable debate regarding whether the same information is utilized and processed in the same manner in the two tasks. The Duncker Illusion, also known as induced motion, is an illusion of motion that results when there is background movement, and it neatly dissociates true from perceived motion. We examined the open-loop period of smooth eye tracking of a target that had an illusory component to its trajectory due to background motion. It was found that the eyes moved in the direction of background motion and of true target motion but not in the illusory direction, despite the strong percept of illusory motion experienced by all subjects. This finding lends support to the hypothesis of separate neurological pathways for the processing of visual information used to create the conscious percept and visual information used to drive motor actions. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, IL-52900 Ramat Gan, Israel. NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. RP Zivotofsky, AZ (reprint author), Bar Ilan Univ, Gonda Multidisciplinary Brain Res Ctr, IL-52900 Ramat Gan, Israel. EM zivotoa@mail.biu.ac.il NR 37 TC 9 Z9 9 U1 0 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3940 J9 NEUROSCI LETT JI Neurosci. Lett. PD MAR 11 PY 2005 VL 376 IS 2 BP 81 EP 86 DI 10.1016/j.neulet.2004.11.031 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 900IR UT WOS:000227209100003 PM 15698925 ER PT J AU Hewitt, SC Deroo, BJ Korach, KS AF Hewitt, SC Deroo, BJ Korach, KS TI A new mediator for an old hormone? SO SCIENCE LA English DT Editorial Material ID MEMBRANE ESTROGEN-RECEPTORS; G-PROTEIN; CELLS; ROLES C1 NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Hewitt, SC (reprint author), NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM korach@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X NR 12 TC 44 Z9 48 U1 0 U2 6 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 MAR 11 PY 2005 VL 307 IS 5715 BP 1572 EP 1573 DI 10.1126/science.1110345 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 906ED UT WOS:000227622400031 PM 15761144 ER PT J AU Chang, BL Gillanders, EM Isaacs, SD Wiley, KE Adams, T Turner, AR Zheng, SL Meyers, DA Carpten, JD Walsh, PC Trent, JM Xu, JF Isaacs, WB AF Chang, BL Gillanders, EM Isaacs, SD Wiley, KE Adams, T Turner, AR Zheng, SL Meyers, DA Carpten, JD Walsh, PC Trent, JM Xu, JF Isaacs, WB TI Evidence for a general cancer susceptibility locus at 3p24 in families with hereditary prostate cancer SO CANCER LETTERS LA English DT Article DE cancer; linkage; genome-wide scan; hereditary; prostate cancer ID GENOME-WIDE SCAN; LINKAGE ANALYSIS; BREAST; RISK AB To identify genes that generally increase the risk of cancer, we performed a systematic search throughout the genome in 188 families primarily ascertained for prostate cancer but which also included individuals with other cancers. We observed significant evidence for linkage between susceptibility to all cancers and markers at 3p24, with a peak HLOD of 3.08 (P = 0.0002). Compared to families with less than three other cancers and prostate cancer only, evidence for linkage at this region was stronger among families with at least three other cancers. This is the first reported example of a genome-wide search for general cancer susceptibility genes among hereditary prostate cancer families. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Wake Forest Univ, Sch Med, Ctr Human Genome, Winston Salem, NC 27157 USA. NHGRI, NIH, Bethesda, MD USA. Johns Hopkins Med Inst, Dept Urol, Baltimore, MD USA. Translat Genom Res Inst, Phoenix, AZ USA. RP Xu, JF (reprint author), Wake Forest Univ, Sch Med, Ctr Human Genome, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM jxu@wfubmc.edu FU NCI NIH HHS [CA58236, CA95052, CA89600] NR 15 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD MAR 10 PY 2005 VL 219 IS 2 BP 177 EP 182 DI 10.1016/j.canlet.2004.10.005 PG 6 WC Oncology SC Oncology GA 908DE UT WOS:000227766700007 PM 15723717 ER PT J AU Park, JM Terabe, M van den Broeke, LT Donaldson, DD Berzofsky, JA AF Park, JM Terabe, M van den Broeke, LT Donaldson, DD Berzofsky, JA TI Unmasking immunosurveillance against a syngeneic colon cancer by elimination of CD4(+) NKT regulatory cells and IL-13 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE lung metastasis; CT26; NKT cells; IL-13 inhibitor; immunosurveillance ID KILLER T-CELLS; TUMOR-IMMUNITY; ANTITUMOR IMMUNITY; STIMULATING FACTOR; T(H)2 BIAS; IN-VIVO; INTERLEUKIN-13; IMMUNOTHERAPY; SUPPRESSION; DEPLETION AB We have previously observed a novel role of natural killer T (NKT) cells in negative regulation of antitumor immune responses against an immunogenic regressor tumor expressing a transfected viral antigen. Here, we investigated whether hidden spontaneous antitumor immunosurveillance, in the absence of a vaccine, could be revealed by disruption of this negative regulatory pathway involving CD4(+) NKT cells and interieukin-13 (IL-13), in a murine pulmonary metastasis model of a nontransfected, nonregressor, syngeneic tumor, the CT26 colon carcinoma. Lung metastases of CT26 were decreased in CD4(+) T cell-depleted BALB/c mice, suggesting that CD4(+) T cells were involved in negative regulation of antitumor responses. CD1-knock out (CD1-KO) mice, which have conventional CD4(+) T cells and CD4(+)CD25(+) regulatory T cells but lack CD1-restricted CD4(+) NKT cells, were significantly resistant to lung metastasis of CT26. The metastases were not further decreased in CD4(+) T cell-depleted CDl-KO mice, implying that CD4(+) NKT cells might be the primary negative regulator of antitumor immune responses in BALB/c mice. CD8(+) T cells were found to act as effectors in antitumor immune responses, since the inhibition of lung metastases observed in naive CD1-KO or CD4(+) T cell-depleted mice was abrogated by depletion of CD8(+) T cells. Lung metastases were significantly decreased by treatment of mice with an IL-13 inhibitor, but not by deficiency or inhibition of IL-4. Thus, even for a nonregressor tumor, immunosurveillance exists but is negatively regulated via CD4(+) NKT cells possibly mediated by IL-13, and can be unmasked by removal of these negative regulatory components. Published 2004 Wiley-Liss, Inc. C1 NCI, Vaccine Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Wyeth Res, Cambridge, MA USA. RP Berzofsky, JA (reprint author), NCI, Vaccine Branch, Canc Res Ctr, NIH, Bldg 10,Room 6B-04, Bethesda, MD 20892 USA. EM berzofsk@helix.nih.gov NR 54 TC 57 Z9 60 U1 0 U2 1 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 MAR 10 PY 2005 VL 114 IS 1 BP 80 EP 87 DI 10.1002/ijc.20669 PG 8 WC Oncology SC Oncology GA 893QK UT WOS:000226734100009 PM 15523692 ER PT J AU Ohta, S Lai, EW Pang, ALY Brouwers, FM Chan, WY Eisenhofer, G de Krijger, R Ksinantova, L Breza, J Blazicek, P Kvetnansky, R Wesley, RA Pacak, K AF Ohta, S Lai, EW Pang, ALY Brouwers, FM Chan, WY Eisenhofer, G de Krijger, R Ksinantova, L Breza, J Blazicek, P Kvetnansky, R Wesley, RA Pacak, K TI Downregulation of metastasis suppressor genes in malignant pheochromocytoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE pheochromocytoma; metastasis; real-time PCR ID E-CADHERIN; CANCER; EXPRESSION; BENIGN; ANGIOGENESIS; FEATURES; TUMORS; PCR AB There is no reliable method currently available to predict malignant potential of pheochromocytorria based on conventional histology or genetic, molecular or inummohistochemical markers. Metastasis suppressor genes affect the spread of several cancers and, therefore, may provide promise as prognostic markers or therapeutic targets for malignant pheochromocytoma. We hypothesized that the downlregulation of metastasis suppressor genes in malignant pheochromocytoma may play a role in malignant behavior. We applied quantitative real-time polymerase chain reaction (QRT-PCR) to 11 metastasis suppressor genes. These genes are known to be involved in the regulation of important cancerrelated cellular events, such as cell growth regulation and apoptosis (nm23-H1, TIMP-1, TIMP-2, TIMP-3, TIMP-4, TXNIP and CRSP-3), cell-cell communication (BRMS-1), invasion (CRMP-1) and cell adhesion (E-Cad and KiSS1). The study included 15 benign and 10 malignant pheochromocytomas. Six metastasis suppressor genes (nm23-H1, TIMP-4, BRAIS-1, TXNIP, CRSP-3 and E-Cad) were down regulated significantly in malignant compared to benign pheochromocytoma (p < 0.05, Mann-Whitney U-test). We applied a non-linear rule using median malignant value (MMV) as a threshold to use metastasis suppressor genes to distinguish malignant from benign samples. After cross-validation, the non-linear rule produced no errors in 10 malignant samples and 3 errors in the 15 benign samples, with an overall error rate of 12%. These results suggest that downregulation of metastasis suppressor genes reflect malignant pheochromocytorna with a high degree of sensitivity. Thus, we conclude that altered function of these metastasis suppressor gene pathways may play an important role in the malignant behavior of pheochromocytoma. Published 2004 Wiley-Liss, Inc. C1 NICHHD, Pediat & Reprod Endocrinol Branch, Unit Clin Neuroendocrinol, PREB,NIH, Bethesda, MD 20892 USA. NICHHD, Sect Dev Genom, Bethesda, MD 20892 USA. NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. Erasmus MC, Josephine Nefkens Inst, Dept Pathol, Rotterdam, Netherlands. Slovak Acad Sci, Inst Expt Endocrinol, Bratislava, Slovakia. Komensky Fac Med, Dept Urol, Bratislava, Slovakia. Military Hosp, Bratislava, Slovakia. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Pacak, K (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, Unit Clin Neuroendocrinol, PREB,NIH, Bldg 10,Room 9D42,10 Ctr Dr MSC 1583, Bethesda, MD 20892 USA. EM karel@mail.nih.gov NR 30 TC 73 Z9 80 U1 1 U2 1 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 MAR 10 PY 2005 VL 114 IS 1 BP 139 EP 143 DI 10.1002/ijc.20670 PG 5 WC Oncology SC Oncology GA 893QK UT WOS:000226734100017 PM 15523699 ER PT J AU van't Veer, LJ Paik, S Hayes, DF AF van't Veer, LJ Paik, S Hayes, DF TI Gene expression profiling of breast cancer: A new tumor marker SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID CHEMOTHERAPY; DOXORUBICIN; PACLITAXEL; PATTERNS C1 Univ Michigan, Ctr Comprehens Canc, Breast Oncol Program, Ann Arbor, MI 48109 USA. Netherlands Canc Inst, Div Diagnost Oncol, Amsterdam, Netherlands. Natl Surg Adjuvant Breast & Bowel Project, Div Pathol, Pittsburgh, PA USA. RP Hayes, DF (reprint author), Univ Michigan Hlth Syst, Breast Oncol Program, 1500 E Med Ctr Dr,CCGC 6203, Ann Arbor, MI 48109 USA. EM hayesdf@umich.edu NR 28 TC 91 Z9 92 U1 0 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 10 PY 2005 VL 23 IS 8 BP 1631 EP 1635 DI 10.1200/JCO.2005.12.005 PG 5 WC Oncology SC Oncology GA 905RL UT WOS:000227587200013 PM 15755970 ER PT J AU Lomenzo, SA Rhoden, JB Izenwasser, S Wade, D Kopajtic, T Katz, JL Trudell, ML AF Lomenzo, SA Rhoden, JB Izenwasser, S Wade, D Kopajtic, T Katz, JL Trudell, ML TI Synthesis and biological evaluation of meperidine analogues at monoamine transporters SO JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article ID ACID METHYL-ESTERS; NON-NITROGEN INHIBITORS; DOPAMINE UPTAKE SITES; COCAINE RECEPTORS; LIGAND-BINDING; 3-PHENYLTROPANE ANALOGS; SEROTONIN TRANSPORTERS; NONHUMAN-PRIMATES; RAT; AFFINITIES AB A series of aryl-substituted meperidine analogues was synthesized, and the binding affinities were determined at the DAT, SERT, and NET as well as at mu-opioid receptors. Generally the analogues exhibited increased affinity for the DAT and SERT relative to meperidine but exhibited low binding affinity for the NET. The 2-naphthyl derivative 7f was the most potent ligand at the SERT (K-i = 0.0072 muM) and was the most selective ligand for the SERT over the DAT (DAT/SERT = 158) and mu-opioid receptors (mu/SERT = 281). The 3,4-dichlorophenyl derivative 7e was the most potent ligand at the DAT (K-i = 0. 125 muM) and was the most selective ligand for the DAT over mu-opioid receptors (mu/DAT = 16.3) but remained slightly more selective for the SERT over the DAT(DAT/SERT = 6.68). Three compounds, the 3,4-dichlorophenyl derivative 7e and the 2-naphthyl analogues 6f and 7f, were identified that were more potent at the DAT than meperidine and that exhibited well-defined biphasic dopamine uptake inhibition similar to meperidine. However, none of the analogues tested produced locomotor effects or substituted for cocaine in drug discrimination studies, suggesting that they-opioid effects of these analogues may contribute to the poor efficacy observed in vivo. C1 Univ New Orleans, Dept Chem, New Orleans, LA 70148 USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. NIDA, Psychobiol Sect, Intramural Res Program, Baltimore, MD 21224 USA. RP Trudell, ML (reprint author), Univ New Orleans, Dept Chem, New Orleans, LA 70148 USA. EM mtrudell@uno.edu RI Izenwasser, Sari/G-9193-2012; OI Katz, Jonathan/0000-0002-1068-1159 FU NIDA NIH HHS [DA 11528] NR 38 TC 14 Z9 14 U1 1 U2 4 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 MAR 10 PY 2005 VL 48 IS 5 BP 1336 EP 1343 DI 10.1021/jm0401614 PG 8 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 902YI UT WOS:000227392200006 PM 15743177 ER PT J AU Mueller, KL Hoon, MA Erlenbach, I Chandrashekar, J Zuker, CS Ryba, NJP AF Mueller, KL Hoon, MA Erlenbach, I Chandrashekar, J Zuker, CS Ryba, NJP TI The receptors and coding logic for bitter taste SO NATURE LA English DT Article ID MAMMALIAN SWEET; MICE; SACCHARIN; RESPONSES; PATHWAYS; STIMULI; FAMILY; MOUSE; CELLS AB The sense of taste provides animals with valuable information about the nature and quality of food. Bitter taste detection functions as an important sensory input to warn against the ingestion of toxic and noxious substances. T2Rs are a family of approximately 30 highly divergent G-protein-coupled receptors (GPCRs)(1,2) that are selectively expressed in the tongue and palate epithelium(1) and are implicated in bitter taste sensing(1-8). Here we demonstrate, using a combination of genetic, behavioural and physiological studies, that T2R receptors are necessary and sufficient for the detection and perception of bitter compounds, and show that differences in T2Rs between species ( human and mouse) can determine the selectivity of bitter taste responses. In addition, we show that mice engineered to express a bitter taste receptor in 'sweet cells'(9) become strongly attracted to its cognate bitter tastants, whereas expression of the same receptor ( or even a novel GPCR) in T2R-expressing cells resulted in mice that are averse to the respective compounds. Together these results illustrate the fundamental principle of bitter taste coding at the periphery: dedicated cells act as broadly tuned bitter sensors that are wired to mediate behavioural aversion. C1 Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Biol, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. RP Zuker, CS (reprint author), Univ Calif San Diego, Howard Hughes Med Inst, La Jolla, CA 92093 USA. EM charles@flyeye.ucsd.edu; nick.ryba@nih.gov NR 21 TC 261 Z9 274 U1 15 U2 66 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAR 10 PY 2005 VL 434 IS 7030 BP 225 EP 229 DI 10.1038/nature03352 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 904JU UT WOS:000227494500048 PM 15759003 ER PT J AU Sithanandam, G Fornwald, LW Fields, J Anderson, LM AF Sithanandam, G Fornwald, LW Fields, J Anderson, LM TI Inactivation of ErbB3 by siRNA promotes apoptosis and attenuates growth and invasiveness of human lung adenocarcinoma cell line A549 SO ONCOGENE LA English DT Article DE lung adenocarcinoma; ErbB3; siRNA; Akt; apoptosis; invasion ID BREAST-CANCER CELLS; NF-KAPPA-B; C-ERBB-3 PROTEIN EXPRESSION; FACTOR RECEPTOR; KINASE-B; ENHANCES MOTILITY; AKT ACTIVATION; IN-VITRO; HEREGULIN; OVEREXPRESSION AB The ErbB3 receptor and the downstream signaling kinase Akt are implicated in proliferation of lung adenocarcinoma cells. Inhibition by siRNAs to ErbB3 and Akt isoforms 1, 2 and 3 was utilized to investigate the contribution of these molecules to tumor survival, spreading and invasiveness, and the roles of specific Akt isoforms. ErbB3 siRNA stably and dose-dependently suppressed ErbB3 protein for 2 days or more, and reduced cell numbers, by both suppressing cell cycle and causing apoptosis and necrosis. It also inhibited soft agar growth, cell motility and migration, and invasiveness. Akt1, 2 and 3 siRNAs had similar suppressive effects on cell number, apoptosis/ necrosis and soft agar growth. However, although Akt1 siRNA had no effect on cell migration or invasion, Akt2 siRNA effectively suppressed both activities, and Akt3 siRNA had moderate effectiveness. In A549 cells, ErbB3 is indicated as having major effects on cell division, survival, motility, migration and invasiveness. All three Akt isoforms are to varying degrees involved in these cell behaviors, with Akt2 especially implicated in migration and invasion. ErbB3 and the Akts are promising targets for therapy, and siRNAs may be useful for this purpose. C1 NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. NCI, Comparat Carcinogenesis Lab, Ft Detrick, MD 21702 USA. RP Sithanandam, G (reprint author), NCI, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. EM sithanan@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 62 TC 51 Z9 59 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD MAR 10 PY 2005 VL 24 IS 11 BP 1847 EP 1859 DI 10.1038/sj.onc.1208381 PG 13 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 905BH UT WOS:000227542000004 PM 15688028 ER PT J AU Truglio, JJ Rhau, B Croteau, DL Wang, LQ Skorvaga, M Karakas, E DellaVecchia, MJ Wang, H Van Houten, B Kisker, C AF Truglio, JJ Rhau, B Croteau, DL Wang, LQ Skorvaga, M Karakas, E DellaVecchia, MJ Wang, H Van Houten, B Kisker, C TI Structural insights into the first incision reaction during nucleotide excision repair SO EMBO JOURNAL LA English DT Article DE crystallography; DNA damage; DNA repair; nucleotide excision repair; UvrC ID DNA-POLYMERASE-I; C-TERMINAL REGION; ESCHERICHIA-COLI; HELICASE-II; (A)BC EXCINUCLEASE; CATALYTIC SITE; THYMINE DIMERS; ACTIVE-SITE; PROTEIN; UVRB AB Nucleotide excision repair is a highly conserved DNA repair mechanism present in all kingdoms of life. The incision reaction is a critical step for damage removal and is accomplished by the UvrC protein in eubacteria. No structural information is so far available for the 30 incision reaction. Here we report the crystal structure of the N-terminal catalytic domain of UvrC at 1.5 Angstrom resolution, which catalyzes the 30 incision reaction and shares homology with the catalytic domain of the GIY-YIG family of intron-encoded homing endonucleases. The structure reveals a patch of highly conserved residues surrounding a catalytic magnesium-water cluster, suggesting that the metal binding site is an essential feature of UvrC and all GIY-YIG endonuclease domains. Structural and biochemical data strongly suggest that the N-terminal endonuclease domain of UvrC utilizes a novel one-metal mechanism to cleave the phosphodiester bond. C1 SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. Natl Inst Environm Hlth Sci, Mol Genet Lab, NIH, Res Triangle Pk, NC USA. Slovak Acad Sci, Canc Res Inst, Dept Mol Genet, Bratislava, Slovakia. RP Kisker, C (reprint author), SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. EM kisker@pharm.sunysb.edu RI Wang, Hong/F-3164-2014 OI Wang, Hong/0000-0003-0165-3559 FU NIGMS NIH HHS [GM070873, R01 GM070873] NR 49 TC 48 Z9 49 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 9 PY 2005 VL 24 IS 5 BP 885 EP 894 DI 10.1038/sj.emboj.7600568 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 904JZ UT WOS:000227495100002 PM 15692561 ER PT J AU Kim, Y Lampert, SM Philpott, CC AF Kim, Y Lampert, SM Philpott, CC TI A receptor domain controls the intracellular sorting of the ferrichrome transporter, ARN1 SO EMBO JOURNAL LA English DT Article DE iron; major facilitator; siderophore; trafficking; ubiquitin ID MAJOR FACILITATOR SUPERFAMILY; YEAST SACCHAROMYCES-CEREVISIAE; MICROBIAL IRON TRANSPORT; PLASMA-MEMBRANE; ESCHERICHIA-COLI; SIDEROPHORE-IRON; LACTOSE PERMEASE; PROTEIN; MECHANISM; UBIQUITIN AB The Saccharomyces cerevisiae transporter Arn1p takes up the ferric-siderophore ferrichrome, and extracellular ferrichrome dramatically influences the intracellular trafficking of Arn1p. In the absence of ferrichrome, Arn1p sorts directly to the endosomal compartment. At low concentrations of ferrichrome, Arn1p stably relocalizes to the plasma membrane, yet little to no uptake of ferrichrome occurs at these low concentrations. At higher concentrations of ferrichrome, Arn1p cycles between the plasma membrane and endosome. Arn1p contains two binding sites for ferrichrome: one site has an affinity similar to the K-T for transport, but the second site has a much higher affinity. Here we report that this high-affinity binding site lies within a unique extracytosolic, carboxyl-terminal domain. Mutations within this domain lead to loss of ferrichrome binding and uptake activities and missorting of Arn1p, including a failure to relocalize to the plasma membrane in the presence of ferrichrome. Mutation of phenylalanine residues in the cytosolic tail of Arn1p also lead to missorting, but without defects in ferrichrome binding. We propose that the carboxyl terminus of Arn1p contains a receptor domain that controls the intracellular trafficking of the transporter. C1 NIDDKD, Liver Dis Sect, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Philpott, CC (reprint author), NIDDKD, Liver Dis Sect, Liver Dis Branch, NIH, Bldg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM carolinep@intra.niddk.nih.gov NR 38 TC 26 Z9 26 U1 0 U2 1 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 MAR 9 PY 2005 VL 24 IS 5 BP 952 EP 962 DI 10.1038/sj.emboj.7600579 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 904JZ UT WOS:000227495100008 PM 15719020 ER PT J AU Pla, AF Maric, D Brazer, SC Giacobini, P Liu, XB Chang, YH Ambudkar, IS Barker, JL AF Pla, AF Maric, D Brazer, SC Giacobini, P Liu, XB Chang, YH Ambudkar, IS Barker, JL TI Canonical transient receptor potential 1 plays a role in basic fibroblast growth factor (bFGF)/FGF receptor-1-induced Ca2+ entry and embryonic rat neural stem cell proliferation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE calcium [ Ca]; cortex; development; proliferation; TRPC; neural stem cells ID SALIVARY-GLAND CELLS; CEREBRAL-CORTEX; SIGNALING COMPLEX; CORTICAL-CELLS; TRP CHANNELS; ACTIVATION; CALCIUM; NEURONS; INFLUX; INHIBITION AB Basic fibroblast growth factor (bFGF) and its major receptor FGF receptor-1 (FGFR-1) play an important role in the development of the cortex. The mechanisms underlying the mitogenic role of bFGF/FGFR-1 signaling have not been elucidated. Intracellular Ca2+ concentrations ([Ca2+](i)) in proliferating cortical neuroepithelial cells are markedly dependent on Ca2+ entry (Maric et al., 2000a). The absence of voltage-dependent Ca2+ entry channels, which emerge later, indicates that other membrane mechanisms regulate [Ca2+](i) during proliferation. Canonical transient receptor potential (TRPC) family channels are candidates because they are voltage independent and are expressed during CNS development (Strubing et al., 2003). Here, we investigated the involvement of TRPC1 in bFGF-mediated Ca2+ entry and proliferation of embryonic rat neural stem cells (NSCs). Both TRPC1 and FGFR-1 are expressed in the embryonic rat telencephalon and coimmunoprecipitate. Quantitative fluorescence-activated cell sorting analyses of phenotyped telencephalic dissociates show that similar to80% of NSCs are TRPC1(+), proliferating, and express FGFR-1. Like NSCs profiled ex vivo,NSC-derived progeny proliferating in vitro coexpress TRPC1 and FGFR1. Antisense knock-down of TRPC1 significantly decreases bFGF-mediated proliferation of NSC progeny, reduces the Ca2+ entry component of the Ca-i(2+) response to bFGF without affecting Ca2+ release from intracellular stores or 1-oleoyl-2-acetyl-sn-glycerol-induced Ca2+ entry, and significantly blocks an inward cation current evoked by bFGF in proliferating NSCs. Both Ca2+ influx evoked by bFGF and NSC proliferation are attenuated by Gd3+ and SKF96365, two antagonists of agonist-stimulated Ca2+ entry. Together, these results show that TRPC1 contributes to bFGF/FGFR-1-induced Ca2+ influx, which is involved in self-renewal of embryonic rat NSCs. C1 Univ Turin, Physiol Lab, Dept Human & Anim Biol, I-10123 Turin, Italy. NINDS, Neurophysiol Lab, NIH, Bethesda, MD 20892 USA. NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Secretory & Physiol Sect, Gene Therapy & Therapeut Branch, NIH, Bethesda, MD 20892 USA. Univ Turin, Dept Human & Anim Biol, I-10123 Turin, Italy. RP Pla, AF (reprint author), Univ Turin, Physiol Lab, Dept Human & Anim Biol, I-10123 Turin, Italy. EM alessandra.fiorio@uniti.it; barkerj@ninds.nih.gov RI Fiorio Pla, Alessandra/B-6646-2012; Giacobini, Paolo/P-5451-2015 OI Fiorio Pla, Alessandra/0000-0003-4576-1594; Giacobini, Paolo/0000-0002-3075-1441 NR 46 TC 76 Z9 79 U1 0 U2 3 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 MAR 9 PY 2005 VL 25 IS 10 BP 2687 EP 2701 DI 10.1523/JNEUROSCI.0951-04.2005 PG 15 WC Neurosciences SC Neurosciences & Neurology GA 904WK UT WOS:000227528600028 ER PT J AU Ramakrishnan, B Boeggeman, E Qasba, PK AF Ramakrishnan, B Boeggeman, E Qasba, PK TI Mutation of arginine 228 to lysine enhances the glucosyltransferase activity of bovine beta-1,4-galactosyltransferase I SO BIOCHEMISTRY LA English DT Article ID DONOR SUBSTRATE-SPECIFICITY; ALPHA-LACTALBUMIN LA; GLCNAC-BETA-R; CRYSTAL-STRUCTURE; GALACTOSYL TRANSFERASE; CONFORMATIONAL-CHANGES; N-ACETYLGLUCOSAMINE; LACTOSE SYNTHETASE; ESCHERICHIA-COLI; CATALYTIC DOMAIN AB beta-1,4-Galactosyltransferase I (beta4Gal-Tl) normally transfers Gal from UDP-Gal to GIcNAc in the presence of Mn2+ ion (Gal-T activity) and also transfers Glc from UDP-Glc to GIcNAc (Glc-T activity), albeit at only 0.3% efficiency. In addition, alpha-lactalbumin (LA) enhances this Glc-T activity more than 25 times. Comparison of the crystal structures of UDP-Gal- and UDP-Glc-bound beta4Gal-Tl reveals that the O4 hydroxyl group in both Gal and Glc moieties forms a hydrogen bond with the side chain carboxylate group of Glu317. The orientation of the O4 hydroxyl of glucose causes a steric hindrance to the side chain carboxylate group of Glu317, accounting for the enzyme's low Glc-T activity. In this study, we show that mutation of Arg228, a residue in the vicinity of Glu317, to lysine (R228K-Gal-Tl) results in a 15-fold higher Glc-T activity, which is further enhanced by LA to nearly 25% of the Gal-T activity of the wild type. The kinetic parameters indicate that the main effect of the mutation of Arg228 to lysine is on the k(cat), of Glc-T, which increases 3-4-fold, both in the absence and in the presence of LA; simultaneously, the k(cat) for the Gal-T reaction is reduced 30-fold. The crystal structure of R228K-Gal-Tl complexed with LA, UDP-Gal, and Mn2+ determined at 1.9 Angstrom resolution shows that the Asp318 side chain exhibits a minor alternate conformation, compared to that in the wild type. This alternate conformation now causes a steric hindrance to the O4 hydroxyl group of the Gal moiety of UDP-Gal, probably causing the dissociation of UDP-Gal and the reduced k(cat) of the Gal-T reaction. C1 NCI, SAIC Frederick Inc, Canc Res Ctr, Struct Glycobiol Sect,Lab Expt & Computat Biol, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Canc Res Ctr, Basic Res Program, Frederick, MD 21702 USA. RP Qasba, PK (reprint author), NCI, SAIC Frederick Inc, Canc Res Ctr, Struct Glycobiol Sect,Lab Expt & Computat Biol, Frederick, MD 21702 USA. EM qasba@helix.nih.gov FU PHS HHS [N01-C0-12400] NR 36 TC 16 Z9 18 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 8 PY 2005 VL 44 IS 9 BP 3202 EP 3210 DI 10.1021/bi0479454 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903IE UT WOS:000227418500010 PM 15736931 ER PT J AU Cho, SY Blackford, JA Simons, SS AF Cho, SY Blackford, JA Simons, SS TI Role of activation function domain-1, DNA binding, and coactivator GRIP1 in the expression of partial agonist activity of glucocorticoid receptor-antagonist complexes SO BIOCHEMISTRY LA English DT Article ID HUMAN ESTROGEN-RECEPTOR; INDUCED CONFORMATIONAL-CHANGES; RETINOID-X-RECEPTOR; PROGESTERONE-RECEPTOR; INDUCTION PROPERTIES; ANDROGEN RECEPTOR; RESPONSE ELEMENTS; TRANSACTIVATION DOMAIN; MODULATORY ELEMENT; TRANSCRIPTIONAL COACTIVATOR AB The determinants of the partial agonist activity of most antisteroids complexed with steroid receptors are not well understood. We now examine the role of the N-terminal half of the glucocorticoid receptor (GR) including the activation domain (AF-1), the DNA binding site sequence, receptor contact with DNA, and coactivator binding on the expression of partial agonist activity in two cell lines for GRs bound by five antiglucocorticoids: dexamethasone mesylate (Dex-Mes), dexamethasone oxetanone (Dex-Ox), progesterone (Prog), deoxycorticosterone (DOC), and RU486. Using truncated GRs, we find that the N-terminal half of GR and the AF-1 domain are dispensable for the partial agonist activity of antiglucocorticoids. This contrasts with the AF-1 domain being required for the partial agonist activity of antisteroids with most steroid receptors. DNA sequence (MMTV vs a simple GRE enhancer) and cell-specific factors (CV-1 vs Cos-7) exert minor effects on the level of partial agonist activity. Small activity differences for some complexes of GAL4/GR chimeras with GR- vs GAL-responsive reporters suggest a contribution of DNA-induced conformational changes. A role for steroid-regulated coactivator binding to GRs is compatible with the progressively smaller increase in partial agonist activity of Dex-Mes > Prog > RU486 with added GRIP1 in CV-1 cells. This hypothesis is consistent with titration experiments, where low concentrations of GRIP1 more effectively increase the partial agonist activity of Dex-Mes than Prog complexes. Furthermore, ligand-dependent GRIP1 binding to DNA-bound GR complexes decreases in the order of Dex > Dex-Mes > Prog > RU486. Thus, the partial agonist activity of a given GR-steroid complex in CV-1 cells correlates with its cell-free binding of GRIP1. The ability to modify the levels of partial agonist activity through changes in steroid structure, DNA sequence, specific DNA-induced conformational changes, and coactivator binding suggests that useful variations in endocrine therapies may be possible by the judicious selection of these parameters to afford gene and tissue selective results. C1 NIDDK, LMCB, Steroid Hormones Sect, NIH, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDK, LMCB, Steroid Hormones Sect, NIH, Bldg 8,Room B2A-07, Bethesda, MD 20892 USA. EM steroids@helix.nih.gov NR 97 TC 18 Z9 18 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAR 8 PY 2005 VL 44 IS 9 BP 3547 EP 3561 DI 10.1021/bi048777i PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 903IE UT WOS:000227418500043 PM 15736964 ER PT J AU Hoffman, RM Stone, SN Espey, D Potosky, AL AF Hoffman, RM Stone, SN Espey, D Potosky, AL TI Differences between men with screening-detected versus clinically diagnosed prostate cancers in the USA SO BMC CANCER LA English DT Article; Proceedings Paper CT 26th Annual Meeting of the Society-of-General-Internal-Medicine CY APR 30-MAY 03, 2003 CL VANCOUVER, CANADA SP Soc Gen Internal Med ID PREVENTIVE-SERVICES; UNITED-STATES; OUTCOMES; VALIDATION; CARCINOMA; PATTERNS; STAGE AB Background: The advent of prostate specific antigen (PSA) testing in the United States of America (USA) has led to a dramatic increase in the incidence of prostate cancer in the United States as well as the number of men undergoing aggressive treatment with radical prostatectomy and radiation therapy. We compared patient characteristics and treatment selection between American men with screening-detected versus clinically diagnosed prostate cancers. Methods: We evaluated 3,173 men with prostate cancer in the USA. Surveys and medical records provided information on demographics, socioeconomic status, comorbidities, symptoms, tumor characteristics, and treatment. We classified men presenting with symptoms of advanced cancer bone pain, weight loss, or hematuria-as "clinically diagnosed"; asymptomatic men and those with only lower urinary tract symptoms were considered "screening-detected." We used multivariate analyses to determine whether screening predicted receiving aggressive treatment for a clinically localized cancer. Results: We classified 11% of cancers as being clinically diagnosed. Men with screening-detected cancers were more often non-Hispanic white (77% vs. 65%, P < 0.01), younger (36% < 65 years vs. 25%, P <= 0.01), better educated (80% >= high school vs. 67%, P < 0.01), healthier (18% excellent health vs. 10%, P < 0.01), and diagnosed with localized disease (90% vs. 75%, P < 0.01). Men with screening-detected localized cancers more often underwent aggressive treatment, 76% vs. 70%, P = 0.05. Conclusion: Most cancers were detected by screening in this American cohort. Appropriately, younger, healthier men were more likely to be diagnosed by screening. Minority status and lower socio-economic status appeared to be screening barriers. Screening detected earlier-stage cancers and was associated with receiving aggressive treatment. C1 Univ New Mexico, Hlth Sci Ctr, New Mexico Tumor Registry, Albuquerque, NM 87131 USA. New Mexico VA Hlth Care Syst, Med Serv, Albuquerque, NM USA. London Sch Hyg & Trop Med, Noncommunicable Dis Epidemiol Unit, London WC1, England. CDC, Div Canc Prevent & Control, Albuquerque, NM USA. Indian Hlth Serv Natl Epidemiol Program, Albuquerque, NM USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Stone, SN (reprint author), Univ New Mexico, Hlth Sci Ctr, New Mexico Tumor Registry, Albuquerque, NM 87131 USA. EM rhoffman@unm.edu; noells@nmtr.unm.edu; david.espey@ihs.gov; potoskya@mail.nih.gov FU NCI NIH HHS [N01 PC067010, N01 CN067009, N01 PC067006, N01PC67000, N01PC67010, N01PC67007, N01PC67005]; ODCDC CDC HHS [U48/CCU610818-06-4] NR 29 TC 27 Z9 28 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2407 J9 BMC CANCER JI BMC Cancer PD MAR 8 PY 2005 VL 5 AR 27 DI 10.1186/1471-2407-5-27 PG 9 WC Oncology SC Oncology GA 911LE UT WOS:000228003100001 PM 15755329 ER PT J AU Franklin, SS Pio, JR Wong, ND Larson, MG Leip, EP Vasan, RS Levy, D AF Franklin, SS Pio, JR Wong, ND Larson, MG Leip, EP Vasan, RS Levy, D TI Predictors of new-onset diastolic and systolic hypertension - The Framingham heart study SO CIRCULATION LA English DT Article DE blood pressure; hypertension; aging; obesity; epidemiology ID NUTRITION EXAMINATION SURVEY; BLOOD-PRESSURE; NATIONAL-HEALTH; PULSE PRESSURE; YOUNG; RISK; STROKE AB Background - Factors leading differentially to the development of isolated diastolic (IDH), systolic-diastolic (SDH), and isolated systolic ( ISH) hypertension are poorly understood. We examined the relations of blood pressure ( BP) and clinical risk factors to the new onset of the 3 forms of hypertension. Methods and Results - Participants in the Framingham Heart Study were included if they had undergone 2 biennial examinations between 1953 and 1957 and were free of antihypertensive therapy and cardiovascular disease. Compared with optimal BP ( SBP < 120 and DBP < 80 mm Hg), the adjusted hazard ratios (HRs) for developing new-onset IDH over the ensuing 10 years were 2.75 for normal BP, 3.29 for high-normal BP ( both P < 0.0001), 1.31 ( P = 0.40) for SDH, and 0.61 ( P = 0.36) for ISH. The HRs of developing new-onset SDH were 3.32, 7.96, 7.10, and 23.12 for the normal BP, high-normal BP, ISH, and IDH groups, respectively ( all P < 0.0001). The HRs of developing ISH were 3.26 for normal and 4.82 for high-normal BP ( both P < 0.0001), 1.39 ( P = 0.24) for IDH, and 1.69 ( P < 0.01) for SDH. Increased body mass index (BMI) during follow-up predicted new-onset IDH and SDH. Other predictors of IDH were younger age, male sex, and BMI at baseline. Predictors of ISH included older age, female sex, and increased BMI during follow-up. Conclusion - Given the propensity for increased baseline BMI and weight gain to predict new-onset IDH and the high probability of IDH to transition to SDH, it is likely that IDH is not a benign condition. ISH arises more commonly from normal and high-normal BP than from "burned-out" diastolic hypertension. C1 Univ Calif Irvine, Heart Dis Prevent Program, Irvine, CA 92697 USA. Framingham Heart Dis Epidemiol Study, Framingham, MA USA. NHLBI, Bethesda, MD 20892 USA. RP Franklin, SS (reprint author), Univ Calif Irvine, Heart Dis Prevent Program, C240 Med Sci, Irvine, CA 92697 USA. EM ssfranklinmd@earthlink.net OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [N01-HC-25195] NR 25 TC 103 Z9 122 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAR 8 PY 2005 VL 111 IS 9 BP 1121 EP 1127 DI 10.1161/01.CIR.0000157159.39889.EC PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 904BH UT WOS:000227469600006 PM 15723980 ER PT J AU Koonin, EV AF Koonin, EV TI Virology: Gulliver among the lilliputians SO CURRENT BIOLOGY LA English DT Editorial Material ID GENOME; VIRUS; COMPLEXITY AB The discovery and genome sequencing of the mimivirus, a parasite of Acanthamoeba, blurs the boundary between viruses and cells: the 1.2 Mb genome of the mimivirus is predicted to contain 1262 genes and is much bigger than the genomes of many parasitic bacteria. C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA. EM koonin@ncbi.nlm.nih.gov NR 12 TC 35 Z9 36 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 8 PY 2005 VL 15 IS 5 BP R167 EP R169 DI 10.1016/j.cub.2005.02.042 PG 3 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 907CC UT WOS:000227691700011 PM 15753027 ER PT J AU Ostrander, G Ostrander, E AF Ostrander, G Ostrander, E TI Q & A - Gary and Elaine Ostrander SO CURRENT BIOLOGY LA English DT Editorial Material C1 Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Johns Hopkins Univ, Dept Comparat Med, Baltimore, MD 21218 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Ostrander, G (reprint author), Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD MAR 8 PY 2005 VL 15 IS 5 BP R151 EP R152 DI 10.1016/j.cub.2005.02.035 PG 2 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 907CC UT WOS:000227691700004 PM 15753020 ER PT J AU Hammouda, B Horkay, F Becker, ML AF Hammouda, B Horkay, F Becker, ML TI Clustering and solvation in poly(acrylic acid) polyelectrolyte solutions SO MACROMOLECULES LA English DT Article ID LIGHT-SCATTERING; MULTIMACROION DOMAINS; DEPENDENCE; STABILITY; DYNAMICS C1 Natl Inst Stand & Technol, Ctr Neutron Res, Gaithersburg, MD 20899 USA. NICHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. Natl Inst Stand & Technol, Div Polymers, Biomat Grp, Gaithersburg, MD 20899 USA. RP Hammouda, B (reprint author), Natl Inst Stand & Technol, Ctr Neutron Res, 100 Bur Dr, Gaithersburg, MD 20899 USA. EM hammouda@nist.gov NR 16 TC 21 Z9 21 U1 4 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0024-9297 J9 MACROMOLECULES JI Macromolecules PD MAR 8 PY 2005 VL 38 IS 5 BP 2019 EP 2021 DI 10.1021/ma047960g PG 3 WC Polymer Science SC Polymer Science GA 903TJ UT WOS:000227448200065 ER PT J AU Iyer, MB Mattu, U Grafman, J Lomarev, M Sato, S Wassermann, EM AF Iyer, MB Mattu, U Grafman, J Lomarev, M Sato, S Wassermann, EM TI Safety and cognitive effect of frontal DC brain polarization in healthy individuals SO NEUROLOGY LA English DT Article ID DIRECT-CURRENT STIMULATION; HUMAN MOTOR CORTEX; VERBAL FLUENCY; EXCITABILITY; CURRENTS AB Background: Data from the human motor cortex suggest that, depending on polarity, direct current ( DC) brain polarization can depress or activate cortical neurons. Activating effects on the frontal lobe might be beneficial for patients with frontal lobe disorders. This phase 1 study tested the safety of frontal DC, including its effects on frontal and other brain functions. Methods: The authors applied 20 minutes of anodal, cathodal, or sham DC to the left prefrontal cortex in three groups of right-handed subjects and looked for effects on global measures of processing and psychomotor speed, emotion, and verbal fluency, a measure of local cortical function. In one experiment (n = 30), the authors tested before and after 1 mA DC and monitored EEG in 9 subjects. In two other experiments using 1 mA (n = 43) and 2 mA (n = 30), the authors tested before and then starting 5 minutes after the onset of DC. Results: All subjects tolerated DC well. There were no significant effects on performance with 1 mA DC. At 2 mA, verbal fluency improved significantly with anodal and decreased mildly with cathodal DC. There were no clinically significant effects on the other measures. Conclusions: Limited exposure to direct current polarization of the prefrontal cortex is safe and can enhance verbal fluency selectively in healthy subjects. As such, it deserves consideration as a procedure to improve frontal lobe function in patients. C1 NINDS, Brain Stimulat Unit, NIH, Bethesda, MD 20892 USA. NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NINDS, EEG Sect, NIH, Bethesda, MD 20892 USA. RP Wassermann, EM (reprint author), Bldg 10,Room 5N254,10 Ctr Dr MSC 1430, Bethesda, MD 20892 USA. EM wassermanne@ninds.nih.gov OI Grafman, Jordan H./0000-0001-8645-4457 NR 18 TC 323 Z9 333 U1 2 U2 36 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD MAR 8 PY 2005 VL 64 IS 5 BP 872 EP 875 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 904BL UT WOS:000227470000020 PM 15753425 ER PT J AU Kanugula, S Pauly, GT Moschel, RC Pegg, AE AF Kanugula, S Pauly, GT Moschel, RC Pegg, AE TI A bifunctional DNA repair protein from Ferroplasma acidarmanus exhibits O-6-alkylguanine-DNA alkyltransferase and endonuclease V activities SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE deamination; genotoxicity; alkylation ID ESCHERICHIA-COLI K-12; ACID-MINE DRAINAGE; ALKYLATING-AGENTS; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; NITROSATIVE DEAMINATION; THERMOTOGA-MARITIMA; CRYSTAL-STRUCTURE; NITRIC-OXIDE; INACTIVATION; SITE AB A recently discovered DNA repair protein of 303 aa from the archaeal organism Ferroplasma acidarmanus was studied. This protein (AGTendoV) consists of a fusion of the C-terminal active site domain of O-6-alkylguanine-DNA alkyltransferase (AGT) with an endonuclease V domain. The AGTendoV recombinant protein expressed in Escherichia coii and purified to homogeneity repaired O-6-methylguanine lesions in DNA via alkyl transfer action despite the complete absence of the N-terminal domain and some differences in key active site residues present in known AGTs. The AGTendoV recombinant protein also cleaved DNA substrates that contained the deaminated bases uracil, hypoxanthine, or xanthine in a similar manner to E. coli endonuclease V. Expression of AGTendoV in E. coli GWR109, a strain that lacks endogenous AGT activity, protected against both the killing and mutagenic activity of N-methyl-N'-nitro-N-nitrosoguanidine and was more effective in preventing mutations than human alkyltransferase, suggesting that the endonuclease V activity may also repair a promutagenic lesion produced by this alkylating agent. Expression of AGTendoV in a DNA repair-deficient E. coli nfi(-)alkA(-) strain protected from spontaneous mutations arising in saturated cultures and restored the mutation frequency to that found in the nfi(+) alkA(+) strain. These results demonstrate the physiological occurrence of two completely different but functional DNA repair activities in a single polypeptide chain. C1 Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Pegg, AE (reprint author), Penn State Univ, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. EM aep1@psu.edu FU NCI NIH HHS [CA 71976, R37 CA018137, CA 97209, R01 CA097209, CA 18137, R01 CA018137, R01 CA071976] NR 41 TC 22 Z9 24 U1 2 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 8 PY 2005 VL 102 IS 10 BP 3617 EP 3622 DI 10.1073/pnas.0408719102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 904XY UT WOS:000227533100019 PM 15731349 ER PT J AU Chudasama, Y Nathwani, F Robbins, TW AF Chudasama, Y Nathwani, F Robbins, TW TI D-amphetamine remediates attentional performance in rats with dorsal prefrontal lesions SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE rat; attention; working memory; D-amphetamine; dorsal prefrontal cortex ID SPATIAL WORKING-MEMORY; REACTION-TIME-TASK; DEFICIT HYPERACTIVITY DISORDER; AGED MONKEYS; EXCITOTOXIC LESIONS; FRONTAL-CORTEX; 6-HYDROXYDOPAMINE LESIONS; DOPAMINE-RECEPTORS; LOCOMOTOR FUNCTION; PROMOTES RECOVERY AB Although amphetamine treatment has been shown to promote recovery of motor function in animals with cortical ablations, the potential therapeutic effect of amphetamine on processes other than motor control, such as attention and working memory, has been relatively unexplored. Accordingly, we investigated the beneficial effect of D-amphetamine treatment in animals with dorsal prefrontal cortex lesions (dPFC) compared with sham controls on a novel combined attention-memory task (CAM) that simultaneously measures attention to a visual stimulus and memory for that stimulus. The dPFC group was impaired in their ability to correctly detect the visual stimulus. Although this deficit occurred together with increased omissions and slow response latencies, these associated deficits largely recovered within the 10 post-operative baseline sessions revealing a selective attentional deficit in this group of animals. Nonetheless, the dPFC lesion did not substantially affect the working memory component of the task. The systemic administration Of D-amphetamine served to ameliorate the attentional deficit in the dPFC group at the low dose only (0.2 mg/kg). By contrast, the dPFC group were less sensitive to the detrimental effects of the high dose (0.8 mg/kg) on any aspect of task performance. However, despite improving attention to the visual Stimulus, D-amphetamine did not improve memory for that stimulus which instead appeared to deteriorate. The results provide apparently the first demonstration that low doses Of D-amphetamine can ameliorate an attentional. deficit in animals with selective dPFC lesions and may be a useful model of cognitive deficit in ADHD, schizophrenia or frontal brain injury. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. RP Chudasama, Y (reprint author), NIMH, Neuropsychol Lab, 49 Convent Dr,Bldg 49,Room 1B80, Bethesda, MD 20892 USA. EM yogita@ln.nimh.nih.gov NR 74 TC 27 Z9 28 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-4328 J9 BEHAV BRAIN RES JI Behav. Brain Res. PD MAR 7 PY 2005 VL 158 IS 1 BP 97 EP 107 DI 10.1016/j.bbr.2004.08.011 PG 11 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 897RC UT WOS:000227021500010 PM 15680198 ER PT J AU Balla, A Tuymetova, G Toth, B Steinbach, P Balla, T AF Balla, A Tuymetova, G Toth, B Steinbach, P Balla, T TI Structure-driven mutagenesis utilizing molecular modeling of type-III phosphatidylinositol 4-kinases SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NICHD, ERRB, NIH, Bethesda, MD 20892 USA. NIH, CIT, CMM, Bethesda, MD 20892 USA. RI Toth, Balazs/B-4252-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1388 EP A1389 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610902610 ER PT J AU Barile, M Pisitkun, T Chou, C Verbalis, M Knepper, M AF Barile, M Pisitkun, T Chou, C Verbalis, M Knepper, M TI Large-scale LC-MS/MS identification of proteins in aquaporin-2 (AQP2) vesicles immunoisolated from renal inner medullary collecting duct SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1606 EP A1606 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610904279 ER PT J AU Bartali, B Frongillo, EA Bandinelli, S Lauretani, F Semba, RD Fried, LP Ferrucci, L AF Bartali, B Frongillo, EA Bandinelli, S Lauretani, F Semba, RD Fried, LP Ferrucci, L TI Deficient nutrient intake is an essential component of frailty in older persons SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Cornell Univ, Dept Nutr Sci, Ithaca, NY 14850 USA. INRCA, ASF, Geriatr Rehabil Unit, I-50100 Florence, Italy. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, Longitudinal Studies Sect, NIH, Baltimore, MD 21225 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1701 EP A1701 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610904713 ER PT J AU Batkail, S Pacher, P Kunos, G AF Batkail, S Pacher, P Kunos, G TI Endocannabinoids are potent modulators of cardiovascular function in hypertension SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIAAA, Lab Physiol Studies, NIA, Bethesda, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1616 EP A1616 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610904324 ER PT J AU Busija, DW Kis, B Rajapakse, N Domoki, F Katakam, P Bari, F AF Busija, DW Kis, B Rajapakse, N Domoki, F Katakam, P Bari, F TI Effects of ATP-sensitive potassium channel activators diazoxide and BMS-191095 on membrane potential and reactive oxygen species production in isolated piglet mitochondria SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Wake Forest Univ, Hlth Sci Ctr, Winston Salem, NC 27157 USA. NIEHS, NIH, Signal Transduct Lab, Res Triangle Pk, NC 27709 USA. Univ Szeged, H-6720 Szeged, Hungary. RI Domoki, Ferenc/K-5336-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1216 EP A1216 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610901461 ER PT J AU Carlson, BA Gladyshev, VN Hatfield, DL AF Carlson, BA Gladyshev, VN Hatfield, DL TI Partial replacement of the selenoprotein population in mouse liver as a model for elucidating the role of selenoproteins in health SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, MBSS, LCP, CCR,NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1347 EP A1347 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610902409 ER PT J AU Carlson, BA Xu, XM Kryukov, GV Rao, M Berry, MJ Gladyshev, VN Hatfield, DL AF Carlson, BA Xu, XM Kryukov, GV Rao, M Berry, MJ Gladyshev, VN Hatfield, DL TI Identification and characterization of phosphoseryl-tRNA ([Ser]Sec) kinase SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, MBSS, LCP, CCR,NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Beadle Ctr N151, Lincoln, NE 68588 USA. Univ Hawaii Manoa, Dept Cell & Mol Biol, Honolulu, HI 96822 USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1012 EP A1012 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900186 ER PT J AU Chin, DA Means, A Armstrong, D AF Chin, DA Means, A Armstrong, D TI Calmodulin mutants selectively activate calmodulin kinase II or calcineurin SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIEHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Durham, NC 27710 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1379 EP A1379 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610902567 ER PT J AU Combs, GF Patterson, B Brindak, M Midthune, D Taylor, P Veillon, C Patterson, K Hill, D Levander, OA AF Combs, GF Patterson, B Brindak, M Midthune, D Taylor, P Veillon, C Patterson, K Hill, D Levander, OA TI Thyroid hormone levels in subjects supplemented with oral selenomethionine SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 USDA, ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. NCI, NCI, EPN, Bethesda, MD 20892 USA. USDA, Beltsville Human Nutr Res Ctr, ARS, Beltsville, MD 20705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1016 EP A1016 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900205 ER PT J AU Crowder, A Druey, K AF Crowder, A Druey, K TI G protein coupled receptor agonist-mediated changes in regulator of G protein signalling 5 (RGS5) levels in airway smooth muscle SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIAID, Rockville, MD 20852 USA. NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1101 EP A1101 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900598 ER PT J AU DiPaolo, RJ Shevach, EM AF DiPaolo, RJ Shevach, EM TI CD4+CD25+ T cells inhibit autoimmune gastritis (AIG) by suppressing the differentiation of autoreactive effector T cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1413 EP A1413 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903056 ER PT J AU Du, Q Hussain, P Park, KS Guo, Z Shao, LF He, PJ Nagashima, M Curtis, CC Geller, DA AF Du, Q Hussain, P Park, KS Guo, Z Shao, LF He, PJ Nagashima, M Curtis, CC Geller, DA TI Human iNOS expression is induced by Wnt beta-catenin signaling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Pittsburgh, Pittsburgh, PA 15261 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1514 EP A1514 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903524 ER PT J AU Fan, FR Tao, XL Penzak, S Hess, S Ma, K Lipsky, P AF Fan, FR Tao, XL Penzak, S Hess, S Ma, K Lipsky, P TI Metabolism of triptolide, the major active component of the Chinese herbal medicine Tripterygium wilfordii Hook F, in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIAMS, NIH, Bethesda, MD 20892 USA. NIH, Pharma CC, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. SUNY Stony Brook, ICBDD, Stony Brook, NY 11794 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1111 EP A1111 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900649 ER PT J AU Gao, P Wange, RL Zhang, N Oppenheim, JJ Howard, OMZ AF Gao, P Wange, RL Zhang, N Oppenheim, JJ Howard, OMZ TI Negative regulation of CXCR4-mediated chemotaxis by the lipid phosphatase activity of tumor suppressor PTEN SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NIA, Lab Cellular & Mol Biol, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1414 EP A1415 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903064 ER PT J AU Gollasch, M Dietrich, A Schnitzler, MMY Gross, V Storch, U Dubrovska, G Lauterbach, B Herz, U Obst, M Essin, K Renz, H Luft, FC Gudermann, T Birnbaumer, L AF Gollasch, M Dietrich, A Schnitzler, MMY Gross, V Storch, U Dubrovska, G Lauterbach, B Herz, U Obst, M Essin, K Renz, H Luft, FC Gudermann, T Birnbaumer, L TI Increased airway and vascular smooth muscle contractility in TRPC6-deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Humboldt Univ, Charite, Virchow Klinikum, D-13353 Berlin, Germany. Univ Marburg, D-35033 Marburg, Germany. HELIOS Klinikum Berlin Franz Volhard Clin, D-13125 Berlin, Germany. MDC, D-13125 Berlin, Germany. NIEHS, Res Triangle Pk, NC 27709 USA. RI Dietrich, Alexander/G-8619-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1136 EP A1136 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610901092 ER PT J AU Goodman, MF Schlacher, K Wyman, C Woodgate, R Cox, MM AF Goodman, MF Schlacher, K Wyman, C Woodgate, R Cox, MM TI DNA polymerase V and RecA protein, a minimal mutasome SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ So Calif, Los Angeles, CA 90089 USA. NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI 53706 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1710 EP A1710 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610904757 ER PT J AU Gorbachev, AV Kobayashi, H Shu, SY Farber, JM Fairchild, RL AF Gorbachev, AV Kobayashi, H Shu, SY Farber, JM Fairchild, RL TI Fibrosarcoma growth is enhanced by chemokine MIG deficiency SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Cleveland Clin Fdn, Surg Res Ctr, Cleveland, OH 44195 USA. NIAID, Clin Invest Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1408 EP A1408 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903032 ER PT J AU Gregg, JP Namba, R Maglione, J Young, L MacLeod, CL Borowsky, A Cardiff, R AF Gregg, JP Namba, R Maglione, J Young, L MacLeod, CL Borowsky, A Cardiff, R TI Mammary hyperplasias from transgenic polyomavirus middle T mice as a model for human DCIS SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Calif Davis, Dept Pathol, Sacramento, CA 95817 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. Univ Calif Davis, Dept Pathol, Davis, CA 95616 USA. Univ Calif Davis, CCM, Davis, CA 95616 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1516 EP A1517 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903537 ER PT J AU Hansen, PB Friis, UG Jensen, BL Castrop, H Skott, O Briggs, J Schnermann, J AF Hansen, PB Friis, UG Jensen, BL Castrop, H Skott, O Briggs, J Schnermann, J TI Direct effect of furosemide on renin secretion by juxtaglomerular cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ So Denmark, DK-5000 Odense, Denmark. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1141 EP A1141 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610901115 ER PT J AU Hartmann, J Kiewert, C Greig, NH Duysen, E Lockridge, O Klein, J AF Hartmann, J Kiewert, C Greig, NH Duysen, E Lockridge, O Klein, J TI Regulation of central cholinergic function in acetylcholinesterase-knockout mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Texas Tech, Sch Pharm, Amarillo, TX 79106 USA. NIA, Neurosci Lab, Baltimore, MD 21224 USA. Univ Nebraska, Eppley Inst, Nebraska Med Ctr, Omaha, NE 68198 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1076 EP A1076 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900482 ER PT J AU Houston, DV Ohno, M Jacobson, KA Harden, TK AF Houston, DV Ohno, M Jacobson, KA Harden, TK TI Synthesis and characterization of [32P]MRS2500, a novel P2Y1 receptor radioligand SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ N Carolina, Dept Pharmacol, Chapel Hill, NC 27514 USA. NIDDK, Mol Recognit Sect, NIH, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1095 EP A1095 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900571 ER PT J AU Howard, OMZ Dong, HF Su, SB Caspi, RR Chen, X Plotz, P Oppenheim, JJ AF Howard, OMZ Dong, HF Su, SB Caspi, RR Chen, X Plotz, P Oppenheim, JJ TI Autoantigens interact with chemokine receptors: Uveitis antigens induce CXCR3 and CXCR5 expressing lymphocytes and immature dendritic cells to migrate SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, Frederick Canc Res & Dev Ctr, CCR, LMI, Frederick, MD 21702 USA. SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. NEI, LI, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Arthrities & Rheumatism Branch, Bethesda, MD 20892 USA. RI Howard, O M Zack/B-6117-2012; Chen, Xin/I-6601-2015 OI Howard, O M Zack/0000-0002-0505-7052; Chen, Xin/0000-0002-2628-4027 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1416 EP A1416 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903072 ER PT J AU Huang, NN Han, SB Kehrl, JH AF Huang, NN Han, SB Kehrl, JH TI B cells productively engage soluble antigen pulsed dendritic cells: Visualization of the live-cell dynamics of B cell-dendritic cell interaction in 3D collagen matrix SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1409 EP A1409 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903039 ER PT J AU Iribarren, P Hu, JY Chen, KQ Zhou, Y Gong, WH Zhang, X Wang, JM AF Iribarren, P Hu, JY Chen, KQ Zhou, Y Gong, WH Zhang, X Wang, JM TI The role of microglial cell FPR2 receptor expression in Alzheimer's disease: Opposing effects of TNFaplha and IL-4 on FPR2 expression SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, Lab Mol Immunoregulat, Frederick, MD 21702 USA. NCI, Expt Immunol Lab, Frederick, MD 21702 USA. SAIC, Mol Immunoregulat Lab, Frederick, MD 21702 USA. RI Zhang, Xia/B-8152-2008 OI Zhang, Xia/0000-0002-9040-1486 NR 0 TC 2 Z9 2 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1418 EP A1418 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903080 ER PT J AU Irons, R Carlson, BA Hatfield, DL Davis, CD AF Irons, R Carlson, BA Hatfield, DL Davis, CD TI Selenoprotein expression in the colon of mice that express a mutant Sec tRNA ([Ser]Sec) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, Nutr Sci Res Grp, Bethesda, MD 20892 USA. NCI, MBSS, LCP, Bethesda, MD 20892 USA. 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PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1013 EP A1013 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900191 ER PT J AU Just, A Schnermann, J Arendshorst, WJ AF Just, A Schnermann, J Arendshorst, WJ TI Autoregulation of renal blood flow in the absence of A1 adenosine receptors: Evidence for a third regulatory mechanism SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ N Carolina, Dept Cellular & Mol Physiol, Chapel Hill, NC 27599 USA. NIH, NIDDK, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1140 EP A1141 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610901111 ER PT J AU Jutkiewicz, EM Chang, KJ Rice, KC Woods, JH AF Jutkiewicz, EM Chang, KJ Rice, KC Woods, JH TI Characterization of a novel nonpeptide delta-opioid agonist analog DPI287 with antidepressant-like activity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Michigan, Ann Arbor, MI 48109 USA. Ardent Pharmaceut Inc, Durham, NC 27713 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1542 EP A1542 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903657 ER PT J AU Kant, AK Graubard, BI AF Kant, AK Graubard, BI TI Trends in the association of socioeconomic position with dietary energy and macronutrient intake: NHANES 1971-1975 to 1999-2002 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 CUNY Queens Coll, Dept FNES, Flushing, NY 11367 USA. NCI, Div Canc Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. 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PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1342 EP A1342 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610902387 ER PT J AU Kawada, N Solis, G Ivey, N Conner, S Kawada, JT Imai, E Langenbach, R Welch, WJ Wilcox, CS AF Kawada, N Solis, G Ivey, N Conner, S Kawada, JT Imai, E Langenbach, R Welch, WJ Wilcox, CS TI Cyclooxigenase-1 deficient mice have high sleep-to-awake BP ratios and renal vasoconstriction SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Georgetown Univ, Washington, DC 20057 USA. Osaka Univ, Suita, Osaka 6650021, Japan. NIEHS, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1592 EP A1592 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610904212 ER PT J AU Khaled, AR Kittipatarin, C Bulavin, D Li, WQ Kim, K Young, HA Fornace, A Durum, SK AF Khaled, AR Kittipatarin, C Bulavin, D Li, WQ Kim, K Young, HA Fornace, A Durum, SK TI Cytokine-driven cell cycling is mediated through Cdc25A SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Cent Florida, Biomol Sci Ctr, Orlando, FL 32826 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Bethesda, MD 20892 USA. RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1415 EP A1415 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903067 ER PT J AU Kim, S Mizel, D Briggs, JP AF Kim, S Mizel, D Briggs, JP TI Adenosine as an inhibitory mediator in macula densa control of renin secretion SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1146 EP A1146 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610901136 ER PT J AU Le Foll, B Goldberg, SR AF Le Foll, B Goldberg, SR TI Blockade of cannabinoid CB1 or dopamine D3 receptors disrupts nicotine-induced conditioned place preferences, without affecting discriminative-stimulus effects of nicotine in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIDA, NIH, Preclin Pharmacol Sect, Baltimore, MD 21224 USA. RI Le Foll, Bernard/K-2952-2014 OI Le Foll, Bernard/0000-0002-6406-4973 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1073 EP A1074 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900472 ER PT J AU Lee, JS Kritchevsky, SB Tylavsky, F Harris, T Ayonayon, H Newman, AB AF Lee, JS Kritchevsky, SB Tylavsky, F Harris, T Ayonayon, H Newman, AB TI Factors associated with reported impaired appetite in well functioning community-dwelling elderly SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Pittsburgh, Pittsburgh, PA 15213 USA. Wake Forest Univ, Winston Salem, NC 27157 USA. Univ Tennessee, Memphis, TN 38105 USA. NIA, Epidemiol Demog & Biometry, Bethesda, MD USA. Univ Calif San Francisco, San Francisco, CA 94105 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 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1700 EP A1700 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610904712 ER PT J AU Ma, G Greenwell-Wild, T Lei, KJ Jin, WW Swisher, J Hardegen, N Wild, CT Wahl, SM AF Ma, G Greenwell-Wild, T Lei, KJ Jin, WW Swisher, J Hardegen, N Wild, CT Wahl, SM TI Identification of annexin II as a SLPI binding protein involved in macrophage HIV-1 infection SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIDCR, NIH, Bethesda, MD 20892 USA. Panacos Pharmaceut Inc, Gaithersburg, MD 20877 USA. 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PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1433 EP A1433 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903154 ER PT J AU Mamedova, L Capra, V Accomazzo, MR Gao, ZG Ferrario, S Fumagalli, M Abbracchio, MP Rovati, GE Jacobson, KA AF Mamedova, L Capra, V Accomazzo, MR Gao, ZG Ferrario, S Fumagalli, M Abbracchio, MP Rovati, GE Jacobson, KA TI Cys-leukotriene inhibitors also inhibit P2Y receptor-mediated signaling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIDDK, NIH, Mol Recognit Sect, Bethesda, MD 20892 USA. Univ Milan, Dept Pharmacol Sci, I-20133 Milan, Italy. RI Jacobson, Kenneth/A-1530-2009; Capra, Valerie/B-6225-2008; Abbracchio, Maria Pia/B-9342-2014 OI Jacobson, Kenneth/0000-0001-8104-1493; Capra, Valerie/0000-0003-3956-0833; Abbracchio, Maria Pia/0000-0002-7833-3388 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1095 EP A1095 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900573 ER PT J AU Masilamani, M Borrego, F Coligan, JE AF Masilamani, M Borrego, F Coligan, JE TI Role of the actin cytoskeleton in the natural killer cell CD94/NKG2A inhibitory receptor immunological synapse and membrane dynamics SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIAID, Lab Allerg Dis, Receptor Cell Biol Sect, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1410 EP A1411 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903046 ER PT J AU Mehta, NR Chappell, R Millen, A Albert, D Mares, J AF Mehta, NR Chappell, R Millen, A Albert, D Mares, J TI Association between serum vitamin D and age-related maculopathy (ARM) in the Third National Health and Nutrition Examination Survey (NHANES III) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Wisconsin, Dept Stat, Madison, WI 53726 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A986 EP A986 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900068 ER PT J AU Nagineni, CN Kutty, V Detrick, B Hooks, JJ AF Nagineni, CN Kutty, V Detrick, B Hooks, JJ TI Differential regulation of TGF-beta 1 and beta 2 expression in human retinal pigment epithelial cells by interferon-gamma SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1041 EP A1041 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900323 ER PT J AU Natarajan, K Hicks, A Robinson, H Guan, R Mariuzza, RA Margulies, DH AF Natarajan, K Hicks, A Robinson, H Guan, R Mariuzza, RA Margulies, DH TI X-ray crystallographic structure of the murine cytomegalovirus encoded MHC-1 immunoevasin m144 suggests a ligand-binding site SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. RI Margulies, David/H-7089-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1428 EP A1428 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903129 ER PT J AU Ojaimi, C Csiszar, A Pacher, P Li, W Kaley, G Hintze, TH AF Ojaimi, C Csiszar, A Pacher, P Li, W Kaley, G Hintze, TH TI Microarray analysis of aged eNos knockout male mice with congestive heart failure SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1240 EP A1240 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610901570 ER PT J AU Ojaimi, C Li, W Csiszar, A Pacher, P Kaley, G Hintze, TH AF Ojaimi, C Li, W Csiszar, A Pacher, P Kaley, G Hintze, TH TI Gene expression profile analysis of aged male and female eNOS knockout mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 New York Med Coll, Dept Physiol, Valhalla, NY 10595 USA. NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1239 EP A1239 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610901567 ER PT J AU Olivecrona, G Gotberg, M Harnek, J Wang, LW Jacobson, KA Erlinge, D AF Olivecrona, G Gotberg, M Harnek, J Wang, LW Jacobson, KA Erlinge, D TI Coronary artery reperfusion: ADP acting on P2Y1 receptors mediates early reactive hyperemia in vivo in pigs SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Lund Hosp, SE-22185 Lund, Sweden. NIH, Mol Recognit Sect, Bethesda, MD 20892 USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1258 EP A1258 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610901654 ER PT J AU Orlov, SN Akimova, OA Bagrov, AY Tremblay, J Hamet, P AF Orlov, SN Akimova, OA Bagrov, AY Tremblay, J Hamet, P TI Different action of cardiotonic steroids on intracellular Na plus concentration and [Na plus ]i/[K plus ]i-independent signaling in renal epithelial cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Montreal, Ctr Hosp, Ctr Rech, Montreal, PQ H2W 1T7, Canada. NIA, NIH, Baltimore, MD 21224 USA. RI ORLOV, SERGEI/I-4071-2013; Cossette, Suzanne/I-8008-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1669 EP A1670 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610904569 ER PT J AU Patterson, B Wastney, ME Combs, GF Brindak, R Patterson, KY Veillon, C Taylor, P Levander, OA AF Patterson, B Wastney, ME Combs, GF Brindak, R Patterson, KY Veillon, C Taylor, P Levander, OA TI Se metabolism in humans is altered by long-term supplementation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut, Int Union Physiol Sci C1 NCI, Biometry Res Grp, Bethesda, MD 20892 USA. Metab Modeling Serv Ltd, Hamilton, New Zealand. Cornell Univ, Ithaca, NY 14853 USA. USDA, Human Nutr Res Ctr, Grand Forks, ND 58202 USA. Cornell Univ, Ithaca, NY 14853 USA. USDA, Human Nutr Res Ctr, Beltsville, MD 20705 USA. NCI, NIH, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1015 EP A1016 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900203 ER PT J AU Peterson, ME Norris, HH Stebbins, C Wetzel, B Bundoc, V Urban, J Long, E Keane-Meyers, A AF Peterson, ME Norris, HH Stebbins, C Wetzel, B Bundoc, V Urban, J Long, E Keane-Meyers, A TI Eosinophil-mediated allergic inflammation is controlled by the inhibitory receptor gp49B SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIAID, LIG, LAD, Rockville, MD 20852 USA. USDA, Beltsville Human Nutr Res Ctr, Nutr Requirements & Funct Lab, Beltsville, MD 20705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1451 EP A1452 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903240 ER PT J AU Pisitkun, T Wang, GH Wu, W Knepper, MA AF Pisitkun, T Wang, GH Wu, W Knepper, MA TI Proteomic analysis of long-term vasopressin action in the inner medullary collecting duct (IMCD) using isotope-coded affinity tag technique SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1607 EP A1607 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610904280 ER PT J AU Poloso, NJ Roche, PA AF Poloso, NJ Roche, PA TI MHC class II eptiope CDw78 is not predictive of class II association with tetraspans SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1431 EP A1431 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903142 ER PT J AU Polozova, A Salem, N AF Polozova, A Salem, N TI Role of liver and plasma lipoproteins in sorting and allocation of essential fatty acids SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIAAA, LMBB, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A981 EP A981 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900046 ER PT J AU Roberts, AB AF Roberts, AB TI TGF-beta - journey of discovery and promise SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1370 EP A1370 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610902523 ER PT J AU Rodriguez-Galan, MC Watanabe, M Young, HA AF Rodriguez-Galan, MC Watanabe, M Young, HA TI Toxicity vs antitumor effects of hydrodynamic IL-12 (interleukin-12) and IL-18 cDNA injections SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, Expt Immunol Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1406 EP A1406 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903024 ER PT J AU Romanovsky, AA Steiner, AA Chakravarty, S Robbins, JR Dragic, AS Pan, J Herkenham, M AF Romanovsky, AA Steiner, AA Chakravarty, S Robbins, JR Dragic, AS Pan, J Herkenham, M TI Febrile and hypothermic responses to lipopolysaccharide (LPS): are they triggered by a contaminant of LPS preparations? SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 St Joseph Hosp, Syst Inflammat Lab, Phoenix, AZ 85013 USA. NIMH, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1190 EP A1191 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610901343 ER PT J AU Sengupta, A Weaver, JA Carlson, BA Gladyshev, VN Hatfield, DL AF Sengupta, A Weaver, JA Carlson, BA Gladyshev, VN Hatfield, DL TI Global gene analysis of liver selenocysteine tRNA knockout mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, MBSS, LCP, CCR,NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1012 EP A1012 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900187 ER PT J AU Shirakawa, A Liao, F Wu, DQ Farber, J AF Shirakawa, A Liao, F Wu, DQ Farber, J TI B cell activators differentially affect chemokine receptor signaling, in part by regulating levels of PLC-beta2 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIAID, NIH, Bethesda, MD 20892 USA. Acad Sinica, Inst Biomed Sci, Taipei 11529, Taiwan. Univ Connecticut, Ctr Hlth, Dept Genet & Dev Biol, Farmington, CT 06030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1419 EP A1419 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903085 ER PT J AU Shrimali, RK Lobanov, A Xu, XM Rao, M Carlson, BA Mahadeo, DC Parent, CA Gladyshev, VN Hatfield, DL AF Shrimali, RK Lobanov, A Xu, XM Rao, M Carlson, BA Mahadeo, DC Parent, CA Gladyshev, VN Hatfield, DL TI Selenocvsteine tRNA identification in Dictyostelium discoideum and Tetrahymena thermophila SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, MBSS, LCP, CCR,NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. NCI, LCMB, CCR, NIH, Bethesda, MD 20892 USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1013 EP A1013 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900189 ER PT J AU Shrimali, RK Weaver, JA Miller, GF Carlson, BA Gladyshev, VN Hatfield, DL AF Shrimali, RK Weaver, JA Miller, GF Carlson, BA Gladyshev, VN Hatfield, DL TI Selenoproteins: Crucial factors in mammalian development SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, MBSS, LCP, CCR,NIH, Bethesda, MD 20892 USA. NIH, DVR, ORS, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1012 EP A1012 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900188 ER PT J AU Small-Howard, AL Morozova, N Mansell, JB Harney, J Carlson, BA Hatfield, DL Berry, MJ AF Small-Howard, AL Morozova, N Mansell, JB Harney, J Carlson, BA Hatfield, DL Berry, MJ TI Redefining the supra-molecular complexes responsible for selenocysteine incorporation and biosynthesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Hawaii, Honolulu, HI 96822 USA. Brigham & Womens Hosp, Div Thyroid, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NCI, Mol Biol Selenium Sect, Lab Canc Prevent, NIH,CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1016 EP A1016 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900206 ER PT J AU Song, J Liu, HT Khan, O Hu, XQ Ecelbarger, C AF Song, J Liu, HT Khan, O Hu, XQ Ecelbarger, C TI Microarray analysis of gene expression in the kidneys of obese zucker rat treated with rosiglitazone SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Georgetown Univ, Dept Med, Washington, DC 20007 USA. NCI, Biometr Res Branch, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1607 EP A1607 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610904282 ER PT J AU Stark, KD Masood, A Salem, N AF Stark, KD Masood, A Salem, N TI A simplified and efficient method for the analysis of fatty acid methyl esters suitable for large clinical studies SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Waterloo, Waterloo, ON N2L 3G1, Canada. NIAAA, NIH, Rockville, MD 20852 USA. RI Stark, Ken/I-1347-2016 OI Stark, Ken/0000-0001-7828-4072 NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1037 EP A1037 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900304 ER PT J AU Stark, KD Bazinet, RP AF Stark, KD Bazinet, RP TI Blood biomarkers of n-3 fatty acid status in humans SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Waterloo, Waterloo, ON N2L 3G1, Canada. NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A974 EP A974 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900016 ER PT J AU Steiner, AA Rudaya, AY Robbins, JR Dragic, AS Langenbach, R Romanovsky, AA AF Steiner, AA Rudaya, AY Robbins, JR Dragic, AS Langenbach, R Romanovsky, AA TI Expanding the role of cyclooxygenase-2 in lipopolysaccharide fever: where no one has gone before SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Informat Syst Lab, St Joseph Hosp, Phoenix, AZ 85013 USA. NIH, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1190 EP A1190 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610901341 ER PT J AU Talley, TT Kem, WR Soti, F Taylor, PW AF Talley, TT Kem, WR Soti, F Taylor, PW TI Binding of the selective alpha7 partial agonist DMXBA (GTS-21) and its Phase 1 metabolites to molluscan ACh binding proteins SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Expt Therapeut, Int Union Physiol Sci C1 NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RI Talley, Todd/B-3630-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1075 EP A1075 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900480 ER PT J AU Tang, Y Gavrilova, O Choi, YH Hockman, S Billings, E Manganiello, VC AF Tang, Y Gavrilova, O Choi, YH Hockman, S Billings, E Manganiello, VC TI Increased energy dissipation in cyclic nucleotide phosphodiesterase 3B (PDE3B) knockout mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NHLBI, PCCMB, NIH, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1002 EP A1003 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900143 ER PT J AU Teller, LS Torres-Cabala, C Vocke, C Linehan, WM Sobel, ME Merino, MJ AF Teller, LS Torres-Cabala, C Vocke, C Linehan, WM Sobel, ME Merino, MJ TI Molecular analysis of multi-focal tumors in a patient with Birt-Hogg-Dube syndrome SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. Amer Soc Invest Pathol, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1533 EP A1533 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903613 ER PT J AU Tiwari, S Abernethy, DR Soldatov, NM AF Tiwari, S Abernethy, DR Soldatov, NM TI Ca(v)1.2 channels remodeling associated with atherosclerosis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1087 EP A1087 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900535 ER PT J AU Tuo, JS Ning, BT Bojanowski, CM Lin, ZL Kadlubar, FF Chew, E Chan, CC AF Tuo, JS Ning, BT Bojanowski, CM Lin, ZL Kadlubar, FF Chew, E Chan, CC TI Variation in regulatory region of Cockyne Syndrome B gene and disposition towards age-related macular degeneration in Caucasian Patients SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NEI, Bethesda, MD 20892 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1510 EP A1510 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903505 ER PT J AU Uthus, EO Ross, S Davis, C AF Uthus, EO Ross, S Davis, C TI Differential effects of dietary selenium (Se) and folate on methyl metabolism in liver and colon of rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 USDA ARS, Grand Forks Human Nutr Res Ctr, Grand Forks, ND 58202 USA. NCI, Nutr Sci Res Grp, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1013 EP A1013 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900192 ER PT J AU Vega-Warner, V Ransom, RF Jia, YF Smoyer, WE AF Vega-Warner, V Ransom, RF Jia, YF Smoyer, WE TI Hic-5 regulates focal adhesion formation in murine podocytes SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1061 EP A1061 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900415 ER PT J AU Wall, SM Knepper, MA Hassell, KA Fischer, M Shin, WK Lorenz, J Shull, G Kim, YH AF Wall, SM Knepper, MA Hassell, KA Fischer, M Shin, WK Lorenz, J Shull, G Kim, YH TI NKCC1 null mice have reduced blood pressure and are hypochloremic SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Emory Univ, Sch Med, Atlanta, GA 30322 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Houston, TX 77030 USA. Univ Cincinnati, Cincinnati, OH 45267 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1590 EP A1590 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610904203 ER PT J AU Xu, XM Carlson, BA Gladyshev, VN Berry, MJ Hatfield, DL AF Xu, XM Carlson, BA Gladyshev, VN Berry, MJ Hatfield, DL TI SecP43 affects the methylation of Sec tRNA SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, MBSS, LCP, CCR,NIH, Bethesda, MD 20892 USA. Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. Univ Hawaii Manoa, Dept Cell & Mol Biol, Honolulu, HI 96822 USA. RI Gladyshev, Vadim/A-9894-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1347 EP A1347 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610902410 ER PT J AU Xue, HH Bollenbacher, J Leonard, WJ AF Xue, HH Bollenbacher, J Leonard, WJ TI Differential regulation of IL-7 receptor alpha chain in T and B cells by GA binding protein and PU.1 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NIH, Lab Mol Immunol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAR 7 PY 2005 VL 19 IS 5 SU S BP A1415 EP A1416 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903069 ER PT J AU Zhu, GZ Fujii, K Liu, Y Hallam, J James, M Herrero, J Shaw, S AF Zhu, GZ Fujii, K Liu, Y Hallam, J James, M Herrero, J Shaw, S TI Exceptional disfavor for proline at the P+1 position amongst AGC and CAMK kinases establishes reciprocal specificity between them and the proline-directed kinases SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. AxCell Biosci, Newtown, PA 18940 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1378 EP A1378 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610902562 ER PT J AU Abashkin, YG Burt, SK AF Abashkin, YG Burt, SK TI (salen)Mn-III compounds as nonpeptidyl mimics of catalase. Mechanism-based tuning of catalase activity: A theoretical study SO INORGANIC CHEMISTRY LA English DT Article ID (SALEN)MN(III)-CATALYZED EPOXIDATION REACTION; MEDIATED ALKENE EPOXIDATION; TRANSITION-METAL COMPOUNDS; SUPEROXIDE-DISMUTASE; ACYLPEROXO COMPLEXES; MANGANESE CATALASE; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; LIFE-SPAN; REACTIVITY AB We present the results of the first theoretical investigation of salen-manganese complexes as synthetic catalytic scavengers of hydrogen peroxide molecules that mimic catalase enzymes. Catalase mimics can be used as therapeutic agents against oxidative stress in treatment of many diseases, including Alzheimer's disease, stroke, heart disease, aging, and cancer. A ping-pong mechanism approach has been considered to describe the H2O2 dismutation reaction. The real compounds reacting with a peroxide molecule were utilized in our BP density functional calculations to avoid uncertainties connected with using incomplete models. Part I of the dismiltation reactionconvening a peroxide molecule into a water molecule with simultaneous oxidation of the metal atom of the catalystcan be done quite effectively at the Mn catalytic center. To act as catalytic scavengers of hydrogen peroxide, the oxomanganese salen complexes have to be deoxidized during part II of the dismutation reaction. It has been shown that there are two possible reaction routes for the second part of the dismutation reaction: the top and the side substrate approach routes. Our results suggest that the catalyst could be at least temporarily deactivated (poisoned) in the side approach reaction route due to the formation of a kinetically stable intermediate. Overall, the side approach reaction route for the catalyst recovery is the bottleneck for the whole dismutation process. On the basis of the detailed knowledge of the mode of action of the (salen)Mn-III catalase mimics, we suggest and rationalize structural changes of the catalyst that should lead to better therapeutic properties. The available experimental data support our conclusions. Our findings on the reaction dismutation mechanism could be the starting point for further improvement of salen-manganese complexes as synthetic catalytic scavengers of reactive oxygen species. C1 SAIC Frederick Inc, Adv Biomed Comp Ctr, NCI, Frederick, MD 21702 USA. RP Abashkin, YG (reprint author), SAIC Frederick Inc, Adv Biomed Comp Ctr, NCI, POB B, Frederick, MD 21702 USA. EM abashkin@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 57 TC 29 Z9 31 U1 3 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD MAR 7 PY 2005 VL 44 IS 5 BP 1425 EP 1432 DI 10.1021/ic048714o PG 8 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 902HU UT WOS:000227346300042 PM 15732983 ER PT J AU Rehermann, B Shin, EC AF Rehermann, B Shin, EC TI Private aspects of heterologous immunity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Editorial Material ID HEPATITIS-C VIRUS; T-CELL RESPONSES; ANTIVIRAL IMMUNITY; VIRAL CLEARANCE; INFECTION; IMMUNOPATHOLOGY; PERSISTENCE; CD4(+); LUNG; CD8 AB Clinical manifestations of viral infections are highly variable, both in type and severity, among individual patients. Differences in host genetics and in dose and route of infection contribute to this variability but do not fully explain it. New studies now show that each subject's history of past infections individualizes the memory T cell pool. Private T cell receptor specificities of these preexisting memory T cell populations influence both disease severity and outcome of subsequent, unrelated virus infections. C1 NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Rehermann, B (reprint author), NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. EM Rehermann@nih.gov RI Shin, Eui-Cheol/C-1690-2011 NR 29 TC 24 Z9 24 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 MAR 7 PY 2005 VL 201 IS 5 BP 667 EP 670 DI 10.1084/jem.20050220 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 906XY UT WOS:000227679500002 PM 15753200 ER PT J AU Arita, M Bianchini, F Aliberti, J Sher, A Chiang, N Hong, S Yang, R Petasis, NA Serhan, CN AF Arita, M Bianchini, F Aliberti, J Sher, A Chiang, N Hong, S Yang, R Petasis, NA Serhan, CN TI Stereochemical assignment, antiinflammatory properties, and receptor for the omega-3 lipid mediator resolvin E1 SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID POLYUNSATURATED FATTY-ACIDS; PROTEIN-COUPLED RECEPTOR; DIETARY SUPPLEMENTATION; IN-VIVO; INFLAMMATION; ASPIRIN; NEUTROPHIL; LIGAND; CELLS; RECRUITMENT AB The essential fatty acid eicosapentaenoic acid (EPA) present in fish oils displays beneficial effects in a range of human disorders associated with inflammation including cardiovascular disease. Resolvin E1 (RvE1), a new bioactive oxygenated product of EPA, was identified in human plasma and prepared by total organic synthesis. Results of bioaction and physical matching studies indicate that the complete structure of RvE1 is 5S,12R,18R-trihydroxy-6Z,8E,10E,14Z,16E-EPA. At nanomolar levels, RvE1 dramatically reduced dermal inflammation, peritonitis, dendritic cell (DC) migration, and interleukin (IL) 12 production. We screened receptors and identified one, denoted earlier as ChemR23, that mediates RvE1 signal to attenuate nuclear factor-kappa B. Specific binding of RvE1 to this receptor was confirmed using synthetic [H-3]-labeled RvE1. Treatment of DCs with small interference RNA specific for ChemR23 sharply reduced RvE1 regulation of IL-12. These results demonstrate novel counterregulatory responses in inflammation initiated via RvE1 receptor activation that provide the first evidence for EPA-derived potent endogenous agonists of antiinflammation. C1 Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA. Univ So Calif, Loker Hydrocarbon Res Inst, Los Angeles, CA 90089 USA. RP Serhan, CN (reprint author), Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med, Boston, MA 02115 USA. EM cnserhan@zeus.bwh.harvard.edu RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013; OI Aliberti, Julio/0000-0003-3420-8478; Petasis, Nicos/0000-0002-8864-4446 FU NIDCR NIH HHS [P50 DE016191, P50- DE-016191]; NIGMS NIH HHS [GM38765, R01 GM038765, R37 GM038765] NR 28 TC 442 Z9 466 U1 2 U2 33 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 MAR 7 PY 2005 VL 201 IS 5 BP 713 EP 722 DI 10.1084/jem.20042031 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 906XY UT WOS:000227679500009 PM 15753205 ER PT J AU Muraro, PA Douek, DC Packer, A Chung, K Guenaga, FJ Cassiani-Ingoni, R Campbell, C Memon, S Nagle, JW Hakim, FT Gress, RE McFarland, HF Burt, RK Martin, R AF Muraro, PA Douek, DC Packer, A Chung, K Guenaga, FJ Cassiani-Ingoni, R Campbell, C Memon, S Nagle, JW Hakim, FT Gress, RE McFarland, HF Burt, RK Martin, R TI Thymic output generates a new and diverse TCR repertoire after autologous stem cell transplantation in multiple sclerosis patients SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NAIVE T-CELLS; HOMEOSTASIS-DRIVEN PROLIFERATION; BONE-MARROW RECIPIENTS; MEMORY-LIKE PHENOTYPE; PERIPHERAL-BLOOD; REPLICATIVE SENESCENCE; INTENSIVE CHEMOTHERAPY; RECONSTITUTION; LYMPHOCYTES; CD8(+) AB Clinical trials have indicated that autologous hematopoietic stem cell transplantation (HSCT) can persistently suppress inflammatory disease activity in a subset of patients with severe multiple sclerosis (MS), but the mechanism has remained unclear. To understand whether the beneficial effects on the course of disease are mediated by lympho-depletive effects alone or are sustained by a regeneration of the immune repertoire, we examined the long-term immune reconstitution in patients with MS who received HSCT. After numeric recovery of leukocytes, at 2-yr follow-up there was on average a doubling of the frequency of naive CD4(+) T cells at the expense of memory T cells. Phenotypic and T cell receptor excision circle (TREC) analysis confirmed a recent thymic origin of the expanded naive T cell subset. Analysis of the T cell receptor repertoire showed the reconstitution of an overall broader clonal diversity and an extensive renewal of clonal specificities compared with pretherapy. These data are the first to demonstrate that long-term suppression of inflammatory activity in MS patients who received HSCT does not depend on persisting lymphopenia and is associated with profound qualitative immunological changes that demonstrate a de novo regeneration of the T cell compartment. C1 NCI, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NCI, Informat Technol Program, NIH, Bethesda, MD 20892 USA. NCI, DNA Sequencing Core Facil, NINDS, NIH, Bethesda, MD 20892 USA. NCI, Human Immunol Sect, Vaccine Res Ctr, NIAID,NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Feinberg Sch Med, Dept Med, Div Immunotherapy, Evanston, IL 60208 USA. RP Muraro, PA (reprint author), NCI, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. EM murarop@ninds.nih.gov; martinr@ninds.nih.gov OI Muraro, Paolo/0000-0002-3822-1218 NR 49 TC 240 Z9 250 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD MAR 7 PY 2005 VL 201 IS 5 BP 805 EP 816 DI 10.1084/jem.20041679 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 906XY UT WOS:000227679500017 PM 15738052 ER PT J AU Lin, JP Myers, RH Almasy, L Coon, HH Arnett, DK Hong, YL Hunt, SC AF Lin, JP Myers, RH Almasy, L Coon, HH Arnett, DK Hong, YL Hunt, SC TI Linkage of the cholesterol 7 alpha-hydroxylase gene and low-density lipoprotein cholesterol conditional on apolipoprotein E association: the National Heart, Lung, and Blood Institute Family Heart Study SO CHINESE MEDICAL JOURNAL LA English DT Article DE linkage analysis; CYP7 gene; apoE gene; low-density lipoprotein cholesterol ID COMBINED HYPERLIPIDEMIA; HYPERCHOLESTEROLEMIA MAPS; PLASMA; LOCUS; POLYMORPHISM; MUTATIONS; PROTEIN; GENOME; LIPIDS; BIAS AB Background Genetic factors account for approximately 50% of the individual variation in plasma, low-density lipoprotein cholesterol (LDL-C) concentrations in the general population. Several candidate genes have been proposed but their relative contributions to the variance in LDL-C are not known, except for apolipoprotein E (apoE). We report here an investigation of the relationship between LDL-C and cholesterol 7 alpha-hydroxylase (CYP7), as well as apoE and low-density lipoprotein receptor (LDLR) three pivotal genes in LDL metabolism. Methods Our study population included more than 200 nuclear families with increased coronary heart disease (CHD) risk from the National Heart, Lung, and Blood Institute (NHLBI) Family Heart Study. Variance-component linkage methods, a measured genotype approach, and a variance-component linkage analysis conditional on a measured genotype association were used. Results The results showed significant linkage between a genetic determinant of plasma LDL-C concentrations and a polymorphism near CYP7 with its allelic variation accounting for 27% of the total LDL-C variation. There is significant association between plasma LDL-C concentrations and apoE genotypes. Conditional on the apoE association, the total LDL-C variation accounted by allelic variation of a polymorphism near CYP7 was increased significantly. Conclusion Our results suggest the apoE and CYP7 may be two important genes accounting for the genetic variation of plasma LDL-C concentrations in a population with cardiovascular diseases. C1 NHLBI, Off Biostat Res, Salt Lake City, UT 84108 USA. Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. SW Fdn Biomed Res, Dept Genet, San Antonio, TX 78245 USA. Univ Alabama Birmingham, Div Epidemiol, Birmingham, AL 35294 USA. Univ Utah, Dept Psychiat, Salt Lake City, UT 84112 USA. Amer Heart Assoc, Natl Ctr, Dallas, TX 75231 USA. Univ Utah, Dept Internal Med, Salt Lake City, UT 84108 USA. RP Lin, JP (reprint author), NCI, Off Biostat Res, NHLBI, NIH, 6701 Rockledge Dr,Room 8HD, Bethesda, MD 20892 USA. EM linj@nhlbi.nih.gov FU NHLBI NIH HHS [U01 HL56568, U01 HL56564, U01 HL56569, U01 HL56566, U01 HL56565, U01 HL56563, U01 HL56567] NR 35 TC 4 Z9 5 U1 0 U2 0 PU CHINESE MEDICAL ASSOC PI BEIJING PA 42 DONGSI XIDAJIE, BEIJING 100710, PEOPLES R CHINA SN 0366-6999 J9 CHINESE MED J-PEKING JI Chin. Med. J. PD MAR 5 PY 2005 VL 118 IS 5 BP 362 EP 369 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 907JD UT WOS:000227712000003 PM 15780204 ER PT J AU Issaq, HJ Chan, KC Janini, GM Conrads, TP Veenstra, TD AF Issaq, HJ Chan, KC Janini, GM Conrads, TP Veenstra, TD TI Multidimensional separation of peptides for effective proteomic analysis SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Review DE multidimensional separation; peptides; proteomic analysis ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CODED AFFINITY TAGS; PROTEIN IDENTIFICATION TECHNOLOGY; CAPILLARY-ZONE-ELECTROPHORESIS; IONIZATION MASS-SPECTROMETRY; HUMAN SERUM PROTEOME; COMPLEX-MIXTURES; GEL-ELECTROPHORESIS; 2-DIMENSIONAL ELECTROPHORESIS; SAMPLE PREPARATION AB Current solution based proteomic analysis methods are generally based on enzymatic digestion of a protein mixture followed by separation using multidimensional liquid chromatography and/or electrophoresis where peptide identification is typically accomplished by tandem mass spectrometry (MS/MS). It is generally accepted that no single chromatographic or electrophoretic procedure is capable of resolving the complex mixture of peptides that results from a global proteolytic digest of a proteome. Therefore, combining two or more orthogonal (multimodal) separation procedures dramatically improves the overall resolution and results in a larger number of peptides being identified from complex proteome digests. Separation of a proteome digest is a particularly challenging analytical problem due to the large number of peptides and the wide concentration dynamic range. While it has been demonstrated that increasing the number of dimensions of separation prior to MS analysis increases the number of peptides that may be identified, a balance between the time invested and the overall results obtained must be carefully considered. This manuscript provides a review of two- and three-dimensional peptide separation strategies combined with MS for the analysis of complex peptide mixtures. (C) 2004 Elsevier B.V. All rights reserved. C1 SAIC Frederick Inc, Lab Proteom & Analyt Technol, NCI, Frederick, MD 21702 USA. RP Issaq, HJ (reprint author), SAIC Frederick Inc, Lab Proteom & Analyt Technol, NCI, POB B, Frederick, MD 21702 USA. EM issaqh@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 68 TC 138 Z9 144 U1 1 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD MAR 5 PY 2005 VL 817 IS 1 BP 35 EP 47 DI 10.1016/j.jchromb.2004.07.042 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 896FD UT WOS:000226919100005 PM 15680787 ER PT J AU Lee, SH Kim, JS Yamaguchi, K Eling, TE Baek, SJ AF Lee, SH Kim, JS Yamaguchi, K Eling, TE Baek, SJ TI Indole-3-carbinol and 3,3 '-diindolylmethane induce expression of NAG-1 in a p53-independent manner SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE 13C; GDF-15; NAG-1; ATF3; p53 DIM; apoptosis ID DRUG-ACTIVATED GENE; BREAST-CANCER CELLS; BETA SUPERFAMILY MEMBER; GROWTH-FACTOR-BETA; CYCLE ARREST; COLON-CANCER; DIETARY INDOLE-3-CARBINOL; MORPHOGENETIC PROTEIN; CARCINOMA-CELLS; DNA-DAMAGE AB Indole-3-carbinol (13C), present in cruciferous vegetables, and its major in vivo product 3,3'-diindolylmethane (DIM), have been reported to suppress cancer development. However, the responsible molecular mechanisms are not fully understood. Nonsteroidal anti-inflaminatory drug-activated gene-1 (NAG-1) is a TGF-beta superfamily gene associated with pro-apoptotic and anti-tumorigenic activities. The present study was performed to investigate whether 13C and DIM influence NAG-1 expression and to provide the potential molecular mechanism of their effects oil anti-tumorigenesis. The 13C repressed cell proliferation and induced NAG-1 expression in a concentration-dependent manner. In addition, DIM increased the expression of NAG-1 as well as activating transcription factor 3 (ATF3), and the induction of ATF3 was earlier than that of NAG-1. The DIM treatment increased luciferase activity of NAG-1 in HCT-116 cells transfected with NAG-1 promoter construct. The results suggest that 13C represses cell proliferation through up-regulation of NAG-1 and that ATF3 may play a pivotal role in DIM-induced NAG-1 expression ill human colorectal cancer cells. Furthermore, the mixture of 13C with resveratrol enhances NAG-1 expression, suggesting the synergistic effect of these two unrelated compounds on NAG-1 expression. (C) 2005 Elsevier Inc. All rights reserved. C1 Univ Tennessee, Lab Environm Carciogenesis, Dept Pathobiol, Coll Vet Med, Knoxville, TN 37996 USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Baek, SJ (reprint author), Univ Tennessee, Lab Environm Carciogenesis, Dept Pathobiol, Coll Vet Med, Knoxville, TN 37996 USA. EM sbaek2@utk.edu OI Baek, Seung/0000-0001-7866-7778 NR 45 TC 93 Z9 99 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD MAR 4 PY 2005 VL 328 IS 1 BP 63 EP 69 DI 10.1016/j.bbrc.2004.12.138 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 894NU UT WOS:000226799600011 PM 15670751 ER EF