FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Khan, MAS Chock, PB Stadtman, ER AF Khan, MAS Chock, PB Stadtman, ER TI Knockout of caspase-like gene, YCA1, abrogates apoptosis and elevates oxidized proteins in Saccharomyces cerevisiae SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE H2O2; metacaspase; programmed cell death; proteasome activity; protein carbonyl ID CELL-DEATH; OXYGEN RADICALS; 26S PROTEASOME; YEAST; DEGRADATION; ACTIVATION; REGULATOR; OXIDATION; RESIDUES; DISEASE AB In our previous study, we established that inhibition of apoptosis by the general caspase inhibitor is associated with an increase in the level of oxidized proteins in a multicellular eukaryotic system. To gain further insight into a potential link between oxidative stress and apoptosis, we carried out studies with Saccharomyces cerevisiae, which contains a gene (YCA1) that encodes synthesis of metacaspase, a homologue of the mammalian caspase, and is known to play a crucial role in the regulation of yeast apoptosis. We show that upon exposure to H2O2, the accumulation of protein carbonyls is much greater in a Delta yca1 strain lacking the YCA1 gene than in the wild type and that apoptosis was abrogated in the Delta yca1 strain, whereas wild type underwent apoptosis as measured by externalization of phosphatidylserine and the display of TUNEL-positive nuclei. We also show that H2O2-mediated stress leads to up-regulation of the 20S proteasome and suppression of ubiquitinylation activities. These findings suggest that deletion of the apoptotic-related caspase-like gene leads to a large H2O2-dependent accumulation of oxidized proteins and up-regulation of 20S proteasome activity. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Stadtman, ER (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Room 2140,50 S Dr,MSC-8012, Bethesda, MD 20892 USA. EM erstadtman@nih.gov FU Intramural NIH HHS NR 40 TC 70 Z9 77 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 NOV 29 PY 2005 VL 102 IS 48 BP 17326 EP 17331 DI 10.1073/pnas.0508120102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 990RX UT WOS:000233762000013 PM 16301538 ER PT J AU Rodondi, N Newman, AB Vittinghoff, E de Rekeneire, N Satterfield, S Harris, TB Bauer, DC AF Rodondi, N Newman, AB Vittinghoff, E de Rekeneire, N Satterfield, S Harris, TB Bauer, DC TI Subclinical hypothyroidism and the risk of heart failure, other cardiovascular events, and death SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID PLACEBO-CONTROLLED TRIAL; L-THYROXINE THERAPY; THYROID-DYSFUNCTION; DOUBLE-BLIND; MYOCARDIAL-INFARCTION; OLDER PERSONS; ALL-CAUSE; DISEASE; HEALTH; ASSOCIATION AB Background: Subclinical hypothyroidism has been associated with systolic and diastolic cardiac dysfunction and an elevated cholesterol level, but data on cardiovascular outcomes and death are limited. Methods: We studied 2730 men and women, aged 70 to 79 years, with baseline thyrotropin (TSH) measurements and 4-year follow-up data to determine whether subclinical hypothyroidism was associated with congestive heart failure (CHF), coronary heart disease, stroke, peripheral arterial disease, and cardiovascular-related and total mortality. After the exclusion of participants with abnormal thyroxine levels, subclinical hypothyroidism was defined as a TSH level of 4.5 mIU/L or greater, and was further classified according to TSH levels (4.5-6.9, 7.0-9.9, and >= 10.0 mIU/L). Results: Subclinical hypothyroidism was present in 338 (12.4%) of the participants. Compared with euthyroid participants, CHF events occurred more frequently among those with a TSH level of 7.0 mIU/L or greater (35.0 vs 16.5 per 1000 person-years; P=.006), but not among those with TSH levels between 4.5 and 6.9 mIU/L. In multivariate analyses, the risk of CHF was higher among those with high TSH levels (TSH of 7.0-9.9 mIU/L: hazard ratio, 2.58 [95% confidence interval, 1.19-5.60]; and TSH of >= 10.0 mIU/L: hazard ratio, 3.26 [95% confidence interval, 1.37-7.77]). Among the 2555 participants without CHF at baseline, the hazard ratio for incident CHF events was 2.33 (95% confidence interval, 1.10-4.96; P=.03) in those with a TSH of 7.0 mIU/L or greater. Subclinical hypothyroidism was not associated with increased risk for coronary heart disease, stroke, peripheral arterial disease, or cardiovascular-related or total mortality. Conclusions: Subclinical hypothyroidism is associated with an increased risk of CHF among older adults with a TSH level of 7.0 mIU/L or greater, but not with other cardiovascular events and mortality. Further investigation is warranted to assess whether subclinical hypothyroidism causes or worsens preexisting heart failure. C1 Univ Lausanne, Dept Commun Med & Publ Hlth, CH-1011 Lausanne, Switzerland. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Gen Internal Med, Dept Med, San Francisco, CA 94143 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Tennessee, Coll Med, Dept Prevent Med, Memphis, TN USA. RP Rodondi, N (reprint author), Univ Lausanne, Dept Commun Med & Publ Hlth, Bugnon 44, CH-1011 Lausanne, Switzerland. EM Nicolas.Rodondi@hospvd.ch RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 48 TC 240 Z9 255 U1 1 U2 4 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 28 PY 2005 VL 165 IS 21 BP 2460 EP 2466 DI 10.1001/archinte.165.21.2460 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 987HY UT WOS:000233510200004 PM 16314541 ER PT J AU Wilson, PWF Nam, BH Pencina, M D'Agostino, RB Benjamin, EJ O'Donnell, CJ AF Wilson, PWF Nam, BH Pencina, M D'Agostino, RB Benjamin, EJ O'Donnell, CJ TI C-reactive protein and risk of cardiovascular disease in men and women from the Framingham Heart Study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID MIDDLE-AGED MEN; MYOCARDIAL-INFARCTION; ATHEROSCLEROSIS RISK; PLASMA-CONCENTRATION; METABOLIC SYNDROME; RANDOMIZED-TRIAL; CORONARY EVENTS; PREDICTION; INFLAMMATION; ASSOCIATION AB Background: Determination of C-reactive protein (CRP) level has been suggested to improve cardiovascular disease (CVD) risk assessment. This study examines the utility of CRP levels to assess CVD risk in a community setting. Methods: We performed a prospective observational cohort study on a community population sample. A total of 1949 men and 2497 women without CVD from the Framingham Heart Study underwent CVD risk factor assessment. Initial CVD events during 8 years of follow-up were recorded. Results: There were 283 major CVD and 160 major coronary heart disease incident events. Age-, sex-, and multivariable-adjusted analyses generally used CRP level categories of less than 1, 1 to 3, and greater than 3 mg/L. In age- and sex-adjusted models, the traditional risk factors and elevated CRP levels indicated increased risk. The age- and sex-adjusted relative risk (RR) and 95% confidence interval (CI) of CRP level greater than 3 mg/L for major CVD was elevated (RR, 1.60; 95% CI, 1.19-2.1.4), with evidence of attenuation (RR, 1.22; 95% CI, 0.90-1.66) in multivariable models. The C statistic, a measure of the discriminatory capability of the prediction models, was 0.74 for prediction of major CVD with age and CRP level. In multivariable models that included traditional risk factors, the C statistic was 0.78, a value that was unchanged with the addition of CRP to the multivariable model. Similar relations were noted for major coronary heart disease events. Conclusion: Elevated CRP level provided no further prognostic information beyond traditional office risk factor assessment to predict future major CVD and major coronary heart disease in this population sample. C1 Med Univ S Carolina, Gen Clin Res Ctr, Charleston, SC 29425 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Univ, Dept Cardiol, Sch Med, Boston, MA 02215 USA. NHLBI, Framingham, MA USA. RP Wilson, PWF (reprint author), Med Univ S Carolina, Gen Clin Res Ctr, 96 Jonathan Lucas St,Clin Sci Bldg,Suite 215, Charleston, SC 29425 USA. EM wilsonpw@musc.edu OI Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01-HC-25195, R01-HL 073272] NR 45 TC 150 Z9 153 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 28 PY 2005 VL 165 IS 21 BP 2473 EP 2478 DI 10.1001/archinte.165.21.2473 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 987HY UT WOS:000233510200006 PM 16314543 ER PT J AU Ballantyne, CM Hoogeveen, RC Bang, H Coresh, P Folsom, AR Chambless, LE Myerson, M Wu, KK Sharrett, AR Boerwinkle, E AF Ballantyne, CM Hoogeveen, RC Bang, H Coresh, P Folsom, AR Chambless, LE Myerson, M Wu, KK Sharrett, AR Boerwinkle, E TI Lipoprotein-associated phospholipase A(2), high-sensitivity C-reactive protein, and risk for incident ischemic stroke in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ACTIVATING-FACTOR ACETYLHYDROLASE; HUMAN ENDOTHELIAL-CELLS; CORONARY-HEART-DISEASE; CASE-COHORT DESIGN; CARDIOVASCULAR-DISEASE; CHOLESTEROL; SUBFRACTIONS; INFLAMMATION; FENOFIBRATE; PREVENTION AB Background: Measurement of inflammatory markers has been reported to identify individuals at increased risk for ischemic stroke. Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is a proinflammatory enzyme secreted by macrophages. We assessed Lp-PLA(2) and C-reactive protein (CRP) levels along with traditional risk factors to examine their relation to ischemic stroke. Methods: A proportional hazards model was used in a prospective case-cohort study of 12 762 apparently healthy middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study who were observed for about 6 years. Results: Mean Lp-PLA2 and CRP levels adjusted for sex, race, and age were higher in the 194 stroke cases than the 766 noncases, whereas low-density lipoprotein cholesterol (LDL-C) level was not significantly different. Both Lp-PLA2 and CRP levels were associated with ischemic stroke after adjustment for age, sex, and race: hazard ratios were 2.23 for the highest vs the lowest tertile of Lp-PLA(2) and 2.70 for CRP level higher than 3 vs lower than 1 mg/L. In a model that included smoking, systolic hypertension, lipid levels, and diabetes, Lp-PLA(2) and CRP levels in the highest category were associated with hazard ratios of 1.91 (95% confidence interval, 1.15-3.18; P=.01) and 1.87 (95% confidence interval, 1.13-3. 10; P=.02), respectively. Individuals with high levels of both CRP and Lp-PLA(2) were at the highest risk after adjusting for traditional risk factors compared with individuals with low levels of both, whereas others were at intermediate risk. Conclusion: Levels of Lp-PLA(2) and CRP may be complementary beyond traditional risk factors in identifying middle-aged individuals at increased risk for ischemic stroke. C1 Baylor Coll Med, Dept Med, Sect Atherosclerosis & Lipoprot Res, Houston, TX 77030 USA. Methodist DeBakey Heart Ctr, Ctr Cardiovasc Dis Prevent, Houston, TX USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. Johns Hopkins Univ, John Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21201 USA. Univ Minnesota, Sch Publ Hlth, Div Epidemiol, Minneapolis, MN USA. NHLBI, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Vasc Biol Res Ctr, Dept Internal Med, Houston, TX USA. Univ Texas, Hlth Sci Ctr, Sch Publ Hlth, Ctr Human Genet, Houston, TX USA. RP Ballantyne, CM (reprint author), Baylor Coll Med, Dept Med, Sect Atherosclerosis & Lipoprot Res, 6565 Fannin,Mail Stop A-601, Houston, TX 77030 USA. EM cmb@bcm.tmc.edu RI Ballantyne, Christie/A-6599-2008; Wu, Kenneth Kun-Yu/B-1070-2010 FU NHLBI NIH HHS [N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022] NR 41 TC 172 Z9 182 U1 0 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD NOV 28 PY 2005 VL 165 IS 21 BP 2479 EP 2484 DI 10.1001/archinte.165.21.2479 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 987HY UT WOS:000233510200007 PM 16314544 ER PT J AU Abbott, KC Kimmel, PL Dharnidharka, V Oglesby, RJ Agodoa, LY Caillard, S AF Abbott, KC Kimmel, PL Dharnidharka, V Oglesby, RJ Agodoa, LY Caillard, S TI New-onset gout after kidney transplantation: Incidence, risk factors and implications SO TRANSPLANTATION LA English DT Article DE new-onset gout; cyclosporine; creatinine; glomerular filtration rate; age; body mass index; obesity; medicare claim; kidney transplant; end stage kidney disease; USRDS ID CYCLOSPORINE-INDUCED HYPERURICEMIA; CHRONIC HEART-FAILURE; URIC-ACID; CARDIOVASCULAR-DISEASE; RENAL-DISEASE; HYPERTENSION; RECIPIENTS; EPIDEMIOLOGY; TACROLIMUS; SURVIVAL AB Background. Although cyclosporine use has been associated with an increased risk of new-onset gout after renal transplantation, the incidence and risk factors for new-onset gout have not been reported in the era of modern immunosuppression. Methods. We conducted a retrospective cohort study of Medicare primary renal transplant patients reported in the United States Renal Data System (USRDS), using Medicare claims data to determine the incidence of new-onset gout. Cox regression analysis was used to calculate adjusted hazard ratios (AHR) for cyclosporine (including separate analysis of Neoral) compared directly with tacrolimus, for the risk of new-onset gout, adjusted for baseline demographic factors and posttransplant renal function. Results. The cumulative incidence of new-onset gout was 7.6% at 3 years posttransplant. The following factors were independently associated with an increased risk of new-onset gout: use of Neoral (vs. tacrolimus, AHR 1.25, 95% CI 1.07-1.47) at discharge, recipient male sex (AHR 1.44, 95% CI 1.25-1.67), older age, higher body mass index, and more recent year of transplant. No other immunosuppressive medications were associated with new-onset gout. Diabetes was associated with a significantly lower risk of new-onset gout. The development of new-onset gout was independently associated with decreased patient survival (AHR 1.26, 95% CI 1.08-1.47) as well as death-censored graft survival. Conclusions. Cyclosporine is an independent risk factor for new-onset gout after transplantation. The incidence of new-onset gout appears to be increasing even while the use of cyclosporine is decreasing, and the development of new-onset gout was an independent predictor for death and graft loss in this population. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. George Washington Univ, Med Ctr, Dept Med, Washington, DC 20037 USA. Univ Florida, Div Renal, Gainesville, FL USA. Walter Reed Army Med Ctr, Rheumatol Serv, Washington, DC 20307 USA. NIDDKD, NIH, Bethesda, MD USA. RP Abbott, KC (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM kevin.abbott@na.amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 41 TC 34 Z9 41 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 2005 VL 80 IS 10 BP 1383 EP 1391 DI 10.1097/01.tp.0000188722.84775.af PG 9 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 994YH UT WOS:000234066600005 PM 16340779 ER PT J AU Cendales, LC Xu, H Bacher, J Eckhaus, MA Kleiner, DE Kirk, AD AF Cendales, LC Xu, H Bacher, J Eckhaus, MA Kleiner, DE Kirk, AD TI Composite tissue allotransplantation: Development of a preclinical model in nonhuman primates SO TRANSPLANTATION LA English DT Article DE composite tissue allotransplantation; nonhuman primates; animal model; transplantation; allograft ID UPPER EXTREMITY RECONSTRUCTION; RHESUS-MONKEY; TRANSPLANTATION; TOLERANCE; HAND; CYCLOSPORINE; TACROLIMUS; ALLOGRAFT AB Background. Composite tissue allotransplantation (CTA) has been recently introduced as a potential treatment for tissue loss secondary to burns, injuries, or resections. However, the optimal strategies to prevent CTA rejection remain undefined. Presently, no CTA model exists to evaluate human-specific immunosuppressants or the relative immunogenicity of all CTA tissues. Methods. We established a NHP CTA model utilizing a sensate osteomyocutaneous radial forearm flap that avoids functional impairment even in the case of graft loss. The model was evaluated in 19 monkeys that underwent auto- or allotransplantation, with or without subtherapeutic immunosuppression to temporarily characterize rejection. Results. Autografts showed no evidence of rejection. Nonimmunosuppressed allografts were rapidly rejected showing a perivenular T-cell infiltrate. This was associated with subsequent alloantibody formation and led to graft thrombosis without prominent dermal infiltration. Subtherapeutically immunosuppressed animals also developed alloantibody and rejected in a delayed fashion exhibiting a marked dermal lymphocytic infiltrate similar in magnitude and distribution to previously reported human cases. Conclusion. Our NHP model for CTA is well tolerated by NHPs, results in allosensitization, is responsive to immunosuppression, allows for the evaluation of CTA histology and can be used for the systematic preclinical evaluation of therapeutic maneuvers to improve allograft survival. C1 NIAMSD, Orthoped Sect, NIH, Bethesda, MD 20892 USA. NIDDKD, Transplantat Branch, NIH, Bethesda, MD 20892 USA. NIH, Div Vet Res, Off Res Serv, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Cendales, LC (reprint author), 10 Ctr Dr,MSC 1102,CRC Room 1-5140, Bethesda, MD 20892 USA. EM cendalesl@mail.nih.gov RI Kirk, Allan/B-6905-2012; OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 20 TC 47 Z9 49 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 27 PY 2005 VL 80 IS 10 BP 1447 EP 1454 DI 10.1097/01.tp.0000183292.57349.27 PG 8 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 994YH UT WOS:000234066600016 PM 16340790 ER PT J AU Song, JW Clair, T Noh, JH Eun, JW Ryu, SY Lee, SN Ahn, YM Kim, SY Lee, SH Park, WS Yoo, NJ Lee, JY Nam, SW AF Song, JW Clair, T Noh, JH Eun, JW Ryu, SY Lee, SN Ahn, YM Kim, SY Lee, SH Park, WS Yoo, NJ Lee, JY Nam, SW TI Autotaxin (lysoPLD/NPP2) protects fibroblasts from apoptosis through its enzymatic product, lysophosphatidic acid, utilizing albumin-bound substrate SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE autotaxin; anti-apoptosis; lysophosphatidic acid; apoptosis; lysophospholipase D ID LYSOPHOSPHOLIPASE-D ACTIVITY; HUMAN-MELANOMA CELLS; GROWTH-FACTOR; MOTILITY; EXPRESSION; INDUCTION; MIGRATION; SURVIVAL; SPHINGOSINE-1-PHOSPHATE; PHOSPHODIESTERASE AB Autotaxin (ATX) was originally identified as a potent tumor cell motility-stimulating factor that displays multiple enzymatic activities including ATPase, Type I nucleotide pyi-ophosphatase/phospliodiesterase, and lysophospholipase D. depending on its substrates. We demonstrate herein that ATX is a key regulator of extracellular lysophosphatidic acid (LPA) that can act as survival factor, in addition to its mitogenic activity in mouse fibroblasts. Introduction of atx gene into NIH3T3 cells resulted in resistance to conditional apoptosis induced by serum-deprivation, and exogenous ATX protein prevented cells from death by starvation. Flow cytometric analysis showed that co-treatment of ATX with lysophosphatidylcholine as substrate rescued NIH3T3 cells from cellular apoptosis, and this survival activity of ATX was also demonstrated by caspase-3 degradation and PARP cleavage resulting from the enzymatic activity of extracellular ATX. Furthermore, the effect of ATX in preventing apoptosis appears to be mediated through the G-protein-coupled receptor pathway followed by the activation of phosphoinositide 3-kinase and Akt pathway leading to enhanced cell survival. These findings provide novel insights into understanding the functions of ATX as a key regulator of bioactive phospholipids and suggest interventions to correct dysfunction in conditions of tumor cell growth and metastasis. (c) 2005 Elsevier Inc. All rights reserved. C1 Catholic Univ Korea, Coll Med, Dept Pathol, Seoul 137701, South Korea. Catholic Univ Korea, Microdissect Genom Res Ctr, Seoul 137701, South Korea. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Ewha Womans Univ, Coll Med, Dept Pathol, Seoul 120750, South Korea. Kyung Hee Univ, Coll Oriental Med, Dept Kidney Syst, Seoul, South Korea. RP Nam, SW (reprint author), Catholic Univ Korea, Coll Med, Dept Pathol, Banpo Dong 505, Seoul 137701, South Korea. EM swnam@catholic.ac.kr NR 40 TC 21 Z9 22 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 25 PY 2005 VL 337 IS 3 BP 967 EP 975 DI 10.1016/j.bbrc.2005.09.140 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 978YY UT WOS:000232910300030 PM 16219296 ER PT J AU Qi, HY Shelhamer, JH AF Qi, HY Shelhamer, JH TI Toll-like receptor 4 signaling regulates cytosolic phospholipase A(2) activation and lipid generation in lipopolysaccharide-stimulated macrophages SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CYTOSOLIC PHOSPHOLIPASE A(2); TOLL-LIKE RECEPTORS; NF-KAPPA-B; ARACHIDONIC-ACID; HUMAN NEUTROPHILS; CUTTING EDGE; MAST-CELLS; KEY ROLE; SEPSIS; EXPRESSION AB Inflammatory lipid mediators such as prostaglandins and leukotrienes play crucial roles in the pathogenesis of bacterial lipopolysaccharide (LPS)-induced inflammation. Cytosolic phospholipase A(2) (cPLA(2)) is a key enzyme in the generation of pro-inflammatory lipid mediators. Here, we found that Toll-like receptor 4 (TLR4) is essential for LPS-induced cPLA2 activation and lipid release. Inhibition of TLR4 protein expression by TLR4 small interfering RNA or neutralization of TLR4 by the specific antibody against TLR4/MD2 blocked cPLA(2) phosphorylation and cPLA(2)-hydrolyzed arachidonic acid release. Furthermore, activation of the TLR4 signaling pathway by LPS regulated cPLA(2) activation and lipid release. cPLA(2) phosphorylation and cPLA(2)-hydrolyzed lipid release were significantly impaired when TLR4 adaptor protein, either MyD88 or TRIF, was knocked down in LPS-stimulated macrophages. Similarly, LPS-induced arachidonate release was inhibited in cells transfected with a dominant-negative MyD88 or TRIF construct. Subsequently, cPLA(2) activation could be suppressed by inhibition of the TLR4 adaptor protein-directed p38 and ERK MAPK pathways. These findings suggest that, in LPS-induced inflammation, the TLR4-mediated MyD88-and TRIF-dependent MAPK pathways result in cPLA(2) activation and production of pro-inflammatory lipid mediators. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Shelhamer, JH (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Rm 7-D-43, Bethesda, MD 20892 USA. EM jshelhamer@nih.gov NR 65 TC 72 Z9 77 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 NOV 25 PY 2005 VL 280 IS 47 BP 38969 EP 38975 DI 10.1074/jbc.M509352200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 985FL UT WOS:000233362200010 PM 16176925 ER PT J AU Gallagher, PG Liem, RI Wong, E Weiss, MJ Bodine, DM AF Gallagher, PG Liem, RI Wong, E Weiss, MJ Bodine, DM TI GATA-1 and Oct-1 are required for expression of the human alpha-hemoglobin-stabilizing protein gene SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HIGH-LEVEL EXPRESSION; BETA-THALASSEMIA; SPECTRIN GENE; ERYTHROID PROMOTER; MAMMALIAN-CELLS; POU DOMAIN; ERYTHROPOIESIS; ACTIVATION; CHAPERONE; INSIGHTS AB alpha-Hemoglobin-stabilizing protein (AHSP) is an erythroid protein that binds and stabilizes alpha-hemoglobin during normal erythropoiesis and in pathological states of alpha-hemoglobin excess. AHSP has been proposed as a candidate gene in some Heinz body hemolytic anemias and as a modifier gene in the beta-thalassemia syndromes. To gain additional insight into the molecular mechanisms controlling the erythroid-specific expression of the AHSP gene and provide the necessary tools for further genetic studies of these disorders, we have initiated identification and characterization of the regulatory elements controlling the human AHSP gene. We mapped the 5'-end of the AHSP erythroid cDNA and cloned the 5'-flanking genomic DNA containing the putative AHSP gene promoter. In vitro studies using transfection of promoter/reporter plasmids in human tissue culture cell lines, DNase I footprinting analyses and gel mobility shift assays, identified an AHSP gene erythroid promoter with functionally important binding sites for GATA-1- and Oct-1-related proteins. In transgenic mice, a reporter gene directed by a minimal human AHSP promoter was expressed in bone marrow, spleen, and reticulocytes, but not in nonerythroid tissues. In vivo studies using chromatin immunoprecipitation assays demonstrated hyperacetylation of the promoter region and occupancy by GATA-1. The AHSP promoter is an excellent candidate region for mutations associated with decreased AHSP gene expression. C1 Yale Univ, Dept Pediat, Sch Med, New Haven, CT 06520 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Univ Penn, Philadelphia, PA 19104 USA. NHGRI, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. RP Gallagher, PG (reprint author), Yale Univ, Dept Pediat, Sch Med, 333 Cedar St,POB 208064, New Haven, CT 06520 USA. EM patrick.gallagher@yale.edu RI Weiss, Mitchell/A-1245-2013 FU NHLBI NIH HHS [HL65448]; NIDDK NIH HHS [DK061692, R01 DK061692, DK/HL62039] NR 30 TC 21 Z9 25 U1 1 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 2005 VL 280 IS 47 BP 39016 EP 39023 DI 10.1074/jbc.M506062200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 985FL UT WOS:000233362200015 PM 16186125 ER PT J AU Azarov, I Huang, KT Basu, S Gladwin, MT Hogg, N Kim-Shapiro, DB AF Azarov, I Huang, KT Basu, S Gladwin, MT Hogg, N Kim-Shapiro, DB TI Nitric oxide scavenging by red blood cells as a function of hematocrit and oxygenation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ERYTHROCYTE CONSUMPTION; FREE HEMOGLOBIN; RELAXING FACTOR; DIFFUSION; BINDING; MODEL; NO; OXIDATION; BARRIER; BIOAVAILABILITY AB The reaction rate between nitric oxide and intraerythrocytic hemoglobin plays a major role in nitric oxide bioavailability and modulates homeostatic vascular function. It has previously been demonstrated that the encapsulation of hemoglobin in red blood cells restricts its ability to scavenge nitric oxide. This effect has been attributed to either factors intrinsic to the red blood cell such as a physical membrane barrier or factors external to the red blood cell such as the formation of an unstirred layer around the cell. We have performed measurements of the uptake rate of nitric oxide by red blood cells under oxygenated and deoxygenated conditions at different hematocrit percentages. Our studies include stopped-flow measurements where both the unstirred layer and physical barrier potentially participate, as well as competition experiments where the potential contribution of the unstirred layer is limited. We find that deoxygenated erythrocytes scavenge nitric oxide faster than oxygenated cells and that the rate of nitric oxide scavenging for oxygenated red blood cells increases as the hematocrit is raised from 15% to 50%. Our results 1) confirm the critical biological phenomenon that hemoglobin compartmentalization within the erythrocyte reduces reaction rates with nitric oxide, 2) show that extra-erythocytic diffusional barriers mediate most of this effect, and 3) provide novel evidence that an oxygen-dependent intrinsic property of the red blood cell contributes to this barrier activity, albeit to a lesser extent. These observations may have important physiological implications within the microvasculature and for pathophysiological disruption of nitric oxide homeostasis in diseases. C1 Wake Forest Univ, Dept Phys, Sch Med, Winston Salem, NC 27109 USA. Wake Forest Univ, Dept Biomed Engn, Sch Med, Winston Salem, NC 27109 USA. NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Free Rad Res Ctr, Milwaukee, WI 53226 USA. RP Kim-Shapiro, DB (reprint author), Wake Forest Univ, Dept Phys, Sch Med, Winston Salem, NC 27109 USA. EM shapiro@wfu.edu OI Azarov, Ivan/0000-0002-9886-3298 FU NHLBI NIH HHS [K02-HL078706, R01 HL058091, HL58091]; NIGMS NIH HHS [GM55792] NR 49 TC 92 Z9 94 U1 1 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 NOV 25 PY 2005 VL 280 IS 47 BP 39024 EP 39032 DI 10.1074/jbc.M509045200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 985FL UT WOS:000233362200016 PM 16186121 ER PT J AU Hizi, A Levin, HL AF Hizi, A Levin, HL TI The integrase of the long terminal repeat-retrotransposon Tf1 has a chromodomain that modulates integrase activities SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HIV-1 REVERSE-TRANSCRIPTASE; SUBSTRATE-SPECIFICITY; HISTONE ACETYLATION; DNA INTEGRATION; TYPE-1; PROTEIN; TRANSPOSITION; MECHANISM; RNA AB Chromodomains in a variety of proteins mediate the formation of heterochromatin by interacting directly with histone H3, DNA, or RNA. A diverse family of long terminal repeat (LTR)-retrotransposons possesses chromodomains in their integrases (IN), suggesting that the chromodomains may control integration. The LTR-retrotransposon Tf1 of Schizosaccharomyces pombe is highly active and possesses a chromodomain in the COOH terminus of its IN. To test this chromodomain for a role in integration, recombinant INs with and without the chromodomain were assayed for activity in in vitro reactions. The full-length IN had integration activity with oligonucleotide substrates that modeled both the insertion reaction and a reverse reaction known as disintegration. The INs of retroviruses possess an additional activity termed 3' processing that must remove 2-3 nucleotides from the 3' ends of the viral cDNA before insertion can occur. These additional nucleotides are added during reverse transcription because of the position of the minus strand primer downstream of the LTR. The position of the primer for Tf1 suggests no nucleotides are added 3' of the LTR. It was therefore surprising that Tf1 IN was capable of 3' cleavage. The most unexpected result reported here was that the IN lacking the chromodomain had significantly higher activity and substantially reduced substrate specificity. These results reveal that both the activity and specificity of enzymes can be modulated by their chromodomains. C1 NICHD, Sect Eukaryot Transposable Elements, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Fac Med, Dept Cell & Dev Biol, IL-69978 Tel Aviv, Israel. RP Levin, HL (reprint author), 18 Lib Dr,Rm 106, Bethesda, MD 20892 USA. EM henry_levin@nih.gov FU Intramural NIH HHS NR 47 TC 18 Z9 18 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 NOV 25 PY 2005 VL 280 IS 47 BP 39086 EP 39094 DI 10.1074/jbc.M506363200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 985FL UT WOS:000233362200023 PM 16188891 ER PT J AU Hambleton, R Krall, J Tikishvili, E Honeggar, M Ahmad, F Manganiello, VC Movsesian, MA AF Hambleton, R Krall, J Tikishvili, E Honeggar, M Ahmad, F Manganiello, VC Movsesian, MA TI Isoforms of cyclic nucleotide phosphodiesterase PDE3 and their contribution to cAMP hydrolytic activity in subcellular fractions of human myocardium SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DEPENDENT PROTEIN-KINASE; GUANYLYL CYCLASE-A; HUMAN VENTRICULAR MYOCARDIUM; RAT CARDIAC MYOCYTES; NITRIC-OXIDE; NATRIURETIC-PEPTIDE; HEART-FAILURE; SARCOPLASMIC-RETICULUM; CA2+ CURRENT; ROLIPRAM INHIBITION AB Three isoforms of PDE3 (cGMP-inhibited) cyclic nucleotide phosphodiesterase regulate cAMP content in different intracellular compartments of cardiac myocytes in response to different signals. We characterized the catalytic activity and inhibitor sensitivity of these isoforms by using recombinant proteins. We determined their contribution to cAMP hydrolysis in cytosolic and microsomal fractions of human myocardium at 0.1 and 1.0 mu M cAMP in the absence and presence of Ca2+/calmodulin. We examined the effects of cGMP on cAMP hydrolysis in these fractions. PDE3A-136, PDE3A118, and PDE3A-94 have similar K-m and k(cat) values for cAMP and are equal in their sensitivities to inhibition by cGMP and cilostazol. In microsomes, PDE3A-136, PDE3A-118, and PDE3A-94 comprise the majority of cAMP hydrolytic activity under all conditions. In cytosolic fractions, PDE3A-118 and PDE3A-94 comprise > 50% of the cAMP hydrolytic activity at 0.1 mu M cAMP, in the absence of Ca2+/calmodulin. At 1.0 mu M cAMP, in the presence of Ca2+/calmodulin, activation of Ca2+/calmodulin-activated (PDE1) and other non-PDE3 phosphodiesterases reduces their contribution to < 20% of cAMP hydrolytic activity. cGMP inhibits cAMP hydrolysis in microsomal fractions by inhibiting PDE3 and in cytosolic fractions by inhibiting both PDE3 and PDE1. These findings indicate that the contribution of PDE3 isoforms to the regulation of cAMP hydrolysis in intracellular compartments of human myocardium and the effects of PDE3 inhibition on cAMP hydrolysis in these compartments are highly dependent on intracellular [Ca2+] and [cAMP], which are lower in failing hearts than in normal hearts. cGMP may amplify cAMP-mediated signaling in intracellular compartments of human myocardium by PDE3-dependent and PDE3-independent mechanisms. C1 Vet Affairs Salt Lake City Hlth Care Syst, Cardiol Sect, Salt Lake City, UT 84148 USA. Univ Utah, Sch Med, Dept Internal Med Cardiol, Salt Lake City, UT 84132 USA. Univ Utah, Sch Med, Dept Pharmacol, Salt Lake City, UT 84132 USA. NHLBI, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Movsesian, MA (reprint author), Vet Affairs Salt Lake City Hlth Care Syst, Cardiol Sect, 500 Foothill Blvd, Salt Lake City, UT 84148 USA. EM matthew.movsesian@hsc.utah.edu NR 70 TC 46 Z9 48 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 25 PY 2005 VL 280 IS 47 BP 39168 EP 39174 DI 10.1074/jbc.M506760200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 985FL UT WOS:000233362200032 PM 16172121 ER PT J AU Lee, JW Kusumoto, R Doherty, KM Lin, GX Zeng, WY Cheng, WH von Kobbe, C Brosh, RM Hu, JS Bohr, VA AF Lee, JW Kusumoto, R Doherty, KM Lin, GX Zeng, WY Cheng, WH von Kobbe, C Brosh, RM Hu, JS Bohr, VA TI Modulation of Werner syndrome protein function by a single mutation in the conserved RecQ domain SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ISOTOPICALLY ENRICHED PROTEINS; BLOOMS-SYNDROME PROTEIN; SYNDROME GENE-PRODUCT; DNA HELICASE; FLAP ENDONUCLEASE-1; SUBSTRATE-SPECIFICITY; COLI RECQ; D-LOOPS; BINDING; REPLICATION AB Naturally occurring mutations in the human RECQ3 gene result in truncated Werner protein (WRN) and manifest as a rare premature aging disorder, Werner syndrome. Cellular and biochemical studies suggest a multifaceted role of WRN in DNA replication, DNA repair, recombination, and telomere maintenance. The RecQ C-terminal (RQC) domain of WRN was determined previously to be the major site of interaction for DNA and proteins. By using site-directed mutagenesis in the WRN RQC domain, we determined which amino acids might be playing a critical role in WRN function. A site-directed mutation at Lys-1016 significantly decreased WRN binding to fork or bubble DNA substrates. Moreover, the Lys-1016 mutation markedly reduced WRN helicase activity on fork, D-loop, and Holliday junction substrates in addition to reducing significantly the ability of WRN to stimulate FEN-1 incision activities. Thus, DNA binding mediated by the RQC domain is crucial for WRN helicase and its coordinated functions. Our nuclear magnetic resonance data on the three-dimensional structure of the wild-type RQC and Lys-1016 mutant proteins display a remarkable similarity in their structures. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Spanish Natl Canc Ctr, Ctr Nacl Invest Oncol, Breast & Gynaecol Canc Grp, Mol Pathol Program, Madrid, Spain. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. Univ Maryland, Ctr Biomol Struct & Org, College Pk, MD 20742 USA. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, Box 1,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bohrv@grc.nia.nih.gov FU Intramural NIH HHS NR 51 TC 29 Z9 31 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 NOV 25 PY 2005 VL 280 IS 47 BP 39627 EP 39636 DI 10.1074/jbc.M506112200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 985FL UT WOS:000233362200086 PM 16150736 ER PT J AU Habibian, R Dzioba, J Barrett, J Galperin, MY Loewen, PC Dibrov, P AF Habibian, R Dzioba, J Barrett, J Galperin, MY Loewen, PC Dibrov, P TI Functional analysis of conserved polar residues in Vc-NhaD, Na+/H+ antiporter of Vibrio cholerae SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; BACILLUS-SUBTILIS; PH; MEMBRANE; PROTEINS; MECHANISM; SODIUM; HISTIDINE-226; EXPRESSION; EXCHANGE AB Vc-NhaD is a Na+/H+ antiporter from Vibrio cholerae with a sharp maximum of activity at pH similar to 8.0. NhaD homologues are present in many bacteria as well as in higher plants. However, very little is known about structure-function relations in NhaD-type antiporters. In this work 14 conserved polar residues associated with putative transmembrane segments of Vc-NhaD have been screened for their possible role in the ion translocation and pH regulation of Vc-NhaD. Substitutions S150A, D154G, N155A, N189A, D199A, T201A, T202A, S389A, N394G, S428A, and S431A completely abolished the Vc-NhaD-mediated Na+-dependent H+ transfer in inside-out membrane vesicles. Substitutions T157A and S428A caused a significant increase of apparent Km values for alkali cations, with the K-m for Li+ elevated more than that for Na+, indicating that Thr-157 and Ser-428 are involved in alkali cation binding/translocation. Of six conserved His residues, mutation of only His-93 and His-210 affected the Na+(Li+)/H+ antiport, resulting in an acidic shift of its pH profile, whereas H93A also caused a 7-fold increase of apparent K-m for Na+ without affecting the Km for Li+. These data suggest that side chains of His-93 and His-210 are involved in proton binding and that His-93 also contributes to the binding of Na+ ions during the catalytic cycle. These 15 residues are clustered in three distinct groups, two located at opposite sides of the membrane, presumably facilitating the access of substrate ions to the third group, a putative catalytic site in the middle of lipid bilayer. The distribution of these key residues in Vc-NhaD molecule also suggests that transmembrane segments IV, V, VI, X, XI, and XII are situated close to one another, creating a transmembrane relay of charged/polar residues involved in the attraction, coordination, and translocation of transported cations. C1 Univ Manitoba, Dept Microbiol, Winnipeg, MB R3T 2N2, Canada. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Dibrov, P (reprint author), Univ Manitoba, Dept Microbiol, Ft Garry Campus,Rm 425 Buller Bldg, Winnipeg, MB R3T 2N2, Canada. EM dibrovp@ms.umanitoba.ca RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 FU Intramural NIH HHS NR 47 TC 14 Z9 17 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 NOV 25 PY 2005 VL 280 IS 47 BP 39637 EP 39643 DI 10.1074/jbc.M509328200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 985FL UT WOS:000233362200087 PM 16186100 ER PT J AU Luzzio, FA Duveau, DY Lepper, ER Figg, WD AF Luzzio, FA Duveau, DY Lepper, ER Figg, WD TI Synthesis of racemic cis-5-hydroxy-3-phthalimidoglutarimide. A metabolite of thalidomide isolated from human plasma SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID GAMMA-HYDROXYGLUTAMIC ACID; IN-VITRO; HYDROXYLATED METABOLITES; AMINO-ACIDS; TNF-ALPHA; ANALOGS; ANGIOGENESIS; DERIVATIVES AB A synthesis of the glutarimide-derived metabolite of thalidomide, 5'-hydroxythalidomide (2), is described. The synthesis employed the lactone derivative of N-benzyloxycarbonyl (CBZ)-protected 4-hydroxyglutamic acid 12, which is prepared by a de novo route from diethyl acetamidomalonate. The reaction of 12 with 4-methoxybenzylamine gave the corresponding isoglutamine, which then provided the key CBZ-protected N-PMB-glutarimide 14 after dehydration. Deprotection of both the CBZ and PMB groups followed by phthalimidation and deacetylation of the 3-amino-5-acetoxyglutarimide 16 afforded 2. C1 Univ Louisville, Dept Chem, Louisville, KY 40292 USA. NCI, Clin Pharmacol, NIH, Bethesda, MD 20892 USA. RP Luzzio, FA (reprint author), Univ Louisville, Dept Chem, 2320 S Brook St, Louisville, KY 40292 USA. EM faluzz01@gwise.louisville.edu RI Figg Sr, William/M-2411-2016 NR 29 TC 16 Z9 16 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD NOV 25 PY 2005 VL 70 IS 24 BP 10117 EP 10120 DI 10.1021/jo0514772 PG 4 WC Chemistry, Organic SC Chemistry GA 987TC UT WOS:000233539200059 PM 16292851 ER PT J AU Leon-Sarmiento, FE Bara-Jimenez, W Wassermann, EM AF Leon-Sarmiento, FE Bara-Jimenez, W Wassermann, EM TI Visual deprivation effects on human motor cortex excitability SO NEUROSCIENCE LETTERS LA English DT Article ID ISCHEMIC NERVE BLOCK; MAGNETIC STIMULATION; RAPID MODULATION; ACTIVATION; MONKEY; DEAFFERENTATION; PLASTICITY; RESPONSES; NEURONS AB Single and paired-pulse transcranial magnetic stimulation (TMS) were applied to the motor cortex of 12 healthy volunteers, who were instructed to relax under eyes-open and eyes-closed conditions with room lights on and after 30 min of blindfolding. Compared to the eyes-open condition, significantly larger motor-evoked potentials and less intracortical inhibition were observed during blindfolding. Visual deafferentation changes resting human motor cortex excitability and might be a novel way to promote brain plasticity. These results raise the issue of how widespread the effects of temporary deafferentation may be and whether they are mediated by discrete or diffuse systems. These findings also illustrate an important potential confound in TMS studies of the motor cortex. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Natl Inst Neurol Disorders & Stroke, Brain Stimulat Unit, NIH, Bethesda, MD USA. Natl Inst Neurol Disorders & Stroke, Expt Therapeut Branch, NIH, Bethesda, MD USA. RP Leon-Sarmiento, FE (reprint author), 1604 Marshall Ave, Rockville, MD 20851 USA. EM feleoness@yahoo.com NR 23 TC 21 Z9 23 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 NOV 25 PY 2005 VL 389 IS 1 BP 17 EP 20 DI 10.1016/j.neulet.2005.06.061 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 964PX UT WOS:000231894100004 PM 16040193 ER PT J AU Hassan, SA AF Hassan, SA TI Amino acid side chain interactions in the presence of salts SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID SOLVENT-INDUCED FORCES; PROTEIN-FOLDING THERMODYNAMICS; LIQUID WATER; MOLECULAR-DYNAMICS; HYDROPHOBIC ATTRACTION; COMPUTER-SIMULATIONS; HYDRATION; ENERGY; ASSOCIATION; SOLVATION AB The effects of salt on the intermolecular interactions between polar/charged amino acids are investigated through molecular dynamics simulations. The mean forces and associated potentials are calculated for NaCl salt in the 0-2 M concentration range at 298 K. It is found that the addition of salt may stabilize or destabilize the interactions, depending on the nature of the interacting molecules. The degree of (de)stabilization is quantified, and the origin of the salt-dependent modulation is discussed based upon an analysis of solvent density profiles. To gain insight into the molecular origin of the salt modulation, spatial distribution functions (sdf's) are calculated, revealing a high degree of solvent structuredness in all cases. The peaks in the sdf's are consistent with long-range hydrogen-bonding networks connecting the solute hydrophilic groups, and that contribute to their intermolecular solvent-induced forces. The restructuring of water around the solutes as they dissociate from close contact is analyzed. This analysis offers clues on how the solvent structure modulates the effective intermolecular interactions in complex solutes. This modulation results from a critical balance between bulk electrostatic forces and those exerted by (i) the water molecules in the structured region between the monomers, which is disrupted by ions that transiently enter the hydration shells, and (ii) the ions in the hydration shells in direct interactions with the solutes. The implications of these findings in protein/ligand (noncovalent) association/dissociation mechanisms are briefly discussed. C1 NIH, Ctr Mol Modeling, Div Computat Biosci, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hassan, SA (reprint author), NIH, Ctr Mol Modeling, Div Computat Biosci, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM mago@helix.nih.gov FU CIT NIH HHS [Z01 CT000265-09]; Intramural NIH HHS NR 53 TC 31 Z9 31 U1 1 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 NOV 24 PY 2005 VL 109 IS 46 BP 21989 EP 21996 DI 10.1021/jp054042r PG 8 WC Chemistry, Physical SC Chemistry GA 986GC UT WOS:000233437100074 PM 16479276 ER PT J AU Smith, DL Dushoff, J Snow, RW Hay, SI AF Smith, DL Dushoff, J Snow, RW Hay, SI TI The entomological inoculation rate and Plasmodium falciparum infection in African children SO NATURE LA English DT Article ID GLOBAL DISTRIBUTION; MALARIA; TRANSMISSION; POPULATION; DISEASE; MODEL; RISK AB Malaria is an important cause of global morbidity and mortality. The fact that some people are bitten more often than others has a large effect on the relationship between risk factors and prevalence of vector-borne diseases(1-3). Here we develop a mathematical framework that allows us to estimate the heterogeneity of infection rates from the relationship between rates of infectious bites and community prevalence. We apply this framework to a large, published data set that combines malaria measurements from more than 90 communities(4). We find strong evidence that heterogeneous biting or heterogeneous susceptibility to infection are important and pervasive factors determining the prevalence of infection: 20% of people receive 80% of all infections. We also find that individual infections last about six months on average, per infectious bite, and children who clear infections are not immune to new infections. The results have important implications for public health interventions: the success of malaria control will depend heavily on whether efforts are targeted at those who are most at risk of infection. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Princeton Univ, Dept Ecol & Evolutionary Biol, Princeton, NJ 08544 USA. KEMRI, Ctr Geog Med, Malaria Publ Hlth & Epidemiol Grp, Kenyatta Hosp, Nairobi 00100, Kenya. Univ Oxford, John Radcliffe Hosp, Ctr Trop Med, Oxford OX3 9DS, England. Univ Oxford, Dept Zool, TALA Res Grp, Oxford OX1 3PS, England. RP NIH, Fogarty Int Ctr, Bldg 16,16 Ctr Dr, Bethesda, MD 20892 USA. EM smitdave@helix.nih.gov RI Smith, David/L-8850-2013; Hay, Simon/F-8967-2015; OI Smith, David/0000-0003-4367-3849; Hay, Simon/0000-0002-0611-7272; Snow, Robert/0000-0003-3725-6088 FU Wellcome Trust [, 058992, 069045] NR 29 TC 147 Z9 148 U1 0 U2 15 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD NOV 24 PY 2005 VL 438 IS 7067 BP 492 EP 495 DI 10.1038/nature04024 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 986NY UT WOS:000233458200048 PM 16306991 ER PT J AU Buchsbaum, BR Olsen, RK Koch, P Berman, KF AF Buchsbaum, BR Olsen, RK Koch, P Berman, KF TI Human dorsal and ventral auditory streams subserve rehearsal-based and echoic processes during verbal working memory SO NEURON LA English DT Article ID SHORT-TERM-MEMORY; PRECATEGORICAL ACOUSTIC STORAGE; POSITRON-EMISSION-TOMOGRAPHY; SUPERIOR TEMPORAL GYRUS; EVENT-RELATED FMRI; SPEECH-PERCEPTION; FUNCTIONAL NEUROANATOMY; SELECTIVE IMPAIRMENT; EPISODIC RETRIEVAL; EXECUTIVE CONTROL AB To hear a sequence of words and repeat them requires sensory-motor processing and something more-temporary storage. We investigated neural mechanisms of verbal memory by using fMRI and a task designed to tease apart perceptually based ("echoic") memory from phonological-articulatory memory. Sets of two- or three-word pairs were presented bimodally, followed by a cue indicating from which modality (auditory or visual) items were to be retrieved and rehearsed over a delay. Although delay-period activation in the planum temporale (PT) was insensible to the source modality and showed sustained delay-period activity, the superior temporal gyrus (STG) activated more vigorously when the retrieved items had arrived to the auditory modality and showed transient delay-period activity. Functional connectivity analysis revealed two topographically distinct fronto-temporal circuits, with STG coactivating more strongly with ventrolateral prefrontal cortex and PT coactivating more strongly with dorsolateral prefrontal cortex. These argue for separate contributions of ventral and dorsal auditory streams in verbal working memory. C1 NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch,Dept Hlth & Human Ser, NIH,Intramural Res Program, Bethesda, MD 20892 USA. RP Buchsbaum, BR (reprint author), NIMH, Sect Integrat Neuroimaging, Clin Brain Disorders Branch,Dept Hlth & Human Ser, NIH,Intramural Res Program, Bethesda, MD 20892 USA. EM buchsbab@intra.nimh.nih.gov OI Olsen, Rosanna/0000-0002-2918-4152 FU Intramural NIH HHS NR 63 TC 135 Z9 136 U1 2 U2 22 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0896-6273 J9 NEURON JI Neuron PD NOV 23 PY 2005 VL 48 IS 4 BP 687 EP 697 DI 10.1016/j.neuron.2005.09.029 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 989MF UT WOS:000233677300020 PM 16301183 ER PT J AU Kirby, TW DeRose, EF Beard, WA Wilson, SH London, RE AF Kirby, TW DeRose, EF Beard, WA Wilson, SH London, RE TI A thymine isostere in the templating position disrupts assembly of the closed DNA polymerase beta ternary complex SO BIOCHEMISTRY LA English DT Article ID INDUCED-FIT MECHANISM; ACTIVE-SITE; STRUCTURAL INSIGHTS; CHEMICAL-SHIFTS; MINOR-GROOVE; FIDELITY; REPAIR; REPLICATION; EFFICIENCY; SEQUENCE AB The high fidelity of the DNA polymerization process is critically important for the stability of the cellular genome. The role of template and incoming nucleotide base pairing, in polymerase fidelity has recently been explored by the use of nucleotide isosteres, which preserve the steric but not the electronic properties of the corresponding bases. The DNA repair enzyme, DNA polymerase beta (Pol beta), is among the most discriminating, being inactive when the thymine isostere difluorotoluene (DFT) is present in the templating base position. To explore the physical basis for this inactivity, we have performed NMR studies on [methyl-C-13]methionine-labeled Pol beta complexed with double-hairpin DNA, used to model the gapped nucleotide substrate, and having either a thymine or a DFT isostere at the templating base position. The six methionine residues distributed throughout the enzyme provide useful conformational probes of the lyase and polymerase domains and subdomains. Analysis of the proton shift of Met282 that results from formation of an abortive Pol beta-gapped DNA-dATP complex is consistent with an open to closed conformational change of the enzyme predicted from crystal structures. In contrast, the same resonance is nearly unshifted when a ternary complex is formed from dATP and gapped DNA in which a DFT isostere replaces thymine at the templating base position. Alternatively, the resonances of Met191 and Met155, located in the catalytic subdomain, show perturbations upon formation of the abortive ternary complex, which are qualitatively similar, but significantly weaker, than the changes observed when thymine is present at the templating base position. The changes in the Met155 and Met191 methyl resonances are in fact more similar to those observed in the binary Pol beta-dATP complex. These studies demonstrate that the block in catalysis is directly related to the absence of the set of conformational transitions that include the "open" to "closed" transition monitored by Met282. C1 NIEHS, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP London, RE (reprint author), NIEHS, Struct Biol Lab, NIH, MR-01,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM london@niehs.nih.gov NR 35 TC 27 Z9 27 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 22 PY 2005 VL 44 IS 46 BP 15230 EP 15237 DI 10.1021/bi0511742 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 986MF UT WOS:000233453000015 PM 16285726 ER PT J AU Goldschmidt-Clermont, PJ Creager, MA Lorsordo, DW Lam, GKW Wassef, M Dzau, VJ AF Goldschmidt-Clermont, PJ Creager, MA Lorsordo, DW Lam, GKW Wassef, M Dzau, VJ TI Atherosclerosis 2005 - Recent discoveries and novel hypotheses SO CIRCULATION LA English DT Article DE aging; atherosclerosis; stem cells; inflammation; genes ID ENDOTHELIAL PROGENITOR CELLS; CORONARY-ARTERY-DISEASE; NITRIC-OXIDE SYNTHASE; C-REACTIVE PROTEIN; VASCULAR ENDOTHELIUM; CARDIOVASCULAR-DISEASE; SHEAR-STRESS; MECHANISMS; RISK; GENES C1 Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. Harvard Univ, Sch Med, Boston, MA USA. Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. Tufts Univ, Sch Med, Div Cardiovasc Res, St Elizabeths Med Ctr, Boston, MA 02111 USA. NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. RP Goldschmidt-Clermont, PJ (reprint author), Duke Univ, Med Ctr, Dept Med, Div Cardiol, Box 3703, Durham, NC 27710 USA. EM Golds017@mc.duke.edu FU NHLBI NIH HHS [P01 HL73042, R01 HL71536]; NIA NIH HHS [R01 AG023073] NR 50 TC 53 Z9 64 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 22 PY 2005 VL 112 IS 21 BP 3348 EP 3353 DI 10.1161/CIRCULATIONAHA.105.577460 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 986CZ UT WOS:000233428200020 PM 16301361 ER PT J AU Liu, XX Rubin, JS Kimmel, AR AF Liu, XX Rubin, JS Kimmel, AR TI Rapid, Wnt-induced changes in GSK3 beta associations that regulate beta-catenin stabilization are mediated by G alpha proteins SO CURRENT BIOLOGY LA English DT Article ID RECEPTOR-RELATED PROTEIN-5; SIGNALING PATHWAY; FRIZZLED FAMILY; AXIN; DROSOPHILA; WINGLESS; PHOSPHORYLATION; TRANSDUCTION; FIBROBLASTS; STABILITY AB Background: In the absence of Writ stimulation, the transcriptional cofactor beta-catenin is destabilized via phosphorylation by protein kinase GSK3 beta in complex with Axin family members. In the "canonical" Wnt signaling pathway, Disheveled (Dvl) is required to functionally inhibit the activity of the GSK3 beta/Axin complex and thereby stabilize b-catenin. Yet, the mechanisms that underlie Wnt regulation of GSK3 and stabilization of b-catenin are still not fully appreciated. Results: Here, we examine time-dependent changes in protein-protein interactions that occur in response to Wnt treatment. We show that GSK3b/Axin complexes are rapidly t(1/2) < 3 min) disrupted upon Wnt stimulation and that changes in GSK3 beta/Axin association substantially precede both P-catenin stabilization and Axin degradation. We further demonstrate that depletion of G alpha(o). or G alpha(q) will inhibit, respectively, the Wnt-induced disruption of GSK3 beta/Axin2 and GSK3 beta/Axin complexes and diminish Wnt stabilization of P-catenin. We also show that direct activation of G proteins in vivo with GTP gamma S in the absence of exogenous Wnt will disrupt GSK3 beta/Axin2 complexes and stabilize beta-catenin. Finally, we demonstrate an association of G alpha(o), with Fz that is also very rapidly (t(1/2) < 1 min) perturbed upon Wnt-3a stimulation and that the Wnt-dependent effects on both GSK3 beta/AxM2 and Ga-o/Fz are pertussis-toxin sensitive. Collectively, these data implicate a role for G proteins in the regulation of Wnt-mediated protein-protein interactions and signaling to beta-catenin. Conclusions: We conclude that rapid disruption of GSK3 beta/Axin interactions in response to Wnt leads to the initial stabilization of beta-catenin and that Gao and G alpha(q) signaling contributes to Wnt-mediated GSK3 beta/Axin disruption and the ultimate stabilization of beta-catenin. C1 NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Kimmel, AR (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM ark1@helix.nih.gov NR 45 TC 137 Z9 143 U1 2 U2 7 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0960-9822 J9 CURR BIOL JI Curr. Biol. PD NOV 22 PY 2005 VL 15 IS 22 BP 1989 EP 1997 DI 10.1016/j.cub.2005.10.050 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 990VI UT WOS:000233770900019 PM 16303557 ER PT J AU Berl, MM Balsamo, LM Xu, B Moore, EN Weinstein, SL Conry, JA Pearl, PL Sachs, BC Grandin, CB Frattali, C Ritter, FJ Sato, S Theodore, WH Gaillard, WD AF Berl, MM Balsamo, LM Xu, B Moore, EN Weinstein, SL Conry, JA Pearl, PL Sachs, BC Grandin, CB Frattali, C Ritter, FJ Sato, S Theodore, WH Gaillard, WD TI Seizure focus affects regional language networks assessed by fMRI SO NEUROLOGY LA English DT Article ID TEMPORAL-LOBE EPILEPSY; RIGHT-HEMISPHERIC ORGANIZATION; FUNCTIONAL MRI; WADA TEST; AUDITORY COMPREHENSION; BRAIN ACTIVATION; SENTENCE COMPREHENSION; DEVELOPMENTAL ASPECTS; PREFRONTAL CORTEX; NEURAL-NETWORKS AB Objective: To investigate the degree of language dominance in patients with left and right hemisphere seizure foci compared to normal volunteers using a fMRI reading comprehension task. Methods: Fifty patients with complex partial epilepsy, aged 8 to 56 years and 33 normal volunteers, aged 7 to 34 had fMRI ( 1.5 T) and neuropsychological testing. Participants silently named an object described by a sentence compared to a visual control. Data were analyzed with region of interest (ROI) analysis based on t maps for inferior frontal gyrus (IFG), midfrontal gyrus (MFG), and Wernicke area (WA). Regional asymmetry indices (AIs) were calculated [( L - R)/( L - R)]; AI > 0.20 was deemed left dominant and AI < 0.20 as atypical language. Results: Left hemisphere focus patients had a higher likelihood of atypical language than right hemisphere focus patients (21% vs 0%, chi(2) < 0.002). Left hemisphere focus patients, excluding those with atypical language, had lower regional AI in IFG, MFG, and WA than controls. Right hemisphere focus patients were all left language dominant and had a lower AI than controls in WA and MFG, but not for IFG. AI in MFG and WA were similar between left hemisphere focus/left language patients and right hemisphere focus patients. Patients activated more voxels than healthy volunteers. Lower AIs were attributable to greater activation in right homologous regions. Less activation in the right-side WA correlated with better verbal memory performance in right focus/left hemisphere-dominant patients, whereas less strongly lateralized activation in IFG correlated better with Verbal IQ in left focus/left hemisphere-dominant patients. Conclusions: Patients had lower asymmetry indices than healthy controls, reflecting increased recruitment of homologous right hemisphere areas for language processing. Greater right hemisphere activation may reflect greater cognitive effort in patient populations, the effect of epilepsy, or its treatment. Regional activation patterns reflect adaptive efforts at recruiting more widespread language processing networks that are differentially affected based on hemisphere of seizure focus. C1 George Washington Univ, Dept Neurosci, Childrens Natl Med Ctr, Sch Med, Washington, DC 20010 USA. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD 20892 USA. NIH, Speech Language Pathol Sect, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. Minnesota Epilepsy Grp, St Paul, MN USA. RP Gaillard, WD (reprint author), George Washington Univ, Dept Neurosci, Childrens Natl Med Ctr, Sch Med, 111 Michigan Ave NW, Washington, DC 20010 USA. EM wgaillar@cnmc.org FU NICHD NIH HHS [P30HD40677]; NINDS NIH HHS [K08-NS1663, R01 NS44280] NR 69 TC 60 Z9 61 U1 7 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 22 PY 2005 VL 65 IS 10 BP 1604 EP 1611 DI 10.1212/01.wnl.0000184502.06647.28 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 986CY UT WOS:000233428100018 PM 16301489 ER PT J AU Vermeulen, R Lan, Q Zhang, LP Gunn, L McCarthy, D Woodbury, RL McGuire, M Podust, VN Li, GL Chatterjee, N Mu, RD Yin, SN Rothman, N Smith, MT AF Vermeulen, R Lan, Q Zhang, LP Gunn, L McCarthy, D Woodbury, RL McGuire, M Podust, VN Li, GL Chatterjee, N Mu, RD Yin, SN Rothman, N Smith, MT TI Decreased levels of CXC-chemokines in serum of benzene-exposed workers identified by array-based proteomics SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE biomarker; leukemia; mass spectrometry; platelet; molecular epidemiology ID SELDI MASS-SPECTROMETRY; PROTEIN PROFILES; CHINESE WORKERS; PLATELET-FACTOR-4; CANCER; HEMATOTOXICITY; NEOPLASMS; DISCOVERY; CELLS AB Benzene is an important industrial chemical and environmental contaminant that causes leukemia. To obtain mechanistic insight into benzene's mechanism of action, we examined the impact of benzene on the human serum proteome in a study of exposed healthy shoe-factory workers and unexposed controls. Two sequential studies were performed, each using sera from 10 workers exposed to benzene (overall mean benzene air level > 30 ppm) and 10 controls. Serum samples were subjected to anion-exchange fractionation and bound to three types of ProteinChip arrays (Ciphergen Biosystems, Fremont, CA) [hydrophobic (11150), metal affinity (IMAC3-Cu), and cation exchange (WCX2)]. Protein-expression patterns were detected by surf ace-enhanced laser desorption/ionization (SELDI)-TOF MS. Three proteins (4.1, 7.7, and 9.3 kDa) were consistently down-regulated in exposed compared with control subjects in both studies. All proteins were highly inversely correlated with individual estimates of benzene exposure (r > 0.75). The 7.7- and 9.3-kDa proteins were subsequently identified as platelet factor (PF)4 and connective tissue activating peptide (CTAP)-III. Initial proteomic results for PF4 and CTAP-III were subsequently confirmed in a single experiment using a ProteinChip-array-based immunoassay(Ciphergen Biosystems). The altered expression of the platelet-derived CXC-chemokines (40% and 63% for PF4 and CTAP-III, respectively) could not be explained by changes in absolute platelet counts. Thus, SELDI-TOF analysis of a limited number of exposed and unexposed subjects revealed that lowered expression of PF4 and CTAP-III proteins is a potential biomarker of benzene's early biologic effects and may play a role in the immunosuppressive effects of benzene. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS, Rockville, MD 20852 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Ciphergen Biosyst, Fremont, CA 94555 USA. China Ctr Dis Control & Prevent, Natl Inst Occupat Hlth & Poison Control, Beijing 100050, Peoples R China. Tianjin Ctr Hlth & Dis Control & Prevent, Tianjin 300011, Peoples R China. RP Vermeulen, R (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS, 6120 Execut Blvd, Rockville, MD 20852 USA. EM vermeulr@mail.nih.gov RI Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 FU NIEHS NIH HHS [R01 ES -6721, P30 ES 01896, P30 ES001896, R01 ES006721] NR 28 TC 40 Z9 47 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 NOV 22 PY 2005 VL 102 IS 47 BP 17041 EP 17046 DI 10.1073/pnas.0508573102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 986PW UT WOS:000233463200026 PM 16286641 ER PT J AU Yang, GB Obiakor, H Sinha, RK Newman, BA Hood, BL Conrads, TP Veenstra, TD Mage, RG AF Yang, GB Obiakor, H Sinha, RK Newman, BA Hood, BL Conrads, TP Veenstra, TD Mage, RG TI Activation-induced deaminase cloning, localization, and protein extraction from young V-H-Mutant rabbit appendix SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mass spectrometry; gene conversion; somatic hypermutation ID INDUCED CYTIDINE DEAMINASE; STRAND BREAK REPAIR; CLASS SWITCH RECOMBINATION; URACIL DNA GLYCOSYLASE; SOMATIC HYPERMUTATION; GENE CONVERSION; B-CELLS; POSITIVE SELECTION; GERMINAL-CENTERS; ALICIA RABBITS AB Studies in mouse, human, and chicken suggest that activation-induced deaminase (AID) is involved in three known processes leading to antibody diversification: somatic hypermutation, gene conversion, and class-switch recombination. Developing rabbit appendix provides a particularly good site for studying all three of these B cell maturation events. We report here successful cloning of rabbit AID and isolation of AID protein from rabbit appendix-cell nuclear and cytoplasmic extracts. We succeeded in identifying and locating AID protein in cells by immunohistochemical and immunofluorescent staining techniques and examined colocalization of AID and other molecules important for Ab diversification. This report extends our knowledge about AID to a mammalian species that uses gene conversion to diversify rearranged Ig genes. Although much work remains to understand fully the mechanism of action of AID and its association with other cellular components, the rabbit system now offers a particularly useful model for future studies of these dynamics. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Frederick, MD 21701 USA. RP Mage, RG (reprint author), NIAID, Immunol Lab, NIH, Bldg 10,Room 11N311,10 Ctr Dr,MSC 1892, Bethesda, MD 20892 USA. EM rm3z@nih.gov FU NCI NIH HHS [N01CO12400, N01 CO 12400] NR 39 TC 20 Z9 20 U1 1 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 NOV 22 PY 2005 VL 102 IS 47 BP 17083 EP 17088 DI 10.1073/pnas.0501338102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 986PW UT WOS:000233463200033 PM 16280388 ER PT J AU Greig, NH Utsuki, T Ingram, DK Wang, Y Pepeu, G Scali, C Yu, QS Mamczarz, J Holloway, HW Giordano, T Chen, DM Furukawa, K Sambamurti, K Brossi, A Lahiri, DK AF Greig, NH Utsuki, T Ingram, DK Wang, Y Pepeu, G Scali, C Yu, QS Mamczarz, J Holloway, HW Giordano, T Chen, DM Furukawa, K Sambamurti, K Brossi, A Lahiri, DK TI Selective butyrylcholinesterase inhibition elevates brain acetylcholine, augments learning and lowers Alzheimer beta-amyloid peptide in rodent SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE anticholinesterase; long-term potentiation; dementia; memory; neurodegeneration ID LONG-TERM POTENTIATION; AGED RATS; HYDROLYZE ACETYLCHOLINE; SYNAPTIC PLASTICITY; PRECURSOR PROTEIN; DISEASE; DEMENTIA; HIPPOCAMPUS; SYSTEMS; MICE AB Like acetylcholinesterase, butyrylcholinesterase (BChE) inactivates the neurotransmitter acetylcholine (ACh) and is hence a viable therapeutic target in Alzheimer's disease, which is characterized by a cholinergic deficit. Potent, reversible, and brain-targeted BChE inhibitors (cymserine analogs) were developed based on binding domain structures to help elucidate the role of this enzyme in the central nervous system. In rats, cymserine analogs caused long-term inhibition of brain BChE and elevated extracellular ACh levels, without inhibitory effects on acetylcholinesterase. In rat brain slices, selective BChE inhibition augmented long-term potentiation. These compounds also improved the cognitive performance (maze navigation) of aged rats. In cultured human SK-N-SH neuroblastoma cells, intra- and extracellular beta-amyloid precursor protein, and secreted beta-amyloid peptide levels were reduced without affecting cell viability. Treatment of transgenic mice that over-expressed human mutant amyloid precursor protein also resulted in lower beta-amyloid peptide brain levels than controls. Selective, reversible inhibition of brain BChE may represent a treatment for Alzheimer's disease, improving cognition and modulating neuropathological markers of the disease. C1 NIA, Neurosci Lab, Baltimore, MD 21224 USA. NIA, Lab Expt Gerontol, Intramural Res Program, Baltimore, MD 21224 USA. Univ Florence, Dept Pharmacol, I-50139 Florence, Italy. Louisiana State Univ, Dept Biochem & Mol Biol, Shreveport, LA 71130 USA. Med Univ S Carolina, Dept Physiol & Neurosci, Charleston, SC 29425 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. Indiana Univ, Sch Med, Dept Psychiat, Inst Psychiat Res, Indianapolis, IN 46202 USA. RP Greig, NH (reprint author), NIA, Neurosci Lab, Baltimore, MD 21224 USA. EM greign@grc.nia.nih.gov FU NIA NIH HHS [R01 AG018884, AG 023055-02, AG 18379, AG 18884, R01 AG018379, R01 AG023055] NR 50 TC 297 Z9 304 U1 0 U2 24 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 NOV 22 PY 2005 VL 102 IS 47 BP 17213 EP 17218 DI 10.1073/pnas.0508575102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 986PW UT WOS:000233463200055 PM 16275899 ER PT J AU Rodriguez-Sosa, M Elizondo, G Lopez-Duran, RM Rivera, I Gonzalez, FJ Vega, L AF Rodriguez-Sosa, M Elizondo, G Lopez-Duran, RM Rivera, I Gonzalez, FJ Vega, L TI Over-production of IFN-gamma and IL-12 in AhR-null mice SO FEBS LETTERS LA English DT Article DE aryl hydrocarbon receptor; immune system; cytokine ID ARYL-HYDROCARBON RECEPTOR; TOXOPLASMA-GONDII INFECTION; CYTOKINE GENE-EXPRESSION; CONTROLS T-CELL; LIPOXIN A(4); TAENIA-CRASSICEPS; DEFICIENT MICE; ACTIVATION; INDUCTION; RESPONSES AB The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that mediates toxicity of environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin. The exposure to AhR agonists results in profound suppression of cellular and humoral immune responses and compromises host to infectious disease. Therefore, to define the role of AhR in the immune response, spleen cells from ovalbumin (OVA)-immunized and naive mice were removed and stimulated in vitro with either OVA or mitogen concanavalin-A (Con A), respectively. Proliferation, CD19+, F4/80+, CD4+ and CD8+ T cells expansion and cytokines production were measured in C57BL/6AhR-/- mice (AhR-/-) and compared with immune response in similarly immunized age-matched wild type (AhR+/+) mice. In response to OVA immunization, AhR-/- mice had similar levels of serum OVA-specific IgG2a, IgG1, and IgG2b compared with AhR+/+ animals. However, AhR-/- mice showed splenomegalia and an increase in B cells. No changes were observed on proliferation and IL-4 secretion, although AhR-/- cells produced more IFN-gamma and IL-12 than AhR+/+ cells. Similar results were observed with Con A stimulation, a decrease on IL-5 and no change on IL-2 secretion were observed on AhR-/- cells compared with AhR+/+ cells in response to Con A stimulation. High levels of IFN-gamma mRNA were detected in AhR-/- lymphocytes, but IL-4 mRNA levels in AhR-/- cells were similar to those in AhR+/+ mice. These data suggest that AhR may play an important role in the normal development and function of immune system by down-regulating IFN-gamma and IL-12 expression. C1 Ctr Invest & Estudios Avanzados, Secc Externa Toxicol, Mexico City 07360, DF, Mexico. Univ Nacl Autonoma Mexico, Unidad Biomed, Fac Estudio Super Iztacala, Mexico City 54090, DF, Mexico. NCI, NIH, Lab Metab, Bethesda, MD 20892 USA. RP Vega, L (reprint author), Ctr Invest & Estudios Avanzados, Secc Externa Toxicol, Av IPN 2508,San Pedro Zacatenco, Mexico City 07360, DF, Mexico. EM lvega@cinvestav.mx RI Vega, Libia/C-3391-2013; OI Vega, Libia/0000-0002-4993-5267; Rodriguez-Sosa, Miriam/0000-0003-2911-9390 NR 33 TC 37 Z9 38 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 21 PY 2005 VL 579 IS 28 BP 6403 EP 6410 DI 10.1016/j.febslet.2005.10.023 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 987LZ UT WOS:000233520700018 PM 16289099 ER PT J AU Weihe, E Schutz, B Hartschuh, W Anlauf, M Schafer, MK Eiden, LE AF Weihe, E Schutz, B Hartschuh, W Anlauf, M Schafer, MK Eiden, LE TI Coexpression of cholinergic and noradrenergic phenotypes in human and nonhuman autonomic nervous system SO JOURNAL OF COMPARATIVE NEUROLOGY LA English DT Article DE cotransmission; vesicular neurotransmitter transporter; vesicular acetylcholine transporter; sympathetic; parasympathetic; skin nerves; cardiac innervation ID VESICULAR ACETYLCHOLINE TRANSPORTER; ECCRINE SWEAT GLANDS; SYMPATHETIC NEURONS; NEUROTRANSMITTER PHENOTYPE; MONOAMINE TRANSPORTER; ENDOCRINE TUMORS; GENE LOCUS; 2 ISOFORMS; EXPRESSION; INNERVATION AB It has long been known that the sympathetic innervation of the sweat glands is cholinergic in most mammalian species and that, during development, rodent sympathetic cholinergic sweat gland innervation transiently expresses noradrenergic traits. We show here that some noradrenergic traits persist in cholinergic sympathetic innervation of the sweat glands in rodents but that lack of expression of the vesicular monoamine transporter renders these cells functionally nonnoradrenergic. Adult human sweat gland innervation, however, is not only cholinergic but coexpresses all of the proteins required for full noradrenergic function as well, including tyrosine hydroxylase, aromatic amino acid decarboxylase, dopamine P-hydroxylase, and the vesicular monoamine transporter VMAT2. Thus, cholinergic/noradrenergic cotransmission is apparently a unique feature of the primate autonomic sympathetic nervous system. Furthermore, sympathetic neurons innervating specifically the cutaneous arteriovenous anastomoses (Hoyer-Grosser organs) in humans also possess a full cholinergic/noradrenergic cophenotype. Cholinergic/noradrenergic coexpression is absent from other portions of the human sympathetic nervous system but is extended in the parasympathetic nervous system to intrinsic neurons innervating the heart. These observations suggest a mode of autonomic regulation, based on corelease of norepinephrine and acetylcholine at parasympathocardiac, sudomotor, and selected vasomotor neuroeffector junctions, that is unique to the primate peripheral nervous system. C1 Univ Marburg, Inst Anat & Cell Biol, Dept Mol Neurosci, D-35033 Marburg, Germany. Univ Heidelberg, Dept Dermatol, D-69120 Heidelberg, Germany. Univ Kiel, Inst Pathol, D-24105 Kiel, Germany. NIMH, Lab Cellular & Mol Regulat, Mol Neurosci Sect, Bethesda, MD 20892 USA. RP Weihe, E (reprint author), Univ Marburg, Inst Anat & Cell Biol, Dept Mol Neurosci, Robert Koch Str 8, D-35033 Marburg, Germany. EM weihe@staff.uni-marburg.de OI Eiden, Lee/0000-0001-7524-944X FU Intramural NIH HHS [Z01 MH002386-21] NR 40 TC 46 Z9 48 U1 1 U2 4 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 NOV 21 PY 2005 VL 492 IS 3 BP 370 EP 379 DI 10.1002/cne.20745 PG 10 WC Neurosciences; Zoology SC Neurosciences & Neurology; Zoology GA 982AD UT WOS:000233128200008 PM 16217790 ER PT J AU Price, DA Brenchley, JM Ruff, LE Betts, MR Hill, BJ Roederer, M Koup, RA Migueles, SA Gostick, E Wooldridge, L Sewell, AK Connors, M Douek, DC AF Price, DA Brenchley, JM Ruff, LE Betts, MR Hill, BJ Roederer, M Koup, RA Migueles, SA Gostick, E Wooldridge, L Sewell, AK Connors, M Douek, DC TI Avidity for antigen shapes clonal dominance in CD8+T cell populations specific for persistent DNA viruses SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID MINOR HISTOCOMPATIBILITY ANTIGENS; CYTOTOXIC T-LYMPHOCYTES; PEPTIDE-MHC COMPLEXES; IN-VIVO; AFFINITY MATURATION; RECEPTOR RECOGNITION; SELECTIVE EXPANSION; FUNCTIONAL AVIDITY; CHRONIC RESPONSE; STRUCTURAL BASIS AB The forces that govern clonal selection during the genesis and maintenance of specific T cell responses are complex, but amenable to decryption by interrogation of constituent clonotypes within the antigen-experienced T cell pools. Here, we used point-mutated peptide-major histocompatibility complex class I ( pMHCI) antigens, unbiased TCRB gene usage analysis, and polychromatic flow cytometry to probe directly ex vivo the clonal architecture of antigen-specific CD8(+) T cell populations under conditions of persistent exposure to structurally stable virus-derived epitopes. During chronic infection with cytomegalovirus and Epstein-Barr virus, CD8(+) T cell responses to immunodominant viral antigens were oligoclonal, highly skewed, and exhibited diverse clonotypic configurations; TCRB CDR3 sequence analysis indicated positive selection at the protein level. Dominant clonotypes demonstrated high intrinsic antigen avidity, defined strictly as a physical parameter, and were preferentially driven toward terminal differentiation in phenotypically heterogeneous populations. In contrast, subdominant clonotypes were characterized by lower intrinsic avidities and proportionately greater dependency on the pMHCI - CD8 interaction for antigen uptake and functional sensitivity. These findings provide evidence that interclonal competition for antigen operates in human T cell populations, while preferential CD8 coreceptor compensation mitigates this process to maintain clonotypic diversity. Vaccine strategies that reconstruct these biological processes could generate T cell populations that mediate optimal delivery of antiviral effector function. C1 NIAID, Human Immunol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIAID, Immunotechnol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Univ Oxford, John Radcliffe Hosp, Nuffield Dept Clin Med, Oxford OX3 9DU, England. RP Price, DA (reprint author), NIAID, Human Immunol Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM davidprice@nih.gov; ddouek@nih.gov RI Roederer, Mario/G-1887-2011; Price, David/C-7876-2013 OI Price, David/0000-0001-9416-2737 FU Medical Research Council [G108/441] NR 55 TC 223 Z9 225 U1 0 U2 4 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 NOV 21 PY 2005 VL 202 IS 10 BP 1349 EP 1361 DI 10.1084/jem.20051357 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 986DK UT WOS:000233429500006 PM 16287711 ER PT J AU Sondergaard, K Kristensen, JL Palner, M Gillings, N Knudsen, GM Roth, BL Begtrup, M AF Sondergaard, K Kristensen, JL Palner, M Gillings, N Knudsen, GM Roth, BL Begtrup, M TI Synthesis and binding studies of 2-arylapomorphines SO ORGANIC & BIOMOLECULAR CHEMISTRY LA English DT Article ID PARKINSONS-DISEASE; DOPAMINE AGONISTS; ERECTILE DYSFUNCTION; ACID IBX; APOMORPHINE; POTENT; CODEINONE; MORPHINE; ANALOGS; DRUG AB From codeine, four different 2-aryl substituted apomorphines were synthesised in 6 steps each. Oxidation of codeine with IBX followed by acid catalysed rearrangement gave morphothebaine, which was selectively triflylated at the 2-position and subsequently O-acetylated at the 11-position. The resulting triflate was coupled in a Suzuki-Miyaura type reaction with a series of 4-substituted arylboronic esters which, after deprotection, gave the desired 2-aryl apomorphines. The analogues were tested for affinity towards a range of dopaminergic, serotonergic and adrenergic receptors. 2-(4-Hydroxyphenyl)-apomorphine exhibited high affinity for the dopamine D, receptor. A putative ligand-receptor interaction was put forward. C1 Danish Univ Pharmaceut Sci, Dept Med Chem, DK-2100 Copenhagen, Denmark. Copenhagen Univ Hosp, Rigshosp, Neurobiol Res Unit, DK-2100 Copenhagen, Denmark. Copenhagen Univ Hosp, Rigshosp, PET & Cyclotron Unit, DK-2100 Copenhagen, Denmark. Case Western Reserve Univ, Dept Biochem, SOM W444, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, NIMH Psychoact Drug Screening Program, Cleveland, OH 44106 USA. RP Begtrup, M (reprint author), Danish Univ Pharmaceut Sci, Dept Med Chem, Univ Pk 2, DK-2100 Copenhagen, Denmark. EM mb@dfuni.dk RI Roth, Bryan/F-3928-2010; Kristensen, Jesper/E-3581-2010; Farma, KU, MedChemGroup/E-7778-2011; Knudsen, Gitte/C-1368-2013; Palner, Mikael/B-2966-2014 OI Kristensen, Jesper/0000-0002-5613-1267; Knudsen, Gitte/0000-0003-1508-6866; Palner, Mikael/0000-0001-6014-2084 NR 31 TC 28 Z9 28 U1 0 U2 2 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1477-0520 J9 ORG BIOMOL CHEM JI Org. Biomol. Chem. PD NOV 21 PY 2005 VL 3 IS 22 BP 4077 EP 4081 DI 10.1039/b507195j PG 5 WC Chemistry, Organic SC Chemistry GA 988KK UT WOS:000233599800021 PM 16267586 ER PT J AU Rollison, DE Shah, KV Major, EO AF Rollison, DE Shah, KV Major, EO TI Response from authors: Re: Investigation of human brain tumors for the presence of polyomavirus genome sequences by two independent laboratories SO INTERNATIONAL JOURNAL OF CANCER LA English DT Letter C1 NINDS, Lab Mol Med & Neurosci, Mol Med & Virol Sect, Bethesda, MD 20892 USA. H Lee Moffit Canc Ctr & Res Inst, Div Canc Prevent & Control, Tampa, FL USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. RP Major, EO (reprint author), NINDS, Lab Mol Med & Neurosci, Mol Med & Virol Sect, Bldg 36,Room 5W21,36 Convent Dr,MSC 4164, Bethesda, MD 20892 USA. EM majorg@ninds.nih.gov NR 1 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 20 PY 2005 VL 117 IS 4 BP 695 EP 696 DI 10.1002/ijc.21162 PG 2 WC Oncology SC Oncology GA 975ML UT WOS:000232666500025 ER PT J AU Schiffmann, R Ries, M AF Schiffmann, R Ries, M TI Fabry's disease - an important risk factor for stroke SO LANCET LA English DT Editorial Material ID ENZYME REPLACEMENT THERAPY; GALACTOSIDASE-A DEFICIENCY; CEREBRAL HYPERPERFUSION; DIALYSIS; REVERSAL C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Schiffmann, R (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. EM RS4e@nih.gov OI Ries, Markus/0000-0002-5054-5741 NR 17 TC 17 Z9 20 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 19 PY 2005 VL 366 IS 9499 BP 1754 EP 1756 DI 10.1016/S0140-6736(05) PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 987KQ UT WOS:000233517200005 PM 16298202 ER PT J AU Pihlstrom, BL Michalowicz, BS Johnson, NW AF Pihlstrom, BL Michalowicz, BS Johnson, NW TI Periodontal diseases SO LANCET LA English DT Review ID CORONARY-HEART-DISEASE; LOW-BIRTH-WEIGHT; HUMAN-IMMUNODEFICIENCY-VIRUS; PAPILLON-LEFEVRE-SYNDROME; C-REACTIVE PROTEIN; SERUM INFLAMMATORY MARKERS; FLAP DEBRIDEMENT SURGERY; TYPE-2 DIABETES-MELLITUS; BONE-MINERAL DENSITY; PRETERM BIRTH AB The periodontal diseases are highly prevalent and can affect up to 90% of the worldwide population. Gingivitis, the mildest form of periodontal disease, is caused by the bacterial biofilm (dental plaque) that accumulates on teeth adjacent to the gingiva (gums). However, gingivitis does not affect the underlying supporting structures of the teeth and is reversible. Periodontitis results in loss of connective tissue and bone support and is a major cause of tooth loss in adults. In addition to pathogenic microorganisms in the biofilm, genetic and environmental factors, especially tobacco use, contribute to the cause of these diseases. Genetic, dermatological, haematological, granulomatous, immunosuppressive, and neoplastic disorders can also have periodontal manifestations. Common forms of periodontal disease have been associated with adverse pregnancy outcomes, cardiovascular disease, stroke, pulmonary disease, and diabetes, but the causal relations have not been established. Prevention and treatment are aimed at controlling the bacterial biofilm and other risk factors, arresting progressive disease, and restoring lost tooth support. C1 Natl Inst Dent & Craniofacial Res, Clin Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Sch Dent, Div Periodontol, Minneapolis, MN 55455 USA. Griffith Univ, Sch Dent & Oral Hlth, Southport, Qld, Australia. RP Pihlstrom, BL (reprint author), Natl Inst Dent & Craniofacial Res, Clin Res Ctr, NIH, Bethesda, MD 20892 USA. EM bruce.pihlstrom@nih.gov NR 198 TC 1145 Z9 1189 U1 45 U2 321 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 19 PY 2005 VL 366 IS 9499 BP 1809 EP 1820 DI 10.1016/S0140-6736(05)67728-8 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 987KQ UT WOS:000233517200027 PM 16298220 ER PT J AU Schneider, MF Gange, SJ Williams, CM Anastos, K Greenblatt, RM Kingsley, L Detels, R Munoz, A AF Schneider, MF Gange, SJ Williams, CM Anastos, K Greenblatt, RM Kingsley, L Detels, R Munoz, A TI Patterns of the hazard of death after AIDS through the evolution of antiretroviral therapy: 1984-2004 SO AIDS LA English DT Article DE AIDS; effectiveness; HAART; hazard; survival ID HUMAN-IMMUNODEFICIENCY-VIRUS; INJECTION-DRUG USERS; CD4 CELL COUNTS; VIRAL LOAD; HIV; WOMEN; MULTICENTER; INFECTION; COHORT; ADHERENCE AB Objective: To characterize changing survival patterns after development of clinical AIDS from 1984 to 2004, when different antiretroviral therapies were being introduced. Design: Cohort of homosexual men since 1984 and cohort of women since 1994. Methods: A total of 1504 men and 461 women were followed for all-cause mortality after an incident AIDS diagnosis. Relative hazards of death and relative times to death were determined in five therapy eras: no/monotherapy (July 1984-December 1989), monotherapy/combination therapy (January 1990-December 1994), HAART introduction (January 1995-June 1998), short-term stable HAART use (July 1998-June 2001), and moderate-term stable HAART use (July 2001 -December 2003). Results: A total of 1057 (54%) study participants died. The time at which 25% of individuals died after an AIDS diagnosis increased significantly from 0.56 years [95% confidence interval (CI), 0.50-0.64] in the no/monotherapy era to 0.74 (95% Cl, 0.67-0.82), 1.78 (95% Cl, 1.29-2.44), 4.22 (95% Cl, 2.94-6.05) and 5.08 years (95% Cl, 2.39-10.79) in the four subsequent therapy eras, respectively. Inferences on the beneficial effects of HAART were confirmed after adjustment by age, sex, type of AIDS diagnosis and CD4 cell count at diagnosis. The pattern of the hazard of death after AIDS changed from increasing in the pre-HAART era to being lower and non-increasing in the eras of HAART. Conclusions: The sustained beneficial effect of HAART, even in individuals with clinical AIDS and extensive treatment histories, attenuates concerns about emergence of resistance but augurs that a substantial number of HIV-infected individuals may require care for very long periods. (C) 2005 Lippincott Williams & Wilkins. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. NIAID, Div AIDS, NIH, Bethesda, MD 20892 USA. Montefiore Med Ctr, Dept Med, Bronx, NY 10467 USA. Montefiore Med Ctr, Dept Epidemiol & Populat Hlth, Bronx, NY 10467 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA USA. Univ Calif Los Angeles, Sch Publ Hlth, Dept Epidemiol, Los Angeles, CA 90024 USA. RP Munoz, A (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Room E7648,615 N Wolfe St, Baltimore, MD 21205 USA. EM jvaldez@jhsph.edu OI Gange, Stephen/0000-0001-7842-512X FU NCRR NIH HHS [M01-RR-00071, M01-RR-00079, 5-M01-RR-00722, M01-RR-00083]; NIAID NIH HHS [UO1-AI-34994, UO-AI-35042, UO-AI-35043, UO1-AI-31834, UO1-AI-34989, UO1-AI-34993, UO1-AI-35004, UO1-AI-35039, UO1-AI-35040, UO1-AI-35041, UO1-AI-37613, UO1-AI-37984, UO1-AI-42590]; OID CDC HHS [UO1-CH-32632] NR 37 TC 87 Z9 92 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 18 PY 2005 VL 19 IS 17 BP 2009 EP 2018 DI 10.1097/01.aids.0000189864.90053.22 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 986IV UT WOS:000233444200010 PM 16260908 ER PT J AU Ackers, M Alexander, SB Allen, M Bakari, M Barsdorf, N Barth-Jones, D Birx, D Cunningham, CK DeCock, K Francis, D Fuchs, J Hemelaar, J Ireland, J Kapoor, S Karamov, E Klein, M Levendal, E Lie, R Macklin, R Mathieson, B Mathur, R Mukengetshibaka, L Nanvubya, A Nakwagala, F Nixon, S Pantaleo, G Pitisuttithum, P Rogers, AS dos Santos, VGV Sheets, R Safrit, J Smit, T Thorpe, P Verlinde, C Villafana, T Warren, M Xu, J Mhalu, F Thior, I Amin, A Bouesseau, MC Chang, ML Henri, M Kieny, MP Labelle, S Malonza, I Obermeyer, CM Osmanov, S Otani, J Pagliusiuhe, S Schmid, G Sigurdson, J Collins, C Hankins, C Thiam, MB AF Ackers, M Alexander, SB Allen, M Bakari, M Barsdorf, N Barth-Jones, D Birx, D Cunningham, CK DeCock, K Francis, D Fuchs, J Hemelaar, J Ireland, J Kapoor, S Karamov, E Klein, M Levendal, E Lie, R Macklin, R Mathieson, B Mathur, R Mukengetshibaka, L Nanvubya, A Nakwagala, F Nixon, S Pantaleo, G Pitisuttithum, P Rogers, AS dos Santos, VGV Sheets, R Safrit, J Smit, T Thorpe, P Verlinde, C Villafana, T Warren, M Xu, J Mhalu, F Thior, I Amin, A Bouesseau, MC Chang, ML Henri, M Kieny, MP Labelle, S Malonza, I Obermeyer, CM Osmanov, S Otani, J Pagliusiuhe, S Schmid, G Sigurdson, J Collins, C Hankins, C Thiam, MB CA WHO-UNAIDS Expert Grp TI Gender, age, and ethnicity in HIV vaccine-related research and clinical trials - Report from a WHO-UNAIDS consultation, 26-28 August 2004. Lausanne, Switzerland SO AIDS LA English DT Article DE HIV vaccines; clinical trials; vaccine efficacy; gender; age; ethnicity; ethics; regulatory aspects; community preparedness ID COST-EFFECTIVENESS; HERD-IMMUNITY; INFECTION; PROGRAMS; EFFICACY; ESCAPE; IMPACT AB This report summarizes the presentations and recommendations from a consultation held in Lausanne, Switzerland (26-28 August 2004) organized by the joint World Health Organization (WHO) - United Nations Programme on HlV/AIDS (UNAIDS) HIV Vaccine Initiative. The consultation discussed issues related to gender, ethnicity, and age in HIV vaccine research and clinical trial recruitment. A special focus of the meeting was the participation of women and adolescents in clinical trials. Also discussed were the experiences and lessons from various research programs, trials, and studies in different countries. Implementing the recommendations from this meeting will require prioritization and active participation from the research community, funders of research, local and national governments, non-governmental organizations, and industry, as well as the individuals and communities participating in clinical trials. This report contains the collective views of an international group of experts, and does not necessarily represent the decisions or the stated policy of the WHO. The contribution of the co-chairs (R. Macklin and F. Mhalu) and the rapporteurs (H. Lasher, M. Klein, M. Ackers, N. Barsdorf, A. Smith Rogers, E. Levendal, T. Villafana and M. Warren) during the consultation and in the preparation of this report is much appreciated. S. Labelle and J. Otani are also acknowledged and thanked for their efficient assistance in the preparation of the consultation and the report. C1 Ctr Dis Control & Prevent, Atlanta, GA USA. HIV Vaccine Trials Network, Washington, DC USA. NIH, Bethesda, MD 20892 USA. Muhimbili Univ, Coll Hlth Sci, Dar Es Salaam, Tanzania. Univ KwaZulu Natal, Sch Psychol, Scottsville, South Africa. Ctr Healthcare Effectiveness Res, Detroit, MI USA. Dept Internal Med, Detroit, MI USA. Walter Reed Army Inst Res, Silver Spring, MD USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. Ctr Dis Control & Prevent, Nairobi, Kenya. San Francisco Dept Publ Hlth, San Francisco, CA USA. Univ Oxford, Sch Med, Oxford, England. Elizabeth Glazer Pediat AIDS Fdn, Washington, DC USA. Int AIDS Vaccine Initiat, New York, NY USA. Minist Hlth, Moscow, Russia. Canadian Network Vaccines & Immunotherapeut, Quebec City, PQ, Canada. S African AIDS Vaccine Initiat, Tygerberg, South Africa. Univ Bergen, Bergen, Norway. Albert Einstein Coll Med, New York, NY USA. Indian Council Med Res, New Delhi, India. Canadian Int Dev Agcy, Quebec City, PQ, Canada. Uganda Virus Res Inst, Entebbe, Uganda. Canadian HIV AIDS Legal Network, Toronto, ON, Canada. CHU Vaudois, CH-1011 Lausanne, Switzerland. Mahidol Univ, Bangkok 10700, Thailand. Ctr Referencia Ensaios Clin HIV AIDS, Rio De Janeiro, Brazil. S African AIDS Vaccine Initiat, Tygerberg, South Africa. Int AIDS Vaccine Initiat, New York, NY USA. Botswana Harvard AIDS Inst, Gaborone, Botswana. AIDS Vaccine Advocacy Coalit, New York, NY USA. Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. Muhmbili Univ, Coll Hlth Sci, Dar Es Salaam, Tanzania. RP Osmanov, S (reprint author), WHO, UNAIDS HIV Vaccine Initiat, Geneva, Switzerland. EM osmanovs@who.int RI Pantaleo, Giuseppe/K-6163-2016 NR 15 TC 4 Z9 4 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 18 PY 2005 VL 19 IS 17 BP W7 EP W28 PG 22 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 986IV UT WOS:000233444200025 ER PT J AU Lee, KO Luu, N Kaneski, CR Schiffmann, R Brady, RO Murray, GJ AF Lee, KO Luu, N Kaneski, CR Schiffmann, R Brady, RO Murray, GJ TI Improved intracellular delivery of glucocerebrosidase mediated by the HIV-1 TAT protein transduction domain SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE glucocerebrosidase; Gaucher disease; enzyme replacement therapy; TAT; protein transduction ID ENZYME REPLACEMENT THERAPY; GAUCHER-DISEASE; BETA-GLUCURONIDASE; BCL-XL; RAT; CELLS; DEFICIENCY AB Enzyme replacement therapy (ERT) for Gaucher disease designed to target glucocerebrosidase (GC) to macrophages via mannose-specific endocytosis is very effective in reversing hepatosplenomegaly, and normalizing hematologic parameters but is less effective in improving bone and lung involvement and ineffective in brain. Recombinant GCs containing an in-frame fusion to the HIV-1 trans-activator protein transduction domain (TAT) were expressed in eukaryotic cells in order to obtain active, normally glycosylated GC fusion proteins for enzyme uptake studies. Despite the absence of mannose-specific endocytic receptors on the plasma membranes of various fibroblasts, the recombinant GCs with C-terminal TAT fusions were readily internalized by these cells. Immunofluorescent confocal microscopy demonstrated the recombinant TAT-fusion proteins with a mixed endosomal and lysosomal localization. Thus, TAT-modified GCs represent a novel strategy for a new generation of therapeutic enzymes for ERT for Gaucher disease. Published by Elsevier Inc. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Murray, GJ (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, Bldg 10,Room 3D04,10 Ctr Dr, Bethesda, MD 20892 USA. EM murrayg@ninds.nih.gov OI Kaneski, Christine/0000-0003-1453-2502 NR 25 TC 15 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD NOV 18 PY 2005 VL 337 IS 2 BP 701 EP 707 DI 10.1016/j.bbrc.2005.05.207 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 977ZF UT WOS:000232841300043 PM 16223608 ER PT J AU Castle, PE Ashfaq, R Ansari, F Muller, CY AF Castle, PE Ashfaq, R Ansari, F Muller, CY TI Immunohistochemical evaluation of heat shock proteins in normal and preinvasive lesions of the cervix SO CANCER LETTERS LA English DT Article DE cervical intraepithelial neoplasia; human papillomavirus (HPV); heat shock proteins; HSP40; HSP60; HSP70; HSP90; immunohistochemistry ID HUMAN-PAPILLOMAVIRUS; OVARIAN-CARCINOMA; IMMUNE-RESPONSE; UTERINE CERVIX; CELL CARCINOMA; EXPRESSION; CANCER; HSP27; HSP90; HSP70 AB Heat Shock Proteins (HSPs) are molecular chaperons with multiple functions relating to cellular homeostasis. Primary, HSPs are expressed in response to cellular stresses that may also include carcinogenesis. Patterns of expression have not been extensively evaluated in the multi-step carcinogenesis of cervical cancer (Normal -> HPV infection -> Cervical Precancer Cancer). We evaluated the expression of HSP40, HSP60, HSP70, and HSP90 in normal tissues (N 30), in cervical intraepithelial neoplasia grade 1 (CIN1)(synonymous with productive HPV infections) (N=32), and in CIN3 (cervical precancer)(N=25) by immunohistochemistry staining (graded 0-3) and compared the results to p16(INK4)a, a biomarker of oncogenic HPV infections and CIN3. We found strong patterns of increased HSP40, HSP60, and HSP70 immunostaining with increasing severity of the lesion in a manner similar to p16(INK4a) (P-Trend < 0.0005). No difference in staining intensity by grade of lesion was observed for HSP90 (P-Trend=0.8). Tissue patterns in CIN3 of diffuse immunostaining for HSP40 and HSP70 were analogous to those observed for p 16(INK4a); HSP60 immunostaining appeared more punctate within cells than for other antigens although similar tissue patterns were observed. We conclude that HSP40, HSP60, and HSP70 expressions are up-regulated in response to the development of CIN3 akin to p16(INK4a) expression. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 NCI, Div Canc Epidemio & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Pathol, Dallas, TX 75230 USA. Univ Texas, SW Med Ctr, Dept Obstet & Gynecol, Dallas, TX 75230 USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemio & Genet, NIH, DHHS, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov NR 25 TC 32 Z9 33 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 18 PY 2005 VL 229 IS 2 BP 245 EP 252 DI 10.1016/j.canlet.2005.06.045 PG 8 WC Oncology SC Oncology GA 984UD UT WOS:000233328900009 PM 16112431 ER PT J AU Plenz, D AF Plenz, D TI Comment on "Critical branching captures activity in living neural networks and maximizes the number of metastable states" SO PHYSICAL REVIEW LETTERS LA English DT Editorial Material C1 NIMH, Unit Neural Network Physiol, Lab Syst Neurosci, Bethesda, MD 20892 USA. RP Plenz, D (reprint author), NIMH, Unit Neural Network Physiol, Lab Syst Neurosci, 35 Convent Dr, Bethesda, MD 20892 USA. EM plenzd@mail.nih.gov NR 2 TC 6 Z9 6 U1 0 U2 3 PU AMERICAN PHYSICAL SOC PI COLLEGE PK PA ONE PHYSICS ELLIPSE, COLLEGE PK, MD 20740-3844 USA SN 0031-9007 J9 PHYS REV LETT JI Phys. Rev. Lett. PD NOV 18 PY 2005 VL 95 IS 21 AR 219801 DI 10.1103/PhysRevLett.95.219801 PG 1 WC Physics, Multidisciplinary SC Physics GA 985FK UT WOS:000233362100077 PM 16384195 ER PT J AU Tassabehji, M Hammond, P Karmiloff-Smith, A Thompson, P Thorgeirsson, SS Durkin, ME Popescu, NC Hutton, T Metcalfe, K Rucka, A Stewart, H Read, AP Maconochie, M Donnai, D AF Tassabehji, M Hammond, P Karmiloff-Smith, A Thompson, P Thorgeirsson, SS Durkin, ME Popescu, NC Hutton, T Metcalfe, K Rucka, A Stewart, H Read, AP Maconochie, M Donnai, D TI GTF2IRD1 in craniofacial development of humans and mice SO SCIENCE LA English DT Article ID WILLIAMS-BEUREN-SYNDROME; TFII-I FAMILY; TRANSCRIPTION FACTORS; GENE-EXPRESSION; BINDING PROTEIN; DELETION; MEMBER; HEMIZYGOSITY; ENHANCER; BEN AB Craniofacial abnormalities account for about one-third of all human congenital defects, but our understanding of the genetic mechanisms governing craniofacial development is incomplete. We show that GTF2/RD1 is a genetic determinant of mammalian craniofacial and cognitive development, and we implicate another member of the TFII-I transcription factor family, GTF2I, in both aspects. Gtf2ird1-null mice exhibit phenotypic abnormalities reminiscent of the human microdeletion disorder Williams-Beuren syndrome (WBS); craniofacial imaging reveals abnormalities in both skull and jaws that may arise through misregulation of goosecoid, a downstream target of Gtf2ird1. In humans, a rare WBS individual with an atypical deletion, including GTF2IRD1, shows facial dysmorphism and cognitive deficits that differ from those of classic WBS cases. We propose a mechanism of cumulative dosage effects of duplicated and diverged genes applicable to other human chromosomal disorders. C1 Univ Manchester, St Marys Hosp, Acad Unit Med Genet, Manchester M13 9PL, Lancs, England. UCL, Eastman Dent Inst, London WC1E 6BT, England. UCL, Inst Child Hlth, London WC1E 6BT, England. NCI, Bethesda, MD 20892 USA. Churchill Hosp, Oxford OX3 7LJ, England. Univ Sussex, Sch Life Sci, Brighton BN1 9RH, E Sussex, England. RP Tassabehji, M (reprint author), Univ Manchester, St Marys Hosp, Acad Unit Med Genet, Manchester M13 9PL, Lancs, England. EM m.tassabehji@manchester.ac.uk RI Karmiloff-Smith, Annette/N-4535-2014 OI Karmiloff-Smith, Annette/0000-0002-2470-5609 FU Wellcome Trust NR 26 TC 117 Z9 120 U1 0 U2 7 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD NOV 18 PY 2005 VL 310 IS 5751 BP 1184 EP 1187 DI 10.1126/science.1116142 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 986GE UT WOS:000233437300045 PM 16293761 ER PT J AU Dudko, OK Berezhkovskii, AM Weiss, GH AF Dudko, OK Berezhkovskii, AM Weiss, GH TI Time-dependent diffusion coefficients in periodic porous materials SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID SELF-DIFFUSION; LIGAND-BINDING; MACROMOLECULES; RECEPTORS; COLLOIDS; RELEASE; SYSTEMS; MEDIA; RATES AB We derive an approximate solution for the Laplace transform of the time-dependent diffusion coefficient, D(t), of a molecule diffusing in a periodic porous material. In our model, the material is represented by a simple cubic lattice of identical cubic cavities filled with a solvent and connected by small circular apertures in otherwise reflecting cavity walls, the thickness of which can be neglected. The solution describes the decrease of D(t) from its initial value, D(0) = D, where D is the diffusion constant in the free solvent, to its asymptotic value, D(infinity) = D-eff, which is much smaller than D. A simple heuristic formula for the mean-squared displacement of the diffusing molecule is suggested. The theoretically predicted results are in good agreement with the data obtained from Brownian dynamics simulations. C1 NIH, Div Computat Biosci, Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD 20892 USA. RP Dudko, OK (reprint author), NIH, Div Computat Biosci, Ctr Informat Technol, Math & Stat Comp Lab, Bethesda, MD 20892 USA. NR 32 TC 31 Z9 31 U1 3 U2 7 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 NOV 17 PY 2005 VL 109 IS 45 BP 21296 EP 21299 DI 10.1021/jp051172r PG 4 WC Chemistry, Physical SC Chemistry GA 984CR UT WOS:000233280600009 PM 16853761 ER PT J AU Schiffman, M Castle, PE AF Schiffman, M Castle, PE TI The promise of global cervical-cancer prevention SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PARTICLE VACCINE; YOUNG-WOMEN; EFFICACY; TYPE-18; TRIAL C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Prevent, NIH, Bethesda, MD 20892 USA. RP Schiffman, M (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Prevent, NIH, Bethesda, MD 20892 USA. NR 3 TC 121 Z9 127 U1 1 U2 7 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 NOV 17 PY 2005 VL 353 IS 20 BP 2101 EP 2104 DI 10.1056/NEJMp058171 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 984FT UT WOS:000233288600001 PM 16291978 ER PT J AU Meltzer, PS AF Meltzer, PS TI Genetic diversity in melanoma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 NHGRI, Mol Genet Sect, Canc Genet Branch, Bethesda, MD 20892 USA. RP Meltzer, PS (reprint author), NHGRI, Mol Genet Sect, Canc Genet Branch, Bethesda, MD 20892 USA. NR 4 TC 4 Z9 5 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 NOV 17 PY 2005 VL 353 IS 20 BP 2104 EP 2107 DI 10.1056/NEJMp058173 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 984FT UT WOS:000233288600002 PM 16291979 ER PT J AU Yanovski, SZ AF Yanovski, SZ TI Pharmacology for obesity - Promise and uncertainty. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID WEIGHT-LOSS; INTERVENTION; REDUCTION; TRIAL C1 NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. RP Yanovski, SZ (reprint author), NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. NR 16 TC 25 Z9 25 U1 1 U2 4 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 17 PY 2005 VL 353 IS 20 BP 2187 EP 2189 DI 10.1056/NEJMe058243 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 984FT UT WOS:000233288600013 PM 16291989 ER PT J AU Mulshine, JL Sullivan, DC AF Mulshine, JL Sullivan, DC TI Lung-cancer screening - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NCI, Bethesda, MD 20892 USA. NCI, Rockville, MD 20852 USA. RP Mulshine, JL (reprint author), NCI, Bethesda, MD 20892 USA. EM james_l_mulshine@rush.edu NR 4 TC 0 Z9 0 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 17 PY 2005 VL 353 IS 20 BP 2194 EP 2195 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 984FT UT WOS:000233288600023 ER PT J AU Acton, RT Barton, JC Passmore, L Adams, PC Speechley, MR Dawkins, FW Sholinsky, P Reboussin, DM McLaren, GD Harris, EL Bent, TC Vogt, T Castro, O AF Acton, RT Barton, JC Passmore, L Adams, PC Speechley, MR Dawkins, FW Sholinsky, P Reboussin, DM McLaren, GD Harris, EL Bent, TC Vogt, T Castro, O TI Relationships of serum ferritin, transferrin saturation, and HFE mutations and self-reported diabetes mellitus in the hemochromatosis and iron overload screening (HEIRS) study. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. London Hlth Sci Ctr, Dept Med, London, ON, Canada. Univ Western Ontario, London, ON, Canada. Howard Univ, Dept Med, Washington, DC 20059 USA. NHLBI, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Med, Irvine, CA 92717 USA. Vet Affairs Long Beach Healthcare Syst, Hematol Oncol, Long Beach, CA USA. Kaiser Permanente, Ctr Hlth Res, Portland, OR USA. Kaiser Permanente, Ctr Hlth Res, Honolulu, HI USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3713 BP 5B EP 5B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426100012 ER PT J AU Machado, R Steinberg, M Bonds, D Ballas, S Blackwelder, W Barton, B Waclawiw, M Castro, O Gladwin, M AF Machado, R Steinberg, M Bonds, D Ballas, S Blackwelder, W Barton, B Waclawiw, M Castro, O Gladwin, M CA MSH Investigators TI Natriuretic peptide levels correlate with pulmonary pressures and prospective mortality in SCD: Use of this biomarker to identify prevalence and mortality of pulmonary hypertension in the MSH cohort. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. Boston Univ, Boston, MA 02215 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Howard Univ, Washington, DC 20059 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1 BP 5A EP 5A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000002 ER PT J AU Saito, M Phan, RT Morse, HC Pasqualucci, L Dalla-Favera, R AF Saito, M Phan, RT Morse, HC Pasqualucci, L Dalla-Favera, R TI Pathologic co-expression and physical interaction of c-MYC and BCL6 in B-Cell lymphomas. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Inst Canc Genet, New York, NY USA. Herbert Irving Comprehens Canc Ctr, New York, NY USA. NIAID, Immunopathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2 BP 5A EP 5A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000003 ER PT J AU Yau, YY Bolan, CD Cecco, SA Rehak, NN Collins, M Reynolds, J Leitman, SF AF Yau, YY Bolan, CD Cecco, SA Rehak, NN Collins, M Reynolds, J Leitman, SF TI Clinical evaluation of bone mineral density (BMD) and bone metabolism in hereditary hemochromatosis (HH). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Natl Inst Dent & Craniofacial Res, Lab Med, Ctr Clin, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3727 BP 9B EP 10B PN 2 PG 2 WC Hematology SC Hematology GA 986CG UT WOS:000233426100026 ER PT J AU d'Agostino, C Dejam, A Pelletier, M Sibmooh, N Rizzatti, F Schechter, AN AF d'Agostino, C Dejam, A Pelletier, M Sibmooh, N Rizzatti, F Schechter, AN TI Nitrite ion fluxes in human erythocytes. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIDDKD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3731 BP 10B EP 11B PN 2 PG 2 WC Hematology SC Hematology GA 986CG UT WOS:000233426100030 ER PT J AU Alter, BP AF Alter, BP TI Cancer as the initial presentation in patients with Fanconi's anemia. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3745 BP 14B EP 14B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426100044 ER PT J AU Scheinberg, P Nunez, O Wu, CO Young, NS AF Scheinberg, P Nunez, O Wu, CO Young, NS TI Treatment of severe aplastic anemia with combined immunosuppression: Antithymocyte globulin (ATG), cyclosporine A (CSA), and mycophenolate mofetil (MMF). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat, DECA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3758 BP 18B EP 18B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426100057 ER PT J AU Kochenderfer, J Chien, C Simpson, J Gress, R AF Kochenderfer, J Chien, C Simpson, J Gress, R TI A vaccination regimen incorporating the synergistic combination of CpG-containing oligodeoxynucleotides and IL-2 can elicit CD8+T cell responses that effect anti-tumor immunity from T cell repertoires undergoing reconstitution by homeostatic peripheral expansion after BMT. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 61 BP 22A EP 23A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426000062 ER PT J AU Bohn, G Allroth, A Thiel, J Schaffer, AA Brandes, G Glocker, E Teis, D Taub, N Zeidler, C Geffers, R Buer, J Huber, LA Welte, K Grimbacher, B Klein, C AF Bohn, G Allroth, A Thiel, J Schaffer, AA Brandes, G Glocker, E Teis, D Taub, N Zeidler, C Geffers, R Buer, J Huber, LA Welte, K Grimbacher, B Klein, C TI A variant of congenital neutropenia is caused by a 3'-UTR mutation in the gene encoding the endosomal adaptor protein p14 (MAPBPIP). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Hannover Med Sch, Dept Pediat Hematol & Oncol, D-3000 Hannover, Germany. Hannover Med Sch, Dept Cell Biol, D-3000 Hannover, Germany. Univ Freiburg, Dept Clin Immunol, Freiburg, Germany. NIH, Natl Ctr Biotechnol Informat, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Innsbruck Med Univ, Bioctr, Div Cell Biol, Innsbruck, Austria. German Ctr Biotechnol, Dept Mucosal Immun, Braunschweig, Germany. RI Schaffer, Alejandro/F-2902-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 92 BP 31A EP 31A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000093 ER PT J AU Sabaawy, HE Azuma, M Embree, L Starost, MF Hickstein, DD AF Sabaawy, HE Azuma, M Embree, L Starost, MF Hickstein, DD TI TEL-AML1 transgenic zebrafish model of acute lymphoblastic leukemia (ALL) SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NIH, Div Vet Resources, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2005 VL 106 IS 11 MA 102 BP 34A EP 34A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000103 ER PT J AU English, MA Lei, L Blake, T Sood, R Liu, PP AF English, MA Lei, L Blake, T Sood, R Liu, PP TI Mutation in the zebrafish homolog of the RNA helicase DHX8 result in hematopoietic defects SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHGRI, NIH, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 126 BP 41A EP 41A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000127 ER PT J AU Chen, JC Young, NS AF Chen, JC Young, NS TI A murine model of bone marrow failure mediated by disparity in minor histocompatibility antigens. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 132 BP 42A EP 42A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000133 ER PT J AU Montero, A Savani, BN Mielke, S Solomon, SR Childs, R Barrett, AJ AF Montero, A Savani, BN Mielke, S Solomon, SR Childs, R Barrett, AJ TI T-cell depleted PBSCT mitigates acute GVHD, but preserves protective chronic GVHD. Long term follow up of 138 patients. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 140 BP 44A EP 45A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426000141 ER PT J AU Stroncek, DF Shankar, RA Skubitz, KM AF Stroncek, DF Shankar, RA Skubitz, KM TI Subcelluar distribution of myeloid-related protein 8 (MRP8) and MRP14 in human neutrophils. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. 3M Pharmaceut, St Paul, MN USA. Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. Masonic Canc Ctr, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3864 BP 47B EP 47B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426100163 ER PT J AU Iqbal, J Greiner, TC Patel, K Ji, J Dave, BJ Horsman, DE Shen, Y Weisenburger, DD Campo, E Rosenwald, A Gascoyne, RD Jaffe, ES Ott, G Delabie, J Rimsza, L McKeithan, T Staudt, LM Chan, WC AF Iqbal, J Greiner, TC Patel, K Ji, J Dave, BJ Horsman, DE Shen, Y Weisenburger, DD Campo, E Rosenwald, A Gascoyne, RD Jaffe, ES Ott, G Delabie, J Rimsza, L McKeithan, T Staudt, LM Chan, WC TI Distinctive patterns of BCL6 molecular alterations in different subsets of diffuse large B-cell lymphoma and their functional consequences. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Nebraska, Med Ctr, Omaha, NE 68182 USA. Univ Barcelona, Barcelona, Spain. BCCA, Vancouver, BC, Canada. Univ Wurzburg, Wurzburg, Germany. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Norwegian Radium Hosp, Oslo, Norway. Univ Arizona, Tucson, AZ USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 160 BP 50A EP 50A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000161 ER PT J AU Goldman, JM Hughes, T Radich, J Branford, S Hochhaus, A So, C Gathmann, I Wehrle, E Kaeda, J AF Goldman, JM Hughes, T Radich, J Branford, S Hochhaus, A So, C Gathmann, I Wehrle, E Kaeda, J TI Continuing reduction in level of residual disease after 4 years in patients with CML in chronic phase responding to first-line imatinib (IM) in the IRIS study. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Inst Med & Vet Sci, Adelaide, SA 5000, Australia. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Heidelberg, Med Klin Mannheim 3, D-6800 Mannheim, Germany. Novartis Pharmaceut, E Hanover, NJ USA. Novartis Pharm AG, Basel, Switzerland. Hammersmith Hosp, London, England. NR 0 TC 15 Z9 16 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 163 BP 51A EP 51A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000164 ER PT J AU Seggewiss, R Lore, K Guenaga, FJ Pittaluga, S Matappallil, JJ Ambrozak, D Bailer, RT Koup, RA Donahue, RE Blazar, BR Hollander, GA Douek, DC Dunbar, CE AF Seggewiss, R Lore, K Guenaga, FJ Pittaluga, S Matappallil, JJ Ambrozak, D Bailer, RT Koup, RA Donahue, RE Blazar, BR Hollander, GA Douek, DC Dunbar, CE TI Keratinocyte growth factor increases thymic output of naive T-cells after total body irradiation and autologous peripheral blood progenitor cell transplantation in rhesus macaques. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, Immunol Lab, DHHS,NIH, Bethesda, MD 20892 USA. NIAID, Human Immunol Sect, Immunol Lab, DHHS,NIH, Bethesda, MD 20892 USA. NCI, DHHS, Hematopathol Sect, NIH, Bethesda, MD 20892 USA. NIAID, DHHS, Immuno Technol Sect, Vaccine Res Ctr,NIH, Bethesda, MD 20892 USA. Pediat Blood & Marrow Transplantat Program, Dept Pediat, Minneapolis, MN USA. Univ Basel, Dept Res, Basel, Switzerland. Univ Basel, Dept Clin Biol Sci, Basel, Switzerland. Univ Chicago Hosp, Basel, Switzerland. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 187 BP 58A EP 58A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000188 ER PT J AU Mariotti, J Foley, J Borenstein, T Han, S Fowler, DH AF Mariotti, J Foley, J Borenstein, T Han, S Fowler, DH TI Rapamycin generated murine Th2/Tc2 cells potently abrogate fully MHC-mismatched hematopoietic stem cell (HSC) graft rejection. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 192 BP 59A EP 60A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426000193 ER PT J AU Solomou, EE Keyvanfar, K Young, NS AF Solomou, EE Keyvanfar, K Young, NS TI Decreased TCR zeta-chain expression in T cells from patients with aplastic anemia. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3916 BP 59B EP 59B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426100215 ER PT J AU Du, Y Jenkins, NA Copeland, NG AF Du, Y Jenkins, NA Copeland, NG TI Insertional mutagenesis identifies genes that promote the immortalization/self-renewal of primary bone marrow progenitor cells. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Mouse Canc Genet Program, Frederick, MD 21701 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 193 BP 60A EP 60A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000194 ER PT J AU Bracci, L Stroncek, DF Slezak, S Spagnoli, GC Provenzano, M AF Bracci, L Stroncek, DF Slezak, S Spagnoli, GC Provenzano, M TI Comprehensive analysis of CD8 T cell immune response specific for two novel HLA-A*0201 restricted CMV pp65 peptides. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Basel Hosp, Div Res, CH-4031 Basel, Switzerland. Ist Super Sanita, I-00161 Rome, Italy. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2005 VL 106 IS 11 MA 3928 BP 62B EP 62B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426100227 ER PT J AU Kim-Shapiro, DB Azarov, I Huang, KT Hogg, N Gladwin, MT AF Kim-Shapiro, DB Azarov, I Huang, KT Hogg, N Gladwin, MT TI Hematocrit and oxygen dependence of nitric oxide scavenging by red blood cells. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Med Coll Wisconsin, Free Radical Res Ctr, Milwaukee, WI 53226 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 205 BP 63A EP 63A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000206 ER PT J AU Sachdev, V Machado, RF Shizukudu, Y Rao, Y Sidenko, S Ernst, I Peter, MS Coles, WA Rosing, D Blackwelder, WC Castro, O Kato, GJ Gladwin, MT AF Sachdev, V Machado, RF Shizukudu, Y Rao, Y Sidenko, S Ernst, I Peter, MS Coles, WA Rosing, D Blackwelder, WC Castro, O Kato, GJ Gladwin, MT TI Diastolic dysfunction is an independent risk factor for death in patients with sickle cell disease. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Echocardiog Lab, Cardiovasc Branch, Bethesda, MD 20892 USA. NHLBI, Vasc Therapeut Sect, Cardiovasc Branch, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. Howard Univ, Coll Med, Ctr Sickle Cell Dis, Washington, DC 20059 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 206 BP 63A EP 64A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426000207 ER PT J AU Hsu, LL Champion, HC Manci, E Diwan, B Schimel, D Cochard, A Wang, X Holtzclaw, JD Schechter, A Noguchi, CT Gladwin, M AF Hsu, LL Champion, HC Manci, E Diwan, B Schimel, D Cochard, A Wang, X Holtzclaw, JD Schechter, A Noguchi, CT Gladwin, M TI Spontaneous pulmonary hypertension in Transgenic sickle cell mice - Hemodynamics and histology suggest abnormal nitric oxide production and scavenging. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 St Christophers Hosp Children, Marian Anderson Sickle Cell Ctr, Philadelphia, PA 19133 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Univ S Alabama, Sickle Cell Pathol Unit, Mobile, AL 36688 USA. NCI, SAIC, Frederick, MD 21701 USA. NASA, Lyndon B Johnson Space Ctr, Houston, TX 77058 USA. NIH, Bethesda, MD 20892 USA. RI Hsu, Lewis/A-3360-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 208 BP 64A EP 64A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000209 ER PT J AU Piekarz, RL Frye, R Turner, M Wright, J Allen, S Kirschbaum, MH Zain, J Prince, M Bates, SE AF Piekarz, RL Frye, R Turner, M Wright, J Allen, S Kirschbaum, MH Zain, J Prince, M Bates, SE TI Completion of the first cohort of patients with cutaneous T-cell lymphoma enrolled on a phase II trial of depsipeptide. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Natl Canc Inst, Canc Res Ctr, Bethesda, MD USA. NCI, CTEP, Bethesda, MD 20892 USA. N Shore Univ Hosp, Manhasset, NY USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 231 BP 71A EP 71A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000232 ER PT J AU Svensson, A Whiteley, G Callas, P Bovill, E AF Svensson, A Whiteley, G Callas, P Bovill, E TI Surface-enhanced laser desorption/ionization mass spectral plasma profiles distinguish individuals of a protein C-deficient family with a thrombotic episode before the age of 40 from age-matched family members without a history of thrombosis. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Vermont, Burlington, VT USA. NCI, Clin Proteom Reference Lab, SAIC Frederick, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 261 BP 79A EP 80A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426000262 ER PT J AU Takahashi, Y Tawab, A Kurlander, R Elshal, M Bolan, C Read, EJ Leitman, S McCoy, JP Lundqvist, A Bahceci, E Childs, R AF Takahashi, Y Tawab, A Kurlander, R Elshal, M Bolan, C Read, EJ Leitman, S McCoy, JP Lundqvist, A Bahceci, E Childs, R TI AMD3100 mobilized apheresis products are rich in T-cells that do not undergo a Th-2 type cytokine polarization: Implications for allografting. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NHLBI, Flow Cytometry Core, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Sect Med Oncol, New Haven, CT USA. RI Elshal, Mohamed/H-7953-2012 NR 0 TC 4 Z9 4 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 296 BP 90A EP 90A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000297 ER PT J AU Francischetti, IMB Seydel, KB Monteiro, RQ AF Francischetti, IMB Seydel, KB Monteiro, RQ TI Critical role of the blood coagulation in malaria: Plasmodium falciparum-infected red blood cells induce tissue factor expression by endothelial cells and support the assembly of coagulation complexes. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. Univ Fed Rio de Janeiro, Inst Bioquim Med, Rio De Janeiro, Brazil. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 4044 BP 91B EP 91B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426100343 ER PT J AU Castro, O Kato, G Sachdev, V Machado, R Ernst, I Coles, WA Nichols, JS Hunter, LA Gladwin, MT AF Castro, O Kato, G Sachdev, V Machado, R Ernst, I Coles, WA Nichols, JS Hunter, LA Gladwin, MT TI The sickle cell-pulmonary hypertension screening study: ECHO findings at two-years of follow up. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Howard Univ, Coll Med, Ctr Sickle Cell Dis, Washington, DC 20059 USA. NIH, Ctr Clin, Crit Care Dept, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 314 BP 95A EP 96A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426000315 ER PT J AU Dave, SS Fu, K Wright, G Lam, L Greiner, TC Weisenberger, DD Kluin, PM Boerma, E Rosenwald, A Ott, G Muller-Hermelink, HK Gascoyne, RD Delabie, J Rimsza, LM Braziel, RM Grogan, TM Campo, E Jaffe, ES Vose, J Armitage, JO Connors, JM Smeland, EB Kvaloy, S Holte, H Miller, TP Fisher, RI Montserrat, E Wilson, WH Bahl, M Zhao, H Yang, L Powell, J Simon, R Chan, WC Staudt, LM AF Dave, SS Fu, K Wright, G Lam, L Greiner, TC Weisenberger, DD Kluin, PM Boerma, E Rosenwald, A Ott, G Muller-Hermelink, HK Gascoyne, RD Delabie, J Rimsza, LM Braziel, RM Grogan, TM Campo, E Jaffe, ES Vose, J Armitage, JO Connors, JM Smeland, EB Kvaloy, S Holte, H Miller, TP Fisher, RI Montserrat, E Wilson, WH Bahl, M Zhao, H Yang, L Powell, J Simon, R Chan, WC Staudt, LM TI Gene expression distinguishes Burkitt lymphoma from other aggressive lymphomas and identifies patients who are highly curable with intensive chemotherapeutic regimens. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, CCR, Bethesda, MD 20892 USA. Univ Nebraska, Lincoln, NE 68583 USA. Univ Groningen, Med Ctr, Groningen, Netherlands. Univ Wurzburg, Wurzburg, Germany. British Columbia Canc Agcy, Vancouver, BC, Canada. Univ Barcelona, Barcelona, Spain. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 415 BP 125A EP 125A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000416 ER PT J AU Bauer, TR Allen, JM Tuschong, LM Olson, EM Burkholder, T Hickstein, DD Russell, DW AF Bauer, TR Allen, JM Tuschong, LM Olson, EM Burkholder, T Hickstein, DD Russell, DW TI Therapeutic levels of gene corrected neutrophils following foamy viral vector mediated gene transfer in a canine model of leukocyte adhesion deficiency. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NIH, Div Vet Serv, Off Res Serv, Bethesda, MD 20892 USA. Univ Washington, Dept Hematol, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 458 BP 138A EP 138A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000459 ER PT J AU Hai, M Bauer, TR Sokolic, RA Go, YC Tuschong, LM Hickstein, DD AF Hai, M Bauer, TR Sokolic, RA Go, YC Tuschong, LM Hickstein, DD TI Expression of CD18 in leukocytes following retroviral mediated gene transfer reverses the clinical phenotype in canine leukocyte adhesion deficiency. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RI Sokolic, Robert/I-6072-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 459 BP 138A EP 139A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426000460 ER PT J AU Lauchle, JO Kim, DLD Tran, M Peterson, A Przybranowski, S Parada, L Wolff, L Leopold, J Shannon, KM AF Lauchle, JO Kim, DLD Tran, M Peterson, A Przybranowski, S Parada, L Wolff, L Leopold, J Shannon, KM TI Disease stage strongly modulates responsiveness to targeted agents in Nf1 mutant mice with myeloprolfierative disease (MPD) and acute myeloid leukemia (AML) SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calgary, Calgary, AB T2N 1N4, Canada. Pfizer, Ann Arbor, MI USA. NCI, Bethesda, MD 20892 USA. Univ Texas SW, Dallas, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 496 BP 148A EP 149A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426000497 ER PT J AU Gallagher, PG Arcasoy, MO Vayda, SE Dressman, HK Bieker, JJ Bodine, DM AF Gallagher, PG Arcasoy, MO Vayda, SE Dressman, HK Bieker, JJ Bodine, DM TI A differentiation block in erythroid cells lacking erythroid krupple-like factor (EKLF). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Yale Univ, Sch Med, New Haven, CT USA. Duke Univ, Med Ctr, Durham, NC USA. NHGRI, GMMB, NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 526 BP 157A EP 157A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426000527 ER PT J AU Chavakis, T Orlova, V Song, K Andrei-Selmer, CL Santoso, S AF Chavakis, T Orlova, V Song, K Andrei-Selmer, CL Santoso, S TI Heterophilic and homophilic interactions of junctional adhesion molecule-C (JAM-C) mediate different intercellular adhesive interactions. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Giessen, Inst Clin Immunol & Transfus Med, D-6300 Giessen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 534 BP 159A EP 159A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001003 ER PT J AU Pawelczyk, E Arbab, AS Pundit, S Frank, JA AF Pawelczyk, E Arbab, AS Pundit, S Frank, JA TI Cellular iron metabolism studies demonstate safety of magnetic tracking of mesenchymal stem cells. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIH, Mol Imaging Lab, Ctr Clin, Bethesda, MD 20892 USA. Henry Ford Hlth Syst, Dept Radiol, Detroit, MI USA. NIH, Expt Neuroimaging Sect, Lab Diagnost Radiol Res, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 4320 BP 160B EP 160B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426101023 ER PT J AU Herby, S Milliron, M Mackall, C Fry, T AF Herby, S Milliron, M Mackall, C Fry, T TI Subclinical GVHD impairs responses to dendritic cell vaccines following allogeneic transplantation. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 571 BP 169A EP 170A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426001040 ER PT J AU Hsieh, M Linde, S Metzger, M Fourney, P Lin, A Donahue, R Tisdale, JF AF Hsieh, M Linde, S Metzger, M Fourney, P Lin, A Donahue, R Tisdale, JF TI Chronic intermittent administration of HIF prolyl hydroxylase inhibitor significantly induces erythropoietin and increases total hemoglobin in normal rhesus macaques. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIDDK, MCHB, NIH, Bethesda, MD USA. FibroGen Inc, San Francisco, CA USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 BP 169A EP 169A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001039 ER PT J AU Mielke, S Rezvani, K Solomon, SR Kilical, Y Savani, BN Wish, L Carter, CS Schindler, J Hensel, N Kurlander, R Read, EJ Vitetta, ES Barrett, AJ AF Mielke, S Rezvani, K Solomon, SR Kilical, Y Savani, BN Wish, L Carter, CS Schindler, J Hensel, N Kurlander, R Read, EJ Vitetta, ES Barrett, AJ TI Reconstitution of regulatory T cells after selective depletion of CD25+host-reactive donor lymphocytes from allografts and association with acute graft-versus-host-disease. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Cell Proc Sect, Dept Transfus Med, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dept Microbiol, Dallas, TX USA. Univ Texas, SW Med Ctr, Ctr Canc Immunobiol, Dallas, TX 75235 USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 595 BP 177A EP 177A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001064 ER PT J AU Rosenberg, PS Alter, BP Bolyard, AA Bonilla, MA Boxer, LA Cham, B Fier, C Freedman, M Kannourakis, G Kinsey, S Schwinzer, B Zeidler, C Welte, K Dale, DC AF Rosenberg, PS Alter, BP Bolyard, AA Bonilla, MA Boxer, LA Cham, B Fier, C Freedman, M Kannourakis, G Kinsey, S Schwinzer, B Zeidler, C Welte, K Dale, DC TI The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Biostat Branch, Rockville, MD USA. NCI, Clin Genet Branch, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 669 BP 197A EP 197A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001138 ER PT J AU Wiestner, A Marti, GE Billings, EM Liu, H Lee, E White, T Wilson, WH AF Wiestner, A Marti, GE Billings, EM Liu, H Lee, E White, T Wilson, WH TI Differential gene expression in CLL cells from bone marrow and peripheral blood suggests a role of bone marrow stroma in leukemic cell proliferation. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NHLBI, Bioinformat Core Facil, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 708 BP 209A EP 209A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001177 ER PT J AU Haack, B McCullar, V Lenvik, T Pitt, M Anderson, S Miller, JS AF Haack, B McCullar, V Lenvik, T Pitt, M Anderson, S Miller, JS TI C-MYC induces KIR expression via a novel control region upstream of the conventional adult KIR promoter. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Minnesota, Dept Med, Minneapolis, MN 55455 USA. NCI, SAIC Frederick, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 764 BP 225A EP 226A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426001233 ER PT J AU Owen, AN Liem, RI Pilon, AM Gallagher, PG Bodine, DM AF Owen, AN Liem, RI Pilon, AM Gallagher, PG Bodine, DM TI Chromatin conformation and a distal regulatory element activate the human erythroid ankyrin-1 promoter. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHGRI, Hematopoiesis Sect, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 803 BP 237A EP 237A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001272 ER PT J AU Anong, WA Mohandas, N An, XL Bodine, DM Markham, NO Gallagher, PG Low, PS AF Anong, WA Mohandas, N An, XL Bodine, DM Markham, NO Gallagher, PG Low, PS TI Adducin forms a bridge between the spectrin-actin junctional complex and band 3 SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Purdue Univ, W Lafayette, IN 47907 USA. New York Blood Inst, New York, NY USA. NHGRI, Hematopoiesis Sect, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 808 BP 238A EP 238A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001277 ER PT J AU Bhanu, NV Lee, YT Oneal, PA Rognerud, CL Ou, CN Miller, JL AF Bhanu, NV Lee, YT Oneal, PA Rognerud, CL Ou, CN Miller, JL TI Silencing reversed: Coordinated expression of embryonic and fetal globin genes in adult human erythroblasts. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. Texas Childrens Hosp, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 821 BP 242A EP 242A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001290 ER PT J AU Goh, SH Joselyn, M Lee, YT Reed, C Miller, JL AF Goh, SH Joselyn, M Lee, YT Reed, C Miller, JL TI Identification of switching-related transcription factors from a comparison of cord and adult human blood reticulocytes transcriptomes. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIDDKD, Mol Med Branch, NIH, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 825 BP 243A EP 243A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001294 ER PT J AU Solomou, EE Keyvanfar, K Sloand, EM Weinstein, B Nunez, O Young, NS AF Solomou, EE Keyvanfar, K Sloand, EM Weinstein, B Nunez, O Young, NS TI T-bet over-expression in T cells from patients with aplastic anemia. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 832 BP 245A EP 245A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001301 ER PT J AU Cerhan, JR Engels, E Cozen, W Davis, S Severson, RK Gridley, G Hartge, P Linet, M AF Cerhan, JR Engels, E Cozen, W Davis, S Severson, RK Gridley, G Hartge, P Linet, M TI Blood transfusion, anesthesia, surgery and risk of non-Hodgkin lymphoma. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Wayne State Univ, Detroit, MI USA. Univ So Calif, Los Angeles, CA USA. NCI, DCEG, Bethesda, MD 20892 USA. Mayo Clin, Coll Med, Rochester, MN USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2005 VL 106 IS 11 MA 4697 BP 254B EP 254B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426101399 ER PT J AU Wiestner, A Dunleavy, K Rizzatti, EG Liu, H Marti, GE White, T Wilson, W AF Wiestner, A Dunleavy, K Rizzatti, EG Liu, H Marti, GE White, T Wilson, W TI Potent single agent activity and tumor selectivity of bortezomib in mantle cell lymphoma: First impressions from a randomized phase II study of EPOCH-rituximab-bortezomib in untreated mantle cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 4744 BP 266B EP 266B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426101446 ER PT J AU Dunleavy, K Wayne, A Little, R Grant, N Steinberg, S Jaffe, ES Pittaluga, S Yarchoan, R Carrasquillo, J Janik, J Wilson, WH AF Dunleavy, K Wayne, A Little, R Grant, N Steinberg, S Jaffe, ES Pittaluga, S Yarchoan, R Carrasquillo, J Janik, J Wilson, WH TI The addition of rituximab to dose-adjusted EPOCH with HAART suspension is highly effective and tolerable in AIDS-related lymphoma (ARL) and allows the delivery of abbreviated chemotherapy SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Natl Canc Inst, Ctr Canc Res, Bethesda, MD USA. Natl Inst Hlth, Ctr Clin, Bethesda, MD USA. RI Carrasquillo, Jorge/E-7120-2010 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 930 BP 273A EP 274A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426001399 ER PT J AU Dunleavy, K Pittaluga, S Janik, J Grant, N Steinberg, S Staudt, L Jaffe, E Wilson, WH AF Dunleavy, K Pittaluga, S Janik, J Grant, N Steinberg, S Staudt, L Jaffe, E Wilson, WH TI Primary mediastinal large B-cell lymphoma (PMBL) outcome is significantly improved by the addition of rituximab to dose adjusted (DA)-EPOCH and overcomes the need for radiation SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Natl Canc Inst, Ctr Canc Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 929 BP 273A EP 273A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001398 ER PT J AU Lin, TS Fischer, B Moran, ME Buckner, MM Shank, R Kraut, EH Porcu, P Farag, SS Eisenbeis, CF Colevas, D Grever, MR Byrd, JC AF Lin, TS Fischer, B Moran, ME Buckner, MM Shank, R Kraut, EH Porcu, P Farag, SS Eisenbeis, CF Colevas, D Grever, MR Byrd, JC TI Flavopiridol, fludarabine and rituximab is a highly active regimen in indolent B-cell lymphoproliferative disorders including mantle cell lymphoma SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Ohio State Univ, Div Hematol & Oncol, Columbus, OH 43210 USA. Natl Canc Inst, Canc Therapy Evaluat Program, Rockville, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 944 BP 278A EP 278A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001413 ER PT J AU Adams, RJ Barredo, J Bonds, DR Brown, C Casella, J Daner, L Gerber, AR Iyer, R Luden, J Miller, S Minniti, C Rana, S Rees, R Rogers, Z Toledano, S Wang, W Ware, R Zimmerman, S AF Adams, RJ Barredo, J Bonds, DR Brown, C Casella, J Daner, L Gerber, AR Iyer, R Luden, J Miller, S Minniti, C Rana, S Rees, R Rogers, Z Toledano, S Wang, W Ware, R Zimmerman, S TI TCD in infants: A report from the BABY HUG Trial SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Med Coll Georgia, Augusta, GA 30912 USA. Med Univ S Carolina, Charleston, SC 29425 USA. NHLBI, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. NICHD, Bethesda, MD 20892 USA. Univ Mississippi, Med Ctr, University, MS 38677 USA. Howard Univ, Coll Med, Washington, DC 20059 USA. SW Texas State Univ, San Marcos, TX 78666 USA. Univ Miami, Sch Med, Coral Gables, FL 33124 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 952 BP 280A EP 280A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001421 ER PT J AU Stevens, WT Reese, AM Wesley, R Stroncek, DF Read, EJ Donohue, T Wayne, AS Fowler, DH Savani, B Barrett, AJ Leitman, SF Childs, RW Bolan, CD AF Stevens, WT Reese, AM Wesley, R Stroncek, DF Read, EJ Donohue, T Wayne, AS Fowler, DH Savani, B Barrett, AJ Leitman, SF Childs, RW Bolan, CD TI Prospective evaluation of immune hemolysis in minor-ABO incompatible reduced-intensity peripheral blood (PB) hematopoietic cell transplantation (HCT) SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. USN, Med Ctr, San Diego, CA 92152 USA. NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 960 BP 282A EP 282A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001429 ER PT J AU Cha, SC Biragyn, A Ruffini, PA Qin, H Neelau, SS Kwak, LW AF Cha, SC Biragyn, A Ruffini, PA Qin, H Neelau, SS Kwak, LW TI Cloning of B cell lymphoma-associated antigens using modified phage displayed expression cDNA library and immune patient sera SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA. NIA, Immunol Lab, Ctr Gerontol Res, Baltimore, MD 21224 USA. Osped Niguarda Ca Granda, Div Oncol Med Falck, Milan, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 977 BP 287A EP 287A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001446 ER PT J AU Elghetany, MT Bryant, BJ Alter, BP AF Elghetany, MT Bryant, BJ Alter, BP TI Bone marrow patterns of expression of p53, caspase-3, Ki-67, P21(waf) and WT-1 proteins may provide a tool to differentiate inherited from acquired cytopenias: A study of 199 patients. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Texas, Med Branch, Galveston, TX 77550 USA. NCI, Clin Canc Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1035 BP 302A EP 302A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001504 ER PT J AU Lu, J Wong, S Basu, A Young, NS Brown, KE AF Lu, J Wong, S Basu, A Young, NS Brown, KE TI Analysis of cytokine profiling in hepatitis-associated aplastic anemia. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1036 BP 302A EP 303A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426001505 ER PT J AU Savage, SA Calado, RT Young, NS Chanock, SJ AF Savage, SA Calado, RT Young, NS Chanock, SJ TI Genetic variation in TERF1 but not TERF2 is associated with aplastic anemia risk. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RI Calado, Rodrigo/G-2619-2011; Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1037 BP 303A EP 303A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001506 ER PT J AU Lemery, SJ More, KF Young, NS Sloand, EM AF Lemery, SJ More, KF Young, NS Sloand, EM TI Daclizumab-Associated erythroderma is associated with rebound increases in CD25-Positive CD4 cells following treatment of aplastic anemia and pure red cell aplasia. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Naval Hosp, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1042 BP 304A EP 304A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001511 ER PT J AU Hill, A Wang, X Sapsford, RJ Russell, RP Farrell, AL Jessop, HA McGawley, GM Oxborough, DL Pleasants, P Richards, SJ Arnold, LM Buchanan, DM Rollinson, S Gladwin, MT Hillmen, P AF Hill, A Wang, X Sapsford, RJ Russell, RP Farrell, AL Jessop, HA McGawley, GM Oxborough, DL Pleasants, P Richards, SJ Arnold, LM Buchanan, DM Rollinson, S Gladwin, MT Hillmen, P TI Nitric oxide consumption and pulmonary hypertension in patients with paroxysmal nocturnal hemoglobinuria. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Leeds Teaching Hosp NHS Trust, Dept Haematol, Leeds, W Yorkshire, England. NHLBI, Vasc Therapeut Sect, NIH, Bethesda, MD 20892 USA. Leeds Teaching Hosp NHS Trust, Dept Echocardiog, Leeds, W Yorkshire, England. Alex Pharmaceut Inc, Dept Discovery Res, Cheshire, CT USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1046 BP 305A EP 305A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001515 ER PT J AU Sloand, EM Shah, S Neal, Y AF Sloand, EM Shah, S Neal, Y TI Dual role of soluble urokinase plasminogen activator receptor released by the paroxysmal nocturnal hemoglobinuria cell in stimulation of proliferation and inhibitor of apoptosis of PNH cells but suppression of normal phenotype cell growth. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1045 BP 305A EP 305A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001514 ER PT J AU Calado, RT Bruno, T Wilkerson, KL Young, NS AF Calado, RT Bruno, T Wilkerson, KL Young, NS TI Evidence for T-cell oligoclonal expansion in aplastic anemia associated with telomerase complex mutations: Pathophysiological and clinical implications. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RI Calado, Rodrigo/G-2619-2011 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1052 BP 307A EP 307A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001521 ER PT J AU Giri, N Batista, D Stratakis, C Tsilou, ET Kim, HJ Alter, BP AF Giri, N Batista, D Stratakis, C Tsilou, ET Kim, HJ Alter, BP TI NCI Fanconi's anemia cohort: Hematology and beyond. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Clin Genet Branch, DCEG, Bethesda, MD 20892 USA. NICHD, Endocrine Branch, Bethesda, MD USA. NEI, Ophthalm Genet & Visual Funct Branch, Bethesda, MD 20892 USA. NIDCD, Neurootol Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1057 BP 308A EP 308A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426001526 ER PT J AU Bahceci, E Komarovskaya, M Kreitman, R Cooper, D Pastan, I AF Bahceci, E Komarovskaya, M Kreitman, R Cooper, D Pastan, I TI Improvement of selective depletion of alloreactive T cells. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Yale Univ, Sch Med, New Haven, CT USA. Natl Canc Inst, Mol Biol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1067 BP 311A EP 311A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002002 ER PT J AU Miwa, H Teramoto, H Patel, V Letwin, N Castellone, MD Imai, N Shikami, M Imamura, A Gutkind, S Nitta, M Lee, NH AF Miwa, H Teramoto, H Patel, V Letwin, N Castellone, MD Imai, N Shikami, M Imamura, A Gutkind, S Nitta, M Lee, NH TI Genes important for disease progression of MDS-leukemia revealed by 40K cDNA microarray. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Aichi Med Univ, Dept Internal Med, Div Hematol, Aichi, Japan. Kojin Hosp, Dept Internal Med, Aichi, Japan. NIDR, Oral & Pharyngeal Canc Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. Inst Genom Res, Dept Funct Genom, Rockville, MD USA. RI Gutkind, J. Silvio/A-1053-2009 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 4929 BP 312B EP 312B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426102031 ER PT J AU Grant, S Karp, JE Koc, ON Cooper, B Luger, S Figg, WD Egorin, M Druker, BJ Jacobberger, JW Ramakrishnan, V Perkins, EB Colevas, AD Roberts, JD AF Grant, S Karp, JE Koc, ON Cooper, B Luger, S Figg, WD Egorin, M Druker, BJ Jacobberger, JW Ramakrishnan, V Perkins, EB Colevas, AD Roberts, JD TI Phase I study of flavopiridol in combination with imatinib mesylate (ST1571, gleevec) in Bcr/Abl plus hematological malignancies. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA USA. Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA. Case Western Reserve Univ, Ireland Canc Ctr, Cleveland, OH 44106 USA. Univ Penn, Ctr Canc, Philadelphia, PA 19104 USA. NCI, Canc Therapeut Branch, Bethesda, MD 20892 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Oregon Hlth Sci Univ, Howard Hughes Med Inst, Portland, OR 97201 USA. NCI, Canc Treatment & Evaluat Program, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1102 BP 321A EP 321A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002037 ER PT J AU Savani, BN Srinivasan, R Montero, A Singh, A Shenoy, A Kamipour, S Childs, R Barrett, AJ AF Savani, BN Srinivasan, R Montero, A Singh, A Shenoy, A Kamipour, S Childs, R Barrett, AJ TI Pulmonary function abnormalities 5 years or more following myeloablative and non-myeloablative allogeneic stem cell transplantation for hematological disorders - Impact of chronic GVHD. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1116 BP 325A EP 325A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002051 ER PT J AU Cozen, W Gebregziabher, M Vandenberg, D Conti, D Coetzee, G Bernstein, L Wang, SS Rothman, N Hartge, P Wang, W Coetzee, S Ingles, SA AF Cozen, W Gebregziabher, M Vandenberg, D Conti, D Coetzee, G Bernstein, L Wang, SS Rothman, N Hartge, P Wang, W Coetzee, S Ingles, SA TI Interleukin-6 promoter and receptor polymorphisms, body mass index and risk of multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ So Calif, Los Angeles, CA USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 5101 BP 357B EP 358B PN 2 PG 2 WC Hematology SC Hematology GA 986CG UT WOS:000233426102203 ER PT J AU Grube, M Moritz, S Obermann, E Rezvani, K Mackensen, A Andreesen, R Holler, E AF Grube, M Moritz, S Obermann, E Rezvani, K Mackensen, A Andreesen, R Holler, E TI Is survivin a possible target antigen for cellular immunotherapy in multiple myeloma? SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Regensburg, D-8400 Regensburg, Germany. NHLBI, Stem Cell Allogen Transplantat Unit, Hematol Branch, NIH, Bethesda, MD 20892 USA. RI Obermann, Ellen/E-7802-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 5145 BP 369B EP 369B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426102247 ER PT J AU Williams, KM Chu, YW Gress, RE AF Williams, KM Chu, YW Gress, RE TI Androgen modulates thymopoiesis by regulating thymocyte precursor immigration. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Natl Canc Inst, Expt Transplantat Immunol Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1271 BP 370A EP 370A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002206 ER PT J AU Samakoglu, S Usachenko, Y Budak-Alpdogan, T Acuto, S DiMarzo, R Maggio, A Tisdale, J Riviere, I Sadelain, M AF Samakoglu, S Usachenko, Y Budak-Alpdogan, T Acuto, S DiMarzo, R Maggio, A Tisdale, J Riviere, I Sadelain, M TI Genetic correction of sickle cell disease by co-regulated gamma-globin transgene expression and beta S interference. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Mem Sloan Kettering Canc Ctr, Lab Gene Transfer & Gene Express, New York, NY 10021 USA. Mem Sloan Kettering Canc Ctr, Gene Transfer & Somat Cell Engn Facil, New York, NY 10021 USA. Unita Ric Piera Cutino, Div Ematol 2, Palermo, Italy. NIDDK, MCHB, NIH, DHHS, Bethesda, MD USA. Mem Sloan Kettering Canc Ctr, Lab Gene Transfer & Gene Express, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1280 BP 372A EP 373A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426002215 ER PT J AU Yoshimitsu, M Siatskas, C Liang, SB Rasaiah, VI Higuchi, K Murray, GJ Takenaka, T Tei, C Brady, RO Medin, JA AF Yoshimitsu, M Siatskas, C Liang, SB Rasaiah, VI Higuchi, K Murray, GJ Takenaka, T Tei, C Brady, RO Medin, JA TI Long-term and sustained correction of the alpha-galactosidase A deficiency in Fabry mice and patient cells receiving lentivirally transduced hematopoietic stem/progenitor cells. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Toronto, Hlth Network, Ontario Canc Inst, Div Stem Cell & Differentiat, Toronto, ON M5S 1A1, Canada. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. Kagoshima Univ, Dept Cardiovasc Resp & Metab Med, Kagoshima 890, Japan. Univ Toronto, Dept Med Biophys, Toronto, ON M5S 1A1, Canada. Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1285 BP 374A EP 374A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002220 ER PT J AU Hu, JQ Ferris, A Hughes, S Dunbar, CE AF Hu, JQ Ferris, A Hughes, S Dunbar, CE TI Avian sarcoma leukosis virus (ASLV) derived retroviral vectors efficiently transduce CD34+cells and have a distinct integration profile in the rhesus macaque transplantation model. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Natl Canc Inst, HIV Drug Resistance Program, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1290 BP 375A EP 375A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002225 ER PT J AU Welniak, LA Berner, V Blazar, BR Wiltrout, RH Murphy, WJ AF Welniak, LA Berner, V Blazar, BR Wiltrout, RH Murphy, WJ TI Antibodies to CD40 promote dendritic cell recovery and anti-tumor effects after syngeneic bone marrow transplant (BMT). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Nevada, Reno, NV 89557 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Natl Canc Inst, Expt Immunol Lab, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1305 BP 379A EP 379A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002240 ER PT J AU Lundqvist, A Samsel, L Eckhaus, M Srinivasan, R Takahashi, Y Snoeijs, M McCoy, PJ Berg, M Childs, R AF Lundqvist, A Samsel, L Eckhaus, M Srinivasan, R Takahashi, Y Snoeijs, M McCoy, PJ Berg, M Childs, R TI Adoptive infusion of allogeneic KIR ligand mismatched NK cells reduce GVHD in an MHC matched allogeneic stem cell transplantation model. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. Natl Inst Hlth, Div Vet Resources, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1310 BP 380A EP 381A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426002245 ER PT J AU Sato, T Neschadim, A Rasaiah, VI Konrad, M Fowler, DH Lavie, A Medin, JA AF Sato, T Neschadim, A Rasaiah, VI Konrad, M Fowler, DH Lavie, A Medin, JA TI Improved suicide gene therapy: Lentiviral gene transfer of equine herpes virus type 4 thymidine kinase into target cells SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 UHN, OCI, Div Stem Cell & Differentiat, Toronto, ON, Canada. Max Planck Inst Biophys Chem, Gottingen, Germany. NCI, Ctr Canc Res, MIH, Bethesda, MD 20892 USA. Univ Illinois, Chicago, IL USA. Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. RI Lavie, Arnon/H-4927-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 5251 BP 396B EP 397B PN 2 PG 2 WC Hematology SC Hematology GA 986CG UT WOS:000233426102352 ER PT J AU Sato, T Neschadim, A Rasaiah, VI Konrad, M Fowler, DH Lavie, A Medin, JA AF Sato, T Neschadim, A Rasaiah, VI Konrad, M Fowler, DH Lavie, A Medin, JA TI A novel suicide gene therapy approach for reduction of GvHD using lentiviral delivery of a modified human thymidylate monophosphate kinase SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 UHN, OCI, Div Stem Cell & Differentiat, Toronto, ON, Canada. Max Planck Inst Biophys Chem, Gottingen, Germany. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Illinois, Chicago, IL USA. Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. RI Lavie, Arnon/H-4927-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 5252 BP 397B EP 397B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426102353 ER PT J AU Scharenberg, C Gessner, M Hoffmann, J Robey, R Neubauer, A Brendel, C AF Scharenberg, C Gessner, M Hoffmann, J Robey, R Neubauer, A Brendel, C TI Hematopoietic stem cells actively extrude imatinib-mesylate due to high ABCG2-transporter activity. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Marburg Giessen Univ, Dept Anat & Cell Biol, Marburg, Germany. Marburg Giessen Univ, Dept Hematol Oncol & Immunol, Marburg, Germany. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2005 VL 106 IS 11 MA 1372 BP 397A EP 397A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002307 ER PT J AU Calado, RT Young, NS Chen, JC AF Calado, RT Young, NS Chen, JC TI Lin-CD1171 hematopoietic cells preferentially home to spleen and their migration is affected by selectins. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RI Calado, Rodrigo/G-2619-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1400 BP 404A EP 405A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426002335 ER PT J AU Savani, BN Montero, A Mielke, S Rezvani, K Shenoy, A Childs, R Barrett, AJ AF Savani, BN Montero, A Mielke, S Rezvani, K Shenoy, A Childs, R Barrett, AJ TI Transplant outcome in acute myeloid but not acute lymphocytic leukemia following T cell depleted allogeneic stem cell transplantation may be favorably influenced by early recovery of NK cells. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1405 BP 406A EP 406A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002340 ER PT J AU Hakim, FT Allen, K Carson, JM Boyiadzis, M Memon, SA Dean, R Odom, J Wayne, A Fowler, D Bishop, MR Gress, RE AF Hakim, FT Allen, K Carson, JM Boyiadzis, M Memon, SA Dean, R Odom, J Wayne, A Fowler, D Bishop, MR Gress, RE TI IL-15 plays a critical role in CD8+T-cell recovery after allogeneic transplantation. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RI Memon, Sarfraz/E-1198-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1414 BP 408A EP 408A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002349 ER PT J AU Boyiadzis, M Carson, J Allen, K Memon, SA Dean, RA Odom, J Bishop, MR Gress, RE Hakim, FT AF Boyiadzis, M Carson, J Allen, K Memon, SA Dean, RA Odom, J Bishop, MR Gress, RE Hakim, FT TI Up-regulation of NK cell activating receptors associated with elevated IL-15 levels post-transplant SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. RI Memon, Sarfraz/E-1198-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1417 BP 409A EP 409A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002352 ER PT J AU Rezvani, K Mielke, S Kilical, Y Savani, B Keyvanfar, K Hensel, N Kurlander, R Barrett, AJ AF Rezvani, K Mielke, S Kilical, Y Savani, B Keyvanfar, K Hensel, N Kurlander, R Barrett, AJ TI Inverse correlation of early regulatory T cell reconstitution post-transplant and acute and chronic graft-versus-host-disease. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. DLM, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1416 BP 409A EP 409A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002351 ER PT J AU Scheinberg, P Fischer, SH Li, L Nunez, O Wu, CO Young, NS Barrett, AJ AF Scheinberg, P Fischer, SH Li, L Nunez, O Wu, CO Young, NS Barrett, AJ TI Subclinical EBV and CMV reactivations commonly occur following antibody-based immunosuppressive regimens for patients with severe aplastic anemia. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Off Biostat, NIH, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1428 BP 412A EP 413A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426002363 ER PT J AU Zhang, XF Wang, JF Kunos, G Goopman, JE AF Zhang, XF Wang, JF Kunos, G Goopman, JE TI The potential role of delta(9)-tetrahydrocannabinol in the pathogenesis of Kaposi's sarcoma. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Surg, BIDMC, Boston, MA 02115 USA. NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1429 BP 413A EP 413A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002364 ER PT J AU Staak, JO Colcher, D Nagata, S Wang, JY Pastan, IH Raubitschek, AA AF Staak, JO Colcher, D Nagata, S Wang, JY Pastan, IH Raubitschek, AA TI CD30 as target for radioimmunotherapy (RIT) of lymphoma. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 City Hope Comprehens Canc Ctr, Div Canc Immunotherapeut & Tumor Immunol, Dept Radioimmunotherapy, Duarte, CA USA. NCI, Canc Res Ctr, Mol Biol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1501 BP 432A EP 432A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002436 ER PT J AU Hardy, NM Fellowes, V Mariotti, J Carter, C June, C Levine, BL Hakim, F Vonderheide, R Gress, R Read, EJ Fowler, D Bishop, MR AF Hardy, NM Fellowes, V Mariotti, J Carter, C June, C Levine, BL Hakim, F Vonderheide, R Gress, R Read, EJ Fowler, D Bishop, MR TI Pilot clinical trial of adoptive immunotherapy with chimeric, co-stimulated tumor-infiltrating lymphocytes after allogeneic hematopoietic stem cell transplantation SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. RI Levine, Bruce/D-1688-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 5407 BP 438B EP 438B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426102508 ER PT J AU Landgren, O Gridley, G Turesson, I Caporaso, NE Goldin, LR Baris, D Fears, TR Hoover, RN Linet, MS AF Landgren, O Gridley, G Turesson, I Caporaso, NE Goldin, LR Baris, D Fears, TR Hoover, RN Linet, MS TI Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African-American and white veterans in the US SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD USA. Lund Univ, Malmo Univ Hosp, Sect Hematol, Dept Med, Malmo, Sweden. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1541 BP 442A EP 442A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002476 ER PT J AU Kang, EM Hsieh, M Powell, JD Link, B Donohue, T Kato, G Machado, R Gladwin, M Rodgers, G Tisdale, JF AF Kang, EM Hsieh, M Powell, JD Link, B Donohue, T Kato, G Machado, R Gladwin, M Rodgers, G Tisdale, JF TI A novel allogeneic transplant conditioning regimen designed for tolerance induction in patients with severe sickle cell disease. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIAID, LHD, NIH, Bethesda, MD 20892 USA. NIDDK, MCHB, NIH, Bethesda, MD USA. Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD USA. NHLBI, HB, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NHLBI, VT Sect, CB, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 5429 BP 443B EP 443B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426102530 ER PT J AU Hanamura I Iida, S Ueda, R Kuehl, M Cullraro, C Bergsagel, L Sawyer, J Barlogie, B Shaughnessy, J AF Hanamura, I Iida, S Ueda, R Kuehl, M Cullraro, C Bergsagel, L Sawyer, J Barlogie, B Shaughnessy, J TI Identification of three novel chromosomal translocation partners involving the immunoglobulin loci in newly diagnosed myeloma and human myeloma cell SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR USA. Nagoya City Univ, Dept Internal Med, Nagoya, Aichi, Japan. Grad Sch Med Sci, Kawasumi, Japan. Natl Canc Inst, Genet Branch, Bethesda, MD USA. Mayo Clin, Scottsdale, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1552 BP 445A EP 445A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002487 ER PT J AU Kiziltepe, T Ishitsuka, K Hideshima, T Raje, N Shiraishi, N Yasui, H Catley, L Chauhan, D Saavedra, JE Keefer, LK Shami, PJ Anderson, KC AF Kiziltepe, T Ishitsuka, K Hideshima, T Raje, N Shiraishi, N Yasui, H Catley, L Chauhan, D Saavedra, JE Keefer, LK Shami, PJ Anderson, KC TI JS-K, a GST-activated nitric oxide generator, induces apoptosis and overcomes in vitro drug resistance in multiple myeloma cells. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Med Oncol, Jerome Lipper Multiple Myeloma Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. SAIC, Frederick, MD USA. NCI, Comparat Carcinogenesis Lab, NIH, Frederick, MD 21701 USA. Univ Utah, Div Med Oncol, Salt Lake City, UT USA. Salt Lake City Vet Adm Med Ctr, Salt Lake City, UT USA. RI Catley, Laurence/E-5313-2013; Keefer, Larry/N-3247-2014 OI Keefer, Larry/0000-0001-7489-9555 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1593 BP 456A EP 456A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002528 ER PT J AU Slape, C Lin, YW Bies, J Wolff, L Aplan, PD AF Slape, C Lin, YW Bies, J Wolff, L Aplan, PD TI Acceleration of leukemogenesis in NUP98-HOXD13 transgenic mice by infection with the MOL407OLTR virus, and identification of collaborating genes SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Canc Res Ctr, Genet Branch, NIH, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Cellular Oncol Lab, Leukemogenesis Sect,NIH, Bethesda, MD 20892 USA. RI Slape, Christopher/H-8586-2016; Aplan, Peter/K-9064-2016 OI Slape, Christopher/0000-0002-8407-3092; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1597 BP 457A EP 457A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002532 ER PT J AU Markus, J Garin, MT Galili, N Raza, A Thirman, MJ LeBeau, MM Rowley, JD Wolff, L AF Markus, J Garin, MT Galili, N Raza, A Thirman, MJ LeBeau, MM Rowley, JD Wolff, L TI Methylation-independent silencing of the tumor suppressor p15INK4B by CBFb-SMMHC in acute myeloid leukemias with inv(16). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Rush Canc Inst, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1615 BP 462A EP 462A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426002550 ER PT J AU Markham, NO Parry, EM Stefanovic, M Gallagher, PG Low, PS Bodine, DM AF Markham, NO Parry, EM Stefanovic, M Gallagher, PG Low, PS Bodine, DM TI Genetic evidence that an 11 amino acid beta-hairpin loop in the cytoplasmic domain of band 3 is responsible for at least 50% of ankyrin binding in mouse erythrocytes. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHGRI, Hematopoiesis Sect, Bethesda, MD 20892 USA. Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. Yale Univ, Dept Pediat, New Haven, CT 06520 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1659 BP 473A EP 474A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426003021 ER PT J AU Walia, JS Yoshimitsu, M Silvertown, JD Poeppl, A Rasaiah, VI Donahue, RE Andrews, RG McCart, JA Medin, JA AF Walia, JS Yoshimitsu, M Silvertown, JD Poeppl, A Rasaiah, VI Donahue, RE Andrews, RG McCart, JA Medin, JA TI Initiation of a pre-clinical gene therapy study in non-human primates using lentivectors targeting hematopoietic cells for correction of Fabry disease. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Hlth Network, Ontario Canc Inst, Div Stem Cell & Differentiat, Toronto, ON, Canada. NHLBI, NIH, Rockville, MD USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Toronto Gen Res Inst, Toronto, ON, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Univ Toronto, Inst Med Biophys, Toronto, ON, Canada. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 5542 BP 474B EP 474B PN 2 PG 1 WC Hematology SC Hematology GA 986CG UT WOS:000233426102643 ER PT J AU Shiva, S Huang, Z Ringwood, LA Lefer, DJ Gladwin, MT AF Shiva, S Huang, Z Ringwood, LA Lefer, DJ Gladwin, MT TI Reduction of nitrite to nitric oxide by myoglobin modulates mitochondrial respiration during ischemia and limits reperfusion injury. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, CV Branch, Vasc Therapeut Sect, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Physiol, Shreveport, LA 71105 USA. NR 0 TC 0 Z9 0 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 NOV 16 PY 2005 VL 106 IS 11 MA 1673 BP 477A EP 477A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426003035 ER PT J AU Yokota, T Sato, S Kawakami, Y Nagai, Y Ma, JX Tsai, JY Oritani, K Tomiyama, Y Matsumura, I Kincade, PW Kanakura, Y AF Yokota, T Sato, S Kawakami, Y Nagai, Y Ma, JX Tsai, JY Oritani, K Tomiyama, Y Matsumura, I Kincade, PW Kanakura, Y TI Hematopoietic stem cells fail to trans-differentiate into smooth muscle-lineage cells in vivo. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Osaka Univ, Grad Sch Med, Dept Hematol & Oncol, Suita, Osaka, Japan. Univ Oklahoma, Hlth Sci Ctr, Sect Endocrinol & Diabet, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Immunobiol & Canc Program, Oklahoma City, OK 73104 USA. NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1703 BP 486A EP 486A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426003065 ER PT J AU Larochelle, A Perez, CL Krouse, A Metzger, M Fricker, S Bridger, G Orlic, D Donahue, RE Abkowitz, JL Dunbar, CE AF Larochelle, A Perez, CL Krouse, A Metzger, M Fricker, S Bridger, G Orlic, D Donahue, RE Abkowitz, JL Dunbar, CE TI Mobilization as a preparative regimen for hematopoietic stem cell (HSC) transplantation in rhesus macaques. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. AnorMED Inc, Langley, BC, Canada. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1709 BP 487A EP 487A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426003071 ER PT J AU Shepherd, BE Kiem, HP Dunbar, CE Larochelle, A Donahue, RE Seggewiss, R Lansdorp, PM Guttorp, P Abkowitz, JL AF Shepherd, BE Kiem, HP Dunbar, CE Larochelle, A Donahue, RE Seggewiss, R Lansdorp, PM Guttorp, P Abkowitz, JL TI Estimating the replication rate of hematopoietic stem cells in non-human primates: A test of Hayflick's hypothesis. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Washington, Seattle, WA 98195 USA. NHLBI, Bethesda, MD 20892 USA. BC Canc Agcy, Terry Fox Lab, Vancouver, BC, Canada. NR 0 TC 1 Z9 1 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1710 BP 487A EP 487A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426003072 ER PT J AU Nemeth, M Anderson, S Kirby, M Bodine, D AF Nemeth, M Anderson, S Kirby, M Bodine, D TI Hmgb3 regulates the balance between HSC differentiation and self renewal. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHGRI, Hematopoiesis Sect, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1718 BP 489A EP 489A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426003080 ER PT J AU Pilon, AM Zhou, D Weiss, MJ Townes, TM Bodine, DM Gallagher, PG AF Pilon, AM Zhou, D Weiss, MJ Townes, TM Bodine, DM Gallagher, PG TI The human alpha hemoglobin stabilizing protein (AHSP) gene locus in EKLF-deficient erythroid cells. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHGRI, GMBB, NIH, Bethesda, MD 20892 USA. Univ Alabama, Birmingham, AL USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Yale Univ, Sch Med, New Haven, CT USA. RI Weiss, Mitchell/A-1245-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1740 BP 495A EP 495A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426003102 ER PT J AU Srinivasan, R Geller, N Dorrance, C Espinoza-Delgado, I Barrett, AJ Takahashi, Y Childs, RW AF Srinivasan, R Geller, N Dorrance, C Espinoza-Delgado, I Barrett, AJ Takahashi, Y Childs, RW TI High response rates in acute steroid refractory graft-versus-host disease (GVHD) following combined tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) blockade SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. NHLBI, Off Biostat, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1801 BP 512A EP 512A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426003163 ER PT J AU Cornely, O Maertens, J Winston, D Perfect, J Helfgott, D Ullmann, A Holowiecki, J Stockelberg, D Goh, YT Petrini, M Walsh, T Gogate, J Hardalo, C Angulo-Gonzalez, D AF Cornely, O Maertens, J Winston, D Perfect, J Helfgott, D Ullmann, A Holowiecki, J Stockelberg, D Goh, YT Petrini, M Walsh, T Gogate, J Hardalo, C Angulo-Gonzalez, D TI Posaconazole vs standard azole (FLU/ITRA) therapy for prophylaxis of invasive fungal infections (IFIs) among high-risk neutropenic patients: Results of a randomized, multicenter trial. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Cologne, IM, Cologne, Germany. Univ Hosp Gasthuisberg, B-3000 Louvain, Belgium. Univ Calif Los Angeles, Los Angeles, CA USA. Duke Univ Hosp, ID, Durham, NC USA. Cornell Univ, Med Ctr, ID, New York, NY 10021 USA. Univ Mainz, Med Clin 3, D-6500 Mainz, Germany. L Warynski Silesian Med Acad, Katowice, Poland. Sahlgrenska Univ Hosp, Gothenburg, Sweden. Singapore Gen Hosp, Singapore 0316, Singapore. Hosp Santa Chiara, Pisa, Italy. Natl Canc Inst, Bethesda, MD USA. Schering Plough Res Inst, AI, Kenilworth, NJ USA. NR 0 TC 4 Z9 5 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1844 BP 524A EP 524A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426003206 ER PT J AU Rudelius, M Pittaluga, S Pham, THT Fountaine, T Quintanilla-Martinez, L Fend, F Jaffe, ES Raffeld, M AF Rudelius, M Pittaluga, S Pham, THT Fountaine, T Quintanilla-Martinez, L Fend, F Jaffe, ES Raffeld, M TI Constitutive activation of AKT contributes to the pathogenesis and survival of blastoid variants of mantle cell lymphoma. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Pathol Lab, NIH, Bethesda, MD USA. Tech Univ Munich, Inst Pathol, Munich, Germany. GSF, Natl Res Ctr Hlth & Environm, Inst Pathol, Neuherberg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1908 BP 541A EP 542A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426003270 ER PT J AU Pulsipher, M Kurian, S Leitman, SF Anderlini, P Haagenson, M Logan, B Horowitz, MM Confer, DL AF Pulsipher, M Kurian, S Leitman, SF Anderlini, P Haagenson, M Logan, B Horowitz, MM Confer, DL TI Unrelated-donor PBSC collection facilitated by the NMPD, 1999-2005: Efficacy and toxicities, serious unexpected events, and outcomes of standard vs. large volume collections SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Utah, Salt Lake City, UT USA. CIBMTR, Milwaukee, WI USA. NIH, Bethesda, MD 20892 USA. MDACC, Houston, TX USA. NMDP, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1965 BP 556A EP 557A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426003327 ER PT J AU Yong, ASM Szydlo, RM Goldman, JM Apperley, JF Melo, JV AF Yong, ASM Szydlo, RM Goldman, JM Apperley, JF Melo, JV TI Molecular profiling of CD34+cells from diagnosis in CML patients identifies low expression of CD7 with high expression of proteinase 3 or elastase as predictors of longer survival SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ London Imperial Coll Sci Technol & Med, Dept Haematol, Hammersmith Hosp, London, England. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 1984 BP 562A EP 562A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426003346 ER PT J AU Bashey, A Medina, B Corringham, S Pasek, M Carrier, E Streicher, H Lowy, I Mason, J Soiffer, RJ Ball, ED AF Bashey, A Medina, B Corringham, S Pasek, M Carrier, E Streicher, H Lowy, I Mason, J Soiffer, RJ Ball, ED TI Phase I study of a neutralizing monoclonal anti-CTLA4 antibody (MDX-010) in patients with relapse of malignancy after allogeneic hematopoietic stem cell transplantation SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Calif San Diego, Blood & Marrow Transplantat Program, Moores Canc Ctr, La Jolla, CA 92093 USA. NCI, Pharmaceut Management Branch, Bethesda, MD 20892 USA. Medarex Inc, Bloomsbury, NJ USA. Scripps Clin, BMT, La Jolla, CA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2017 BP 571A EP 571A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426003379 ER PT J AU Chen, WW Raffeld, M Pittaluga, S Sorbara, L Jaffe, ES AF Chen, WW Raffeld, M Pittaluga, S Sorbara, L Jaffe, ES TI Mutational status of chronic lymphocytic leukemia (CLL) determines clonlal evolution in classical Hodgkin's lymphoma variant of Richter's transformation. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Natl Canc Inst, Canc Res Ctr, Pathol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2107 BP 596A EP 596A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426003469 ER PT J AU Orchard, K Cooper, M Lewington, V Tristram, M Zivanovic, M Thom, J Quadri, S Richardson, D Causer, L Johnson, P AF Orchard, K Cooper, M Lewington, V Tristram, M Zivanovic, M Thom, J Quadri, S Richardson, D Causer, L Johnson, P TI Targeted radiotherapy in the conditioning prior to haematopoietic stem cell transplantation: Results of a phase I radiation dose escalation study using yttrium-90-labelled anti-CD66 monoclonal antibody demonstrating high BM uptake of radiation. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Southampton Univ Hosp, Dept Haematol, Southampton, Hants, England. St Bartholomews Hosp, Dept Nucl Med, London, England. Southampton Univ Hosp, Dept Nucl Med & Med Phys, Southampton, Hants, England. Southampton Univ Hosp, Div Canc Sci, Southampton, Hants, England. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2189 BP 618A EP 618A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004036 ER PT J AU Ugarte, FA Lehmann, R Malech, HL Roesler, J Roesen-Wolff, A Brenner, S AF Ugarte, FA Lehmann, R Malech, HL Roesler, J Roesen-Wolff, A Brenner, S TI SIP1 overexpression inhibits SDF1/CXCR4 dependent migration and in vivo homing of hematopoietic stem cells. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Clin Dresden, Dept Pediat, Dresden, Germany. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RI Brenner, Sebastian/D-7456-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2188 BP 618A EP 618A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004035 ER PT J AU Bozorgmehr, F Laufs, S Buss, EC Nagy, KZ Sellers, SE Zeller, WJ Dunbar, CE Fruehauf, S AF Bozorgmehr, F Laufs, S Buss, EC Nagy, KZ Sellers, SE Zeller, WJ Dunbar, CE Fruehauf, S TI Quantitative real time PCR analysis of MDR1 transduced rhesus macaque hematopoietic stem cells shows no indication for proliferative advantage after long-term follow-up. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Heidelberg, Dept Internal Med 5, Heidelberg, Germany. German Canc Res Ctr, Dept E0120, D-6900 Heidelberg, Germany. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2198 BP 620A EP 621A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426004045 ER PT J AU Longo, DL Bie, A Metter, JE Guralnik, JM Woodman, RC Ferrucci, L AF Longo, DL Bie, A Metter, JE Guralnik, JM Woodman, RC Ferrucci, L TI Hemoglobin and all-cause mortality: Results from the Baltimore longitudinal study of aging (BLSA). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Natl Inst Aging, Ctr Gerontol Res, Baltimore, MD USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Ortho Biotech LSS, Clin Affairs, Bridgewater, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 BP 636A EP 636A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004104 ER PT J AU Weksberg, D Feng, CG Sher, A Goodell, MA AF Weksberg, D Feng, CG Sher, A Goodell, MA TI The interferon-inducible GTPase LRG-47 regulates hematopoietic stem cell proliferation and is required for maintenance of normal hematopoiesis during microbial infection. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Baylor Coll Med, Dept Mol & Human Genet, Houston, TX USA. Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX USA. Baylor Coll Med, Dept Pediat, Houston, TX USA. Natl Inst Allergy & Infect Dis, Lab Parasit Dis, Immunobiol Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 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 NOV 16 PY 2005 VL 106 IS 11 MA 2266 BP 638A EP 639A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426004113 ER PT J AU Nemeth, M Bodine, D AF Nemeth, M Bodine, D TI Wnt5a inhibits Wnt3a-mediated HSC differentiation. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHGRI, Hematopoiesis Sect, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2271 BP 640A EP 640A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004118 ER PT J AU Kajiguchi, T Chung, EJ Kiyoi, H Naoe, T Neckers, L Trepel, J AF Kajiguchi, T Chung, EJ Kiyoi, H Naoe, T Neckers, L Trepel, J TI Novel mechanism of activated FLT3-associated leukemogenisis: FLT3 regulates writ signaling by phosphorylating beta-catenin and promoting beta-catenin nuclear localization. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Natl Canc Inst, Bethesda, MD USA. Nagoya Univ, Dept Infect Dis, Nagoya, Aichi, Japan. Nagoya Univ, Grad Sch Med, Dept Hematol, Nagoya, Aichi, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2295 BP 646A EP 646A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004142 ER PT J AU Ryser, MF Roesler, J Malech, HL Roesen-Wolff, A Brenner, S AF Ryser, MF Roesler, J Malech, HL Roesen-Wolff, A Brenner, S TI Physiological gradients of serum albumin regulate SDF-1/CXCR4 dependent migration. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Clin Dresden, Dept Pediat, Dresden, Germany. Natl Inst Allergy & Infect Dis, Lab Host Def, NIH, Bethesda, MD USA. RI Brenner, Sebastian/D-7456-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2308 BP 649A EP 649A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004155 ER PT J AU Miura, Y Gao, ZG Miura, M Seo, BM Sonoyama, W Chen, WJ Gronthos, S Zhang, L Shi, ST AF Miura, Y Gao, ZG Miura, M Seo, BM Sonoyama, W Chen, WJ Gronthos, S Zhang, L Shi, ST TI Culture-expanded human bone marrow stromal stem cells organize functional bone marrow niches in vivo. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Natl Inst Dent & Craniofacial Res, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Sidney Kimmel Oncol Ctr, Div Immunol Hematol, Baltimore, MD USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD USA. Inst Med & Vet Sci, Div Haematol, Adelaide, SA, Australia. Univ Maryland, Sch Med, Dept Physiol, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 BP 651A EP 651A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004161 ER PT J AU Hsu, LL Dejam, A Pelletier, M Cochard, AE Diwan, B Gladwin, M Schechter, AN Noguchi, C AF Hsu, LL Dejam, A Pelletier, M Cochard, AE Diwan, B Gladwin, M Schechter, AN Noguchi, C TI Sexual dimorphism in whole blood nitrite and susceptibility to hypoxic sickle cell vaso-occlusive injury in mice. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 St Christophers Hosp Children, Marian Anderson Sickle Cell Ctr, Philadelphia, PA USA. Natl Heart Lung & Blood Inst, Vasc Therapeut Branch, Bethesda, MD USA. Natl Inst Diabet Digest & Kidney Disorders, Mol Med Branch, Bethesda, MD USA. RI Hsu, Lewis/A-3360-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2327 BP 655A EP 655A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004174 ER PT J AU Mack, AK Machado, RR Sachdev, V Gladwin, MT Kato, GJ AF Mack, AK Machado, RR Sachdev, V Gladwin, MT Kato, GJ TI Sodium nitrite increases regional blood flow in patients with sickle cell disease. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Natl Canc Inst, Pediat Oncol Branch, NIH, Bethesda, MD USA. Natl Heart Lung & Blood Inst, Cardiovasc Branch, NIH, Bethesda, MD USA. Crit Care Med Dept, Clin Ctr, NIH, Bethesda, MD USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Dept Pediat, Baltimore, MD USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2328 BP 655A EP 655A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004175 ER PT J AU Wu, CJ Krishnamurti, L Gladwin, MT Biernacki, M Rogers, SA Wang, XD Zahrieh, D Antin, JH Ritz, J AF Wu, CJ Krishnamurti, L Gladwin, MT Biernacki, M Rogers, SA Wang, XD Zahrieh, D Antin, JH Ritz, J TI Mixed hematopoietic chimerism for sickle cell disease prevents intravascular hemolysis and corrects biomarkers of endothelial function. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Dana Farber Canc Inst, Dept Hematol Neoplasia, Boston, MA USA. Brigham & Womens Hosp, Dept Med, Boston, MA USA. Childrens Hosp Pittsburgh, Pittsburgh, PA USA. NHLBI, Cardiovasc Branch, Vasc Therapeut Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2333 BP 656A EP 656A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004180 ER PT J AU Partovi, K Martyr, S McGowan, V Machado, R Taylor, J Kato, G Gladwin, M Little, J AF Partovi, K Martyr, S McGowan, V Machado, R Taylor, J Kato, G Gladwin, M Little, J TI Early predictors of fetal hemoglobin response to hydroxyurea in sickle cell disease. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI CC, Vasc Therapeut Sect, NIH, Bethesda, MD USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2344 BP 659A EP 660A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426004191 ER PT J AU Piknova, B Gladwin, MT Hillery, CA Hogg, N AF Piknova, B Gladwin, MT Hillery, CA Hogg, N TI Electron paramagnetic resonance study of cell-free hemoglobin in sickle cell disease: Potential antioxidant role of haptoglobin. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Med Coll Wisconsin, Milwaukee, WI USA. Childrens Res Inst & Med Coll Wisconsin, Milwaukee, WI USA. NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2345 BP 660A EP 660A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004192 ER PT J AU Fitzhugh, C Lauder, N Jonassaint, J Gilliam, FR Telen, MJ De Castro, LM AF Fitzhugh, C Lauder, N Jonassaint, J Gilliam, FR Telen, MJ De Castro, LM TI Morbidity and associated sudden death in sickle cell disease. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD USA. Johns Hopkins Univ, Baltimore, MD USA. Duke Univ, Durham, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2348 BP 661A EP 661A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004195 ER PT J AU Melenhorst, JJ Solomon, SR Mielke, S Hensel, NF Barrett, AJ AF Melenhorst, JJ Solomon, SR Mielke, S Hensel, NF Barrett, AJ TI Robust expansion of cytomegalovirus (CMV) antigen-specific CD4+ and CD8+ T cells using gene-modified activated T cells as antigen presenting cells. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2384 BP 671A EP 671A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004231 ER PT J AU Snyder, K Zhang, H Vance, B June, CH Vonderheide, R Mackall, C AF Snyder, K Zhang, H Vance, B June, CH Vonderheide, R Mackall, C TI Evaluation of the CD8+ tumor associated vs. non-tumor associated immune repertoire in cancer patients following induction of lymphopenia and following CD3/4-1BB based expansion. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Penn, Abramson Canc Ctr, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2390 BP 673A EP 673A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004237 ER PT J AU Rao, VK Dowdell, KC Dugan, F Dale, JK Pesnicak, L Bi, LL Penzak, S Avila, NA Fleisher, TA Puck, JM Straus, SE AF Rao, VK Dowdell, KC Dugan, F Dale, JK Pesnicak, L Bi, LL Penzak, S Avila, NA Fleisher, TA Puck, JM Straus, SE TI Pyrimethamine does not diminish lymphoproliferation in MRL/lpr-/- mice and patients with autoimmune Lymphoproliferative syndrome (ALPS). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIAID, NHGRI, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2396 BP 674A EP 674A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004243 ER PT J AU Cheng, YF Tang, Y Young, NS AF Cheng, YF Tang, Y Young, NS TI T cells response and autoantibodies to human heat shock proteins in aplastic anemia patients. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2403 BP 676A EP 676A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004250 ER PT J AU Cheng, YF Tang, Y Green, S Keyvanfar, K Bruno, T Young, NS AF Cheng, YF Tang, Y Green, S Keyvanfar, K Bruno, T Young, NS TI A longitudinal analysis of the T-cell receptor v beta repertoire in aplastic anemia patients at initial presentation, remission, and relapse. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2402 BP 676A EP 676A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004249 ER PT J AU Rizzatti, EG Mora-Jensen, HI Billings, E Lai, R Wiestner, A AF Rizzatti, EG Mora-Jensen, HI Billings, E Lai, R Wiestner, A TI Gene expression analysis uncovers possible resistance mechanisms to bortezomib in mantle cell lymphoma that differ from mechanisms identified in other lymphoid malignancies. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NHLBI, Bioinformat Core Facil, Bethesda, MD 20892 USA. Univ Alberta, Dept Lab Med & Pathol, Edmonton, AB, Canada. NR 0 TC 0 Z9 0 U1 1 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2412 BP 678A EP 678A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004259 ER PT J AU Santos, C Stern, L Katz, L Watson, T Barry, G AF Santos, C Stern, L Katz, L Watson, T Barry, G TI BiovaxID (TM) vaccine therapy of follicular lymphoma in first remission: Long-term follow-up of a phase II trial and status of a controlled, randomized phase III trial. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Accentia Biopharmaceut Inc, New York, NY USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2441 BP 686A EP 686A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004288 ER PT J AU Fujita, K Kim, JS Eckhardt, LA Shaughnessy, JD Janz, S AF Fujita, K Kim, JS Eckhardt, LA Shaughnessy, JD Janz, S TI Dkk1 transgenic mice for the study of bone lesions in human multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Genet Lab, NIH, Bethesda, MD USA. Korea Res Inst Biosci & Biotechnol, Taejon, South Korea. CUNY, Dept Biol Sci, New York, NY USA. Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2505 BP 704A EP 704A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004352 ER PT J AU Sloand, EM Greenberg, P Wu, C Young, NS Barrett, J AF Sloand, EM Greenberg, P Wu, C Young, NS Barrett, J TI Immunosuppressive treatment is associated with durable responses and a survival advantage in younger patients with int-1 myelodysplastic syndrome. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. Stanford Univ, Div Hematol, Stanford, CA USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2519 BP 707A EP 707A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004366 ER PT J AU Kurzrock, R Verstovsek, S Wright, JJ Pilat, SR Cortes, JE Estey, EH Giles, FJ Beran, M Kantarjian, HM AF Kurzrock, R Verstovsek, S Wright, JJ Pilat, SR Cortes, JE Estey, EH Giles, FJ Beran, M Kantarjian, HM TI Alternate week administration of the farnesyltransferase inhibitor tipifarnib (ZARNESTRA (R), R115777) in patients with myelodysplastic syndrome: Results of a phase 1 study. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 MD Anderson Canc Ctr, Houston, TX USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2521 BP 708A EP 708A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004368 ER PT J AU Somlo, G Bellamy, W Zimmerman, TM Frankel, P Tuscano, J O'Donnell, M Mohrbacher, A Forman, S Chen, H Doroshow, J Gandara, D AF Somlo, G Bellamy, W Zimmerman, TM Frankel, P Tuscano, J O'Donnell, M Mohrbacher, A Forman, S Chen, H Doroshow, J Gandara, D TI Phase II randomized trial of bevacizumab versus bevacizumab and thalidomide for relapsed/refractory multiple myeloma. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Illinois, Chicago, IL 60680 USA. Natl Inst Hlth, Div Canc Treatment Diag & Ctr, Bethesda, MD USA. Univ So Calif, Los Angeles, CA 90089 USA. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2571 BP 723A EP 723A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004418 ER PT J AU Niesvizky, R Ely, S Diliberto, M Cho, HJ Gelbshtein, UY Jayabalan, DS Aggarwal, S Gabrilove, JL Pearse, RN Pekle, K Zafar, F Goldberg, Z Leonard, JP Wright, JJ Chen-Kiang, S Coleman, M AF Niesvizky, R Ely, S Diliberto, M Cho, HJ Gelbshtein, UY Jayabalan, DS Aggarwal, S Gabrilove, JL Pearse, RN Pekle, K Zafar, F Goldberg, Z Leonard, JP Wright, JJ Chen-Kiang, S Coleman, M TI Multicenter phase II trial of the histone deacetylase inhibitor depsipeptide (FK228) for the treatment of relapsed or refractory multiple myeloma (MM). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Cornell Univ, Weill Med Coll, New York, NY 10021 USA. Montefiore Med Ctr, Bronx, NY 10467 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. NCI, CTEP, Invest Drug Branch, Bethesda, MD 20892 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2574 BP 724A EP 724A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004421 ER PT J AU Castleberry, RP Loh, ML Jayaprakash, N Peterson, A Casey, V Chang, M Widemann, B Emanuel, PD AF Castleberry, RP Loh, ML Jayaprakash, N Peterson, A Casey, V Chang, M Widemann, B Emanuel, PD TI Phase II window study of the farnesyltransferase inhibitor R115777 (Zarnestra (R)) in untreated juvenile myelomonocytic leukemia (JMML): A children's oncology group study. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Alabama, Div Pediat Hematol Oncol, Birmingham, AL USA. Univ Calif San Francisco, Div Pediat Hematol Oncol, San Francisco, CA 94143 USA. NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Florida, Dept Epidemiol & Hlth Policy Res, Gainesville, FL 32611 USA. Childrens Oncol Grp, Arcadia, CA USA. NR 0 TC 21 Z9 22 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2587 BP 727A EP 728A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426004434 ER PT J AU Lin, YW Nichols, RA Letterio, JJ Aplan, PD AF Lin, YW Nichols, RA Letterio, JJ Aplan, PD TI Acquired Notch1 mutations in murine precursor-T leukemia/lymphoma models. SO BLOOD LA Rumanian DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Genet Brach, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, Ctr Canc Res, Natl Inst Hlth, Bethesda, MD 20892 USA. RI Aplan, Peter/K-9064-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2612 BP 734A EP 734A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004459 ER PT J AU Shang, DZ Zheng, XW Ai, JH Long Zheng X AF Shang, DZ Zheng, XW Ai, JH Long Zheng, X TI Comparative genomic analysis of the 5'-upstream sequences of von Willebrand factor and 27 other endothelial-specific genes identifies conserved noncoding sequences that are DNase hypersensitive. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. Natl Human Genome Res Inst, NIH, Bethesda, MD USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Howard Hughes Med Inst, Ann Arbor, MI 48109 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2652 BP 744A EP 744A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426004497 ER PT J AU Rogers, HM Noguchi, CT AF Rogers, HM Noguchi, CT TI g-Globin induction in human erythroid progenitor cells by histone deacetylase inhibitor OSI-2040 gamma. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2700 BP 759A EP 759A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005020 ER PT J AU Rezvani, K Mielke, S Kilical, Y Grube, M Fujiwara, H Sconocchia, G Lee, J El-Ouriaghi, F Hensel, N Barrett, AJ AF Rezvani, K Mielke, S Kilical, Y Grube, M Fujiwara, H Sconocchia, G Lee, J El-Ouriaghi, F Hensel, N Barrett, AJ TI Identification of novel MHC class I and class II epitopes of WT1 using a peptide library screen SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2764 BP 775A EP 775A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005084 ER PT J AU Karp, JE Gojo, I Greer, J Smith, BD Klein, M Lancet, JE Gore, SD Morris, L Thibault, A Rybak, ME Wright, JJ AF Karp, JE Gojo, I Greer, J Smith, BD Klein, M Lancet, JE Gore, SD Morris, L Thibault, A Rybak, ME Wright, JJ TI Tipifarnib (Zarnestra, R115777) as maintenance therapy for adults in complete remission (CR) following induction and consolidation therapies for poor-risk acute myelogenous leukemia: A phase II trial SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Johns Hopkins Sidney Kimmel Canc Ctr, Baltimore, MD USA. Univ Maryland, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Bone Marrow Transplant Grp Georgia, Atlanta, GA USA. Johnson & Johnson PRD, Raritan, NJ USA. Natl Canc Inst, IDB, CTEP, Rockville, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2783 BP 780A EP 781A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426005103 ER PT J AU Karp, JE Smith, BD Greer, J Briel, J Levis, MJ McDevitt, MA Gore, SD Dimitrios, A Colevas, AD AF Karp, JE Smith, BD Greer, J Briel, J Levis, MJ McDevitt, MA Gore, SD Dimitrios, A Colevas, AD TI Phase II clinical trial of flavopiridol (FL) followed by ara-c and mitoxantrone (AM) for adults with relapsed and refractory acute leukemias SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Johns Hopkins Univ, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2784 BP 781A EP 781A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005104 ER PT J AU Klisovic, RB Blum, W Wei, X Liu, S Kefauver, C Huynh, L Zwiebel, JA Byrd, JC Grever, MR Marcucci, G AF Klisovic, RB Blum, W Wei, X Liu, S Kefauver, C Huynh, L Zwiebel, JA Byrd, JC Grever, MR Marcucci, G TI A phase I study of GTI-2040, an antisense to ribonucleotide reductase (RNR) in combination with high-dose cytarabine (HiDAC) in relapsed or refractory acute myeloid leukemia (AML): Pharmacokinetics (PK), pharmacodynamic (PD) and clinical results SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Ohio State Univ, Div Hem Onc, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NCI, CTEP, Bethesda, MD 20892 USA. RI Blum, William/E-2769-2011 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2790 BP 782A EP 783A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426005110 ER PT J AU Cortes, J Garcia-Manero, G O'Brien, S Verstovsek, S Estrov, Z Giles, F Ravandi, F Wright, J Kantarjian, H AF Cortes, J Garcia-Manero, G O'Brien, S Verstovsek, S Estrov, Z Giles, F Ravandi, F Wright, J Kantarjian, H TI Farnesyl transferase inhibitor (tipifarnib, zarnestra; Z) in combination with standard chemotherapy with idarubicin (Ida) and cytarabine (ara-c) for patients (pts) with newly diagnosed acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Invest Drug Branch, Canc Therapy Evaluat Program, Rockville, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2796 BP 784A EP 784A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005116 ER PT J AU Cheng, Y Zhang, ZH Slape, C Aplan, PD AF Cheng, Y Zhang, ZH Slape, C Aplan, PD TI A human SIL-SCL fusion gene displays a development block at the CD4- CD8- to CD4+ CD8+ transition in transgenic mice SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Genet Branch, Bethesda, MD 20892 USA. RI Slape, Christopher/H-8586-2016; Aplan, Peter/K-9064-2016 OI Slape, Christopher/0000-0002-8407-3092; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2833 BP 794A EP 794A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005153 ER PT J AU Janz, S John, SD AF Janz, S John, SD TI Mouse model of MYC-dereguilating chromosomal translocations associated with human Burkitt lymphoma and multiple myeloma SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, NIH, Genet Lab, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2832 BP 794A EP 794A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005152 ER PT J AU Cheney, MD Liu, YZ Gaudet, JJ Chruszcz, M Lukasik, SM Sugiyama, D Lary, J Cole, J Dauter, Z Minor, W Speck, NA Bushweller, JH AF Cheney, MD Liu, YZ Gaudet, JJ Chruszcz, M Lukasik, SM Sugiyama, D Lary, J Cole, J Dauter, Z Minor, W Speck, NA Bushweller, JH TI Structural and functional characterization of the NHR2 and Runt domains of AML1/ETO SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH USA. Univ Virginia, Dept Mol Physiol & Biol Phys, Charlottesville, VA USA. Univ Virginia, Dept Chem, Charlottesville, VA USA. Univ Connecticut, Natl Analyt Ultracentrifugat Facil, Storrs, CT USA. Univ Connecticut, Dept Mol & Cell Biol, Storrs, CT USA. Brookhaven Natl Lab, NCI, Macromol Crystallog Lab, Upton, NY 11973 USA. RI Chruszcz, Maksymilian/E-6407-2011; Minor, Wladek/F-3096-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2854 BP 800A EP 800A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005174 ER PT J AU Lee, SY Chen, JJ Zhou, GL Shi, R Kocherginsky, M Karrison, TG Kim, YC Ge, XJ Jayathilaka, N Neilly, MB Bouffard, G Young, A Kornblau, S Bloomfield, C Bohlander, S Liu, PP Sun, M Wang, SM Rowley, JD AF Lee, SY Chen, JJ Zhou, GL Shi, R Kocherginsky, M Karrison, TG Kim, YC Ge, XJ Jayathilaka, N Neilly, MB Bouffard, G Young, A Kornblau, S Bloomfield, C Bohlander, S Liu, PP Sun, M Wang, SM Rowley, JD TI Gene expression profiles in acute myeloid leukemia (AML): From diagnosis to prognosis. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Dept Hlth Studies, Chicago, IL 60637 USA. Northwestern Univ, ENH Res Inst, Chicago, IL 60611 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Kyungpook Natl Univ, Sch Life Sci & Biotechnol, Taegu, South Korea. MD Anderson Canc Ctr, Houston, TX USA. Ohio State Comprehens Canc Ctr, Columbus, OH USA. Univ Hosp Grosshadern, Dept Med 3, Munich, Germany. RI Kornblau, Steven/A-9366-2009; Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2996 BP 839A EP 840A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426005316 ER PT J AU Riz, R Akimov, SS Eaker, SS Marino-Ramirez, L Landsman, D Hawley, TS Hawley, RG AF Riz, R Akimov, SS Eaker, SS Marino-Ramirez, L Landsman, D Hawley, TS Hawley, RG TI TLX1/HOX11-mediated disruption of hematopoietic differentiation programs. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 George Washington Univ, Med Ctr, Dept Anat & Cell Biol, Washington, DC USA. NIH, Natl Ctr Biotechnol Informat, Bethesda, MD USA. George Washington Univ, Med Ctr, Flow Cytometry Core Facil, Washington, DC 20037 USA. RI Landsman, David/C-5923-2009; Marino-Ramirez, Leonardo/I-5759-2013 OI Marino-Ramirez, Leonardo/0000-0002-5716-8512 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 2997 BP 840A EP 840A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005317 ER PT J AU Martinez-Delgado, B Bahl, M Cuadros, M Fernandez, V Benitez, J Jaffe, ES Staudt, L AF Martinez-Delgado, B Bahl, M Cuadros, M Fernandez, V Benitez, J Jaffe, ES Staudt, L TI Biological differences in peripheral T-cell lymphomas identified by DNA microarrays. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Spanish Natl Canc Ctr, Madrid, Spain. NCI, Lymphois Malignancies Sect, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RI Cuadros, Marta/K-1576-2014 OI Cuadros, Marta/0000-0002-8329-4854 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3012 BP 844A EP 844A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005332 ER PT J AU Medin, JA Liang, SB Poeppl, A Yoshimitsu, M Walia, JS Cai, JH Rasaiah, VI Fowler, DH AF Medin, JA Liang, SB Poeppl, A Yoshimitsu, M Walia, JS Cai, JH Rasaiah, VI Fowler, DH TI Functional engraftment of retrovirally transduced and pre-selected hematopoietic cells into partially ablated recipient Fabry mice. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Toronto, Div Stem Cell & Differentiat, Ontario Canc Inst, Toronto, ON, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Univ Toronto, Inst Med Sci, Toronto, ON, Canada. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3023 BP 847A EP 847A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005343 ER PT J AU Hsieh, M Chin, K Link, B Stroncek, D Wang, F Everhart, J Tisdale, JF Rodgers, G AF Hsieh, M Chin, K Link, B Stroncek, D Wang, F Everhart, J Tisdale, JF Rodgers, G TI Benign ethnic neutropenia in individuals of African descent: Incidence, granulocyte mobilization, and gene expression profiling. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIDDKD, NIH, Bethesda, MD 20892 USA. NIH, DTM CC, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3069 BP 858A EP 859A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426005389 ER PT J AU Walia, JS Cai, JH Fowler, DH Medin, JA AF Walia, JS Cai, JH Fowler, DH Medin, JA TI Genetically modified DCs engineered to express PSA and/or PSMA can induce a potent immune response against prostate cancer cells. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Ontario Canc Inst, Div Stem Cell & Differentiat, Toronto, ON M4X 1K9, Canada. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Toronto, Dept Med Biophys, Toronto, ON, Canada. Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A1, Canada. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3075 BP 860A EP 860A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005395 ER PT J AU Gu, YC Sokolic, RA Bauer, TR Tuschong, LM Hai, M Burkholder, T Bacher, J Starost, MF Hickstein, DD AF Gu, YC Sokolic, RA Bauer, TR Tuschong, LM Hai, M Burkholder, T Bacher, J Starost, MF Hickstein, DD TI Selective migration of CD18+Neutrophils into the tissue results in reversal of the phenotype in canine leukocyte adhesion deficiency. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIH, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. NIH, Div Vet Resources, Bethesda, MD 20892 USA. RI Sokolic, Robert/I-6072-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3084 BP 862A EP 862A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005404 ER PT J AU Lundqvist, A Hamoui, N Andersson, J Elshal, M Takahashi, Y Srinivasan, R Suffredini, D Mccoy, PJ Childs, R AF Lundqvist, A Hamoui, N Andersson, J Elshal, M Takahashi, Y Srinivasan, R Suffredini, D Mccoy, PJ Childs, R TI Allograft cell content and GVHD differ in murine recipients of AMD3100 versus G-CSF mobilized peripheral blood stem cells. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. RI Elshal, Mohamed/H-7953-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3108 BP 869A EP 869A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005428 ER PT J AU Mitchell, S Reeve, B Cowen, E Fall-Dickson, J Gerber, L Guadagnini, JP Robinson, M Turner, M Willis, G Schubert, M Bolanos-Meade, J Higman, M Jacobsohn, D Thormann, K Vogelsang, G Pavletic, S AF Mitchell, S Reeve, B Cowen, E Fall-Dickson, J Gerber, L Guadagnini, JP Robinson, M Turner, M Willis, G Schubert, M Bolanos-Meade, J Higman, M Jacobsohn, D Thormann, K Vogelsang, G Pavletic, S TI Feasibility and reproducibility of the new NIH consensus criteria to evaluate response in chronic GvHD - A pilot study. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, CGvHD Study Grp, Bethesda, MD 20892 USA. Seattle Canc Care Alliance, Seattle, WA USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, BMT, Baltimore, MD USA. Childrens Mem Hosp, Chicago, IL 60614 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3121 BP 873A EP 873A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005441 ER PT J AU Richter, R Bistrian, R Henschler, R AF Richter, R Bistrian, R Henschler, R TI Platelet activation is linked to the severity of pulmonary hypertension in sickle cell disease and normalizes on sildenafil therapy. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Vasc Therapeut Sect, CVB, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Childrens Res Inst, Washington, DC 20010 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3166 BP 884A EP 884A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005486 ER PT J AU Gordeuk, VR Gladwin, MT Kato, G Castro, O AF Gordeuk, VR Gladwin, MT Kato, G Castro, O TI Prevalence of pulmonary hypertension and renal dysfunction by systemic blood pressure categories in sickle cell disease. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Howard Univ, Coll Med, Ctr Sickle Cell Dis, Washington, DC 20059 USA. Natl Inst Hlth, Ctr Clin, Crit Care Dept, Bethesda, MD USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3169 BP 885A EP 885A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005489 ER PT J AU Yuditskaya, S Hoehn, G Suffredini, A Xu, XL Munson, P Gladwin, M Kato, GJ AF Yuditskaya, S Hoehn, G Suffredini, A Xu, XL Munson, P Gladwin, M Kato, GJ TI Proteomic identification of dysregulated apolipoprotein expression in pulmonary hypertension secondary to sickle cell disease. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3168 BP 885A EP 885A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005488 ER PT J AU Rogers, ZR Thompson, B Ware, RE Wang, WC Iyer, RV Miller, ST Minniti, C Rana, S Barredo, JC Toledano, S Zimmerman, SA Casella, JF Files, BA Waclawiw, MA Gerber, AR Bonds, DR AF Rogers, ZR Thompson, B Ware, RE Wang, WC Iyer, RV Miller, ST Minniti, C Rana, S Barredo, JC Toledano, S Zimmerman, SA Casella, JF Files, BA Waclawiw, MA Gerber, AR Bonds, DR TI Pharmacokinetics of hydroxyurea in young children with sickle cell anemia: A report from the BABY HUG trial SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. C TASC, Baltimore, MD USA. St Jude, Memphis, TN USA. Univ Mississippi, Jackson, MS 39216 USA. Suny Downstate Med Ctr, Brooklyn, NY 11203 USA. CNMC, Washington, DC USA. Howard Univ, Washington, DC 20059 USA. Univ Miami, Miami, FL 33152 USA. MUSC, Charleston, SC USA. Duke Univ, Durham, NC USA. Johns Hopkins, Baltimore, MD USA. CHOA, Atlanta, GA USA. Emory, Atlanta, GA USA. NHLBI, Bethesda, MD 20892 USA. NICHD, Bethesda, MD USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3184 BP 890A EP 890A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005504 ER PT J AU Kato, GJ McGowan, V Machado, RF Little, JA Taylor, J Morris, CR Nichols, JS Wang, XD Poljakovic, M Morris, SM Gladwin, MT AF Kato, GJ McGowan, V Machado, RF Little, JA Taylor, J Morris, CR Nichols, JS Wang, XD Poljakovic, M Morris, SM Gladwin, MT TI Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension and death in patients with sickle cell disease SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, Vasc Therapeut Sect, Cardiovasc Branch, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. Childrens Hosp & Res Ctr Oakland, Dept Emergency Med, Oakland, CA USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3188 BP 891A EP 891A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005508 ER PT J AU Asakura, T Abdulmalik, O Iyamu, E Chen, QK Yang, JS Abraham, DJ Safo, MK Brugnara, C Evans, G AF Asakura, T Abdulmalik, O Iyamu, E Chen, QK Yang, JS Abraham, DJ Safo, MK Brugnara, C Evans, G TI Various drugs with or without an antisickling effect in the in vitro tests showed a strong antisickling effect in the in vivo studies in transgenic sickle mice SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Childrens Mercy Hosp, Kansas City, MO 64108 USA. Virginia Commonwealth Univ, Inst Biol Struct, Richmond, VA USA. Childrens Hosp, Boston, MA 02115 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RI Brugnara, Carlo/A-8041-2010 OI Brugnara, Carlo/0000-0001-8192-8713 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3190 BP 892A EP 892A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426005510 ER PT J AU Chung, EJ Lee, MJ Lee, S Oh, HJ Hwang, SG Rubin, JS Trepel, JB AF Chung, EJ Lee, MJ Lee, S Oh, HJ Hwang, SG Rubin, JS Trepel, JB TI Posttranslational control of beta-catenin signaling regulates peripheral blood lymphocyte activation SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3301 BP 923A EP 923A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006085 ER PT J AU Krupica, TP Feng, CG Mackall, CL Fry, TJ AF Krupica, TP Feng, CG Mackall, CL Fry, TJ TI Two categories of biologic effects induced by IL-7 on human T cells SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. HHMI NIIH, Res Scholar Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3303 BP 923A EP 923A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006087 ER PT J AU Melenhorst, JJ Zeilah, J Sosa, E Follmann, D Hensel, NF Barrett, AJ AF Melenhorst, JJ Zeilah, J Sosa, E Follmann, D Hensel, NF Barrett, AJ TI Analysis of the human T cell receptor (TCR) repertoire from birth to old age suggests that TCRV beta frequencies are established independent of HLA SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NHLBI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3313 BP 926A EP 926A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006097 ER PT J AU El Kassar, N Choudhury, B Flomerfelt, F Lucas, PJ Kapoor, V Telford, W Bare, CV Mahmud, S Bhandoola, A Gress, RE AF El Kassar, N Choudhury, B Flomerfelt, F Lucas, PJ Kapoor, V Telford, W Bare, CV Mahmud, S Bhandoola, A Gress, RE TI IL-7 effects on thymocyte progenitors. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Expt Transplantat Immunol Branch, NIH, Bethesda, MD 20892 USA. Etab Francais Sang PL, Angers, France. UPRES, EA 3863, Fac Med, Angers, France. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3318 BP 927A EP 928A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426006102 ER PT J AU Wang, HS Lee, CH Qi, CF Kerrikatte, N Tailor, P Ozato, K Morse, HC AF Wang, HS Lee, CH Qi, CF Kerrikatte, N Tailor, P Ozato, K Morse, HC TI Transcription factor 1CSBP/1RF8 regulates B cell development at multiple checkpoints SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIAID, Immunopathol Lab, Rockville, MD USA. NICHHD, Lab Mol Growth Regulat, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3314 BP 927A EP 927A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006098 ER PT J AU Gerecitano, J Goy, A MacGregor-Cortelli, B Neylon, E Wright, J Esseltine, D Schenkein, D Gonen, M O'Connor, OA AF Gerecitano, J Goy, A MacGregor-Cortelli, B Neylon, E Wright, J Esseltine, D Schenkein, D Gonen, M O'Connor, OA TI Drug-induced cutaneous vasculitis in patients with non-Hodgkin's lymphoma receiving bortezomib: A possible surrogate marker of response. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Hackensack Univ Hosp, Hackensack, NJ USA. NCI, Rockville, MD USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RI Gonen, Mithat/E-4826-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3334 BP 931A EP 932A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426006118 ER PT J AU Grant, S Sullivan, D Roodman, D Stuart, R Perkins, EB Ramakrishnan, V Wright, J Dimitrios Colevas, A Roberts, JD AF Grant, S Sullivan, D Roodman, D Stuart, R Perkins, EB Ramakrishnan, V Wright, J Dimitrios Colevas, A Roberts, JD TI Phase I trial of Bortezomib (NSC 681239) and flavopiridol (NSC 649890) in patients with recurrent or refractory indolent B-cell neoplasms. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Virginia Commonwealth Univ, Massey Canc Ctr, Richmond, VA 23298 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. Med Univ S Carolina, Hollings Canc Ctr, Charleston, SC 29425 USA. NCI, Canc Treatment & Evaluat Program, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3338 BP 933A EP 933A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006122 ER PT J AU Janik, JE Dunleavy, K Pittaluga, S Jaffe, ES Grant, N Shovlin, M Stetler-Stevenson, M Wilson, WH AF Janik, JE Dunleavy, K Pittaluga, S Jaffe, ES Grant, N Shovlin, M Stetler-Stevenson, M Wilson, WH TI A pilot trial of Campath-1H and dose-adjusted EPOCH in CD52-expressing aggressive T-cell malignancies. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Metab Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3348 BP 936A EP 936A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006132 ER PT J AU O'Mahony, D Morris, JC Moses, L O'Hagan, D Gao, W Stetler-Stevenson, M Taylor, M Hammiershaimb, L Waldmann, TA Janik, JE AF O'Mahony, D Morris, JC Moses, L O'Hagan, D Gao, W Stetler-Stevenson, M Taylor, M Hammiershaimb, L Waldmann, TA Janik, JE TI Phase I trial of siplizumab in CD2-positive lymphoproliferative disease SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Metab Branch, Bethesda, MD 20892 USA. MedImmune Oncol, Gaithersburg, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3353 BP 937A EP 937A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006137 ER PT J AU Bushweller, JH Gorczynski, MJ Grembecka, J Newman, M Corpora, T Zhou, Y Kong, Y Jeon, JP Liu, PP Brown, ML AF Bushweller, JH Gorczynski, MJ Grembecka, J Newman, M Corpora, T Zhou, Y Kong, Y Jeon, JP Liu, PP Brown, ML TI Development of small molecule inhibitors of the CBF beta-SMMHC oncoprotein SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Virginia, Charlottesville, VA USA. NHGRI, NIH, Bethesda, MD 20892 USA. RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3359 BP 939A EP 939A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006143 ER PT J AU Dore, LC Vakoc, CR Blobel, GA Hardison, RC Bodine, DM Gallagher, PG Weiss, MJ AF Dore, LC Vakoc, CR Blobel, GA Hardison, RC Bodine, DM Gallagher, PG Weiss, MJ TI Genomic organization, chromatin structure, and transcriptional regulation of the murine Alpha Hemoglobin Stabilizing Protein (AHSP) gene SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Childrens Hosp Philadelphia, Div Hematol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. Penn State Univ, Dept Biochem & Mol Biol, University Pk, PA 16802 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06510 USA. RI Hardison, Ross/G-1142-2010; Weiss, Mitchell/A-1245-2013; Dore, Louis/A-5689-2009 OI Hardison, Ross/0000-0003-4084-7516; Dore, Louis/0000-0002-7837-5887 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3633 BP 1012A EP 1012A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006417 ER PT J AU Rudrabhatla, P Miller, JL AF Rudrabhatla, P Miller, JL TI Expression of fetal hemoglobin among adult human prythroblasts is associated with an altered expression pattern for the transcription factor c-Myb SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIDDK, Mol Genom & Therapeut Sect, Mol Med Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3615 BP 1012A EP 1012A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006419 ER PT J AU Morris, CR Kuypers, FA Kato, G Gardner, J Larkin, S Singer, T Vichinsky, E AF Morris, CR Kuypers, FA Kato, G Gardner, J Larkin, S Singer, T Vichinsky, E TI Dysregulated arginine metabolism and elevated arginase activity in thalassemia. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Childrens Hosp & Res Ctr, Oakland, CA USA. NIH, Bethesda, MD 20892 USA. RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3644 BP 1014A EP 1014A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006428 ER PT J AU Cokic, VP Bhattacharya, B Puri, RK Alan, N AF Cokic, VP Bhattacharya, B Puri, RK Alan, N TI Developmental and differential changes of gene expression in erythroid progenitor cells. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Inst Med Res, Lab Expt Hematol, Belgrade, Serbia Monteneg. US FDA, Lab Mol & Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3648 BP 1015A EP 1016A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426006432 ER PT J AU Hallock, JL Sterner, LJ Little, JA AF Hallock, JL Sterner, LJ Little, JA TI Enhanced erythroid differentiation of murine embryoid bodies that are exposed to short-chain fatty acids during development. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIDDD, LCDB, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3646 BP 1015A EP 1015A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006430 ER PT J AU Zoueva, OP Bodine, D Rodgers, GP AF Zoueva, OP Bodine, D Rodgers, GP TI Human beta-globin expression during erythroid cells development in Transgenic mice bearing human beta-globin gene with mutated BP1 binding site SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NIDDK, MCHB, NIH, Bethesda, MD USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3651 BP 1016A EP 1016A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006435 ER PT J AU Dean, RM Fowler, DH Hardy, NM Odom, J Castro, K Krumlauf, M Hakim, FT Sportes, C Gress, RE Bishop, MR AF Dean, RM Fowler, DH Hardy, NM Odom, J Castro, K Krumlauf, M Hakim, FT Sportes, C Gress, RE Bishop, MR TI Allograft T cell content influences early engraftment after reduced-intensity stem cell transplantation (RIST). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Cleveland Clin Fdn, Taussig Canc Ctr, Cleveland, OH 44195 USA. NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3662 BP 1019A EP 1019A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006446 ER PT J AU Bociek, RG Talmadge, JE Lynch, JC Enke, CA Kuszynski, CA Bierman, PJ Vose, JM Armitage, JO Devetten, MP Maness, LJ McGuire, TR Wisecarver, JL Joshi, SS Pavletic, ZS AF Bociek, RG Talmadge, JE Lynch, JC Enke, CA Kuszynski, CA Bierman, PJ Vose, JM Armitage, JO Devetten, MP Maness, LJ McGuire, TR Wisecarver, JL Joshi, SS Pavletic, ZS TI Nommyeloablative allogeneic stem cell transplantation (NST) for hematologic malignancies (HM) using pentostatin/low-dose total body irradiation (TBI). SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Univ Nebraska, Med Ctr, Omaha, NE USA. NIH, Washington, DC USA. RI Talmadge, James/A-5916-2008 OI Talmadge, James/0000-0002-6328-6056 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3671 BP 1022A EP 1022A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006455 ER PT J AU Fry, TJ Salzman, TC Hakim, F Love, C Layton, P Gress, R Fowler, D Bishop, MR Mackall, CL Wayne, AS AF Fry, TJ Salzman, TC Hakim, F Love, C Layton, P Gress, R Fowler, D Bishop, MR Mackall, CL Wayne, AS TI Non-myeloablative allogeneic hematopoietic stem cell transplantation (SCT) with pre-transplant targeted immune depletion results in rapid full donor engraftment in pediatric patients with malignancy. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Pediat Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3672 BP 1022A EP 1023A PN 1 PG 2 WC Hematology SC Hematology GA 986CF UT WOS:000233426006456 ER PT J AU Chavakis, T Bdeir, K Cines, DB Fogt, F Bdeir, Y Lubkowski, J Preissner, KT Hammes, HP Economopoulou, M AF Chavakis, T Bdeir, K Cines, DB Fogt, F Bdeir, Y Lubkowski, J Preissner, KT Hammes, HP Economopoulou, M TI Inhibition of pathological retinal neovascularization by alpha-defensins. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD USA. Univ Clin Mannheim, Dept Internal Med 5, Mannheim, Germany. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. NCI, Macromol Assembly Struct & Cell Signaling Sect, Frederick, MD USA. Univ Giessen, Inst Biochem, Giessen, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3678 BP 1024A EP 1024A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006462 ER PT J AU Zhang, XF Wang, JF Maor, Y Kunos, G Groopman, JE AF Zhang, XF Wang, JF Maor, Y Kunos, G Groopman, JE TI Endogenous cannabinoid-like arachidonoyl serine induces angiogenesis through novel pathways. SO BLOOD LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Society-of-Hematology CY DEC 10-13, 2005 CL Atlanta, GA SP Amer Soc Hematol C1 Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Expt Med, Boston, MA USA. Harvard Univ, Sch Med, Dept Surg, BIDMC, Boston, MA USA. Hebrew Univ Jerusalem, Dept Med Chem & Nat Prod, Jerusalem, Israel. NIAAA, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2005 VL 106 IS 11 MA 3690 BP 1027A EP 1027A PN 1 PG 1 WC Hematology SC Hematology GA 986CF UT WOS:000233426006474 ER PT J AU Thuille, N Heit, I Fresser, F Krumbock, N Bauer, B Leuthaeusser, S Darnmeier, S Graham, C Copeland, TD Shaw, S Baier, G AF Thuille, N Heit, I Fresser, F Krumbock, N Bauer, B Leuthaeusser, S Darnmeier, S Graham, C Copeland, TD Shaw, S Baier, G TI Critical role of novel Thr-219 autophosphorylation for the cellular function of PKC theta in T lymphocytes SO EMBO JOURNAL LA English DT Article DE autophosphorylation; cellular function; IL-2 activation; PKC theta; T cells ID PROTEIN-KINASE-C; KAPPA-B ACTIVATION; IN-VIVO; PEPTIDE SPECIFICITY; HYDROPHOBIC-MOTIF; PHOSPHORYLATION; CELLS; BINDING; IDENTIFICATION; EPSILON AB Phosphopeptide mapping identified a major autophosphorylation site, phospho (p)Thr-219, between the tandem Cl domains of the regulatory fragment in protein kinase C (PKC)theta. Confirmation of this identification was derived using (p)Thr-219 antisera that reacted with endogenous PKC theta in primary CD3(+) T cells after stimulation with phorbol ester, anti-CD3 or vanadate. The T219A mutation abrogated the capacity of PKC theta to mediate NF-kappa B, NF-AT and interleukin-2 promoter transactivation, and reduced PKC theta's ability in Jurkat T cells to phosphorylate endogenous cellular substrates. In particular, the T219A mutation impaired crosstalk of PKC theta with Akt/PKB alpha in NF-kappa B activation. Yet, this novel (p)Thr-219 site did not affect catalytic activity or second-messenger lipid-binding activity in vitro. Instead, the T219A mutation prevented proper recruitment of PKC theta in activated T cells. The PKC theta T219A mutant defects were largely rescued by addition of a myristoylation signal to force its proper membrane localization. We conclude that autophosphorylation of PKC theta at Thr-219 plays an important role in the correct targeting and cellular function of PKC theta upon antigen receptor ligation. C1 Innsbruck Med Univ, Sect Human Genet, Dept Med Genet Mol & Clin Pharmacol, A-6020 Innsbruck, Austria. ALTANA Pharma AG, Constance, Germany. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Baier, G (reprint author), Innsbruck Med Univ, Sect Human Genet, Dept Med Genet Mol & Clin Pharmacol, Schoepfstr 41, A-6020 Innsbruck, Austria. EM gottfried.baier@uibk.ac.at RI Baier, Gottfried/E-8755-2012; OI Thuille, Nikolaus/0000-0002-2253-3946 NR 28 TC 43 Z9 45 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD NOV 16 PY 2005 VL 24 IS 22 BP 3869 EP 3880 DI 10.1038/sj.emboj.7600856 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 990LM UT WOS:000233744500005 PM 16252004 ER PT J AU Morris, CR Vichinsky, EP Kato, GJ Gladwin, MT Hazen, S Morris, SM AF Morris, CR Vichinsky, EP Kato, GJ Gladwin, MT Hazen, S Morris, SM TI Arginine metabolism, pulmonary hypertension, and sickle cell disease - In reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID DIMETHYLARGININE; HEMOLYSIS C1 Childrens Hosp & Res Ctr Oakland, Dept Emergency Med, Oakland, CA 94609 USA. Childrens Hosp & Res Ctr Oakland, Dept Hematol Oncol, Oakland, CA USA. NHLBI, Vasc Therapeut Sect, Cardiovasc Branch, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Ctr Cardiovasc Diagnost & Prevent, Cleveland, OH 44195 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. RP Morris, CR (reprint author), Childrens Hosp & Res Ctr Oakland, Dept Emergency Med, Oakland, CA 94609 USA. EM claudiamorris@comcast.net RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 NR 6 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 16 PY 2005 VL 294 IS 19 BP 2433 EP 2434 DI 10.1001/jama.294.19.2433-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 984BL UT WOS:000233277400016 ER PT J AU Appel, LJ Sacks, FM Carey, VJ Obarzanek, E Swain, JF Miller, ER Conlin, PR Erlinger, TP Rosner, BA Laranjo, NM Charleston, J McCarron, P Bishop, LM AF Appel, LJ Sacks, FM Carey, VJ Obarzanek, E Swain, JF Miller, ER Conlin, PR Erlinger, TP Rosner, BA Laranjo, NM Charleston, J McCarron, P Bishop, LM CA OmniHeart Collaborative Res Grp TI Effects of protein, monounsaturated fat, and carbohydrate intake on blood pressure and serum lipids - Results of the OmniHeart randomized trial SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CORONARY-HEART-DISEASE; DIETARY-PROTEIN; HYPERTENSION PREVENTION; MEDITERRANEAN DIET; EDUCATION-PROGRAM; GLYCEMIC INDEX; WEIGHT-LOSS; OLIVE OIL; RISK; CHOLESTEROL AB Context Reduced intake of saturated fat is widely recommended for prevention of cardiovascular disease. The type of macronutrient that should replace saturated fat remains uncertain. Objective To compare the effects of 3 healthful diets, each with reduced saturated fat intake, on blood pressure and serum lipids. Design, Setting, and Participants Randomized, 3-period, crossover feeding study (April 2003 to June 2005) conducted in Baltimore, Md, and Boston, Mass. Participants were 164 adults with prehypertension or stage 1 hypertension. Each feeding period lasted 6 weeks and body weight was kept constant. Interventions A diet rich in carbohydrates; a diet rich in protein, about half from plant sources; and a diet rich in unsaturated fat, predominantly monounsaturated fat. Main Outcome Measures Systolic blood pressure and low-density lipoprotein cholesterol. Results Blood pressure, low-density lipoprotein cholesterol, and estimated coronary heart disease risk were lower on each diet compared with baseline. Compared with the carbohydrate diet, the protein diet further decreased mean systolic blood pressure by 1.4 mm Hg (P=.002) and by 3.5 mm Hg (P=.006) among those with hypertension and decreased low-density lipoprotein cholesterol by 3.3 mg/dL (0.09 mmol/L; P=.01), high-density lipoprotein cholesterol by 1.3 mg/dL (0.03 mmol/L; P=.02), and triglycerides by 15.7 mg/dL (0.18 mmol/L; P<.001). Compared with the carbohydrate diet, the unsaturated fat diet decreased systolic blood pressure by 1.3 mm Hg (P=.005) and by 2.9 mm Hg among those with hypertension (P=.02), had no significant effect on low-density lipoprotein cholesterol, increased high-density lipoprotein cholesterol by 1.1 mg/dL (0.03 mmol/L; P=.03), and lowered triglycerides by 9.6 mg/dL (0.11 mmol/L; P=.02). Compared with the carbohydrate diet, estimated 10-year coronary heart disease risk was lower and similar on the protein and unsaturated fat diets. Conclusion In the setting of a healthful diet, partial substitution of carbohydrate with either protein or monounsaturated fat can further lower blood pressure, improve lipid levels, and reduce estimated cardiovascular risk. Clinical Trials Registration ClinicalTrials.gov Identifier: NCT00051350. C1 Johns Hopkins Univ, Sch Med, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Epidemiol, Baltimore, MD 21205 USA. Bloomberg Sch Publ Hlth, Baltimore, MD USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Brigham & Womens Hosp, Div Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Brigham & Womens Hosp, Gen Clin Res Ctr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. VA Boston Healthcare Syst, Div Endocrinol, Boston, MA USA. RP Appel, LJ (reprint author), Johns Hopkins Univ, Sch Med, Welch Ctr Prevent Epidemiol & Clin Res, 2024 E Monument St,Suite 2-618, Baltimore, MD 21205 USA. EM lappel@jhmi.edu FU NCRR NIH HHS [RR02635]; NHLBI NIH HHS [HL67098, HL68712]; NIDDK NIH HHS [DK63214] NR 47 TC 487 Z9 500 U1 10 U2 62 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 16 PY 2005 VL 294 IS 19 BP 2455 EP 2464 DI 10.1001/jama.294.19.2455 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 984BL UT WOS:000233277400024 PM 16287956 ER PT J AU Turner, A Chen, SN Joike, MK Pendland, SL Pauli, GF Farnsworth, NR AF Turner, A Chen, SN Joike, MK Pendland, SL Pauli, GF Farnsworth, NR TI Inhibition of uropathogenic Escherichia coli by cranberry juice: A new antiadherence assay SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Escherichia coli; cranberry; Vaccinium macrocarpon; uroepithelial; bacterial adhesin; bacterial adhesion; papG protein; P-fimbriae; 1-methoxygalactose; prunin; phloridzin; alpha-D-galactopyranosyl-(1 -> 4)-alpha-D-galactopyranose; galabiose; botanical dietary supplement standardization ID URINARY-TRACT INFECTIONS; B2 EPICATECHIN-(4-BETA-8)-EPICATECHIN; D-GALACTOPYRANOSE; PMR SPECTROSCOPY; BLUEBERRY JUICES; NMR-SPECTROSCOPY; EPITHELIAL-CELLS; ADHESIN ACTIVITY; PAPG ADHESINS; ADHERENCE AB A combination of microplate, technology and turbidity assessment for testing the adherence of P-fimbriated Escherichia coli to human uroepithelial cell line T24, validated with the addition of the known inhibitor 4-O-alpha-D-galactopyranosyl-alpha-D-galactopyranose (galabiose), resulted in a highthroughput, biologically relevant assessment of cranberry (Vaccinium macrocarpon). P-fimbriated ATCC E. coli strains 25922, 29194, and 49161 were inhibited by galabiose. ATCC 29194, a representative urine isolate containing the papGII allele (Class II fimbrial adhesin) and demonstrating the most significant inhibition in the presence of galabiose, was chosen for further testing. In this assay, a low-polarity fraction of cranberry juice cocktail demonstrated dose-dependent inhibition of E coli adherence. Reported here, for the first time in V. macrocarpon, are 1-O-methyl galactose, prunin, and phlorizin, identified in an active fraction of cranberry juice concentrate. This in vitro assay will be useful for the standardization of cranberry dietary supplements and is currently being used for bioassay-guided fractionation of cranberry juice concentrate. C1 UIC, NIH, Ctr Bot Dietary Supplements Res Womens Hlth, Dept Med Ctr & Pharmacognosy,Coll Pharm, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Dept Biol, Mol Biol Lab, Chicago, IL 60612 USA. Univ Illinois, Coll Pharm, Antimicrobial Res Ctr, Chicago, IL 60612 USA. RP Farnsworth, NR (reprint author), UIC, NIH, Ctr Bot Dietary Supplements Res Womens Hlth, Dept Med Ctr & Pharmacognosy,Coll Pharm, MC781, Chicago, IL 60612 USA. EM norman@uic.edu OI Pauli, Guido/0000-0003-1022-4326 FU NCCIH NIH HHS [F3AT00623, P50AT00155] NR 64 TC 34 Z9 37 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD NOV 16 PY 2005 VL 53 IS 23 BP 8940 EP 8947 DI 10.1021/jf052035u PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 984LP UT WOS:000233306700011 PM 16277386 ER PT J AU Guo, HB Wlodawer, A Guo, H AF Guo, HB Wlodawer, A Guo, H TI A general acid-base mechanism for the stabilization of a tetrahedral adduct in a serine-carboxyl peptidase: A computational study SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID NEURONAL CEROID-LIPOFUSCINOSIS; ANGSTROM CRYSTAL-STRUCTURE; MOLECULAR-DYNAMICS; PROTEINASE; PROTEASES; FAMILY; ENERGY; SITE; SPECIFICITY; KUMAMOLISIN C1 Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA. Univ Tennessee, Ctr Excellence Struct Biol, Knoxville, TN 37996 USA. NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Univ Tennessee, Dept Biochem & Cellular & Mol Biol, Knoxville, TN 37996 USA. EM hguo1@utk.edu RI Guo, Hao-Bo/B-7486-2009; Guo, Hong/E-6357-2010 OI Guo, Hao-Bo/0000-0003-1321-1758; NR 29 TC 23 Z9 24 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 16 PY 2005 VL 127 IS 45 BP 15662 EP 15663 DI 10.1021/ja0520565 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 987RQ UT WOS:000233535400001 PM 16277482 ER PT J AU Stoyanovsky, DA Tyurina, YY Tyurin, VA Anand, D Mandavia, DN Gius, D Ivanova, J Pitt, B Billiar, TR Kagan, VE AF Stoyanovsky, DA Tyurina, YY Tyurin, VA Anand, D Mandavia, DN Gius, D Ivanova, J Pitt, B Billiar, TR Kagan, VE TI Thioredoxin and lipoic acid catalyze the denitrosation of low molecular weight and protein S-nitrosothiols SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID DISULFIDE INTERCHANGE REACTIONS; ELECTRON-PARAMAGNETIC-RESONANCE; TRIOXODINITRATE ANGELIS SALT; NITRIC-OXIDE SYNTHASE; SODIUM TRIOXODINITRATE; DIHYDROLIPOIC ACID; ACTIVE-SITE; NITROXYL ANION; HUMAN PLASMA; REDUCTION AB The nitrosation of cellular thiols has attracted much interest as a regulatory mechanism that mediates some of the pathophysiological effects of nitric oxide (NO). In cells, virtually all enzymes contain cysteine residues that can be subjected to S-nitrosation, whereby this process often acts as an activity switch. Nitrosation of biological thiols is believed to be mediated by N2O3, metal-nitrosyl complexes, and peroxynitrite. To date, however, enzymatic pathways for S-denitrosation of proteins have not been identified. Herein, we present experimental evidence that two ubiquitous cellular dithiols, thioredoxin and dihydrolipoic acid, catalyze the denitrosation of S-nitrosoglutathione, S-nitrosocaspase 3, S-nitrosoalbumin, and S-nitrosometallothionenin to their reduced state with concomitant generation of nitroxyl (HNO), the one-electron reduction product of NO. In these reactions, formation of NO and HNO was assessed by ESR spectrometry, potentiometric measurements, and quantification of hydroxylamine and sodium nitrite as end reaction products. Nitrosation and denitrosation of caspase 3 was correlated with its proteolytic activity. We also report that thioredoxin-deficient HeLa cells with mutated thioredoxin reductase denitrosate S-nitrosothiols less efficiently. We conclude that both thioredoxin and dihydrolipoic acid may be involved in the regulation of cellular S-nitrosothiols. C1 Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Environm & Occupat Hlth, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Ctr Free Rad & Antioxidant Hlth, Pittsburgh, PA 15213 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Kings Coll London, Sch Life & Hlth Sci, London SE1 9NH, England. RP Stoyanovsky, DA (reprint author), Univ Pittsburgh, Dept Surg, Pittsburgh, PA 15213 USA. EM stoyanovskyd@upmc.edu; kagan@pitt.edu OI Stoyanovsky, Detcho/0000-0001-5591-4780; Tyurin, Vladimir/0000-0002-3474-1697 FU NHLBI NIH HHS [HL64145, P01HL070807, R01HL070755]; NIEHS NIH HHS [ES09648]; NIGMS NIH HHS [GM44100] NR 78 TC 101 Z9 103 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 16 PY 2005 VL 127 IS 45 BP 15815 EP 15823 DI 10.1021/ja0529135 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 987RQ UT WOS:000233535400043 PM 16277524 ER PT J AU Fisher, B Costantino, JP Wickerham, DL Cecchini, RS Cronin, WM Robidoux, A Bevers, TB Kavanah, MT Atkins, JN Margolese, RG Runowicz, CD James, JM Ford, LG Wolmark, N AF Fisher, B Costantino, JP Wickerham, DL Cecchini, RS Cronin, WM Robidoux, A Bevers, TB Kavanah, MT Atkins, JN Margolese, RG Runowicz, CD James, JM Ford, LG Wolmark, N TI Tamoxifen for the prevention of breast cancer: Current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID RANDOMIZED-TRIAL; POSTMENOPAUSAL WOMEN; AROMATASE INHIBITORS; SERUM-LIPOPROTEINS; ANTITHROMBIN-III; PLASMA-LIPIDS; RISK-FACTORS; THERAPY; CHEMOPREVENTION; CARCINOMA AB Background. Initial findings from the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial (P-1) demonstrated that tamoxifen reduced the risk of estrogen receptor-positive tumors and osteoporotic fractures in women at increased risk for breast cancer. Side effects of varying clinical significance were observed. The trial was unblinded because of the positive results, and follow-up continued. This report updates our initial findings. Methods: Women (n = 13 388) were randomly assigned to receive placebo or tamoxifen for 5 years. Rates of breast cancer and other events were compared by the use of risk ratios (RRs) and 95% confidence intervals (CIs). Estimates of the net benefit from 5 years of tamoxifen therapy were compared by age, race, and categories of predicted breast cancer risk. Statistical tests were two-sided. Results: After 7 years of follow-up, the cumulative rate of invasive breast cancer was reduced from 42.5 per 1000 women in the placebo group to 24.8 per 1000 women in the tamoxifen group (RR = 0.57, 95% CI = 0.46 to 0.70) and the cumulative rate of noninvasive breast cancer was reduced from 15.8 per 1000 women in the placebo group to 10.2 per 1000 women in the tamoxifen group (RR = 0.63, 95% CI = 0.45 to 0.89). These reductions were similar to those seen in the initial report. Tamoxifen led to a 32% reduction in osteoporotic fractures (RR = 0.68, 95% CI = 0.51 to 0.92). Relative risks of stroke, deep-vein thrombosis, and cataracts (which increased with tamoxifen) and of ischemic heart disease and death (which were not changed with tamoxifen) were also similar to those initially reported. Risks of pulmonary embolism were approximately 11% lower than in the original report, and risks of endometrial cancer were about 29% higher, but these differences were not statistically significant. The net benefit achieved with tamoxifen varied according to age, race, and level of breast cancer risk. Conclusions: Despite the potential bias caused by the unblinding of the P-1 trial, the magnitudes of all beneficial and undesirable treatment effects of tamoxifen were similar to those initially reported, with notable reductions in breast cancer and increased risks of thromboembolic events and endometrial cancer. Readily identifiable subsets of individuals comprising 2.5 million women could derive a net benefit from the drug. C1 Operat Ctr, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Univ Pittsburgh, Ctr Biostat, Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Hop Hotel Dieu, Montreal, PQ, Canada. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Med Ctr, Boston, MA USA. SE Canc Control Consortium, Winston Salem, NC USA. Jewish Gen Hosp, Montreal, PQ, Canada. Univ Connecticut, Neag Comprehens Canc Ctr, Farmington, CT USA. Fox Chase Canc Ctr, Philadelphia, PA USA. NCI, Bethesda, MD 20892 USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. RP Fisher, B (reprint author), Univ Pittsburgh, Dept Surg, Magee Womens Hosp, 300 Halket St,Suite 350, Pittsburgh, PA 15213 USA. EM fisherb2@upmc.edu OI Cecchini, Reena/0000-0002-9075-9357 FU NCI NIH HHS [U10-CA-37377, U10-CA-69974] NR 64 TC 609 Z9 629 U1 4 U2 34 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 NOV 16 PY 2005 VL 97 IS 22 BP 1652 EP 1662 DI 10.1093/jnci/dji372 PG 11 WC Oncology SC Oncology GA 985DM UT WOS:000233356300008 PM 16288118 ER PT J AU Bernstein, L Patel, AV Ursin, G Sullivan-Halley, J Press, MF Deapen, D Berlin, JA Daling, JR McDonald, JA Norman, SA Malone, KE Strom, BL Liff, J Folger, SG Simon, MS Burkman, RT Marchbanks, PA Weiss, LK Spirtas, R AF Bernstein, L Patel, AV Ursin, G Sullivan-Halley, J Press, MF Deapen, D Berlin, JA Daling, JR McDonald, JA Norman, SA Malone, KE Strom, BL Liff, J Folger, SG Simon, MS Burkman, RT Marchbanks, PA Weiss, LK Spirtas, R TI Lifetime recreational exercise activity and breast cancer risk among black women and white women SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID HORMONE-BINDING GLOBULIN; MENSTRUAL-CYCLE PATTERNS; PHYSICAL-ACTIVITY; POSTMENOPAUSAL WOMEN; PREMENOPAUSAL WOMEN; INSULIN-RESISTANCE; AMERICAN WOMEN; SEX-HORMONES; YOUNG-WOMEN; AGE AB Back round. Physical inactivity is a potentially modifiable breast cancer risk factor. Because few data on this relationship exist for black women, we examined the relationship between breast cancer risk and lifetime and time- or age-specific measures of recreational exercise activity among white women and among black women. Methods: The Women's Contraceptive and Reproductive Experiences Study was a multicenter population-based case-control study of black women and white women aged 35-64 years with newly diagnosed invasive breast cancer. We collected detailed histories of lifetime recreational exercise activity during in-person interviews with 4538 case patients with breast cancer (1605 black and 2933 white) and 4649 control subjects (1646 black and 3033 white). Control subjects were frequency-matched to case patients on age, race, and study site. We examined associations between exercise activity measures (metabolic equivalents of energy expenditure [MET]-hours per week per year) and breast cancer risk overall and among subgroups defined by race, other breast cancer risk factors, and tumor characteristics by use of unconditional logistic regression. All statistical tests were two-sided. Results: Among all women, decreased breast cancer risk was associated with increased levels of lifetime exercise activity (e.g., average MET-hours per week per year, P-trend = .002). An average annual lifetime exercise activity that was greater than the median level for active control subjects was associated with an approximately 20% lower risk of breast cancer, compared with that for inactivity (for 6.7-15.1 MET-hours/week/year, odds ratio [OR] = 0.82, 95% confidence interval [CI] = 0.71 to 0.93; for >= 15.2 MET-hours/week/year, OR = 0.80, 95% CI = 0.70 to 0.92). The inverse associations did not differ between black and white women (for MET-hours/week/year, P-trend = .003 and P-trend = .09, respectively; homogeneity of trends P = .16). No modification of risk was observed by disease stage, estrogen receptor status, or any breast cancer risk factor other than first-degree family history of breast cancer. Conclusions: This study supports an inverse association between physical activity and breast cancer among black women and among white women. C1 Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90033 USA. Univ So Calif, Keck Sch Med, Dept Pathol, Los Angeles, CA 90033 USA. Univ Oslo, Dept Nutr, Oslo, Norway. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. Johnson & Johnson Pharmaceut Res & Dev, Titusville, NJ USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Ctr Dis Control & Prevent, Div Reprod Hlth, Atlanta, GA USA. Univ Penn, Sch Med, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Emory Univ, Sch Publ Hlth, Atlanta, GA USA. Wayne State Univ, Dept Internal Med, Karmanos Canc Inst, Detroit, MI 48202 USA. Baystate Med Ctr, Dept Obstet & Gynecol, Springfield, MA USA. NCI, Canc Ctr Branch, Bethesda, MD 20892 USA. NICHHD, Contracept & Reprod Hllth Branch, Populat Res Ctr, NIH, Bethesda, MD 20892 USA. RP Bernstein, L (reprint author), Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, 1441 Eastlake Ave, Los Angeles, CA 90033 USA. EM lbern@usc.edu FU NCI NIH HHS [N01-CN-0532, N01-PC-67006, N01-CN-67010, N01-CN-65064]; NICHD NIH HHS [N01 HD 2-3166, N01 HD 3-3168, N01 HD 3-3176, Y01 HD 7022, N01 HD 3-3174, N01 HD 3-3175] NR 52 TC 104 Z9 108 U1 1 U2 4 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 NOV 16 PY 2005 VL 97 IS 22 BP 1671 EP 1679 DI 10.1093/jnci/dji374 PG 9 WC Oncology SC Oncology GA 985DM UT WOS:000233356300010 PM 16288120 ER PT J AU Sherman, ME Carreon, JD Lacey, JV Devesa, SS AF Sherman, ME Carreon, JD Lacey, JV Devesa, SS TI Impact of hysterectomy on endometrial carcinoma rates in the United States SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CANCER INCIDENCE; TRENDS; CORPUS AB In the United States, endometrial carcinoma incidence rates, uncorrected for hysterectomy prevalence, are higher among white women than black women. We estimated corrected endometrial carcinoma rates by racial/ethnic groups and age (30-74 years) for 1992-2000 using data from the Surveillance, Epidemiology, and End Results program and the Behavioral Risk Factor Surveillance Survey. Hysterectomy prevalence was higher among black women than among Hispanic and white non-Hispanic women. Correcting for hysterectomy prevalence increased age-adjusted endometrial carcinoma rates per 105 woman-years from 29.2 to 48.7 (66.8% increase) overall, from 14.6 to 28.5 (95.3% increase) in blacks, from 18.8 to 29.6 (57.6% increase) in Hispanics, and from 33.2 to 54.9 (65.1%) in white non-Hispanics. This correction reduced the rate ratio for white non-Hispanics compared with blacks from 2.27 to 1.93. Among blacks but not Hispanics or white non-Hispanics, the endometrial carcinoma risk factors of obesity and diabetes were more prevalent among hysterectomized than non-hysterectomized women. Failure to correct for hysterectomy prevalence may lead to underestimates of endometrial carcinoma risk, especially among blacks. The high prevalence of hysterectomy among blacks with strong endometrial cancer risk factors may partly account for lower cancer rates in this group. C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Sherman, ME (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Room 7080, Bethesda, MD 20892 USA. EM shermanm@mail.nih.gov NR 14 TC 32 Z9 33 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD NOV 16 PY 2005 VL 97 IS 22 BP 1700 EP 1702 DI 10.1093/jnci/dji378 PG 3 WC Oncology SC Oncology GA 985DM UT WOS:000233356300014 PM 16288124 ER PT J AU Epstein, SL Kong, WP Misplon, JA Lo, CY Tumpey, TM Xu, L Nabel, GJ AF Epstein, SL Kong, WP Misplon, JA Lo, CY Tumpey, TM Xu, L Nabel, GJ TI Protection against multiple influenza A subtypes by vaccination with highly conserved nucleoprotein SO VACCINE LA English DT Article DE influenza; DNA vaccines; adenovirus vectors; conserved antigens; animal models; H5N1 influenza; heterosubtypic immunity ID CD8(+) T-CELLS; HETEROSUBTYPIC IMMUNITY; VIRUS-INFECTION; DNA VACCINES; IN-VITRO; MICE; HUMANS; IMMUNOGENICITY; REPLICATION; VECTOR AB Influenza epidemic and pandemic strains cannot be predicted with certainty. Current vaccines elicit antibodies effective against specific strains, but new strategies are urgently needed for protection against unexpected strains. DNA vaccines encoding conserved antigens protect animals against diverse subtypes, but their potency needs improvement. We tested DNA prime-recombinant adenoviral boost immunization to nucleoprotein (NP). Strong antibody and T cell responses were induced. Protection against challenge was T cell-dependent and substantially more potent than DNA vaccination alone. Importantly, vaccination protected against lethal challenge with highly pathogenic H5N1 virus. Thus, gene-based vaccination with NP may contribute to protective immunity against diverse influenza viruses through its ability to stimulate cellular immunity. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Immunol & Dev Biol, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Influenza Branch, Div Viral & Rickettsial Dis, Atlanta, GA 30333 USA. RP Epstein, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Immunol & Dev Biol, Bethesda, MD 20892 USA. EM epsteins@cber.fda.gov NR 35 TC 190 Z9 202 U1 0 U2 8 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 NOV 16 PY 2005 VL 23 IS 46-47 BP 5404 EP 5410 DI 10.1016/j.vaccine.2005.04.047 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 989NL UT WOS:000233680700020 PM 16011865 ER PT J AU Walker, RI Van de Verg, LL Hall, RH Schmitt, CK Woo, K Hale, V AF Walker, RI Van de Verg, LL Hall, RH Schmitt, CK Woo, K Hale, V TI Enteric vaccines for pediatric use - Workshop summary SO VACCINE LA English DT Editorial Material DE pediatric vaccines; enteric pathogens; vaccine development and implementation AB Diarrheal diseases remain a major cause of death in children under 5 in less developed countries (LDCs). Vaccine development and implementation offers the best near-term approach to alleviating this problem. For this reason, a workshop to examine the possibilities for making enteric vaccines available to meet the specific needs of children in LDCs was convened in Virginia on April 24-26, 2004. Discussants considered research and development needs, regulatory and business issues, and previous experiences with enteric vaccine development and implementation. No insurmountable roadblocks to progress in this area were noted, and the possibility currently exists that property supported efforts will enable the realization of enteric vaccines for pediatric use. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Rockville, MD 20851 USA. NIAID, Enter & Hepat Dis Branch, DMID, NIH, Bethesda, MD 20892 USA. Inst OneWorld Hlth, San Francisco, CA 94104 USA. RP Walker, RI (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, 1401 Rockville Pike,HFM-425, Rockville, MD 20851 USA. EM walkerri@cber.fda.gov NR 0 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 16 PY 2005 VL 23 IS 46-47 BP 5432 EP 5439 DI 10.1016/j.vaccine.2005.01.161 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 989NL UT WOS:000233680700024 PM 16286159 ER PT J AU Lim, U Schenk, M Kelemen, LE Davis, S Cozen, W Hartge, P Ward, MH Stolzenberg-Solomon, R AF Lim, U Schenk, M Kelemen, LE Davis, S Cozen, W Hartge, P Ward, MH Stolzenberg-Solomon, R TI Dietary determinants of one-carbon metabolism and the risk of non-Hodgkin's lymphoma: NCI-SEER case-control study, 1998-2000 SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alcohol drinking; case-control studies; folic acid; lymphoma; non-Hodgkin; methionine; riboflavin; vitamin B-6; vitamin B-12 ID SERINE HYDROXYMETHYLTRANSFERASE GENES; CYSTATHIONINE BETA-SYNTHASE; ALCOHOL-CONSUMPTION; UNITED-STATES; MALIGNANT-LYMPHOMA; HISTORY QUESTIONNAIRE; THYMIDYLATE SYNTHASE; DNA HYPOMETHYLATION; HISTOLOGIC SUBTYPE; CONNECTICUT WOMEN AB The role of dietary one-carbon determinants remains largely unexplored for non-Hodgkin's lymphoma (NHL). In a population-based case-control study of non-African-American adult (aged 20-74 years) women and men from four US Surveillance, Epidemiology, and End Results study centers (Detroit, Michigan; Iowa; Los Angeles, California; and Seattle, Washington; 1998-2000), the authors examined folate; vitamins B-2, B-6, and B-12; methionine; and a one-carbon antagonist, alcohol, in 425 incident NHL cases and 359 controls who completed a detailed food frequency questionnaire. Adjusted odds ratios and 95% confidence intervals were estimated by using unconditional logistic regression. Higher intake of one-carbon determinants from food was associated with a lower risk of NHL, but that for only vitamin B-6 (highest vs. lowest quartile: odds ratio = 0.57, 95% confidence interval: 0.34, 0.95; p trend = 0.01) and methionine (odds ratio = 0.49, 95% confidence interval: 0.31, 0.76; p trend = 0.002) reached statistical significance. Folate from food was inversely associated with diffuse subtype (odds ratio = 0.47, 95% confidence interval: 0.23, 0.94; p trend = 0.03). The authors found no association between total (food plus supplement) vitamins and NHL. Nonusers of alcohol had an elevated NHL risk compared with users, and alcohol did not modify other nutrient-NHL associations. Findings suggest that one-carbon nutrients, particularly vitamin B-6 and methionine, may be protective against NHL. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Wayne State Univ, Karmanos Canc Inst, Dept Family Med, Detroit, MI USA. Mayo Clin, Coll Med, Dept Hlth Sci Res, Rochester, MN USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD USA. RP Stolzenberg-Solomon, R (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 320, Rockville, MD 20852 USA. EM stolzenr@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [N01-PC-67008, N01-PC-67009, N01-PC-67010, N02-PC-71105, N01-PC-65064] NR 59 TC 34 Z9 35 U1 2 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 15 PY 2005 VL 162 IS 10 BP 953 EP 964 DI 10.1093/aje/kwi310 PG 12 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 983GG UT WOS:000233218800003 PM 16221809 ER PT J AU Madiraju, C Edler, MC Hamel, E Raccor, BS Balachandran, R Zhu, GY Giuliano, KA Vogt, A Shin, YS Fournier, JH Fukui, YH Bruckner, AM Curran, DP Day, BW AF Madiraju, C Edler, MC Hamel, E Raccor, BS Balachandran, R Zhu, GY Giuliano, KA Vogt, A Shin, YS Fournier, JH Fukui, YH Bruckner, AM Curran, DP Day, BW TI Tubulin assembly, taxoid site binding, and cellular effects of the microtubule-stabilizing agent dictyostatin SO BIOCHEMISTRY LA English DT Article ID OVARIAN-CANCER CELLS; MARINE SPONGE ORIGIN; PACLITAXEL TAXOL; BIOLOGICAL EVALUATION; PURIFIED TUBULIN; DRUG DISCOVERY; EPOTHILONE-B; DISCODERMOLIDE; RESISTANT; ANALOGS AB (-)-Dictyostatin is a sponge-derived, 22-member macrolactone natural product shown to cause cells to accumulate in the G2/M phase of the cell cycle, with changes in intracellular microtubules analogous to those observed with paclitaxel treatment. Dictyostatin also induces assembly of purified tubulin more rapidly than does paclitaxel, and nearly as vigorously as does dictyostatin's close structural congener, (+)-discodermolide (Isbrucker et al. (2003), Biochern. Phannacol. 65, 75-82). We used synthetic (-)dictyostatin to study its biochemical and cytological activities in greater detail. The antiproliferative activity of dictyostatin did not differ greatly from that of paclitaxel or discodermolide. Like discodermolide, diclyostatin retained antiproliferative activity against human ovarian carcinoma cells resistant to paclitaxel due to beta-tubulin mutations and caused conversion of cellular soluble tubulin pools to microtubules. Detailed comparison of the abilities of dictyostatin and discodermolide to induce tubulin assembly demonstrated that the compounds had similar potencies. Dictyostatin inhibited the binding of radiolabeled discodermolide to microtubules more potently than any other compound examined, and dictyostatin and discodermolide had equivalent activity as inhibitors of the binding of both radiolabeled epothilone B and paclitaxel to microtubules. These results are consistent with the idea that the macrocyclic structure of dictyostatin represents the template for the bioactive conformation of discodermolide. C1 Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Pharmacol, Pittsburgh, PA 15261 USA. NCI, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Ft Detrick, MD 21702 USA. RP Day, BW (reprint author), Univ Pittsburgh, Dept Pharmaceut Sci, 721 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. EM bday@pitt.edu OI ZHU, Guangyu/0000-0002-4710-7070 FU NCI NIH HHS [CA078039] NR 52 TC 70 Z9 72 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 15 PY 2005 VL 44 IS 45 BP 15053 EP 15063 DI 10.1021/bi0506861 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 984IG UT WOS:000233295900037 PM 16274252 ER PT J AU Perlman, WR Tomaskovic-Crook, E Montague, DM Webster, MJ Rubinow, DR Kleinman, JE Weickert, CS AF Perlman, WR Tomaskovic-Crook, E Montague, DM Webster, MJ Rubinow, DR Kleinman, JE Weickert, CS TI Alteration in estrogen receptor alpha mRNA levels in frontal cortex and hippocampus of patients with major mental illness SO BIOLOGICAL PSYCHIATRY LA English DT Review DE age of onset; bipolar disorder; gender difference; major depression; psychosis; schizophrenia ID PITUITARY-GONADAL AXIS; FORCED SWIM TEST; DORSOLATERAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL BLOOD-FLOW; MENSTRUAL-CYCLE; ER-ALPHA; RIBONUCLEIC-ACID; MOOD DISORDERS; POSTPARTUM DEPRESSION AB Background: Gender differences have been described in major mental illnesses (MMI). The dorsolateral prefrontal cortex (DLPFC) and hippocampus are estrogen-sensitive brain regions structurally and functionally altered in patients with MMI. We hypothesized that gender-specific alterations in DLPFC and hippocampus estrogen receptor alpha (ER alpha) mRNA levels may exist in MMI patients. Methods: We used Northern blot analysis to survey the expression of ER alpha mRNA transcripts in brain and body, detected by our human ER alpha riboprobe and in situ hybridization, to examine the expression pattern and quantify ER alpha mRNA levels in DLPFC and anterior hippocampus of patients with major depressive disorder (MDD), schizophrenia, and bipolar disorder compared with normal control subjects. Results: Northern blotting revealed brain-region-specific differences in expression levels of a 5 kb ER alpha mRNA transcript. By in situ hybridization, ER alpha mRNA was detected in all layers of DLPFC and anll hippocampal subfields in all subjects. We detected greater DLPFC ER alpha mRNA expression in male compared with female MDD subjects and reduced ER alpha mRNA levels in the dentate gyrus of schizophrenics compared with control subjects. Conclusions: Our results suggest that alterations in ER alpha mRNA levels exist in distinct telencephalic regions in male and female MDD patients, and in both genders in schizophrenia. C1 NIMH, Clin Brain Disorders Branch, MiNDS Unit, NIH,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIMH, Behav Endocrinol Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. NIMH, Intramural Res Program, NIH, US Dept HHS, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Stanley Fdn, Brain Res Lab, Dept Psychiat, Bethesda, MD 20814 USA. RP Weickert, CS (reprint author), NIMH, Clin Brain Disorders Branch, MiNDS Unit, NIH,US Dept Hlth & Human Serv, 10 Ctr Dr,Room 4D18, Bethesda, MD 20892 USA. EM shannowc@mail.nih.gov RI Shannon Weickert, Cynthia/G-3171-2011; Tomaskovic-Crook, Eva/C-9339-2016 OI Tomaskovic-Crook, Eva/0000-0002-7818-9013 NR 107 TC 51 Z9 54 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD NOV 15 PY 2005 VL 58 IS 10 BP 812 EP 824 DI 10.1016/j.biopsych.2005.04.047 PG 13 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 987WM UT WOS:000233548300007 PM 16112656 ER PT J AU Lieto, LD Borrego, F Coligan, JE AF Lieto, LD Borrego, F Coligan, JE TI CD94 1A/1B: a window opens into NK-cell development SO BLOOD LA English DT Editorial Material ID DUAL PROMOTERS; NATURAL-KILLER; GENE AB Lin and colleagues report that patients with lymphoblastic lymphomas (LBLs) expressing CD94 1A transcripts had a better prognosis than patients with LBLs lacking CD94 1A transcript expression. C1 NIAID, Bethesda, MD 20892 USA. RP Lieto, LD (reprint author), NIAID, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2005 VL 106 IS 10 BP 3338 EP 3339 DI 10.1182/blood-2005-08-3493 PG 2 WC Hematology SC Hematology GA 982US UT WOS:000233187700009 ER PT J AU Hill, DA Gilbert, E Dores, GM Gospodarowicz, M van Leeuwen, FE Holowaty, E Glimelius, B Andersson, M Wiklund, T Lynch, CF van't Veer, M Storm, H Pukkala, E Stovall, M Curtis, RE Allan, JM Boice, JD Travis, LB AF Hill, DA Gilbert, E Dores, GM Gospodarowicz, M van Leeuwen, FE Holowaty, E Glimelius, B Andersson, M Wiklund, T Lynch, CF van't Veer, M Storm, H Pukkala, E Stovall, M Curtis, RE Allan, JM Boice, JD Travis, LB TI Breast cancer risk following radiotherapy for Hodgkin lymphoma: modification by other risk factors SO BLOOD LA English DT Article ID X-RAY THERAPY; FAMILY-HISTORY; RADIATION HYPERSENSITIVITY; CONTRALATERAL BREAST; POOLED ANALYSIS; BOMB SURVIVORS; MAMMARY-TUMORS; ATM MUTATIONS; YOUNG-WOMEN; DISEASE AB The importance of genetic and other risk factors in the development of breast cancer after radiotherapy (FIT) for Hodgkin lymphoma (HL) has not been determined. We analyzed data from a breast cancer case-control study (105 patients, 266 control subjects) conducted among 3 817 survivors of HL diagnosed at age 30 years or younger in 6 population-based cancer registries. Odds ratios (ORs) and excess relative risks (ERRs) were calculated using conditional regression. Women who received RT exposure (>= 5 Gy radiation dose to the breast) had a 2.7-fold increased breast cancer risk (95% confidence interval (CI) 1.4-5.2), compared with those given less than 5 Gy. RT exposure (>= 5 Gy) was associated with an OR of 0.8 (95% CI, 0.2-3.4) among women with a first- or second-degree family history of breast or ovarian cancer, and 5.8 (95% CI, 2.1-16.3) among all other women (interaction P = .03). History of a live birth appeared to increase the breast cancer risk associated with RT among women not treated with ovarian-damaging therapies. Breast cancer risk following RT varied little according to other factors. The additional increased relative risk of breast cancer after RT for HL is unlikely to be larger among women with a family history of breast or ovarian cancer than among other women. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Netherlands Canc Inst, Amsterdam, Netherlands. Canc Care Ontario, Toronto, ON, Canada. Uppsala Univ, Uppsala, Sweden. Danish Canc Soc, Copenhagen, Denmark. Univ Helsinki, Cent Hosp, Helsinki, Finland. Univ Iowa, Iowa City, IA USA. Finnish Canc Registry, FIN-00170 Helsinki, Finland. Dr Daniel Den Hoed Canc Ctr, NL-3008 AE Rotterdam, Netherlands. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ York, Epidemiol & Genet Unit, York YO10 5DD, N Yorkshire, England. Int Epidemiol Inst, Rockville, MD USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. RP Hill, DA (reprint author), Univ New Mexico, Hlth Sci Ctr, Dept Internal Med, MSC 08 4630,1 Univ New Mexico, Albuquerque, NM 87131 USA. EM dahill@salud.unm.edu RI Allan, James/B-4448-2009; OI Storm, Hans/0000-0001-7223-8198 NR 48 TC 56 Z9 57 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2005 VL 106 IS 10 BP 3358 EP 3365 DI 10.1182/blood-2005-04-1535 PG 8 WC Hematology SC Hematology GA 982US UT WOS:000233187700014 PM 16051739 ER PT J AU Palena, C Foon, KA Panicali, D Yafal, AG Chinsangaram, J Hodge, JW Schlom, J Tsang, KY AF Palena, C Foon, KA Panicali, D Yafal, AG Chinsangaram, J Hodge, JW Schlom, J Tsang, KY TI Potential approach to immunotherapy of chronic lymphocytic leukemia (CLL): enhanced immunogenicity of CLL cells via infection with vectors encoding for multiple costimulatory molecules SO BLOOD LA English DT Article ID VACCINIA VIRUS ANKARA; ANTIGEN-PRESENTING CELLS; CYTOTOXIC T-LYMPHOCYTES; HUMAN B-CELLS; GENE-TRANSFER; DENDRITIC CELLS; CD40 LIGAND; TRIAD; ACTIVATION; EXPRESSION AB Chronic lymphocytic leukemia (CLL) is a disease of CD5(+) B lymphocytes (designated as CLL cells) that are inefficient antigen-presenting cells. Their poor ability to present antigens to the T cells, largely due to an inadequate costimulatory capacity, is manifested as a failure to stimulate proliferation of both allogeneic and autologous T cells. We have investigated the ability of in vitro manipulated CLL cells, via hyperexpression of a triad of costimulatory molecules (B7-1, intercellular adhesion molecule 1 [ICAM-1], and leukocyte-function-associated antigen 3 [LFA-3], designated TRICOM), to stimulate effective antitumor T-cell responses. A recombinant modified vaccinia virus strain Ankara (MVA), which is a highly attenuated, replication-impaired virus variant, was successfully used to infect and deliver the simultaneous expression of the 3 human costimulatory molecules in TRICOM on the surface of the CLL cells. Proliferation of allogeneic and autologous T cells was observed when MVA-TRICOM-infected CLL cells were used as stimulators in proliferation assays. Cytotoxic T lymphocytes, generated in vitro by stimulation of autologous T cells with MVA-TRICOM-infected CLL cells, showed cytotoxicity against unmodified/uninfected CLL cells. Therefore, our findings suggest that the use of CLL cells infected ex vivo with MVA-TRICOM or direct injection of MVA-TRICOM in patients with CLL has potential for the immunotherapy of CLL. C1 NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Div Hematol Oncol, Inst Canc, Pittsburgh, PA 15260 USA. Therion Biol Corp, Cambridge, MA USA. RP Schlom, J (reprint author), NCI, Tumor Immunol & Biol Lab, Canc Res Ctr, NIH, 10 Ctr Dr,Rm 8B09,MSC 1750, Bethesda, MD 20892 USA. EM js141c@nih.gov RI Hodge, James/D-5518-2015 OI Hodge, James/0000-0001-5282-3154 FU NCI NIH HHS [Z01 BC010425-06, Z01 BC010427-06] NR 50 TC 20 Z9 20 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2005 VL 106 IS 10 BP 3515 EP 3523 DI 10.1182/blood-2005-03-1214 PG 9 WC Hematology SC Hematology GA 982US UT WOS:000233187700037 PM 16081691 ER PT J AU Herbeuval, JP Grivel, JC Boasso, A Hardy, AW Chougnet, C Dolan, MJ Yagita, H Lifson, JD Shearer, GM AF Herbeuval, JP Grivel, JC Boasso, A Hardy, AW Chougnet, C Dolan, MJ Yagita, H Lifson, JD Shearer, GM TI CD4(+) T-cell death induced by infectious and noninfectious HIV-1: role of type 1 interferon-dependent, TRAEL/DR5-mediated apoptosis SO BLOOD LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; LIGAND TRAIL; PERIPHERAL-BLOOD; DENDRITIC CELLS; HIV-1-INFECTED PATIENTS; GASTROINTESTINAL-TRACT; LYMPH-NODES; FAS; ALPHA; LYMPHOCYTES AB It has been proposed that direct and indirect mechanisms contribute to the unresolved issue of CD4(+) T-cell depletion that results from HIV-1 infection. We recently reported that plasma levels of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) are elevated in HIV-1-infected patients and that they correlate with viral load. The present study investigates the expression of TRAIL death receptor 5 (DR5) in the peripheral-blood mononuclear cells (PBMCs) of HIV-1-infected patients and its role in CD4(+) T-cell death. DR5 expression was elevated and associated with the apoptotic marker annexin V. Apoptosis was reduced in CD4(+) T cells when cultured with anti-DR5 antibody.The decreased viral loads and increased anti-DR5 antibody. CD4(+), but not CD8(+), T cells from uninfected donors expressed TRAIL, DR5, and activated caspase-3 when cultured with infectious or noninfectious HIV-1, resulting in preferential apoptosis of CD4(+) T cells. TRAIL, caspase-3 expression, and apoptosis were type 1 interferon (IFN) dependent. Induction of apoptosis and DR5 expression required glycoprotein 120 (gp120)-CD4 interaction. Finally, we analyzed DR5 expression CD4 counts of HAART-responsive patients were associated with a decrease in DR5 mRNA expression by CD4(+) T lymphocytes. We propose a novel model in which a type 1 IFN-regulated TRAIL/DR5 mechanism induces apoptosis of HIV-1-exposed CD4(+) T cells. C1 NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. Childrens Hosp Res Fdn, Div Mol Immunol, Cincinnati, OH 45229 USA. Wilford Hall USAF Med Ctr, Infect Dis Serv, Lackland AFB, TX 78236 USA. Juntendo Univ, Sch Med, Dept Immunol, Tokyo 113, Japan. NCI, AIDS Vaccine Program, SAIC Frederick Inc, 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 NCI NIH HHS [N01-CO-12400] NR 51 TC 126 Z9 135 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2005 VL 106 IS 10 BP 3524 EP 3531 DI 10.1182/blood-2005-03-1243 PG 8 WC Hematology SC Hematology GA 982US UT WOS:000233187700038 PM 16046522 ER PT J AU Kundu, M Compton, S Garrett-Beal, L Stacy, T Starost, MF Eckhaus, M Speck, NA Liu, PP AF Kundu, M Compton, S Garrett-Beal, L Stacy, T Starost, MF Eckhaus, M Speck, NA Liu, PP TI Runx1 deficiency predisposes mice to T-lymphoblastic lymphoma SO BLOOD LA English DT Article ID ACUTE MYELOGENOUS LEUKEMIA; ACUTE MYELOID-LEUKEMIA; AML1/PEBP2-ALPHA-B GENE; POINT MUTATIONS; FUSION GENE; HEMATOPOIESIS; CBFA2; AML1; LEUKEMOGENESIS; TRANSLOCATION AB Chromosomal rearrangements affecting RUNX1 and CBFB are common in acute leukemias. These mutations result in the expression of fusion proteins that act dominant-negatively to suppress the normal function of the Runt-related transcription factor 1 (RUNX)/core binding factor beta (CBF beta) complexes. In addition, loss-of-function mutations in Runt-related transcription factor 1 (RUNX1) have been identified in sporadic cases of acute myeloid leukemia (AML) and in association with the familial platelet disorder with propensity to develop AML (FPD/AML). In order to examine the hypothesis that decreased gene dosage of RUNX1 may be a critical event in the development of leukemia, we treated chimeric mice generated from Runx1(lacZ/lacZ) embryonic stem (ES) cells that have homozygous disruption of the Runx1 gene with N-ethyl-N-nitrosourea (ENU). We observed an increased incidence of T-lymphoblastic lymphoma in Runx1(lacZ/lacZ) compared with wildtype chimeras and confirmed that the tumors were of ES-cell origin. Our results therefore suggest that deficiency of Runx1 can indeed predispose mice to hematopoietic malignancies. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH USA. NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. RP Liu, PP (reprint author), 49 Convent Dr,Bldg 49,Rm 3A26, Bethesda, MD 20892 USA. EM pliu@mail.nih.gov RI Liu, Paul/A-7976-2012 OI Liu, Paul/0000-0002-6779-025X FU NCI NIH HHS [R01 CA058343] NR 18 TC 28 Z9 28 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2005 VL 106 IS 10 BP 3621 EP 3624 DI 10.1182/blood-2005-04-1447 PG 4 WC Hematology SC Hematology GA 982US UT WOS:000233187700051 PM 16051740 ER PT J AU Sconocchia, G Lau, M Provenzano, M Rezvani, K Wongsena, W Fujiwara, H Hensel, N Melenhorst, J Li, JM Ferrone, S Barrett, AJ AF Sconocchia, G Lau, M Provenzano, M Rezvani, K Wongsena, W Fujiwara, H Hensel, N Melenhorst, J Li, JM Ferrone, S Barrett, AJ TI The antileukemia effect of HLA-matched NK and NK-T cells in chronic myelogenous leukemia involves NKG2D-target-cell interactions SO BLOOD LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; NATURAL-KILLER-CELLS; BONE-MARROW-TRANSPLANTATION; LYMPHOCYTES-T; IN-VITRO; EXPRESSION; LIGANDS; NKG2D; CYTOTOXICITY; RECEPTORS AB To study natural killer (NK) cell-mediated antileukemic activity in chronic myelogenous leukemia (CIVIL), we investigated the ability of HLA-matched and mismatched CD56(+) cells to inhibit granulocyte macrophage-colony-forming unit (CFU-GM) formation by leukemic CD34(+) cells. In 14 HLA-identical donor-recipient pairs, donor CD56(+) cells inhibited CIVIL CFU-GM comparably to effectors from 14 HLA-mismatched unrelated individuals (mean inhibition 42% +/- 9% vs 39.5% +/- 7% at a 10:1 effector-to-target (E/T) ratio), suggesting that killer inhibitory receptor (KIR) incompatibility was not essential for an antileukemic effect. Both CD56(+)CD3(-) (natural killer [NK]) and CD56(+)CD3(+)(NK-T) cells inhibited CFU-GM growth of CML but not normal CD34(+) cells. A mechanism for this leukemia-specific cytotoxicity was suggested by the abnormal overexpression of major histocompatibility class I chain-related gene A or gene B (MICA/B) on CIVIL CD34 cells and their ability to bind the NK activation ligand NKG2D. However, in vivo, CIVIL cells may avoid NK-cell-mediated immune destruction by immune escape, shedding MICA into the plasma, thereby down-regulating NKG2D on CIVIL CD56(+) cells. C1 NHLBI, Stem Cell Allotransplantat Sect, Hematol Branch, Bethesda, MD 20892 USA. NIH, Mol Immunol Sect, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Dept Immunol, Buffalo, NY 14263 USA. RP Barrett, AJ (reprint author), Bldg 10,Rm 7C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM barrettj@nhlbi.nih.gov NR 34 TC 49 Z9 58 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 15 PY 2005 VL 106 IS 10 BP 3666 EP 3672 DI 10.1182/blood-2005-02-0479 PG 7 WC Hematology SC Hematology GA 982US UT WOS:000233187700058 PM 16046526 ER PT J AU Staib, F Robles, AI Varticovski, L Wang, XW Zeeberg, BR Sirotin, M Zhurkin, VB Hofseth, LJ Hussain, SP Weinstein, JN Galle, PR Harris, CC AF Staib, F Robles, AI Varticovski, L Wang, XW Zeeberg, BR Sirotin, M Zhurkin, VB Hofseth, LJ Hussain, SP Weinstein, JN Galle, PR Harris, CC TI The p53 tumor suppressor network is a key responder to microenvironmental components of chronic inflammatory stress SO CANCER RESEARCH LA English DT Article ID NITRIC-OXIDE SYNTHASE; GENE-EXPRESSION; REPLICATION ARREST; HYDROGEN-PEROXIDE; MUTATION LOAD; DNA-DAMAGE; WILD-TYPE; HYPOXIA; CANCER; CELLS AB Activation of the p53 network plays a central role in the inflammatory stress response associated with ulcerative colitis and may modulate cancer risk in patients afflicted with this chronic disease. Here, we describe the gene expression profiles associated with four microenvironmental components of the inflammatory response (NOcenter dot, H2O2, DNA replication arrest, and hypoxia) that result in p53 stabilization and activation. Isogenic HCT116 and HCT116 TP53(-/-) colon cancer cells were exposed to the NOcenter dot donor Sper/NO, H2O2, hypoxia, or hydroxyurea, and their mRNA was analyzed using oligonucleotide microarrays. Overall, 1,396 genes changed in a p53-dependent manner (P < 0.001), with the majority representing a "unique" profile for each condition. Only 14 genes were common to all four conditions. Included were eight known p53 target genes. Hierarchical sample clustering distinguished p early (1 and 4 hours) from late responses (8, 12, and 24 hours), and each treatment was differentiated from the others. Overall, NOcenter dot and hypoxia stimulated similar transcriptional responses. Gene ontology analysis revealed cell cycle as a key feature of stress responses and confirmed the similarity between NOcenter dot and hypoxia. Cell cycle profiles analyzed by flow cytometry showed that NOcenter dot and hypoxia induced quiescent S-phase and G(2)-M arrest. Using a novel bioinformatic algorithm, we identified several putative p53-responsive elements among the genes induced in a p53-dependent manner, including four [KIAA0247, FLJ12484, p53CSV (HSPC132), and CNK (PLK3)] common to all exposures. In summary, the inflammatory stress response is a complex, integrated biological network in which p53 is a key molecular node regulating gene expression. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NCI, Lab Expt & Computat Biol, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ S Carolina, Coll Pharm, Dept Basic Pharmaceut Sci, Columbia, SC 29208 USA. Univ Mainz, Dept Internal Med 1, D-6500 Mainz, Germany. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, 37 Convent Dr,Room 3068,MSC 4255, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov RI Wang, Xin/B-6162-2009 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005795-11] NR 51 TC 72 Z9 73 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2005 VL 65 IS 22 BP 10255 EP 10264 DI 10.1158/0008-5472.CAN-05-1714 PG 10 WC Oncology SC Oncology GA 985ZV UT WOS:000233418900021 PM 16288013 ER PT J AU Camphausen, KV Purow, B Sproull, M Scott, T Ozawa, T Deen, DF Tofilon, PJ AF Camphausen, KV Purow, B Sproull, M Scott, T Ozawa, T Deen, DF Tofilon, PJ TI Orthotopic growth of human glioma cells quantitatively and qualitatively influences radiation-induced changes in gene expression SO CANCER RESEARCH LA English DT Article ID FALSE DISCOVERY RATE; BREAST-CANCER CELLS; MICROARRAY ANALYSIS; IONIZING-RADIATION; IN-VITRO; RESPONSES; METASTASES; VIVO AB The effect of radiation on gene expression has been most frequently studied using tissue culture models. To determine the influence of experimental growth condition on radiation-induced changes in gene expression, microarray analysis was done on two human glioma cell lines (U87 and U251) grown in tissue culture and as s.c. or i.e. xenografts. Compared with tissue culture, the number of genes, whose expression was affected by radiation in both cell lines, was increased in the s.c. xenografts and further increased in the orthotopic tumors. Furthermore, in each growth condition, radiation modulated the expression of a different set of genes. In addition, whereas there were few commonly affected genes after irradiation of U87 and U251 in tissue culture, there were 729 common changes after orthotopic irradiation. These results indicate that the influence of the orthotopic environment on radiation-induced modulation of gene expression in glioma cells was both quantitative and qualitative. Moreover, they suggest that investigations of the functional consequence of radiation-induced gene expression will require accounting for experimental growth conditions. C1 Natl Canc Inst, Canc Res Ctr, Radiat Oncol Branch, Bethesda, MD 20892 USA. Natl Canc Inst, Neurooncol Branch, Bethesda, MD 20892 USA. Natl Canc Inst, Mol Radiat Therapeut Branch, Bethesda, MD 20892 USA. Natl Inst Neurol Disorder & Stroke, Bethesda, MD USA. Univ Calif San Francisco, Sch Med, Brain Tumor Res Ctr, Dept Neurol Surg, San Francisco, CA 94143 USA. RP Camphausen, KV (reprint author), Natl Canc Inst, Canc Res Ctr, Radiat Oncol Branch, 10 Ctr Dr,Bldg 10,Room B2-3561,MSC 1682, Bethesda, MD 20892 USA. EM camphauk@mail.nih.gov NR 14 TC 26 Z9 26 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 NOV 15 PY 2005 VL 65 IS 22 BP 10389 EP 10393 DI 10.1158/0008-5472.CAN-05-1904 PG 5 WC Oncology SC Oncology GA 985ZV UT WOS:000233418900037 PM 16288029 ER PT J AU Burger, AM Gao, YG Amemiya, Y Kahn, HJ Kitching, R Yang, YL Sun, P Narod, SA Hanna, WM Seth, AK AF Burger, AM Gao, YG Amemiya, Y Kahn, HJ Kitching, R Yang, YL Sun, P Narod, SA Hanna, WM Seth, AK TI A novel RING-type ubiquitin ligase breast cancer-associated gene 2 correlates with outcome in invasive breast cancer SO CANCER RESEARCH LA English DT Article ID CARCINOMA CELLS; PROTEIN; OVEREXPRESSION; PROGNOSIS; RECEPTOR; MDM2; AUTOUBIQUITINATION; DEGRADATION; INHIBITION; EXPRESSION AB The RING finger family of proteins possess ubiquitin ligase activity and play pivotal roles in protein degradation and receptor-mediated endocytosis. In this study, we examined whether the breast cancer-associated gene 2 (BCA2), a novel RING domain protein, has E3 ubiquitin ligase activity and investigated its expression status in breast tumors. The full-length BCA2 gene was cloned from the human breast cancer cell line MDA-MB-468. It encodes an open reading frame of 304 amino acids and contains a RING-H2 domain. BCA2 maps to chromosome 1q21.1, a region known to harbor cytogenetic aberrations in breast cancers. We found that the BCA2 protein has an intrinsic autoubiquitination activity, the hallmark of E3 ligases, whereas mutant RING protein is not autoubiquitinated. This indicates that the BCA2 ubiquitin ligase activity is dependent on the RING-H2 domain. Using tissue microarrays and immunohistochemistry, we found strong to intermediate BCA2 staining in 56% of 945 invasive breast cancers cases, which was significantly correlated with positive estrogen receptor status [odds ratio (OR), 1.51; P = 0.004], negative lymph node status (OR, 0.73; P = 0.02), and an increase in disease-free survival for regional recurrence (OR, 0.45; P = 0.03). Overexpression of BCA2 increased proliferation and small interfering RNA inhibited growth of T47D human breast cancer cells and NIH3T3 mouse cells. The autoubiquitination activity of BCA2 indicates that it is a novel RING-type E3 ligase. Its association with clinical measures and its effects on cell growth indicate that BCA2 may be important for the ubiquitin modification of proteins crucial to breast carcinogenesis and growth. C1 Sunnybrook & Womens Coll, Hlth Sci Ctr, Dept Pathol Anat, Lab Mol Pathol, Toronto, ON M4N 3M5, Canada. Sunnybrook & Womens Coll, Hlth Sci Ctr, Dept Pathol Anat, Immunopathol Lab, Toronto, ON M4N 3M5, Canada. Sunnybrook & Womens Coll, Hlth Sci Ctr, Div Mol & Cellular Biol, Toronto, ON M4N 3M5, Canada. Sunnybrook & Womens Coll, Hlth Sci Ctr, Ctr Res Womens Hlth, Toronto, ON M4N 3M5, Canada. Univ Toronto, Canadian Inst Hlth, Dept Lab Med & Pathobiol, Res Grp Matrix Dynam, Toronto, ON, Canada. NCI, Regulat Cell Growth Lab, Canc Res Ctr, Frederick, MD 21701 USA. RP Seth, AK (reprint author), Sunnybrook & Womens Coll, Hlth Sci Ctr, Dept Pathol Anat, Lab Mol Pathol, Room E423A,2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM arun.seth@utoronto.ca NR 32 TC 49 Z9 50 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 NOV 15 PY 2005 VL 65 IS 22 BP 10401 EP 10412 DI 10.1158/0008-5472.CAN-05-2103 PG 12 WC Oncology SC Oncology GA 985ZV UT WOS:000233418900039 PM 16288031 ER PT J AU Joesting, MS Perrin, S Elenbass, B Fawell, SE Rubin, JS Franco, OE Hayward, SW Cunha, GR Marker, PC AF Joesting, MS Perrin, S Elenbass, B Fawell, SE Rubin, JS Franco, OE Hayward, SW Cunha, GR Marker, PC TI Identification of SFRP1 as a candidate mediator of stromal-to-epithelial signaling in prostate cancer SO CANCER RESEARCH LA English DT Article ID FRIZZLED-RELATED PROTEIN-1; BETA-CATENIN MUTATIONS; WNT ANTAGONIST SFRP1; GROWTH-FACTOR-BETA; CELL-LINE MODEL; TUMOR PROGRESSION; BONE FIBROBLASTS; UP-REGULATION; EXPRESSION; CARCINOMA AB Genetic changes in epithelial cells initiate the development of prostatic adenocarcinomas. As nascent tumors grow and undergo progression, epithelial tumor cells are intimately associated with stromal cells. Stromal cells within the tumor microenvironment acquire new properties, including the capacity to promote phenotypic and genetic progression in adjacent epithelial cells. Affymetrix microarrays were used to identify 119 genes differentially expressed between normal-derived and carcinoma-derived prostatic stromal cells. These included 31 genes encoding extracellular proteins that may act as stromal-to-epithelial paracrine signals. Further investigation of one of these genes, secreted frizzled related protein 1 (SFKP1), revealed that its expression parallels prostatic growth with high expression during prostatic development, low expression in the adult prostate, and elevated expression in prostatic tumor stroma. In addition, as prostatic epithelial cells progressed to a tumorigenic state under the influence of tumor stroma, SFRP1 became overexpressed in the progressed epithelial cells. To further understand the roles of SFKP1 in the prostate, we tested the affects of increased SFRP1 levels on prostatic tissues and cells. Treatment of developing prostates with SFRP1 in culture led to increased organ growth. Treatment of a human prostatic epithelial cell line with SFRP1 led to increased proliferation, decreased apoptosis, and decreased signaling through the Wnt/beta-catenin pathway in vitro and increased proliferation in vivo. These data suggest that overexpression of SFRP1 by prostatic tumor stroma may account for the previously reported capacity of prostatic tumor stroma to provide a pro-proliferative paracrine signal to adjacent epithelial cells. C1 Univ Minnesota, Ctr Canc, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. Biogen Idec Inc, Cambridge, MA USA. Natl Canc Inst, Cellular & Mol Biol Lab, Bethesda, MD USA. Vanderbilt Univ, Med Ctr, Dept Urol Surg, Nashville, TN USA. Univ Calif San Francisco, Dept Urol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. RP Marker, PC (reprint author), Univ Minnesota, Ctr Canc, Dept Genet Cell Biol & Dev, MMC 806,420 Delaware St SE, Minneapolis, MN 55455 USA. EM marke032@umn.edu FU Intramural NIH HHS NR 45 TC 107 Z9 109 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2005 VL 65 IS 22 BP 10423 EP 10430 DI 10.1158/0008-5472.CAN-05-0824 PG 8 WC Oncology SC Oncology GA 985ZV UT WOS:000233418900041 PM 16288033 ER PT J AU Hibino, S Shibuya, M Hoffman, MP Engbring, JA Hossain, R Mochizuki, M Kudoh, S Nomizu, M Kleinman, HK AF Hibino, S Shibuya, M Hoffman, MP Engbring, JA Hossain, R Mochizuki, M Kudoh, S Nomizu, M Kleinman, HK TI Laminin alpha 5 chain metastasis- and angiogenesis-inhibiting peptide blocks fibroblast growth factor 2 activity by binding to the heparan sulfate chains of CD44 SO CANCER RESEARCH LA English DT Article ID FIBROBLAST-GROWTH-FACTOR; G-DOMAIN; ALPHA-1 CHAIN; SYNTHETIC PEPTIDES; PROGNOSTIC VALUE; GLOBULAR DOMAIN; GAMMA-1 CHAIN; CELL-ADHESION; BETA-1 CHAIN; TUMOR-GROWTH AB Recently, we reported that the laminin alpha 5 synthetic peptide A5G27 (RLVSYNGIIFFLK, residues 2,892-2,904) binds to the CD44 receptor of B16-FIO melanoma cells via the glycosaminoglycans on CD44 and inhibits tumor cell migration, invasion, and angiogenesis in a dominant-negative manner. Here, we have identified the potential mechanism of A5G27 activity using WiDr human colorectal carcinoma cells. WiDr cells bound to the A5G27 peptide via the heparin-like and chondroitin sulfate B glycosaminoglycan side chains of CD44. Cell binding to fibroblast growth factor (FGF2) was blocked by laminin peptide A5G27 but not by either a scrambled version of this peptide or by another laminin peptide known to bind cell surface proteoglycans. FGF2 signaling involving tyrosine phosphorylation was also blocked by laminin peptide A5G27 but was not affected by peptide controls. Finally, we have shown that peptide A5G27 directly blocks FGF2 binding to heparin. Peptide A5G27 has sequence homology to a region on FGF2 that binds heparin and the FGF receptor and is important in FGF2 central cavity formation. We conclude that peptide A5G27 inhibits metastasis and angiogenesis by blocking FGF2 binding to the heparan sulfate side chains of CD44 variant 3, thus decreasing FGF2 bioactivity. C1 Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. Tokyo Metropolitan Komagome Hosp, Resp Div Internal Med, Tokyo, Japan. Tokyo Univ Pharm, Sch Pharm, Lab Clin Biochem, Tokyo, Japan. Hokkaido Univ, Grad Sch Environm Earth Sci, Sapporo, Hokkaido 060, Japan. RP Kleinman, HK (reprint author), Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bldg 30,Room 433,30 Convent Dr,MSC 4370, Bethesda, MD 20892 USA. EM hkleinman@dir.nidcr.nih.gov NR 43 TC 25 Z9 25 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2005 VL 65 IS 22 BP 10494 EP 10501 DI 10.1158/0008-5472.CAN-05-0314 PG 8 WC Oncology SC Oncology GA 985ZV UT WOS:000233418900050 PM 16288042 ER PT J AU Wang, LX Li, R Yang, GJ Lim, M O'Hara, A Chu, YW Fox, BA Restifo, NP Urba, WJ Hu, HM AF Wang, LX Li, R Yang, GJ Lim, M O'Hara, A Chu, YW Fox, BA Restifo, NP Urba, WJ Hu, HM TI Interleukin-7-dependent expansion and persistence of melanoma-specific T cells in lymphodepleted mice lead to tumor regression and editing SO CANCER RESEARCH LA English DT Article ID HOMEOSTATIC PROLIFERATION; CANCER REGRESSION; DENDRITIC CELLS; ANTITUMOR LYMPHOCYTES; SELECTIVE EXPRESSION; PROTECTIVE IMMUNITY; IN-VIVO; AUTOIMMUNITY; RECEPTOR; RESPONSES AB Active-specific immunotherapy with dendritic cells loaded with peptide derived from the melanoma antigen, gp100, failed to mediate regression of established B16F10 melanoma in normal mice. Dendritic cell vaccination induced activation and subsequent deletion of adoptively transferred naive CD8(+) T-cell receptor transgenic (pmel-1) T cells specific for gpl00 in normal mice. In lymphodepleted mice, dendritic cell vaccination produced greater T-cell expansion, long-term persistence of memory T cells, and tumor regression. Most tumors that persisted in the presence of functional memory T cells had either lost or exhibited reduced expression of MHC class I or gp100 proteins. In contrast to other naive T cells, pmel-1 T cells adoptively transferred to lymphodepleted mice exhibited faster proliferation and a more differentiated phenotype after exposure to peptide-pulsed dendritic cells. Proliferation and persistence of pmel-1 T cells was highly dependent on interieukin-7 (IL-7) in irradiated mice, and IL-15 when IL-7 was neutralized, two critical homeostatic cytokines produced in response to the irradiation-induced lymphodepletion. C1 Providence Portland Med Ctr, Lab Canc Immunobiol, Robert W Franz Canc Ctr, Earle A Chiles Res Inst, Portland, OR 97213 USA. Providence Portland Med Ctr, Lab Mol & Tumor Immunol, Earle A Chiles Res Inst, Portland, OR 97213 USA. Southeast Univ, Sch Med, Dept Microbiol & Immunol, Nanjing, Jiangsu, Peoples R China. Fudan Univ, Shanghai Med Sch, Dept Immunol, Shanghai 200433, Peoples R China. NCI, NIH, Bethesda, MD 20892 USA. RP Hu, HM (reprint author), Providence Portland Med Ctr, Lab Canc Immunobiol, Robert W Franz Canc Ctr, Earle A Chiles Res Inst, 4805 NE Glisan St, Portland, OR 97213 USA. EM hhu@providence.org RI Restifo, Nicholas/A-5713-2008; OI Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999]; NCI NIH HHS [R01 CA107243, R01-CA107243] NR 40 TC 63 Z9 74 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2005 VL 65 IS 22 BP 10569 EP 10577 DI 10.1158/0008-5472.CAN-05-2117 PG 9 WC Oncology SC Oncology GA 985ZV UT WOS:000233418900058 PM 16288050 ER PT J AU Bonome, T Lee, JY Park, DC Radonovich, M Pise-Masison, C Brady, J Gardner, GJ Hao, K Wong, WH Barrett, JC Lu, KH Sood, AK Gershenson, DM Mok, SC Birrer, MJ AF Bonome, T Lee, JY Park, DC Radonovich, M Pise-Masison, C Brady, J Gardner, GJ Hao, K Wong, WH Barrett, JC Lu, KH Sood, AK Gershenson, DM Mok, SC Birrer, MJ TI Expression profiling of serous low malignant potential, low-grade, and high-grade tumors of the ovary. SO CANCER RESEARCH LA English DT Article ID BORDERLINE TUMORS; DNA-REPLICATION; CANCER; P53; CARCINOMA; PROTEIN; GENE; CELLS; ADHESION; PATHWAY AB Papillary serous low malignant potential (LMP) tumors are characterized by malignant features and metastatic potential yet display a benign clinical course. The role of LMP tumors in the development of invasive epithelial cancer of the ovary is not clearly defined. The aim of this study is to determine the relationships among LMP tumors and invasive ovarian cancers and identify genes contributing to their phenotypes. Affymetrix U133 Plus 2.0 microarrays (Santa Clara, CA) were used to interrogate 80 microdissected serous LMP tumors and invasive ovarian malignancies along with 10 ovarian surface epithelium (OSE) brushings. Gene expression profiles for each tumor class were used to complete unsupervised hierarchical clustering analyses and identify differentially expressed genes contributing to these associations. Unsupervised hierarchical clustering analysis revealed a distinct separation between clusters containing borderline and high-grade lesions. The majority of low-grade tumors clustered with LMP tumors. Comparing OSE with high-grade and LMP expression profiles revealed enhanced expression of genes linked to cell proliferation, chromosomal instability, and epigenetic silencing in high-grade cancers, whereas LMP tumors displayed activated p53 signaling. The expression profiles of LMP, low-grade, and high-grade papillary serous ovarian carcinomas suggest that LMP tumors are distinct from high-grade cancers; however, they are remarkably similar to low-grade cancers. Prominent expression of p53 pathway members may play an important role in the LMP tumor phenotype. C1 NCI, Cell & Canc Biol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Lab Gynecol Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gynecol Oncol, Houston, TX 77030 USA. RP Birrer, MJ (reprint author), NCI, Cell & Canc Biol Branch, Canc Res Ctr, 9000 Rockville Pike 37-1130, Bethesda, MD 20892 USA. EM birrerm@bprb.nci.nih.gov FU NCI NIH HHS [P50CA165009, R33CA103595] NR 51 TC 196 Z9 202 U1 2 U2 8 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 NOV 15 PY 2005 VL 65 IS 22 BP 10602 EP 10612 DI 10.1158/0008-5472.CAN-05-2240 PG 11 WC Oncology SC Oncology GA 985ZV UT WOS:000233418900062 PM 16288054 ER PT J AU Wilson, PWF D'Agostino, RB Parise, H Sullivan, L Meigs, JB AF Wilson, PWF D'Agostino, RB Parise, H Sullivan, L Meigs, JB TI Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus SO CIRCULATION LA English DT Article DE diabetes mellitus; coronary disease; epidemiology; glucose; obesity ID CORONARY-HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; C-REACTIVE PROTEIN; INSULIN-RESISTANCE; ASSOCIATION CONFERENCE; ATHEROSCLEROSIS RISK; UNITED-STATES; MORTALITY; ADULTS; COMMUNITIES AB Background - The incidence of cardiovascular disease ( CVD), coronary heart disease ( CHD), and type 2 diabetes mellitus ( T2DM) has not been well defined in persons with the metabolic syndrome ( at least 3 of the following: abdominal adiposity, low HDL cholesterol, high triglycerides, hypertension, and impaired fasting glucose). The objective was to investigate risk for CVD, CHD, and T2DM according to metabolic syndrome traits. Methods and Results - The study followed a cohort of 3323 middle-aged adults for the development of new CVD, CHD, and T2DM over an 8-year period. In persons without CVD or T2DM at baseline, the prevalence of the metabolic syndrome ( >= 3 of 5 traits) was 26.8% in men and 16.6% in women. There were 174 incident cases of CVD, 107 of CHD, and 178 of T2DM. In men, the metabolic syndrome age-adjusted relative risk ( RR) and 95% CIs were RR = 2.88 ( 95% CI 1.99 to 4.16) for CVD, RR = 2.54 ( 95% CI 1.62 to 3.98) for CHD, and RR = 6.92 ( 95% CI 4.47 to 10.81) for T2DM. Event rates and RRs were lower in women for CVD ( RR = 2.25, 95% CI 1.31 to 3.88) and CHD ( RR = 1.54, 95% CI 0.68 to 3.53), but they were similar for T2DM ( RR = 6.90, 95% CI 4.34 to 10.94). Population-attributable risk estimates associated with metabolic syndrome for CVD, CHD, and T2DM were 34%, 29%, and 62% in men and 16%, 8%, 47% in women. Conclusions - Metabolic syndrome is common and is associated with an increased risk for CVD and T2DM in both sexes. The metabolic syndrome accounts for up to one third of CVD in men and approximately half of new T2DM over 8 years of follow-up. C1 Med Univ S Carolina, Gen Clin Res Ctr, Charleston, SC 29425 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Massachsetts Hosp, Div Gen Med, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Boston, MA USA. RP Wilson, PWF (reprint author), Med Univ S Carolina, Gen Clin Res Ctr, 96 Jonathan Lucas,Clin Sci Bldg,Suite 815, Charleston, SC 29425 USA. EM wilsonpw@musc.edu OI Sullivan, Lisa/0000-0003-0726-7149 FU NHLBI NIH HHS [N01-HC-38038, R01-HL 073272-01]; NIA NIH HHS [AG 41398]; NIAMS NIH HHS [AR 41398] NR 38 TC 797 Z9 836 U1 10 U2 49 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 15 PY 2005 VL 112 IS 20 BP 3066 EP 3072 DI 10.1161/CIRCULATIONAHA.105.539528 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 983TN UT WOS:000233255100008 PM 16275870 ER PT J AU Ahmet, I Wan, RQ Mattson, MP Lakatta, EG Talan, M AF Ahmet, I Wan, RQ Mattson, MP Lakatta, EG Talan, M TI Cardioprotection by intermittent fasting in rats SO CIRCULATION LA English DT Article DE myocardial infarction; diet; remodeling; apoptosis; inflammation ID ISCHEMIA-REPERFUSION INJURY; CALORIC RESTRICTION; DIETARY RESTRICTION; MYOCARDIAL-INFARCTION; OXIDATIVE STRESS; WALL STRESS; BRAIN; HEART; RISK; CARDIOMYOPATHY AB Background - Intermittent fasting ( IF), a dietary regimen in which food is available only every other day, increases the life span and reduces the incidence of age-associated diseases in rodents. We have reported neuroprotective effects of IF against ischemic injury of the brain. In this study, we examined the effects of IF on ischemic injury of the heart in rats. Methods and Results - After 3 months of IF or regular every- day feeding ( control) diets started in 2-month-old rats, myocardial infarction ( MI) was induced by coronary artery ligation. Twenty-four hours after MI, its size in the IF group was 2-fold smaller, the number of apoptotic myocytes in the area at risk was 4-fold less, and the inflammatory response was significantly reduced compared with the control diet group. Serial echocardiography revealed that during 10 weeks after MI ( with continuation of the IF regimen), the left ventricular ( LV) remodeling and MI expansion that were observed in the control diet group were absent in the IF group. In a subgroup of animals with similar MI size at 1 week after MI, further observation revealed less remodeling, better LV function, and no MI expansion in the IF group compared with the control group. Conclusions - IF protects the heart from ischemic injury and attenuates post-MI cardiac remodeling, likely via antiapoptotic and antiinflammatory mechanisms. C1 NIA, Cardiovasc Sci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. NIA, Neurosci Lab, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Talan, M (reprint author), Ctr Gerontol Res, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM talanm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 38 TC 91 Z9 92 U1 1 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 15 PY 2005 VL 112 IS 20 BP 3115 EP 3121 DI 10.1161/CIRCULATIONAHA.105.563817 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 983TN UT WOS:000233255100014 PM 16275865 ER PT J AU Kelloff, GJ Krohn, KA Larson, SM Weissleder, R Mankoff, DA Hoffman, JM Link, JM Guyton, KZ Eckelman, WC Scher, HI O'Shaughnessy, J Cheson, BD Sigman, CC Tatum, JL Mills, GQ Sullivan, DC Woodcock, J AF Kelloff, GJ Krohn, KA Larson, SM Weissleder, R Mankoff, DA Hoffman, JM Link, JM Guyton, KZ Eckelman, WC Scher, HI O'Shaughnessy, J Cheson, BD Sigman, CC Tatum, JL Mills, GQ Sullivan, DC Woodcock, J TI The progress and promise of molecular imaging probes in oncologic drug development SO CLINICAL CANCER RESEARCH LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; BLOOD-BRAIN-BARRIER; METASTATIC PROSTATE-CANCER; STEROID-HORMONE RECEPTORS; P-GLYCOPROTEIN TRANSPORT; ADVANCED BREAST-CANCER; NON-HODGKINS-LYMPHOMA; IN-VIVO; ESTROGEN-RECEPTOR; ANNEXIN-V AB As addressed by the recent Food and Drug Administration Critical Path Initiative, tools are urgently needed to increase the speed, efficiency and cost effectiveness of drug development for cancer and other diseases. Molecular imaging probes developed based on recent scientific advances have a great potential as oncological drug development tools. Basic science studies using molecular imaging probes can help to identify and characterize disease-specific targets for oncologic drug therapy. Imaging end points, based on these disease-specific biomarkers, hold great promise to better define, stratify, and enrich study groups and to provide direct biological measures of response. Imaging-based biomarkers also have promise for speeding drug evaluation by supplementing or replacing preclinical and clinical pharmocokinetic and pharmacodynamic evaluations, including target interaction and modulation. Such analysis may be particularly valuable in early comparative studies among candidates designed to interact with the same molecular target. Finally, as response biomarkers, imaging end points that characterize tumor vitality, growth, or apoptosis can also serve as early surrogates of therapy success. this article outlines the scientific basis for oncology imaging probes and presents examples of probes that could facilitate progress. The current regulatory opportunities for new and existing probe development and testing are also reviewed, with a focus on recent Food and Drug Administration guidance to facilitate early clinical development of promising probes. C1 NCI, Canc Imaging Program, Div Canc Treatment & Diagnosis, NIH, Bethesda, MD 20892 USA. Mol Tracer LLC, Bethesda, MD USA. Univ Washington, Dept Radiol, Div Nucl Med, Seattle, WA 98195 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Ctr Mol Imaging Res, Charlestown, MA USA. CCS Associates, Mountain View, CA USA. Baylor Charles A Sammons Canc Ctr, Dallas, TX USA. Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. Off Drug Evaluat, Div Med Imaging & Radiopharmaceut Drug Prod, Rockville, MD USA. US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Kelloff, GJ (reprint author), NCI, Canc Imaging Program, Div Canc Treatment & Diagnosis, NIH, EPN 6130 Execut Blvd,Suite 6058, Bethesda, MD 20892 USA. EM kelloffg@mail.nih.gov RI Mankoff, David/F-9576-2010 FU NCI NIH HHS [P01 CA042045] NR 182 TC 160 Z9 162 U1 2 U2 17 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 NOV 15 PY 2005 VL 11 IS 22 BP 7967 EP 7985 DI 10.1158/1078-0432.CCR-05-1302 PG 19 WC Oncology SC Oncology GA 987HI UT WOS:000233508600003 PM 16299226 ER PT J AU Henningsson, A Marsh, S Loos, WJ Karlsson, MO Garsa, A Mross, K Mielke, S Vigano, L Locatelli, A Verweij, J Sparreboom, A McLeod, HL AF Henningsson, A Marsh, S Loos, WJ Karlsson, MO Garsa, A Mross, K Mielke, S Vigano, L Locatelli, A Verweij, J Sparreboom, A McLeod, HL TI Association of CYP2C8, CYP3A4, CYP3A5, and ABCB1 polymorphisms with the pharmacokinetics of paclitaxel SO CLINICAL CANCER RESEARCH LA English DT Article ID BODY-SURFACE AREA; GENETIC POLYMORPHISMS; UNBOUND PACLITAXEL; P-GLYCOPROTEIN; IN-VIVO; INTERINDIVIDUAL VARIABILITY; PLASMA-CONCENTRATIONS; CYTOCHROME-P450 2C8; CLINICAL-RELEVANCE; DRUG DISPOSITION AB Purpose: To retrospectively evaluate the effects of six known allelic variants in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes on the pharmacokinetics of the anticancer agent paclitaxel (Taxol). Experimental Design: A cohort of 97 Caucasian patients with cancer (median age, 57 years) received paclitaxel as an i.v. infusion (dose range, 80-225 mg/m(2)). Genomic DNA was analyzed using PCR RFLP or using Pyrosequencing. Pharmacokinetic variables for unbound paclitaxel were estimated using nonlinear mixed effect modeling. The effects of genotypes on typical value of clearance were evaluated with the likelihood ratio test within NONMEM. In addition, relations between genotype and individual pharmacokinetic variable estimates were evaluated with oneway ANOVA. Results: The allele frequencies for the CYP2C8*2, CYP2C8*3, CYP2C8*4, CYP3A4*3, CYP3A5*3C, and ABCB1 3435C > T variants were 0.7%,9.2%,2.1%, 0.5%,93.2%, and 47.1%, respectively, and all were in Hardy-Weinberg equilibrium. The population typical value of clearance of unbound paclitaxel was 301 L/h (individual clearance range, 83.7-1055 L/h). The CYP2C8 or CYP3A4/5 genotypes were not statistically significantly associated with unbound clearance of paclitaxel. Likewise, no statistically significant association was observed between the ABCB1 3435C > T variant and any of the studied pharmacokinetic variables. Conclusions: This study indicates that the presently evaluated variant alleles in the CYP2C8, CYP3A4, CYP3A5, and ABCB1 genes do not explain the substantial interindividual variability in paclitaxel pharmacokinetics. C1 NCI, Med Oncol Branch, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. Uppsala Univ, Fac Pharm, Dept Pharmaceut Biosci, Uppsala, Sweden. Washington Univ, Sch Med, Dept Med, St Louis, MO USA. Erasmus MC Daniel Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. Univ Freiburg, Tumor Biol Ctr, D-7800 Freiburg, Germany. Univ Freiburg, Ctr Med, Dept Hematol & Oncol, D-7800 Freiburg, Germany. Ist Nazl Tumori, Div Med Oncol, I-20133 Milan, Italy. RP Sparreboom, A (reprint author), NCI, Med Oncol Branch, Clin Pharmacol Res Core, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM SparrebA@mail.nih.gov RI Sparreboom, Alex/B-3247-2008 FU NIGMS NIH HHS [U01 GM63340] NR 62 TC 124 Z9 134 U1 0 U2 6 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD NOV 15 PY 2005 VL 11 IS 22 BP 8097 EP 8104 DI 10.1158/1078-0432.CCR-05-1152 PG 8 WC Oncology SC Oncology GA 987HI UT WOS:000233508600018 PM 16299241 ER PT J AU Patterson, TF Boucher, HW Herbrecht, R Denning, DW Lortholary, O Ribaud, P Rubin, RH Wingard, JR DePauw, B Schlamm, HT Troke, P Bennett, JE AF Patterson, TF Boucher, HW Herbrecht, R Denning, DW Lortholary, O Ribaud, P Rubin, RH Wingard, JR DePauw, B Schlamm, HT Troke, P Bennett, JE CA EORTC IFIG Pfizer Global Aspergillus Study TI Strategy of following voriconazole versus amphotericin B therapy with other licensed antifungal therapy for primary treatment of invasive aspergillosis: Impact of other therapies on outcome SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID EFFICACY; ITRACONAZOLE; CASPOFUNGIN; INFECTIONS; SAFETY; MODEL AB Background. In a previous randomized trial of voriconazole versus amphotericin B deoxycholate for primary therapy of invasive aspergillosis, voriconazole demonstrated superior efficacy and better survival. In that trial, treatment with voriconazole or amphotericin B deoxycholate could be followed with other licensed antifungal therapies (OLAT). Here, we report the impact of OLAT on the outcome of patients with invasive aspergillosis. Methods. Data on dose, duration, and the reason for switching to the first OLAT were analyzed, and outcome at week 12 was assessed. Results. Fewer patients in the voriconazole group ( 52 [36%] of 144) switched to OLAT, compared with patients in the amphotericin B deoxycholate group ( 107 [80%] of 133). Lipid formulations of amphotericin B were the most common OLAT (38% of patients). Switches were made because of intolerance or insufficient response in 70% for patients in the amphotericin B deoxycholate group, compared with 24% of patients in the voriconazole group. Favorable responses to OLAT in the amphotericin B deoxycholate group occurred in only 19% of patients with initial insufficient response and 38% of patients with intolerance. Salvage therapy with a lipid formulation of amphotericin B after initial treatment with amphotericin B deoxycholate was successful for only 30% of patients ( 14 of 47). Treatment success among patients randomized to receive amphotericin B, including those whose treatment was switched to OLAT, was 32%, compared with 55% among patients who received voriconazole alone ( P <.001). Conclusions. This study highlights the limited efficacy of salvage antifungal therapy, including therapy with lipid formulations of amphotericin B, and demonstrates the importance of effective initial therapy in invasive aspergillosis. C1 Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Univ Florida, Gainesville, FL USA. Pfizer, New York, NY USA. NIH, Bethesda, MD 20892 USA. Hop Hautepierre, Strasbourg, France. Hop Necker Enfants Malad, Paris, France. Univ Paris Descartes, Inst Pasteur, Paris, France. Univ Manchester, Manchester, Lancs, England. Pfizer, Sandwich, Kent, England. St Radboud Hosp, Nijmegen, Netherlands. RP Patterson, TF (reprint author), Univ Texas, Hlth Sci Ctr, Dept Med, Mail Code 7881,7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM patterson@uthscsa.edu RI Herbrecht, Raoul/D-3471-2013 NR 12 TC 64 Z9 68 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 NOV 15 PY 2005 VL 41 IS 10 BP 1448 EP 1452 DI 10.1086/497126 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 975NY UT WOS:000232670400008 PM 16231256 ER PT J AU Schwartz, DA Cook, DN AF Schwartz, DA Cook, DN TI Polymorphisms of the toll-like receptors and human disease SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 3rd Annual International Sepsis Forum Colloquium on Identifying Responsive Populations in Sepsis CY JUL 10-12, 2004 CL Cambridge, ENGLAND ID ANTI-DNA ANTIBODIES; INFLAMMATORY-BOWEL-DISEASE; BACTERIAL LIPOPOLYSACCHARIDES; TOLL-LIKE-RECEPTOR-4 GENE; ASP299GLY POLYMORPHISM; LEPROMATOUS LEPROSY; ULCERATIVE-COLITIS; T-LYMPHOCYTES; MUTATIONS; ENDOTOXIN AB The Toll-like receptor (TLR) family regulates both innate and adaptive immune responses. Given its broad effect on immunity, the function of TLRs in various human diseases has been investigated largely by comparing the incidence of disease among persons with different polymorphisms in the genes that participate in TLR signaling. These studies demonstrate that TLR function affects several diseases, including sepsis, immunodeficiencies, atherosclerosis, and asthma. These findings have resulted in new opportunities to study the pathogenesis of disease, identify subpopulations at greater risk of disease, and, potentially, identify novel therapeutic approaches. C1 Duke Univ, Ctr Med, Dept Med, Durham, NC USA. Durham Vet Affairs Med Ctr, Durham, NC USA. RP Schwartz, DA (reprint author), Natl Inst Environm Hlth Sci, POB 12233, Res Triangle Pk, NC 27709 USA. EM david.schwartz@niehs.nih.gov FU NHLBI NIH HHS [HL-66604, HL-66611]; NIEHS NIH HHS [ES-011961, ES-012496, ES-07498, ES-11375] NR 57 TC 36 Z9 40 U1 1 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 NOV 15 PY 2005 VL 41 SU 7 BP S403 EP S407 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 975NU UT WOS:000232670000003 PM 16237638 ER PT J AU Cassiani-Ingoni, R Greenstone, HL Donati, D Fogdell-Hahn, A Martinelli, E Refai, D Martin, R Berger, EA Jacobson, S AF Cassiani-Ingoni, R Greenstone, HL Donati, D Fogdell-Hahn, A Martinelli, E Refai, D Martin, R Berger, EA Jacobson, S TI CD46 on glial cells can function as a receptor for viral glycoprotein-mediated cell-cell fusion SO GLIA LA English DT Article DE MCP; oligodendrocyte; HHV-6; MV; cell fusion; multiple sclerosis ID MEMBRANE COFACTOR PROTEIN; SUBACUTE SCLEROSING PANENCEPHALITIS; HUMAN-HERPESVIRUS-6 VARIANT-A; RECOMBINANT VACCINIA VIRUS; MEASLES-VIRUS; MULTIPLE-SCLEROSIS; MONOCLONAL-ANTIBODIES; HUMAN HERPESVIRUS-6; PURKINJE NEURONS; GENE-EXPRESSION AB Membrane cofactor protein (CD46) is a regulator of complement activation that also serves as the entry receptor for human herpes virus 6 (HHV-6) and measles virus (MV) into human cells. While it is clear that oligodendrocytes and astrocytes are cell types commonly infected by these viruses, it is unclear whether oligodendrocytes express CD46, or which are the cellular mechanisms underlying the infection. We show that adult oligodendrocytes, as well as astrocytes and microglial cells, express CD46 on the cellular surface. Moreover, we employed a quantitative fusion assay to demonstrate that HHV-6A infection of T lymphocytes enables cell-cell fusion of these cells to astrocytes or to oligodendroglial cells. This fusion is mediated by the interaction between viral glycoproteins expressed on the membrane of the infected cells and CD46 on the glial targets, and is also observed using cells expressing recombinant MV glycoproteins. These data suggest a mechanism that involves cell-cell fusion by which certain viruses could spread the infection from the periphery to the cells in the nervous system. Published 2005 Wiley-Liss, Inc.dagger C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Roma La Sapienza, Dept Human Physiol & Pharmacol, Ctr Excellence Biol & Mol Med, Rome, Italy. RP Jacobson, S (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Rm 5B16, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov NR 40 TC 12 Z9 12 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0894-1491 J9 GLIA JI Glia PD NOV 15 PY 2005 VL 52 IS 3 BP 252 EP 258 DI 10.1002/glia.20219 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 978RW UT WOS:000232891700010 PM 15920733 ER PT J AU McCampbell, A Truong, D Broom, DC Allchorne, A Gable, K Cutler, RG Mattson, MP Woolf, CJ Frosch, MP Harmon, JM Dunn, TM Brown, RH AF McCampbell, A Truong, D Broom, DC Allchorne, A Gable, K Cutler, RG Mattson, MP Woolf, CJ Frosch, MP Harmon, JM Dunn, TM Brown, RH TI Mutant SPTLC1 dominantly inhibits serine palmitoyltransferase activity in vivo and confers an age-dependent neuropathy SO HUMAN MOLECULAR GENETICS LA English DT Article ID HEREDITARY SENSORY NEUROPATHY; PERIPHERAL-NERVE INJURY; SPHINGOLIPID SYNTHESIS; CONDUCTION-VELOCITY; NEUROTROPHIC FACTOR; DELTA-SUBUNIT; YEAST LCB1; NEURONS; EXPRESSION; CERAMIDE AB Mutations in enzymes involved in sphingolipid metabolism and trafficking cause a variety of neurological disorders, but details of the molecular pathophysiology remain obscure. SPTLC1 encodes one subunit of serine palmitoyltransferase (SPT), the rate-limiting enzyme in sphingolipid synthesis. Mutations in SPTLC1 cause hereditary sensory and autonomic neuropathy (type I) (HSAN1), an adult onset, autosomal dominant neuropathy. HSAN1 patients have reduced SPT activity. Expression of mutant SPTLC1 in yeast and mammalian cell cultures dominantly inhibits SPT activity. We created transgenic mouse lines that ubiquitously overexpress either wild-type (SPTLC1(WT)) or mutant SPTLC1 (SPTLC1(C133W)). We report here that SPTLC1(C133W) mice develop age-dependent weight loss and mild sensory and motor impairments. Aged SPTLC1(C133W) mice lose large myelinated axons in the ventral root of the spinal cord and demonstrate myelin thinning. There is also a loss of large myelinated axons in the dorsal roots, although the unmyelinated fibers are preserved. In the dorsal root ganglia, IB4 staining is diminished, whereas expression of the injury-induced transcription factor ATF3 is increased. These mice represent a novel mouse model of peripheral neuropathy and confirm the link between mutant SPT and neuronal dysfunction. C1 Massachusetts Gen Hosp, Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Mass Gen Inst Neurodegenerat Dis, Alzheimers Res Unit, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, Neural Plast Res Grp, Dept Anesthesia & Crit Care, Charlestown, MA 02129 USA. Massachusetts Gen Hosp, CS Kubik Lab Neuropathol, Dept Pathol, Charlestown, MA 02129 USA. Harvard Univ, Sch Med, Charlestown, MA 02129 USA. Uniformed Serv Univ Hlth Sci, Dept Pharmacol, Bethesda, MD 20184 USA. Uniformed Serv Univ Hlth Sci, Dept Biochem & Mol Biol, Bethesda, MD 20184 USA. NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP McCampbell, A (reprint author), Massachusetts Gen Hosp, Day Lab Neuromuscular Res, Charlestown, MA 02129 USA. EM amccampbell@partners.org RI Mattson, Mark/F-6038-2012; OI Harmon, Jeffrey/0000-0001-7833-931X FU NINDS NIH HHS [5R01NS047717-02, F32 NS044695-03] NR 58 TC 33 Z9 35 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD NOV 15 PY 2005 VL 14 IS 22 BP 3507 EP 3521 DI 10.1093/hmg/ddi380 PG 15 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 983FL UT WOS:000233216600017 PM 16210380 ER PT J AU Andreev, S Reichman, DR Hummer, G AF Andreev, S Reichman, DR Hummer, G TI Effect of flexibility on hydrophobic behavior of nanotube water channels SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID MOLECULAR-DYNAMICS SIMULATIONS; COARSE-GRAINED MODEL; SINGLE-FILE PORES; CARBON NANOTUBES; MECHANOSENSITIVE CHANNEL; GRAMICIDIN CHANNEL; FLUID EXPERIMENTS; TRANSPORT; MEMBRANES; MECHANISM AB Carbon nanotubes can serve as simple nonpolar water channels. Here we report computer simulations exploring the relationship between the mechanical properties of such channels and their interaction with water. We show that on one hand, increasing the flexibility of the carbon nanotubes increases their apparent hydrophobic character, while on the other hand the presence of water inside the channel makes them more resistant to radial collapse. We quantify the effect of increasing flexibility on the hydrophobicity of the nanotube water channel. We also show that flexibility impedes water transport across the nanotube channel by increasing the free-energy barriers to such motion. Conversely, the presence of water inside the nanotube is shown to affect the energetics of radial collapse in a water nanotube, an ostensibly mechanical property. We quantify the magnitude of the effect and show that it arises from the formation of energetically favorable low-dimensional water structures inside the nanotube such as one-dimensional wires and two-dimensional sheets. (c) 2005 American Institute of Physics. C1 Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. Columbia Univ, Dept Chem, New York, NY 10027 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Andreev, S (reprint author), Harvard Univ, Dept Chem & Biol Chem, Cambridge, MA 02138 USA. EM hummer@helix.nih.gov RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X FU Intramural NIH HHS NR 62 TC 57 Z9 57 U1 5 U2 24 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD NOV 15 PY 2005 VL 123 IS 19 AR 194502 DI 10.1063/1.2104529 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 985CH UT WOS:000233353200026 PM 16321095 ER PT J AU Mandal, AK Zhang, ZJ Kim, SJ Tsai, PC Mukherjee, AB AF Mandal, AK Zhang, ZJ Kim, SJ Tsai, PC Mukherjee, AB TI Cutting edge: Yin-Yang: Balancing act of prostaglandins with opposing functions to regulate inflammation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYCLOPENTENONE PROSTAGLANDINS; CYCLOOXYGENASES; INHIBITORS AB For many years, cyclooxygenase-2 (COX-2), a critical enzyme for PG production, has been the favorite target for anti-inflammatory drug development. However, recent revelations regarding the adverse effects of selective COX-2 inhibitors have stimulated intense debate. Interestingly, in the early phase of inflammation, COX-2facilitates inflammatory PG production while in the late phase it has anti-inflammatory effects. Moreover, although some PGs are proinflammatory, others have anti-inflammatory effects. Thus, it is likely that PGs with opposing effects maintain homeostasis, although the molecular mechanism(s) remains unclear. We report here that an inflammatory PG, PGD(2), via its receptor, mediates the activation of NF-kappa B stimulating COX-2 gene expression. Most interestingy, an anti-inflammatory PG (PGA(1)) suppresses NF-kappa B activation and inhibits COX-2 gene expression. We propose that while pro-and anti-inflammatory PGs counteract each other to maintain homeostasiss selective COX-2 inhihitors may disrupt this balance, thereby resulting in reported adverse effects. C1 NICHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Mukherjee, AB (reprint author), NICHD, Sect Dev Genet, Heritable Disorders Branch, NIH, Bldg 10,Room 9D42, Bethesda, MD 20892 USA. EM mukherja@exchange.nih.gov NR 9 TC 14 Z9 15 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 NOV 15 PY 2005 VL 175 IS 10 BP 6271 EP 6273 PG 3 WC Immunology SC Immunology GA 981ZK UT WOS:000233126300005 PM 16272277 ER PT J AU Su, SB Silver, PB Grajewski, RS Agarwal, RK Tang, J Chan, CC Caspi, RR AF Su, SB Silver, PB Grajewski, RS Agarwal, RK Tang, J Chan, CC Caspi, RR TI Essential role of the MyD88 pathway, but nonessential roles of TLRs 2, 4, and 9, in the adjuvant effect promoting Th1-mediated autoimmunity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; ENCEPHALITOGENIC T-CELLS; CUTTING EDGE; MYCOBACTERIUM-TUBERCULOSIS; MYD88-DEFICIENT MICE; IL-18-DEFICIENT MICE; ADAPTER PROTEIN; DENDRITIC CELLS; INNATE IMMUNITY; DEFICIENT MICE AB Induction of tissue-specific experimental autoimmune diseases involves an obligatory adjuvant effect to trigger an innate response of a type that will drive a Th1-biased adaptive response. This is achieved by use of CFA containing mycobacteria (Mycobacterium tuberculosis), whose recognition by cells of the innate immune system depends on TLRs that signal through the adaptor molecule MyD88. We examined the role of selected components of the MyD88 pathway in promoting experimental autoimmune uveitis (EAU). Mice deficient in MyD88, TLR2, TLR4, or TLR9 were immunized with the retinal Ag interphotoreceptor retinoid-binding protein in CFA, and their EAU scores and associated immunological responses were examined. MyD88(-/-) mice were completely resistant to EAU and had a profound defect in Th1, but not Th2, responses to autoantigen challenge. Surprisingly, TLR2(-/-), TLR4(-/-), and TLR9(-/-) mice were fully susceptible to EAU and had unaltered adaptive responses to interphotoreceptor retinoid-binding protein. Examination of IL-1R family members, which share the common adaptor MyD88 with the TLR family, revealed that IL-1R-deficient mice, but not IL-18-deficient mice, are resistant to EAU and have profoundly reduced Th1 and Th2 responses. These data are compatible with the interpretation that TLR9, TLR4, and TLR2 signaling is either not needed, or, more likely, redundant in the adjuvant effect needed to induce EAU. In contrast, signaling through the IL-1R plays a necessary and nonredundant role in EAU and can by itself account for the lack of EAU development in MyD88 mice. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,10-10N222, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov NR 50 TC 92 Z9 98 U1 2 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2005 VL 175 IS 10 BP 6303 EP 6310 PG 8 WC Immunology SC Immunology GA 981ZK UT WOS:000233126300009 PM 16272281 ER PT J AU Fritsch, RD Shen, XL Sims, GP Hathcock, KS Hodes, RJ Lipsky, PE AF Fritsch, RD Shen, XL Sims, GP Hathcock, KS Hodes, RJ Lipsky, PE TI Stepwise differentiation of CD4 memory T cells defined by expression of CCR7 and CD27 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HIGH ENDOTHELIAL VENULES; EFFECTOR FUNCTIONS; HUMAN NAIVE; IN-VIVO; LYMPHOCYTES; CHEMOKINE; SUBSETS; ACTIVATION; RECEPTOR; PHENOTYPE AB To study the steps in the differentiation of human memory CD4 T cells, we characterized the functional and lineage relationships of three distinct memory CD4 subpopulations distinguished by their expression of the cysteine chemokine receptor CCR7 and the TNFR family member CD27. Using the combination of these phenotypic markers, three populations were defined: the CCR7(+)CD27(+), the CCR7(-)CD27(+), and the CCR7(-)CD27(-) population. In vitro stimulation led to a stepwise differentiation from naive to CCR7(+)CD27(+) to CCR7(-)CD27(+) to CCR7(-)CD27(-). Telomere length in these subsets differed significantly (CCR7(+)CD27(+) > CCR7(-)CD27(+) > CCR7(-)CD27(-)), suggesting that these subsets constituted a differentiative pathway with progressive telomere shortening reflecting antecedent in vivo proliferation. The in vitro proliferative response of these populations declined, and their susceptibility to apoptosis increased progressively along this differentiation pathway. Cytokine secretion showed a differential functional capacity of these subsets. High production of IL-10 was only observed in CCR7(+)CD27(+), whereas IFN-gamma was produced by CCR7(-)CD27(+) and to a slightly lesser extent by CCR7-CD27- T cells. IL-4 secretion was predominantly conducted by CCR7(-)CD27(-) memory CD4 T cells. Thus, by using both CCR7 and CD27, distinct maturational stages of CD4 memory T cells with different functional activities were defined. C1 NIAMSD, NIH, Autoimmun Branch, Bethesda, MD 20892 USA. Natl Canc Inst, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Aging, NIH, Bethesda, MD 20892 USA. RP Lipsky, PE (reprint author), NIAMSD, NIH, Autoimmun Branch, Bldg 10,Room 6D47C, Bethesda, MD 20892 USA. EM lipskyp@mail.nih.gov RI Fritsch-sTork, Ruth/G-9702-2012 NR 35 TC 113 Z9 116 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 NOV 15 PY 2005 VL 175 IS 10 BP 6489 EP 6497 PG 9 WC Immunology SC Immunology GA 981ZK UT WOS:000233126300031 PM 16272303 ER PT J AU Delale, T Paquin, A Asselin-Paturel, C Dalod, M Brizard, G Bates, EEM Kastner, P Chan, S Akira, S Vicari, A Biron, CA Trinchieri, G Briere, F AF Delale, T Paquin, A Asselin-Paturel, C Dalod, M Brizard, G Bates, EEM Kastner, P Chan, S Akira, S Vicari, A Biron, CA Trinchieri, G Briere, F TI MyD88-dependent and -independent murine cytomegalovirus sensing for IFN-alpha release and initiation of immune responses in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; TOLL-LIKE RECEPTOR-9; PLASMACYTOID DENDRITIC CELLS; DOUBLE-STRANDED-RNA; VIRAL-INFECTION; ANTIVIRAL DEFENSE; INTERFERON-GAMMA; NK CELLS; MOUSE-CYTOMEGALOVIRUS; ACTIVATION RECEPTOR AB Antiviral immunity requires early and late mechanisms in which IFN-alpha and IL-12 play major roles. However, the initial events leading to their production remain largely unclear. Given the crucial role of TLR in innate recognition, we investigated their role in antiviral immunity in vivo. Upon murine CMV (MCMV) infection, both MyD88(-/-) and TLR9(-/-) mice were more susceptible and presented increased viral loads compared with C57BL/6, TLR2(-/-), TLR3(-/-), or TLR4(-/-) mice. However, in terms of resistance to infection, IFN-a production and in many other parameters of early inflammatory responses, the MyD88(-/-) mice showed a more defective response than TLR9(-/-) mice. In the absence of the TLR9/MyD88 signaling pathway, cytokine production was dramatically impaired with a complete abolition of bioactive IL-12p70 serum release contrasting with a high flexibility for IFN-a release, which is initially (36 h) plasmacytoid dendritic cell- and MyD88-dependent, and subsequently (44 h) PDC-, MyD88-independent and, most likely, TLR-independent. NK cells from MCMV-infected MyD88(-/-) and TLR9(-/-) mice displayed a severely impaired IFN-gamma production, yet retained enhanced cytotoxic activity. In addition, dendritic cell activation and critical inflammatory cell trafficking toward the liver were still effective. In the long term, except for isotype switching to MCMV-specific IgG1, the establishment of Ab responses was not significantly altered. Thus, our results demonstrate a critical requirement of TLR9 in the process of MCMV sensing to assure rapid antiviral responses, coordinated with other TLR-dependent and -independent events that are sufficient to establish adaptive immunity. C1 Schering Plough Corp, Lab Immunol Res, Dardilly, France. Univ Mediterranee, INSERM, CNRS, Ctr Immunol Marseille Luminy, Marseille, France. Univ Strasbourg 1, INSERM, CNRS, Inst Genet & Biol Mol & Cellulaire, Illkirch Graffenstaden, France. Osaka Univ, Res Inst Microbial Dis, Dept Host Def, Osaka, Japan. Brown Univ, Dept Mol Microbiol & Immunol, Div Biol & Med, Providence, RI 02912 USA. RP Trinchieri, G (reprint author), NIAID, Parasit Dis Lab, NIH, Bldg 50,Room 6150,50 S Dr,Mail Code 8003, Bethesda, MD 20892 USA. EM Giorgio_Trinchieri@yahoo.com RI Akira, Shizuo/C-3134-2009; BRIZARD, Geraldine/C-2845-2013 FU NCI NIH HHS [R01 CA041268]; NIAID NIH HHS [R01 AI055677] NR 61 TC 144 Z9 155 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 NOV 15 PY 2005 VL 175 IS 10 BP 6723 EP 6732 PG 10 WC Immunology SC Immunology GA 981ZK UT WOS:000233126300056 PM 16272328 ER PT J AU Carey, MA Bradbury, JA Seubert, JM Langenbach, R Zeldin, DC Germolec, DR AF Carey, MA Bradbury, JA Seubert, JM Langenbach, R Zeldin, DC Germolec, DR TI Contrasting effects of cyclooxygenase-1 (COX-1) and COX-2 deficiency on the host response to influenza A viral infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; CYSTEINYL LEUKOTRIENES; MONONUCLEAR-CELLS; SICKNESS BEHAVIOR; PROSTAGLANDIN E-2; GENE DISRUPTION; MICE; CYTOKINE; SLEEP; ASTHMA AB Influenza is a significant cause of morbidity and mortality worldwide despite extensive research and vaccine availability. The cyclooxygenase (COX) pathway is important in modulating immune responses and is also a major target of nonsteroidal antiinflammatory drugs (NSAIDs) and the newer COX-2 inhibitors. The purpose of the present study was to examine the effect of deficiency of COX-1 or COX-2 on the host response to influenza. We used an influenza A viral infection model in wild type (WT), COX-1(-/-), and COX-2(-/-) mice. Infection induced less severe illness in COX-2(-/-) mice in comparison to WT and COX-1(-/-) mice as evidenced by body weight and body temperature changes. Mortality was significantly reduced in COX-2(-/-) mice. COX-1(-/-) mice had enhanced inflammation and earlier appearance of proinflammatory cytokines in the BAL fluid, whereas the inflammatory and cytokine responses were blunted in COX-2(-/-) mice. However, lung viral titers were markedly elevated in COX-2(-/-) mice relative to WT and COX-1(-/-) mice on day 4 of infection. Levels of PGE(2) were reduced in COX-1(-/-) airways whereas cysteinyl leukotrienes were elevated in COX-2(-/-) airways following infection. Thus, deficiency of COX-1 and COX-2 leads to contrasting effects in the host response to influenza infection, and these differences are associated with altered production of prostaglandins and leukotrienes following infection. COX-1 deficiency is detrimental whereas COX-2 deficiency is beneficial to the host during influenza viral infection. C1 NIH, NIEHS, Div Intramural Res, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. NIH, NIEHS, Div Intramural Res, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. NIH, NIEHS, Div Intramural Res, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. RP Germolec, DR (reprint author), NIH, NIEHS, Div Intramural Res, Lab Resp Biol, 111 TW Alexander Dr,Bldg 101, Res Triangle Pk, NC 27709 USA. EM germolec@niehs.nih.gov FU Intramural NIH HHS NR 47 TC 55 Z9 58 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2005 VL 175 IS 10 BP 6878 EP 6884 PG 7 WC Immunology SC Immunology GA 981ZK UT WOS:000233126300074 PM 16272346 ER PT J AU Zhou, JH Shen, XL Huang, JP Hodes, RJ Rosenberg, SA Robbins, PF AF Zhou, JH Shen, XL Huang, JP Hodes, RJ Rosenberg, SA Robbins, PF TI Telomere length of transferred lymphocytes correlates with in vivo persistence and tumor regression in melanoma patients receiving cell transfer therapy SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD8(+) T-CELLS; REPLICATIVE SENESCENCE; REVERSE-TRANSCRIPTASE; CANCER REGRESSION; EXPRESSION; CLONES; DIFFERENTIATION; SUBPOPULATIONS; ACTIVATION; CULTURES AB Recent studies have indicated that adoptive immunotherapy with autologous antitumor tumor-infiltrating lymphocytes (TILs) following nonmyeloablative chemotherapy mediates tumor regression in similar to 50% of treated patients with metastatic melanoma, and that tumor regression is correlated with the degree of persistence of adoptively transferred T cells in peripheral blood. These findings, which suggested that the proliferative potential of transferred T cells may play a role in clinical responses, led to the current studies in which telomere length as well as phenotypic markers expressed on the administered TILs were examined. TILs that were associated with objective clinical responses following adoptive transfer possessed a mean telomere length of 6.3 kb, whereas TILs that were not associated with significant clinical responses were significantly shorter, averaging 4.9 kb (P < 0.01). Furthermore, individual TIL-derived T cell clonotypes that persisted in vivo following adoptive cell transfer possessed telomeres that were longer than telomeres of T cell clonotypes that failed to persist (6.2 vs 4.5 kb, respectively; p < 0.001). Expression of the costimulatory molecule CD28 also appeared to be associated with long telomeres and T cell persistence. These results, indicating that the telomere length of transferred lymphocytes correlated with in vivo T cell persistence following adoptive transfer, and coupled with the previous observation that T cell persistence was associated with clinical responses in this adoptive immunotherapy trial, suggest that telomere length and the proliferative potential of the transferred T cells may play a significant role in mediating response to adoptive immunotherapy. C1 NCI, Surg Branch, NIH, CRC, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Zhou, JH (reprint author), NCI, Surg Branch, NIH, CRC, Room 3W-3-3832,Bldg 10,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM juhua_zhou@nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 SC003811-31] NR 31 TC 209 Z9 213 U1 2 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 NOV 15 PY 2005 VL 175 IS 10 BP 7046 EP 7052 PG 7 WC Immunology SC Immunology GA 981ZK UT WOS:000233126300094 PM 16272366 ER PT J AU Viboud, C Grais, RF Lafont, BAP Miller, MA Sugaya, N Simonsen, L AF Viboud, C Grais, RF Lafont, BAP Miller, MA Sugaya, N Simonsen, L CA Multinatl Influenza Seasonal Morta TI It's not about smoldering or neuraminidase: There were 2 variants of the A(H3N2) pandemic virus differing in internal genes - Reply SO JOURNAL OF INFECTIOUS DISEASES LA English DT Letter ID HONG-KONG INFLUENZA; MORTALITY; POPULATION; PNEUMONIA; IMPACT; US C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Keiyu Hosp, Yokohama, Kanagawa, Japan. RP Viboud, C (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA. RI Lafont, Bernard/B-7236-2014 NR 17 TC 1 Z9 1 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 NOV 15 PY 2005 VL 192 IS 10 BP 1860 EP 1862 DI 10.1086/497155 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 975ZG UT WOS:000232702000029 ER PT J AU Kim, J Wei, DS Hoffman, DA AF Kim, J Wei, DS Hoffman, DA TI Kv4 potassium channel subunits control action potential repolarization and frequency-dependent broadening in rat hippocampal CA1 pyramidal neurones SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID DENDRITIC K+ CHANNELS; PROTEIN-KINASE; FAST TRANSIENT; EXPRESSION; CURRENTS; MODULATION; BRAIN; INTERNEURONS; CELLS; INTEGRATION AB A-type potassium channels regulate neuronal firing frequency and the back-propagation of action potentials (APs) into dendrites of hippocampal CA1 pyramidal neurones. Recent molecular cloning studies have found several families of voltage-gated K+ channel genes expressed in the mammalian brain. At present, information regarding the relationship between the protein products of these genes and the various neuronal functions performed by voltage-gated K+ channels is lacking. Here we used a combination of molecular, electrophysiological and imaging techniques to show that one such gene, Kv4.2, controls AP half-width, frequency-dependent AP broadening and dendritic action potential propagation. Using a modified Sindbis virus, we expressed either the enhanced green fluorescence protein (EGFP)-tagged Kv4.2 or an EGFP-tagged dominant negative mutant of Kv4.2 (Kv4.2g(W362F)) in CA1 pyramidal neurones of organotypic slice cultures. Neurones expressing Kv4.2g(W362F) displayed broader action potentials with an increase in frequency-dependent AP broadening during a train compared with control neurones. In addition, Ca2+ imaging of Kv4.2g(W362F) expressing dendrites revealed enhanced AP back-propagation compared to control neurones. Conversely, neurones expressing an increased A-type current through overexpression of Kv4.2 displayed narrower APs with less frequency dependent broadening and decreased dendritic propagation. These results point to Kv4.2 as the major contributor to the A-current in hippocampal CA1 neurones and suggest a prominent role for Kv4.2 in regulating AP shape and dendritic signalling. As Ca2+ influx occurs primarily during AP repolarization, Kv4.2 activity can regulate cellular processes involving Ca2+-dependent second messenger cascades such as gene expression and synaptic plasticity. C1 NICHHD, Mol Neurophysiol & Biophys Unit, Lab Synapt & Cellular Neurophysiol, NIH,Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. RP Hoffman, DA (reprint author), NICHHD, Mol Neurophysiol & Biophys Unit, Lab Synapt & Cellular Neurophysiol, NIH,Porter Neurosci Res Ctr, 35 Lincoln Dr,Bldg 35,Room 3C-905, Bethesda, MD 20892 USA. EM hoffmand@mail.nih.gov RI Hoffman, Dax/E-5155-2011 OI Hoffman, Dax/0000-0001-6999-2157 FU Intramural NIH HHS [Z99 HD999999] NR 52 TC 130 Z9 133 U1 0 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV 15 PY 2005 VL 569 IS 1 BP 41 EP 57 DI 10.1113/physiol.2005.095042 PG 17 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 990LO UT WOS:000233744800005 PM 16141270 ER PT J AU Cheatham, MA Zheng, J Huynh, KH Du, GG Gao, J Zuo, J Navarrete, E Dallos, R AF Cheatham, MA Zheng, J Huynh, KH Du, GG Gao, J Zuo, J Navarrete, E Dallos, R TI Cochlear function in mice with only one copy of the prestin gene SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID OUTER HAIR-CELLS; MOTOR PROTEIN PRESTIN; HEARING-LOSS; MECHANICAL RESPONSES; BASILAR-MEMBRANE; VOLTAGE SENSOR; TUNING CURVES; KNOCKOUT MICE; INNER-EAR; RT-PCR AB Targeted deletion of the prestin gene reduces cochlear sensitivity and eliminates both frequency selectivity and outer hair cell (OHC) somatic electromotility. In addition, it has been reported by Liberman and colleagues that F2 generation heterozygotes exhibit a 6 dB reduction in sensitivity, as well as a decrease in protein and electromotility. Considering that the active process is non-linear, a halving of somatic electromotility would be expected to produce a much larger change in sensitivity. We therefore re-evaluated comparisons between heterozygotes and wildtype mice using both in vivo and in vitro electrophysiology, as well as molecular biology. Data reported here for F3-F5 generation mice indicate that compound action potential thresholds and tuning curves, as well as the cochlear microphonic, are similar in heterozygotes and wildtype controls. Measurements of non-linear capacitance in isolated OHCs demonstrate that charge density, as well as the voltage dependence and sensitivity of motor function, is indistinguishable in the two genotypes, as is somatic electromotility. In addition, both immunocytochemistry and western blot analysis in young adult mice suggest that prestin protein in heterozygotes is near normal. In contrast, prestin mRNA is always less than in wildtype mice at all ages tested. Results from F3-F5 generation mice suggest that one copy of the prestin gene is capable of compensating for the deleted copy and that heterozygous mice do not suffer peripheral hearing impairment. C1 Northwestern Univ, Dept Commun Sci & Disorders, Evanston, IL 60208 USA. Northwestern Univ, Dept Neurobiol & Physiol, Evanston, IL 60208 USA. St Jude Childrens Res Hosp, Dept Dev Neurobiol, Memphis, TN 38105 USA. NIDCD, Sect Struct Cell Biol, Bethesda, MD 20892 USA. RP Cheatham, MA (reprint author), Northwestern Univ, Dept Commun Sci & Disorders, 2-240 Frances Searle Bldg,2240 Campus Dr, Evanston, IL 60208 USA. EM m-cheatham@northwestern.edu RI Zheng, Jing/F-5273-2017 FU NCI NIH HHS [P30 CA021765, CA21765]; NIDCD NIH HHS [DC00089, DC06471, R01 DC000089, R01 DC006471] NR 50 TC 30 Z9 31 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD NOV 15 PY 2005 VL 569 IS 1 BP 229 EP 241 DI 10.1113/jphysiol.2005.093518 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 990LO UT WOS:000233744800018 PM 16166160 ER PT J AU Chung, MK Shemanski, L Sherman, DG Greene, HL Hogan, DB Kellen, JC Kim, SG Martin, LW Rosenberg, Y Wyse, DG AF Chung, MK Shemanski, L Sherman, DG Greene, HL Hogan, DB Kellen, JC Kim, SG Martin, LW Rosenberg, Y Wyse, DG CA AFFIRM Investigators TI Functional status in rate- versus rhythm-control strategies for atrial fibrillation - Results of the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) functional status substudy SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID CHRONIC HEART-FAILURE; 6-MINUTE WALK TEST; QUALITY-OF-LIFE; CARDIAC-RESYNCHRONIZATION THERAPY; MINI-MENTAL-STATE; COGNITIVE FUNCTION; EXERCISE CAPACITY; ANGINA-PECTORIS; OXYGEN-UPTAKE; STROKE AB OBJECTIVES The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) functional status substudy aimed to test the hypothesis that functional status is similar in rate-control and rhythm-control strategies. BACKGROUND Randomized studies, including the AFFIRM study, have failed to demonstrate survival benefits between rate-control and rhythm-control strategies for atrial fibrillation (AF). However, AF may cause functional capacity or cognitive impairment that might justify maintenance of sinus rhythm. METHODS Investigators of the AFFIRM study, enrolled 4,060 patients with AF who required long-term therapy and who were 65 years of age or older or who had another risk factor for stroke or death. New York Heart Association functional class (NYHA-FC) and Canadian Cardiovascular Society Angina Classification were assessed at initial and each follow-up visit. From 22 randomly chosen functional status substudy sites, 245 participants underwent 6-min walk tests and Mini-Mental State Examination (MMSE) at initial, two-month, and Yearly visits. Patients were assigned randomly to rate-controlling drugs, allowing AF to persist, or rhythm-controlling antiarrhythmic drugs, to maintain sinus rhythm. RESULTS The NYHA-FC worsened with time in both rate-control and rhythm-control groups, with no differences between groups. Presence of AF was associated with worse NTYHA-FC (p < 0.0001). No differences were observed in Canadian Cardiovascular Society Angina Classification or MMSE scores. Six-minute walk distance improved over time in both study arms. On average, walk distance was 94 feet greater in the rhythm-control group (adjusted p = 0.049). CONCLUSIONS Modest improvement in 6-min walk distance was noted in the rhythm-control arm. Presence of AF was associated with worse NYHA-FC. No difference in cognitive function was detected. C1 Cleveland Clin Fdn, Dept Cardiovasc Med, Cleveland, OH 44195 USA. Axio Res Corp, Seattle, WA USA. Univ Texas, Dept Med, Div Neurol, San Antonio, TX 78285 USA. Univ Calgary, Fac Med, Calgary, AB, Canada. Univ Calgary, Dept Med, Calgary, AB, Canada. Montefiore Med Ctr, Bronx, NY 10467 USA. Kaiser Permanente Mid Atlantic Reg, Washington, DC USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Chung, MK (reprint author), Cleveland Clin Fdn, Dept Cardiovasc Med, 9500 Euclid Ave,Desk F-15, Cleveland, OH 44195 USA. EM chungm@ccf.org RI Hogan, David/I-4360-2013; OI Hogan, David/0000-0002-9462-5460; Martin, Lisa Warsinger/0000-0003-4352-0914 FU NHLBI NIH HHS [N01-HC-55139] NR 45 TC 78 Z9 85 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD NOV 15 PY 2005 VL 46 IS 10 BP 1891 EP 1899 DI 10.1016/j.jacc.2005.07.040 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 986GX UT WOS:000233439200018 PM 16286177 ER PT J AU Cohen, LG AF Cohen, LG TI Plasticity in motor control SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 18th World Congress of Neurology CY NOV 05-11, 2005 CL Sydney, AUSTRALIA C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. NINDS, Stroke Neurorehabil Clin, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2005 VL 238 SU 1 BP S23 EP S23 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 009CF UT WOS:000235088000093 ER PT J AU Hallett, M AF Hallett, M TI Movement disorders: What goes wrong in the basal ganglia? SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 18th World Congress of Neurology CY NOV 05-11, 2005 CL Sydney, AUSTRALIA C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2005 VL 238 SU 1 BP S26 EP S26 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 009CF UT WOS:000235088000106 ER PT J AU Hallett, M AF Hallett, M TI The cutting edge of clinical neurophysiology: Cerebral mechanisms - EEG analyses for studies of motor control and its disorders SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 18th World Congress of Neurology CY NOV 05-11, 2005 CL Sydney, AUSTRALIA C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2005 VL 238 SU 1 BP S33 EP S33 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 009CF UT WOS:000235088000136 ER PT J AU Lovas, G Hudson, L Szuchet, S AF Lovas, G Hudson, L Szuchet, S TI Perineuronal oligodendrocytes - A forgotten phenotype - in experimental demyelination and multiple sclerosis SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 18th World Congress of Neurology CY NOV 05-11, 2005 CL Sydney, AUSTRALIA C1 Jahn Ferenc Hosp, Dept Neurol, Budapest, Hungary. NINDS, Dept Genet Sect, NIH, Bethesda, MD 20892 USA. Univ Chicago, Dept Neurol, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2005 VL 238 SU 1 BP S234 EP S234 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 009CF UT WOS:000235088002149 ER PT J AU Ohtani, R Tornimoto, H Wakita, H Kitaguchi, H Nakaji, K Akiguchi, I Takahashi, I AF Ohtani, R Tornimoto, H Wakita, H Kitaguchi, H Nakaji, K Akiguchi, I Takahashi, I TI Expression of S-100 protein and protective effect of arundic acid on the rat brain of chronic cerebral hypoperfusion SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 18th World Congress of Neurology CY NOV 05-11, 2005 CL Sydney, AUSTRALIA C1 Kyoto Univ, Dept Neurol, Grad Sch Med, Kyoto, Japan. NINDS, NIH, Bethesda, MD 20892 USA. Koseikai Takeda Hosp, Dept Neurol, Kyoto, Japan. 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 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2005 VL 238 SU 1 BP S437 EP S437 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 009CF UT WOS:000235088004073 ER PT J AU Puccioni-Sohler, M Yamano, Y Goncalves, RG Vasconcelos, CCF Papais-Alvarenga, R Jacobson, S AF Puccioni-Sohler, M Yamano, Y Goncalves, RG Vasconcelos, CCF Papais-Alvarenga, R Jacobson, S TI The importance of the detection of proviral load in PBMNC and CSF in the differential diagnosis between HAM/TSP and multiple sclerosis SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 18th World Congress of Neurology CY NOV 05-11, 2005 CL Sydney, AUSTRALIA C1 UNIRIO, HUGG, EMC, Dept Neurol, Rio De Janeiro, Brazil. UFRJ, CSF Lab, Clin Pathol Serv, HUCFF, Rio De Janeiro, Brazil. Neurolife, CSF Lab, Rio De Janeiro, Brazil. NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2005 VL 238 SU 1 BP S305 EP S306 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 009CF UT WOS:000235088003027 ER PT J AU Thompson, AJ Polman, CH Reingold, SC Edan, G Filippi, M Hartung, HP Kappos, L Lublin, FD Metz, LM McFarland, HF O'Connor, PW Sandberg-Wollheim, M Weinshenker, BY Wolinsky, JS AF Thompson, AJ Polman, CH Reingold, SC Edan, G Filippi, M Hartung, HP Kappos, L Lublin, FD Metz, LM McFarland, HF O'Connor, PW Sandberg-Wollheim, M Weinshenker, BY Wolinsky, JS TI New criteria for the diagnosis of multiple sclerosis SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 18th World Congress of Neurology CY NOV 05-11, 2005 CL Sydney, AUSTRALIA C1 UCL Inst Neurol, London WC1N 3BG, England. Free Univ Amsterdam, Amsterdam, Netherlands. Natl Multiple Sclerosis Soc, LLC, New York, NY USA. Sci & Clin Review Associates, New York, NY USA. CHRU, Hosp San Raffaele, Dept Neurol, Neuroimaging Res Unit, Rennes, France. Univ Milan, I-20122 Milan, Italy. Univ Dusseldorf, D-4000 Dusseldorf, Germany. Kantonsspital, CH-4031 Basel, Switzerland. Mt Sinai Sch Med, New York, NY USA. Foothills Med Ctr, Calgary, AB, Canada. NINDS, Bethesda, MD 20892 USA. St Michaels Hosp, Toronto, ON M5B 1W8, Canada. Univ Lund Hosp, Coll Med, S-22185 Lund, Sweden. Mayo Clin, Hlth Sci Ctr, Rochester, MN USA. Univ Texas, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2005 VL 238 SU 1 BP S16 EP S17 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 009CF UT WOS:000235088000066 ER PT J AU Wickremaratchi, MM Momeni, P Hardy, J Neal, J Morris, HR AF Wickremaratchi, MM Momeni, P Hardy, J Neal, J Morris, HR TI Familial fronto-temporal dementia in Wales SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Meeting Abstract CT 18th World Congress of Neurology CY NOV 05-11, 2005 CL Sydney, AUSTRALIA C1 Univ Cardiff Wales, Sch Med, Dept Neurol Ophthalmol & Audiol Med, Cardiff, Wales. NIA, Neurogenet Lab, Bethesda, MD 20892 USA. Univ Hosp Wales, Dept Pathol, Cardiff, Wales. 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 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD NOV 15 PY 2005 VL 238 SU 1 BP S159 EP S160 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 009CF UT WOS:000235088001254 ER PT J AU Collins, MD Hummer, G Quillin, ML Matthews, BW Gruner, SM AF Collins, MD Hummer, G Quillin, ML Matthews, BW Gruner, SM TI Cooperative water filling of a nonpolar protein cavity observed by high-pressure crystallography and simulation SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE hydrophobic effect; T4 lysozyme ID CREATING MUTATIONS; LYSOZYME; STABILIZATION; MOLECULES; HYDRATION; BINDING; NMR AB Formation of a water-expelling nonpolar core is the paradigm of protein folding and stability. Although experiment largely confirms this picture, water buried in "hydrophobic" cavities is required for the function of some proteins. Hydration of the protein core has also been suggested as the mechanism of pressure-induced unfolding. We therefore are led to ask whether even the most nonpolar protein core is truly hydrophobic (i.e., waterrepelling). To answer this question we probed the hydration of an approximate to 160-angstrom(3), highly hydrophobic cavity created by mutation in T4 lysozynne by using high-pressure crystallography and molecular dynamics simulation. We show that application of modest pressure causes approximately four water molecules to enter the cavity while the protein itself remains essentially unchanged. The highly cooperative filling is primarily due to a small change in bulk water activity, which implies that changing solvent conditions or, equivalently, cavity polarity can dramatically affect interior hydration of proteins and thereby influence both protein activity and folding. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Cornell Univ, Dept Phys, Ithaca, NY 14853 USA. Univ Oregon, Dept Phys, Eugene, OR 97403 USA. Univ Oregon, Howard Hughes Med Inst, Inst Mol Phys, Eugene, OR 97403 USA. RP Gruner, SM (reprint author), NIDDK, Phys Chem Lab, NIH, Bldg 4, Bethesda, MD 20892 USA. EM smg26@cornell.edu RI Hummer, Gerhard/A-2546-2013; Gruner, Sol/G-2924-2010 OI Hummer, Gerhard/0000-0001-7768-746X; Gruner, Sol/0000-0002-1171-4426 FU NIGMS NIH HHS [R01 GM021967, GM21967, DMR0225180] NR 32 TC 124 Z9 128 U1 3 U2 21 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 NOV 15 PY 2005 VL 102 IS 46 BP 16668 EP 16671 DI 10.1073/pnas.0508224102 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 986PT UT WOS:000233462900027 PM 16269539 ER PT J AU Furuya, T Mu, JB Hayton, K Liu, A Duan, JH Nkrumah, L Joy, DA Fidock, DA Fujioka, H Vaidya, AB Wellems, TE Su, XZ AF Furuya, T Mu, JB Hayton, K Liu, A Duan, JH Nkrumah, L Joy, DA Fidock, DA Fujioka, H Vaidya, AB Wellems, TE Su, XZ TI Disruption of a Plasmodium falciparum gene linked to male sexual development causes early arrest in gametocytogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE gametocyte; genetic mapping; malaria; microarray ID HUMAN MALARIA PARASITE; CONTINUOUS CULTURE; MALE GAMETOGENESIS; COMMITMENT; INDUCTION; DEFECT; IDENTIFICATION; RECOMBINATION; GAMETOCYTES; RESISTANCE AB A male gametocyte defect in the Plasmodium falciparum Dd2 parasite was previously discovered through the observation that all progeny clones in a Dd2 x HB3 genetic cross were the result of fertilization events between Dd2 female and HB3 male gametes. A determinant linked to the defect in Dd2 was subsequently mapped to an 800-kb segment on chromosome 12. Here, we report further mapping of the determinant to an 82-kb region and the identification of a candidate gene, P. faiciparum male development gene 1 (pfmdv-1), that is expressed at a lower level in Dd2 compared with the wild-type normal male gametocyte-producing ancestor W2. Pfmdv-1 protein is sexual-stage specific and is located on the gametocyte plasma membrane, parasitophorous vacuole membrane, and the membranes of cleft-like structures within the erythrocyte. Disruption of pfmdv-1 results in a dramatic reduction in mature gametocytes, especially functional male gametocytes, with the majority of sexually committed parasites developmentally arrested at stage 1. The pfmdv-1-knockout parasites show disturbed membrane structures, particularly multimembrane vesicles/tubes that likely derive from deformed cleft-like structures. Mosquito infectivity of the knockout parasites was also greatly reduced but not completely lost. The results suggest that pfmdv-1 plays a key role in gametocyte membrane formation and integrity. C1 NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20850 USA. Albert Einstein Coll Med, Dept Immunol & Microbiol, Bronx, NY 10461 USA. Case Western Reserve Univ, Inst Pathol, Cleveland, OH 44106 USA. Drexel Univ, Coll Med, Dept Microbiol & Immunol, Philadelphia, PA 19129 USA. RP Su, XZ (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Room 3E-24B,12735 Twinbrook Pkwy, Rockville, MD 20850 USA. EM xsu@niaid.nih.gov RI Furuya, Tetsuya/J-5916-2013; Furuya, Tetsuya/H-2412-2013; OI Fidock, David/0000-0001-6753-8938; Furuya, Tetsuya/0000-0003-3979-7072; Su, Xinzhuan/0000-0003-3246-3248 FU Intramural NIH HHS; NIAID NIH HHS [R01 AI041879] NR 35 TC 49 Z9 50 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 NOV 15 PY 2005 VL 102 IS 46 BP 16813 EP 16818 DI 10.1073/pnas.0501858102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 986PT UT WOS:000233462900052 PM 16275909 ER PT J AU Panchenko, AR Wolf, YI Panchenko, LA Madej, T AF Panchenko, AR Wolf, YI Panchenko, LA Madej, T TI Evolutionary plasticity of protein families: Coupling between sequence and structure variation SO PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS LA English DT Article DE protein structural evolution; sequence variation; protein loops; sequence-structure correlation AB In this work we examine how protein structural changes are coupled with sequence variation in the course of evolution of a family of homologs. The sequence-structure correlation analysis performed on 81 homologous protein families shows that the majority of them exhibit statistically significant linear correlation between the measures of sequence and structural similarity. We observed, however, that there are cases where structural variability cannot be mainly explained by sequence variation, such as protein families with a number of disulfide bonds. To understand whether structures from different families and/or folds evolve in the same manner, we compared the degrees of structural change per unit of sequence change ("the evolutionary plasticity of structure") between those families with a significant linear correlation. Using rigorous statistical procedures we find that, with a few exceptions, evolutionary plasticity does not show a statistically significant difference between protein families. Similar sequence-structure analysis performed for protein loop regions shows that evolutionary plasticity of loop regions is greater than for the protein core C1 NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. Moscow MV Lomonosov State Univ, Dept Biol, Moscow, Russia. RP Panchenko, AR (reprint author), NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Bldg 38A, Bethesda, MD 20894 USA. EM panch@ncbi.nlm.nih.gov FU Intramural NIH HHS; NLM NIH HHS [Z01 LM000057-12] NR 42 TC 26 Z9 27 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-3585 J9 PROTEINS JI Proteins PD NOV 15 PY 2005 VL 61 IS 3 BP 535 EP 544 DI 10.1002/prot.20644 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 980PF UT WOS:000233029800010 PM 16184609 ER PT J AU Zahn, TP Pickar, D AF Zahn, TP Pickar, D TI Autonomic activity in relation to symptom ratings and reaction time in unmedicated patients with schizophrenia SO SCHIZOPHRENIA RESEARCH LA English DT Article DE schizophrenia; electrodermal activity; heart rate; symptoms; reaction time ID CONDUCTANCE ORIENTING RESPONSE; BILATERAL SKIN-CONDUCTANCE; ELECTRODERMAL ACTIVITY; SPONTANEOUS FLUCTUATIONS; ONSET SCHIZOPHRENIA; CLINICAL RATINGS; STATE; HABITUATION; MEDICATION; MODEL AB Problem: High autonomic base levels and low responsivity are frequently observed in unmedicated patients with schizophrenia. We previously reported that patients in the present cohort, compared to normal controls, had high autonomic tonic baselines and low reactivity to the meaningful stimuli in a reaction time (RT) task but not to novel but innocuous stimuli. This paper explores further the role of autonomic activity in the pathogenesis of schizophrenia by relating differences in the autonomic variables among patients to symptom ratings and RT. Methods: Electrodermal activity and heart rate were recorded during rest, a tone series, and a RT task in 73 patients with schizophrenia taking placebo. Symptoms were rated with the Brief Psychiatric Rating Scale. Results: Patients with higher autonomic baselines both at rest and under mild stress and those with greater electrodermal responsivity to both simple tones and the RT stimuli had more severe positive, "active", and total Symptoms than patients with lower baselines and responsivity. RT was slower in patients with higher baselines. Conclusions: High autonomic activity in general, reactivity as well as base levels, under all conditions used in this study was associated with symptom severity independent of differences from controls. Thus elevated autonomic activity and responsivity may themselves be disturbing or index states that are disturbing in schizophrenia. Some patients might attempt to cope with novel or demanding situations and stimuli by a passive-avoidant strategy of low attention and effort in order to attenuate their responsivity. Less symptomatic patients may better cope in this manner. (c) 2005 Elsevier B.V All rights reserved. C1 NIH, Lab Brain & Cognit, Bethesda, MD 20892 USA. NIMH, Expt Therapeut Branch, Bethesda, MD 20892 USA. RP Zahn, TP (reprint author), NIH, Lab Brain & Cognit, Bldg 10,Rm 4C104,MSC 1366, Bethesda, MD 20892 USA. EM tpz@mail.nih.gov NR 40 TC 26 Z9 26 U1 3 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-9964 J9 SCHIZOPHR RES JI Schizophr. Res. PD NOV 15 PY 2005 VL 79 IS 2-3 BP 257 EP 270 DI 10.1016/j.schres.2005.05.025 PG 14 WC Psychiatry SC Psychiatry GA 981GC UT WOS:000233074600012 PM 16006104 ER PT J AU Troendle, JF Liu, AY Wu, CQ Yu, KF AF Troendle, JF Liu, AY Wu, CQ Yu, KF TI Sequential testing for efficacy in clinical trials with non-transient effects SO STATISTICS IN MEDICINE LA English DT Article DE Bonferroni; familywise; longitudinal; multiple testing; sequential AB This paper describes a new type of sequential testing for clinical trials. The sequential nature of the data is not from additional patients, but rather from longer follow-up times. At each analysis, the null hypothesis that all treatments are equivalent in effect on the Outcome after that amount of time is tested. The trial might still have staggered entry or not, but the key feature is that a different statistical hypothesis is tested at each analysis. It is assumed that any effect of treatment is non-transient, allowing a conclusion to be drawn in favour of one treatment or the other based on a difference at a single follow-up time. It is shown that a general method based on the Bonferroni inequality can be used to obtain critical cutpoints for sequential testing, that controls the chance of a type I error for the clinical decision. This method is applicable regardless of the test used at each analysis. In the case of a two-armed trial with a Gaussian outcome variable, it is shown how simulation can be used to obtain critical cutpoints that maintain the chance of a type I error for the clinical decision. The methods are compared by Monte-Carlo simulation, and it is seen that in most practical cases the Bonferroni method is not very conservative. The Bonferroni procedure is illustrated on the results of a real clinical trial of Pirfenidone on pulmonary fibrosis in Hermansky-Pudlak Syndrome. Published in 2005 by John Wiley & Sons, Ltd. C1 NICHHD, Biometry & Math Stat Branch, Div Epidemiol Stat & Prevent Res, NIH,DHHS, Bethesda, MD 20892 USA. RP Troendle, JF (reprint author), NICHD, DHHS, NIH, DESPR,BMSB, 6100 Execut Blvd,Room 7B05, Bethesda, MD 20892 USA. EM jt3t@nih.gov OI Liu, Aiyi/0000-0002-6618-5082 NR 7 TC 1 Z9 1 U1 0 U2 2 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 NOV 15 PY 2005 VL 24 IS 21 BP 3239 EP 3250 DI 10.1002/sim.2194 PG 12 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 976LT UT WOS:000232735700001 PM 16206248 ER PT J AU Caillard, S Dharnidharka, V Agodoa, L Bohen, E Abbott, K AF Caillard, S Dharnidharka, V Agodoa, L Bohen, E Abbott, K TI Posttransplant lymphoproliferative disorders after renal transplantation in the United States in era of modern immunosuppression SO TRANSPLANTATION LA English DT Article DE kidney transplantation; posttransplant lymphoproliferative disorders; immunosuppression; United States Renal Data System ID BARR-VIRUS INFECTION; KIDNEY-TRANSPLANTATION; MYCOPHENOLATE-MOFETIL; GRAFT-SURVIVAL; ORGAN-TRANSPLANTATION; RISK; RECIPIENTS; DISEASE; TACROLIMUS; SANDIMMUNE AB Background. Posttransplant lymphoproliferative disorders (PTLD) still represent a major preoccupation after renal transplantation, even in the most recent years. Methods. We analyzed the incidence, risk, and prognostic factors of PTLD in a cohort of kidney recipients using the United States Renal Data System. Results. Among 25,127 Medicare patients transplanted between 1996 and 2000, 344 developed a PTLD defined as a non-Hodgkin lymphoma (1.4%). History of pretransplant malignancy (adjusted hazard ratio [AHR] =3.54, CI 2.31-5.43), younger age (AHR=1.91, CI 1.18-3.1), fewer HLA matches (AHR= 1.32, CI 1.1-1.59) and treatment by ATG (AHR= 1.55, CI 1.2-1.99) and OKT3 (AHR= 1.37, CI 1-1.76), especially if given for rejection therapy were associated with an increased risk of PTLD. Mycophenolate and azathioprine were associated with a lower risk of PTLD (AHR=0.6, CI 0.47-0.78 and AHR=0.66, CI 0.46-0.95, respectively). IL2-receptor inhibitors and sirolinius did not modify the risk of PTLD. Patients without induction therapy treated with tacrolimus were at greater risk of lymphoma than those treated with new formulations of cyclosporine and those treated with antimetabolites (mycophenolate and azathioprine) have a lower risk of PTLD than those without. Patients with PTLD had poor survival (64% vs. 80% at 5 years). Older age, pretransplant malignancy and OKT3 were risk factors for death whereas treatment with mycophenolate was associated with a better survival (AHR=0.49, CI=0.28-0.82). Conclusions. Our study highlights the contribution of patient history and immunosuppression in the risk of PTLD in the era of modern immunosuppression. C1 Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Univ Florida, Pediat Nephrol Serv, Gainesville, FL 32611 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Abbott, K (reprint author), Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. EM kevin.abbott@na.amedd.army.mil OI Abbott, Kevin/0000-0003-2111-7112 NR 32 TC 206 Z9 212 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD NOV 15 PY 2005 VL 80 IS 9 BP 1233 EP 1243 DI 10.1097/01.tp.0000179639.98338.39 PG 11 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 990HA UT WOS:000233732600015 PM 16314791 ER PT J AU Zhang, QJ Zulfiqar, F Riazuddin, SA Xiao, XS Yasmeen, A Rogan, PK Caruso, R Sieving, PA Riazuddin, S Hejtmancik, JF AF Zhang, QJ Zulfiqar, F Riazuddin, SA Xiao, XS Yasmeen, A Rogan, PK Caruso, R Sieving, PA Riazuddin, S Hejtmancik, JF TI A variant form of Oguchi disease mapped to 13q34 associated with partial deletion of GRK1 gene SO MOLECULAR VISION LA English DT Article ID STATIONARY NIGHT BLINDNESS; RECESSIVE RETINITIS-PIGMENTOSA; HUMAN RHODOPSIN KINASE; NULL MUTATION; ARRESTIN GENE; BETA-SUBUNIT; ROD; LIGHT; PHOSPHODIESTERASE AB Purpose: The purpose of this paper is to map the locus for a variant form of Oguchi disease in a Pakistani family and to identify the causative mutation. Methods: Family 61029 was ascertained in the Punjab province of Pakistan. It includes three 13- to 19-year-old patients with night blindness and 12 unaffected family members. A complete ophthalmological examination including fundus photography and electroretinography (ERG) was performed on each family member. A genome-wide scan was performed using microsatellite markers at about 10 cM intervals, and two-point lod scores were calculated. Polymerase chain reaction (PCR) cycle dideoxynucleotide sequencing was used to screen candidate genes inside the linked region for mutations and to delineate the deletion. Multiplex PCR and long template PCR were used to detect deletions and to define the size of deletions. Evaluation of fundus changes and ERG, lod score estimation, and identification of a mutation in the GRK1 gene were carried out. Results: All patients had night blindness since early childhood. Irregular coarse pigmentation was observed in the peripheral retina of each patient. The fundus appearance before and after 4 h of dark adaptation was similar except that the peripheral retinal pigmentary changes were slightly less evident after extended dark adaptation. Minimal or no rod function with normal cone function on ERG recordings were detected in all three affected members. The rod showed slow recovery to nearly normal amplitude after 4 h in the dark ERG in one individual but not in two other patients. A genome-wide scan showed linkage only to D13S285. Fine mapping defined a region from D13S1315 to 13qter, with a lod score of 2.89 at theta=0 shown by D13S285 and 2.90 at theta=0 by the D13S261-D13S285-D13S1295-D13S293 haplotype. Analysis of the GRK1 gene, which is included in this interval, identified a c.827+623_883del mutation. This intragenic deletion cosegregates with the disease in the family and is only homozygous in affected individuals. This mutation was not detected in 96 controls. Conclusions: The retinal disease in the family reported here has several features differing from typical Oguchi disease, including an atypical Mizuo-Nakamura phenomenon and a non-recordable rod ERG even after 4 h of dark adaptation. Normal visual acuity, normal caliber of retinal blood vessels, and normal cone response on ERG recording suggest retinal dysfunction rather than degeneration (i.e., a variant form of Oguchi disease but unlikely to be retinitis pigmentosa). The disease in the Pakistani family localizes to 13q34 and is caused by a novel deletion including Exon 3 of the GRK1 gene. C1 NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore, Pakistan. Sun Yat Sen Univ, Minist Educ, Key Lab Ophthalmol, Guangzhou, Peoples R China. Sun Yat Sen Univ, Zhongshan Ophthalm Ctr, Guangzhou, Peoples R China. Univ Missouri, Childrens Mercy Hosp, Lab Human Mol Genet, Kansas City, MO 64108 USA. RP Hejtmancik, JF (reprint author), NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bldg 10,Room 10B10,10 Ctr Dr,MSC 1860, Bethesda, MD 20892 USA. EM f3h@helix.nih.gov RI SHEIKH, RIAZUDDIN/L-2406-2015; Rogan, Peter/B-9845-2017 OI Rogan, Peter/0000-0003-2070-5254 NR 28 TC 12 Z9 13 U1 0 U2 0 PU MOLECULAR VISION PI ATLANTA PA C/O JEFF BOATRIGHT, LAB B, 5500 EMORY EYE CENTER, 1327 CLIFTON RD, N E, ATLANTA, GA 30322 USA SN 1090-0535 J9 MOL VIS JI Mol. Vis. PD NOV 14 PY 2005 VL 11 IS 117 BP 977 EP 985 PG 9 WC Biochemistry & Molecular Biology; Ophthalmology SC Biochemistry & Molecular Biology; Ophthalmology GA 988LI UT WOS:000233602300001 PM 16319817 ER PT J AU Malley, JD Fine, A AF Malley, JD Fine, A TI Noncommuting observables and local realism SO PHYSICS LETTERS A LA English DT Article DE entanglement; local realism; commuting observables ID QUANTUM CORRELATIONS; HIDDEN-VARIABLES; PROBABILITY AB A standard approach in the foundations of quantum mechanics studies local realism and hidden variables models exclusively in terms of violations of Bell-like inequalities. Thus quantum nonlocality is tied to the celebrated no-go theorems, and these comprise a long list that includes the Kochen-Specker and Bell theorems, as well as elegant refinements by Mermin, Peres, Hardy, GHZ, and many others. Typically entanglement or carefully prepared multipartite systems have been considered essential for violations of local realism and for understanding quantum nonlocality. Here we show, to the contrary, that sharp violations of local realism arise almost everywhere without entanglement. The pivotal fact driving these violations is just the noncommutativity of quantum observables. We demonstrate how violations of local realism occur for arbitrary noncommuting projectors, and for arbitrary quantum pure states. Finally, we point to elementary tests for local realism, using single particles and without reference to entanglement, thus avoiding experimental loopholes and efficiency issues that continue to bedevil the Bell inequality related tests. (c) 2005 Elsevier B.V. All rights reserved. C1 Ctr Informat Technol, NIH, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. RP Fine, A (reprint author), Ctr Informat Technol, NIH, Bethesda, MD 20892 USA. EM afine@u.washington.edu NR 8 TC 16 Z9 16 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0375-9601 J9 PHYS LETT A JI Phys. Lett. A PD NOV 14 PY 2005 VL 347 IS 1-3 BP 51 EP 55 DI 10.1016/j.physleta.2005.06.032 PG 5 WC Physics, Multidisciplinary SC Physics GA 986ZB UT WOS:000233487100009 ER PT J AU Fremond, C Allie, N Dambuza, I Grivennikov, SI Yeremeev, V Quesniaux, VFJ Jacobs, M Ryffel, B AF Fremond, C Allie, N Dambuza, I Grivennikov, SI Yeremeev, V Quesniaux, VFJ Jacobs, M Ryffel, B TI Membrane TNF confers protection to acute mycobacterial infection SO RESPIRATORY RESEARCH LA English DT Article ID TUMOR-NECROSIS-FACTOR; BACILLUS-CALMETTE-GUERIN; BONE-MARROW-TRANSPLANTATION; CELL-MEDIATED-IMMUNITY; NITRIC-OXIDE SYNTHASE; BOVIS BCG INFECTION; TUBERCULOSIS INFECTION; TRANSMEMBRANE TNF; DEFICIENT MICE; FACTOR-ALPHA AB Background: Tumour necrosis factor (TNF) is crucial for the control of mycobacterial infection as TNF deficient ( KO) die rapidly of uncontrolled infection with necrotic pneumonia. Here we investigated the role of membrane TNF for host resistance in knock-in mice with a non-cleavable and regulated allele (mem-TNF). Methods: C57BL/6, TNF KO and mem-TNF mice were infected with M. tuberculosis H37Rv (Mtb at 100 CFU by intranasal administration) and the survival, bacterial load, lung pathology and immunological parameters were investigated. Bone marrow and lymphocytes transfers were used to test the role of membrane TNF to confer resistance to TNF KO mice. Results: While TNF-KO mice succumbed to infection within 4-5 weeks, mem-TNF mice recruited normally T cells and macrophages, developed mature granuloma in the lung and controlled acute Mtb infection. However, during the chronic phase of infection mem-TNF mice succumbed to disseminated infection with necrotic pneumonia at about 150 days. Reconstitution of irradiated TNF-KO mice with mem-TNF derived bone marrow cells, but not with lymphocytes, conferred host resistance to Mtb infection in TNF-KO mice. Conclusion: Membrane expressed TNF is sufficient to allow cell-cell signalling and control of acute Mtb infection. Bone marrow cells, but not lymphocytes from mem-TNF mice confer resistance to infection in TNF-KO mice. Long-term infection control with chronic inflammation likely disrupting TNF mediated cell-cell signalling, additionally requires soluble TNF. C1 CNRS, F-45071 Orleans, France. Univ Cape Town, Dept Immunol, Inst Infect Dis & Mol Med, ZA-7700 Rondebosch, South Africa. NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21702 USA. Max Planck Inst Infect Biol, Dept Immunol, D-10117 Berlin, Germany. RP Ryffel, B (reprint author), CNRS, F-45071 Orleans, France. EM fremond@cnrs-orleans.fr; allie@uctgsh1.uct.ac.za; dambuza@uctgsh1.uct.ac.za; serggriv@mail.ru; yeremeev@mpiib-berlin.mpg.de; quesniaux@cnrs-orleans.fr; mjacobs@uctgsh1.uct.ac.za; bryffel@cnrs-orleans.fr RI Yeremeev, Vladimir/F-6507-2014 OI Yeremeev, Vladimir/0000-0001-6608-7557 FU Wellcome Trust NR 47 TC 39 Z9 39 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-9921 J9 RESP RES JI Respir. Res. PD NOV 14 PY 2005 VL 6 AR 136 DI 10.1186/1465-9921-6-136 PG 9 WC Respiratory System SC Respiratory System GA 999FP UT WOS:000234374600001 PM 16285886 ER PT J AU Shulzhenko, N Yambartsev, A Goncalves-Primo, A Gerbase-DeLima, M Morgun, A AF Shulzhenko, N Yambartsev, A Goncalves-Primo, A Gerbase-DeLima, M Morgun, A TI Selection of control genes for quantitative RT-PCR based on microarray data SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE normalization; RT-PCR; microarray; housekeeping gene; internal reference genes; heart transplant ID POLYMERASE CHAIN-REACTION; EXPRESSION; NORMALIZATION; IDENTIFICATION; VALIDATION AB Use of internal reference gene(s) is necessary for adequate quantification of target gene expression by RT-PCR. Herein, we elaborated a strategy of control gene selection based on microarray data and illustrated it by analyzing endomyocardial biopsies with acute cardiac rejection and infection. Using order statistics and binomial distribution we evaluated the probability of finding low-varying genes by chance. For analysis, the microarray data were divided into two sample subsets. Among the first 10% of genes with the lowest standard deviations, we found 14 genes common to both subsets. After normalization using two selected genes, high correlation was observed between expression of target genes evaluated by microarray and RT-PCR, and in independent dataset by RT-PCR (r = 0.9, p < 0.001). In conclusion, we showed a simple and reliable strategy of selection and validation of control genes for RT-PCR from microarray data that can be easily applied for different experimental designs and tissues. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Fed Sao Paulo, Dept Pediat, Div Immunogenet, Sao Paulo, SP, Brazil. Univ Sao Paulo, Inst Math & Stat, Sao Paulo, SP, Brazil. RP Morgun, A (reprint author), NIAID, Ghost Lab, LCMI, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM morguna@niaid.nih.gov RI Gerbase-DeLima, Maria/K-2515-2015 NR 16 TC 14 Z9 14 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 NOV 11 PY 2005 VL 337 IS 1 BP 306 EP 312 DI 10.1016/j.bbrc.2005.09.048 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 974IE UT WOS:000232584000045 PM 16182241 ER PT J AU Liu, HJ Colavitti, R Rovira, II Finkel, T AF Liu, HJ Colavitti, R Rovira, II Finkel, T TI Redox-dependent transcriptional regulation SO CIRCULATION RESEARCH LA English DT Review DE Yap1; ref; Nrf2; atherosclerosis; oxidative stress ID DISULFIDE BOND FORMATION; VASCULAR SMOOTH-MUSCLE; DNA-BINDING ACTIVITY; OXIDATIVE STRESS; GENE-EXPRESSION; HISTONE DEACETYLASE; SIGNAL-TRANSDUCTION; STRUCTURAL BASIS; NRF2 ACTIVATION; REACTIVE OXYGEN AB Reactive oxygen species contribute to the pathogenesis of a number of disparate disorders including tissue inflammation, heart failure, hypertension, and atherosclerosis. In response to oxidative stress, cells activate expression of a number of genes, including those required for the detoxification of reactive molecules as well as for the repair and maintenance of cellular homeostasis. In many cases, these induced genes are regulated by transcription factors whose structure, subcellular localization, or affinity for DNA is directly or indirectly regulated by the level of oxidative stress. This review summarizes the recent progress on how cellular redox status can regulate transcription-factor activity and the implications of this regulation for cardiovascular disease. C1 NIH, Cardiol Branch, NHLBI, Bethesda, MD 20892 USA. RP Finkel, T (reprint author), NIH, Cardiol Branch, NHLBI, Bldg 10,CRC 5-3330,10 Ctr Dr, Bethesda, MD 20892 USA. EM finkelt@nih.gov FU Intramural NIH HHS NR 65 TC 249 Z9 263 U1 2 U2 21 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV 11 PY 2005 VL 97 IS 10 BP 967 EP 974 DI 10.1161/01.RES.0000188210.72062.10 PG 8 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 982PI UT WOS:000233173700005 PM 16284189 ER PT J AU Chen, QH Liu, JB Horak, KM Zheng, HQ Kumarapeli, ARK Li, J Li, FQ Gerdes, AM Wawrousek, EF Wang, XJ AF Chen, QH Liu, JB Horak, KM Zheng, HQ Kumarapeli, ARK Li, J Li, FQ Gerdes, AM Wawrousek, EF Wang, XJ TI Intrasarcoplasmic amyloidosis impairs proteolytic function of proteasomes in cardiomyocytes by compromising substrate uptake SO CIRCULATION RESEARCH LA English DT Article DE proteasome; ubiquitin; protein aggregation; alpha beta-crystallin; desmin-related cardiomyopathy; amyloidosis; transgenic mice ID ALPHA-B-CRYSTALLIN; PROTEIN AGGREGATION; UBIQUITIN LIGASE; 26S PROTEASOME; MOUSE MODEL; SYSTEM; CARDIOMYOPATHY; DESMIN; HEART; MICE AB The presence of increased ubiquitinated proteins and amyloid oligomers in failing human hearts strikingly resembles the characteristic pathology in the brain of many neurodegenerative diseases. The ubiquitin-proteasome system ( UPS) is responsible for degradation of most cellular proteins and plays essential roles in virtually all cellular processes. UPS impairment by aberrant protein aggregation was previously shown in cell culture but remains to be demonstrated in intact animals. Mechanisms underlying the impairment are poorly understood. We report here that UPS proteolytic function is severely impaired in the heart of a mouse model of intrasarcoplasmic amyloidosis caused by cardiac-restricted expression of a human desmin-related myopathy-linked missense mutation of alpha B-crystallin (CryAB(R120G)). The UPS impairment was detected before cardiac hypertrophy, and failure became discernible, suggesting that defective protein turnover likely contributes to cardiac remodeling and failure in this model. Further analyses reveal that the impairment is likely attributable to insufficient delivery of substrate proteins into the 20S proteasomes, and depletion of key components of the 19S subcomplex may be responsible. The derangement is likely caused by aberrant protein aggregation rather than loss of function of the CryAB gene because UPS malfunction was not evident in CryAB-null hearts and inhibition of aberrant protein aggregation by Congo red or a heat shock protein significantly attenuated CryAB(R120G)-induced UPS malfunction in cultured cardiomyocytes. Because of the central role of the UPS in cell regulation and the high intrasarcoplasmic amyloidosis prevalence in failing human hearts, our data suggest a novel pathogenic process in cardiac disorders with abnormal protein aggregation. C1 Univ S Dakota, Sch Med, Inst Cardiovasc Res, S Dakota Hlth Res Fdn, Sioux Falls, SD 57105 USA. Sioux Valley Hosp & Hlth Syst, Sioux Falls, SD USA. NEI, NIH, Bethesda, MD 20892 USA. Guangzhou Med Coll, Dept Pathophysiol, Guangzhou, Guangdong, Peoples R China. Univ S Dakota, Sch Med, Dept Lab Med, Sioux Falls, SD USA. Univ S Dakota, Sch Med, Div Basic Biomed Sci, Sioux Falls, SD USA. RP Wang, XJ (reprint author), Univ S Dakota, Sch Med, Inst Cardiovasc Res, S Dakota Hlth Res Fdn, 1100 E 21st St,Ste 700, Sioux Falls, SD 57105 USA. EM xwang@usd.edu RI Wawrousek, Eric/A-4547-2008; Wang, Xuejun/K-8874-2013 OI Wang, Xuejun/0000-0001-9267-1343 FU NCRR NIH HHS [P20 RR-17662]; NHLBI NIH HHS [R01 HL072166, HL72166] NR 35 TC 94 Z9 97 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD NOV 11 PY 2005 VL 97 IS 10 BP 1018 EP 1026 DI 10.1161/01.RES.0000189262.92896.0b PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 982PI UT WOS:000233173700011 PM 16210548 ER PT J AU LaRonde-LeBlanc, N Wlodawer, A AF LaRonde-LeBlanc, N Wlodawer, A TI A family portrait of the RIO kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Review ID PRE-RIBOSOMAL-RNA; PROTEIN-KINASE; CRYSTAL-STRUCTURE; SACCHAROMYCES-CEREVISIAE; WINGED-HELIX; FULGIDUS RIO2; GENE; PATTERNS; BACTERIA; SUBUNIT AB The RIO family of atypical serine protein kinases has been first characterized only recently. It consists of enzymes that contain a unique domain with a characteristic kinase sequence motif and usually some additional domains. At least two RIO proteins, Rio1 and Rio2, are present in organisms varying from Archaea to humans, with a third Rio3 subfamily present only in multicellular eukaryotes. Yeast Rio1 and Rio2 proteins have been implicated in the processing of 20 S pre-rRNA and are necessary for survival of the cells. Crystal structures of Archaeoglobus fulgidus Rio1 and Rio2 have shown that whereas the overall fold of these enzymes resembles typical protein kinases, some of the structural domains, particularly those involved in peptide substrate binding, are not present. The mode of binding of nucleotides also differs from that found in typical protein kinases. Although it has been shown that both Rio1 and Rio2 have the enzymatic activity of kinases and are capable of autophosphorylation, the biological substrates of RIO proteins and their full biological role still remain to be discovered. C1 NCI, Prot Struct Sect, MCL, NIH, Frederick, MD 21702 USA. RP Wlodawer, A (reprint author), NCI, Prot Struct Sect, MCL, NIH, Bldg 536,Rm 5, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov RI LaRonde-LeBlanc, Nicole/C-3399-2009 OI LaRonde-LeBlanc, Nicole/0000-0002-2778-8358 FU Intramural NIH HHS NR 28 TC 48 Z9 50 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 NOV 11 PY 2005 VL 280 IS 45 BP 37297 EP 37300 DI 10.1074/jbc.R500013200 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 980UU UT WOS:000233044500002 PM 16183636 ER PT J AU Barbour, LA Rahman, SM Gurevich, I Leitner, JW Fischer, SJ Roper, MD Knotts, TA Vo, Y McCurdy, CE Yakar, S LeRoith, D Kahn, CR Cantley, LC Friedman, JE Draznin, B AF Barbour, LA Rahman, SM Gurevich, I Leitner, JW Fischer, SJ Roper, MD Knotts, TA Vo, Y McCurdy, CE Yakar, S LeRoith, D Kahn, CR Cantley, LC Friedman, JE Draznin, B TI Increased p85 alpha is a potent negative regulator of skeletal muscle insulin signaling and induces in vivo insulin resistance associated with growth hormone excess SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PHOSPHOINOSITIDE 3-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE PHOSPHORYLATION; TRANSGENIC MICE; P85 ALPHA; SUBUNIT; SENSITIVITY; EXPRESSION; INHIBITION; LACKING AB Insulin resistance is a cardinal feature of normal pregnancy and excess growth hormone (GH) states, but its underlying mechanism remains enigmatic. We previously found a significant increase in the p85 regulatory subunit of phosphatidylinositol kinase ( PI3-kinase) and striking decrease in IRS-1-associated PI 3-kinase activity in the skeletal muscle of transgenic animals overexpressing human placental growth hormone. Herein, using transgenic mice bearing deletions in p85 alpha, p85 beta, or insulin-like growth factor-1, we provide novel evidence suggesting that overexpression of p85 alpha is a primary mechanism for skeletal muscle insulin resistance in response to GH. We found that the excess in total p85 was entirely accounted for by an increase in the free p85 alpha-specific isoform. In mice with a liver-specific deletion in insulin-like growth factor-1, excess GH caused insulin resistance and an increase in skeletal muscle p85 alpha, which was completely reversible using a GH-releasing hormone antagonist. To understand the role of p85 alpha in GH-induced insulin resistance, we used mice bearing deletions of the genes coding for p85 alpha or p85 beta, respectively (p85 alpha(+/-) and p85 beta(-/-)). Wild type and p85 beta(-/-) mice developed in vivo insulin resistance and demonstrated overexpression of p85 alpha and reduced insulin-stimulated PI 3-kinase activity in skeletal muscle in response to GH. In contrast, p85 alpha(+/-) mice retained global insulin sensitivity and PI 3-kinase activity associated with reduced p85 alpha expression. These findings demonstrated the importance of increased p85 alpha in mediating skeletal muscle insulin resistance in response to GH and suggested a potential role for reducing p85 alpha as a therapeutic strategy for enhancing insulin sensitivity in skeletal muscle. C1 Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Obstet & Gynecol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Pediat, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Biochem & Mol Genet, Denver, CO 80262 USA. Denver Vet Affairs Med Ctr, Vet Affairs Res Serv, Denver, CO 80220 USA. NIDDK, Diabet Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Childrens Hosp, Joslin Diabet Ctr,Res Div, Boston, MA 02215 USA. Harvard Univ, Sch Med, Dept Syst Biol, Boston, MA 02115 USA. RP Friedman, JE (reprint author), Univ Colorado, Hlth Sci Ctr, Mail Stop 8106,POB 6511, Aurora, CO 80045 USA. EM Jed.Friedman@uchsc.edu RI Cantley, Lewis/D-1800-2014 OI Cantley, Lewis/0000-0002-1298-7653 FU NIDDK NIH HHS [DK062155]; NIGMS NIH HHS [GM41890, R01 GM041890] NR 26 TC 71 Z9 72 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 NOV 11 PY 2005 VL 280 IS 45 BP 37489 EP 37494 DI 10.1074/jbc.M506967200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 980UU UT WOS:000233044500025 PM 16166093 ER PT J AU Takino, T Nakada, M Miyamori, H Watanabe, Y Sato, T Gantulga, D Yoshioka, K Yamada, KM Sato, H AF Takino, T Nakada, M Miyamori, H Watanabe, Y Sato, T Gantulga, D Yoshioka, K Yamada, KM Sato, H TI JSAP1/JIP3 cooperates with focal adhesion kinase to regulate c-Jun N-terminal kinase and cell migration SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; JNK SIGNALING PATHWAY; SCAFFOLD PROTEIN; TYROSINE PHOSPHORYLATION; MATRIX ADHESION; INVASION; FAK; SRC; MICROTUBULES; P130(CAS) AB c-Jun N-terminal kinase (JNK)/stress-activated protein kinase-associated protein 1 (JSAP1) ( also termed JNK-interacting protein 3; JIP3) is a member of a family of scaffold factors for the mitogen-activated protein kinase ( MAPK) cascades, and it also forms a complex with focal adhesion kinase (FAK). Here we demonstrate that JSAP1 serves as a cooperative scaffold for activation of JNK and regulation of cell migration in response to fibronectin (FN) stimulation. JSAP1 mediated an association between FAK and JNK, which was induced by either co-expression of Src or attachment of cells to FN. Complex formation of FAK with JSAP1 and p130 Crk-associated substrate (p130(Cas)) resulted in augmentation of FAK activity and phosphorylation of both JSAP1 and p130(Cas), which required p130(Cas) hyperphosphorylation and was abolished by inhibition of Src. JNK activation by FN was enhanced by JSAP1, which was suppressed by disrupting the FAK/p130(Cas) pathway by expression of a dominant-negative form of p130(Cas) or by inhibiting Src. We also documented the co-localization of JSAP1 with JNK and phosphorylated FAK at the leading edge and stimulation of cell migration by JSAP1 expression, which depended on its JNK binding domain and was suppressed by inhibition of JNK. The level of JSAP1 mRNA correlated with advanced malignancy in brain tumors, unlike other JIPs. We propose that the JSAP1 center dot FAK complex functions cooperatively as a scaffold for the JNK signaling pathway and regulator of cell migration on FN, and we suggest that JSAP1 is also associated with malignancy in brain tumors. C1 Kanazawa Univ, Canc Res Inst, Dept Mol Oncol & Virol, Kanazawa, Ishikawa 9200934, Japan. Kanazawa Univ, Canc Res Inst, Dept Cell Cycle Regulat, Kanazawa, Ishikawa 9200934, Japan. Kanazawa Univ, Grad Sch Med Sci, Dept Neurosurg, Div Neurosci, Kanazawa, Ishikawa 9200934, Japan. NIDCR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Takino, T (reprint author), Kanazawa Univ, Canc Res Inst, Dept Mol Oncol & Virol, Kanazawa, Ishikawa 9200934, Japan. EM ttakino@kenroku.kanazawa-u.ac.jp RI TAKINO, Takahisa/D-8460-2015; SATO, Hiroshi/D-8454-2015; OI Yamada, Kenneth/0000-0003-1512-6805 NR 42 TC 51 Z9 51 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 NOV 11 PY 2005 VL 280 IS 45 BP 37772 EP 37781 DI 10.1074/jbc.M505241200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 980UU UT WOS:000233044500056 PM 16141199 ER PT J AU Wei, QZ AF Wei, QZ TI Pitx2a binds to human papillomavirus type 18 E6 protein and inhibits E6-mediated p53 degradation in HeLa cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CERVICAL-CANCER CELLS; MAMMALIAN-CELLS; RIEGER-SYNDROME; MOUSE PITX2; ONCOPROTEIN; GENE; APOPTOSIS; TARGET; LIGASE; GROWTH AB Binding of high risk human papillomavirus (HPV) E6 protein to E6-associated protein (E6AP), a cellular ubiquitin-protein ligase, enables E6AP to ubiquitinate p53, leading to p53 degradation in cervical cancer cells such as HeLa cells. Here we report that Pitx2a, a bicoid-type homeodomain transcription factor, can bind to HPV E6 protein and inhibit E6/E6AP-mediated p53 degradation. Deletion of the Pitx2a homeodomain abrogates its ability to bind to HPV E6 protein and to induce p53 accumulation in HeLa cells, suggesting that the homeodomain of Pitx2a is essential for inhibition of E6/E6AP-mediated p53 degradation. Recombinant Pitx2a can also block E6/E6AP-mediated p53 degradation in vitro, indicating that this function of Pitx2a is independent of its transcription activity. Pitx2a does not regulate Hdm2-mediated p53 degradation, because Pitx2a does not affect p53 protein levels in HPV-negative cells, such as HCT116, U2OS, and C33A cells. In addition, Pitx2a-induced p53 is transcriptionally active and maintains its specific DNA binding activity in HeLa cells. Taken together, these findings suggest that, by binding to E6, Pitx2a interferes with E6/E6AP-mediated p53 degradation, leading to the accumulation of functional p53 protein in HeLa cells. C1 Kansas State Univ, Dept Biochem, Manhattan, KS 66506 USA. NHLBI, Mol Cardiol Lab, NIH, Bethesda, MD 20892 USA. RP Wei, QZ (reprint author), Kansas State Univ, Dept Biochem, 103 Willard Hall, Manhattan, KS 66506 USA. EM weiq@ksu.edu FU NHLBI NIH HHS [K22 HL071542-01, K22 HL071542] NR 50 TC 22 Z9 23 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 NOV 11 PY 2005 VL 280 IS 45 BP 37790 EP 37797 DI 10.1074/jbc.M502974200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 980UU UT WOS:000233044500058 PM 16129685 ER PT J AU Labunskyy, VM Ferguson, AD Fomenko, DE Chelliah, Y Hatfield, DL Gladyshev, VN AF Labunskyy, VM Ferguson, AD Fomenko, DE Chelliah, Y Hatfield, DL Gladyshev, VN TI A novel cysteine-rich domain of Sep15 mediates the interaction with UDP-glucose : glycoprotein glucosyltransferase SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALRETICULIN P-DOMAIN; ENDOPLASMIC-RETICULUM; 15-KDA SELENOPROTEIN; QUALITY-CONTROL; RIBONUCLEASE B; PROTEIN; CALNEXIN; SELENIUM; EXPRESSION; CHAPERONE AB Selenium is an essential trace element with potent cancer prevention activity in mammals. The 15-kDa selenoprotein (Sep15) has been implicated in the chemopreventive effect of dietary selenium. Although the precise function of Sep15 remains elusive, Sep15 co-purifies with UDP-glucose: glycoprotein glucosyltransferase (GT), an essential regulator of quality control mechanisms within the endoplasmic reticulum. Recent studies identified two GT and two Sep15 homologues in mammals. We characterize interactions between these protein families in this report. Sep15 and GT form a tight 1: 1 complex, and these interactions are conserved between mammals and fruit flies. In mammalian cells, Sep15 co-immunoprecipitates with both GT isozymes. In contrast, a Sep15 homologue, designated selenoprotein M(SelM), does not form a complex with GT. Sequence analysis of members of the Sep15 family identified a novel N-terminal cysteine-rich domain in Sep15 that is absent in SelM. This domain contains six conserved cysteine residues that form two CxxC motifs that do not coordinate metal ions. If this domain is deleted or the cysteines are mutated, Sep15 no longer forms a complex with GT. Conversely, if the cysteine-rich domain of Sep15 is fused to the N-terminus of SelM, the resulting chimera is capable of binding GT. These data indicate that the cysteine-rich domain of Sep15 exclusively mediates protein-protein interactions with GT. C1 Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Howard Hughes Med Inst, Dallas, TX 75390 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev1@unl.edu RI Gladyshev, Vadim/A-9894-2013 FU NCI NIH HHS [CA080946] NR 40 TC 38 Z9 39 U1 1 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 NOV 11 PY 2005 VL 280 IS 45 BP 37839 EP 37845 DI 10.1074/jbc.M508685200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 980UU UT WOS:000233044500064 PM 16129668 ER PT J AU To, KKW Huang, LE AF To, KKW Huang, LE TI Suppression of hypoxia-inducible factor 1 alpha (HIF-1 alpha) transcriptional activity by the HIF prolyl hydroxylase EGLN1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID FACTOR-I; FACTOR 1-ALPHA; ALPHA-SUBUNIT; DNA-BINDING; PROTEIN; OXYGEN; PATHWAY; VHL; DEGRADATION; ACTIVATION AB The cellular response to hypoxia is, at least in part, mediated by the transcriptional regulation of hypoxia-responsive genes involved in balancing the intracellular ATP production and consumption. Recent evidence suggests that the transcription factor, HIF-1 alpha, functions as a master regulator of oxygen homeostasis by controlling a broad range of cellular events in hypoxia. In normoxia, HIF-1 alpha is targeted for destruction via prolyl hydroxylation, an oxygen-dependent modification that signals for recognition by the ubiquitin ligase complex containing the von Hippel-Lindau tumor suppressor. Three HIF prolyl hydroxylases (EGLN1, EGLN2, and EGLN3) have been identified in mammals, among which EGLN1 and EGLN3 are hypoxia-inducible at their mRNA levels in an HIF-1 alpha-dependent manner. In this study, we demonstrated that apart from promoting HIF-1 alpha proteolysis in normoxia, EGLN1 specifically represses HIF-1 alpha transcriptional activity in hypoxia. Ectopic expression of EGLN1 inhibited HIF-1 alpha transcriptional activity without altering its protein levels in a von Hippel-Lindau-deficient cell line, indicating a discrete activity of EGLN1 in transcriptional repression. Conversely, silencing of EGLN1 expression augmented HIF-1 alpha transcriptional activity and its target gene expression in hypoxia. Thus, we proposed that the accumulated EGLN1 in hypoxia acts as a negative-feedback mechanism to modulate HIF-1 alpha target gene expression. Our finding also provided new insight into the pharmacological manipulation of the HIF prolyl hydroxylase for ischemic diseases. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Huang, LE (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Rm 3044B,37 Convent Dr, Bethesda, MD 20892 USA. EM huange@mail.nih.gov RI To, Kenneth /M-4500-2013 OI To, Kenneth /0000-0003-2755-0283 FU Intramural NIH HHS; NCI NIH HHS [Z01 BC010424-06] NR 51 TC 51 Z9 54 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 11 PY 2005 VL 280 IS 45 BP 38102 EP 38107 DI 10.1074/jbc.M504342200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 980UU UT WOS:000233044500094 PM 16157596 ER PT J AU Louis, JM Bewley, CA Gustchina, E Aniana, A Clore, GM AF Louis, JM Bewley, CA Gustchina, E Aniana, A Clore, GM TI Characterization and HIV-1 fusion inhibitory properties of monoclonal fabs obtained from a human non-immune phage library epitopes of the ectodomain selected against diverse of HIV-1 gp41 SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV-1 fusion; virus; HIV envelope; gp41; fusion inhibitors ID IMMUNODEFICIENCY-VIRUS TYPE-1; PROXIMAL EXTERNAL REGION; TRIMERIC COILED-COIL; MEDIATED CELL-FUSION; ENVELOPE GLYCOPROTEIN; POTENT INHIBITORS; ATOMIC-STRUCTURE; HUMAN-ANTIBODIES; ENTRY; NEUTRALIZATION AB Using a human non-immune phage library comprising more than 10(9) functional human antibody specificities in Fab format, we have been able to select a set of eight monoclonal Fabs targeted against diverse epitopes of the ectodomain of gp41 from HIV-1. The antigens used for panning the antibodies comprised two soluble, disulfide-linked, trimeric polypeptides derived from gp41, N-CCG-gp41 and N35(CCG)-N13. The former comprises an exposed trimeric coiled-coil of the N-helices of gp41 fused in helical phase to the minimal thermostable ectodomain of gp41, while the latter comprises only the trimeric coiled-coil of N-helices. The selected Fabs were probed by Western blot analysis against four antigens: N-CCG-gp41, N35(CCG)-N13, N34(CCG) (a smaller version of N35(CCG)-N13), and the minimal thermostable ectodomain core of gp41 in its six-helix bundle conformation (6-HB). Three classes of Fabs were found: class A (two Fabs) interact predominantly with the 6-HB; class B (four Fabs) interact with both the 6-HB and the internal trimeric coiled-coil of N-helices; and class C (two Fabs) interact specifically with the internal trimeric coiled-coil of N-helices. The IC50 values for the Fabs, expressed as bivalent mini-antibodies, ranged from 6 mu g/ml to 60 mu g/ml in a quantitative vaccinia virus-based reporter gene assay for HIV-1 envelope-mediated cell fusion using the envelope from the HIV-1 T tropic strain LAV. The two most potent fusion inhibitors belonged to class B. This panel of Fabs provides a set of useful probes for studying HIV-1 envelope-mediated cell fusion and may serve as a basis for developing Fab-based anti-HIV-1 therapeutics. Published by Elsevier Ltd. C1 NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Bewley, CA (reprint author), NIDDKD, Phys Chem Lab, NIH, Bldg 5,Room B1-301, Bethesda, MD 20892 USA. EM caroleb@mail.nih.gov; mariusc@intra.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 FU Intramural NIH HHS NR 34 TC 24 Z9 26 U1 1 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 NOV 11 PY 2005 VL 353 IS 5 BP 945 EP 951 DI 10.1016/j.jmb.2005.09.044 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 983BS UT WOS:000233206700003 PM 16216270 ER PT J AU Suh, JY Tang, C Cai, ML Clore, GM AF Suh, JY Tang, C Cai, ML Clore, GM TI Visualization of the phosphorylated active site loop of the cytoplasmic B domain of the mannitol transporter IIMannitol of the Escherichia coli phosphotransferase system by NMR spectroscopy and residual dipolar couplings SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE phosphotransferase system; IIBMannitol; phosphorylated state; solution structure; NMR ID TRANSPORTER IIMANNITOL; HYDROGEN-BONDS; ENZYME IIB; PROTEIN; COMPLEX; MACROMOLECULES; PHOSPHATASE; REFINEMENT; DYNAMICS; DATABASE AB The solution structure of a stably phosphorylated form of the cytoplasmic B domain of the mannitol-specific transporter (IIBMtl) of the Escherichia coli phosphotransferase system, containing a mutation of the active site Cys384 to Ser, has been solved by NMR. The strategy employed relies principally on backbone residual dipolar couplings recorded in three different alignment media, supplemented by nuclear Overhauser enhancement data and torsion angle restraints related specifically to the active site loop (residues 383-393). As judged from the dipolar coupling data, the remainder of the structure is unchanged upon phosphorylation within the errors of the coordinates of the previously determined solution structure of unphosphorylated wild-type IIBMtl. Thus, only the active site loop v as refined. Phosphorylation results in a backbone atomic rms shift of similar to 0.7 angstrom in the active site loop. The resulting conformation is less than 0.5 angstrom away from the equivalent P-loop in both the low and high molecular mass eukaryotic tyrosine phosphatases. (3)J(NP) coupling constant measurements using quantitative J-correlation spectroscopy provide a direct demonstration of a hydrogen bond between the phosphoryl group and the backbone amide of Ser391 at position i + 7 from phospho-Ser384, with an approximately linear P-O-H-N bond angle. The structure also reveals additional hydrogen bonding interactions involving the backbone amides of residues at positions i+4 and i+5, and the hydroxyl groups of two serine residues at positions i+6 and i+7 that stabilize the phosphoryl group. Published by Elsevier Ltd. C1 NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Clore, GM (reprint author), NIDDK, Chem Phys Lab, NIH, Bldg 5, Bethesda, MD 20892 USA. EM mariusc@intra.niddk.nih.gov RI Clore, G. Marius/A-3511-2008 OI Clore, G. Marius/0000-0003-3809-1027 NR 29 TC 10 Z9 10 U1 0 U2 1 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 NOV 11 PY 2005 VL 353 IS 5 BP 1129 EP 1136 DI 10.1016/j.jmb.2005.09.033 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 983BS UT WOS:000233206700019 PM 16219324 ER PT J AU Kocisko, DA Engel, AL Harbuck, K Arnold, KM Olsen, EA Raymond, LD Vilette, D Caughey, B AF Kocisko, DA Engel, AL Harbuck, K Arnold, KM Olsen, EA Raymond, LD Vilette, D Caughey, B TI Comparison of protease-resistant prion protein inhibitors in cell cultures infected with two strains of mouse and sheep scrapie SO NEUROSCIENCE LETTERS LA English DT Article DE sheep scrapie; mouse scrapie; prion; inhibitors; therapeutics ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; POTENT INHIBITION; INCUBATION PERIOD; PRP ACCUMULATION; HAMSTERS; THERAPY; MICE; INFECTIVITY; PROLONG; DELAYS AB The transmissible spongiform encephalopathies (TSEs) are fatal neurodegenerative diseases. A primary therapeutic target for TSE intervention has been a protease-resistant form of prion protein known as PrPSc or PrP-res. In vitro testing of mouse scrapie-infected cell cultures has identified many PrP-res inhibitors that also have activity in vivo. Here we identify 32 new inhibitors of two strains of mouse scrapie PrP-res. Furthermore, to investigate the species-specificity of these and other PrP-res inhibitors, we have developed a high-throughput cell culture assay based on Rov9 cells chronically-infected with sheep scrapie. Of 32 inhibitors of murine PrP-res that were also tested in the Rov9 cells, only six showed inhibitory activity against sheep PrP-res. The three most potent inhibitors of both murine and ovine PrP-res formation (with 50% inhibition at <= 5 mu M) were tannic acid, pentosan polysulfate and Fe(III) deuteroporphyrin 2,4-bisethyleneglycol. The latter two have anti-mouse scrapie activity in vivo. These results identify new inhibitors of murine and ovine PrP-res formation and reinforce the idea that compounds effective against PrP-res from one species or strain cannot be assumed to be active against others. C1 NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. INRA, Unite Virol & Immunol Mol, F-78350 Jouy En Josas, France. RP Caughey, B (reprint author), NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM BCaughey@niaid.nih.gov NR 28 TC 32 Z9 36 U1 0 U2 1 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 NOV 11 PY 2005 VL 388 IS 2 BP 106 EP 111 DI 10.1016/j.neulet.2005.06.053 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 963WX UT WOS:000231838100010 PM 16039063 ER PT J AU Huang, CC Tang, M Zhang, MY Majeed, S Montabana, E Stanfield, RL Dimitrov, DS Korber, B Sodroski, J Wilson, IA Wyatt, R Kwong, PD AF Huang, CC Tang, M Zhang, MY Majeed, S Montabana, E Stanfield, RL Dimitrov, DS Korber, B Sodroski, J Wilson, IA Wyatt, R Kwong, PD TI Structure of a V3-containing HIV-1 gp120 core SO SCIENCE LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ENVELOPE GLYCOPROTEIN; SOLUBLE CD4; V3 LOOP; CRYSTAL-STRUCTURE; TYPE-1; RECEPTOR; ANTIBODY; BINDING; NEUTRALIZATION AB The third variable region (V3) of the HIV-1 gp120 envelope glycoprotein is immunodominant and contains features essential for coreceptor binding. We determined the structure of V3 in the context of an HIV-1 gp120 core complexed to the CD4 receptor and to the X5 antibody at 3.5 angstrom resolution. Binding of gp120 to cell-surface CD4 would position V3 so that its coreceptor-binding tip protrudes 30 angstroms from the core toward the target cell membrane. The extended nature and antibody accessibility of V3 explain its immunodominance. Together, the results provide a structural rationale for the role of V3 in HIV entry and neutralization. C1 NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. SAIC Frederick, Basic Res Program, Frederick, MD USA. NCI, Prot Interact Grp, Ctr Canc Res, Nanobiol Program, Frederick, MD 21702 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. Los Alamos Natl Lab, Los Alamos, NM 87545 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Wyatt, R (reprint author), NIAID, Vaccine Res Ctr, Bethesda, MD 20892 USA. EM richw@mail.nih.gov; pdkwong@nih.gov FU Intramural NIH HHS [Z99 AI999999]; NIAID NIH HHS [AI39429, AI24755, AI31783, AI40895]; NIGMS NIH HHS [GM46192] NR 35 TC 516 Z9 533 U1 1 U2 38 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 NOV 11 PY 2005 VL 310 IS 5750 BP 1025 EP 1028 DI 10.1126/science.1118398 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 984YN UT WOS:000233343400046 PM 16284180 ER PT J AU Benyamini, H Gunasekaran, K Wolfson, H Nussinov, R AF Benyamini, H Gunasekaran, K Wolfson, H Nussinov, R TI Fibril modelling by sequence and structure conservation analysis combined with protein docking techniques: beta 2-microglobulin amyloidosis SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article; Proceedings Paper CT Workshop on Dialysis-Related Amyloidosis - From Molecular Mechanism to Therapies CY DEC 09, 2004 CL Univ Pavia, Pavia, ITALY SP Japanese & Italian Res Grp HO Univ Pavia DE fibril modelling; protein; beta(2)-microglobuljn ID BINDING-SITE; NEUTRAL PH; IN-VITRO; IMMUNOGLOBULIN FOLD; MOLECULAR-MODEL; DISULFIDE BOND; BETA(2)-MICROGLOBULIN; AGGREGATION; ALIGNMENT; DOMAIN AB Obtaining atomic resolution structural models of amyloid fibrils is currently impossible, yet crucial for our understanding of the amyloid mechanism. Different pathways in the transformation of a native globular domain to an amyloid fibril invariably involve domain destabilization. Hence, locating the unstable segments of a domain is important for understanding its amyloidogenic transformation and possibly control it. Since relative conservation is suggested to relate to local stability [H. Benyamini, K. Gunasekaran, H. Wolfson, R. Nussinov, Conservation and amyloid formation: a study of the gelsolin-like family, Proteins 51 (2003) 266-282. [24]], we performed an extensive, sequence and structure conservation analysis of the beta(2)-microglobulin (beta(2)-m) domain. Our dataset include 51 high resolution structures belonging to the "C1 set domain" family and 132 clustered PSI-BLAST search results. Segments of the beta(2)-m domain corresponding to strands A (residues 12-18), D (45-55) and G (91-95) were found to be less conserved and stable, while the central strands B (residues 22-28), C (36-41), E (62-70) and F (78-83) were found conserved and stable. Our findings are supported by accumulating observations from various experimental methods, including urea denaturation, limited proteolysis, H/D exchange and structure determination by both NMR and X-ray crystallography. We used our conservation findings together with experimental literature information to suggest a structural model for the polymerized unit of beta(2)-m. Pairwise protein docking and subsequent monomer stacking in the same manner suggest a fibril model consistent with the cross-beta structure. (c) 2005 Elsevier B.V. All rights reserved. C1 NCI, SAIC Frederick Inc, Basic Res Program, Lab Expt & Computat Biol, Frederick, MD 21702 USA. Tel Aviv Univ, George S Wise Fac Life Sci, Bioinformat Unit, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Raymond & Beverly Sackler Fac Exact Sci, Sch Comp Sci, IL-69978 Tel Aviv, Israel. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, SAIC Frederick Inc, Basic Res Program, Lab Expt & Computat Biol, Bldg 469,Rm 151, Frederick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Wolfson, Haim/A-1837-2011 FU NCI NIH HHS [N01-CO-12400] NR 55 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD NOV 10 PY 2005 VL 1753 IS 1 BP 121 EP 130 DI 10.1016/j.bbapap.2005.07.012 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 986LE UT WOS:000233450300014 PM 16107326 ER PT J AU Kishikawa, M Koyama, K Iseki, M Kobuke, T Yonehara, S Soda, M Ron, E Tokunaga, M Preston, DL Mabuchi, K Tokuoka, S AF Kishikawa, M Koyama, K Iseki, M Kobuke, T Yonehara, S Soda, M Ron, E Tokunaga, M Preston, DL Mabuchi, K Tokuoka, S TI Histologic characteristics of skin cancer in Hiroshima and Nagasaki: Background incidence and radiation effects SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE basal cell carcinoma of the skin; squamous cell carcinoma of the skin; ionizing radiation; sun exposure ID ATOMIC-BOMB SURVIVORS; ACTINIC KERATOSIS; UNITED-STATES; SUN EXPOSURE; BASAL-CELL; JAPAN; MELANOMA; HAWAII; KAUAI AB Skin cancers, though rare in Japan, have reportedly been on the rise, but little else is known about epidemiologic features of different histologic types of skin cancer. The Life Span Study cohort, which consists of 93,700 atomic-bomb survivors, many of whom were exposed to negligibly low radiation doses, and 26,600 people not exposed to radiation, enables a population-based study of spontaneous as well as radiation-related cancer risk. Skin tumor incident cases diagnosed between 1958 and 1987 were ascertained by linkage to the Hiroshima and Nagasaki tumor registries augmented by searches of other data sources. Study pathologists reviewed tumor specimens and pathology reports and classified tumors using the World Health Organization classification scheme. They identified 274 primary incident skin cancers, of which 106 were basal cell carcinoma (BCC), 81 were squamous cell carcinoma (SCC), and 14 were malignant melanomas. Background incidence rates and radiation effects were assessed by Poisson regression models allowing for the effects of demographic and other covariates. BCC and SCC background incidence rates were both about 3 per 100,000 per year. BCCs were mainly on the head/neck (81%), whereas SCCs occurred most frequently on the arms/legs (45%) and head/neck (29%), consistent with the presumed role played by solar UV exposure in skin cancer. The BCC rates increased significantly between 1958 and 1987, whereas the SCC rates remained unchanged. The excess absolute risk of BCC per unit skin surface area related to atomic-bomb radiation exposure did not differ between UV-exposed and shielded parts of the body, suggesting the additivity of the radiation-related and background BCC risks. (c) 2005 Wiley-Liss, Inc. C1 Radiat Effects Res Fdn, Minami Ku, Hiroshima 7320815, Japan. Nagasaki Inst Diagnost Pathol, Isahaya, Japan. Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima, Japan. Radiat Effects Res Fdn, Dept Epidemiol, Nagasaki, Japan. Sasebo Kyosai Hosp, Dept Pathol & Lab Med, Nagasaki, Japan. Koseiren Onomichi Hosp, Div Clin Res Labs, Onomichi, Japan. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. Radiat Effects Res Fdn, Dept Stat, Hiroshima, Japan. RP Tokuoka, S (reprint author), Radiat Effects Res Fdn, Minami Ku, 5-2 Hijiyama Pk, Hiroshima 7320815, Japan. EM tokuoka@rerf.or.jp FU NCI NIH HHS [N01-CP-31012, N01-CP-71015] NR 33 TC 20 Z9 21 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 NOV 10 PY 2005 VL 117 IS 3 BP 363 EP 369 DI 10.1002/ijc.21156 PG 7 WC Oncology SC Oncology GA 971UW UT WOS:000232411300005 PM 15900592 ER PT J AU Kelsey, KT Hirao, T Hirao, S Devi-Ashok, T Nelson, HH Andrew, A Colt, J Baris, D Morris, JS Schned, A Karagas, M AF Kelsey, KT Hirao, T Hirao, S Devi-Ashok, T Nelson, HH Andrew, A Colt, J Baris, D Morris, JS Schned, A Karagas, M TI TP53 alterations and patterns of carcinogen exposure in a US population-based study of bladder cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE bladder cancer; occupation; hair dye; arsenic ID TRANSITIONAL-CELL CARCINOMA; PERMANENT HAIR-DYES; P53 GENE-MUTATIONS; URINARY-BLADDER; IMMUNOHISTOCHEMICAL DETECTION; PROTEIN OVEREXPRESSION; CIGARETTE-SMOKING; ARSENIC EXPOSURE; TOBACCO SMOKING; NUCLEAR-PROTEIN AB The molecular pathology of bladder cancer has been the subject of considerable interest, and current efforts are targeted toward elucidating the interrelationships between individual somatic gene loss and both etiologic and prognostic factors. Mutation of the TP53 gene has been associated with more invasive bladder cancer, and evidence suggests that TP53 mutation, independent of stage, may be predictive of outcome in this disease. However, there is no consensus in the literature that bladder carcinogen exposure is associated with inactivation of the TP53 gene. Work to date has been primarily hospital based and, as such, subject to possible bias associated with selection of more advanced cases for study. We examined exposure relationships with both TP53 gene mutation and TP53 protein alterations in a population-based study of 330 bladder cancer cases in New Hampshire. Tobacco smoking was not associated with TP53 alterations. We found a higher prevalence of TP53 inactivation (i.e., mutation and nuclear accumulation) among hair dye users (odd ratio [OR] = 4.1; 95% confidence interval [CI] 1.2-14.7), and the majority of these mutations were transversions. Men who had "at risk" occupations were more likely to have mutated TP53 tumors (OR = 2.9; 95% CI 1.1-7.6). There also was a relative absence of TP53 mutation (OR = 0.4; 95% CI 0.0-2.9) and TP53 protein alterations (OR = 0.6; 95% CI 0.3-1.4) in bladder cancers from individuals with higher arsenic exposure. Our data suggest that there is exposure-specific heterogeneity in inactivation of the TP53 pathway in bladder cancers and that integration of the spectrum of pathway alterations in population-based approaches (capturing the full range of exposures to bladder carcinogens) may provide important insights into bladder tumorigenesis. (c) 2005 Wiley-Liss, Inc. C1 Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA. Dartmouth Coll Sch Med, Dept Pathol, Hanover, NH USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. Dartmouth Coll Sch Med, Dept Family & Community Med, Hanover, NH USA. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Rockville, MD USA. Univ Missouri, Res Reactor Ctr, Columbia, MO USA. RP Kelsey, KT (reprint author), Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, 665 Huntington Ave, Boston, MA 02115 USA. EM kelsey@hsph.harvard.edu RI Kelsey, Karl/I-1252-2014 FU NIEHS NIH HHS [ES00002, P42 ES007373, P42 ES005947] NR 55 TC 26 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD NOV 10 PY 2005 VL 117 IS 3 BP 370 EP 375 DI 10.1002/ijc.21195 PG 6 WC Oncology SC Oncology GA 971UW UT WOS:000232411300006 PM 15906354 ER PT J AU Monzavi-Karbassi, B Whitehead, TL Jousheghany, F Artaud, C Hennings, L Shaaf, S Slaughter, A Korourian, S Kelly, T Blaszczyk-Thurin, M Kieber-Emmons, T AF Monzavi-Karbassi, B Whitehead, TL Jousheghany, F Artaud, C Hennings, L Shaaf, S Slaughter, A Korourian, S Kelly, T Blaszczyk-Thurin, M Kieber-Emmons, T TI Deficiency in surface expression of E-selectin ligand promotes lung colonization in a mouse model of breast cancer SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE sialyl Lewis(x) antigen; metastasis; 4T1 cells; breast cancer ID SIALYL-LEWIS-X; CARBOHYDRATE-PROTEIN INTERACTIONS; ASN-LINKED OLIGOSACCHARIDES; HEPATOCARCINOMA CELL-LINE; COLON-CARCINOMA CELLS; P-SELECTIN; GASTRIC-CANCER; TUMOR-CELLS; E-CADHERIN; IN-VIVO AB Expression of sialyl Lewis(x) (sLe(x)) and sLe(a) on tumor cells is thought to facilitate metastasis by promoting cell adhesion to selectins on vascular endothelial cells. Experiments supporting this concept usually bypass the early steps of the metastatic process by employing tumor cells that are injected directly into the blood. We investigated the relative role of sLe(x) oligosaccharide in the dissemination of breast carcinoma, employing a spontaneous murine metastasis model. An sLex deficient subpopulation of the 4T1 mammary carcinoma cell line was produced by negative selection using the sLe(x)-reactive KM93 MAb. This subpopulation was negative for E-selectin binding but retained P-selectin binding. Both sLe(x)-negative and -positive cells grew at the same rate; however, sLe(x)-negative cells spread more efficiently on plates and had greater motility in wound-scratch assays. Mice inoculated in the mammary fat pad with sLex-negative and -positive variants produced lung metastases. However, the number of lung metastases was significantly increased in the group inoculated with the sLe(x)-negative variant (p = 0.0031), indicating that negative selection for the sLe(x) epitope resulted in enrichment for a subpopulation of cells with a high metastatic phenotype. Cell variants demonstrated significant differences in cellular morphology and pattern of tumor growth in primary and secondary tumor sites. These results strongly suggest that loss of sLex may facilitate the metastatic process by contributing to escape from the primary tumor mass. (c) 2005 Wiley-Liss, Inc. C1 Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. NCI, Canc Diagnosis Program, Div Canc Treatment & Diagnosis, NIH, Rockville, MD USA. RP Kieber-Emmons, T (reprint author), Univ Arkansas Med Sci, Arkansas Canc Res Ctr, 4301 W Markham St,Slot 824, Little Rock, AR 72205 USA. EM tke@uams.edu OI Kelly, Thomas/0000-0001-5781-0619 FU NCI NIH HHS [CA089480] NR 69 TC 14 Z9 14 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 NOV 10 PY 2005 VL 117 IS 3 BP 398 EP 408 DI 10.1002/ijc.21192 PG 11 WC Oncology SC Oncology GA 971UW UT WOS:000232411300010 PM 15906360 ER PT J AU Purdue, MP From, L Kahn, HJ Armstrong, BK Kricker, A Gallagher, RP McLaughlin, JR Klar, NS Marrettt, LD AF Purdue, MP From, L Kahn, HJ Armstrong, BK Kricker, A Gallagher, RP McLaughlin, JR Klar, NS Marrettt, LD CA Genes Env Melanoma Working Grp TI Etiologic factors associated with p53 immunostaining in cutaneous malignant melanoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE melanoma; p53; risk factor; etiology; epidemiology; case-only study ID HDM2 PROTEIN OVEREXPRESSION; SUN EXPOSURE; MELANOCYTIC NEVI; RISK-FACTORS; SITE DISTRIBUTION; BRAF MUTATIONS; PROGNOSTIC-SIGNIFICANCE; WESTERN-AUSTRALIA; SKIN-CANCER; EXPRESSION AB Findings from a case-control study of cutaneous malignant melanoma (CMM) in Queensland, Australia, suggest that melanomas exhibiting p53 immunostaining possess different risk factors from those of other melanomas. To further explore this hypothesis, a case-only analysis of risk factors for p53 immunostaining with anti-p53 MAb DO-7 was undertaken in 523 people diagnosed with CMM in Canada and Australia. Phenotypic factors and past sun exposure were measured using a self-administered questionnaire and telephone interview. The presence of strong p53 staining (> 10% of cell nuclei positively stained vs. < 1% staining) was positively associated with some indicators of high cumulative sun exposure: lentigo maligna melanoma subtype (OR = 3.2 vs. superficial spreading subtype), melanoma location on the head and neck (OR = 2.8 vs. back), histopathologic evidence of solar elastosis (OR = 2.1) and previous diagnosis of nonmelanoma skin cancer (OR = 2.4). Strong staining was negatively associated with high nevus density on the back (OR = 0.2 for > 25 nevi vs. 0-3 nevi) and histologic evidence of a coexisting nevus (OR = 0.3). Other factors associated with strong p53 immunostaining include greater Breslow thickness (OR = 7.4 for > 4.00 vs. < 0.76 mm), male sex (OR = 2.2) and dense freckling (OR = 6.6 vs. few freckles). Of these, thickness, male sex, dense freckling, low nevus density on the back, histologic subtype and history of nonmelanoma skin cancer appeared to be independently associated with strong p53 staining. Our findings are consistent with the Queensland study in suggesting that variables indicating high accumulated sun exposure are positively associated with p53 staining and that an increased number of nevi is positively associated with its absence; they may reflect etiologic and pathogenetic heterogeneity in melanoma. (c) 2005 Wiley-Liss, Inc. C1 Canc Care Ontario, Div Prevent Oncol, Toronto, ON, Canada. Sunnybrook & Womens Coll Hlth Sci Ctr, RK Schachter Dermatol Ctr, Toronto, ON, Canada. Sunnybrook & Womens Coll Hlth Sci Ctr, Dept Pathol, Toronto, ON, Canada. Univ Sydney, Sch Publ Hlth, Sydney, NSW 2006, Australia. British Columbia Canc Agcy, Canc Control Res Program, Vancouver, BC V5Z 4E6, Canada. Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada. RP Purdue, MP (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,EPS 8111, Rockville, MD 20852 USA. EM purduem@mail.nih.gov RI McLaughlin, John/E-4577-2013; Armstrong, Bruce/K-9464-2015; Purdue, Mark/C-9228-2016 OI Armstrong, Bruce/0000-0001-8940-7525; Purdue, Mark/0000-0003-1177-3108 FU NCI NIH HHS [CA103394, U01 CA083180] NR 41 TC 15 Z9 15 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 NOV 10 PY 2005 VL 117 IS 3 BP 486 EP 493 DI 10.1002/ijc.21196 PG 8 WC Oncology SC Oncology GA 971UW UT WOS:000232411300020 PM 15900597 ER PT J AU Patlolla, AK Tchounwou, PB AF Patlolla, AK Tchounwou, PB TI Cytogenetic evaluation of arsenic trioxide toxicity in Sprague-Dawley rats SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE arsenic trioxide; chromosomal aberrations; micronucleus formation; mitotic index; genotoxic; Sprague-Dawley rats ID INDUCED CELL-TRANSFORMATION; HAMSTER EMBRYO CELLS; CHROMOSOMAL-ABERRATIONS; SODIUM ARSENITE; DRINKING-WATER; WEST-BENGAL; MICRONUCLEI; INDIVIDUALS; MECHANISMS; EXPOSURE AB Acute exposure to arsenic trioxide has been reported to induce death and/or multiple organ damage with symptoms including nausea, vomiting, diarrhea, gastrointestinal hemorrhage, cerebral edema, tachycardia, dysrhythmias and hypovolemic shock. Its toxic effects are due to its ability to bind to sulfhydryl groups of proteins and to inhibit energy production. Although the chronic exposure to arsenic trioxide has been linked to various types of cancer, such as skin, liver, lung, bladder and kidney neoplasms, studies of its carcinogenic potential in animals have not been conclusive. In this study, we investigated the genotoxic potential of arsenic trioxide in bone-marrow cells obtained from Sprague-Dawley rats; using chromosomal aberrations (CA), mitotic index (MI) and micronuclei (MN) formation as the toxicological endpoints. Four groups of six male rats each, weighing approximately 60 +/- 2 g per rat, were injected intraperitoneally, once a day for 5 days with doses of 5, 10, 15 and 20 mg/kg body weight (BW) of arsenic trioxide dissolved in distilled water. A control group was also made of six animals injected with distilled water without chemical. All the animals were sacrificed at the end of the treatment period. Chromosome and micronuclei preparation was obtained from bone-marrow cells following standard protocols. Arsenic trioxide exposure significantly increased the number of structural chromosomal aberrations, the frequency of micronucleated cells and decreased the mitotic index in treated groups when compared with the control group. Our results demonstrate that arsenic trioxide has a clastogenic/genotoxic potential as measured by the bone-marrow CA and MN tests in Sprague-Dawley rats. (c) 2005 Elsevier B.V All rights reserved. C1 Jackson State Univ, Coll Sci Engn & Technol, Ctr Environm Hlth, Mol Toxicol Res Lab,NIH, Jackson, MS 39217 USA. RP Tchounwou, PB (reprint author), Jackson State Univ, Coll Sci Engn & Technol, Ctr Environm Hlth, Mol Toxicol Res Lab,NIH, Jackson, MS 39217 USA. EM paul.b.tchounwou@jsums.edu FU NCRR NIH HHS [1G12RR13459] NR 54 TC 36 Z9 40 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD NOV 10 PY 2005 VL 587 IS 1-2 BP 126 EP 133 DI 10.1016/j.mrgentox.2005.08.007 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 982GV UT WOS:000233147000015 PM 16213187 ER PT J AU Zhao, J Voltan, R Peng, B Davis-Warren, A Kalyanaraman, VS Alvord, WG Aldrich, K Bernasconi, D Butto, S Cafaro, A Ensoli, B Robert-Guroff, M AF Zhao, J Voltan, R Peng, B Davis-Warren, A Kalyanaraman, VS Alvord, WG Aldrich, K Bernasconi, D Butto, S Cafaro, A Ensoli, B Robert-Guroff, M TI Enhanced cellular immunity to SIV Gag following co-administration of adenoviruses encoding wild-type or mutant HIV Tat and SIV Gag SO VIROLOGY LA English DT Article DE AIDS vaccine; HIV Tat; adenovirus recombinant ID IMMUNODEFICIENCY-VIRUS-INFECTION; LONG-TERM PROTECTION; RHESUS MACAQUES; CYNOMOLGUS MONKEYS; VACCINATED MACAQUES; SIVMAC251 CHALLENGE; ANTIBODY-RESPONSE; DENDRITIC CELLS; ACCESSORY GENE; DNA VACCINES AB Among candidate antigens for human immunodeficiency virus (HIV) prophylactic vaccines, the regulatory protein Tat is a critical early target, but has a potential for immune suppression. Adenovirus (Ad) recombinants encoding wild-type HIV Tat (Tat-wt) and a transdominant negative mutant HIV Tat (Tat22) were constructed and administered to mice separately or together with Ad-SIVgag. Immumogenicity and effects on immune responses to the co-administered Gag immunogen were evaluated. Wild-type and mutant Tat recombinants elicited similar Tat-specific cellular and humoral immune responses. Co-administration of either Tat immunogen with Ad-SIVgag induced modest but significant enhancement of Gag-specific interferon-gamma secreting T cells and lymphoproliferative responses. Neither the Ad-recombinant encoding Tat-wt nor Tat22 suppressed induction of anti-Tat or anti-Gag antibodies. Based on the immune responses observed in mice, both recombinants appear to be suitable vaccine candidates. Their contribution to protective efficacy remains to be determined in a non-human primate model. Published by Elsevier Inc. C1 NCI, Bethesda, MD 20892 USA. Adv Biosci Labs Inc, Kensington, MD 20895 USA. NCI, Data Management Serv, Frederick, MD 21702 USA. Ist Super Sanita, AIDS Div, Dept Infect Parasit & Immunomediated Dis, I-00161 Rome, Italy. RP Robert-Guroff, M (reprint author), NCI, 41 Medlars Dr,Bldg 41,Room D804, Bethesda, MD 20892 USA. EM guroffm@mail.nih.gov RI Ensoli, Barbara/J-9169-2016; Cafaro, Aurelio/K-5314-2016 OI Ensoli, Barbara/0000-0002-0545-8737; FU Intramural NIH HHS NR 62 TC 15 Z9 15 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 2005 VL 342 IS 1 BP 1 EP 12 DI 10.1016/j.virol.2005.07.016 PG 12 WC Virology SC Virology GA 984GH UT WOS:000233290100001 PM 16109434 ER PT J AU Venter, M Myers, TG Wilson, MA Kindt, TJ Paweska, JT Burt, FJ Leman, PA Swanepoel, R AF Venter, M Myers, TG Wilson, MA Kindt, TJ Paweska, JT Burt, FJ Leman, PA Swanepoel, R TI Gene expression in mice infected with West Nile virus strains of different neurovirulence SO VIROLOGY LA English DT Article DE West Nile virus; neuroinvasion; strain virulence; encephalitis; DNA microarrays; gene expression ID CELL-MEDIATED HEPATITIS; CENTRAL-NERVOUS-SYSTEM; SERUM AMYLOID-A; CD8(+) T-CELLS; ENCEPHALITIS-VIRUS; IFN-GAMMA; JAPANESE ENCEPHALITIS; NEGATIVE REGULATION; MULTIPLE-SCLEROSIS; SIGNALING PATHWAY AB West Nile virus causes febrile illness in humans with a proportion of cases progressing to meningoencephalitis, encephalitis, hepatitis, and death. Isolates of the virus fall into two genetic lineages, with differences in neuroinvasiveness for mice occurring between strains within both lineages. We used DNA microarrays to compare gene expression in mice infected peripherally with seven lineage I and 2 strains confirmed to be of either high or low neuroinvasiveness in mice and associated with severe or benign infection in humans and birds. The 4 strains with highest neuroinvasiveness induced increased expression of 47 genes in the brain, 111 genes in the liver, and 70 genes in the spleen, relative to the 3 least neuroinvasive strains. Genes involved in interferon signaling pathways, protein degradation, T-cell recruitment, MHC class I and II antigen presentation, and apoptosis were identified that may have both pathogenic and protective effects, but increased expression of certain acute proteins, central nervous system specific proteins and proteins associated with T-cell hepatitis, implicate mechanisms related to exalted virulence. Published by Elsevier Inc. C1 Natl Inst Communicable Dis, Special Pathogens Unit, ZA-2131 Johannesburg, South Africa. NIAID, NIH, Bethesda, MD 20892 USA. RP Venter, M (reprint author), Natl Inst Communicable Dis, Special Pathogens Unit, Private Bag X4, ZA-2131 Johannesburg, South Africa. EM mariav@nicd.ac.za RI Venter, Marietjie/H-3032-2011; Venter, Marietjie/P-9604-2016 OI Venter, Marietjie/0000-0003-2696-824X NR 91 TC 48 Z9 53 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 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 2005 VL 342 IS 1 BP 119 EP 140 DI 10.1016/j.virol.2005.07.013 PG 22 WC Virology SC Virology GA 984GH UT WOS:000233290100011 PM 16125213 ER PT J AU Ichikawa, H Jin, HW Terayama, R Yamaai, T Jacobowitz, DM Sugimoto, T AF Ichikawa, H Jin, HW Terayama, R Yamaai, T Jacobowitz, DM Sugimoto, T TI Calretinin-containing neurons which co-express parvalbumin and calbindin D-28k in the rat spinal and cranial sensory ganglia; triple immunofluorescence study SO BRAIN RESEARCH LA English DT Article DE calretinin; calbindin D-28k; dorsal root ganglion; jugular ganglion; nodose ganglion; parvalbumin; petrosal ganglion; trigeminal ganglion ID CALCIUM-BINDING PROTEINS; DORSAL-ROOT GANGLIA; MOLAR TOOTH-PULP; PERIODONTAL-LIGAMENT; IMMUNOHISTOCHEMICAL LOCALIZATION; ENDINGS; INNERVATION; VAGAL; IMMUNOREACTIVITY; COEXISTENCE AB The co-expression of calretinin with parvalbumin and calbindin D-28k was examined in the rat cranial and spinal sensory ganglia by triple immunofluorescence method. In the trigeminal and nodose ganglia, 9% and 5% of calretinin-immunoreactive neurons, respectively, also contained both parvalbumin- and calbindin D-28k immunoreactivity. These neurons had large cell bodies. In the trigeminal ganglion, they were restricted to the caudal portion. Such neurons were evenly distributed throughout the nodose ganglion. The co-expression could not be detected in the dorsal root, jugular or petrosal ganglia. Nerve fibers which co-expressed all the three calcium-binding proteins were observed in the inferior alveolar nerve but not the infraorbital nerve or palate. In the periodontal ligament, these nerve fibers formed Ruffini-like endings. These findings suggest that (1) the co-expression in trigeminal neurons is intimately related to their peripheral receptive fields; (2) the three calcium-binding proteins (calretinin, parvalbumin, calbindin D-28k) co-expressed in the trigeminal neurons may have mechanoreceptive function in the periodontal ligament. (c) 2005 Elsevier B.V. All rights reserved. C1 Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Oral Funct & Anat, Okayama 7008525, Japan. NIMH, Clin Sci Lab, Bethesda, MD 20892 USA. RP Ichikawa, H (reprint author), Okayama Univ, Grad Sch Med Dent & Pharmaceut Sci, Dept Oral Funct & Anat, 2-5-1 Shikata Cho, Okayama 7008525, Japan. EM hiroichi@md.okayama-u.ac.jp NR 25 TC 13 Z9 13 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 NOV 9 PY 2005 VL 1061 IS 2 BP 118 EP 123 DI 10.1016/j.brainres.2005.08.014 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 991CP UT WOS:000233790200007 PM 16242674 ER PT J AU Colvis, CM Pollock, JD Goodman, RH Impey, S Dunn, J Mandel, G Champagne, FA Mayford, M Korzus, E Kumar, A Renthal, W Theobald, DEH Nestler, EJ AF Colvis, CM Pollock, JD Goodman, RH Impey, S Dunn, J Mandel, G Champagne, FA Mayford, M Korzus, E Kumar, A Renthal, W Theobald, DEH Nestler, EJ TI Epigenetic mechanisms and gene networks in the nervous system SO JOURNAL OF NEUROSCIENCE LA English DT Article DE addiction; chromatin remodeling; epigenetic modifications; maternal behavior; memory consolidation; transcription ID LONG-TERM-MEMORY; RUBINSTEIN-TAYBI-SYNDROME; GENOME-WIDE ANALYSIS; TRANSCRIPTIONAL COACTIVATORS P300; COVALENT HISTONE MODIFICATIONS; ELEMENT-BINDING PROTEIN; CAMP-RESPONSIVE ELEMENT; MATERNAL-CARE; CHROMATIN-STRUCTURE; SYNAPTIC PLASTICITY C1 Natl Inst Drug Abuse, Div Basic Neurosci & Behav Res, Genet & Mol Neurobiol Res Branch, Bethesda, MD 20892 USA. Oregon Hlth Sci Univ, Vollum Inst, Portland, OR 97201 USA. Brookhaven Natl Lab, Dept Biol, Upton, NY 11973 USA. SUNY Stony Brook, Dept Neurobiol & Behav, Howard Hughes Med Inst, Stony Brook, NY 11794 USA. Univ Cambridge, Subdept Anim Behav, Cambridge CB3 8AA, England. Scripps Res Inst, Inst Childhood & Neglected Dis, Dept Cell Biol, La Jolla, CA 92037 USA. Univ Texas, SW Med Ctr, Dept Psychiat, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Ctr Basic Neurosci, Dallas, TX 75390 USA. RP Colvis, CM (reprint author), Natl Inst Drug Abuse, Div Basic Neurosci & Behav Res, Genet & Mol Neurobiol Res Branch, 6001 Execut Blvd, Bethesda, MD 20892 USA. EM ccolvis@nida.nih.gov RI Pollock, Jonathan/B-1554-2009 FU NIDDK NIH HHS [R37 DK45423]; NIMH NIH HHS [R01 MH57368-05] NR 94 TC 100 Z9 108 U1 1 U2 6 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 9 PY 2005 VL 25 IS 45 BP 10379 EP 10389 DI 10.1523/JNEUROSCI.4119-05.2005 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 982DB UT WOS:000233137000011 PM 16280577 ER PT J AU Tian, JH Wu, ZX Unzicker, M Lu, L Cai, Q Li, CL Schirra, C Matti, U Stevens, D Deng, CX Rettig, J Sheng, ZH AF Tian, JH Wu, ZX Unzicker, M Lu, L Cai, Q Li, CL Schirra, C Matti, U Stevens, D Deng, CX Rettig, J Sheng, ZH TI The role of snapin in neurosecretion: Snapin knock-out mice exhibit impaired calcium-dependent exocytosis of large dense-core vesicles in chromaffin cells SO JOURNAL OF NEUROSCIENCE LA English DT Article DE exocytosis; neurosecretion; SNARE proteins; synaptic vesicle release; chromaffin cell; catecholamine ID NEUROTRANSMITTER RELEASE; SYNAPTIC-TRANSMISSION; REGULATED EXOCYTOSIS; MEMBRANE-FUSION; SNARE COMPLEX; SYNAPTOTAGMIN; PROTEIN; IDENTIFICATION; SNAP-25; LYSOSOMES AB Identification of the molecules that regulate the priming of synaptic vesicles for fusion and the structural coupling of the calcium sensor with the soluble N-ethyl maleimide sensitive factor adaptor protein receptor (SNARE)-based fusion machinery is critical for understanding the mechanisms underlying calcium-dependent neurosecretion. Snapin binds to synaptosomal-associated protein 25 kDa (SNAP-25) and enhances the association of the SNARE complex with synaptotagmin. In the present study, we abolished snapin expression in mice and functionally evaluated the role of Snapin in neuroexocytosis. We found that the association of synaptotagmin-1 with SNAP-25 in brain homogenates of snapin mutant mice is impaired. Consequently, the absence of Snapin in embryonic chromaffin cells leads to a significant reduction of calcium-dependent exocytosis resulting from a decreased number of vesicles in releasable pools. Overexpression of Snapin fully rescued this inhibitory effect in the mutant cells. Furthermore, Snapin is relatively enriched in the purified large dense-core vesicles of chromaffin cells and associated with synaptotagmin-1. Thus, our biochemical and electrophysiological studies using snapin knock-out mice demonstrate that Snapin plays a critical role in modulating neurosecretion by stabilizing the release-ready vesicles. C1 NINDS, Synapt Funct Unit, NIH, Bethesda, MD 20892 USA. Univ Saarland, Inst Phys, D-66424 Homburg Saar, Germany. NIDDKD, Mammalian Genet Sect, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Rettig, J (reprint author), NINDS, Synapt Funct Unit, NIH, Bldg 35,Room 3B203,35 Convent Dr, Bethesda, MD 20892 USA. EM jrettig@uniklinik-saarland.de; shengz@ninds.nih.gov RI Wu, Zheng-Xing/G-4695-2011; Rettig, Jens/K-5103-2013; deng, chuxia/N-6713-2016; OI Rettig, Jens/0000-0001-6160-3954; Matti, Ulf/0000-0001-5548-1081 FU Intramural NIH HHS; NINDS NIH HHS [Z01 NS002946-09] NR 38 TC 57 Z9 61 U1 2 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 9 PY 2005 VL 25 IS 45 BP 10546 EP 10555 DI 10.1523/JNEUROSCI.3275-05.2005 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 982DB UT WOS:000233137000026 PM 16280592 ER PT J AU Han, SS Shaffer, AL Peng, LP Chung, ST Lim, JH Maeng, S Kim, JS McNeil, N Ried, T Staudt, LM Janz, S AF Han, Seong Su Shaffer, Arthur L. Peng, Liangping Chung, Seung Tae Lim, Jae Hwan Maeng, Sungho Kim, Joong Su McNeil, Nicole Ried, Thomas Staudt, Louis M. Janz, Siegfried TI Molecular and cytological features of the mouse B-cell lymphoma line iMyc(E mu)-1 SO MOLECULAR CANCER LA English DT Article ID C-MYC; DIFFERENTIATION; EXPRESSION; NEOPLASMS; MICE AB Background: Myc-induced lymphoblastic B-cell lymphoma (LBL) in iMyc(E mu) mice may provide a model system for the study of the mechanism by which human MYC facilitates the initiation and progression of B cell and plasma cell neoplasms in human beings. We have recently shown that gene-targeted iMyc(E mu) mice that carry a His(6)-tagged mouse Myc cDNA, Myc(His), just 5' of the immunoglobulin heavy-chain enhancer, E mu, are prone to B cell and plasma cell tumors. The predominant tumor (similar to 50%) that arose in the iMyc(E mu) mice on the mixed genetic background of segregating C57BL/6 and 129/SvJ alleles was LBL. The purpose of this study was to establish and characterize a cell line, designated iMyc(E mu)-I, for the in-depth evaluation of LBL in vitro. Methods: The morphological features and the surface marker expression profile of the iMyc(E mu)-1 cells were evaluated using cytological methods and FACS, respectively. The cytogenetic make-up of the iMycE mu-1 cells was assessed by spectral karyotyping (SKY). The expression of the inserted Myc(His) gene was determined using RT-PCR and qPCR. Clonotypic immunoglobulin gene arrangements were detected by Southern blotting. The global gene expression program of the iMyc(E mu)-1 cells and the expression of 768 "pathway" genes were determined with the help of the Mouse Lymphochip((c)) and Superarray((c)) cDNA micro- and macroarrays, respectively. Array results were verified, in part, by RT-PCR and qPCR. Results: Consistent with their derivation from LBL, the iMyc(E mu)- 1 cells were found to be neoplastic IgMhighIgDlow lymphoblasts that expressed typical B- cell surface markers including CD40, CD54 ( ICAM- 1), CD80 ( B7- 1) and CD86 ( B7- 2). The iMyc(E mu)- 1 cells harbored a reciprocal T( 9; 11) and three non- reciprocal chromosomal translocations, overexpressed MycHis at the expense of normal Myc, and exhibited gene expression changes on Mouse Lymphochip c microarrays that were consistent with MycHis- driven B- cell neoplasia. Upon comparison to normal B cells using eight different Superarray c cDNA macroarrays, the iMyc(E mu)- 1 cells showed the highest number of changes on the NF.B array. C1 Natl Canc Inst, Genet Lab, Canc Res Ctr, NIH, Bethesda, MD USA. NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Metab Lab, CCR, NIH, Bethesda, MD 20892 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, CCR, NIH, Bethesda, MD 20892 USA. NCI, Genet Branch, CCR, NIH, Bethesda, MD 20892 USA. Korea Res Inst Biosci & Biotechnol, Taejon, South Korea. Andong Natl Univ, Dept Biol Sci, Andong, South Korea. RP Janz, S (reprint author), Natl Canc Inst, Genet Lab, Canc Res Ctr, NIH, Bethesda, MD USA. EM hanse@mail.nih.gov; as275s@nih.gov; lp242e@NIH.GOV; chungs@mail.nih.gov; jhlim@andong.ac.kr; sm446f@NIH.GOV; joongsu@kribb.re.kr; mcneiln@mail.nih.gov; tr92o@NIH.GOV; lstaudt@mail.nih.gov; sj4s@nih.gov FU Intramural NIH HHS NR 12 TC 5 Z9 5 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1476-4598 J9 MOL CANCER JI Mol. Cancer PD NOV 9 PY 2005 VL 4 AR 40 DI 10.1186/1476-4598-4-40 PG 10 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 076OG UT WOS:000239967000001 PM 16277667 ER PT J AU Brady, J Kashanchi, F AF Brady, J Kashanchi, F TI Tat gets the "green" light on transcription initiation SO RETROVIROLOGY LA English DT Review ID IMMUNODEFICIENCY-VIRUS TYPE-1; RNA-POLYMERASE-II; LONG TERMINAL REPEAT; LARGE T-ANTIGEN; HIV-1 TAT; BINDING PROTEIN; P-TEFB; HISTONE ACETYLTRANSFERASE; GENE-EXPRESSION; REPRESSES TRANSCRIPTION AB Human immunodeficiency virus type 1 (HIV-1) Tat transactivation is an essential step in the viral life cycle. Over the past several years, it has become widely accepted that Tat exerts its transcriptional effect by binding the transactivation-responsive region ( TAR) and enhancing transcriptional elongation. Consistent with this hypothesis, it has been shown that Tat promotes the binding of P-TEFb, a transcription elongation factor composed of cyclin T1 and cdk9, and the interaction of Tat with P-TEFb and TAR leads to hyperphosphorylation of the C-terminal domain (CTD) of RNA Pol II and increased processivity of RNA Pol II. A recent report, however, has generated renewed interest that Tat may also play a critical role in transcription complex (TC) assembly at the preinitiation step. Using in vivo chromatin immunoprecipitation assays, the authors reported that the HIV TC contains TBP but not TBP-associated factors. The stimulatory effect involved the direct interaction of Tat and P-TEFb and was evident at the earliest step of TC assembly, the TBP-TATA box interaction. In this article, we will review this data in context of earlier data which also support Tat's involvement in transcriptional complex assembly. Specifically, we will discuss experiments which demonstrated that Tat interacted with TBP and increased transcription initiation complex stability in cell free assays. We will also discuss studies which demonstrated that over expression of TBP alone was sufficient to obtain Tat activated transcription in vitro and in vivo. Finally, studies using self-cleaving ribozymes which suggested that Tat transactivation was not compatible with pausing of the RNA Pol II at the TAR site will be discussed. C1 George Washington Univ, Sch Med, Dept Biochem & Mol Biol, Washington, DC 20037 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Kashanchi, F (reprint author), George Washington Univ, Sch Med, Dept Biochem & Mol Biol, Washington, DC 20037 USA. EM bradyj@dce41.nci.nih.gov; bcmfxk@gwumc.edu FU NIAID NIH HHS [AI43894, AI44357, R01 AI043894, R29 AI044357]; PHS HHS [13969] NR 71 TC 100 Z9 107 U1 0 U2 3 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 NOV 9 PY 2005 VL 2 AR 69 DI 10.1186/1742-4690-2-69 PG 8 WC Virology SC Virology GA 033OD UT WOS:000236857300001 PM 16280076 ER PT J AU Sun, QA Su, D Novoselov, SV Carlson, BA Hatfield, DL Gladyshev, VN AF Sun, QA Su, D Novoselov, SV Carlson, BA Hatfield, DL Gladyshev, VN TI Reaction mechanism and regulation of mammalian thioredoxin/glutathione reductase SO BIOCHEMISTRY LA English DT Article ID THIOREDOXIN-GLUTATHIONE-REDUCTASE; SELENOCYSTEINE TRANSFER-RNA; ESCHERICHIA-COLI; SELENOPROTEIN SYNTHESIS; SELENIUM BIOCHEMISTRY; REDOX REGULATION; SECIS ELEMENTS; GENE TRSP; MITOCHONDRIAL; EXPRESSION AB Thioredoxin/glutathione reductase (TGR) is a recently discovered member of the selenoprotein thioredoxin reductase family in mammals. In contrast to two other mammalian thioredoxin reductases, it contains an N-terminal glutaredoxin domain and exhibits a wide spectrum of enzyme activities. To elucidate the reaction mechanism and regulation of TGR, we prepared a recombinant mouse TGR in the selenoprotein form as well as various mutants and individual domains of this enzyme. Using these proteins, we showed that the glutaredoxin and thioredoxin reductase domains of TGR could independently catalyze reactions normally associated with each domain. The glutaredoxin domain is a monothiol glutaredoxin containing a CxxS motif at the active site, which could receive electrons from either the thioredoxin reductase domain of TGR or thioredoxin reductase 1. We also found that the C-terminal penultimate selenocysteine was required for transfer of reducing equivalents from the thiol/disulfide active site of TGR to the glutaredoxin domain. Thus, the physiologically relevant NADPH-dependent activities of TGR were dependent on this residue. In addition, we examined the effects of selenium levels in the diet and perturbations in selenocysteine tRNA function on TGR biosynthesis and found that expression of this protein was regulated by both selenium and tRNA status in liver, but was more resistant to this regulation in testes. C1 Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. NCI, Sect Mol Biol Selenium, Lab Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev1@unl.edu RI Su, Dan/B-1972-2010; Gladyshev, Vadim/A-9894-2013; OI Novoselov, Sergey/0000-0003-0104-6492 FU NIGMS NIH HHS [GM065204] NR 55 TC 50 Z9 53 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 8 PY 2005 VL 44 IS 44 BP 14528 EP 14537 DI 10.1021/bi051321w PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 981DZ UT WOS:000233068900015 PM 16262253 ER PT J AU Zhu, ZZ Cong, WM Liu, SF Xian, ZH Wu, WQ Wu, MC Gao, B Hou, LF Zhu, GS AF Zhu, ZZ Cong, WM Liu, SF Xian, ZH Wu, WQ Wu, MC Gao, B Hou, LF Zhu, GS TI A p53 polymorphism modifies the risk of hepatocellular carcinoma among non-carriers but not carriers of chronic hepatitis B virus infection SO CANCER LETTERS LA English DT Article DE p53; hepatitis B virus; DNA polymorphisms; hepatocellular carcinoma ID P21 CODON-31 POLYMORPHISMS; CANCER RISK; X PROTEIN; GENETIC POLYMORPHISMS; PROSTATE-CANCER; LIVER-CANCER; SKIN-CANCER; TAIWAN; SUSCEPTIBILITY; ASSOCIATION AB To clarify the modifying effect of the codon 72 p53 polymorphism on hepatocellular carcinoma (HCC) stratified by chronic hepatitis B virus (HBV) infection status, 111 incident cases of HCC and 424 controls in HBV-negative subjects and 135 cases and 125 controls in HBV-positive subjects were identified. No correlation between the polymorphism and HCC risk was found when comparing the HBV-positive cases to controls. However, in HBV-negative subjects, Arg/Pro and Pro/Pro genotypes had a 1.97-fold and a 3.36-fold increased risk for HCC, respectively. In subjects with the Pro allele and family history of HCC yielded an 11.81-fold increased risk of HCC. (C) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Eastern Hepatobiliary Surg Hosp, Dept Pathol, Shanghai 200438, Peoples R China. Tongji Univ, Railway Hosp, Dept Gastroenterol, Shanghai 200072, Peoples R China. NIAAA, NIH, Bethesda, MD 20852 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Changhai Hosp, Dept Infect Dis, Shanghai 200433, Peoples R China. RP Cong, WM (reprint author), Eastern Hepatobiliary Surg Hosp, Dept Pathol, 225 Changhai Rd, Shanghai 200438, Peoples R China. EM wmcong@smmu.edu.cn NR 40 TC 27 Z9 30 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD NOV 8 PY 2005 VL 229 IS 1 BP 77 EP 83 DI 10.1016/j.canlet.2005.04.014 PG 7 WC Oncology SC Oncology GA 971WB UT WOS:000232414500009 PM 15979781 ER PT J AU Lederman, RJ AF Lederman, RJ TI Cardiovascular interventional magnetic resonance imaging SO CIRCULATION LA English DT Review DE imaging; magnetic resonance imaging; catheterization; peripheral vascular disease ID VENA-CAVA FILTER; GUIDED PERCUTANEOUS ANGIOPLASTY; RESOLUTION INTRAVASCULAR MRI; PASSIVE CATHETER TRACKING; ARTERY STENT PLACEMENT; ATRIAL SEPTAL-DEFECTS; IN-VIVO; ANIMAL-MODEL; CARDIAC-CATHETERIZATION; SWINE MODEL C1 NHLBI, Cardiovasc Branch, Clin Res Program, Div Intramural Res,NIH, Bethesda, MD 20892 USA. RP Lederman, RJ (reprint author), NHLBI, Cardiovasc Branch, Clin Res Program, Div Intramural Res,NIH, Bldg 10,Room 2c713,MSC 1538, Bethesda, MD 20892 USA. EM Lederman@nih.gov FU NHLBI NIH HHS [Z01 HL005062-03, Z01 HL005062] NR 111 TC 47 Z9 48 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD NOV 8 PY 2005 VL 112 IS 19 BP 3009 EP 3017 DI 10.1161/CIRCULATIONHA.104.531368 PG 9 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 981UT UT WOS:000233114200019 PM 16275886 ER PT J AU Hirtz, D Iannaccone, S Heemskerk, J Gwinn-Hardy, K Moxley, R Rowland, LP AF Hirtz, D Iannaccone, S Heemskerk, J Gwinn-Hardy, K Moxley, R Rowland, LP TI Challenges and opportunities in clinical trials for spinal muscular atrophy SO NEUROLOGY LA English DT Article ID VALPROIC ACID INCREASES; DUCHENNE DYSTROPHY; NATURAL-HISTORY; PROTEIN-LEVEL; SMN LEVELS; CHILDHOOD; GENE; PREDNISONE; SEVERITY; CELLS AB Spinal muscular atrophy (SMA) is the most common fatal neuromuscular disease of infancy. SMA type I is the most severe and mortality is usually due to respiratory failure. In type II the disability is of later onset and less severe, and prognosis has improved primarily due to supportive care. Type III is the mildest form with onset usually of weakness in adolescence or young adulthood. SMA is an autosomal recessive disorder with deletions or mutations of the gene at the 5 q11 locus. There is no specific prevention or treatment, but current progress toward potential therapies has been substantial and several candidates including histone deacetylase ( HDAC) inhibitors are under consideration for further evaluation. The authors sought to address the challenges and opportunities for testing new therapies for SMA. C1 NINDS, NIH, Bethesda, MD 20892 USA. SW Texas State Univ, Childrens Med Ctr, Dallas, TX USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. Columbia Univ, New York, NY USA. RP Hirtz, D (reprint author), 6001 Execut Blvd,Room 2212, Bethesda, MD 20892 USA. EM hirtzd@ninds.nih.gov RI Gwinn, Katrina/C-2508-2009 NR 33 TC 32 Z9 33 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 8 PY 2005 VL 65 IS 9 BP 1352 EP 1357 DI 10.1212/01.wnl.0000183282.10946.c7 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 981US UT WOS:000233114100004 PM 16275820 ER PT J AU Barkhof, F Held, U Simon, JH Daumer, M Fazekas, F Filippi, M Frank, JA Kappos, L Li, D Menzler, S Miller, DH Petkau, J Wolinsky, J AF Barkhof, F Held, U Simon, JH Daumer, M Fazekas, F Filippi, M Frank, JA Kappos, L Li, D Menzler, S Miller, DH Petkau, J Wolinsky, J CA Sylvia Lawry Ctr MS Res TI Predicting gadolinium enhancement status in MS patients eligible for randomized clinical trials SO NEUROLOGY LA English DT Article ID ACUTE OPTIC NEURITIS; PROGRESSIVE MULTIPLE-SCLEROSIS; RESONANCE-IMAGING FINDINGS; STATISTICAL POWER; DISEASE-ACTIVITY; MRI; DISABILITY; MODELS; SERIAL AB Background: Gadolinium enhancement is often used in randomized clinical trials to evaluate the efficacy of new drugs in multiple sclerosis (MS). Knowledge about predictors of enhancement status is important for the selection of patients for MRI monitored trials. Methods: Data from 17 trials were available in anonymized format through the Sylvia Lawry Centre for MS Research. In an open part containing 1,328 (non primary progressive) patients, two logistic regression analyses were explored, including demographic, clinical, and MRI predictors. The authors examined the area under the curve (AUC) and the increase in positive predictive value (PPV). The final selection of models was validated in a closed part of 848 comparable patients. Results: Age at onset, disease duration, and disease course (CIS/RR/SP) were important predictors from the multivariate models. Further, a multivariate model including T2 burden of disease was more predictive than one with only clinical predictors (AUC 0.719 vs 0.625, p < 0.001). For the model with T2 burden of disease, the PPV was 66.8%, compared to 58.5% for the model without (a priori chance 46.4%). These findings were unequivocally confirmed in the closed part of the database. Conclusion: Gadolinium status can be predicted by a set of baseline variables, certainly when T2 burden of disease is included. These findings may benefit the design and statistical power of future randomized clinical trials. C1 Vrije Univ Amsterdam, Dept Radiol, Med Ctr, NL-1007 MB Amsterdam, Netherlands. Sylvia Lawry Ctr, Munich, Germany. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Karl Franzens Univ Graz, A-8010 Graz, Austria. Osped San Raffaele, Milan, Italy. NIH, Lab Diagnost Radiol, Bethesda, MD 20892 USA. Kantonsspital, CH-4031 Basel, Switzerland. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. Stiftung Tierzart Hsch, Hannover, Germany. Inst Neurol, London WC1N 3BG, England. Univ Texas, Hlth Sci Ctr, Houston, TX USA. RP Barkhof, F (reprint author), Vrije Univ Amsterdam, Dept Radiol, Med Ctr, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM f.barkhof@vumc.nl RI Held, Ulrike /D-3666-2013 FU Multiple Sclerosis Society [748] NR 30 TC 22 Z9 22 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD NOV 8 PY 2005 VL 65 IS 9 BP 1447 EP 1454 DI 10.1212/01.wnl.0000183149.87975.32 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 981US UT WOS:000233114100022 PM 16275834 ER PT J AU Chattopadhyay, MK Tabor, CW Tabor, H AF Chattopadhyay, MK Tabor, CW Tabor, H TI Studies on the regulation of ornithine decarboxylase in yeast: Effect of deletion in the MEU1 gene SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE methylthioadenosine; methylthioadenosine phosphorylase; polyamines; spermidine; putrescine ID METHYLTHIOADENOSINE PHOSPHORYLASE GENE; SACCHAROMYCES-CEREVISIAE; SPERMIDINE SYNTHASE; S-ADENOSYLMETHIONINE; DEGRADATION; POLYAMINE; METHIONINE; BIOSYNTHESIS; ANTIZYME; 5'-METHYLTHIOADENOSINE AB Methylthioadenosine is formed during the biosynthesis of spermidine and of spermine and is metabolized by methylthioadenosine phosphorylase, an enzyme missing in several tumor cell lines. In Saccharomyces cerevisiae, this enzyme is coded by the MEW gene. We have now studied the effect of the meu1 deletion on polyamine metabolism in yeast. We found that the effects of the meu1 Delta mutation mostly depend on the stage of cell growth. As the cell density increases, there is a marked fall in the level of ornithine decarboxylase (ODC) in the MEU1(+) cells, which we show is caused by an antizyme-requiring degradation system. In contrast, there is only a small decrease in the ODC level in the meu1 Delta cells. The meu1 Delta cells have a higher putrescine and a lower spermidine level than MEU1+ cells, suggesting that the decreased spermidine level in the meu1 Delta cultures is responsible for the greater apparent stability of ODC in the meu1 Delta cells. The lower spermidine level in the meu1 Delta cells probably results from an inhibition of spermidine synthase by the methylthioadenosine that presumably accumulates in these mutants. In both MEU1(+) and the meu1 Delta cultures, the ODC levels were markedly decreased by the addition of spermidine to the media, and thus our results contradict the postulation of Subhi et al. [Subhi, A. L., et al. (2003) J. Bio/. Chem. 278, 4986849873] of a novel regulatory pathway in meu1A cells in which ODC is not responsive to spermicline. C1 NIDDK, Lab Biochem & Genet, NIH, Bethesda, MD 20892 USA. RP Tabor, H (reprint author), NIDDK, Lab Biochem & Genet, NIH, Bldg 8,Room 223, Bethesda, MD 20892 USA. EM tabor@helix.nih.gov FU Intramural NIH HHS NR 37 TC 9 Z9 9 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 NOV 8 PY 2005 VL 102 IS 45 BP 16158 EP 16163 DI 10.1073/pnas.0507299102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 984DW UT WOS:000233283700008 PM 16260735 ER PT J AU Jin, W Kim, BC Tognon, C Lee, HJ Patel, S Lannon, CL Maris, JM Triche, TJ Sorensen, PHB Kim, SJ AF Jin, W Kim, BC Tognon, C Lee, HJ Patel, S Lannon, CL Maris, JM Triche, TJ Sorensen, PHB Kim, SJ TI The ETV6-NTRK3 chimeric tyrosine kinase suppresses TGF-beta signaling by inactivating the TGF-beta type II receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chromosomal translocation; congenital fibrosarcoma; TGF-beta receptor ID GROWTH-FACTOR-BETA; GENE FUSION; CONGENITAL FIBROSARCOMA; MESOBLASTIC NEPHROMA; TRANSFORMATION; EXPRESSION; TRKC; T(12/15)(P13,Q25); TRANSCRIPTION; LEUKEMIA AB An emerging theme in cancer biology is that although some malignancies occur through the sequential acquisition of different genetic alterations, certain dominantly acting oncoproteins such as those associated with chromosomal translocations have multiple functions and do not require additional mutations for cell transformation. The ETV6-NTRK3 (EN) chimeric tyrosine kinase, a potent oncoprotein expressed in tumors derived from multiple cell lineages, functions as a constitutively active protein tyrosine kinase. Here, we show that EN suppresses TGF-beta signaling by directly binding to the type II TGF-beta receptor, thereby preventing it from interacting with the type ITGF-13 receptor. This activity requires a functional EN protein tyrosine kinase, and type 11 TGF-beta receptor appears to be a direct target of EN. Our findings provide evidence for a previously undescribed mechanism by which oncogenic tyrosine kinases can block TGF-beta tumor suppressor activity. C1 British Columbia Childrens Hosp, Dept Pathol, Vancouver, BC V6H 3V4, Canada. Kangwon Natl Univ, Dept Life Sci, Chunchon 200701, South Korea. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Korea Res Inst Biosci & Biotechnol, Taejon 305806, South Korea. Childrens Hosp Philadelphia, Div Oncol, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90033 USA. Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA 90033 USA. RP Sorensen, PHB (reprint author), British Columbia Childrens Hosp, Dept Pathol, Vancouver, BC V6H 3V4, Canada. EM psor@interchange.ubc.ca; kims@mail.nih.gov FU Intramural NIH HHS; NCI NIH HHS [U01 CA088199, U01 CA88199, Z01 BC005617-17] NR 26 TC 21 Z9 21 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 NOV 8 PY 2005 VL 102 IS 45 BP 16239 EP 16244 DI 10.1073/pnas.0503137102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 984DW UT WOS:000233283700022 PM 16258068 ER PT J AU Araki, O Ying, H Furuya, F Zhu, XG Cheng, SY AF Araki, O Ying, H Furuya, F Zhu, XG Cheng, SY TI Thyroid hormone receptor beta mutants: Dominant negative regulators of peroxisome proliferator-activated receptor gamma action SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE chromatin immunoprecipitation; dominant negative activity; thyroid hormone receptor mutant; transcription regulation ID RETINOID-X-RECEPTOR; TRANSCRIPTIONAL ACTIVITY; GENERALIZED RESISTANCE; RESPONSE ELEMENT; LIGAND-BINDING; MOUSE MODEL; PPAR-GAMMA; GENE; EXPRESSION; COREPRESSORS AB Thyroid hormone (T3) and peroxisome proliferators have overlapping metabolic effects in the maintenance of lipid homeostasis. Their actions are mediated by their respective receptors: thyroid hormone receptors (TR) and peroxisome proliferator-activated receptors (PPAR). We recently found that a dominantly negative TR beta mutant (PV) that causes a genetic disease, resistance to thyroid hormone, acts to repress the ligand (troglitazone)-mediated transcriptional activity of PPAR gamma in cultured thyroid cells. This finding suggests that TR beta mutants could crosstalk with PPAR gamma-signaling pathways. The present study explored the molecular mechanisms by which PV represses the PPAR gamma transcriptional activity. Gel-shift assays show that the PV, similar to wild-type TR beta, bound to the peroxisome proliferator response element (PPRE) as homodinners and heterodimers with PPAR gamma or the retinoid X receptor (RXR), thereby competing with PPAR gamma for binding to PPRE and for sequestering RXR. Association of PPRE-bound PV with corepressors [e.g., nuclear receptor corepressor (NCoR)] that led to transcriptional repression was independent of T3 and troglitazone. Chromatin immunoprecipitation assay further demonstrated that, despite the presence of ligands, NCoR was recruited to PPRE-bound PV on a PPAR gamma-target gene, the lipoprotein lipase, in vivo, suggesting the dominant action of PV on PPAR gamma-mediated transcriptional activity. Thus, the dominant negative action of PV is not limited on the wild-type TRs. The findings that TR beta mutants affect PPAR gamma functions through dominant negative action provide insights into the molecular mechanisms by which TR regulates the PPAR gamma-target genes involved in metabolic pathways, lipid homeostasis, and carcinogenesis. C1 NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Cheng, SY (reprint author), NCI, Mol Biol Lab, Ctr Canc Res, NIH, 37 Convent Dr,Room 5128, Bethesda, MD 20892 USA. EM sycheng@helix.nih.gov FU Intramural NIH HHS NR 29 TC 29 Z9 32 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 NOV 8 PY 2005 VL 102 IS 45 BP 16251 EP 16256 DI 10.1073/pnas.0508556102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 984DW UT WOS:000233283700024 PM 16260719 ER PT J AU Kar, S Edgar, R Adhya, S AF Kar, S Edgar, R Adhya, S TI Nucleoid remodeling by an altered HU protein: Reorganization of the transcription program SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE bacterial HU; nucleoid condensation; virulence ID DNA-BINDING PROTEIN; ESCHERICHIA-COLI; LARGE-INTESTINE; COMPACTION; CONDENSATION; REGULATOR; BACTERIA AB Bacterial nucleoid organization is believed to have minimal influence on the global transcription program. Using an altered bacterial histone-like protein, HU alpha, we show that reorganization of the nucleoid configuration can dynamically modulate the cellular transcription pattern. The mutant protein transformed the loosely packed nucleoid into a densely condensed structure. The nucleoid compaction, coupled with increased global DNA supercoiling, generated radical changes in the morphology, physiology, and metabolism of wild-type K-12 Escherichia coli. Many constitutive housekeeping genes involved in nutrient utilization were repressed, whereas many quiescent genes associated with virulence were activated in the mutant. We propose that, as in eukaryotes, the nucleoid architecture dictates the global transcription profile and, consequently, the behavior pattern in bacteria. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Adhya, S (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, 37 Convent Dr,Room 5106, Bethesda, MD 20892 USA. EM sadhya@helix.nih.gov FU Intramural NIH HHS NR 30 TC 60 Z9 61 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 NOV 8 PY 2005 VL 102 IS 45 BP 16397 EP 16402 DI 10.1073/pnas.0508032102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 984DW UT WOS:000233283700049 PM 16258062 ER PT J AU Donley, MP Schulkin, J Rosen, JB AF Donley, MP Schulkin, J Rosen, JB TI Glucocorticoid receptor antagonism in the basolateral amygdala and ventral hippocampus interferes with long-term memory of contextual fear SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE amygdala; hippocampus; glucocorticoid receptor; RU 38486; fear ID DIFFERENT ANTEROGRADE AMNESIAS; DORSAL HIPPOCAMPUS; INHIBITORY AVOIDANCE; ELECTROLYTIC LESIONS; POTENTIATED STARTLE; RETROGRADE-AMNESIA; CONDITIONED FEAR; MESSENGER-RNA; RAT-BRAIN; CORTICOSTERONE AB The binding of glucocorticoids to the type II or glucocorticoid receptor (GR) is known to play a role in memory consolidation and long-term memory. The present series of studies investigated the locus for GR effects on learning and memory of contextual fear conditioning. The GR antagonist RU 38486 was administered peripherally (10, 20, or 30 mg/kg/ml), as well as centrally into the lateral ventricle (75 or 150 ng/2 mu L), basolateral amygdala (BLA; 0.3, 3, or 30 ng/0.2 mu L), dorsal hippocampus (DH; 30 ng/mu L) or ventral hippocampus (VH; 30 ng/mu L) prior to contextual fear conditioning. Peripheral administration of RU 38486 did not affect fear-related levels of freezing immediately following a footshock or in a long-term memory test 24 h later. However, administration into the lateral ventricle, BLA, or VH decreased freezing in a 24 h retention test, while leaving post-shock levels of freezing intact. Both post-shock and retention levels of freezing were unaffected in rats that received RU 38486 in the DH compared to vehicle controls; however, vehicle rats also displayed low levels of freezing during retention. The data indicate that GR activation within the BLA and VH is important for the establishment of long-term memory for contextual fear conditioning. (c) 2005 Published by Elsevier B.V. C1 Univ Delaware, Dept Psychol, Behav Neurosci Program, Newark, DE 19716 USA. Georgetown Univ, Dept Physiol & Biophys, Washington, DC 20057 USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20819 USA. RP Rosen, JB (reprint author), Univ Delaware, Dept Psychol, Behav Neurosci Program, 108 Wolf Hall, Newark, DE 19716 USA. EM jrosen@psych.udel.edu FU NIDA NIH HHS [1R03DA12607-1] NR 58 TC 62 Z9 69 U1 2 U2 6 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 NOV 7 PY 2005 VL 164 IS 2 BP 197 EP 205 DI 10.1016/j.bbr.2005.06.020 PG 9 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 973IC UT WOS:000232515100008 PM 16107281 ER PT J AU Thanos, PK Dimitrakakis, ES Rice, O Gifford, A Volkow, ND AF Thanos, PK Dimitrakakis, ES Rice, O Gifford, A Volkow, ND TI Ethanol self-administration and ethanol conditioned place preference are reduced in mice lacking cannabinoid CB1 receptors SO BEHAVIOURAL BRAIN RESEARCH LA English DT Article DE alcoholism; gene therapy; dependency; ingestive behavior; transgenic ID INDUCED DOPAMINE RELEASE; KNOCKOUT MICE; ALCOHOL DEPENDENCE; LOCOMOTOR-ACTIVITY; NUCLEUS-ACCUMBENS; FOOD-INTAKE; RAT-BRAIN; IN-VIVO; CONSUMPTION; ANTAGONIST AB Cannabinoids are postulated to play a role in modulating the reinforcing effects of abused drugs, including alcohol. Experiment 1 examined alcohol self-administration in cannabinoid CB1 receptor knockout (KO), heterozygous (HT) and wild type (WT) mice in a two-bottle choice paradigm. Mice were trained in a limited 8 h access/day to 10% (v/v) EtOH (EtOH) versus water. After baseline drinking levels (% EtOH preference and total EtOH intake (g/kg)), results indicated that the CB1 knockout mice displayed significantly lower baseline EtOH consumption compared to wild type mice. subsequently, treatment with SR141716A (5 mg/kg) significantly attenuated EtOH intake in the WT and HT mice but had little effect on the knockout mice. Experiment 2 examined the CB1 WT And CB 1 KO strains in a conditioned place preference (CPP) procedure between saline and 2 g/kg EtOH. The CB1 WT mice spent significantly more time in the EtOH-paired versus saline-paired chambers, whereas no significant preference was observed in the CB1 KO mice. Finally, we observed that CB1 KO mice were significantly lighter than WT and HT and that SR 141716A did not significantly alter body weight. These results demonstrate that the cannabinoid CB1 receptor is an essential component of the molecular pathways underlying the reinforcing effects of alcohol. Thus, medications targeting the CB1 receptors may be beneficial for the treatment of alcoholism. (c) 2005 Elsevier B.V. All rights reserved. C1 Brookhaven Natl Lab, Dept Med, Behav Pharmacol Lab, Upton, NY 11973 USA. NIAAA, Lab Neuroimaging, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Thanos, PK (reprint author), Brookhaven Natl Lab, Dept Med, Behav Pharmacol Lab, Bldg 490,30 Bell Ave, Upton, NY 11973 USA. EM thanos@bnl.gov FU NIAAA NIH HHS [AA 11034, AA07574, AA07611] NR 57 TC 82 Z9 83 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 NOV 7 PY 2005 VL 164 IS 2 BP 206 EP 213 DI 10.1016/j.bbr.2005.06.021 PG 8 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 973IC UT WOS:000232515100009 PM 16140402 ER PT J AU Moon, KH Kim, BJ Song, BJ AF Moon, KH Kim, BJ Song, BJ TI Inhibition of mitochondrial aldehyde dehydrogenase by nitric oxide-mediated S-nitrosylation SO FEBS LETTERS LA English DT Article DE aldehyde dehydrogenase; glutathione; nitric oxide; NO donors; S-nitrosylation ID RAT-LIVER; HEPATOMA-CELLS; INDUCED APOPTOSIS; OXIDATIVE STRESS; ALCOHOL; PROTEIN; ACID; IDENTIFICATION; GLUTATHIONE; METABOLISM AB Mitochondrial aldehyde dehydrogenase (ALDH2) is responsible for the metabolism of acetaidehyde and other toxic lipid aldehydes. Despite many reports about the inhibition of ALDH2 by toxic chemicals, it is unknown whether nitric oxide (NO) can alter the ALDH2 activity in intact cells or in vivo animals. The aim of this study was to investigate the effects of NO on ALDH2 activity in H4IIE-C3 rat hepatoma cells. NO donors such as S-nitrosoglutathione (GSNO), S-nitroso-N-acetylpenicillamine, and 3-morpholinosydnonimine significantly increased the nitrite concentration while they inhibited the ALDH2 activity. Addition of GSH-ethylester (GSH-EE) completely blocked the GSNO-mediated ALDH2 inhibition and increased nitrite concentration. To directly demonstrate the NO-mediated S-nitrosylation and inactivation, ALDH2 was immunopurified from control or GSNO-treated cells and subjected to immunoblot analysis. The anti-nitrosocysteine antibody recognized the immunopurified ALDH2 only from the GSNO-treated samples. All these results indicate that S-nitrosylation of ALDH2 in intact cells leads to reversible inhibition of ALDH2 activity. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. EM bjs@mail.nih.gov FU NIAAA NIH HHS [Z01 AA000036-19] NR 40 TC 54 Z9 56 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 7 PY 2005 VL 579 IS 27 BP 6115 EP 6120 DI 10.1016/j.febslet.2005.09.082 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 982KT UT WOS:000233157800021 PM 16242127 ER PT J AU Kim, YH Sung, KS Lee, SJ Kim, YO Choi, CY Kim, Y AF Kim, YH Sung, KS Lee, SJ Kim, YO Choi, CY Kim, Y TI Desumoylation of homeodomain-interacting protein kinase 2 (HIPK2) through the cytoplasmic-nuclear shuttling of the SUMO-specific protease SENP1 SO FEBS LETTERS LA English DT Article DE homeodomain-interacting protein kinase 2; SENP1; small ubiquitin-like modifier; nuclear export ID HOMEODOMAIN-INTERACTING-PROTEIN-KINASE-2 HIPK2; COVALENT MODIFICATION; PHOSPHORYLATION; TRANSCRIPTION; YEAST; PML; ISOPEPTIDASE; DROSOPHILA; APOPTOSIS; PROTEINS AB The modification of homeodomain-interacting protein kinase 2 (HIPK2) by small ubiquitin-like modifier 1 (SUMO-1) plays an important role in its targeting into the promyelocytic leukemia body, as well as in its differential interaction with binding partner, but the desumoylation of HIPK2 by SUMO-specific proteases is largely unknown. In this study, we show that HIPK2 is a desumoylation target for the SUMO-specific protease SENP1 that shuttles between the cytoplasm and the nucleus. Mutation analyses reveal that SENP1 contains the nuclear export sequence (NES) within the extreme carboxyl-terminal region, and SENP1 is exported to the cytoplasm in a NES-dependent manner. Sumoylated HIPK2 are deconjugated by SENP1 both in vitro and in cultured cells, and the desumoylation is enhanced either by the forced translocation of SENP1 into the nucleus or by the SENP1 NES mutant. Concomitantly, desumoylation induces dissociation of HIPK2 from nuclear bodies. These results demonstrate that HIPK2 is a target for SENP1 desumoylation, and suggest that the desumoylation of HIPK2 may be regulated by the cytoplasmic-nuclear shuttling of SENP1. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved. C1 NHLBI, Lab Res Program, NIH, Bethesda, MD 20892 USA. Digital Biotech, Ansan 425839, South Korea. Sungkyunkwan Univ, Dept Biol Sci, Suwon 440746, South Korea. RP Choi, CY (reprint author), NHLBI, Lab Res Program, NIH, Bethesda, MD 20892 USA. EM choicy@skku.ac.kr; yongsok@helix.nih.gov FU Intramural NIH HHS NR 36 TC 31 Z9 34 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD NOV 7 PY 2005 VL 579 IS 27 BP 6272 EP 6278 DI 10.1016/j.febslet.2005.10.010 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 982KT UT WOS:000233157800044 PM 16253240 ER PT J AU Filbey, FM Holroyd, T Carver, F Sunderland, T Cohen, RM AF Filbey, FM Holroyd, T Carver, F Sunderland, T Cohen, RM TI A magnetoencephalography spatiotemporal analysis of neural activities during feature binding SO NEUROREPORT LA English DT Article DE cingulate gyrus; feature binding; magnetoencephalography; prefrontal cortex; theta band; time course analysis; working memory ID WORKING-MEMORY TASK; PREFRONTAL CORTEX; SYNCHRONIZATION; OSCILLATIONS; INFORMATION; RETRIEVAL; DYNAMICS; PATTERNS; FMRI AB Previous literature shows that feature binding processes elicit fronto-hippocampal areas. The time course of this process, however, remains unknown. This is the first study that investigates feature binding using magnetoencephalography. Synthetic aperture magnetometry analysis was used to localize sources of increased power in the theta band during the encoding phases of a feature-binding task in the left and right medial frontal gyri (Brodmann's area 10) and left and right anterior cingulate gyri. Theta band synchronization was observed in many of these same areas, but also in other areas not noted to have increased theta band power suggesting a broad network of regions subserving the encoding phase of feature binding. C1 NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. NIMH, MEG Core Facil, Bethesda, MD 20892 USA. RP Filbey, FM (reprint author), Univ Colorado, Dept Psychol, Muenzinger Bldg,D326-B,345 UCB, Boulder, CO 80309 USA. EM Francesca.Filbey@colorado.edu NR 27 TC 3 Z9 3 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD NOV 7 PY 2005 VL 16 IS 16 BP 1747 EP 1752 DI 10.1097/01.wnr.0000185020.75057.19 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 984BO UT WOS:000233277700005 PM 16237320 ER PT J AU Novak, P Moros, EG Parry, JJ Rogers, BE Myerson, RJ Zeug, A Locke, JE Rossin, R Straube, WL Singh, AK AF Novak, P Moros, EG Parry, JJ Rogers, BE Myerson, RJ Zeug, A Locke, JE Rossin, R Straube, WL Singh, AK TI Experience with a small animal hyperthermia ultrasound system (SAHUS): report on 83 tumours SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID NUDE-MICE; LOCAL HYPERTHERMIA; GENE-THERAPY; CANCER; OXYGENATION AB An external local ultrasound (US) system was developed to induce controlled hyperthermia of subcutaneously implanted tumours in small animals (e.g., mice and rats). It was designed to be compatible with a small animal positron emission tomography scanner (microPET) to facilitate studies of hyperthermia-induced tumour re-oxygenation using a PET radiopharmaceutical, but it is applicable for any small animal study requiring controlled heating. The system consists of an acrylic applicator bed with up to four independent 5 MHz planar disc US transducers of I cm in diameter, a four-channel radiofrequency (RF) generator, a multiple thermocouple thermometry unit, and a personal computer with custom monitoring and controlling software. Although the system presented here was developed to target tumours of up to 1 cm in diameter, the applicator design allows for different piezoelectric transducers to be exchanged and operated within the 3.5-6.5 MHz band to target different tumour sizes. Temperature feedback control software was developed on the basis of a proportional-integral-derivative (PID) approach when the measured temperatures were within a selectable temperature band about the target temperature. Outside this band, an on/off control action was applied. Perfused tissue-mimicking phantom experiments were performed to determine optimum controller gain constants, which were later employed successfully in animal experiments. The performance of the SAHUS (small animal hyperthermia ultrasound system) was tested using several tumour types grown in thighs of female nude (nu/nu) mice. To date, the system has successfully treated 83 tumours to target temperatures in the range of 41-43 degrees C for periods of 65 min on average. C1 Washington Univ, Sch Med, Dept Radiat Oncol, St Louis, MO 63108 USA. Washington Univ, Sch Med, Dept Radiol, St Louis, MO 63110 USA. NCI, Radiat Oncol Branch, Bethesda, MD USA. RP Moros, EG (reprint author), Univ Arkansas Med Sci, Coll Med, Dept Radiat Oncol, 4301 W Markham,771, Little Rock, AR 72205 USA. EM emoros@uams.edu OI Moros, Eduardo/0000-0003-1964-2460 FU NCI NIH HHS [R01 CA71638, R01 CA63121, K08 CA88924, CA104457, CA106587] NR 22 TC 8 Z9 9 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 0031-9155 J9 PHYS MED BIOL JI Phys. Med. Biol. PD NOV 7 PY 2005 VL 50 IS 21 BP 5127 EP 5139 DI 10.1088/0031-9155/50/21/012 PG 13 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 991EJ UT WOS:000233794800012 PM 16237245 ER PT J AU Rosen, JB Breman, JG Manclark, CR Meade, BD Collins, WE Lobel, HO Saliou, P Roberts, JM Campaore, P Miller, MA AF Rosen, JB Breman, JG Manclark, CR Meade, BD Collins, WE Lobel, HO Saliou, P Roberts, JM Campaore, P Miller, MA TI Malaria chemoprophylaxis and the serologic response to measles and diphtheria-tetanus-whole-cell pertussis vaccines SO MALARIA JOURNAL LA English DT Article ID PLACEBO-CONTROLLED TRIAL; MENINGOCOCCAL POLYSACCHARIDE VACCINE; STANDARDIZED VIRAL HEMAGGLUTINATION; PLASMODIUM-FALCIPARUM MALARIA; IMMUNE-RESPONSE; ANTIBODY-RESPONSE; INTERMITTENT TREATMENT; AUTOIMMUNE-DISEASE; TANZANIAN INFANTS; GAMBIAN CHILDREN AB Background: Acute malaria has been associated with a decreased antibody response to tetanus and diphtheria toxoids, meningococcal, salmonella, and Hib vaccines. Interest in giving malaria drug therapy and prevention at the time of childhood immunizations has increased greatly following recent trials of intermittent preventive therapy during infancy (IPTi), stimulating this re-analysis of unpublished data. The effect of malaria chemoprophylaxis on vaccine response was studied following administration of measles vaccines and diphtheria-tetanus-whole cell pertussis (DTP) vaccines. Methods: In 1975, six villages divided into two groups of children = 74 months of age from Burkina Faso, were assigned to receive amodiaquine hydrochloride chemoprophylaxis (CH+) every two weeks for seven months or no chemoprophylaxis (CH-). After five months, children in each group received either one dose of measles or two doses of DTP vaccines. Results: For recipients of the measles vaccine, the seroconversion rates in CH+ and CH- children, respectively, were 93% and 96% (P > 0.05). The seroresponse rates in CH+ and CH- children respectively, were 73% and 86% for diphtheria (P > 0.05) and 77% and 91% for tetanus toxoid (P > 0.05). In a subset analysis, in which only children who strictly adhered to chemoprophylaxis criteria were included, there were, likewise, no significant differences in seroconversion or seroresponse for measles, diphtheria, or tetanus vaccines (P > 0.05). While analysis for pertussis showed a 43% (CH+) and 67% (CH-) response (P < 0.05), analyses using logistic regression to control for sex, age, chemoprophylaxis, weight-for-height Z-score, and pre-vaccination geometric mean titer (GMT), demonstrated that chemoprophylaxis was not associated with a significantly different conversion rate following DTP and measles vaccines. Seven months of chemoprophylaxis decreased significantly the malaria IFA and ELISA GMTs in the CH+ group. Conclusion: Malaria chemoprophylaxis prior to vaccination in malaria endemic settings did not improve or impair immunogenicity of DTP and measles vaccines. This is the first human study to look at the association between malaria chemoprophylaxis and the serologic response to whole-cell pertussis vaccine. C1 NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Program, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod Allergen & Parasit Prod, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Soc Pathol Exot, Paris, France. RP Rosen, JB (reprint author), NIH, Div Int Epidemiol & Populat Studies, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM jennifer.rosen@uhmc.sunysb.edu; bremanj@ficod.fic.nih.gov; crm@manclark.com; meade@cber.FDA.gov; wec1@cdc.gov; lobel@hargray.com; psaliou@pasteur.fr; JMR1@CDC.GOV; traoreap@hotmail.com; millemar@mail.nih.gov NR 60 TC 8 Z9 8 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD NOV 6 PY 2005 VL 4 AR 53 DI 10.1186/1475-2875-4-53 PG 9 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 992QN UT WOS:000233899000001 PM 16271153 ER PT J AU Bacanu, SA Bulik, CM Klump, K Fichter, MM Halmi, KA Keel, P Kaplan, AS Mitchell, JE Rotondo, A Strober, M Treasure, J Woodside, DB Sonpar, VA Xie, WT Bergen, AW Berrettini, WH Kaye, WH Devlin, B AF Bacanu, SA Bulik, CM Klump, K Fichter, MM Halmi, KA Keel, P Kaplan, AS Mitchell, JE Rotondo, A Strober, M Treasure, J Woodside, DB Sonpar, VA Xie, WT Bergen, AW Berrettini, WH Kaye, WH Devlin, B TI Linkage analysis of anorexia and bulimia nervosa cohorts using selected behavioral phenotypes as quantitative traits or covariates SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE complex disease; endophenotype; liability; mixture model; regression ID SAMPLE DESCRIPTION; EATING-DISORDERS; PERSONALITY; OBESITY; LOCUS; CHROMOSOME-10; TEMPERAMENT; CHARACTER; WOMEN; PAIRS AB To increase the likelihood of finding genetic variation conferring liability to eating disorders, we measured over 100 attributes thought to be related to liability to eating disorders on affected individuals from multiplex families and two cohorts: one recruited through a proband with anorexia nervosa (AN; AN cohort); the other recruited through a proband with bulimia nervosa (BN; BN cohort). By a multilayer decision process based on expert evaluation and statistical analysis, six traits were selected for linkage analysis (1): obsessionality (OBS), age at menarche (MENAR), and anxiety (ANX) for quantitative trait locus (QTL) linkage analysis; and lifetime minimum body mass index (BMI), concern over mistakes (CM), and food-related obsessions (OBF) for covariate-based linkage analysis. The BN cohort produced the largest linkage signals: for QTL linkage analysis, four suggestive signals: (for MENAR, at 10p13; for ANX, at 1q31.1, 4q35.2, and 8q13.1); for covariate-based linkage analyses, both significant and suggestive linkages (for BMI, one significant [4q21.1] and three suggestive [3p23, 10p13, 5p15.31; for CM, two significant [16p13.3, 14q21.1] and three suggestive [4p15.33, 8q11.23, 10p11.21]; and for OBF, one significant [14q21.1] and five suggestive [4p16.1, 10p13.1, 8q11.23, 16p13.3, 18p11.31]). Results from the AN cohort were far less compelling: for QTL linkage analysis, two suggestive signals (for OBS at 6q21 and for ANX at 9p21.3); for covariate-based linkage analysis, five suggestive signals (for BMI at 4q13.1, for CM at 11p11.2 and 17q25.1, and for OBF at 17q25.1 and 15q26.2). Overlap between the two cohorts was minimal for substantial linkage signals. (c) 2005 Wiley-Liss, Inc. C1 Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. Univ Munich, Klin Roseneck, Hosp Behav Med, Prien Am Chiemsee, Germany. Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, White Plains, NY USA. Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. Toronto Gen Hosp, Program Eating Disorders, Toronto, ON, Canada. Toronto Gen Hosp, Dept Psychiat, Toronto, ON, Canada. Neuropsychiat Res Inst, Fargo, ND USA. Dept Psychiat Neurobiol Pharmacol & Biotechnol, Pisa, Italy. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. S London & Maudsley Natl Hlth Serv Trust, London, England. Inst Psychiat, Eating Disorders Unit, London, England. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Penn, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. RP Kaye, WH (reprint author), Univ Pittsburgh, Dept Psychiat, 3811 Ohara St, Pittsburgh, PA 15213 USA. EM whkaye@upmc.edu; devlinbj@upmc.edu OI Bergen, Andrew/0000-0002-1237-7644; Treasure, Janet/0000-0003-0871-4596 FU NIMH NIH HHS [R01 MH057881, R01 MH057881-10, R01 MH066117, R37 MH057881] NR 31 TC 44 Z9 44 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD NOV 5 PY 2005 VL 139B IS 1 BP 61 EP 68 DI 10.1002/ajmg.b.30226 PG 8 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 979PY UT WOS:000232958500014 PM 16152574 ER PT J AU Bulik, CM Bacanu, SA Klump, KL Fichter, MM Haimi, KA Keel, P Kaplan, AS Mitchell, JE Rotondo, A Strober, M Treasure, J Woodside, DB Sonpar, VA Xie, WT Bergen, AW Berrettini, WH Kaye, WH Devlin, B AF Bulik, CM Bacanu, SA Klump, KL Fichter, MM Haimi, KA Keel, P Kaplan, AS Mitchell, JE Rotondo, A Strober, M Treasure, J Woodside, DB Sonpar, VA Xie, WT Bergen, AW Berrettini, WH Kaye, WH Devlin, B TI Selection of eating-disorder phenotypes for linkage analysis SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE complex disease; endophenotype; liability; clinical judgment; covariate selection; mixture model; regression ID AFFECTED SIBLING PAIRS; ANOREXIA-NERVOSA; BULIMIA-NERVOSA; ANXIETY DISORDERS; SAMPLE DESCRIPTION; PERFECTIONISM; WOMEN; LOCI; TWIN; COMORBIDITY AB Vulnerability to anorexia nervosa (AN) and bulimia nervosa (BN) arise from the interplay of genetic and environmental factors. To explore the genetic contribution, we measured over 100 psychiatric, personality, and temperament phenotypes of individuals with eating disorders from 154 multiplex families accessed through an AN proband (AN cohort) and 244 multiplex families accessed through a BN proband (BN cohort). To select a parsimonious subset of these attributes for linkage analysis, we subjected the variables to a multilayer decision process based on expert evaluation and statistical analysis. Criteria for trait choice included relevance to eating disorders pathology, published evidence for heritability, and results from our data. Based on these criteria, we chose six traits to analyze for linkage. Obsessionality, Age-at-Menarche, and a composite Anxiety measure displayed features of heritable quantitative traits, such as normal distribution and familial correlation, and thus appeared ideal for quantitative trait locus (QTL) linkage analysis. By contrast, some families showed highly concordant and extreme values for three variables-lifetime minimum Body Mass Index (lowest BMI attained during the course of illness), concern over mistakes, and food-related obsessions-whereas others did not. These distributions are consistent with a mixture of populations, and thus the variables were matched with covariate linkage analysis. Linkage results appear in a subsequent report. Our report lays out a systematic roadmap, for utilizing a rich set of phenotypes for genetic analyses, including the selection of linkage methods paired to those phenotypes. (c) 2005 Wiley-Liss, Inc. C1 Univ Pittsburgh, Dept Psychiat, Pittsburgh, PA 15213 USA. Univ N Carolina, Dept Psychiat, Chapel Hill, NC USA. Michigan State Univ, Dept Psychol, E Lansing, MI 48824 USA. Univ Munich, Klin Roseneck, Hosp Behav Med, Prien Am Chiemsee, Germany. Cornell Univ, Weill Med Coll, New York Presbyterian Hosp, White Plains, NY USA. Univ Iowa, Dept Psychol, Iowa City, IA 52242 USA. Toronto Gen Hosp, Program Eating Disorders, Toronto, ON, Canada. Toronto Gen Hosp, Dept Psychiat, Toronto, ON, Canada. Neuropsychiat Res Inst, Fargo, ND USA. Univ Pisa, Dept Psychiat Neurobiol Pharmacol & Biotechnol, Pisa, Italy. Univ Calif Los Angeles, Dept Psychiat & Behav Sci, Los Angeles, CA 90024 USA. S London & Maudsley Natl Hlth Serv Trust, London, England. Inst Psychiat, Eating Disorders Unit, London, England. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Penn, Ctr Neurobiol & Behav, Philadelphia, PA 19104 USA. RP Kaye, WH (reprint author), Univ Pittsburgh, Dept Psychiat, 3811 Ohara St, Pittsburgh, PA 15213 USA. EM kayewh@upmc.edu; devlinbj@upmc.edu OI Bergen, Andrew/0000-0002-1237-7644; Treasure, Janet/0000-0003-0871-4596 FU NIMH NIH HHS [R01 MH066117, R01 MH057881, R01 MH057881-10, R37 MH057881] NR 42 TC 22 Z9 22 U1 2 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD NOV 5 PY 2005 VL 139B IS 1 BP 81 EP 87 DI 10.1002/ajmg.b.30227 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 979PY UT WOS:000232958500017 PM 16152575 ER PT J AU Chapman, RS He, XZ Blair, AE Lan, Q AF Chapman, RS He, XZ Blair, AE Lan, Q TI Improvement in household stoves and risk of chronic obstructive pulmonary disease in Xuanwei, China: retrospective cohort study SO BRITISH MEDICAL JOURNAL LA English DT Article ID INDOOR AIR-POLLUTION; LUNG-CANCER; DEVELOPING-COUNTRIES; CHRONIC-BRONCHITIS; GLOBAL BURDEN; EXPOSURE; MORTALITY; SMOKING; COMBUSTION; WOMEN AB Objective To test whether improvement in household coal stoves affected the incidence of chronic obstructive pulmonary disease (COPD) in Xuanwei County, China. Design Retrospective cohort study (follow-up 1976-92) comparing incidence of COPD between groups with and without chimneys. Participants 20 453 people born into homes with unvented coal stoves; 16 606 (81.2%) subsequently changed to stoves with chimneys. Intervention Installation of a chimney in households in which unvented stoves had been used previously. Results Installation of a chimney was associated with distinct reduction in the incidence of COPD. Compared with people who did not have chimneys, the Cox-modelled risk ratio (relative risk) was 0.58 (95% confidence interval 0.49 to 0.70, P < 0.001) in men and 0.75 (0.62 to 0.92, P = 0.005) in women. Modelled risk ratios were robust to different Cox model specifications. Relative risks decreased with time since stove improvement. In both sexes, the reduction in risk became unequivocal about 10 years after stove improvement. Conclusions In Xuanwei, incidence of COPD decreased markedly after household coal stoves were improved. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Chulalongkorn Univ, Coll Publ Hlth, Bangkok 10330, Thailand. Chinese Acad Prevent Med, Inst Environm Hlth & Engn, Beijing 100050, Peoples R China. RP Lan, Q (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, MSC 7240,6120 Execut Blvd,EPS 8111, Bethesda, MD 20892 USA. EM qingl@mail.nih.gov FU Intramural NIH HHS NR 24 TC 92 Z9 98 U1 0 U2 5 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD NOV 5 PY 2005 VL 331 IS 7524 BP 1050 EP 1052A DI 10.1136/bmj.38628.676088.55 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 983DL UT WOS:000233211200018 PM 16234255 ER PT J AU Ronckers, CM Land, CE Neglia, JP Meadows, AT AF Ronckers, CM Land, CE Neglia, JP Meadows, AT TI Breast cancer SO LANCET LA English DT Letter C1 NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. Univ Minnesota, Sch Med, Dept Pediat, Minneapolis, MN 55455 USA. Childrens Hosp Philadelphia, Dept Pediat, Div Oncol, Philadelphia, PA 19104 USA. RP Ronckers, CM (reprint author), NCI, Radiat Epidemiol Branch, Bethesda, MD 20892 USA. EM ronckerc@mail.nih.gov RI Boyle, Peter/A-4380-2014 OI Boyle, Peter/0000-0001-6251-0610 NR 4 TC 1 Z9 1 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD NOV 5 PY 2005 VL 366 IS 9497 BP 1605 EP 1606 DI 10.1016/S0140-6736(05)67657-X PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 980VU UT WOS:000233047100019 PM 16271638 ER PT J AU Chi, BH Wang, L Read, JS Sheriff, M Fiscus, S Brown, ER Taha, TE Valentine, M Goldenberg, R AF Chi, BH Wang, L Read, JS Sheriff, M Fiscus, S Brown, ER Taha, TE Valentine, M Goldenberg, R TI Timing of maternal and neonatal dosing of nevirapine and the risk of mother-to-child transmission of HIV-1: HIVNET 024 SO AIDS LA English DT Article DE prevention of mother-to-child transmission of HIV-1; mother-to-child transmission; sub-Saharan Africa; nevirapine; HIVNET 024; dose timing ID SINGLE-DOSE NEVIRAPINE; RANDOMIZED CONTROLLED-TRIAL; PREGNANT-WOMEN; INTRAPARTUM; ZIDOVUDINE; PREVENTION; PHARMACOKINETICS; PROGRAM; RESISTANCE; LAMIVUDINE AB Objective: Despite a growing emphasis worldwide on complex and potent antiretroviral drug regimens for the prevention of mother-to-child transmission of HIV-1 (MTCT), two-dose nevirapine (NVP) prophylaxis remains an important choice in many settings. We analyzed data from a multicenter clinical trial to determine whether timing of maternal or infant NVP was associated with MTCT between delivery and 6 weeks of age (intrapartum/early postnatal transmission; I/EP). Methods: HIVNET 024 was a placebo-controlled, double-blind trial of empiric antibiotics to reduce chorioamnionitis-associated MTCT. This secondary analysis used data collected in the original randomized trial. Enrolled women were instructed to self-administer NVP at labor onset; infants were to receive a dose within 72 h of birth. Results: Data regarding 1491 mother-infant pairs were analyzed. The overall I/EP HIV-1 transmission rate was 8.1 % at 6 weeks. Almost all women (93%) ingested NVP within 24 h of delivery; 90% of infants were given NVP within 48 h after delivery. Variations in mother or infant dose timing did not influence transmission rates, even when the combined pattern of both was taken into account through multivariate analysis. In the subset of women ingesting NVP <= 2 h before delivery, early NVP administration to the infant (<4 h after birth) was not associated with lower MTCT risk when compared with later administration (>= 4 h). Conclusion: Variations in the timing of maternal and infant NVP doses (within reasonable proximity to delivery) do not appear to affect the risk of MTCT. (c) 2005 Lippincott Williams & Wilkins. C1 Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35294 USA. Ctr Infect Dis Res, Lusaka, Zambia. SCHARP, Seattle, WA USA. NICHHD, NIH, Bethesda, MD 20892 USA. MUCHS Harvard Res Collaborat, Dar Es Salaam, Tanzania. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. Family Hlth Int, Durham, NC USA. RP Chi, BH (reprint author), Box 34681,5977 Benakale Rd, Lusaka, Zambia. EM bchi@cidrz.org RI Brown, Elizabeth/A-8984-2008 FU NIAID NIH HHS [U01-AI-47972, U01-AI-48005, N01-AI-35173, U01-AI-480006, N01-AI-45200, N01-AI-35173-117/412] NR 23 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0269-9370 J9 AIDS JI Aids PD NOV 4 PY 2005 VL 19 IS 16 BP 1857 EP 1864 DI 10.1097/01.aids.0000189863.82429.2f PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 982PO UT WOS:000233174300015 PM 16227794 ER PT J AU Gandhi, M Ameli, N Bacchetti, P Sharp, GB French, AL Young, M Gange, SJ Anastos, K Holman, S Levine, A Greenblatt, RM AF Gandhi, M Ameli, N Bacchetti, P Sharp, GB French, AL Young, M Gange, SJ Anastos, K Holman, S Levine, A Greenblatt, RM TI Eligibility criteria for HIV clinical trials and generalizability of results: the gap between published reports and study protocols SO AIDS LA English DT Article DE HIV; clinical trials; eligibility criteria; protocols; publications; generalizability ID HUMAN-IMMUNODEFICIENCY-VIRUS; RANDOMIZED CONTROLLED-TRIALS; PLACEBO-CONTROLLED TRIAL; AVIUM COMPLEX DISEASE; ANTIRETROVIRAL THERAPY; INFECTED PATIENTS; CUBIC MILLIMETER; AIDS; ZIDOVUDINE; EFFICACY AB Objective: Applicability of randomized controlled clinical trial (RCT) results to 'real world' situations is dependent on the comparability of trial participants to general patient populations. A full disclosure of criteria employed for trial enrollment is necessary for clinicians to assess generalizability. We sought to assess both the impact on generalizability and the disclosure rate of enrollment criteria for 32 major HIV RCTs in the AIDS Clinical Trial Group (ACTG) and Community Programs for Clinical Research on AIDS (CPCRA) trial networks. Design and methods: Eligibility criteria were compared in complete protocols to criteria listed in publications from these 32 NIH-funded HIV RCTs. We then applied these criteria to the Women's Interagency HIV Study (WIHS), the largest cohort study of HIV-infected women in the US. Results: When applied to WIHS, eligibility criteria from protocols excluded 0-67.6% (median 42%) of WIHS participants (50.6% excluded from ACTG trials). Eligibility criteria in publications excluded 0-62% (median 19.6%) of WIHS (21.2% excluded from ACTC, trials). The number of women in WIHS seemingly ineligible for trial participation per enrollment criteria listed in publications averaged only 60% of those actually excluded based on the protocols. Conclusions: We found that HIV RCT eligibility criteria excluded a large proportion of a representative cohort of HIV-infected women from trial participation. Furthermore, trial publications are not fully reflective of protocols in terms of disclosing eligibility criteria. Standardization and full disclosure of trial methodology will allow clinicians and researchers to more fully assess the generalizability of findings to their patient populations. (c) 2005 Lippincott Williams & Wilkins. C1 Univ Calif San Francisco, Div Infect Dis, Dept Med, San Francisco, CA 94122 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94122 USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Rush Med Coll, Cook Cty Hosp, CORE Ctr, Chicago, IL 60612 USA. Georgetown Univ, Dept Med, Washington, DC 20007 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Lincoln Med & Mental Hlth Ctr, Bronx, NY 10451 USA. SUNY Brooklyn, Dept Prevent Med & Community Hlth, Brooklyn, NY USA. Univ So Calif, Dept Med, Los Angeles, CA USA. RP Gandhi, M (reprint author), Univ Calif San Francisco, Div Infect Dis, Dept Med, 405 Irving St,2nd Floor, San Francisco, CA 94122 USA. EM monica.gandhi@ucsf.edu OI Gange, Stephen/0000-0001-7842-512X FU NCRR NIH HHS [MO1-RR-00071, MO1-RR-00079, MO1-RR-00083]; NIAID NIH HHS [UO1-AI-42590, UO1-AI-31834, UO1-AI-34989, UO1-AI-34993, UO1-AI-34994, UO1-AI-35004]; NIAMS NIH HHS [K12 AR47659]; OID CDC HHS [UO1-CH-32632] NR 71 TC 48 Z9 48 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 EI 1473-5571 J9 AIDS JI Aids PD NOV 4 PY 2005 VL 19 IS 16 BP 1885 EP 1896 DI 10.1097/01.aids.0000189866.67182.f7 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 982PO UT WOS:000233174300018 PM 16227797 ER PT J AU Chernomordik, LV Kozlov, MM AF Chernomordik, LV Kozlov, MM TI Membrane hemifusion: Crossing a chasm in two leaps SO CELL LA English DT Review ID INFLUENZA HEMAGGLUTININ; FUSION PROTEIN; PORE FORMATION; BIOLOGICAL-MEMBRANES; BILAYER-MEMBRANES; PHASE-FORMATION; 6-HELIX BUNDLE; VIRUS TYPE-1; STALK MODEL; CLASS-I AB During membrane fusion, the outer leaflets of the two membranes merge first, whereas the distal membrane leaflets remain separate until the opening of a fusion pore. This intermediate stage, called hemifusion, is a critical event shared by exocytosis, protein trafficking, and viral entry. C1 NICHHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, Sect Membrane Biol,NIH, Bethesda, MD 20892 USA. Tel Aviv Univ, Sackler Fac Med, Dept Physiol & Pharmacol, IL-69978 Tel Aviv, Israel. RP Chernomordik, LV (reprint author), NICHHD, Sect Membrane Biol, Lab Cellular & Mol Biophys, Sect Membrane Biol,NIH, Bethesda, MD 20892 USA. EM chernoml@mail.nih.gov; michk@post.tau.ac.il FU Intramural NIH HHS NR 52 TC 197 Z9 205 U1 2 U2 27 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD NOV 4 PY 2005 VL 123 IS 3 BP 375 EP 382 DI 10.1016/j.cell.2005.10.015 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 983WY UT WOS:000233264300007 PM 16269330 ER PT J AU Valeva, A Walev, I Kemmer, H Weis, S Siegel, I Boukhallouk, F Wassenaar, TM Chavakis, T Bhakdi, S AF Valeva, A Walev, I Kemmer, H Weis, S Siegel, I Boukhallouk, F Wassenaar, TM Chavakis, T Bhakdi, S TI Binding of Escherichia coli hemolysin and activation of the target cells is not receptor-dependent SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HUMAN NEUTROPHILS; ALPHA-HEMOLYSIN; RESPIRATORY BURST; RTX TOXINS; MEMBRANES; ACYLATION; INTEGRIN; ERYTHROCYTES; ASSOCIATION; INSERTION AB Production of a single cysteine substitution mutant, S177C, allowed Escherichia coli hemolysin ( HlyA) to be radioactively labeled with tritiated N-ethylmaleimide without affecting biological activity. It thus became possible to study the binding characteristics of HlyA as well as of toxin mutants in which one or both acylation sites were deleted. All toxins bound to erythrocytes and granulocytes in a nonsaturable manner. Only wild-type toxin and the lytic monoacylated mutant stimulated production of superoxide anions in granulocytes. An oxidative burst coincided with elevation of intracellular Ca2+, which was likely because of passive influx of Ca2+ through the toxin pores. Competition experiments showed that binding to the cells was receptor-independent, and preloading of cells with a nonlytic HlyA mutant did not abrogate the respiratory burst provoked by a subsequent application of wild-type HlyA. In contrast to a previous report, expression or activation of the beta(2) integrin lymphocyte function-associated antigen-1 did not affect binding of HlyA. We conclude that HlyA binds nonspecifically to target cells and a receptor is involved neither in causing hemolysis nor in triggering cellular reactions. C1 Univ Mainz, Inst Med Microbiol & Hyg, D-55101 Mainz, Germany. Mol Microbiol & Genom Consultants, D-55576 Zotzenheim, Germany. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Valeva, A (reprint author), Univ Mainz, Inst Med Microbiol & Hyg, Hochhaus Augustuspl, D-55101 Mainz, Germany. EM avaleva@uni-mainz.de FU Intramural NIH HHS NR 28 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 NOV 4 PY 2005 VL 280 IS 44 BP 36657 EP 36663 DI 10.1074/jbc.M507690200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 978VT UT WOS:000232901800017 PM 16131494 ER PT J AU Ray, K Tisdale, J Dodd, RH Dauban, P Ruat, M Northup, JK AF Ray, K Tisdale, J Dodd, RH Dauban, P Ruat, M Northup, JK TI Calindol, a positive allosteric modulator of the human Ca2+ receptor, activates an extracellular ligand-binding domain-deleted rhodopsin-like seven-transmembrane structure in the absence of Ca2+ SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID METABOTROPIC GLUTAMATE-RECEPTOR; CALCIUM-SENSING RECEPTOR; CELL-SURFACE EXPRESSION; PROTEIN-COUPLED RECEPTORS; TRANSMEMBRANE DOMAIN; GABA(B) RECEPTOR; CA2+-SENSING RECEPTOR; CALCIMIMETIC COMPOUND; HEPTAHELICAL DOMAIN; SIGNAL-TRANSDUCTION AB The extracellular calcium-sensing human Ca2+ receptor (hCaR),(2) a member of the family-3 G-protein-coupled receptors ( GPCR) possesses a large amino-terminal extracellular ligand-binding domain (ECD) in addition to a seven-transmembrane helical domain (7TMD) characteristic of all GPCRs. Two calcimimetic allosteric modulators, NPS R- 568 and Calindol (( R)- 2-{1-(1-naphthyl) ethylaminomethyl} indole), that bind the 7TMD of the hCaR have been reported to potentiate Ca2+ activation without independently activating the wild type receptor. Because agonists activate rhodopsin-like family-1 GPCRs by binding within the 7TMD, we examined the ability of Calindol, a novel chemically distinct calcimimetic, to activate a Ca2+ receptor construct (T903-Rhoc) in which the ECD and carboxyl-terminal tail have been deleted to produce a rhodopsin-like 7TMD. Here we report that although Calindol has little or no agonist activity in the absence of extracellular Ca2+ for the ECD-containing wild type or carboxyl-terminal deleted receptors, it acts as a strong agonist of the T903-Rhoc. In addition, Ca2+ alone displays little or no agonist activity for the hCaR 7TMD, but potentiates the activation by Calindol. We confirm that the activation of T903-Rhoc by Calindol is truly Ca2+ independent using in vitro reconstitution with purified G(q). These findings demonstrate distinct allosteric linkages between Ca2+ site(s) in the ECD and 7TMD and the 7TMD site( s) for calcimimetics. C1 NIDCD, Lab Cellular Biol, NIH, Bethesda, MD 20892 USA. CNRS, UPR 9040, Signal Transduct & Dev Neuropharmacol, F-91198 Gif Sur Yvette, France. CNRS, IFR 2118, Inst Neurobiol Alfred Fessard, F-91198 Gif Sur Yvette, France. CNRS, UPR 2301, Inst Chim Subst Nat, F-91198 Gif Sur Yvette, France. RP Ray, K (reprint author), 5 Res Ct,Rm 2A11, Rockville, MD 20850 USA. EM rayk@nidcd.nih.gov RI Ruat, Martial/E-5544-2016 FU Intramural NIH HHS NR 35 TC 38 Z9 38 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 NOV 4 PY 2005 VL 280 IS 44 BP 37013 EP 37020 DI 10.1074/jbc.M506681200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 978VT UT WOS:000232901800059 PM 16135510 ER PT J AU Maceyka, M Sankala, H Hait, NC Le Stunff, H Liu, H Toman, R Collier, C Zhang, M Satin, LS Merrill, AH Milstien, S Spiegel, S AF Maceyka, M Sankala, H Hait, NC Le Stunff, H Liu, H Toman, R Collier, C Zhang, M Satin, LS Merrill, AH Milstien, S Spiegel, S TI SphK1 and SphK2, sphingosine kinase isoenzymes with opposing functions in sphingolipid metabolism SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CERAMIDE-INDUCED APOPTOSIS; PROTEIN-COUPLED RECEPTORS; ENDOPLASMIC-RETICULUM; GROWTH-FACTOR; SPHINGOSINE-1-PHOSPHATE PHOSPHOHYDROLASE; SACCHAROMYCES-CEREVISIAE; MOLECULAR-CLONING; KEY REGULATOR; CELL-DEATH; CA2+ AB The potent sphingolipid metabolite sphingosine 1-phosphate is produced by phosphorylation of sphingosine catalyzed by sphingosine kinase (SphK) types 1 and 2. In contrast to pro-survival SphK1, the putative BH3-only protein SphK2 inhibits cell growth and enhances apoptosis. Here we show that SphK2 catalytic activity also contributes to its ability to induce apoptosis. Overexpressed SphK2 also increased cytosolic free calcium induced by serum starvation. Transfer of calcium to mitochondria was required for SphK2-induced apoptosis, as cell death and cytochrome c release was abrogated by inhibition of the mitochondrial Ca2+ transporter. Serum starvation increased the proportion of SphK2 in the endoplasmic reticulum and targeting SphK1 to the endoplasmic reticulum converted it from anti-apoptotic to pro-apoptotic. Overexpression of SphK2 increased incorporation of [H-3] palmitate, a substrate for both serine palmitoyltransferase and ceramide synthase, into C16-ceramide, whereas SphK1 decreased it. Electrospray ionization-mass spectrometry/mass spectrometry also revealed an opposite effect on ceramide mass levels. Importantly, specific down-regulation of SphK2 reduced conversion of sphingosine to ceramide in the recycling pathway and conversely, down-regulation of SphK1 increased it. Our results demonstrate that SphK1 and SphK2 have opposing roles in the regulation of ceramide biosynthesis and suggest that the location of sphingosine 1-phosphate production dictates its functions. C1 Virginia Commonwealth Univ, Sch Med, Dept Biochem, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Sch Med, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. Georgia Inst Technol, Sch Biol, Atlanta, GA 30332 USA. NIH, Lab Cellular & Mol Regulat, Bethesda, MD 20892 USA. RP Spiegel, S (reprint author), 1101 E Marshall St, Richmond, VA 23298 USA. EM sspiegel@vcu.edu RI Maceyka, Michael/B-9277-2008 FU NCI NIH HHS [R01CA61774, P30 CA16059]; NIDDK NIH HHS [R01DK46409]; NIGMS NIH HHS [GM069338] NR 71 TC 278 Z9 289 U1 1 U2 14 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 NOV 4 PY 2005 VL 280 IS 44 BP 37118 EP 37129 DI 10.1074/jbc.M502207200 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 978VT UT WOS:000232901800070 PM 16118219 ER PT J AU Burgess, BR Schuck, P Garboczi, DN AF Burgess, BR Schuck, P Garboczi, DN TI Dissection of merozoite surface protein 3, a representative of a family of Plasmodium falciparum surface proteins, reveals an oligomeric and highly elongated molecule SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SECONDARY STRUCTURE PREDICTION; SIZE-DISTRIBUTION ANALYSIS; ANALYTICAL ULTRACENTRIFUGATION; CIRCULAR-DICHROISM; SEDIMENTATION; MALARIA; ANTIGEN; DOMAIN; MACROMOLECULES; CONSERVATION AB Vaccination with the merozoite surface protein 3 (MSP3) of Plasmodium falciparum protects against infection in primates and is under development as a vaccine against malaria in humans. MSP3 is secreted and associates with the parasite membrane but lacks a predicted transmembrane domain or a glycosylphosphatidylinositol anchor. Its role in the invasion of red blood cells is unclear. To study MSP3, we produced recombinant full-length protein and found by size exclusion chromatography that the apparent size of MSP3 was much larger than predicted from its sequence. To investigate this, we used several biophysical techniques to characterize the full-length molecule and four smaller polypeptides. The MSP3 polypeptides contain a large amount of alpha-helix and random coil secondary structure as measured by circular dichroism spectroscopy. The full-length MSP3 forms highly elongated dimers and tetramers as revealed by chemical cross-linking and analytical ultracentrifugation. The dimer is formed through a leucine zipper-like domain located between residues 306 and 362 at the C terminus. Two dimers interact through their C termini to form a tetramer with an apparent association constant of 3 mu M. Sedimentation velocity experiments determined that the MSP3 molecules are highly extended in solution (some with f/f(0)>2). These data, in light of the recent discoveries of three other Plasmodium proteins containing very similar C-terminal sequences, suggest that the members of this newly identified family may adopt highly extended and oligomeric novel structures capable of interacting with a red blood cell at relatively long distances. C1 NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NIH, Div Bioengn & Phys Sci, Off Director, Off Res Serv,NIH, Bethesda, MD 20892 USA. RP Garboczi, DN (reprint author), NIAID, Struct Biol Sect, Immunogenet Lab, NIH, Twinbrook 2,12441 Parklawn Dr, Rockville, MD 20852 USA. EM dgarboczi@niaid.nih.gov OI Schuck, Peter/0000-0002-8859-6966 FU Intramural NIH HHS NR 40 TC 29 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 NOV 4 PY 2005 VL 280 IS 44 BP 37236 EP 37245 DI 10.1074/jbc.M506753200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 978VT UT WOS:000232901800082 PM 16135515 ER PT J AU Buchete, NV Tycko, R Hummer, G AF Buchete, NV Tycko, R Hummer, G TI Molecular dynamics simulations of Alzheimer's beta-amyloid protofilaments SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE amyloid fibrils; molecular dynamics; Alzheimer's disease; fibril structure; molecular hydration ID SOLID-STATE NMR; NUCLEAR-MAGNETIC-RESONANCE; PROTEIN-STRUCTURE; FIBRIL FORMATION; SUPRAMOLECULAR STRUCTURE; POTENTIAL FUNCTIONS; ACCESSIBLE SURFACE; HYDROGEN-EXCHANGE; STRUCTURAL MODEL; CORE STRUCTURE AB Filamentous amyloid aggregates are central to the pathology of Alzheimer's disease. We use all-atom molecular dynamics (MD) simulations with explicit solvent and multiple force fields to probe the structural stability and the conformational dynamics of several models of Alzheimer's beta-amyloid fibril structures, for both wild-type and mutated amino acid sequences. The structural models are based on recent solid state NMR data. In these models, the peptides form in-register parallel P-sheets along the fibril axis, with dimers of two U-shaped peptides located in layers normal to the fibril axis. Four different topologies are explored for stacking the beta-strand regions against each other to form a hydrophobic core. Our MD results suggest that all four NMR-based models are structurally stable, and we find good agreement with dihedral angles estimated from solid-state NMR experiments. Asp23 and Lys28 form buried salt-bridges, resulting in an alternating arrangement of the negatively and positively charged residues along the fibril axis that is reminiscent of a one-dimensional ionic crystal. Interior water molecules are solvating the buried salt-bridges. Based on data from NMR measurements and MD simulations of short amyloid fibrils, we constructed structural models of long fibrils. Calculated X-ray fiber diffraction patterns show the characteristics of packed P-sheets seen in experiments, and suggest new experiments that could discriminate between various fibril topologies. Published by Elsevier Ltd. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. EM gerhard.hummer@nih.gov RI Hummer, Gerhard/A-2546-2013; Buchete, Nicolae-Viorel/C-6200-2015 OI Hummer, Gerhard/0000-0001-7768-746X; Buchete, Nicolae-Viorel/0000-0001-9861-1157 FU Intramural NIH HHS NR 84 TC 181 Z9 185 U1 2 U2 57 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 NOV 4 PY 2005 VL 353 IS 4 BP 804 EP 821 DI 10.1016/j.jmb.2005.08.066 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 980LR UT WOS:000233020500004 PM 16213524 ER PT J AU Bullock, TH Bennett, MVL Johnston, D Josephson, R Marder, E Fields, RD AF Bullock, TH Bennett, MVL Johnston, D Josephson, R Marder, E Fields, RD TI The Neuron Doctrine, redux SO SCIENCE LA English DT Editorial Material ID ACTION-POTENTIALS; CELLS; BRAIN; DENDRITES; SYNAPSES; TRIGGERS; DYNAMICS C1 Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 USA. Univ Texas, Ctr Learning & Memory, Austin, TX 78712 USA. Univ Calif Irvine, Dept Neurobiol & Behav, Irvine, CA 92697 USA. Brandeis Univ, Dept Biol, Waltham, MA 02454 USA. NICHHD, Nervous Syst Dev & Plast Sect, Bethesda, MD 20892 USA. RP Bullock, TH (reprint author), Univ Calif San Diego, Scripps Inst Oceanog, La Jolla, CA 92093 USA. EM fieldsd@mail.nih.gov NR 24 TC 69 Z9 71 U1 1 U2 16 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 NOV 4 PY 2005 VL 310 IS 5749 BP 791 EP 793 DI 10.1126/science.1114394 PG 3 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 981XR UT WOS:000233121800026 PM 16272104 ER PT J AU Cui, XL Zhang, JH Ma, PL Myers, DE Goldberg, IG Sittler, KJ Barb, JJ Munson, PJ Cintron, AD McCoy, JP Wang, SB Danner, RL AF Cui, XL Zhang, JH Ma, PL Myers, DE Goldberg, IG Sittler, KJ Barb, JJ Munson, PJ Cintron, AD McCoy, JP Wang, SB Danner, RL TI cGMP-independent nitric oxide signaling and regulation of the cell cycle SO BMC GENOMICS LA English DT Article ID ACTIVATED-PROTEIN-KINASE; SMOOTH-MUSCLE-CELLS; VASCULAR ENDOTHELIAL-CELLS; TNF-ALPHA PRODUCTION; B-MYB TRANSCRIPTION; NF-KAPPA-B; MESSENGER-RNA; U937 CELLS; INTERLEUKIN-8 PRODUCTION; HUMAN NEUTROPHILS AB Background: Regulatory functions of nitric oxide (NOcenter dot) that bypass the second messenger cGMP are incompletely understood. Here, cGMP-independent effects of NOcenter dot on gene expression were globally examined in U937 cells, a human monoblastoid line that constitutively lacks soluble guanylate cyclase. Differentiated U937 cells (> 80% in G0/G1) were exposed to S-nitrosoglutathione, a NOcenter dot donor, or glutathione alone ( control) for 6 h without or with dibutyryl-cAMP (Bt(2)cAMP), and then harvested to extract total RNA for microarray analysis. Bt(2)cAMP was used to block signaling attributable to NOcenter dot-induced decreases in cAMP. Results: NOcenter dot regulated 110 transcripts that annotated disproportionately to the cell cycle and cell proliferation (47/110, 43%) and more frequently than expected contained AU-rich, post-transcriptional regulatory elements (ARE). Bt2cAMP regulated 106 genes; cell cycle gene enrichment did not reach significance. Like NOcenter dot, Bt(2)cAMP was associated with ARE-containing transcripts. A comparison of NOcenter dot and Bt(2)cAMP effects showed that NOcenter dot regulation of cell cycle genes was independent of its ability to interfere with cAMP signaling. Cell cycle genes induced by NOcenter dot annotated to G1/S (7/8) and included E2F1 and p21/ Waf1/Cip1; 6 of these 7 were E2F target genes involved in G1/S transition. Repressed genes were G2/M associated (24/27); 8 of 27 were known targets of p21. E2F1 mRNA and protein were increased by NOcenter dot, as was E2F1 binding to E2F promoter elements. NOcenter dot activated p38 MAPK, stabilizing p21 mRNA (an ARE-containing transcript) and increasing p21 protein; this increased protein binding to CDE/CHR promoter sites of p21 target genes, repressing key G2/M phase genes, and increasing the proportion of cells in G2/M. Conclusion: NOcenter dot coordinates a highly integrated program of cell cycle arrest that regulates a large number of genes, but does not require signaling through cGMP. In humans, antiproliferative effects of NOcenter dot may rely substantially on cGMP-independent mechanisms. Stress kinase signaling and alterations in mRNA stability appear to be major pathways by which NOcenter dot regulates the transcriptome. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NIH, Math & Stat Comp Lab, Div Computat Biosci, Ctr Informat Technol, Bethesda, MD 20892 USA. NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. Mil 309th Hosp, Intens Care Unit, Beijing, Peoples R China. RP Danner, RL (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM xcuia2003@yahoo.com; jzhang@mail.cc.nih.gov; plma1019@yahoo.com; rdanner@mail.nih.gov; rdanner@cc.nih.gov; ksitt001@umaryland.edu; barbj@mail.nih.gov; munson@mail.nih.gov; acintron@ora.fda.gov; mccoyjp@mail.nih.gov; swang@cc.nih.gov; rdanner@mail.nih.gov FU Intramural NIH HHS NR 87 TC 30 Z9 31 U1 3 U2 4 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 NOV 3 PY 2005 VL 6 AR 151 DI 10.1186/1471-2164-6-151 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 992OH UT WOS:000233892900001 PM 16269079 ER PT J AU Plaut, M Valentine, MD AF Plaut, M Valentine, MD TI Clinical practice - Allergic rhinitis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID PLACEBO-CONTROLLED IMMUNOTHERAPY; GRASS-POLLEN ALLERGOIDS; INTRANASAL CORTICOSTEROIDS; DOUBLE-BLIND; RECEPTOR ANTAGONISTS; BECLOMETHASONE DIPROPIONATE; PERENNIAL RHINITIS; NASAL SPRAY; ASTHMA; EFFICACY AB A Baltimore college student has rhinorrhea, sneezing, nasal congestion, and itchy, watery eyes in the spring. He reports having had similar symptoms the previous spring. Over-the-counter allergy pills have failed to help his symptoms and caused dry mouth and somnolence. He wants relief and assurance that he will not be ill, have dry mouth, or feel drowsy during final examinations. On physical examination, his conjunctivae are injected, and his nasal mucous membranes are pale, wet, and boggy. What are your recommendations? C1 NIAID, Asthma Allergy & Inflmmat Branch, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Div Allergy & Immunol, Baltimore, MD USA. RP Plaut, M (reprint author), NIAID, Asthma Allergy & Inflmmat Branch, Div Allergy Immunol & Transplantat, NIH, 6610 Rockledge Dr,Rm 3093,MSC-6601, Bethesda, MD 20892 USA. EM mplaut@niaid.nih.gov NR 58 TC 88 Z9 91 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD NOV 3 PY 2005 VL 353 IS 18 BP 1934 EP 1944 DI 10.1056/NEJMcp044141 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 979VJ UT WOS:000232972800009 PM 16267324 ER PT J AU Gupta, M Gupta, SK Balliet, AG Hollander, MC Fornace, AJ Hoffman, B Liebermann, DA AF Gupta, M Gupta, SK Balliet, AG Hollander, MC Fornace, AJ Hoffman, B Liebermann, DA TI Hematopoietic cells from Gadd45a- and Gadd45b-deficient mice are sensitized to genotoxic-stress-induced apoptosis SO ONCOGENE LA English DT Article DE gadd45-deficient mice; apoptosis; hematopoietic cells; genotoxic stress; DNA damage ID NEGATIVE GROWTH-CONTROL; P53-REGULATED PROTEIN GADD45; RESPONSE GENE MYD118; NUCLEAR ANTIGEN; DNA-REPAIR; ARREST; EXPRESSION; ACTIVATION; INDUCTION; RADIATION AB Gadd45a, gadd45b and gadd45g (Gadd45/MyD118/CR6) are genes that are rapidly induced by genotoxic stress. However, the exact function of Gadd45 proteins in the response of mammalian cells to genotoxic stress is unclear. Here, advantage was taken of gadd45a- and gadd45b-deficient mice to determine the role gadd45a- and gadd45b play in the response of bone marrow ( BM) cells to genotoxic stress. BM cells from gadd45a- and gadd45b-deficient mice were observed to be more sensitive to ultraviolet radiation chemotherapy (UVC), VP-16 and daunorubicin (DNR)-induced apoptosis compared to wildtype (wt) cells. The increased apoptosis in gadd45a- and gadd45b-deficient cells was evident also by enhanced activation of caspase-3 and poly-ADP-ribose polymerase cleavage and decreased expression of c-inhibitor of apoptotic protein-1, Bcl-2, Bcl-xL compared to wt cells. Reintroduction of gadd45 into gadd45-deficient BM cells restored the wt apoptotic phenotype. Both gadd45a- and gadd45b-deficient BM cells also displayed defective G2/M arrest following exposure to UVC and VP-16, but not to DNR, indicating the existence of different G2/M checkpoints that are either dependent or independent of gadd45. Taken together, these findings identify gadd45a and gadd45b as antiapoptotic genes that increase the survival of hematopoietic cells following exposure to UV radiation and certain anticancer drugs. C1 Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Philadelphia, PA 19140 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Liebermann, DA (reprint author), Temple Univ, Sch Med, Fels Inst Canc Res & Mol Biol, Room 331,3307 N Broad St, Philadelphia, PA 19140 USA. EM lieberma@temple.edu RI Fornace, Albert/A-7407-2008 OI Fornace, Albert/0000-0001-9695-085X FU NCI NIH HHS [R01 CA89718-02]; NHLBI NIH HHS [R01 HL 70530-01] NR 27 TC 65 Z9 71 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 NOV 3 PY 2005 VL 24 IS 48 BP 7170 EP 7179 DI 10.1038/sj.onc.1208847 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 980BY UT WOS:000232990100006 PM 16170381 ER PT J AU Tangirala, R Antony, S Agama, K Pommier, Y Curran, DP AF Tangirala, R Antony, S Agama, K Pommier, Y Curran, DP TI Total synthesis of luotonin and a small library of AB-ring substituted analogues by cascade radical annulation of isonitriles SO SYNLETT LA English DT Article DE camptothecin; topoisomerase I inhibitor; luotonin; isonitrile radical annulation ID CYTOTOXIC ALKALOID LUOTONIN; ANTITUMOR AGENTS; CAMPTOTHECIN; (+/-)-CAMPTOTHECIN; HOMOSILATECANS; PERSPECTIVES; CYCLIZATION; SILATECANS; FAMILY AB A four-step total synthesis of luotonin is deployed to make a small library of AB-ring substituted analogues. These analogues show weak activity in a standard topoisomerase I mediated DNA cleavage assay. C1 Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. NCI, Canc Res Ctr, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Curran, DP (reprint author), Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. EM curran@pitt.edu NR 38 TC 30 Z9 31 U1 2 U2 6 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0936-5214 J9 SYNLETT JI Synlett PD NOV 3 PY 2005 IS 18 BP 2843 EP 2846 DI 10.1055/s-2005-918923 PG 4 WC Chemistry, Organic SC Chemistry GA 982QA UT WOS:000233175500034 ER PT J AU Mamyrova, G Rider, LG Haagenson, L Wong, S Brown, KE AF Mamyrova, G Rider, LG Haagenson, L Wong, S Brown, KE TI Parvovirus B19 and onset of juvenile dermatomyositis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter ID INFECTION C1 NIEHS, Environm Autoimmun Grp, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Mamyrova, G (reprint author), NIEHS, Environm Autoimmun Grp, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM brownk@nhlbi.nih.gov FU Intramural NIH HHS NR 5 TC 13 Z9 13 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD NOV 2 PY 2005 VL 294 IS 17 BP 2170 EP 2171 DI 10.1001/jama.294.17.2170 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 979PQ UT WOS:000232957700018 PM 16264157 ER PT J AU Insel, TR Quirion, R AF Insel, TR Quirion, R TI Psychiatry as a clinical neuroscience discipline SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID GENE-EXPRESSION PROFILES; MAJOR DEPRESSION; PREFRONTAL CORTEX; BRAIN; SCHIZOPHRENIA; DISORDER; STRESS; LIFE; INTERSECTION; POLYMORPHISM C1 NIMH, NIH, Bethesda, MD 20892 USA. Douglas Hosp, Inst Neurosci Mental Hlth & Addict, Canadian Inst Hlth Res, Montreal, PQ, Canada. RP Insel, TR (reprint author), NIMH, NIH, 6001 Execut Blvd,Room 8235, Bethesda, MD 20892 USA. EM tinsel@mail.nih.gov NR 41 TC 107 Z9 111 U1 0 U2 3 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 NOV 2 PY 2005 VL 294 IS 17 BP 2221 EP 2224 DI 10.1001/jama.294.17.2221 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 979PQ UT WOS:000232957700026 PM 16264165 ER PT J AU Dancause, N Barbay, S Frost, SB Plautz, EJ Chen, DF Zoubina, EV Stowe, AM Nudo, RJ AF Dancause, N Barbay, S Frost, SB Plautz, EJ Chen, DF Zoubina, EV Stowe, AM Nudo, RJ TI Extensive cortical rewiring after brain injury SO JOURNAL OF NEUROSCIENCE LA English DT Article DE cortex; neuroanatomy; plasticity; squirrel monkey; stroke; PMv ID PRIMARY MOTOR CORTEX; SOMATOSENSORY AREA 3B; PRIMARY VISUAL-CORTEX; SCIATIC-NERVE CRUSH; PREMOTOR CORTEX; CORTICOSPINAL PROJECTIONS; SENSORIMOTOR CORTEX; FRONTAL-LOBE; OWL MONKEYS; SQUIRREL-MONKEYS AB Previously, we showed that the ventral premotor cortex (PMv) underwent neurophysiological remodeling after injury to the primary motor cortex (M1). In the present study, we examined cortical connections of PMv after such lesions. The neuroanatomical tract tracer biotinylated dextran amine was injected into the PMv hand area at least 5 months after ischemic injury to the M1 hand area. Comparison of labeling patterns between experimental and control animals demonstrated extensive proliferation of novel PMv terminal fields and the appearance of retrogradely labeled cell bodies within area 1/2 of the primary somatosensory cortex after M1 injury. Furthermore, evidence was found for alterations in the trajectory of PMv intracortical axons near the site of the lesion. The results suggest that M1 injury results in axonal sprouting near the ischemic injury and the establishment of novel connections within a distant target. These results support the hypothesis that, after a cortical injury, such as occurs after stroke, cortical areas distant from the injury undergo major neuroanatomical reorganization. Our results reveal an extraordinary anatomical rewiring capacity in the adult CNS after injury that may potentially play a role in recovery. C1 Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Mental Retardat Res Ctr, Kansas City, KS 66160 USA. Univ Kansas, Med Ctr, Landon Ctr Aging, Kansas City, KS 66160 USA. NINDS, Bethesda, MD 20892 USA. RP Dancause, N (reprint author), Univ Kansas, Med Ctr, Dept Mol & Integrat Physiol, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. EM ndancause@kumc.edu RI Nudo, Randolph/B-1623-2009 FU NICHD NIH HHS [HD02528]; NINDS NIH HHS [NS30853] NR 65 TC 363 Z9 370 U1 4 U2 24 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 NOV 2 PY 2005 VL 25 IS 44 BP 10167 EP 10179 DI 10.1523/JNEUROSCI.3256-05.2005 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 980BI UT WOS:000232988500014 PM 16267224 ER PT J AU Nienborg, H Bridge, H Parker, AJ Cumming, BG AF Nienborg, H Bridge, H Parker, AJ Cumming, BG TI Neuronal computation of disparity in V1 limits temporal resolution for detecting disparity modulation SO JOURNAL OF NEUROSCIENCE LA English DT Article DE striate cortex; temporal processing; stereopsis; macaque monkey; correlation; energy model; human psychophysics ID PRIMARY VISUAL-CORTEX; RANDOM-DOT STEREOGRAMS; CATS STRIATE CORTEX; CORTICAL AREA V1; BINOCULAR DISPARITY; RECEPTIVE-FIELDS; DEPTH-PERCEPTION; TRANSIENT RESPONSES; COMPLEX CELLS; ENERGY MODELS AB The human ability to detect modulation of binocular disparity over time is poor compared with detection of luminance modulation. We examined the physiological origin of this limitation by analyzing neuronal responses to temporal modulation of binocular disparity in striate cortex of awake monkeys. When neurons were presented with random-dot stereograms in which disparity varied sinusoidally over time, their responses modulated at the stimulus temporal frequency, with little change in mean firing rate. We calculated modulation amplitude as a function of temporal frequency and compared this with the psychophysical performance of four human observers. Neuronal and psychophysical functions showed similar peak frequencies (2 Hz) and comparable high-cut frequencies (10 and 5.5 Hz, respectively). Thus, V1 ( primary visual cortex) neurons appear to limit psychophysical performance. The temporal resolution of the same neurons for contrast modulation was similar to 2.5 times greater, which parallels the superior psychophysical performance for contrast. There is a simple mathematical explanation for this difference: it results from calculating cross-correlation between temporally broadband monocular images that are bandpass filtered before measuring correlation. The limit on temporal resolution is a direct consequence of the binocular energy model that adds to the list of properties of human stereoscopic performance that are explained by this simple model of disparity encoding in V1: the same neurons can account for the performance of psychophysical tasks that result in either high (contrast) or low (disparity) temporal resolution. Because this principle holds whenever a broadband input is bandpass filtered before computing correlation, it may limit the resolution of other neuronal systems. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Univ Oxford, Univ Lab Physiol, Oxford OX1 3PT, England. RP Nienborg, H (reprint author), 49-2A50 Convent Dr, Bethesda, MD 20892 USA. EM hn@lsr.nei.nih.gov RI Parker, Andrew/I-7867-2013; OI Parker, Andrew/0000-0001-5800-0407; Bridge, Holly/0000-0002-8089-6198 FU Intramural NIH HHS; Wellcome Trust NR 49 TC 24 Z9 24 U1 0 U2 1 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 NOV 2 PY 2005 VL 25 IS 44 BP 10207 EP 10219 DI 10.1523/JNEUROSCI.2342-05.2005 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 980BI UT WOS:000232988500018 PM 16267228 ER PT J AU Barense, MD Bussey, TJ Lee, ACH Rogers, TT Davies, RR Saksida, LM Murray, EA Graham, KS AF Barense, MD Bussey, TJ Lee, ACH Rogers, TT Davies, RR Saksida, LM Murray, EA Graham, KS TI Functional specialization in the human medial temporal lobe SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amnesia; hippocampus; medial temporal lobe; perirhinal cortex; object discrimination; declarative memory; perception; feature conjunctions ID HUMAN PERIRHINAL CORTEX; HIPPOCAMPAL-LESIONS; RECOGNITION MEMORY; EPISODIC MEMORY; DOUBLE DISSOCIATION; OBJECT RECOGNITION; ALZHEIMERS-DISEASE; RELATIONAL MEMORY; ITEM RECOGNITION; SPATIAL MEMORY AB Investigations of memory in rats and nonhuman primates have demonstrated functional specialization within the medial temporal lobe (MTL), a set of heavily interconnected structures including the hippocampal formation and underlying entorhinal, perirhinal, and parahippocampal cortices. Most studies in humans, however, especially in patients with brain damage, suggest that the human MTL is a unitary memory system supporting all types of declarative memory, our conscious memory for facts and events. To resolve this discrepancy, amnesic patients with either selective hippocampal damage or more extensive MTL damage were tested on variations of an object discrimination task adapted from the nonhuman primate literature. Although both groups were equally impaired on standard recall-based memory tasks, they exhibited different profiles of performance on the object discrimination test, arguing against a unitary view of MTL function. Cases with selective hippocampal damage performed normally, whereas individuals with broader MTL lesions were impaired. Furthermore, deficits in this latter group were related not to the number of discriminations to be learned and remembered, but to the degree of "feature ambiguity," a property of visual discriminations that can emerge when features are part of both rewarded and unrewarded stimuli. These findings resolve contradictions between published studies in humans and animals and introduce a new way of characterizing the impairments that arise after damage to the MTL. C1 MRC, Cognit & Brain Sci Unit, Cambridge CB2 2EF, England. Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. Univ Cambridge, Addenbrookes Hosp, Dept Clin Neurosci, Cambridge CB2 2QQ, England. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Barense, MD (reprint author), MRC, Cognit & Brain Sci Unit, 15 Chaucer Rd, Cambridge CB2 2EF, England. EM morgan.barense@mrc-cbu.cam.ac.uk RI Lee, Andy/A-1662-2008; Graham, Kim/A-1672-2010; Bussey, Timothy/M-2758-2016; Saksida, Lisa/M-2753-2016; OI Lee, Andy/0000-0002-8546-5311; Bussey, Timothy/0000-0001-7518-4041; Saksida, Lisa/0000-0002-8416-8171; Murray, Elisabeth/0000-0003-1450-1642; Barense, Morgan/0000-0002-4008-9201; Graham, Kim/0000-0002-1512-7667 FU Wellcome Trust NR 43 TC 139 Z9 140 U1 2 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 NOV 2 PY 2005 VL 25 IS 44 BP 10239 EP 10246 DI 10.1523/JNEUROSCI.2704-05.2005 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 980BI UT WOS:000232988500021 PM 16267231 ER PT J AU Marquez, VE Choi, Y Comin, MJ Russ, P George, C Huleihel, M Ben-Kasus, T Agbaria, R AF Marquez, VE Choi, Y Comin, MJ Russ, P George, C Huleihel, M Ben-Kasus, T Agbaria, R TI Understanding how the herpes thymidine kinase orchestrates optimal sugar and nucleobase conformations to accommodate its substrate at the active site: A chemical approach SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID SIMPLEX-VIRUS TYPE-1; MULTIFUNCTIONAL ENZYME; CARBOCYCLIC THYMIDINE; THYMIDYLATE KINASE; GENITAL HERPES; NUCLEOSIDES; INFECTIONS; CELLS; OLIGONUCLEOTIDES; PSEUDOROTATION AB The herpes virus thymidine kinase (HSV-tk) is a critical enzyme for the activation of anti-HSV nucleosides. However, a successful therapeutic outcome depends not only on the activity of this enzyme but also on the ability of the compound(s) to interact effectively with cellular kinases and with the target viral or cellular DNA polymerases. Herein, we describe the synthesis and study of two nucleoside analogues built on a conformationally locked bicyclo[3.1.0]hexane template designed to investigate the conformational preferences of HSV-tk for the 2'-deoxyribose ring. Intimately associated with the conformation of the 2'deoxyribose ring is the value of the C-N torsion angle chi, which positions the nucleobase into two different domains (syn or anti). The often-conflicting sugar and nucleobase conformational parameters were studied using North and South methanocarbadeoxythymidine analogues (6 and 7), which forced HSV-tk to make a clear choice in the conformation of the substrate. The results provide new insights into the mechanism of action of this enzyme, which cannot be gleaned from a static X-ray crystal structure. C1 Natl Canc Inst, Canc Res Ctr, Med Chem Lab, Ft Detrick, MD 21702 USA. USN, Res Lab, Struct Matter Lab, Washington, DC 20375 USA. Ben Gurion Univ Negev, Fac Hlth Sci, Natl Inst Biotechnol, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Fac Hlth Sci, Dept Virol, IL-84105 Beer Sheva, Israel. Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel. RP Marquez, VE (reprint author), Natl Canc Inst, Canc Res Ctr, Med Chem Lab, 376 Boyles St, Ft Detrick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov RI Choi, Yongseok/F-8375-2012 OI Choi, Yongseok/0000-0002-3622-3439 NR 25 TC 32 Z9 32 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD NOV 2 PY 2005 VL 127 IS 43 BP 15145 EP 15150 DI 10.1021/ja053789s PG 6 WC Chemistry, Multidisciplinary SC Chemistry GA 979HV UT WOS:000232933900060 PM 16248655 ER PT J AU Saxman, S AF Saxman, S TI Doctor ... Will I still be able to have children? SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID LYMPH-NODE DISSECTION; TESTICULAR CANCER; RANDOMIZED-TRIAL; SEMINOMA; SURVEILLANCE; MANAGEMENT; FERTILITY; DISEASE C1 NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Saxman, S (reprint author), NCI, Canc Therapy Evaluat Program, 6130 Execut Blvd,Rm 7025, Bethesda, MD 20892 USA. EM saxmans@ctep.nci.nih.gov NR 12 TC 2 Z9 2 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 NOV 2 PY 2005 VL 97 IS 21 BP 1557 EP 1559 DI 10.1093/jnci/dji387 PG 3 WC Oncology SC Oncology GA 981WB UT WOS:000233117600002 PM 16264170 ER PT J AU Zhang, YW Lan, Q Rothman, N Zhu, Y Zahm, SH Wang, SS Holford, TR Leaderer, B Boyle, P Zhang, B Zou, KY Chanock, S Zheng, TZ AF Zhang, YW Lan, Q Rothman, N Zhu, Y Zahm, SH Wang, SS Holford, TR Leaderer, B Boyle, P Zhang, B Zou, KY Chanock, S Zheng, TZ TI A putative exonic splicing polymorphism in the BCL6 gene and the risk of non-Hodgkin lymphoma SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FINGER ENCODING GENE; CONNECTICUT WOMEN; TRANSLOCATIONS; INFLAMMATION AB Recent studies have shown that the B-cell lymphoma 6 gene (BCL6) is an oncogene that contributes to lymphomagenesis. Exon 6 of BCL6 contains a common single nucleotide polymorphism (SNP) (-195 C>T; dbSNP ID: rs1056932) that alters a potential binding site for an exonic splicing enhancer. We used unconditional logistic regression models to examine the association between this SNP and the risk of non-Hodgkin lymphoma (NHL) in a population-based case-control study of women residing in Connecticut (461 case patients and 535 control subjects). The risk of NHL among women with the CC genotype was more than double that of women with the TT genotype (odds ratio [OR] 2.2, 95% confidence interval [CI] 1.5 to 3.3). Higher risks were observed for two NHL subtypes, namely B-cell chronic lymphatic leukemia/prolymphocytic leukemia/small lymphocytic lymphoma (OR = 3.5, 95% CI = 1.6 to 7.8) and T-cell lymphoma (OR = 5.2, 95% CI = 2.0 to 13.3). Our results support the hypothesis that a genetic variant that could alter mRNA transcripts of BCL6 may contribute to the etiology of NHL and suggest that this variant warrants further investigation. C1 Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Int Agcy Res Canc, F-69372 Lyon, France. McGill Univ, Dept Epidemiol & Biostat, Montreal, PQ, Canada. Yale Univ, Dept Mol Cellular & Dev Biol, New Haven, CT USA. NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Zhang, YW (reprint author), Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, 60 Coll St,Room 442,POB 208034, New Haven, CT 06520 USA. EM yawei.zhang@yale.edu; tongzhang.zheng@yale.edu RI Boyle, Peter/A-4380-2014 OI Boyle, Peter/0000-0001-6251-0610 FU NCI NIH HHS [CA62006] NR 17 TC 27 Z9 27 U1 0 U2 2 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 NOV 2 PY 2005 VL 97 IS 21 BP 1616 EP 1618 DI 10.1093/jnci/dji344 PG 3 WC Oncology SC Oncology GA 981WB UT WOS:000233117600014 PM 16264183 ER PT J AU Simons-Morton, B Lerner, N Singer, J AF Simons-Morton, B Lerner, N Singer, J TI The observed effects of teenage passengers on the. risky driving behavior of teenage drivers SO ACCIDENT ANALYSIS AND PREVENTION LA English DT Article DE motor vehicles; adolescents; risk taking; social influences; speeding; passengers ID PEER; SMOKING AB The association between teenage passengers and crash risks among young drivers may be due to risky driving behavior. We investigated the effect on two measures of risky driving in the presence of young male and female passengers. Vehicles exiting from parking lots at 10 high schools were observed and the occupants were identified by gender and age (teen or adult). At a nearby site, the speed and headway of passing traffic were recorded using video and LIDAR technology. Teenage drivers drove faster than the general traffic and allowed shorter headways, particularly in the presence of a male teenage passenger. Both male and female teenage drivers allowed shorter headways (relative to no passenger or a female passenger) in the presence of a male teenage passenger, while the presence of a female teenage passenger resulted in longer headways for male teenage drivers. Overall, the observed rate of high risk driving (defined as speed >= 15 mph or more above the posted speed limit and/or headway of <= 1.0 s) for the teen male driver/male passenger condition was about double that of general traffic. In conclusion, the presence of male teenage passengers was associated with risky driving behavior among teenage drivers. Published by Elsevier Ltd. C1 NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, Bethesda, MD 20892 USA. Westat Corp, Rockville, MD 20850 USA. RP Simons-Morton, B (reprint author), NICHHD, Prevent Res Branch, Div Epidemiol Stat & Prevent Res, NIH, 6100 Execut Blvd RM 7B13M, Bethesda, MD 20892 USA. EM Mortonb@mail.nih.gov; LERNER1@westat.coom; jeremiahsinger@westat.com OI Simons-Morton, Bruce/0000-0003-1099-6617 NR 12 TC 178 Z9 179 U1 2 U2 21 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0001-4575 J9 ACCIDENT ANAL PREV JI Accid. Anal. Prev. PD NOV PY 2005 VL 37 IS 6 BP 973 EP 982 DI 10.1016/j.aap.2005.04.014 PG 10 WC Ergonomics; Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary; Transportation SC Engineering; Public, Environmental & Occupational Health; Social Sciences - Other Topics; Transportation GA 982SZ UT WOS:000233183200001 PM 15921652 ER PT J AU Raj, DK Mishra, S Das, BR Dash, AP AF Raj, DK Mishra, S Das, BR Dash, AP TI Plasmodium falciparum Pfs25 gene promoter has no polymorphism in natural isolates of eastern India SO ACTA PROTOZOOLOGICA LA English DT Article DE PCR-SSCP; Pfs25 promoter; Plasmodium falciparium; point mutation; polymorphism ID TRANSMISSION-BLOCKING ANTIBODIES; SEXUAL STAGE ANTIGENS; PLASMODIUM-FALCIPARUM; VACCINE CANDIDATE; SURFACE PROTEIN-2; HUMAN MALARIA; PFS25; DNA; IMMUNOGENICITY; EXPRESSION AB Most of the potential vaccine candidate genes show polymorphism or point mutation, which affects the structure of antigen and thereby, production of antibody to protect the host against further infection. In the present study, we have analyzed the promoter regions of 415 base pair (nucleotide position -722 to -308) of Pfs25 gene. Previous studies have shown that, removing these important regions drastically affects the promoter activity and Pfs25 protein expression. We for the first time, report that though promoter regions of Pfs25 gene is AT rich. it doesn't show any polymorphism or point mutation in sequences important for its activity in 155 natural isolates of Plasmodium falciparum from hyper endemic malaria transmission regions. Since, Pfs25 expression is vital for the survival of the parasite in the mosquito vector, a stable promoter sequence of Pfs25 in all the strains may have fair chances Of Survival in the mosquito vector. Our finding of a stable promoter sequence in combination with previous reports of limited polymorphism in the coding regions of Pfs25 indicates that Pfs25 might be a strong candidate for vaccine. C1 Inst Life Sci, Bhubaneswar, Orissa, India. RP Raj, DK (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Room 3E-20B,12735 Twinbrook Pkwy, Rockville, MD 20850 USA. EM draj@mail.nih.gov NR 25 TC 0 Z9 0 U1 0 U2 0 PU NENCKI INST EXPERIMENTAL BIOLOGY PI WARSAW PA UL PASTEURA 3, 02-093 WARSAW, POLAND SN 0065-1583 J9 ACTA PROTOZOOL JI Acta Protozool. PD NOV PY 2005 VL 44 IS 4 BP 289 EP 292 PG 4 WC Microbiology SC Microbiology GA 984YI UT WOS:000233342900001 ER PT J AU Melzer, D Gardener, E Guralnik, JM AF Melzer, D Gardener, E Guralnik, JM TI Mobility disability in the middle-aged: cross-sectional associations in the English Longitudinal Study of Ageing SO AGE AND AGEING LA English DT Article DE chronic disease; disability; elderly; leg; pain; walking ID PHYSICAL-DISABILITY; OLDER WOMEN; POPULATION; PEOPLE; IMPACT AB Background: mobility (locomotor) disability is an early marker of disability progression, health care utilisation and institutionalisation in older people. Whether mobility disability has different causes in the middle-aged has received limited attention. Objectives: to examine associations of mobility disability with sociodemographic, behaviour and disease status and to contrast these with associations in older groups. Design: cross-sectional interview data from the 2002 English Longitudinal Study of Ageing. Mobility status based on reported difficulty walking a quarter of a mile (402 m). Participants: a total of 11,392 community-living respondents aged 50 years and over. Results: in the middle-aged, 8% (95% CI 7-9%) of women and 9% (95% CI 8-11%) of men reported having much difficulty or being unable to walk a quarter of a mile, equating to 787,000 (95% CI 700,000-831,000) people in England. Factors which at least doubled odds of mobility disability in the middle-aged were chronic obstructive lung disease, angina, stroke, recently treated cancer, comorbidity, lower limb and back pain. Factors associated with mobility disability in older groups were similar. Thirty-eight per cent of mobility disability in the middle-aged population was related to high levels of lower limb pain and 15% to high levels of back pain. Conclusions: mobility disability in the middle-aged is relatively common. The associated conditions in the middle-aged are similar to those in older people. Lower limb and back pain make dominant population contributions to mobility disability. Prevention of later disability progression may require more attention being paid to mobility difficulties and its causes in the middle-aged. C1 Peninsula Med Sch, Dept Epidemiol & Publ Hlth, Exeter EX2 5DW, Devon, England. Univ Cambridge, Inst Publ Hlth, Dept Publ Hlth & Primary Care, Cambridge CB2 2SR, England. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. RP Melzer, D (reprint author), Peninsula Med Sch, Dept Epidemiol & Publ Hlth, RD&E Wonford Site,Barrack Rd, Exeter EX2 5DW, Devon, England. EM david.melzer@pms.ac.uk OI Melzer, David/0000-0002-0170-3838 NR 19 TC 41 Z9 41 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0002-0729 J9 AGE AGEING JI Age Ageing PD NOV PY 2005 VL 34 IS 6 BP 594 EP 602 DI 10.1093/ageing/afi188 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 980UT UT WOS:000233044400013 PM 16267185 ER PT J AU Weeraratna, AT AF Weeraratna, AT TI Discovering causes and cures for cancer from gene expression analysis SO AGEING RESEARCH REVIEWS LA English DT Review DE gene expression profiling; cancer; SAGE; microarray ID EPITHELIAL OVARIAN-CANCER; FATTY-ACID SYNTHASE; BREAST-CANCER; PROSTATE-CANCER; CDNA MICROARRAY; SERIAL ANALYSIS; CELL-LINES; MOLECULAR CLASSIFICATION; COLORECTAL-CANCER; DRUG-SENSITIVITY AB Tumorigenesis is governed by a series of complex genetic and epigenetic changes. Both mechanisms can result in either the silencing or aberrant expression of messages in a cell. Gene expression profiling techniques such as the serial analysis of gene expression (SAGE) or microarray analysis can provide global overviews of these changes, as well identify key genes and pathways involved in this process. This review outlines the current roles of these techniques in cancer research, and how they may contribute to finding not only mechanisms of this disease, but potential targets for therapy. Published by Elsevier Ireland Ltd. C1 NIA, Immunol Lab, NIH, Ctr Gerontol Res, Baltimore, MD 21224 USA. RP Weeraratna, AT (reprint author), NIA, Immunol Lab, NIH, Ctr Gerontol Res, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM weerarat@grc.nia.nih.gov NR 75 TC 6 Z9 7 U1 0 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD NOV PY 2005 VL 4 IS 4 BP 548 EP 563 DI 10.1016/j.arr.2005.06.004 PG 16 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 995KM UT WOS:000234099200005 PM 16243590 ER PT J AU Kyng, KJ Bohr, VA AF Kyng, KJ Bohr, VA TI Gene expression and DNA repair in progeroid syndromes and human aging SO AGEING RESEARCH REVIEWS LA English DT Review DE gene expression; progeroid syndromes; DNA repair; human aging; Werner syndrome ID WERNER-SYNDROME PROTEIN; RNA-POLYMERASE-II; HUTCHINSON-GILFORD PROGERIA; GROUP-B GENE; COCKAYNE-SYNDROME; CALORIC RESTRICTION; CELL-LINES; REPLICATIVE SENESCENCE; OXIDATIVE STRESS; EXCISION-REPAIR AB Human progeroid syndromes are caused by mutations in single genes accelerating some but not all features of normal aging. Most progeroid disorders are linked to defects in genome maintenance, and while it remains unknown if similar processes underlie normal and premature aging, they provide useful models for the study of aging. Altered transcription is speculated to play a causative role in aging, and is involved in the pathology of most if not all progeroid syndromes. Previous studies demonstrate that there is a similar pattern of gene expression changes in primary cells from old and Werner syndrome compared to young suggesting a presence of common cellular aging mechanisms in old and progeria. Here we review the role of transcription in progeroid syndromes and discuss the implications of similar transcription aberrations in normal and premature aging. Published by Elsevier Ireland Ltd. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Aarhus Univ, Dept Mol Biol, Danish Ctr Mol Gerontol, DK-8000 Aarhus, Denmark. RP Bohr, VA (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM bohrv@grc.nia.nih.gov OI Kyng, Kasper Jacobsen/0000-0001-7940-1656 NR 80 TC 44 Z9 45 U1 1 U2 4 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1568-1637 J9 AGEING RES REV JI Ageing Res. Rev. PD NOV PY 2005 VL 4 IS 4 BP 579 EP 602 DI 10.1016/j.arr.2005.06.008 PG 24 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 995KM UT WOS:000234099200007 PM 16246641 ER PT J AU Kip, KE Marroquin, OC Shaw, LJ Arant, CB Wessel, TR Olson, MB Johnson, BD Mulukutla, S Sopko, G Merz, CNB Reis, SE AF Kip, KE Marroquin, OC Shaw, LJ Arant, CB Wessel, TR Olson, MB Johnson, BD Mulukutla, S Sopko, G Merz, CNB Reis, SE TI Global inflammation predicts cardiovascular risk in women: A report from the Women's Ischemia Syndrome Evaluation (WISE) study SO AMERICAN HEART JOURNAL LA English DT Article ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; SERUM AMYLOID-A; ARTERY-DISEASE; ATHEROSCLEROTIC PLAQUES; UNSTABLE ANGINA; MARKERS; INTERLEUKIN-6; EVENTS; HEALTH AB Background Measurement of C-reactive protein (CRP), a marker of inflammation, is recommended to improve cardiovascular disease (CVD) risk stratification. However, no studies have collectively evaluated how inflammatory markers cluster empirically and relate to angiographic coronary artery disease and CVD events. Methods From the WISE study, 580 women with fasting plasma samples of inflammatory markers (interleukin [IL]-6, IL-18, tumor necrosis factor alpha, transforming growth factor beta, CRP, serum amyloid A [SAA], and intercellular adhesion molecules) were analyzed over a median of 4.7 years follow-up. All women were referred for coronary angiography (1996-2000) to evaluate suspected myocardial ischemia. Results In factor analysis, a "proinflammation" factor (cluster) loaded on IL-6, CRP, and SAA (r = 0.63-0.87); a "proinflammation and anti-inflammation" cluster loaded on IL-18 and tumor necrosis factor a (r = 0.72, 0.77); and an "immunosuppressive" factor loaded singly on transforming growth factor beta (r = 0.96). No cluster was independently associated with angiographic coronary artery disease. However, quartile increases of the "proinflammation" cluster (IL-6, CRP, and SAA) yielded death rates of 2.6%, 7.2%, 13.1%, 26.6%, respectively (P < .0001). Women with >= 2 of 3 proinflammation markers in the upper quartile had an adjusted relative risk of death of 4.21 (95% CI 1.91-9.25), a higher conferred risk than any single marker alone, all of which were roughly equally predictive. Conclusions Although IL-6, CRP, and SAA all predict CVD risk in women, development of global measures of inflammation and simply counting the number of markers with high levels improve CVD risk stratification. In addition, results indicate that the adverse impact of inflammation may be largely through other mechanisms than promotion of atherogenesis (ie, destabilization of vulnerable plaques). C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA USA. Amer Cardiovasc Res Inst, Atlanta, GA USA. Univ Florida, Coll Med, Div Cardiovasc Med, Gainesville, FL USA. NHLBI, NIH, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. Cedars Sinai Med Ctr, Dept Med, Div Cardiol, Los Angeles, CA 90048 USA. RP Kip, KE (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 DeSoto St,Crabtree Hall,Room 533A, Pittsburgh, PA 15261 USA. EM kipk@edc.pitt.edu RI Reis, Steven/J-3957-2014; Marroquin, Oscar/F-2214-2015 OI Marroquin, Oscar/0000-0002-0909-0319 FU NHLBI NIH HHS [N01-HV-68163, R01-HL-073412-01, U01 HL649241, U01 HL649141, N01-HV-68162, N01-HV-68164, N01-HV-68161]; PHS HHS [U0164829] NR 37 TC 38 Z9 39 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD NOV PY 2005 VL 150 IS 5 BP 900 EP 906 DI 10.1016/j.ahj.2005.02.002 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 986VW UT WOS:000233478800008 PM 16290958 ER PT J AU Lim, JG Shapiro, EP Vaidya, D Najjar, SS Turner, KL Bacher, AC Ouyang, P Stewart, KJ AF Lim, JG Shapiro, EP Vaidya, D Najjar, SS Turner, KL Bacher, AC Ouyang, P Stewart, KJ TI Sex differences in left ventricular function in older persons with mild hypertension SO AMERICAN HEART JOURNAL LA English DT Article ID DIASTOLIC HEART-FAILURE; TISSUE DOPPLER-ECHOCARDIOGRAPHY; GENDER-DIFFERENCES; EJECTION FRACTION; BLOOD-PRESSURE; SYSTOLIC ABNORMALITIES; ANNULAR VELOCITIES; FILLING PRESSURES; HEALTHY-SUBJECTS; LIFETIME RISK AB Background Epidemiologic studies suggest that women are at increased risk of developing heart failure secondary to hypertension. Other studies have documented sex differences in left ventricular systolic and diastolic function in the presence of pressure overload states such as seen in aortic stenosis and hypertension. It is less clear if sex differences are present among older persons with mild hypertension. Methods One hundred seven healthy subjects, aged 55 to 75 years, with blood pressures ranging from 130 to 159 mm Hg systolic and/or 85 to 99 mm Hg diastolic, were examined by standard echocardiography and the newer modalities of tissue Doppler and color M-mode imaging. Results Women had a lower peak mitral annular systolic velocity (Sm), 8.9 (95% CI 8.4-9.5) cm/s versus 10.2 (95% CI 9.6-11.0) cm/s, (P < .01) than men. Among women, increasing age was associated with a reduction in diastolic function. For every decade of age, peak early mitral annular diastolic velocity (Em) declined by 1.6 cm/s (P < .01), mitral inflow velocity of propagation (Vp) declined by 26% (P < .01), E/Vp ratio increased by 20% (P = .03), and E/Em ratio increased by 11% (P = .04) in women. No age-associated changes were seen in men. Conclusions As revealed by newer echocardiographic imaging modalities, women with mild hypertension showed greater reductions in systolic and diastolic function as they aged compared with men. Our findings are consistent with the increased risk older women have of developing heart failure because of hypertension. C1 Johns Hopkins Univ, Johns Hopkins Bayview Med Ctr, Dept Med, Div Cardiol, Baltimore, MD 21224 USA. NIA, Cardiovasc Sci Lab, NIH, Baltimore, MD 21224 USA. RP Johns Hopkins Univ, Johns Hopkins Bayview Med Ctr, Dept Med, Div Cardiol, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM kstewart@jhmi.edu OI Vaidya, Dhananjay/0000-0002-7164-1601 FU NCRR NIH HHS [5M01RR02719]; NHLBI NIH HHS [R01HL59164] NR 49 TC 4 Z9 4 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD NOV PY 2005 VL 150 IS 5 BP 934 EP 940 DI 10.1016/j.ahj.2005.01.013 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 986VW UT WOS:000233478800018 PM 16290968 ER PT J AU Mathew, J Wittes, J McSherry, F Williford, W Garg, R Probstfield, J Yusuf, S AF Mathew, J Wittes, J McSherry, F Williford, W Garg, R Probstfield, J Yusuf, S TI Racial differences in outcome and treatment effect in congestive heart failure SO AMERICAN HEART JOURNAL LA English DT Article ID LEFT-VENTRICULAR DYSFUNCTION; CONVERTING ENZYME-INHIBITION; WHITE PATIENTS; BLACKS; MORTALITY; TRIAL; CARE; RACE AB Background In congestive heart failure (CHF), it is unknown whether race affects mortality and whether the effect of treatments differs by race. Methods This study was a post hoc analysis of data from the DIG study that evaluated the effect of digoxin on morbidity and mortality in CHF. Results Investigators followed 897 black and 6660 white participants for a mean of 37 months. Compared with whites, blacks were younger (60 +/- 13 vs 65 +/- 11 years). Total mortality was 34.2% in blacks and 33.6% in whites; hospitalization for worsening CHF occurred in 39% of blacks and 28% of whites. Cox regressions with race as the only covariate showed no effect of race on risk for death (relative risk = 1.04, 95% CI 0.93-1.18, P = .49) but an increase in CHF hospitalization in blacks (relative risk = 1.52, 95% CI 1.35-1.70, P = .0001). Multivariate Cox regression showed no difference by race in risk for death or death/hospitalization for CHF and no difference in the effect of digoxin on either end point. Conclusion Race is not an independent predictor of mortality in CHF. The effect of digoxin on morbidity and mortality in CHF does not differ in blacks and whites. C1 Wisconsin Cardiovasc Grp, Milwaukee, WI 53215 USA. Univ Iowa, Coll Med, Iowa City, IA USA. Stat Collaborat, Washington, DC USA. VA Med Ctr, Cooperat Studies Program, Perry Point, MD USA. Univ Maryland, Sch Med, Dept Epidemiol & Preventat Med, Baltimore, MD 21201 USA. NHLBI, Bethesda, MD 20892 USA. Univ Washington, Dept Med & Epidemiol, Seattle, WA 98195 USA. McMaster Univ, Div Cardiol, Hamilton, ON, Canada. RP Mathew, J (reprint author), Wisconsin Cardiovasc Grp, 2315 N Lake Dr 613, Milwaukee, WI 53215 USA. EM jamesmathew@earthlink.net NR 18 TC 21 Z9 21 U1 1 U2 2 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 EI 1097-5330 J9 AM HEART J JI Am. Heart J. PD NOV PY 2005 VL 150 IS 5 BP 968 EP 976 DI 10.1016/j.ahj.2005.03.060 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 986VW UT WOS:000233478800023 PM 16290973 ER PT J AU Tofler, GH Massaro, J Levy, D Mittleman, M Sutherland, P Lipinska, I Muller, JE D'Agostino, RB AF Tofler, GH Massaro, J Levy, D Mittleman, M Sutherland, P Lipinska, I Muller, JE D'Agostino, RB TI Relation of the prothrombotic state to increasing age (from the Framingham Offspring Study) SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID C-REACTIVE PROTEIN; LINKED-IMMUNOSORBENT-ASSAY; MYOCARDIAL-INFARCTION; PLASMINOGEN-ACTIVATOR; VONWILLEBRAND-FACTOR; ANGINA-PECTORIS; FACTOR-VIII; CARDIOVASCULAR-DISEASE; SUDDEN-DEATH; RISK FACTOR AB A greater life expectancy has led to an increasing proportion of elderly patients. Increasing age is an important risk factor for cardiovascular disease, but the mechanism of risk is not well understood. Because thrombosis plays a key role in plaque development and the onset of acute coronary syndromes, the age-related increase in cardiovascular risk may be a result of a prothrombotic imbalance. The study aim was to examine the relation between age and thrombotic potential in the Framingham Offspring Cohort. Hemostatic factors previously associated with cardiovascular risk were measured in 3,230 patients (55% women) without evidence of cardiovascular disease who were participating in cycle 5 of the Framingham Offspring Study. The subjects were divided by age into decades. Advancing age was associated with a significant increase in fibrinogen and von Willebrand factor levels and measures of impaired fibrinolytic potential (plasminogen activator inhibitor and tissue plasminogen activator antigens). For men, the mean fibrinogen levels were 21% higher in those >= 70 years versus those aged < 40 years (326 vs 268 mg/dl, p < 0.001 for linear trend). The mean fibrinogen levels were 15% higher in older than in younger women (330 vs 286 mg/dl, p < 0.001). The significant relations persisted after multivariate adjustment. In conclusion, advancing age is associated with elevated levels of hemostatic factors indicative of a prothrombotic state. Because these factors are also associated with endothelial dysfunction, these findings are consistent with an injurious effect of age on the endothelium. Measures to reduce thrombotic potential may be of particular value in the elderly, because they counter the prothrombotic state that develops with aging. (c) 2005 Elsevier Inc. All rights reserved. C1 Royal N Shore Hosp, Sydney, NSW, Australia. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. NHLBI, Framingham, MA USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Math & Stat, Boston, MA USA. RP Tofler, GH (reprint author), Royal N Shore Hosp, Sydney, NSW, Australia. EM gtofler@nsccahs.health.nsw.gov.au OI Massaro, Joseph/0000-0002-2682-4812 FU NHLBI NIH HHS [HC 38038, R01 HL 48157] NR 25 TC 47 Z9 48 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD NOV 1 PY 2005 VL 96 IS 9 BP 1280 EP 1283 DI 10.1016/j.amjcard.2005.06.072 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 984YO UT WOS:000233343500021 PM 16253598 ER PT J AU Schiffman, M Wheeler, CM Dasgupta, A Solomon, D Castle, PE AF Schiffman, M Wheeler, CM Dasgupta, A Solomon, D Castle, PE CA ALTS Grp TI A comparison of a prototype PCR assay and hybrid capture 2 for detection of carcinogenic human papillomavirus DNA in women with equivocal or mildly abnormal papanicolaou smears SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Article DE cervical intraepithelial neoplasa; human papillomavirus; HPV; triage; hybrid capture; polymerase chain reaction; PCR ID ATYPICAL SQUAMOUS-CELLS; ASCUS-LSIL TRIAGE; CERVICAL-CANCER; UNDETERMINED SIGNIFICANCE; RANDOMIZED-TRIAL; INTRAEPITHELIAL NEOPLASIA; CYTOLOGY INTERPRETATIONS; MANAGEMENT STRATEGIES; RISK; HYBRID-CAPTURE-2 AB We evaluated Hybrid Capture 2 (HC2) and polymerase chain reaction (PCR) results for paired specimens collected at 19,187 visits from 5,026 of 5,060 women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study (ALTS). We examined the test agreement between HC2 and PCR detection for any of 13 carcinogenic human papillomavirus types targeted by HC2 and compared clinical performance of the 2 tests for detecting concurrent and follow-up cervical intraepithelial neoplasia (CIN) 3 or cancer. The kappa value for the 2 assays was 0.65 (95% confidence interval, 0.64-0.66), with, 82.7% crude agreement. HC2 was more sensitive (93.6% vs 89.3%; P < .0005) but less specific (41.2% vs 48.5%; P < .0005) than PCR for detecting 2-year cumulative CIN 3 or cancer (n = 503). The presence of multiple types as detected by PCR and/or cytologic abnormality increased the likelihood of an HC2+ result. Increased sensitivity of HC2 compared with PCR was surprising given the theoretical advantages of PCR-based methods for analytic sensitivity. Smaller amounts of material used in PCR could have limited its sensitivity, but our results demonstrate the importance of optimization and standardization of PCR-based assays for clinical applications. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Div Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ New Mexico, Hlth Sci Ctr, Sch Med, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, Sch Med, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,Room 7074,EPS MSC 7234, Bethesda, MD 20892 USA. FU NCI NIH HHS [CN-55154, CN-55156, CN-55153, CN-55159, CN-55155, CN-55158, CN-55157, CN-55105] NR 28 TC 57 Z9 59 U1 0 U2 0 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD NOV PY 2005 VL 124 IS 5 BP 722 EP 732 DI 10.1309/E067X0L1U3CY37NW PG 11 WC Pathology SC Pathology GA 977XJ UT WOS:000232836500008 PM 16203281 ER PT J AU Chen, Z Stewart, PA Davies, S Giller, R Krailo, M Davis, M Robison, L Shu, XO AF Chen, Z Stewart, PA Davies, S Giller, R Krailo, M Davis, M Robison, L Shu, XO TI Parental occupational exposure to pesticides and childhood germ-cell tumors SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE case-control studies; child; germinoma; occupational exposure; pesticides ID CHILDRENS CANCER GROUP; TESTICULAR CANCER; CONTROL SELECTION; UNITED-STATES; RISK-FACTORS; SEX-RATIO; AGRICULTURE; CALIFORNIA; ETIOLOGY; WORKERS AB In a recently completed US case-control study (Children's Oncology Group, 1993-2001) with 253 cases and 394 controls, the authors investigated the association between parental occupational exposure to pesticides and risk of childhood germ-cell tumors. Information on occupational pesticide exposure was collected using job-specific module questionnaires and assessed by an experienced industrial hygienist. Odds ratios for childhood germ-cell tumors associated with maternal exposures before pregnancy, during pregnancy, and after the birth of the index child were 1.0 (95% confidence interval (CI): 0.8, 1.4), 1.1 (95% CI: 0.7, 1.6), and 1.3 (95% CI: 0.9, 1.8), respectively. Paternal exposures before pregnancy, during pregnancy, and after the birth of the index child were not related to germ-cell tumors (odds ratios (ORs) were 0.9 (95% CI: 0.7, 1.2), 0.8 (95% CI: 0.5, 1.2), and 0.8 (95% CI: 0.5, 1.3), respectively). When both parents had ever been occupationally exposed to pesticides before the index pregnancy, the odds ratio was 0.8 (95% CI: 0.4, 1.3). Subgroup analyses showed a positive association between maternal exposure to herbicides during the postnatal period and risk of germ-cell tumors in girls (OR = 2.3, 95% CI: 1.0, 5.2) and an inverse association between paternal exposure to pesticides during the index pregnancy and germ-cell tumors in boys (OR = 0.2, 95% CI: 0.1, 1.0). This study did not provide strong evidence supporting a relation between parental pesticide exposure in the workplace and risk of germ-cell tumors among offspring. C1 Vanderbilt Univ, Ctr Hlth Serv Res, Nashville, TN 37232 USA. Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Dept Med, Nashville, TN 37232 USA. NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Bethesda, MD 20892 USA. Cincinnati Childrens Hosp & Med Ctr, Cincinnati, OH USA. Childrens Hosp, Denver, CO 80218 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA 90089 USA. James Whitcomb Riley Hosp Children, Div Pediat Pathol, Indianapolis, IN 46202 USA. Univ Minnesota, Dept Pediat, Div Epidemiol & Clin Res, Sch Med, Minneapolis, MN 55455 USA. RP Shu, XO (reprint author), Vanderbilt Univ, Ctr Hlth Serv Res, 6th Floor,Med Ctr E,Room 6009, Nashville, TN 37232 USA. EM Xiao-Ou.Shu@vanderbilt.edu FU NCI NIH HHS [R01CA067263] NR 46 TC 20 Z9 22 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 2005 VL 162 IS 9 BP 858 EP 867 DI 10.1093/aje/kwi294 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 976PP UT WOS:000232745900008 PM 16192347 ER PT J AU Infante-Rivard, C Weinberg, CR AF Infante-Rivard, C Weinberg, CR TI Parent-of-origin transmission of thrombophilic alleles to intrauterine growth-restricted newborns and transmission-ratio distortion in unaffected newborns SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE alleles; factor XIII; fetal development; fetal growth retardation; genomic imprinting; polymorphism; genetic; thrombophilia ID GENETIC POLYMORPHISMS; FACTOR-XIII; COMMON POLYMORPHISM; DISEASE; ASSOCIATION; EXPRESSION; INFARCTION; TRIADS AB Findings on the role of thrombophilic polymorphisms in adverse pregnancy outcomes, particularly intrauterine growth restriction, are inconsistent. Such inconsistencies may be partly due to two types of effects which have not been considered before with regard to thrombophilic genes: parent-of-origin effects (imprinting) and transmission-ratio distortion effects (allele transmission differing from that expected in unaffected subjects). In this study of infants born at a Canadian hospital (1998-2000), the authors investigated both types of effects. Cases (n = 493) were defined as newborns whose birth weight for gestational age and sex was below the 10th percentile by national standards, and controls (n = 472) as newborns at or above the 10th percentile. Log-linear models were used to analyze the transmission of variant alleles among case- and control-parent trios. A single copy of a common polymorphism, Val34Leu in factor XIII, increased the risk of intrauterine growth restriction approximately 70% when the parent of origin was the father as opposed to the mother (p < 0.05). Among unaffected newborns, transmission of A1298C in the methylenetetrahydrofolate reductase gene (p < 0.005), transmission of the G1691A variant in factor V Leiden (p < 0.002), and transmission of the G20210A variant in the prothrombin (factor II) gene (p < 0.001) occurred significantly less often than expected (transmission-ratio distortion). Affected newborns also inherited the prothrombin G20210A variant significantly less often than expected. These results suggest that these three genes exhibit segregation distortion or reduce gestational survival. C1 McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, Montreal, PQ H3A 1A3, Canada. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Infante-Rivard, C (reprint author), McGill Univ, Fac Med, Dept Epidemiol Biostat & Occupat Hlth, 1130 Pine Ave W, Montreal, PQ H3A 1A3, Canada. EM claire.infante-rivard@mcgill.ca NR 29 TC 12 Z9 12 U1 1 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD NOV 1 PY 2005 VL 162 IS 9 BP 891 EP 897 DI 10.1093/aje/kwi293 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 976PP UT WOS:000232745900012 PM 16192348 ER PT J AU Shaikh, RS Ramzan, K Nazli, S Sattar, S Khan, SN Riazuddin, S Ahmed, ZM Friedman, TB Riazuddin, S AF Shaikh, RS Ramzan, K Nazli, S Sattar, S Khan, SN Riazuddin, S Ahmed, ZM Friedman, TB Riazuddin, S TI A new locus for nonsyndromic deafness DFNB51 maps to chromosome 11p13-p12 SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Letter ID AUTOSOMAL RECESSIVE DEAFNESS; PDS MUTATIONS; HEARING-LOSS; HAIR-CELLS; MYOSIN-XVA; INNER-EAR; STEREOCILIA; FAMILIES; RADIXIN; WHIRLIN C1 Univ Punjab, Natl Ctr Excellence Mol Biol, Lahore 53700, Pakistan. NIDCD, Sect Human Genet, Mol Genet Lab, NIH, Rockville, MD USA. RP Riazuddin, S (reprint author), Univ Punjab, Natl Ctr Excellence Mol Biol, 87 W Canal Bank Rd, Lahore 53700, Pakistan. EM riaz@lhr.comsats.net.pk RI Shaikh, Rehan Sadiq/B-9101-2009; Nasim Khan, Shaheen/F-2135-2015; SHEIKH, RIAZUDDIN/L-2406-2015 FU Intramural NIH HHS [Z01 DC000039-11]; NIDCD NIH HHS [1 ZO1 DC000035-07, 1 ZO1 DC000039-07, T32 DC000035, Z01 DC000039] NR 27 TC 9 Z9 9 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD NOV 1 PY 2005 VL 138A IS 4 BP 392 EP 395 DI 10.1002/ajmg.a.30949 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 979JI UT WOS:000232937800016 PM 16158433 ER PT J AU Boyd, CM Xue, QL Simpson, CF Guralnik, JM Fried, LP AF Boyd, CM Xue, QL Simpson, CF Guralnik, JM Fried, LP TI Frailty, hospitalization, and progression of disability in a cohort of disabled older women SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE frailty; hospitalization; activities of daily living ID SELF-REPORTED USE; FUNCTIONAL DECLINE; HEALTH-CARE; ADMINISTRATIVE DATA; REGISTRATION DATA; OUTCOMES; HOME; PROGRAM; VULNERABILITY; POPULATION AB PURPOSE: To determine the association between a previously validated frailty phenotype and the development of new-onset dependence in activities of daily living, independent of hospitalizations and other established predictors of disability. SUBJECTS: Seven hundred and forty-nine women enrolled in the Women's Health and Aging Study-I who were independent in all activities in daily living when enrolled in the cohort. METHODS: Assessments and interviews were conducted through home visits at 6-month intervals for 3 years. Frailty was classified using a validated phenotype (>= 3 of the following: weight loss, exhaustion, slow walking, sedentariness, and weak grip), and hospitalizations were identified by self-report. Grouped-time proportional hazard models assessed associations among frailty, hospitalization, and the development of dependence in activities in daily living, adjusting for other factors. RESULTS: Twenty-five percent of the cohort (186/749) were frail at baseline; 56% (104/186) of frail versus 20% (23/117) of nonfrail women developed dependence in activities in daily living (P <.001). In multivariate analysis, frailty was independently associated with the development of dependence in activities in daily living (hazard ratio [HR] = 2.2; 95% confidence interval [CI]: 1.4 to 3.6), adjusting for hospitalization status, age, race, education, baseline functional status, cognition, depressive symptoms, number of chronic diseases, and self-reported health status. Additionally, a dose-response relationship existed between the number of frailty criteria that a woman had and the hazard of subsequent dependence in activities in daily living. CONCLUSION: Frailty, conceptualized as an underlying vulnerability, and hospitalization, which marks an acute deterioration in health, were strongly and independently associated with new-onset dependence in activities in daily living. Additional research is needed to determine if dependence can be minimized by targeting resources and programs to frail older persons. (c) 2005 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Ctr Aging & Hlth, Baltimore, MD 21210 USA. NIA, Dept Med, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA. RP Boyd, CM (reprint author), Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Ctr Aging & Hlth, Suite 2-700,2024 E Monument St, Baltimore, MD 21210 USA. EM cboyd1@jhmi.edu FU NIA NIH HHS [T32-AG00120, N0-1AG-1-2112] NR 38 TC 157 Z9 161 U1 2 U2 12 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD NOV PY 2005 VL 118 IS 11 BP 1225 EP 1231 DI 10.1016/j.amjmed.2005.01.062 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 981YD UT WOS:000233123000010 PM 16271906 ER PT J AU Ferrucci, L Guralnik, JM Woodman, RC Bandinelli, S Lauretani, F Corsi, AM Chaves, PHM Ershler, WB Longo, DL AF Ferrucci, Luigi Guralnik, Jack M. Woodman, Richard C. Bandinelli, Stefania Lauretani, Fulvio Corsi, Anna Maria Chaves, Paulo H. M. Ershler, William B. Longo, Dan L. TI Proinflammatory state and circulating erythropoietin in persons with and without anemia SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Anemia; Inflammation; Cytokines; Erythropoietin; InCHIANTI AB PURPOSE: High circulating levels of proinflammatory cytokines cause anemia, perhaps by interacting with erythropoietin production or biological activity. We characterize the relationships of systemic inflammation, erythropoietin, and hemoglobin. METHODS: Data are from the InCHIANTI (Invecchiare in Chianti, aging in the Chianti area) study population. A sample of 1270 persons aged 65 years or older and 30 men and 30 women from each age-decade 20 to 70 years were randomly selected from the residents in the Chianti, Italy, geographic area. Of the 1714 eligible persons, 1235 had complete data on inflammatory markers, erythropoietin, hemoglobin, potential causes of anemia, and other relevant covariates. Anemia was defined as hemoglobin less than 12 g/dL in women and less than 13 g/dL in men. RESULTS: Independent of age, sex, and hemoglobin, the number of elevated inflammatory markers (C-reactive protein, interleukin-6, interleukin-1beta, and tumor necrosis factor-alpha) was associated with progressively higher erythropoietin in non-anemic participants but lower erythropoietin in anemic participants. Findings were consistent across different causes of anemia. The threshold at which the effect of inflammation on erythropoietin reversed was close to 13.0 g/dL of hemoglobin. CONCLUSIONS: Our findings suggest that anemia of inflammation evolves from a "pre-anemic" stage characterized by a compensatory increment of erythropoietin that maintains normal hemoglobin levels to a stage of clinically evident anemia in which erythropoietin levels are not high enough to maintain normal hemoglobin, possibly because of the inhibitory effect of inflammation on erythropoietin production. This hypothesis requires testing in a longitudinal study. (C) 2005 Elsevier Inc. All rights reserved. C1 [Ferrucci, Luigi; Ershler, William B.; Longo, Dan L.] NIA, Clin Res Branch, Baltimore, MD 21225 USA. [Guralnik, Jack M.] NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21225 USA. [Woodman, Richard C.] Ortho Biotech, Bridgewater, NJ USA. [Bandinelli, Stefania; Lauretani, Fulvio; Corsi, Anna Maria] Italian Natl Inst Res & Care Aging, Lab Clin Epidemiol, Florence, Italy. [Chaves, Paulo H. M.] Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD USA. RP Ferrucci, L (reprint author), NIA, Longitudinal Studies Sect, Clin Res Branch, ASTRA,Harbor Hosp, 5th Floor,3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov NR 28 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD NOV PY 2005 VL 118 IS 11 AR 1288.e11 DI 10.1016/j.amjmed.2005.06.039 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA V30HG UT WOS:000208806500005 ER PT J AU Rodondi, N Vittinghoff, E Cornuz, J Butler, J Ding, JH Satterfield, S Newman, AB Harris, TB Hulley, SB Bauer, DC AF Rodondi, Nicolas Vittinghoff, Eric Cornuz, Jacques Butler, Javed Ding, Jingzhong Satterfield, Suzanne Newman, Anne B. Harris, Tamara B. Hulley, Stephen B. Bauer, Douglas C. CA Hlth Aging Body Composition Study TI Aspirin use for the primary prevention of coronary heart disease in older adults SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE Aspirin; Primary prevention; Coronary heart disease risk AB PURPOSE: Aspirin for the primary prevention of coronary heart disease (has a more favorable risk/benefit profile among adults with high coronary heart disease risk than among low-risk adults, but there is little information on the current patterns of aspirin use for primary prevention. We determined the prevalence of aspirin use in relation to coronary heart disease risk and changes over time. SUBJECTS AND METHODS: We measured regular aspirin use in 2163 black and white older adults without cardiovascular disease in a population-based cohort from 1997 to 1998 and 2002 to 2003. We determined the 10-year coronary heart disease risk by using the Framingham risk score. RESULTS: In 1997-1998, 17% of the cohort were regular aspirin users. Aspirin use increased with coronary heart disease risk from 13% in persons with a 10-year risk less than 6% (low risk) to 23% in those with a 10-year risk greater than 20% (highest risk) (P for trend <.001). Blacks were less likely to use aspirin (13%) than whites (20%). In multivariate analysis, black race was still associated with lower aspirin use (odds ratio 0.66, 95% confidence interval 0.49-0.89). In 1997-1998 and 2002 to 2003, aspirin use increased from 17% to 32% among those still free of coronary heart disease (P <.001), and the association with coronary heart disease risk continued (P for trend <.001). Despite their high coronary heart disease risk, diabetic persons were not more likely to use aspirin than nondiabetic persons, even in 2002 and 2003 (odds ratio 0.89, 95% confidence interval 0.56-1.40). CONCLUSION: Regular use of aspirin by older adults with no history of cardiovascular disease has increased in recent years. Individuals at higher coronary heart disease risk are more likely to take aspirin, but there is room for considerable improvement in targeting those at high risk, particularly diabetic persons and blacks. (C) 2005 Elsevier Inc. All rights reserved. C1 [Rodondi, Nicolas; Vittinghoff, Eric; Hulley, Stephen B.; Bauer, Douglas C.] Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. [Rodondi, Nicolas; Cornuz, Jacques] Univ Lausanne Hosp, Dept Community Med & Publ Hlth, Lausanne, Switzerland. [Butler, Javed] Vanderbilt Univ, Med Ctr, Div Cardiol, Nashville, TN USA. [Ding, Jingzhong] Wake Forest Univ, Sch Med, Dept Internal Med, Winston Salem, NC 27109 USA. [Satterfield, Suzanne] Univ Tennessee, Coll Med, Dept Prevent Med, Memphis, TN USA. [Newman, Anne B.] Univ Pittsburgh, Pittsburgh, PA USA. [Harris, Tamara B.] NIA, Epidemiol Demog & Biometry Program, Bethesda, MD USA. [Bauer, Douglas C.] Univ Calif San Francisco, Dept Med, Div Gen Internal Med, San Francisco, CA USA. RP Rodondi, N (reprint author), Univ Lausanne, Dept Community Med & Publ Hlth, Univ Outpatient Clin, Bugnon 44, CH-1011 Lausanne, Switzerland. EM nicolas.rodandi@hospvd.ch RI Newman, Anne B./C-6408-2013 OI Newman, Anne B./0000-0002-0106-1150 FU National Institute on Aging [NO1-AG-6-2101, NO1-AG-6-2103, NO1-AG-6-2106]; National Institute on Aging funded the Health ABC study; Swiss National Foundation [PBLAB-102353] FX This study was supported by Contracts NO1-AG-6-2101, NO1-AG-6-2103, and NO1-AG-6-2106 of National Institute on Aging. The National Institute on Aging funded the Health ABC study, reviewed the article, and approved its publication. Dr. Rodondi was supported by a grant from the Swiss National Foundation (PBLAB-102353). NR 47 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9343 EI 1555-7162 J9 AM J MED JI Am. J. Med. PD NOV PY 2005 VL 118 IS 11 AR 1288.e1 DI 10.1016/j.amjmed.2005.06.020 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA V30HG UT WOS:000208806500004 ER PT J AU Braverman, NE Mudd, SH Barker, PB Pomper, MG AF Braverman, NE Mudd, SH Barker, PB Pomper, MG TI Characteristic MR imaging changes in severe hypermethioninemic states SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Letter ID ADENOSYLTRANSFERASE-I/III DEFICIENCY C1 Johns Hopkins Med Inst, Dept Pediat, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Neuroradiol, Baltimore, MD 21205 USA. NIMH, Mol Biol Lab, Bethesda, MD 20892 USA. RP Braverman, NE (reprint author), Johns Hopkins Med Inst, Dept Pediat, Baltimore, MD 21205 USA. NR 4 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC NEURORADIOLOGY PI OAK BROOK PA 2210 MIDWEST RD, OAK BROOK, IL 60521 USA SN 0195-6108 J9 AM J NEURORADIOL JI Am. J. Neuroradiol. PD NOV-DEC PY 2005 VL 26 IS 10 BP 2705 EP 2706 PG 2 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 987DB UT WOS:000233497500046 PM 16286426 ER PT J AU Buys, SS Partridge, E Greene, MH Prorok, PC Reding, D Riley, TL Hartge, P Fagerstrom, RM Chia, D Izmirlian, G Fouad, M Ragard, LR Johnson, CC Gohagan, JK AF Buys, SS Partridge, E Greene, MH Prorok, PC Reding, D Riley, TL Hartge, P Fagerstrom, RM Chia, D Izmirlian, G Fouad, M Ragard, LR Johnson, CC Gohagan, JK CA PLCO Project Team TI Ovarian cancer screening in the Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial: Findings from the initial screen of a randomized trial SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article DE ovarian cancer; screening; transvaginal ultrasound; CA-125 ID WOMEN; CARCINOMA; RISK; TUMORS AB Objective: Ovarian cancer screening with transvaginal ultrasound (TVU) and CA-125 was evaluated in the Prostate, Lung, Colorectal and Ovarian (PLCO) Trial. Study design: This was a randomized controlled trial Of Screening Versus usual care. Baseline screening results are reported. Results: Of 39,115 women randomized to receive screening, 28,816 received at least I test. Abnormal TVU was found in 1338 (4.7%), and abnormal CA-125 in 402 (1.4%). Twenty-nine neoplasms were identified (26 Ovarian, 2 fallopian, and 1 primary peritoneal neoplasm). Nine were tumors Of low malignant potential and 20 were invasive. The positive predictive value for invasive cancer was 3.7% for an abnormal CA-125, 1.0% for an abnormal TVU, and 23.5% if both tests were abnormal. Conclusion: The effect of screening on Ovarian cancer mortality in the PLCO cohort has yet to be evaluated and will require longer follow-up. Screening identified both early- and late-state neoplasms, and the predictive value of both tests was relatively low. (C) 2005 Mosby, Inc. All rights reserved. C1 Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA. Univ Alabama, Birmingham, AL USA. NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. NCI, Biometry Res Grp, Div Canc Prevent, NIH,DHHS, Bethesda, MD 20892 USA. Marshfield Clin Res Fdn, Marshfield, WI USA. Informat Management Serv Inc, Rockville, MD USA. NCI, Epidemiol & Biostat Program, Div Canc Epidemiol & Genet,NIH, DHHS, Bethesda, MD 20892 USA. WESTAT Corp, Rockville, MD 20850 USA. Univ Calif Los Angeles, Immunogenet Ctr, Los Angeles, CA USA. Josephine Ford Canc Ctr, Henry Ford Hlth Syst, Detroit, MI USA. NCI, Early Detect Res Grp, Div Canc Prevent, NIH,DHHS, Bethesda, MD 20892 USA. RP Buys, SS (reprint author), Univ Utah, Huntsman Canc Inst, 2000 Circle Hope,Suite 2100, Salt Lake City, UT 84112 USA. EM saundra.buys@hsc.utah.edu OI Johnson, Christine Cole/0000-0002-6864-6604 FU NCI NIH HHS [N01 CN25522] NR 21 TC 159 Z9 164 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD NOV PY 2005 VL 193 IS 5 BP 1630 EP 1639 DI 10.1016/j.ajog.2005.05.005 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 981XU UT WOS:000233122100007 PM 16260202 ER PT J AU Walters, DM Antao-Menezes, A Ingram, JL Rice, AB Nyska, A Tani, Y Kleeberger, SR Bonner, JC AF Walters, DM Antao-Menezes, A Ingram, JL Rice, AB Nyska, A Tani, Y Kleeberger, SR Bonner, JC TI Susceptibility of signal transducer and activator of transcription-1-deficient mice to pulmonary fibrogenesis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; INTERFERON-GAMMA; TYROSINE PHOSPHORYLATION; TARGETED DISRUPTION; INDUCED MITOGENESIS; INDUCED APOPTOSIS; GENE-EXPRESSION; IFN-GAMMA; FIBROSIS; STAT1 AB The signal transducer and activator of transcription (Stat)-1 mediates growth arrest and apoptosis. We postulated that lung fibrosis characterized by excessive proliferation of lung fibroblasts would be enhanced in Stat1-deficient (Stat1(-/-)) mice. Two weeks after bleomycin aspiration (3 U/kg), Stat1(-/-) mice exhibited a more severe fibroproliferative response and significantly elevated total lung collagen compared to wild-type mice. Growth factors [epidermal growth factor (EGF) or platelet-derived growth factor (PDGF)] enhanced [H-3]thymidinc uptake in lung fibroblasts isolated from Stat1(-/-) mice compared to wildtype mice. interferon (IFN)-gamma, which signals growth arrest via Stat1, inhibited EGF- or PDGF-stimulated mitogenesis in wild-type fibroblasts but enhanced [H-3]thymidinc uptake in Stat1(-/-) fibroblasts. Moreover, IFN-gamma treatment in the absence of growth factors induced a concentration-dependent increase in [H-3]thymidine uptake in Stat1(-/-) but not wild-type fibroblasts. Mitogen-activated protein kinase (ERK-1/2) phosphorylation in response to PDGF or EGF did not differ among Stat1(-/-) and wild-type fibroblasts. However, Stat3 phosphorylation induced by PDGF, EGF, or IFN-gamma increased twofold in Stat1(-/-) fibroblasts compared to wild-type fibroblasts. Our findings indicate that Stat1(-/-) mice arc more susceptible to bleomycin-induced lung fibrosis than wild-type mice due to 1) enhanced fibroblast proliferation in response to growth factors (EGF and PDGF), 2) stimulation of fibroblast growth by a Stat1-independent IFN-gamma signaling pathway, and 3) increased activation of Stat3. C1 CIIT Ctr Hlth Res, Div Biol Sci, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, Labs Resp Biol & Expt Pathol, Res Triangle Pk, NC USA. RP Bonner, JC (reprint author), CIIT Ctr Hlth Res, Div Biol Sci, POB 12137, Res Triangle Pk, NC 27709 USA. EM jbonner@ciit.org OI Walters, Dianne/0000-0003-3888-2646 FU Intramural NIH HHS NR 36 TC 30 Z9 31 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2005 VL 167 IS 5 BP 1221 EP 1229 DI 10.1016/S0002-9440(10)61210-2 PG 9 WC Pathology SC Pathology GA 979UK UT WOS:000232970200005 PM 16251407 ER PT J AU Firoved, AM Miller, GF Moayeri, M Kakkar, R Shen, YQ Wiggins, JF McNally, EM Tang, WJ Leppla, SH AF Firoved, AM Miller, GF Moayeri, M Kakkar, R Shen, YQ Wiggins, JF McNally, EM Tang, WJ Leppla, SH TI Bacillus anthracis edema toxin causes extensive tissue lesions and rapid lethality in mice SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID INHALATIONAL ANTHRAX; ADENYLATE-CYCLASE; CYCLIC-AMP; EUKARYOTIC CELLS; KINASE-KINASE; G-CSF; SUSCEPTIBILITY; PATHOLOGY; CALMODULIN; ALPHA AB Bacillus anthracis edema toxin (ET), an adenylyl cyclase, is an important virulence factor that contributes to anthrax disease. The role of ET in anthrax pathogenesis is, however, poorly understood. Previous studies using crude toxin preparations associated ET with subcutaneous edema, and ET-deficient strains of B. anthracis showed a reduction in virulence. We report the first comprehensive study of ET-induced pathology in an animal model. Highly purified ET caused death in BALB/cJ mice at lower doses and more rapidly than previously seen with the other major B. anthracis virulence factor, lethal toxin. Observations of gross pathology showed intestinal intralumenal fluid accumulation followed by focal hemorrhaging of the ileum and adrenal glands. Histopathological analyses of timed tissue harvests revealed lesions in several tissues including adrenal glands, lymphoid organs, bone, bone marrow, gastrointestinal mucosa, heart, and kidneys. Concomitant blood chemistry analyses supported the induction of tissue damage. Several cytokines increased after ET administration, including granulocyte colony-stimulating factor, eotaxin, keratinocyte-derived cytokine, MCP-1/JE, interleukin-6, interleukin-10, and interleukin-1 beta. Physiological measurements also revealed a concurrent hypotension and bradycardia. These studies detail the extensive pathological lesions caused by ET and suggest that it causes death due to multiorgan failure. C1 NIAID, Bacterial Toxins & Therapeut Sect, NIH, Bethesda, MD 20892 USA. NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. RP Leppla, SH (reprint author), NIAID, Bacterial Toxins & Therapeut Sect, NIH, 30 Convent Dr,Bldg 30,Room 303, Bethesda, MD 20892 USA. EM sleppla@niaid.nih.gov OI Tang, Wei-Jen/0000-0002-8267-8995 FU Intramural NIH HHS; NIGMS NIH HHS [GM53459, GM62548, R01 GM062548] NR 57 TC 122 Z9 127 U1 2 U2 8 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2005 VL 167 IS 5 BP 1309 EP 1320 DI 10.1016/S0002-9440(10)61218-7 PG 12 WC Pathology SC Pathology GA 979UK UT WOS:000232970200013 PM 16251415 ER PT J AU Wang, MY Zhang, J Spinetti, G Jiang, LQ Monticone, R Zhao, D Cheng, L Krawczyk, M Talan, M Pintus, G Lakatta, EG AF Wang, MY Zhang, J Spinetti, G Jiang, LQ Monticone, R Zhao, D Cheng, L Krawczyk, M Talan, M Pintus, G Lakatta, EG TI Angiotensin II activates matrix metalloproteinase type II and mimics age-associated carotid arterial remodeling in young rats SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; FACTOR RECEPTOR TRANSACTIVATION; IN-VIVO; GROWTH-FACTOR; CARDIOVASCULAR-DISEASE; NEOINTIMAL FORMATION; INCREASED EXPRESSION; OXIDATIVE STRESS; VASCULAR TISSUE; AGING ARTERIES AB Increased angiotensin II (Ang II), matrix metalloproteinase type II (MMP2), and sympathetic activity accompany age-associated arterial remodeling. To analyze this relationship, we infused a low subpressor dose of Ang II into young (8 months old) rats. This increased carotid arterial MMP2 transcription, translation, and activation, as well as transforming growth factor-beta 1 activity and collagen deposition. A higher Ang II concentration, which increased arterial pressure to that of old (30 months old) untreated rats, produced carotid media thickening and intima infiltration by vascular smooth muscle cells (VSMCs). Ex vivo, Ang II increased MMP2 activity in carotid rings from young rats to that of untreated old rats. Ang II also increased the ability of early passage VSMCs from young rats to invade a synthetic basement membrane, similar to that of untreated VSMCs from old rats. The MMP inhibitor GM6001 and the AT(1) receptor antagonist Losartan inhibited these effects. The alpha-adrenoreceptor agonist phenylephrine increased arterial Ang II protein, causing MMP2 activation and intima and media thickening. Exposure of young VSMCs to phenylephrine in vitro increased Ang II protein and MMP2 activity to the levels of old VSMCs; Losartan abolished these effects. Thus, Ang Pi-induced effects on MMP2, transforming growth factor-beta 1, collagen, and VSMCs are central to the arterial remodeling that accompanies advancing age. C1 NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. RP Lakatta, EG (reprint author), NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, NIH, 5600 Nathan Shock Dr,3-B-03, Baltimore, MD 21224 USA. EM lakattae@grc.nia.nih.gov OI Spinetti, Gaia/0000-0001-7996-6809 FU Intramural NIH HHS NR 56 TC 95 Z9 102 U1 1 U2 5 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD NOV PY 2005 VL 167 IS 5 BP 1429 EP 1442 DI 10.1016/S0002-9440(10)61229-1 PG 14 WC Pathology SC Pathology GA 979UK UT WOS:000232970200024 PM 16251426 ER PT J AU Fuhrer, MJ AF Fuhrer, MJ TI Conducting multiple-site clinical trials in medical rehabilitation research SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Article; Proceedings Paper CT Conference on Multi-site Clinical Trials in Rehabilitation Medicine CY OCT, 2004 CL Denver, CO SP RehabWestNet DE multiple-site clinical trials; outcomes research; medical rehabilitation ID RANDOMIZED CONTROLLED-TRIALS; CHALLENGES; EFFICACY; QUALITY AB This article examines the distinctive opportunities and challenges of multiple-site clinical trials, as distinguished from trials conducted by a single program. Among the topics discussed are: the role of clinical trials generally in medical rehabilitation research; definitions of "clinical trials" and "multiple site"; the distinction between exploratory and capstone trials; the potential advantages and disadvantages of multiple-site trials; planning issues in terms of sampling designs, the choice of outcome measures, approaches to dealing with intervention fidelity, organizational structures, authorship, and the conduct of collateral studies; and implementation issues in terms of pilot-testing procedures, handling emerging issues, and optimizing communication. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Fuhrer, MJ (reprint author), 7508 Broadcloth Way, Columbia, MD 21046 USA. NR 21 TC 10 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD NOV PY 2005 VL 84 IS 11 BP 823 EP 831 DI 10.1097/01.phm.0000184103.57599.01 PG 9 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 979GL UT WOS:000232930300001 PM 16244519 ER PT J AU Kerckhoffs, RCP Faris, OP Bovendeerd, PHM Prinzen, FW Smits, K McVeigh, ER Arts, T AF Kerckhoffs, RCP Faris, OP Bovendeerd, PHM Prinzen, FW Smits, K McVeigh, ER Arts, T TI Electromechanics of paced left ventricle simulated by straightforward mathematical model: comparison with experiments SO AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY LA English DT Article DE eikonal-diffusion equation; electromechanics; ventricular pacing; finite elements ID BUNDLE-BRANCH-BLOCK; ASYNCHRONOUS ELECTRICAL ACTIVATION; DILATED FAILING HEART; CANINE LEFT-VENTRICLE; MECHANICAL ACTIVATION; INTERVENTRICULAR ASYNCHRONY; ENDOCARDIAL ACTIVATION; CARDIAC-MUSCLE; RESYNCHRONIZATION; DEPOLARIZATION AB Intraventricular synchrony of cardiac activation is important for efficient pump function. Ventricular pacing restores the beating frequency but induces more asynchronous depolarization and more inhomogeneous contraction than in the normal heart. We investigated whether the increased inhomogeneity in the left ventricle can be described by a relatively simple mathematical model of cardiac electromechanics, containing normal mechanical and impulse conduction properties. Simulations of a normal heartbeat and of pacing at the right ventricular apex (RVA) were performed. All properties in the two simulations were equal, except for the depolarization sequence. Simulation results of RVA pacing on local depolarization time and systolic midwall circumferential strain were compared with those measured in dogs, using an epicardial sock electrode and MRI tagging, respectively. We used the same methods for data processing for simulation and experiment. Model and experiment agreed in the following aspects. 1) Ventricular pacing decreased systolic pressure and ejection fraction relative to natural sinus rhythm. 2) Shortening during ejection and stroke work declined in early depolarized regions and increased in late depolarized regions. 3) The relation between epicardial depolarization time and systolic midwall circumferential strain was linear and similar for the simulation (slope = -3.80 +/- 0.28 s(-1), R(2) = 0.87) and the experiments [slopes for 3 animals -2.62 +/- 0.43 s(-1) (R(2) = 0.59), -2.97 +/- 0.38 s(-1) (R(2) = 0.69), and -4.44 +/- 0.51 s(-1) (R(2) = 0.76)]. We conclude that our model of electromechanics is suitable to simulate ventricular pacing and that the apparently complex events observed during pacing are caused by well-known basic physiological processes. C1 Eindhoven Univ Technol, Dept Biomed Engn, NL-5600 MB Eindhoven, Netherlands. NHLBI, Cardiac Energet Lab, NIH, Bethesda, MD 20892 USA. Maastricht Univ, Dept Physiol, Maastricht, Netherlands. Maastricht Univ, Dept Lead Modeling, Medtron Bakken Res Ctr, Maastricht, Netherlands. Maastricht Univ, Dept Lead Modeling, Dept Biophys, Maastricht, Netherlands. RP Bovendeerd, PHM (reprint author), Eindhoven Univ Technol, Dept Biomed Engn, POB 513, NL-5600 MB Eindhoven, Netherlands. EM p.h.m.bovendeerd@tue.nl FU Intramural NIH HHS [Z01 HL004609-08] NR 41 TC 37 Z9 37 U1 0 U2 3 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6135 J9 AM J PHYSIOL-HEART C JI Am. J. Physiol.-Heart Circul. Physiol. PD NOV PY 2005 VL 289 IS 5 BP H1889 EP H1897 DI 10.1152/ajpheart.00340.2005 PG 9 WC Cardiac & Cardiovascular Systems; Physiology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Physiology GA 973BI UT WOS:000232497500016 PM 15964924 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 febrigenic role of cyclooxygenase-2 to the previously overlooked responses SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Article DE prostaglandin E(2); cyclooxygenase-1b; cyclooxygenase-1V(1); cyclooxygenase-3; prostaglandin H(2) synthase; body temperature; thermoregulation; febrile phases ID LIPOPOLYSACCHARIDE-INDUCED FEVER; CEREBRAL ENDOTHELIAL-CELLS; PUTATIVE CYCLOOXYGENASE-3; GENE DISRUPTION; BIPHASIC FEVER; GUINEA-PIGS; RAT-BRAIN; EXPRESSION; MICE; ACETAMINOPHEN AB Previous studies on the role of cyclooxygenase (COX)-1 and -2 in fever induced by intravenous LPS have failed to investigate the role of these isoenzymes in the earliest responses: monophasic fever ( response to a low, near-threshold dose of LPS) and the first phase of polyphasic fever ( response to higher doses). We studied these responses in 96 mice that were COX-1 or COX-2 deficient (-/-) or sufficient (-/-). Each mouse was implanted with a temperature telemetry probe into the peritoneal cavity and a jugular catheter. The study was conducted at a tightly controlled, neutral ambient temperature (31 degrees C). To avoid stress hyperthermia ( which masks the onset of fever), all injections were performed through a catheter extension. The +/+ mice responded to intravenous saline with no change in deep body temperature. To a low dose of LPS (1 mu g/kg iv), they responded with a monophasic fever. To a higher dose (56 mu g/kg), they responded with a polyphasic fever. Neither monophasic fever nor the first phase of polyphasic fever was attenuated in the COX-1 -/- mice, but both responses were absent in the COX-2 -/- mice. The second and third phases of polyphasic fever were also missing in the COX-2 -/- mice. The present study identifies a new, critical role for COX-2 in the mediation of the earliest responses to intravenous LPS: monophasic fever and the first phase of polyphasic fever. It also suggests that no product of the COX-1 gene, including the splice variant COX-1b (COX-3), is essential for these responses. C1 St Josephs Hosp, Syst Inflammat Lab, Phoenix, AZ USA. NIEHS, Mol Carcinogenesis Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Romanovsky, AA (reprint author), St Josephs Hosp, 350 W Thomas Rd, Phoenix, AZ 85013 USA. EM aromano@chw.edu RI Steiner, Alexandre/G-1288-2012 OI Steiner, Alexandre/0000-0002-0802-4619 FU NINDS NIH HHS [R01-NS-41233] NR 48 TC 22 Z9 22 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0363-6119 J9 AM J PHYSIOL-REG I JI Am. J. Physiol.-Regul. Integr. Comp. Physiol. PD NOV PY 2005 VL 289 IS 5 BP R1253 EP R1257 DI 10.1152/ajpregu.00371.2005 PG 5 WC Physiology SC Physiology GA 973MZ UT WOS:000232528200005 PM 16081878 ER PT J AU Kim, SW Wang, WD Kwon, TH Knepper, MA Frokiaer, J Nielsen, S AF Kim, SW Wang, WD Kwon, TH Knepper, MA Frokiaer, J Nielsen, S TI Increased expression of ENaC subunits and increased apical targeting of AQP2 in the kidneys of spontaneously hypertensive SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE epithelial sodium channel; aquaporin-2; hypertension; collecting duct ID EPITHELIAL SODIUM-CHANNEL; AGE-RELATED-CHANGES; COLLECTING DUCT; BLOOD-PRESSURE; WATER PERMEABILITY; RENAL HEMODYNAMICS; BETA-SUBUNIT; NA+ CHANNEL; RATS; VASOPRESSIN AB In models of genetic hypertension, renal tubular dysfunction could be involved in the increased sodium and water reabsorption. However, the molecular basis for the increased renal sodium and water retention remains largely undefined in spontaneously hypertensive rats (SHR). We hypothesized that dysregulation of renal epithelial sodium channels (ENaC), sodium (co) transporters, or aquaporin-2 (AQP2) could be involved in the pathogenesis of hypertension in SHR. Six-week-old or twelve-week-old SHR and corresponding age-matched Wistar-Kyoto control rats (WKY) were studied. In both SHR groups, systolic blood pressure was markedly increased, whereas urine output, creatinine clearance, and urinary sodium excretion were decreased compared with corresponding WKY. Moreover, urine osmolality and urine-to-plasma osmolality ratio were increased compared with WKY. Semiquantitative immunoblotting demonstrated that the protein abundance of beta-and gamma-subunits of ENaC was increased in the cortex and outer stripe of the outer medulla and inner stripe of the outer medulla (ISOM) in SHR, whereas alpha-ENaC abundance was increased in ISOM. Immunoperoxidase microscopy confirmed the increased labeling of beta-ENaC and gamma-ENaC subunits in the late distal convoluted tubule, connecting tubule, and cortical and outer medullary collecting duct segments. In contrast, subcellular localization of alpha-ENaC, beta-ENaC, and gamma-ENaC was not changed. Expression of sodium/hydrogen exchanger type 3, bumetanide-sensitive Na-K-2C1 cotransporter, and thiazide-sensitive Na-C1 cotransporter was not altered in SHR. AQP2 levels were increased in the ISOM in SHR, and immunoperoxidase microscopy demonstrated an increased apical labeling of AQP2 in the inner medullary collecting duct in SHR. These results suggest that the increased protein abundance of ENaC subunits as well as the increased apical targeting of AQP2 may contribute to renal sodium and water retention observed during the development of hypertension in SHR. C1 Aarhus Univ, Water & Salt Res Ctr, DK-8000 Aarhus, Denmark. Univ Aarhus, Inst Anat, Aarhus, Denmark. Chonnam Natl Univ, Sch Med, Dept Internal Med, Kwangju, South Korea. Kyungpook Natl Univ, Sch Med, Dept Biochem & Cell Biol, Taegu 702701, South Korea. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Aarhus Univ Hosp, Inst Clin Med, Aarhus, Denmark. RP Nielsen, S (reprint author), Aarhus Univ, Water & Salt Res Ctr, Bldg 233-234, DK-8000 Aarhus, Denmark. EM sn@ana.au.dk FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 55 TC 27 Z9 27 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD NOV PY 2005 VL 289 IS 5 BP F957 EP F968 DI 10.1152/ajprenal.00143.2004 PG 12 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 971LF UT WOS:000232384900003 PM 15956775 ER PT J AU Freo, U Ricciardi, E Pietrini, P Schapiro, MB Rapoport, SI Furey, ML AF Freo, U Ricciardi, E Pietrini, P Schapiro, MB Rapoport, SI Furey, ML TI Pharmacological modulation of prefrontal cortical activity during a working memory task in young and older humans: a PET study with physostigmine SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: Age-associated cholinergic dysfunction may contribute to the cognitive decline observed during aging, including a decline in working memory. The current study was designed to determine how healthy aging influences the neural response to working memory before and during pharmacological potentiation of the cholinergic system. Method: In 13 young and 13 older healthy volunteers, regional cerebral blood flow (rCBF) was measured by using [O-15] H2O and positron emission tomography across 10 scans that alternated between a working-memory-for-faces task and rest. In all subjects, the first two scans were obtained during intravenous saline infusion. Seven young and eight older subjects then received intravenous infusion of physostigmine, a cholinesterase inhibitor, and the remaining six young and five older subjects continued to receive saline. Results: In the placebo condition, task-specific rCBF increases in prefrontal regions were observed in the right middle and inferior frontal cortices in young subjects and in more anterior and ventral prefrontal regions in older individuals. Physostigmine during the working memory task significantly improved performance in both age groups. The right prefrontal regions that were selectively recruited in each age group during the placebo condition showed significantly lower rCBF during physostigmine administration. Conclusions: Cholinergic enhancement does not affect structurally defined cortical regions but rather modulates neural activity in functionally defined regions, that is, in task-related prefrontal cortical areas that are selectively and distinctively recruited in young and older subjects. C1 Univ Pisa, Lab Clin Biochem, Sch Med, Dept Neurol & Psychiat, I-56126 Pisa, Italy. Univ Pisa, Dept Anesthesiol, I-56126 Pisa, Italy. Univ Pisa, Lab Clin Biochem & Mol Biol, Dept Expt Pathol Med Biotechnol Infectivol & Epid, Pisa, Italy. Univ Studies & Doctoral Res, Scuola Super Sant Anna, Pisa, Italy. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. NIA, Brain Physiol & Metab Sect, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Pietrini, P (reprint author), Univ Pisa, Lab Clin Biochem, Sch Med, Dept Neurol & Psychiat, Via Roma 55, I-56126 Pisa, Italy. EM pietro.pietrini@bm.med.unipi.it RI Furey, Maura/H-5273-2013; Ricciardi, Emiliano/E-6929-2011 OI Ricciardi, Emiliano/0000-0002-7178-9534 NR 42 TC 33 Z9 33 U1 0 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2005 VL 162 IS 11 BP 2061 EP 2070 DI 10.1176/appi.ajp.162.11.2061 PG 10 WC Psychiatry SC Psychiatry GA 979XF UT WOS:000232977600011 PM 16263845 ER PT J AU Schulze, TG Ohlraun, S Czerski, PM Schumacher, J Kassem, L Deschner, M Gross, M Tullius, M Heidmann, V Kovalenko, S Abou Jamra, R Becker, T Leszczynska-Rodziewicz, A Hauser, J Illig, T Klopp, N Wellek, S Cichon, S Henn, FA McMahon, FJ Maier, W Propping, P Nothen, MM Rietschel, M AF Schulze, TG Ohlraun, S Czerski, PM Schumacher, J Kassem, L Deschner, M Gross, M Tullius, M Heidmann, V Kovalenko, S Abou Jamra, R Becker, T Leszczynska-Rodziewicz, A Hauser, J Illig, T Klopp, N Wellek, S Cichon, S Henn, FA McMahon, FJ Maier, W Propping, P Nothen, MM Rietschel, M TI Genotype-phenotype studies in bipolar disorder showing association between the DAOA/G30 locus and persecutory delusions: A first step toward a molecular genetic classification of psychiatric phenotypes SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID AMINO-ACID OXIDASE; COMPLEX TRAITS; AMPHETAMINE PSYCHOSIS; CONTROLLED FAMILY; ROSCOMMON FAMILY; SCHIZOPHRENIA; LINKAGE; SCANS; METAANALYSIS; PEDIGREES AB Objective: The authors previously reported an association between the Damino acid oxidase activator (DAOA)/G30 locus and both schizophrenia and bipolar affective disorder. Given the presumed role of DAOA/G30 in the neurochemistry of psychosis and its localization in a schizophrenia and bipolar affective disorder linkage region (13q34), it was hypothesized that the bipolar affective disorder finding would be mainly due to an association with psychotic features. Method: The marker/haplotype associations obtained in a subset of 173 bipolar affective disorder patients with psychotic features were similar to those in the overall patient group, suggesting that stratification on the basis of psychotic features in general might be too crude a procedure. The authors therefore tested whether confining caseness to specific psychotic features would improve detection of genotype-phenotype correlations. Results: In a logistic regression, "persecutory delusions" were found to be the only significant explanatory variable for the DAOA/G30 risk genotype among 21 OPCRIT symptoms of psychosis. The authors therefore tested for association between DAOA/G30 and bipolar affective disorder in the 90 cases with a history of persecutory delusions. Whereas this subset showed strong association (odds ratio=1.83 for the best marker), the remaining larger sample of 165 patients with no such history did not differ from comparison subjects, suggesting that the association between DAOA/G30 and bipolar affective disorder is due to persecutory delusions. This was confirmed in an independent study of 294 bipolar affective disorder patients and 311 comparison subjects from Poland, in which an association between bipolar affective disorder and DAOA/G30 was only seen when case definition was restricted to cases with persecutory delusions. Conclusions: These data suggest that bipolar affective disorder with persecutory delusions constitutes a distinct subgroup of bipolar affective disorder that overlaps with schizophrenia. C1 Univ Heidelberg, Dept Psychiat, Div Genet Epidemiol Psychiat, Heidelberg, Germany. Univ Heidelberg, Div Biostat, Cent Inst Mental Hlth, Heidelberg, Germany. Univ Bonn, Dept Psychiat, D-5300 Bonn, Germany. Inst Human Genet, Bonn, Germany. Inst Med Biometry Informat & Epidemiol, Bonn, Germany. Life & Brain Ctr, Dept Genom, Bonn, Germany. NIMH, Genet Unit, Mood & Anxiety Disorders Program, Bethesda, MD USA. Poznan Univ Med Sci, Dept Adult Psychiat, Poznan, Poland. GSF, Natl Res Ctr Environm & Hlth, Inst Epidemiol, Neuherberg, Germany. GSF, Natl Res Ctr Environm & Hlth, Genome Anal Ctr, Neuherberg, Germany. Univ Antwerp, Dept Med Genet, Antwerp, Belgium. RP Schulze, TG (reprint author), Univ Heidelberg, Dept Psychiat, Div Genet Epidemiol Psychiat, Heidelberg, Germany. EM schulze@zi-mannheim.de RI McMahon, Francis/A-7290-2009; Czerski, Piotr/B-8446-2011; Schulze, Thomas/H-2157-2013; Cichon, Sven/H-8803-2013; Cichon, Sven/B-9618-2014; Abou Jamra, Rami/I-4805-2015; Schumacher, Johannes/F-4970-2015; OI Czerski, Piotr/0000-0003-0745-5916; Cichon, Sven/0000-0002-9475-086X; Cichon, Sven/0000-0002-9475-086X; Abou Jamra, Rami/0000-0002-1542-1399; Schumacher, Johannes/0000-0001-9217-6457; McMahon, Francis/0000-0002-9469-305X NR 41 TC 95 Z9 97 U1 0 U2 4 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2005 VL 162 IS 11 BP 2101 EP 2108 DI 10.1176/appi.ajp.162.11.2101 PG 8 WC Psychiatry SC Psychiatry GA 979XF UT WOS:000232977600016 PM 16263850 ER PT J AU Erickson, K Drevets, WC Clark, L Cannon, DM Bain, EE Zarate, CA Charney, DS Sahakian, BJ AF Erickson, K Drevets, WC Clark, L Cannon, DM Bain, EE Zarate, CA Charney, DS Sahakian, BJ TI Mood-congruent bias in affective Go/No-Go performance of unmedicated patients with major depressive disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article AB Objective: Neuropsychological studies of major depressive disorder have described attentional biases for affectively laden stimuli, but these reports were based on measures obtained from medicated subjects. This study investigated performance of unmedicated depressed patients on the Affective Go/No-Go Task. Method: Twenty depressed patients and 20 healthy comparison subjects, matched for age, gender, and IQ, performed the Affective Go/No-Go Task as well as tests of attention and memory for nonaffective stimuli. Results: Depressed patients did not differ from healthy subjects on memory task performance, but they made more omission errors on the attention task. On the Affective Go/No-Go Task, depressed patients made more omission errors during happy than sad word blocks and required more time to respond to happy than to sad words. In contrast, healthy subjects required more time to respond to sad than to happy words. Conclusions: Unmedicated depressed patients do not show a pattern of generalized cognitive impairment but, rather, specifically display an attentional deficit and a mood-congruent bias toward salient stimuli. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20814 USA. Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. Univ Cambridge, Dept Psychiat, Cambridge CB2 3EB, England. RP Erickson, K (reprint author), NIMH, Mood & Anxiety Disorders Program, 5413 W Cedar Lane,Suite 106-C,Rm 15,MSC 2606, Bethesda, MD 20814 USA. EM ericksok@intra.nimh.nih.gov RI Cannon, Dara/C-1323-2009 OI Cannon, Dara/0000-0001-7378-3411 NR 8 TC 99 Z9 103 U1 1 U2 12 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD NOV PY 2005 VL 162 IS 11 BP 2171 EP U1 DI 10.1176/appi.ajp.162.11.2171 PG 3 WC Psychiatry SC Psychiatry GA 979XF UT WOS:000232977600025 PM 16263859 ER PT J AU Campbell, B Pollick, HF Lituri, KM Horowitz, AM Brown, J Janssen, JA Yoder, K Garcia, RI Deinard, A Hemphill, S de la Torre, MA Shrestha, B Vargas, CM AF Campbell, B Pollick, HF Lituri, KM Horowitz, AM Brown, J Janssen, JA Yoder, K Garcia, RI Deinard, A Hemphill, S de la Torre, MA Shrestha, B Vargas, CM TI Improving the oral health of Alaska natives SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Letter C1 Univ Calif San Francisco, Sch Dent, Dept Prevent & Restorat Dent Sci, San Francisco, CA 94143 USA. Maternal Infant Serv Network Inc, Cent Valley, NY USA. Boston Univ, Sch Dent Med, Dept Hlth Policy & Hlth Serv Res, Boston, MA 02215 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Community Dent, San Antonio, TX USA. Illinois Dept Publ Hlth, Div Oral Hlth, Springfield, IL 62761 USA. Indiana Univ, Sch Med, Div Community Dent, Indianapolis, IN USA. Univ Minnesota, Dept Pediat, Minneapolis, MN 55455 USA. Sinclair Community Coll, Dayton, OH USA. Univ Texas, Hlth Sci Ctr, Sch Allied Hlth Sci, Dept Dent Hlth, San Antonio, TX 78229 USA. Rochester Primary Care Network, Rochester, NY USA. Rochester New York State Oral Hlth Coalit, Rochester, NY USA. Univ Maryland, Dept Hlth Promot & Policy, Sch Dent, Baltimore, MD 21201 USA. RP Pollick, HF (reprint author), Univ Calif San Francisco, Sch Dent, Dept Prevent & Restorat Dent Sci, 707 Parnassus Ave,D-3212, San Francisco, CA 94143 USA. EM howard.pollick@ucsf.edu OI Garcia, Raul/0000-0003-2153-4629 NR 7 TC 2 Z9 2 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD NOV PY 2005 VL 95 IS 11 BP 1880 EP 1880 DI 10.2105/AJPH.2005.074666 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 980XF UT WOS:000233050800003 ER PT J AU Sithanandam, G Smith, GT Fields, JR Fornwald, LW Anderson, LM AF Sithanandam, G Smith, GT Fields, JR Fornwald, LW Anderson, LM TI Alternate paths from epidermal growth factor receptor to Akt in malignant versus nontransformed lung epithelial cells - ErbB3 versus Gab1 SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE EGFR; ErbB3; Gab1; Akt; lung epithelial cells ID C-ERBB-3 PROTEIN EXPRESSION; NORMAL HUMAN ADULT; MOUSE LUNG; PHOSPHATIDYLINOSITOL 3-KINASE; TYROSINE-PHOSPHATASE; SIGNALING NETWORK; TYPE-2 PNEUMOCYTE; FETAL TISSUES; CANCER; ACTIVATION AB In many human lung adenocarcinoma cell lines, a pathway involving epidermal growth factor receptor (EGFR), ErbB2 and ErbB3 receptors, phosphatidyl inositol 3-kinase (Pl3K), Akt, glycogen synthase kinase 3-beta (GSK3-beta), and cyclin D1 controls cell growth, survival, and invasiveness. We have investigated this pathway in paired transformed/nontransformed cell lines from murine peripheral lung epithelium, E9/E10 and A5/C10. The E9 and A5 carcinoma lines expressed ErbB3 and transforming growth factor-alpha (TGF-alpha) and responded to TGF-alpha stimulation with protein complex formation including the p85 regulatory subunit of Pl3K, activation of Akt, phosphorylation of GSK3-beta, and increased cyclin D1 protein and the cell cycle. ErbB3 and TGF-alpha were not detected in the nontransformed E10 and C10 cell lines. Nevertheless, exposure of E10 or C10 cells to TGF-a activated Pl3K and Akt and increased cyclin D1 and cell growth. The effector pathway from the EGFR to Pl3K in these nontransformed cells included the adaptor Grb2, the docking protein Gab1, and the phosphatase Shp2. Gab1 was highly expressed in E10 and C10 cells but not in the malignant E9 and A5 sister lines. Complexes of EGFR/Grb2/Gab1/Shp2 after TGF-alpha stimulation were prominent only in E10 and C10 cells. Thus, alternate pathways downstream of EGFR regulate mitosis in these paired malignant versus nontransformed lung cell lines. C1 SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. RP Sithanandam, G (reprint author), SAIC Frederick, Basic Res Program, Bldg 538, Frederick, MD 21702 USA. EM sithanan@ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 50 TC 27 Z9 30 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1044-1549 J9 AM J RESP CELL MOL JI Am. J. Respir. Cell Mol. Biol. PD NOV PY 2005 VL 33 IS 5 BP 490 EP 499 DI 10.1165/rcmb.2005-0049OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 982SM UT WOS:000233181900011 PM 16055672 ER PT J AU Traverse-Glehen, A Pittaluga, S Gaulard, P Sorbara, L Alonso, MA Raffeld, M Jaffe, ES AF Traverse-Glehen, A Pittaluga, S Gaulard, P Sorbara, L Alonso, MA Raffeld, M Jaffe, ES TI Mediastinal gray zone lymphoma - The missing link between classic Hodgkin's lymphoma and mediastinal large B-cell lymphoma SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 6th International Congress on Hodgkins Lymphoma CY SEP, 2004 CL Cologne, GERMANY DE gray zone lymphoma; composite lymphoma; primary mediastinal large B-cell lymphoma; classic Hodgkin's disease; nodular sclerosis Hodgkin's lymphoma; transcription factor; morphology; immunohistochemistry ID REED-STERNBERG CELLS; DEFECTIVE IMMUNOGLOBULIN TRANSCRIPTION; LASER-CAPTURE-MICRODISSECTION; CHRONIC LYMPHOCYTIC-LEUKEMIA; FOLLICULAR LYMPHOMA; ACTIVATOR PROTEIN; DISEASE; EXPRESSION; GENE; FEATURES AB In recent years, overlap in biologic and morphologic features has been identified between classic Hodgkin lymphoma (cHL) and B-cell non-Hodgkin lymphoma. Nevertheless, the therapeutic approaches for these diseases remain different. We undertook a study of "mediastinal gray zone lymphomas" (MGZL), with features transitional between cHL nodular sclerosis (NS) and primary mediastinal large B-cell lymphoma (MLBCL) to better understand the morphologic and immunophenotypic spectrum of such cases. Twenty-one MGZL cases were identified over a 20-year period. We also studied 6 cases of composite or synchronous lymphoma with two distinct components at the same time (cHL-NS and MLBCL) and 9 sequential cases with MLBCL and cHL-NS at different times. All patients had a large mediastinal mass. Immunohistochemical studies focused on markers known to discriminate between cHL and MLBCL, including B-cell transcription factors. VJ-PCR was performed in 8 cases to look at clonality of the immunoglobulin heavy chain gene (IgH). Of the gray zone cases, I I had morphology reminiscent of cHL-NS, but with unusual features, including a large number of mononuclear variants, diminished inflammatory background, absence of classic Hodgkin phenotype, and strong CD20 expression (I I of 11). Ten cases had morphology of MLBCL, but with admixed Hodgkin/Reed-Sternberg and lacunar cells, absent (3 of 10) or weak (7 of 10) CD20 expression, and positivity for CD15 in 7 cases. B-cell transcription factor expression in the gray zone cases more closely resembled MLBCL than cHL with expression of Pax5, Oct2, and BOB. I in all but I case studied (14 of 15). MAL staining was found in 7 of 10 MGZL, and in at least one component of 6 of 7 evaluable composite or sequential MLBCL/cHL cases. Two cases of sequential lymphoma showed rearrangements of the IgH gene of identical size: one in which MLBCL was the first diagnosis and one in which MLBCL was diagnosed at relapse, indicating clonal identity for the two components of cHL and MLBCL. There is accumulating evidence that MLBCL and cHL are related entities. Further support for a relationship between MLBCL and cHL-NS is provided by composite and metachronous lymphomas in the same patient, as well as the existence of MGZL with transitional morphology and phenotype. C1 NIH, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. Hop Henri Mondor, Dept Pathol, F-94010 Creteil, France. Univ Autonoma Madrid, Ctr Mol Biol, E-28049 Madrid, Spain. RP Jaffe, ES (reprint author), Bldg 10,Room 2N202,10 Ctr Dr,MSC 1500, Bethesda, MD 20892 USA. EM elainejaffe@nih.gov RI Alonso, Miguel/J-3945-2016 OI Alonso, Miguel/0000-0002-7001-8826 FU Intramural NIH HHS NR 58 TC 128 Z9 140 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD NOV PY 2005 VL 29 IS 11 BP 1411 EP 1421 DI 10.1097/01.pas.0000180856.74572.73 PG 11 WC Pathology; Surgery SC Pathology; Surgery GA 978GB UT WOS:000232860500001 PM 16224207 ER PT J AU Higgs, ES Sina, B AF Higgs, ES Sina, B TI Introduction - Plasmodium vivax vaccine research: Steps in the right direction SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Editorial Material ID MALARIA; MONKEYS C1 NIAID, Bethesda, MD 20892 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Higgs, ES (reprint author), NIAID, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2005 VL 73 IS 5 SU S BP 1 EP 2 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 986HL UT WOS:000233440600001 PM 16291759 ER PT J AU Arevalo-Herrera, M Solarte, Y Yasnot, MF Castellanos, A Rincon, A Saul, A Mu, JB Long, C Miller, L Herrera, S AF Arevalo-Herrera, M Solarte, Y Yasnot, MF Castellanos, A Rincon, A Saul, A Mu, JB Long, C Miller, L Herrera, S TI Induction of transmission-blocking immunity in aotus monkeys by vaccination with a Plasmodium vivax clinical grade Pvs25 recombinant protein SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID ANOPHELES-ALBIMANUS; MALARIA VACCINE; FALCIPARUM; ANTIBODIES; MOSQUITOS; EXPRESSION; CANDIDATE; ANTIGENS; PFS25; PFS48/45 AB Aotus monkeys were used to determine the immunogenicity of Pvs25 protein expressed in the zygote/ookinete surface. Animals were immunized in three times with 100 mu g of Pvs25 formulated in Montanide ISA-720. Antibodies to Pvs25 detected by an enzyme-linked immunosorbent assay appeared by day 30 after the first immunization, with a peak of antibodies levels on day 150. These antibodies were still detectable on day 300. Plasma samples on day 150 from experimental group were able to completely block the development of the parasite in Anopheles albimanus mosquitoes artificially fed with human isolates of Plasmodium vivax. Immunized Aotus monkeys were infected with blood forms of the P. vivax Salvador I strain and no boosting effect of blood infection on titers of antibodies to Pvs25 was observed despite the presence of infective gametocytes. In conclusion, Pvs25 protein formulated in Montanide ISA-720 induces efficient and long-lasting transmission-blocking antibodies that cannot be boosted by parasite infection. C1 Malaria Vaccine & Drug Dev Ctr, Cali 26020, Colombia. Univ Valle, Inst Inmunol Valle, Cali, Colombia. NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20892 USA. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Arevalo-Herrera, M (reprint author), Malaria Vaccine & Drug Dev Ctr, Carrera 35 4A-53, Cali 26020, Colombia. EM marevalo@inmuno.org RI Solarte, Yezid/C-1196-2013; Saul, Allan/I-6968-2013 OI Solarte, Yezid/0000-0003-4173-0256; Saul, Allan/0000-0003-0665-4091 FU PHS HHS [49486] NR 26 TC 25 Z9 26 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2005 VL 73 IS 5 SU S BP 32 EP 37 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 986HL UT WOS:000233440600006 PM 16291764 ER PT J AU Arevalo-Herrera, M Solarte, Y Zamora, F Mendez, F Yasnot, MF Rocha, L Long, C Miller, LH Herrera, S AF Arevalo-Herrera, M Solarte, Y Zamora, F Mendez, F Yasnot, MF Rocha, L Long, C Miller, LH Herrera, S TI Plasmodium vivax: Transmission-blocking immunity in a malaria-endemic area of Colombia SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID SRI-LANKA; ANTIBODIES; INFECTION; VACCINE; KATARAGAMA; POPULATION; PARASITES; HUMANS; BURDEN; SERA AB Plasmodium vivax transmission-block in g activity was assessed in sera from acutely infected patients from a malaria-endemic area in Colombia. We measured reduction in the number of oocysts that developed in the midguts of Anopheles albimanus mosquitoes artificially fed with blood from these patients. Of 88 mosquito batches that developed infections when parasites were mixed with normal AB human serum, one-third (36.4%) showed full transmission-blocking activity (>= 90% inhibition) when mixed with autologous sera, 29.6% showed partial activity (50-89%), 17.0% did not block transmission (0-50%), and 17% did not enhance transmission. Transmission-blocking activity correlated with antibody titer by an immunofluorescent antibody test and decreased with the serial dilution of the sera. This activity disappeared at a 1:4 dilution in most sera tested. Afro-Colombian individuals showed lower activity than other ethnic groups and febrile patients produced stronger inhibition than those without fever. C1 Inst Inmunol Valle, Cali, Colombia. Malaria Vaccine & Drug Dev Ctr, Cali, Colombia. Univ Valle, Sch Publ Hlth, Cali, Colombia. NIAID, Malaria Vaccine Dev Branch, NIH, Bethesda, MD 20892 USA. RP Arevalo-Herrera, M (reprint author), Univ Valle, Inst Immunol, Fac Salud, Edificio Microbiol,Tercer Piso, Cali 25574, Colombia. EM marevalo@inmuno.org RI Solarte, Yezid/C-1196-2013 OI Solarte, Yezid/0000-0003-4173-0256 FU PHS HHS [49486] NR 24 TC 15 Z9 15 U1 0 U2 2 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD NOV PY 2005 VL 73 IS 5 SU S BP 38 EP 43 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 986HL UT WOS:000233440600007 PM 16291765 ER PT J AU Attri, AK Minton, AP AF Attri, AK Minton, AP TI Composition gradient static light scattering: A new technique for rapid detection and quantitative characterization of reversible macromolecular hetero-associations in solution SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE protein-protein association equilibria; Rayleigh light scattering ID SOYBEAN TRYPSIN-INHIBITOR; PROTEINS AB A method for rapid detection and quantitative characterization of associations between two proteins in solution is presented, based upon continuous measurement of the Rayleigh light scattering and UV absorbance of a solution whose composition is varied with time in a controlled fashion. Collection and subsequent analysis of data are both rapid and semiautomatic. The results of validation experiments demonstrate that the technique can correctly identify complexes and reliably evaluate equilibrium constants for hetero-association. (C) 2005 Elsevier Inc. All rights reserved. C1 NIDDKD, Lab Biochem & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. Jawaharlal Nehru Univ, Sch Environm Sci, New Delhi 110067, India. RP Minton, AP (reprint author), NIDDKD, Lab Biochem & Genet, NIH, US Dept HHS, Bethesda, MD 20892 USA. EM minton@helix.nih.gov OI Minton, Allen/0000-0001-8459-1247 FU Intramural NIH HHS NR 13 TC 35 Z9 36 U1 0 U2 6 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 NOV 1 PY 2005 VL 346 IS 1 BP 132 EP 138 DI 10.1016/j.ab.2005.08.013 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 978FQ UT WOS:000232859400013 PM 16188220 ER PT J AU Gannon, PJ Kheck, NM Braun, AR Holloway, RL AF Gannon, PJ Kheck, NM Braun, AR Holloway, RL TI Planum parietale of chimpanzees and orangutans: A comparative resonance of human-like planum temporale asymmetry SO ANATOMICAL RECORD PART A-DISCOVERIES IN MOLECULAR CELLULAR AND EVOLUTIONARY BIOLOGY LA English DT Article; Proceedings Paper CT Symposium on Evolution of Neurobiological Specializations in Mammals held at the American-Association-of-Anatomists CY APR, 2005 CL San Diego, CA SP Amer Assoc Anatomists DE brain language areas; evolution; polymodal language; primates; dyslexia; comparative neurobiology; great apes ID HOMO-SAPIENS PAYS; DEVELOPMENTAL DYSLEXIA; CEREBRAL ASYMMETRY; LANGUAGE FUNCTIONS; RIGHT-HEMISPHERE; SPEECH REGION; RIGHT-HANDERS; AREA HOMOLOG; HUMAN-BRAIN; GREAT APES AB We have previously demonstrated that leftward asymmetry of the planum temporale (PT), a brain language area, was not unique to humans since a similar condition is present in great apes. Here we report on a related area in great apes, the planum parietale (PP). PP in humans has a rightward asymmetry with no correlation to the L > R PT, which indicates functional independence. The roles of the PT in human language are well known while PP is implicated in dyslexia and communication disorders. Since posterior bifurcation of the sylvian fissure (SF) is unique to humans and great apes, we used it to determine characteristics of its posterior ascending ramus, an indicator of the PP, in chimpanzee and orang-utan brains. Results showed a human-like pattern of R > L PP (P = 0.04) in chimpanzees with a nonsignificant negative correlation of L > R PT vs. R > L PP (CC = -0.3; P = 0.39). In orangutans, SF anatomy is more variable, although PP was nonsignificantly R > L in three of four brains (P = 0.17). We have now demonstrated human-like hemispheric asymmetry of a second language-related brain area in great apes. Our findings persuasively support an argument for addition of a new component to the comparative neuroanatomic complex that defines brain language or polymodal communication areas. PP strengthens the evolutionary links that living great apes may offer to better understand the origins of these progressive parts of the brain. Evidence mounts for the stable expression of a neural foundation for language in species that we recently shared a common ancestor with. (c) 2005 Wiley-Liss, Inc. C1 CUNY Mt Sinai Sch Med, Dept Otolaryngol, New York, NY 10029 USA. CUNY Mt Sinai Sch Med, Dept Med Educ, New York, NY 10029 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. Columbia Univ, Dept Anthropol, New York, NY 10027 USA. RP Gannon, PJ (reprint author), CUNY Mt Sinai Sch Med, Dept Otolaryngol, Annenbert 10 1189,5th Ave 100th St, New York, NY 10029 USA. EM patrick.gannon@mssm.edu NR 68 TC 15 Z9 17 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4884 J9 ANAT REC PART A JI Anat. Rec. Part A PD NOV PY 2005 VL 287A IS 1 BP 1128 EP 1141 DI 10.1002/ar.a.20256 PG 14 WC Anatomy & Morphology SC Anatomy & Morphology GA 981PM UT WOS:000233100500012 PM 16215971 ER PT J AU Karzai, W Cui, XZ Heinicke, N Niemann, C Gerstenberger, EP Correa, R Banks, S Mehlhorn, B Bloos, F Reinhart, K Eichacker, PQ AF Karzai, W Cui, XZ Heinicke, N Niemann, C Gerstenberger, EP Correa, R Banks, S Mehlhorn, B Bloos, F Reinhart, K Eichacker, PQ TI Neutrophil stimulation with granulocyte colony-stimulating factor worsens ventilator-induced lung injury and mortality in rats SO ANESTHESIOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; TUMOR-NECROSIS-FACTOR; RANDOMIZED CONTROLLED-TRIAL; ESCHERICHIA-COLI PNEUMONIA; SURFACTANT-DEPLETED LUNG; END-EXPIRATORY PRESSURE; MECHANICAL VENTILATION; AIRWAY PRESSURE; OXIDATIVE BURST; PULMONARY-EDEMA AB Background: Based on the association between the neutrophil and ventilator-induced lung injury, the authors hypothesized that neutrophil inhibition with fucoidin would be beneficial and stimulation with granulocyte colony-stimulating factor (G-CSF) would be harmful in a rat model of lethal ventilator-induced lung injury. Methods: Animals (n = 111) were randomly assigned to be pretreated with fucoidin, G-CSF, or placebo (control) before 4 h of low-tidal-volume (10 ml/kg) or high-tidal-volume (40 ml/kg) mechanical ventilation. Results: All low-volume animals survived. With high volumes, compared with controls, fucoidin did not improve survival (3 of 20 control animals and 5 of 20 fucoidin animals died; P = 0.51) but G-CSF significantly worsened it (18 of 22 animals died; P < 0.001). Circulating neutrophils were increased early with G-CSF and late with fucoidin with low and high tidal volumes (P < 0.05 for each treatment and tidal volume). Fucoidin decreased lung neutrophils, but these were only significant with high tidal volumes, whereas G-CSF increased lung neutrophils but only significantly with low tidal volumes (P < 0.01 for each). Fucoldin did not alter any cardiopulmonary measure significantly. Compared with control, G-CSF increased airway pressures with high tidal volumes and worsened lung edema and arterial oxygen with both tidal volumes (P < 0.05 for each). Conclusions: In this model, neutrophil stimulation by G-CSF increased lung dysfunction and with high tidal volumes worsened survival rates. Extrapolated clinically, neutrophil stimulation either by agents such as G-CSF or conditions such as sepsis may aggravate ventilator-induced lung injury. C1 Friedrich Schiller Univ Hosp, Dept Anesthesiol & Crit Care Med, Jena, Germany. NIH, Dept Crit Med, Bethesda, MD 20892 USA. RP Karzai, W (reprint author), Zentralklin Bad Berka, Dept Anesthesia & Intens Care, Robert Kock Allee 9, D-99437 Bad Berka, Germany. EM ana@zentralklinik-bad-berka.de NR 49 TC 20 Z9 28 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2005 VL 103 IS 5 BP 996 EP 1005 DI 10.1097/00000542-200511000-00014 PG 10 WC Anesthesiology SC Anesthesiology GA 980LP UT WOS:000233020300013 PM 16249674 ER PT J AU Brown, DC Iadarola, MJ Perkowski, SZ Erin, H Shofer, F Laszlo, KJ Olah, Z Mannes, AJ AF Brown, DC Iadarola, MJ Perkowski, SZ Erin, H Shofer, F Laszlo, KJ Olah, Z Mannes, AJ TI Physiologic and antinociceptive effects of intrathecal resiniferatoxin in a canine bone cancer model SO ANESTHESIOLOGY LA English DT Article ID CEREBROSPINAL-FLUID; OCCURRING TUMORS; PET DOGS; PAIN; OSTEOSARCOMAS; MECHANISM; CAPSAICIN; DELETION; THERAPY; ANIMALS AB Background: Resiniferatoxin is a potent capsaicin analog. Intrathecal administration leads to selective, prolonged opening of the transient receptor potential V1 ion channel, which is localized mainly to C-fiber primary afferent nociceptive sensory neurons. Following work in laboratory animals, the authors explored the use of intrathecal resiniferatoxin to control spontaneous bone cancer pain in companion (pet) dogs. Methods. Normal canine population: Behavioral testing was performed to establish baseline paw withdrawal latency; subsequently, general anesthesia was induced and resiniferatoxin was administered intrathecally while hemodynamic parameters were recorded. Behavior testing was repeated for 12 days after administration of resiniferatoxin. Clinical canine population: Twenty companion dogs with bone cancer pain were recruited. The animal's baseline level of discomfort and analgesic use were recorded. Resiniferatoxin was administered intrathecally and hemodynamic parameters were monitored while the dogs were under general anesthesia. Dogs were reevaluated up to 14 weeks after resiniferatoxin administration. Results: Normal canine population: In the first minutes after resiniferatoxin injection, there were significant (P < 0.05) increases in mean arterial blood pressure and heart rate from baseline. Two days after injection, limb withdrawal latencies increased to the point of cutoff in the dogs that received at least 1.2 mu g/kg resiniferatoxim. Clinical canine population: From baseline, there were significant (P < 0.05) increases in mean arterial blood pressure and heart rate after resiniferatoxin injection. Comfort scores were significantly improved at 2, 6, 10, and 14 weeks after resiniferatoxin administration (P < 0.0001). There was decreased or discontinued use of supplemental analgesics in 67% of the dogs 2 weeks after resiniferatoxin administration. Conclusions: Intrathecal resiniferatoxin elicits transient hemodynamic effects. in controls, a profound and sustained blockade of thermal stimuli is produced in a dose-dependent fashion. Similar administration in dogs with bone cancer produces a prolonged antinociceptive response. C1 Univ Penn, Sch Vet Med, Dept Clin Studies, Philadelphia, PA 19104 USA. Natl Inst Dent & Craniofacial Res, Pain & Palliat Care Serv, NIH, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, Neuronal Gene Express Unit, Pain & Neurosensory Mech Branch, NIH, Bethesda, MD USA. Acheuron Hungary Ltd, Szeged, Hungary. RP Brown, DC (reprint author), Univ Penn, Sch Vet Med, Dept Clin Studies, Philadelphia, PA 19104 USA. EM dottie@vet.upenn.edu OI Mannes, Andrew/0000-0001-5834-5667 NR 29 TC 89 Z9 91 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD NOV PY 2005 VL 103 IS 5 BP 1052 EP 1059 DI 10.1097/00000542-200511000-00020 PG 8 WC Anesthesiology SC Anesthesiology GA 980LP UT WOS:000233020300019 PM 16249680 ER PT J AU De Roos, AJ Cooper, GS Alavanja, MC Sandler, DP AF De Roos, AJ Cooper, GS Alavanja, MC Sandler, DP TI Rheumatoid arthritis among women in the agricultural health study: Risk associated with farming activities and exposures SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE rheumatoid arthritis; autoimmune diseases; autoimmunity; pesticides; farming; occupation ID CIGARETTE-SMOKING; OCCUPATIONAL-EXPOSURE; CRYSTALLINE SILICA; AUTOIMMUNE-DISEASE; COHORT; DETERMINANTS; CONSUMPTION; POPULATION; PREVALENCE; HERBICIDES AB PURPOSE: Farming has been associated with increased risk of rheumatoid arthritis (RA) in some studies, but specific causes have not been identified. We studied risk factors for RA in the Agricultural Health Study, a cohort of over 57,000 licensed pesticide applicators and their spouses. METHODS: We used a nested case-control design, limited to female participants. Physician-confirmed cases (n = 135) were matched to five controls each (n = 675) by birth date, We used logistic regression, adjusting for birth date and state to examine associations, as estimated by odds ratios (OR) and 95% confidence intervals (CI). RESULTS: Risk of RA was not associated with mixing or applying pesticides overall or with any pesticide class, nor did it vary by number of days or years of use. Certain pesticides were associated with small non-significantly increased risks, including lindane (OR = 1.8, 95% CI: 0.6-5.0). RA risk was associated with welding (OR = 2.1, 95% CI: 0.8-5.4), albeit imprecisely, but not with solvents or sunlight. CONCLUSIONS: We did not identify any strong risk factors for RA. Because of the severe disability associated with this relatively common disease, further investigation into causes is warranted both in the Agricultural Health Study and elsewhere. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98109 USA. Natl Inst Environm Hlth Sci, Program Epidemiol, Res Triangle Pk, NC USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP De Roos, AJ (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M4-B874, Seattle, WA 98109 USA. EM deroos@u.washington.edu OI Sandler, Dale/0000-0002-6776-0018 NR 37 TC 27 Z9 29 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD NOV PY 2005 VL 15 IS 10 BP 762 EP 770 DI 10.1016/j.annepidem.2005.08.001 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 986GM UT WOS:000233438100007 PM 16257361 ER PT J AU De Vocht, F Straif, K Szeszenia-Dabrowska, N Hagmar, L Sorahan, T Burstyn, I Vermeulen, R Kromhout, H AF De Vocht, F Straif, K Szeszenia-Dabrowska, N Hagmar, L Sorahan, T Burstyn, I Vermeulen, R Kromhout, H TI A database of exposures in the rubber manufacturing industry: Design and quality control SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Article DE database; data quality; exposure assessment; multi-centre study; rubber manufacturing industry ID WORKERS; MORTALITY; CANCER; COHORT; NITROSAMINES AB The concerted action EXASRUB was initiated to create a database management system for information on occupational hygiene measurements that could be used to develop exposure models in the European rubber manufacturing industry. Quality of coding was assessed by calculating percentages of agreement and Cohen's kappa statistics (kappa) for an intra- and inter-centre recoding of randomly selected subsets of the measurements. In a 6-month period, 59 609 measurements from 523 surveys in 333 factories from as early as 1956 to 2003 were coded. The database consists primarily of measurements of N-nitrosamines (36%), rubber dust (23%), solvents (14%) and rubber fumes (10%). Coding of epidemiologically relevant information was done consistently with inter-centre kappa between 0.86 and 1.00. For occupational hygiene information, values of kappa were estimated to be between 0.67 and 1.00. The proposed method resulted in a large quantity of exposure measurements with auxiliary information of varying completeness and quality. Analyses showed that coding of epidemiologically relevant information in such a multi-centre, multi-country study was coded consistently. Larger errors however, occurred in coding of occupational hygiene information. This was primarily caused by lack of information in the primary records of measurements, emphasizing the importance of having a universal system in place to collect and store measurement information by occupational hygienists for future use. C1 Univ Utrecht, Inst Risk Assessment Sci, Environm & Occupat Hlth Div, Utrecht, Netherlands. IARC, Lyon, France. Nofer Inst Occupat Med, Lodz, Poland. Univ Lund Hosp, Dept Occupat & Environm Med, S-22185 Lund, Sweden. Univ Alberta, Fac Med & Dent, Dept Publ Hlth Sci, Edmonton, AB, Canada. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Kromhout, H (reprint author), Univ Utrecht, Inst Risk Assessment Sci, Environm & Occupat Hlth Div, Utrecht, Netherlands. EM H.Kromhout@IRAS.uu.nl RI Kromhout, Hans/A-9159-2008; Szeszenia-Dabrowska, Neonila/F-7190-2010; Vermeulen, Roel/F-8037-2011; OI Vermeulen, Roel/0000-0003-4082-8163; de Vocht, Frank/0000-0003-3631-627X NR 28 TC 21 Z9 21 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0003-4878 J9 ANN OCCUP HYG JI Ann. Occup. Hyg. PD NOV PY 2005 VL 49 IS 8 BP 691 EP 701 DI 10.1093/annhyg/mei035 PG 11 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 985SQ UT WOS:000233399200006 PM 16126766 ER PT J AU Maker, AV Nguyen, DM AF Maker, AV Nguyen, DM TI Active malignant pleural effusion captured through the thoracoscope SO ANNALS OF THORACIC SURGERY LA English DT Editorial Material C1 NCI, NIH, Surg Branch, Bethesda, MD 20892 USA. RP Nguyen, DM (reprint author), NCI, NIH, Surg Branch, Bldg 10,Rm 2C710,10 Ctr Dr, Bethesda, MD 20892 USA. EM dao-nguyen@nih.gov NR 0 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD NOV PY 2005 VL 80 IS 5 BP 1941 EP 1941 DI 10.1016/j.athoracsur.2003.11.065 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 979UN UT WOS:000232970500069 PM 16242497 ER PT J AU Nagasawa, H Uto, Y Sasaki, H Okamura, N Murakami, A Kubo, S Kirk, KL Hori, H AF Nagasawa, H Uto, Y Sasaki, H Okamura, N Murakami, A Kubo, S Kirk, KL Hori, H TI Gc protein (vitamin D-binding protein): Gc genotyping and GcMAF precursor activity SO ANTICANCER RESEARCH LA English DT Article; Proceedings Paper CT 8th Annual Meeting of the Society-of-Biotherapeutic-Approaches/3rd Meeting of the Japan-Research-Association-of-Immunotherapeutics CY DEC 04, 2004 CL Fukuoka, JAPAN SP Soc Biotherapeut Approaches, Japan Res Assoc Immunotherapeut DE Gc protein; Gc protein-derived macrophage activating factor (GcMAF); alpha-N-acetylgalactosaminidase; review ID MACROPHAGE ACTIVATING FACTOR; GROUP-SPECIFIC COMPONENT; ALPHA-N-ACETYLGALACTOSAMINIDASE; FACTOR DBP-MAF; EHRLICH ASCITES TUMOR; PHOTODYNAMIC THERAPY; STRUCTURAL BASIS; CANCER-PATIENTS; ANGIOGENESIS; ACTIN AB The Gc protein (human group-specific component (Gc), a vitamin D-binding protein or Gc globulin), has important physiological functions that include involvement in vitamin D transport and storage, scavenging of extracellular G-actin, enhancement of the chemotactic activity of C5a for neutrophils in inflammation and macrophage activation (mediated by a GalNAc-modified Gc protein (GcMAF)). In this review, the structure and function of the Gc protein is focused on especially with regard to Gc genotyping and GcMAF precursor activity. A discussion of the research strategy "GcMAF as a target for drug discovery" is included, based on our own research. C1 Univ Tokushima, Dept Biol Sci & Technol, Fac Engn, Tokushima 7708506, Japan. Univ Tokushima, Inst Hlth Biosci, Dept Forens Med, Grad Sch, Tokushima 7708503, Japan. NIDDK, Bioorgan Chem Lab, DHHS, NIH, Bethesda, MD 20892 USA. RP Hori, H (reprint author), Univ Tokushima, Dept Biol Sci & Technol, Fac Engn, Minamijosanjimacho 2, Tokushima 7708506, Japan. EM hori@bio.tokushima-u.ac.jp NR 35 TC 36 Z9 38 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 2005 VL 25 IS 6A BP 3689 EP 3695 PG 7 WC Oncology SC Oncology GA 984BT UT WOS:000233278200002 PM 16302727 ER PT J AU Lelong-Rebel, IH Cardarelli, CO AF Lelong-Rebel, IH Cardarelli, CO TI Differential phosphorylation patterns of P-glycoprotein reconstituted into a proteoliposome system: Insight into additional unconventional phosphorylation sites SO ANTICANCER RESEARCH LA English DT Article DE P-glycoprotein; multidrug resistance; KB-V1; plasma membrane vesicles; phosphorylation; reconstitution; proteoliposomes; octyl-glucoside ID PROTEIN-KINASE-C; MULTIDRUG-RESISTANT CELLS; OVARIAN PLASMA-MEMBRANES; KB CARCINOMA-CELLS; DRUG TRANSPORT; FUNCTIONAL RECONSTITUTION; MCF-7 CELLS; HL60 CELLS; ATP HYDROLYSIS; LINKER REGION AB Membrane vesicles from the multidrug-resistant KB-V1 and KB-C1 cell lines overexpressing P-glycoprotein (Pgp), responsible for pleiotropic chemotherapeutic agents resistance, were solubilized with octyl-glucoside (OG-EX) and further fractionated on DEAE-sepharose column with increased concentrations of NaCl. The fraction containing Pgp (F3) was reconstituted into proteoliposomes (F3-PLP). Comparisons of the phosphotylation levels of Pgp achieved throughout the purification and reconstitution steps' were addressed in this study. The [gamma(32)P] ATP-driven phosphorylation of Pgp was strongly increased in OG-EX, decreased in F3 and not detected in F3-PLP, when compared to Pgp phosphorylation in native plasma membrane vesicles. [gamma(32)P]ATP-phosphorylation of Pgp in F3-PLP could be restored by exogenously added PKC or by the catalytic sub-unit of PKA. The vanadate-induced hyperphosphorylation effect on Pgp by [gamma(32)P]ATP observed with plasma membrane vesicles was maintained in OG-EX, but was lost in F3 and did not enable labelling in F3-PLP. Enhancement of [gamma(3)P]-labelling of native Pgp via [gamma(32)P]ATP combined with GTP was maintained and also triggered phosphorylation of purified/reconstituted Pgp in F3-PLP as well. Altogether, our data suggest differential phosphorylation patterns of the transporter linked to environmental molecular composition (lipids, presence of detergent) and structure (unfolded versus embedded). In addition, restoration by GTP of Pgp phosphorylation by [gamma(32)P]ATP in the frame of F3-PLP suggests intra-molecular modulations and hints that other phosphorylation sites and processes, different from the classic ones involving PKC and/or PKA, may participate in the transporter's mechanism. C1 ULP, Hop Civil, CNRS, EA 3430,Lab Cancerol Expt & Radiobiol,IRCAD, F-67091 Strasbourg, France. NCI, Cell Biol Lab, HNC 796, NIH, Bethesda, MD 20892 USA. RP Lelong-Rebel, IH (reprint author), ULP, Hop Civil, CNRS, EA 3430,Lab Cancerol Expt & Radiobiol,IRCAD, BP 426, F-67091 Strasbourg, France. EM Isabelle.Lelong@ircad.u-strasbg.fr NR 90 TC 12 Z9 13 U1 0 U2 2 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 2005 VL 25 IS 6B BP 3925 EP 3935 PG 11 WC Oncology SC Oncology GA 984BU UT WOS:000233278300020 PM 16309179 ER PT J AU Liang, XJ Taylor, B Cardarelli, C Yin, JJ Annereau, JP Garfield, S Wincovitch, S Szakacs, G Gottesman, MM Aszalos, A AF Liang, XJ Taylor, B Cardarelli, C Yin, JJ Annereau, JP Garfield, S Wincovitch, S Szakacs, G Gottesman, MM Aszalos, A TI Different roles for K+ channels in cisplatin-resistant cell lines argue against a critical role for these channels in cisplatin resistance SO ANTICANCER RESEARCH LA English DT Article DE cisplatin resistance; K plus channels; ion homeostasis; microarray; confocal microscopy ID AMPHOTERICIN-B; MULTIDRUG-RESISTANCE; INDUCED APOPTOSIS; CARCINOMA-CELLS; DNA DAMAGE; CYTOTOXICITY; EXPRESSION; PLATINUM; SYSTEM; DRUGS AB Cisplatin resistance has been associated with altered K+ fluxes. Here, we focused our investigations on the detection of K+ channels in a series of cisplatin-resistant (CP-r) cells with increasing resistance and on the functional relationship of these K+ channels to resistance. Microarray analysis and confocal microscopy indicated that there was overexpression of the ether-a-gogo gene (HERG) and the inwardly rectifying potassium channel gene (TWIK) in a human epidermal KB and human liver BEL-7404 carcinoma cell line series selected for cisplatin resistance. With increased resistance, the plasma membrane potential, but not the mitochondrial membrane potential, also increases in these two series. For these reasons, we conducted cell proliferation studies in the presence of either antibodies directed against the detected K+ channels, omeprazole (a H+ pump inhibitor) or a specific inhibitor of the HERG channel (WAY-123398-A-5). The antibodies and omeprazole influenced cell growth only very slightly. The specific K+ channel blocker did not alter cisplatin resistance. We also observed that manipulation of K+ fluxes with antibodies and the H+ pump with omeprazole resulted in opposite effects on cisplatin resistance in these two cell lines. We conclude that K+ and H+ homeostasis are not critical factors in cisplatin resistance since they affect cisplatin resistance differently in KB and BEL-7404 cells. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NCI, FACS Core Facil, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Aszalos, A (reprint author), NCI, Cell Biol Lab, NIH, 37 Convent Dr,Room 2112, Bethesda, MD 20892 USA. EM aszalosa@mail.nih.gov RI Szakacs, Gergely/A-2580-2009; Yin, Jun Jie /E-5619-2014 OI Szakacs, Gergely/0000-0002-9311-7827; FU Intramural NIH HHS NR 31 TC 7 Z9 7 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 2005 VL 25 IS 6B BP 4113 EP 4122 PG 10 WC Oncology SC Oncology GA 984BU UT WOS:000233278300048 PM 16309205 ER PT J AU Mielke, S Sparreboom, A Behringer, D Mross, K AF Mielke, S Sparreboom, A Behringer, D Mross, K TI Paclitaxel pharmacokinetics and response to chemotherapy in patients with advanced cancer treated with a weekly regimen SO ANTICANCER RESEARCH LA English DT Article DE paclitaxel; solid tumors ID METASTATIC BREAST-CANCER; NONLINEAR PHARMACOKINETICS; RANDOMIZED-TRIAL; OVARIAN-CANCER; INFUSION; LONG AB Background: Paclitaxel pharmacokinetics were shown to be related to toxicity and survival. Patients and Methods: We evaluated the effects of time above paclitaxel concentrations of 0.05 mu mol/l (T->0.05) and systemic exposures (AUC) to total and unbound paclitaxel (tPAC, uPAC) on response in patients with advanced cancer treated with weekly 1-h or 3-h infusions. Results: After 6 weeks of therapy (WOT), 13 out of 21 assessable patients showed either partial response (PR) or stable disease (SD), while 8 had progressive disease (PD). As compared to patients with PD, those with PR or SD showed similar AUCs to uPAC and tPAC but higher (p<0.05) T->0.05. Patients with T->0.05 >= 20.7 hours had lower probability (p< 0.05) to progress within 12 WOT. Conclusion: Taking the heterogeneity of the studied tumor types into account, we found T,0.05 to be associated with response to treatment. This emphasizes the value of threshold models for the investigation of paclitaxel pharmacodynamics. C1 Univ Freiburg, Ctr Med, Dept Hematol & Oncol, Freiburg, Germany. NCI, Clin Pharmacol Res Core, NIH, Bethesda, MD 20892 USA. Erasmus MC, Dr Daniel Den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. Univ Freiburg, Tumor Biol Ctr, Freiburg, Germany. RP Mielke, S (reprint author), NHLBI, Stem Cell Allogene Transplant Sect, Hematol Branch, DIR,NIH, Bldg 10 CRC Room 3-5288,10 Ctr Dr MSC 1202, Bethesda, MD 20892 USA. EM mielkes@nhlbi.nih.gov RI Sparreboom, Alex/B-3247-2008 NR 17 TC 12 Z9 12 U1 0 U2 0 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 2005 VL 25 IS 6C BP 4423 EP 4427 PG 5 WC Oncology SC Oncology GA 987TL UT WOS:000233540100010 PM 16334120 ER PT J AU Gomez-Flores, R Caballero-Hernandez, D Tamez-Guerra, R Rodriguez-Padilla, C Tamez-Guerra, P Rice, KC Hicks, ME Weber, RJ AF Gomez-Flores, R Caballero-Hernandez, D Tamez-Guerra, R Rodriguez-Padilla, C Tamez-Guerra, P Rice, KC Hicks, ME Weber, RJ TI Increased survival of tumor-bearing mice by the delta opioid SNC 80 SO ANTICANCER RESEARCH LA English DT Article DE SNC 80; non-peptide opioids; delta-opioid agonist; murine tumor cells; L5178Y-R lymphoma; tumor mouse model ID NECROSIS-FACTOR-ALPHA; MACROPHAGE FUNCTIONS; NITRIC-OXIDE; MORPHINE; CELL; CANCER; RECEPTOR; PROLIFERATION; LYMPHOCYTE; ACTIVATION AB Opioids represent a major source of relief from pain. However, opioid abuse may cause immunosuppression and cancer. We have recently reported results on novel non-peptidic delta- and mu-selective opioids that induced immunopotentiation of T cell and macrophage functions in vitro and ex vivo. In the present study, the effects of the delta-opioid receptor agonist and potent analgesic (+)-4-((alpha R)alpha-((2S, 5R)-4-allyl-2, 5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N, N-diethyl-benzamide (SNC80) on in vitro and in vivo tumor cell growth were investigated using the L5178Y-R marine model. SNC80 marginally, but significantly (p < 0.05), inhibited (up to 14%) the in vitro growth of L5178Y-R tumor cells. However, in vivo intratumor administration of SNC80 (2 and 4 mg/kg) reduced up to 60% L5178Y-R tumor-bearing Balb/c mice death, and significantly (p < 0.05) reduced tumor weights (tip to 73% reduction) in these animals. This study may support the evaluation of SNC80 in preclinical and clinical studies. C1 Univ Autonoma Nuevo Leon, Fac Ciencias Biol, Dept Microbiol & Inmunol, San Nicolas de los Garza, NL, Mexico. NIDDK, Med Chem Lab, NIH, Bethesda, MD USA. UIC, Coll Med, Dept Biomed & Therapeut Sci, Peoria, IL USA. RP Gomez-Flores, R (reprint author), Loma Panoram 321-1,Colonia Loma Larga, Nuevo Leon 64710, Mexico. EM rgomez60@hotmail.com OI Caballero-Hernandez, Diana/0000-0002-5446-1238 NR 36 TC 4 Z9 4 U1 0 U2 1 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD NOV-DEC PY 2005 VL 25 IS 6C BP 4563 EP 4567 PG 5 WC Oncology SC Oncology GA 987TL UT WOS:000233540100032 PM 16334142 ER PT J AU Walsh, TJ Adamson, PC Seibel, NL Flynn, PM Neely, MN Schwartz, C Shad, A Kaplan, SL Roden, MM Stone, JA Miller, A Bradshaw, SK Li, SX Sable, CA Kartsonis, NA AF Walsh, TJ Adamson, PC Seibel, NL Flynn, PM Neely, MN Schwartz, C Shad, A Kaplan, SL Roden, MM Stone, JA Miller, A Bradshaw, SK Li, SX Sable, CA Kartsonis, NA TI Pharmacokinetics, safety, and tolerability of caspofungin in children and adolescents SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID INVASIVE FUNGAL-INFECTIONS; AMPHOTERICIN-B; DOUBLE-BLIND; PULMONARY ASPERGILLOSIS; ECHINOCANDIN ANTIFUNGAL; ESOPHAGEAL CANDIDIASIS; FLUCONAZOLE-RESISTANT; RISK-FACTORS; EFFICACY; MK-0991 AB Caspofungin is a parenteral antifungal that inhibits beta-1,3-D-glucan synthesis. Although licensed for adult use, the appropriate caspofungin dosing regimen in pediatric patients is not yet known. We therefore investigated the pharmacokinetics and safety of caspofungin in pediatric patients. Thirty-nine children (ages 2 to 11 years) and adolescents (ages 12 to 17 years) with neutropenia were administered caspofungin using either a weight-based regimen (1 mg/kg of body weight/day) or a body surface area regimen (50 mg/m(2)/day or 70 mg/m(2)/day). Plasma samples for caspofungin profiles were collected on days 1 and 4. These results were compared to those from adults treated with either 50 or 70 mg/day for mucosal candidiasis. In children receiving 1 mg/kg/day (maximum, 50 mg/day), the area under the concentration-time curve over 24 h (AUC(0-24)) was significantly smaller (46% after multiple doses) than that observed in adults receiving 50 mg/day (P < 0.001). In children and adolescents receiving 50 mg/m(2)/day (maximum, 70 mg/day), the AUC(0-24) following multiple doses was similar to that for the exposure in adults receiving 50 mg/day. The AUC(0-24) and concentration trough (at 24 h) in pediatric patients receiving the 50-mg/m(2) daily regimen were consistent across the range of ages. Caspofungin was generally well tolerated in this study. None of the patients developed a serious drug-related adverse event or were discontinued for toxicity. These results demonstrate that caspofungin at I mg/kg/day in pediatric patients is suboptimal. Caspofungin administration at 50 mg/m(2)/day provides a comparable exposure to that of adult patients treated with 50 mg/day. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Childrens Hosp Penn, Philadelphia, PA USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Georgetown Hosp, Washington, DC 20007 USA. Texas Childrens Hosp, Houston, TX 77030 USA. Merck Res Labs, West Point, PA USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10-CRC,Room 1W-5750,10 Ctr Dr, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 33 TC 140 Z9 148 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD NOV PY 2005 VL 49 IS 11 BP 4536 EP 4545 DI 10.1128/AAC.49.11.4536-4545.2005 PG 10 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 980LV UT WOS:000233020900015 PM 16251293 ER PT J AU Pacher, P Szabo, C AF Pacher, P Szabo, C TI Role of poly(ADP-ribose) polymerase-1 activation in the pathogenesis of diabetic complications: Endothelial dysfunction, as a common underlying theme SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID ADP-RIBOSE-POLYMERASE; DNA STRAND BREAKAGE; PEROXYNITRITE DECOMPOSITION CATALYST; INDUCED CARDIOVASCULAR DISORDERS; VASCULAR SUPEROXIDE-PRODUCTION; SISTER CHROMATID EXCHANGES; NITRIC-OXIDE SYNTHASE; PROTEIN-KINASE-C; NF-KAPPA-B; NITROSATIVE STRESS AB Hyperglycemia-induced overproduction of superoxide by mitochondrial electron-transport chain triggers several pathways of injury involved in the pathogenesis of diabetic complications [protein kinase C (PKC), hexosamine and polyol pathway fluxes, advanced glycation end product (AGE) formation] by inhibiting glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity. Increased oxidative and nitrosative stress activates the nuclear enzyme, poly(ADP-ribose) polymerase-1 (PARP). PARP activation, on the one hand, depletes its substrate, NAD+, slowing the rate of glycolysis, electron transport, and ATP formation. On the other hand, it inhibits GAPDH by poly(ADP-ribosy)lation. These processes result in acute endothelial dysfunction in diabetic blood vessels, which importantly contributes to the development of various diabetic complications. Accordingly, hyperglycemia-induced activation of PKC isoforms, hexosaminase pathway flux, and AGE formation is prevented by blocking PARP activity. Furthermore, inhibition of PARP protects against diabetic cardiovascular dysfunction in preclinical models. PARP activation is present in microvasculature of human diabetic subjects. The oxidative/nitrosative stress-PARP pathway leads to diabetes-induced endothelial dysfunction, which may be an important underlying mechanism for the pathogenesis of other diabetic complications (cardiomyopathy, nephropathy, neuropathy, and retinopathy). This review focuses on the role of PARP in diabetic complications and the unique therapeutic potential of PARP inhibition in the prevention or reversal of diabetic complications. C1 Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary. NIAAA, NIH, Lab Physiol Studies, Bethesda, MD USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. RP Semmelweis Univ, Inst Human Physiol & Clin Expt Res, Budapest, Hungary. EM pacher@mail.nih.gov; Szabocsaba@aol.com RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z01 AA000375-02] NR 120 TC 87 Z9 95 U1 0 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD NOV-DEC PY 2005 VL 7 IS 11-12 BP 1568 EP 1580 DI 10.1089/ars.2005.7.1568 PG 13 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 993OD UT WOS:000233962500018 PM 16356120 ER PT J AU Buehler, PW Alayash, AI AF Buehler, PW Alayash, AI TI Redox biology of blood revisited: The role of red blood cells in maintaining circulatory reductive capacity SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID INDEPENDENT OXIDATIVE DAMAGE; ASCORBIC-ACID; VITAMIN-C; DEHYDROASCORBIC ACID; HUMAN ERYTHROCYTES; ENDOTHELIAL-CELLS; HEMOGLOBIN; METHEMOGLOBIN; MICROCIRCULATION; BIOSYNTHESIS AB There is an increasing recognition of the role of red blood cells (RBCs) in cell signaling above and beyond its oxygen (O-2)-carrying function. A recent forum published in the December 2004 issue of Antioxidants & Redox Signaling focused on redox biology of blood and the intricate signaling pathways of RBCs or its free components, i.e., hemoglobin, with the vasculature. The forum provided an up-to-date source of information on this emerging and exciting area of blood biology and the underlying redox chemistry. In the current short review, we have revisited the topic of redox biology of blood and focused on yet another emerging area of research, which deals with the reductive power of blood and the physiological implications. C1 US FDA, CBER, NIH, Lab Biochem & Vasc Biol,Div Hematol, Bethesda, MD 20892 USA. RP US FDA, CBER, NIH, Lab Biochem & Vasc Biol,Div Hematol, Bldg 29,Room 112,8800 Rockville Pike, Bethesda, MD 20892 USA. EM alayash@cber.fda.gov NR 31 TC 20 Z9 21 U1 1 U2 6 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD NOV-DEC PY 2005 VL 7 IS 11-12 BP 1755 EP 1760 DI 10.1089/ars.2005.7.1755 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 993OD UT WOS:000233962500034 PM 16356136 ER PT J AU Santoni-Rugiu, E Jelnes, P Thorgeirsson, SS Bisgaard, HC AF Santoni-Rugiu, E Jelnes, P Thorgeirsson, SS Bisgaard, HC TI Progenitor cells in liver regeneration: molecular responses controlling their activation and expansion SO APMIS LA English DT Review DE hepatic progenitor cell; liver regeneration; growth factors cytokines; chemokines ID HEPATOCYTE GROWTH-FACTOR; RAT OVAL CELLS; LEUKEMIA INHIBITORY FACTOR; HEPATIC STEM-CELLS; ETHIONINE-SUPPLEMENTED DIET; MESSENGER-RNA EXPRESSION; CHOLINE-DEFICIENT DIET; IFN-GAMMA PRODUCTION; BILE-DUCT LIGATION; ONCOSTATIN-M AB Although normally quiescent, the adult mammalian liver possesses a great capacity to regenerate after different types of injuries in order to restore the lost liver mass and ensure maintenance of the multiple liver functions. Major players in the regeneration process are mature residual cells, including hepatocytes, cholangiocytes and stromal cells. However, if the regenerative capacity of mature cells is impaired by liver-damaging agents, hepatic progenitor cells are activated and expand into the liver parenchyma. Upon transit amplification, the progenitor cells may generate new hepatocytes and biliary cells to restore liver homeostasis. In recent years, hepatic progenitor cells have been the subject of increasing interest due to their therapeutic potential in numerous liver diseases as alternative or supportive/complementary tools to liver transplantation. While the first investigations on hepatic progenitor cells have focused on their origin and phenotypic characterization, recent attention has focused on the influence of the hepatic microenvironment on their activation and proliferation. This microenvironment comprises the extracellular matrix, epithelial and non-epithelial resident liver cells, and recruited inflammatory cells as well as the variety of growth-modulating molecules produced and/or harboured by these elements. The cellular and molecular responses to different regenerative stimuli seem to depend on the injury inflicted and consequently on the molecular microenvironment created in the liver by a certain insult. This review will focus on molecular responses controlling activation and expansion of the hepatic progenitor cell niche, emphasizing similarities and differences in the microenvironments orchestrating regeneration by recruitment of progenitor cell populations or by replication of mature cells. C1 Herlev Univ Hosp, Dept Pathol, DK-2730 Herlev, Denmark. Univ Copenhagen, Panum Inst, Danish Stem Cell Res Ctr, Dept Med Biochem & Genet, DK-2200 Copenhagen, Denmark. NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Bisgaard, HC (reprint author), Herlev Univ Hosp, Dept Pathol, DK-2730 Herlev, Denmark. EM hcb@imbg.ku.dk NR 211 TC 73 Z9 80 U1 0 U2 11 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0903-4641 J9 APMIS JI APMIS PD NOV PY 2005 VL 113 IS 11-12 BP 876 EP 902 DI 10.1111/j.1600-0463.2005.apm_386.x PG 27 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 012QG UT WOS:000235353500013 PM 16480456 ER PT J AU Stratigos, AJ Malanos, D Touloumi, G Antoniou, A Potouridou, I Polydorou, D Katsambas, AD Whitby, D Mueller, N Stratigos, JD Hatzahis, A AF Stratigos, AJ Malanos, D Touloumi, G Antoniou, A Potouridou, I Polydorou, D Katsambas, AD Whitby, D Mueller, N Stratigos, JD Hatzahis, A TI Association of clinical progression in classic Kaposi's sarcoma with reduction of peripheral B lymphocytes and partial increase in serum immune activation markers SO ARCHIVES OF DERMATOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HHV8 ASSOCIATED DISEASES; HUMAN-HERPESVIRUS-8 INFECTION; URINARY NEOPTERIN; INTERFERON-GAMMA; RISK-FACTORS; CELLS; THERAPY; MEN; EPIDEMIOLOGY AB Objective: To evaluate various immunologic markets in the peripheral blood of patients with early and advanced classic Kaposi's sarcoma (CKS). Design: Cross-sectional study. Setting: A major referral center for skin and venereal diseases. Patients: Sixty-eight patients with histologically con:firmed CKS staged according to a modified version of the Mitsuyasu-Groopman classification in stage I-II (cutaneous involvement only) and stage IV (skin and systemic involvement). Main Outcome Measures: Concentrations of neopterin and beta(2)-microglobulin, titer of anti-human herpesvirus 8 antibodies, number of natural killer cells, and numbers of total lymphocytes, B lymphocytes, T lymphocytes, and their subsets in peripheral blood. Results: The median values of beta(2)-microglobulin and neopterin were elevated in patients with CKS in stage IV (median, 3.679 mu g/mL [312.72 nmol/L] and 14.0 nmol/L, respectively) compared with patients in stage I-II (median, 2.406 mu g/mL [204.51 nmol/L] and 6.5,nmol/L, respectively). A statistically significant reduction in total lymphocyte and B-lymphocyte counts was observed in patients with advanced-stage CKS (1679/mu L and 79/mu L, respectively) compared with patients in earlier stages of the disease (2142/mu L and 224/mu L, respectively). The human herpesvirus 8 antibody titer, determined by latent immunofluorescent assay, decreased from stage I-II to stage IV, although not at a statistically significant level (P =.14). Conclusion: The evolution of CKS from the early stages of the disease to the more advanced may be associated with a partial activation of the immune system and a gradual decrease in the number of total and B lymphocytes. C1 Univ Athens, Dept Dermatol, Athens 16121, Greece. Univ Athens, Andreas Sygros Hosp, Dept Dermatol, Athens, Greece. Univ Athens, Dept Hyg & Epidemiol, Natl Retroviral Ctr, Athens, Greece. Natl Retroviral Ctr, Dept Hyg & Epidemiol, Bethesda, MD USA. NCI, AIDS Vaccine Program, Viral Epdiemiol Sect, Bethesda, MD USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Stratigos, AJ (reprint author), Univ Athens, Dept Dermatol, 51 Dragoumi St, Athens 16121, Greece. EM alstrat@hol.gr FU NCI NIH HHS [R01 CA44578] NR 45 TC 9 Z9 9 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD NOV PY 2005 VL 141 IS 11 BP 1421 EP 1426 DI 10.1001/archderm.141.11.1421 PG 6 WC Dermatology SC Dermatology GA 982SU UT WOS:000233182700009 PM 16301389 ER PT J AU Aman, MG Arnold, LE Ramadan, Y Witwer, A Lindsay, R McDougle, CJ Posey, DJ Swiezy, N Kohn, A McCracken, JT Shah, B Cronin, P McGough, J Lee, JSY Scahill, L Martin, A Koenig, K Carroll, D Young, C Lancor, A Tierney, E Ghuman, J Gonzalez, NM Grados, M Vitiello, B Ritz, L Chuang, S Davies, M Robinson, J McMahon, D AF Aman, MG Arnold, LE Ramadan, Y Witwer, A Lindsay, R McDougle, CJ Posey, DJ Swiezy, N Kohn, A McCracken, JT Shah, B Cronin, P McGough, J Lee, JSY Scahill, L Martin, A Koenig, K Carroll, D Young, C Lancor, A Tierney, E Ghuman, J Gonzalez, NM Grados, M Vitiello, B Ritz, L Chuang, S Davies, M Robinson, J McMahon, D CA Res Units Pediat Psychopharmacolo TI Randomized, controlled, crossover trial of methylphenidate in pervasive developmental disorders with hyperactivity SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article; Proceedings Paper CT 42nd Meeting of the American-College-of-Neuropsychopharmacology CY DEC 07-11, 2003 CL San Juan, PR SP Amer Coll Neuropsychopharmacol ID MENTAL-RETARDATION; SCHIZOPHRENIC CHILDREN; BORDERLINE IQ; AUTISM; FENFLURAMINE; INDIVIDUALS; EFFICACY; ADHD; MTA AB Context: Hyperactivity and inattention are common symptoms in children with autistic disorder and related pervasive developmental disorders, but studies of stimulants in these conditions have been inconclusive. Objectives: To determine the efficacy and safety of methylphenidate hydrochloride in children with pervasive developmental disorders and hyperactivity. Design: Double-blind, placebo-controlled, crossover trial followed by open-label continuation. Setting: Five academic outpatient clinics. Participants: Seventy-two drug-free children, aged 5 to 14 years, with pervasive developmental disorders accompanied by moderate to severe hyperactivity. Interventions: Prior to randomization, subjects entered a 1-week test-dose phase in which each subject received placebo for 1 day followed by increasing doses of methylphenidate (low, medium, and high doses) that were each given for 2 days. The low, medium, and high doses of methylphenidate hydrochloride were based on weight, and they ranged from 7.5 mg/d to 50.0 mg/d in divided doses. Subjects who tolerated the test dose (n=66) were assigned to receive placebo for 1 week and then 3 methylphenidate doses in random order during a double-blind, crossover phase. Children responding to methylphenidate then entered 8 weeks of open-label treatment at the individually determined best dose. Main Outcome Measures: The primary outcome measure was the teacher-rated hyperactivity subscale of the Aberrant Behavior Checklist. Response was defined as "much improved" or "very much-improved" on the Clinical Global Impressions Improvement item coupled with considerable reductions in the parent-rated and/or teacher-rated Aberrant Behavior Checklist hyperactivity subscale score. Results: Methylphenidate was superior to placebo on the primary outcome measure, with effect sizes ranging from 0.20 to 0.54 depending on dose and rater. Thirty-five (49%) of 72 enrolled subjects were classified as methylphenidate responders. Adverse effects led to the discontinuation of study medication in 13 (18%) of 72 subjects. Conclusions: Methylphenidate was often efficacious in treating hyperactivity associated with pervasive developmental disorders, but the magnitude of response was less than that seen in typically developing children with attention-deficit/hyperactivity disorder. Adverse effects were more frequent. C1 James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. Ohio State Univ, Columbus, OH 43210 USA. Indiana Univ, Indianapolis, IN 46204 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Yale Univ, New Haven, CT 06520 USA. Kennedy Krieger Inst, Baltimore, MD USA. NIMH, Bethesda, MD 20892 USA. Columbia Univ, New York, NY 10027 USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. RP Posey, DJ (reprint author), James Whitcomb Riley Hosp Children, Room 4300,702 Barnhill Dr, Indianapolis, IN 46202 USA. EM dposey@iupui.edu OI Witwer, Andrea/0000-0002-1268-4222; Scahill, Lawrence/0000-0001-5073-1707 NR 27 TC 200 Z9 208 U1 2 U2 16 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0003-990X EI 1538-3636 J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD NOV PY 2005 VL 62 IS 11 BP 1266 EP 1274 PG 9 WC Psychiatry SC Psychiatry GA 980XG UT WOS:000233050900010 ER PT J AU Bagnato, F Gupta, S Richert, ND Stone, RD Ohayon, JM Frank, JA McFarland, HF AF Bagnato, F Gupta, S Richert, ND Stone, RD Ohayon, JM Frank, JA McFarland, HF TI Effects of interferon beta-1b on black holes in multiple sclerosis over a 6-year period with monthly evaluations SO ARCHIVES OF NEUROLOGY LA English DT Article ID ENHANCING LESIONS; CONTROLLED TRIAL; PROGRESSIVE MS; DOUBLE-BLIND; IFN-BETA-1B; EVOLUTION AB Background: Chronic, hypointense black holes (BHs) are recognized as a sign of permanent damage in patients with multiple sclerosis. Although the effects of interferon beta-1b in reducing the formation of new BHs are established, it is not clear whether the drug may reduce BH duration after these lesions are formed. Objective: To analyze the effects of interferon beta-1b in reducing the duration of T1 BHs in patients with multiple sclerosis. Design: Patients were clinically assessed and imaged monthly over a 36-month natural history phase and 36-month therapy phase. Numbers of contrastenhanced lesions and newly formed BHs were counted on each scan. Each BH was counted until it was no longer seen. Setting: Outpatient service of the Neuroimmunology Branch at the National Institutes of Health, Bethesda, Md. Patients: Six patients with relapsing-remitting multiple sclerosis were included. One patient did not form any BHs during the therapy phase. Analyses were performed on the remaining 5 individuals. Interventions: Interferon beta-1b at the dosage of 8 million international units every other day. Main Outcome Measures: Number and duration (in months) of newly formed BHs. Results: Rate of BH accumulation decreased with treatment (P = .01), but Kaplan-Meier models revealed that the duration of BHs did not shorten (X-1(2) = 2.47, P =. 12). Conclusions: Interferon beta-1b reduces the frequency of new BH formation but does not appear to decrease their duration in time. Analyses with larger patient cohorts are needed to confirm these preliminary findings. C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NIH, Lab Diagnost Radiol & Res, Bethesda, MD 20892 USA. New York Med Coll, Valhalla, NY 10595 USA. RP Bagnato, F (reprint author), NINDS, Neuroimmunol Branch, NIH, Bldg 10,Room 5B16,10 Ctr Dr, Bethesda, MD 20892 USA. EM bagnatof@ninds.nih.gov NR 15 TC 17 Z9 17 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD NOV PY 2005 VL 62 IS 11 BP 1684 EP 1688 DI 10.1001/archneur.62.11.noc40499 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 983RX UT WOS:000233250900005 PM 16157739 ER PT J AU Liu, H Li, W Shi, ST Habelitz, S Gao, C DenBesten, P AF Liu, H Li, W Shi, ST Habelitz, S Gao, C DenBesten, P TI MEPE is downregulated as dental pulp stem cells differentiate SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE MEPE; DSP; proliferation; differentiation; dental pulp stem cells; DPSC; osteogenesis superarray; TGF-beta ID ODONTOBLAST-LIKE CELLS; IN-VITRO; ALKALINE-PHOSPHATASE; HUMAN TEETH; BONE SIALOPROTEIN; MATRIX PROTEIN-1; MESSENGER-RNA; GROWTH-FACTOR; EXPRESSION; RAT AB Previous studies on dental pulp cell culture have described heterogenous mixtures of cells that differentiate into odontoblasts and form mineralized dentin. Objective: The aim of this study was to characterize the matrix extracellular phosphogtycoprotein (MEPE) expression by dental pulp stem cells (DPSC), related to cell differentiation. Design: DPSC differentiation to form mineralized nodules was characterized by Alizarin red staining and micro-Raman spectroscopy. Osteogenesis SuperArray analysis was used to broadly screen for osteogenesis- related genes altered by DPSC differentiation. Relative levels of expression of MEPE and DSP were determined by serniquantitative RT-PCR and Western blot. Results: Mineral analysis showed that as DPSC differentiated, they formed a carbonated hydroxyapatite mineral. Differentiation was initially marked by upregulation by Runx2, TGF beta-related genes, EGFR and genes involved in collagen metabolism. ALP activity first increased, as DPSCs reached confluence but later decreased when cells further differentiated three weeks after confluence. MEPE was the only marker that was downregutated as DPSCs differentiated. Conclusion: DPSC differentiation can be characterized by downregulation of MEPE as other markers of DPSC differentiation, such as DSP, are upregulated. Expression of MEPE related to DSP and can be used to monitor DPSC as they are used for studies of odontobtast differentiation, tissue engineering or vital pulp therapy. The downregulation of MEPE as DPSC differentiate, suggests that MEPE is an inhibitor of mineralization. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Peking Univ, Sch Stomatol, Beijing 100871, Peoples R China. NIDCR, Bethesda, MD USA. RP DenBesten, P (reprint author), Univ Calif San Francisco, 521 Parnassus Ave,Rm C734,Box 0640, San Francisco, CA 94143 USA. EM pkdb@itsa.ucsf.edu FU NIDCR NIH HHS [P01-DE09859] NR 36 TC 50 Z9 57 U1 2 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD NOV PY 2005 VL 50 IS 11 BP 923 EP 928 DI 10.1016/j.albchoralbio.2005.03.003 PG 6 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 984NZ UT WOS:000233312900001 PM 16183369 ER PT J AU Jung, SH You, SH Hallett, M Cho, YW Park, CM Cho, SH Lee, HY Kim, TH AF Jung, SH You, SH Hallett, M Cho, YW Park, CM Cho, SH Lee, HY Kim, TH TI Cortical reorganization and associated functional motor recovery after virtual reality in patients with chronic stroke: An experimenter-blind preliminary study SO ARCHIVES OF PHYSICAL MEDICINE AND REHABILITATION LA English DT Article DE computer-assisted instruction; hemiplegia; magnetic resonance imaging; rehabilitation ID INDUCED MOVEMENT THERAPY; UPPER-EXTREMITY; HEMIPARETIC STROKE; REHABILITATION AB Objective: To investigate the effects of virtual reality (VR) on cortical reorganization and motor recovery. Design: Nonparametric pre- and posttest design with experimenter blinded. Setting: University medical center. Participants: Five patients with hemiparesis (age, 59.8+/-3.4y) were recruited. Intervention: Five patients received VR for 60 minutes a day, 5 times a week for 4 weeks. VR was designed to provide a virtual rehabilitation scene where the intensity of practice and sensory feedback could be systematically manipulated to provide the most appropriate, individualized motor retraining program. Main Outcome Measures: Cortical activation and associated motor recovery were measured before and after VR using functional magnetic resonance imaging and standardized motor tests, respectively. Nonparametric tests were used at P less than .05. Results: Prior to VR, the bilateral primary sensorimotor cortices (SM1s), contralesional premotor cortex, and contralesional or ipsilesional supplementary motor area were activated. After VR, the altered activations disappeared and predominantly the ipsilesional SM1 was activated (P<.05). Motor function was improved (P<.05). Conclusions: This is a novel demonstration of VR-induced neuroplastic changes and associated motor recovery in chronic stroke. C1 Hampton Univ, Doctor Phys Therapy Program, Hampton, VA 23668 USA. Yeungnam Univ, Coll Med, Dept Phys Med & Rehabil, Taegu, South Korea. NINDS, Human Motor Control Sect, Bethesda, MD 20892 USA. Yeungnam Univ, Med Ctr, Dept Rehabil Med, Taegu, South Korea. Taegu Univ, Dept Rehabil Sci, Taegu, South Korea. Yonsei Univ, Coll Hlth Sci, Dept Phys Therapy, Inst Hlth Sci, Kangwon Do, South Korea. RP You, SH (reprint author), Hampton Univ, Doctor Phys Therapy Program, Phoenix Hall 219B, Hampton, VA 23668 USA. EM sung.you@hamptonu.edu NR 25 TC 17 Z9 19 U1 0 U2 9 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0003-9993 J9 ARCH PHYS MED REHAB JI Arch. Phys. Med. Rehabil. PD NOV PY 2005 VL 86 IS 11 BP 2218 EP 2223 DI 10.1016/j.apmr.2005.04.015 PG 6 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 983TB UT WOS:000233253900025 ER PT J AU Wormser, U Brodsky, B Proscura, E Foley, JF Jones, T Nyska, A AF Wormser, U Brodsky, B Proscura, E Foley, JF Jones, T Nyska, A TI Involvement of tumor necrosis factor-alpha in sulfur mustard-induced skin lesion; effect of topical iodine SO ARCHIVES OF TOXICOLOGY LA English DT Article DE sulfur mustard; tumor necrosis factor-alpha; neutrophils; iodine; mouse-ear model ID 2-CHLOROETHYL ETHYL SULFIDE; NORMAL HUMAN KERATINOCYTES; EXPOSED MOUSE SKIN; TNF-ALPHA; HISTOPATHOLOGIC FEATURES; CYTOKINE RELEASE; THERMAL-INJURY; LUNG INJURY; PIG SKIN; EXPRESSION AB Sulfur mustard (SM), also termed mustard gas, is a potent vesicant that elicits an inflammatory response upon exposure of the skin. Evaluation of mouse ear 3 h after SM exposure revealed acute inflammatory-cell aggregates in the vascular beds accompanied by strongly TNF-alpha-positive neutrophils. Eight hours after SM exposure, this phenomenon became intensified and associated with infiltration into the adjacent dermis. In ear skin topically treated with iodine, however, no inflammatory cells were observed 3 h after SM exposure; 8 h postexposure, blood vessels contained very few TNF-alpha-positive inflammatory cells. Since TNF-alpha induction was shown to be associated with reactive oxygen species production, we studied the effect of iodine on activated peritoneal mouse neutrophils. Iodine elicited a concentration-dependent reduction in the oxidative burst of activated neutrophils. Iodine also scavenged hydroxyl radicals generated by glucose oxidase in a concentration-dependent manner. The involvement of TNF-alpha in SM-induced skin toxicity was confirmed by reduction of 49 and 30% in ear edema following administration of 1 and 2 mu g anti-TNF-alpha antibodies, respectively. These findings were corroborated by quantitative analysis of the histological findings showing 46% reduction in acute inflammation and no signs of subacute inflammation in the treated group, in contrast to the control group treated with SM only. Other epidermal (microblister formation, ulceration, and necrosis) and dermal (neutrophilia, hemorrhage, and necrosis) parameters also showed marked reductions in the antibodies-treated group in comparison to controls. The combination of iodine and antiTNF-alpha antibodies might constitute a new approach for treatment of SM-exposed individuals. C1 Hebrew Univ Jerusalem, Sch Pharm, Dept Pharmacol, IL-91904 Jerusalem, Israel. Hebrew Univ Jerusalem, Inst Life Sci, Fac Med, IL-91904 Jerusalem, Israel. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. RP Wormser, U (reprint author), Hebrew Univ Jerusalem, Sch Pharm, Dept Pharmacol, Berman Bldg, IL-91904 Jerusalem, Israel. EM wormser@cc.huji.ac.il NR 41 TC 32 Z9 35 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-5761 J9 ARCH TOXICOL JI Arch. Toxicol. PD NOV PY 2005 VL 79 IS 11 BP 660 EP 670 DI 10.1007/s00204-005-0681-5 PG 11 WC Toxicology SC Toxicology GA 983QY UT WOS:000233248400006 PM 16001271 ER PT J AU Kurup, SK Chan, CC AF Kurup, SK Chan, CC TI Immunotherapeutic approaches in ocular inflammatory diseases SO ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS LA English DT Review DE inflammation; uveitis; autoimmune diseases; immunosuppressive medications; adverse effect; therapy ID PROPIONIBACTERIUM-ACNES ENDOPHTHALMITIS; STEM-CELL TRANSPLANTATION; MYCOPHENOLATE-MOFETIL; RENAL-TRANSPLANTATION; POSTERIOR UVEITIS; CLINICAL-TRIAL; IMMUNOSUPPRESSIVE DRUGS; KIDNEY-TRANSPLANTATION; RHEUMATOID-ARTHRITIS; SYSTEMIC-SCLEROSIS AB This comprehensive review discusses immunotherapeutic approaches to ocular inflammatory diseases, updates information provided in the literature, and presents clinical experiences with an emphasis on autoimmune uveitis at the National Eye Institute, United States. Current medical and surgical therapeutic approaches, including medications such as corticosteroids, anti-metabolites, alkylating agents, calcineurin and purine synthesis inhibitors, biologics as well as some anti-infectious agents, are reviewed along with new modalities and experimental approaches. Most immunosuppressive therapies have significant adverse effects. Physicians must be familiar with the pharmacology of the available drugs and aware of the philosophies behind the treatment. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Kurup, SK (reprint author), NEI, NIH, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov NR 79 TC 3 Z9 4 U1 0 U2 0 PU INST IMMUNOLOGY & EXPERIMENTAL THERAPY PI WROCLAW PA POLISH ACADEMY OF SCIENCES CZERSKA 12, 53-114 WROCLAW, POLAND SN 0004-069X J9 ARCH IMMUNOL THER EX JI Arch. Immunol. Ther. Exp. PD NOV-DEC PY 2005 VL 53 IS 6 BP 484 EP 496 PG 13 WC Immunology SC Immunology GA 006VZ UT WOS:000234927100002 PM 16407781 ER PT J AU Kobayashi, SD Voyich, JM Burlak, C DeLeo, FR AF Kobayashi, SD Voyich, JM Burlak, C DeLeo, FR TI Neutrophils in the innate immune response SO ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS LA English DT Review DE neutrophil; phagocytosis; inflammation; infection; apoptosis ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; SUPEROXIDE ANION PRODUCTION; PRIMES HUMAN-NEUTROPHILS; TUMOR-NECROSIS-FACTOR; CHRONIC GRANULOMATOUS-DISEASE; PLATELET-ACTIVATING-FACTOR; COLONY-STIMULATING FACTOR; PROGRAMMED CELL-DEATH; PEPTIDOGLYCAN RECOGNITION PROTEIN; RESPIRATORY BURST OXIDASE AB Polymorphonuclear leukocytes (PMNs or neutrophils) are an essential component of the human innate immune system. Circulating neutrophils are rapidly recruited to sites of infection by host- and/or pathogen-derived components, which also prime these host cells for enhanced microbicidal activity. PMNs bind and ingest microorganisms by a process known as phagocytosis, which typically triggers production of reactive oxygen species and the fusion of cytoplasmic granules with pathogen-containing vacuoles. The combination of neutrophil reactive oxygen species and granule components is highly effective in killing most bacteria and fungi. Inasmuch as PMNs are the most abundant type of leukocyte in humans and contain an arsenal of cytotoxic compounds that are non-specific, neutrophil homeostasis Must be highly regulated. To that end, constitutive PMN turnover is regulated by apoptosis, a process whereby these cells Shut down and are removed safely by macrophages. Notably, apoptosis is accelerated following phagocytosis of bacteria, a process that appears important for the resolution of infection and inflammation. This review provides a general overview of the role of human neutrophils in the innate host response to infection and Summarizes some of the recent advances in neutrophil biology. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP Kobayashi, SD (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS NR 215 TC 119 Z9 122 U1 4 U2 16 PU INST IMMUNOLOGY & EXPERIMENTAL THERAPY PI WROCLAW PA POLISH ACADEMY OF SCIENCES CZERSKA 12, 53-114 WROCLAW, POLAND SN 0004-069X J9 ARCH IMMUNOL THER EX JI Arch. Immunol. Ther. Exp. PD NOV-DEC PY 2005 VL 53 IS 6 BP 505 EP 517 PG 13 WC Immunology SC Immunology GA 006VZ UT WOS:000234927100004 PM 16407783 ER PT J AU Aletaha, D Breedveld, FC Smolen, JS AF Aletaha, D Breedveld, FC Smolen, JS TI The need for new classification criteria for rheumatoid arthritis SO ARTHRITIS AND RHEUMATISM LA English DT Editorial Material ID EARLY INFLAMMATORY POLYARTHRITIS; HLA-DRB1 SHARED EPITOPE; TUMOR-NECROSIS-FACTOR; DISEASE-ACTIVITY; FUNCTIONAL-CAPACITY; ANTIRHEUMATIC DRUGS; PROGNOSTIC-FACTORS; CLINICAL-PRACTICE; ACTIVITY SCORE; DOUBLE-BLIND C1 Med Univ Vienna, Vienna, Austria. NIAMSD, NIH, Bethesda, MD 20892 USA. Leiden Univ Hosp, Leiden, Netherlands. Lainz Hosp, Vienna, Austria. RP Aletaha, D (reprint author), Univ Vienna, Div Rheumatol, Dept Internal Med 3, Vienna Gen Hosp, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM josef.smolen@wienkav.at NR 55 TC 29 Z9 35 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2005 VL 52 IS 11 BP 3333 EP 3336 DI 10.1002/art.21410 PG 4 WC Rheumatology SC Rheumatology GA 984EN UT WOS:000233285400004 PM 16255014 ER PT J AU Jamieson, HA Hilmer, SN Cogger, VC Fraser, R Abernethy, DR De Cabo, R Le Couteur, DG AF Jamieson, H. A. Hilmer, S. N. Cogger, V. C. Fraser, R. Abernethy, D. R. De Cabo, R. Le Couteur, D. G. TI Calorie restriction delays the age-related thickening of the liver sinusoidal endothelium SO AUSTRALASIAN JOURNAL ON AGEING LA English DT Meeting Abstract C1 [Jamieson, H. A.; Hilmer, S. N.; Cogger, V. C.; Le Couteur, D. G.] Concord Hosp, Ctr Educ & Res Ageing, Concord, NSW, Australia. [Hilmer, S. N.] Royal N Shore Hosp, Dept Aged Care, Sydney, NSW, Australia. [Hilmer, S. N.] Royal N Shore Hosp, Dept Clin Pharmacol, Sydney, NSW, Australia. [Fraser, R.] Christchurch Sch Med, Dept Pathol, Christchurch, New Zealand. [Abernethy, D. R.] NIA, Lab Clin Invest, NIH, Baltimore, MD 21224 USA. [De Cabo, R.] NIA, Lab Expt Gerontol, NIH, Baltimore, MD 21224 USA. EM hjamieson@med.usyd.edu.au 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 1440-6381 J9 AUSTRALAS J AGEING JI Australas. Ageing PD NOV PY 2005 VL 24 SU 2 BP A6 EP A7 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA V24YH UT WOS:000208445200019 ER PT J AU Parks, CG Cooper, GS AF Parks, CG Cooper, GS TI Occupational exposures and risk of systemic lupus erythematosus SO AUTOIMMUNITY LA English DT Article DE crystalline silica; solvents; pesticides; SLE; occupational exposures ID THORACIC LYMPH-NODES; SOUTHEASTERN UNITED-STATES; CONNECTIVE-TISSUE DISEASE; ZEALAND MIXED MICE; CRYSTALLINE SILICA; AUTOIMMUNE-DISEASE; ENVIRONMENTAL CONTAMINANT; ANTINUCLEAR ANTIBODIES; DENTAL TECHNICIAN; CIGARETTE-SMOKING AB This review summarizes the growing body of epidemiologic and experimental research pertaining to the relationship between SLE and occupational exposures, such as crystalline silica, solvents, and pesticides. Epidemiologic studies, using different designs in different settings, have demonstrated moderate to strong associations between occupational silica exposure and SLE. Recent experimental studies of silica in lupus-prone mice provide support for the idea that, in addition to its known adjuvant effect, silica exposure increases the generation of apoptotic material, an important source of self-antigen. Despite compelling experimental studies of the organic solvent trichloroethylene (TCE) in lupus-prone mice, there is little evidence of an overall association of SLE and occupational exposure to a broad classification of solvents in humans. However, there is a lack of data on SLE in occupational cohorts with exposures to TCE or other specific solvents. One epidemiologic study reported an association of pesticide mixing and SLE, while a recent experimental study reported accelerated disease in pesticide-treated lupus-prone mice. Other occupational exposures worth investigating include asbestos, metals, and UV radiation. Attention should also be given to the role of gene-environment interactions, which may require large, multi-site studies that collect both genetic material and occupational exposure data. The quality of exposure assessment is an important consideration in designing and evaluating these studies. The use of pre-clinical endpoints (e.g. high-titer autoantibodies) in occupational cohorts with well-characterized exposure histories may reveal occupational risk factors for autoimmunity, and may also provide baseline data for studies of determinants of progression to SLE. C1 NIOSH, Biostat & Epidemiol Branch, Hlth Effects Lab Div, Morgantown, WV 26505 USA. NIEHS, Epidemiol Branch, Durham, NC 27709 USA. RP Parks, CG (reprint author), NIOSH, Biostat & Epidemiol Branch, Hlth Effects Lab Div, 1095 Willowdale Rd, Morgantown, WV 26505 USA. EM cqp8@cdc.gov OI Parks, Christine/0000-0002-5734-3456 NR 78 TC 24 Z9 25 U1 0 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PD NOV PY 2005 VL 38 IS 7 BP 497 EP 506 DI 10.1080/08916930500285493 PG 10 WC Immunology SC Immunology GA 990XN UT WOS:000233776800005 PM 16373255 ER PT J AU Singh, SR Rashkovetsky, E Iliadi, K Nevo, E Korol, A AF Singh, SR Rashkovetsky, E Iliadi, K Nevo, E Korol, A TI Assortative mating in Drosophila adapted to a microsite ecological gradient SO BEHAVIOR GENETICS LA English DT Article DE Drosophila; ecological gradient; mate choice; population divergence ID LOWER NAHAL OREN; EVOLUTION CANYON; SYMPATRIC SPECIATION; REPRODUCTIVE ISOLATION; SEXUAL SELECTION; MELANOGASTER POPULATIONS; DISRUPTIVE SELECTION; INCIPIENT SPECIATION; MICROCLIMATIC CONTRAST; NATURAL-SELECTION AB Elucidating the causes of population divergence, and ultimately speciation, is a central objective of evolutionary biology. A number of previous studies of Drosophila populations from the Nahal Oren canyon (Mt Carmel, Israel) revealed significant interslope differences for a complex of fitness and behavioral traits. Peculiarities in courtship song patterns and nonrandom mating were observed, despite a small interslope distance. Single and multiple mate choice tests with D. melanogaster from the opposite slopes displayed highly significant assortative mating, with preference for sexual partners from the same slope. Here we report the results on mate choice in the sibling species D. melanogaster and D. simulans inhabiting Nahal Oren canyon. Significant assortative mating was found in both species. Genetic heterogeneity in mate choice was found among the isofemale lines of D. melanogaster. Samples of isofemale lines established from females collected in spring and fall seasons show the same mating patterns. C1 Univ Haifa, Inst Evolut, IL-31905 Haifa, Israel. Natl Canc Inst, Immunobiol Lab, Frederick, MD USA. Hosp Sick Children, Res Inst, Program Dev Biol, Toronto, ON M5G 1X8, Canada. RP Rashkovetsky, E (reprint author), Univ Haifa, Inst Evolut, Mt Carmel, IL-31905 Haifa, Israel. EM Eugenia@research.haifa.ac.il RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X NR 64 TC 16 Z9 16 U1 0 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2005 VL 35 IS 6 BP 753 EP 764 DI 10.1007/s10519-005-6119-2 PG 12 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 985PZ UT WOS:000233391600006 PM 16273320 ER PT J AU Ordaz, SJ Rosenthal, MA Clasen, LS Blumenthal, JA Lenroot, R Wallace, GL Schmitt, JE Neale, MC Kendler, KS Giedd, JN AF Ordaz, SJ Rosenthal, MA Clasen, LS Blumenthal, JA Lenroot, R Wallace, GL Schmitt, JE Neale, MC Kendler, KS Giedd, JN TI Heritability of child and adolescent brain morphometry SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 35th Annual Meeting of the Behavior-Genetics-Association CY JUN 29-JUL 02, 2005 CL Hollywood, CA SP Behav Genet Assoc C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Psychiat, Richmond, VA 23298 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Human Genet, Richmond, VA 23298 USA. EM ordazs@mail.nih.gov RI Giedd, Jay/A-3080-2008; Neale, Michael/B-1418-2008; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2005 VL 35 IS 6 BP 816 EP 816 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 985PZ UT WOS:000233391600098 ER PT J AU Taylor, KN Rose, AB Clasen, LS Blumenthal, JA Lenroot, R Wallace, GL Myers, AJ Hardy, J Giedd, JN AF Taylor, KN Rose, AB Clasen, LS Blumenthal, JA Lenroot, R Wallace, GL Myers, AJ Hardy, J Giedd, JN TI Apolipoprotein E and brain development in healthy children SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 35th Annual Meeting of the Behavior-Genetics-Association CY JUN 29-JUL 02, 2005 CL Hollywood, CA SP Behav Genet Assoc C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. EM kristintaylor@mail.nih.gov RI Giedd, Jay/A-3080-2008; Myers, Amanda/B-1796-2010; Giedd, Jay/B-7302-2012; Giedd, Jay/J-9644-2015 OI Myers, Amanda/0000-0002-3100-9396; Giedd, Jay/0000-0003-0827-3460; Giedd, Jay/0000-0003-2002-8978 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2005 VL 35 IS 6 BP 822 EP 822 PG 1 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 985PZ UT WOS:000233391600118 ER PT J AU Xu, K Terry, J Thomas, C Roy, A Lichtermann, D Maier, W Virkkunen, M Goldman, D AF Xu, K Terry, J Thomas, C Roy, A Lichtermann, D Maier, W Virkkunen, M Goldman, D TI Re-sequence and haplotype linkage of Mu opioid receptor gene with substance abuse in four populations SO BEHAVIOR GENETICS LA English DT Meeting Abstract CT 35th Annual Meeting of the Behavior-Genetics-Association CY JUN 29-JUL 02, 2005 CL Hollywood, CA SP Behav Genet Assoc C1 NIAAA, Neurogenet Lab, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD NOV PY 2005 VL 35 IS 6 BP 825 EP 826 PG 2 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 985PZ UT WOS:000233391600130 ER PT J AU Lissek, S Powers, AS McClure, EB Phelps, EA Woldehawariat, G Grillon, C Pine, DS AF Lissek, S Powers, AS McClure, EB Phelps, EA Woldehawariat, G Grillon, C Pine, DS TI Classical fear conditioning in the anxiety disorders: a meta-analysis SO BEHAVIOUR RESEARCH AND THERAPY LA English DT Review DE classical conditioning; fear conditioning; anxiety disorders; psychophysiology ID POSTTRAUMATIC-STRESS-DISORDER; POTENTIATED STARTLE PARADIGM; MEDIAL PREFRONTAL CORTEX; PANIC DISORDER; SOCIAL PHOBIA; EMOTIONAL-REACTIONS; LATENT INHIBITION; RECOGNITION BIAS; EXTINCTION; AMYGDALA AB Fear conditioning represents the process by which a neutral stimulus comes to evoke fear following its repeated pairing with an aversive stimulus. Although fear conditioning has long been considered a central pathogenic mechanism in anxiety disorders, studies employing lab-based conditioning paradigms provide inconsistent support for this idea. A quantitative review of 20 such studies, representing fear-learning scores for 453 anxiety patients and 455 healthy controls, was conducted to verify the aggregated result of this literature and to assess the moderating influences of study characteristics. Results point to modest increases in both acquisition of fear learning and conditioned responding during extinction among anxiety patients. Importantly, these patient-control differences are not apparent when looking at discrimination studies alone and primarily emerge from studies employing simple, single-cue paradigms where only danger cues are presented and no inhibition of fear to safety cues is required. Published by Elsevier Ltd. C1 NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NYU, Dept Psychol, New York, NY 10012 USA. RP Lissek, S (reprint author), NIMH, Mood & Anxiety Disorders Program, 15K N Dr, Bldg 15k,MSC 2670, Bethesda, MD 20892 USA. EM lisseks@intra.nimh.nih.gov RI Lissek, Shmuel/B-6577-2008 FU Intramural NIH HHS NR 121 TC 364 Z9 369 U1 16 U2 101 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0005-7967 J9 BEHAV RES THER JI Behav. Res. Ther. PD NOV PY 2005 VL 43 IS 11 BP 1391 EP 1424 DI 10.1016/j.brat.2004.10.007 PG 34 WC Psychology, Clinical SC Psychology GA 017MQ UT WOS:000235698100001 PM 15885654 ER PT J AU Kim, BC Kim, HG Lee, SA Lim, S Park, EH Kim, SJ Lim, CJ AF Kim, BC Kim, HG Lee, SA Lim, S Park, EH Kim, SJ Lim, CJ TI Genipin-induced apoptosis in hepatoma cells is mediated by reactive oxygen species/c-Jun NH2-terminal kinase-dependent activation of mitochondrial pathway SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE genipin; apoptosis; caspase; NADPH oxidase; reactive oxygen species; mitochondria ID PENTA-ACETYL GENIPOSIDE; C6 GLIOMA-CELLS; SMOOTH-MUSCLE-CELLS; NADPH OXIDASE; CYTOCHROME-C; HYDROGEN-PEROXIDE; RAT HEPATOCYTES; DOWN-REGULATION; GROWTH-FACTOR; CANCER CELLS AB Genipin, the aglycone of geniposide, exhibits anti-inflammatory and anti-angiogenic activities. Here we demonstrate that genipin induces apoptotic cell death in FaO rat hepatoma cells and human hepatocarcinoma Hep3B cells, detected by morphological cellular changes, caspase activation and release of cytochrome c. During genipin-induced apoptosis, reactive oxygen species (ROS) level was elevated, and N-acetyl-(L)-Cysteine (NAC) and glutathione (GSH) suppressed activation of caspase-3, -7 and -9. Stress-activated protein kinase/c-Jun NH2-terminal kinase 1/2(SAPK/JNK1/2) but neither MEK1/2 nor p38 MAPK was activated in genipin-treated hepatoma cells. SP600125, an SAPK/JNK1/2 inhibitor, markedly suppressed apoptotic cell death in the genipin-treated cells. The FaO cells stably transfected with a dominant-negative c-Jun, TAM67, was less susceptible to apoptotic cell death triggered by genipin. Diphenyleneiodonium (DPI), an inhibitor of NADPH oxidase, inhibited ROS generation, apoptotic cell death, caspase-3 activation and JNK activation. Consistently, the stable expression of Nox1-C, a C-terminal region of Nox1 unable to generate ROS, blocked the formation of TUNEL-positive apoptotic cells, and activation of caspase-3 and JNK in FaO cells treated with genipin. Our observations imply that genipin signaling to apoptosis of hepatoma cells is mediated via NADPH oxidase-dependent generation of ROS, which leads to downstream of p JNK. (c) 2005 Elsevier Inc. All rights reserved. C1 Kangweon Natl Univ, Coll Nat Sci, Div Life Sci, Chunchon 200701, South Korea. Sookmyung Womens Univ, Coll Pharm, Seoul 140742, South Korea. NCI, Lab Cell Regulat & Carcinogensis, Bethesda, MD 20892 USA. RP Lim, CJ (reprint author), Kangweon Natl Univ, Coll Nat Sci, Div Life Sci, 192-1 Hyoja-2 Dong, Chunchon 200701, South Korea. EM cjlim@kangwon.ac.kr NR 54 TC 75 Z9 82 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD NOV 1 PY 2005 VL 70 IS 9 BP 1398 EP 1407 DI 10.1016/j.bcp.2005.07.025 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 975SC UT WOS:000232681200014 PM 16143311 ER PT J AU Wong, HK Kim, DY Hogue, BA McNeill, DR Wilson, DM AF Wong, HK Kim, DY Hogue, BA McNeill, DR Wilson, DM TI DNA damage levels and biochemical repair capacities associated with XRCC1 deficiency SO BIOCHEMISTRY LA English DT Article ID BASE-EXCISION-REPAIR; STRAND-BREAK REPAIR; SISTER-CHROMATID EXCHANGE; POLYMERASE-BETA INTERACTION; LIGASE-III; MAMMALIAN DNA; HUMAN-CELLS; CHO CELLS; POLY(ADP-RIBOSE) POLYMERASE; HAMSTER-CELLS AB Base excision repair (BER) is the major corrective pathway for most spontaneous, oxidative, and alkylation DNA base and sugar damage. X-ray cross-complementing I (XRCC1) has been suggested to function at nearly every step of this repair process, primarily through direct protein-protein interactions. Using whole cell extract (WCE) repair assays and DNA damage measurement techniques, we examined systematically the quantitative contribution of XRCC1 to specific biochemical steps of BER and single-strand break repair (SSBR). Our studies reveal that XRCC1-deficient Chinese hamster ovary WCEs exhibit normal base excision activity for 8-oxoguanine (8-OH-dG), 5-hydroxycytosine, ethenoadenine, and uracil lesions. Moreover, XRCC1 mutant EM9 cells possess steady-state levels of endogenous 8-OH-dG base damage similar to those of their wild-type counterparts. Abasic site incision activity was found to be normal in XRCC1-deficient cell extracts, as were the levels of abasic sites in isolated chromosomal DNA from mutant cells. While one- and five-nucleotide gap filling was not affected by XRCC1 status, a significant similar to 2-4-fold reduction in nick ligation activity was observed in EM9 WCEs. Our results herein suggest that the primary biochemical defect associated with XRCC1 deficiency is in the ligation step of BER/SSBR, and that XRCC1 plays no significant role in endogenous base damage and abasic site repair, or in promoting the polymerase gap-filling step. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Cheongju Univ, Dept Genet Engn, Cheongju 360764, South Korea. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wilsonda@grc.nia.nih.gov NR 73 TC 25 Z9 25 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD NOV 1 PY 2005 VL 44 IS 43 BP 14335 EP 14343 DI 10.1021/bi051161o PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 980DE UT WOS:000232993300031 PM 16245950 ER PT J AU Ressom, HW Varghese, RS Abdel-Hamid, M Eissa, SAL Saha, D Goldman, L Petricoin, EF Conrads, TP Veenstra, TD Loffredo, CA Goldman, R AF Ressom, HW Varghese, RS Abdel-Hamid, M Eissa, SAL Saha, D Goldman, L Petricoin, EF Conrads, TP Veenstra, TD Loffredo, CA Goldman, R TI Analysis of mass spectral serum profiles for biomarker selection SO BIOINFORMATICS LA English DT Article ID OVARIAN-CANCER; PROTEOMIC PATTERNS; SPECTROMETRY; IDENTIFICATION; RESOLUTION; DISCOVERY; CARCINOMA; DIAGNOSIS; SAMPLES; MARKER AB Motivation: Mass spectrometric profiles of peptides and proteins obtained by current technologies are characterized by complex spectra, high dimensionality and substantial noise. These characteristics generate challenges in the discovery of proteins and protein-profiles that distinguish disease states, e.g. cancer patients from healthy individuals. We present low-level methods for the processing of mass spectral data and a machine learning method that combines support vector machines, with particle swarm optimization for biomarker selection. Results: The proposed method identified mass points that achieved high prediction accuracy in distinguishing liver cancer patients from healthy individuals in SELDI-QqTOF profiles of serum. C1 Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. NHTMRI, Viral Hepatitis Res Lab, Cairo, Egypt. Natl Canc Inst, Cairo, Egypt. NCI, US FDA, Clin Proteom Program, Ctr Biol Evaluat, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Frederick, MD 21701 USA. NCI, Biomed Proteom Program, Frederick, MD 21701 USA. RP Ressom, HW (reprint author), Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC 20057 USA. EM hwr@georgetown.edu RI Varghese, Rency/A-8770-2012 NR 26 TC 54 Z9 59 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD NOV 1 PY 2005 VL 21 IS 21 BP 4039 EP 4045 DI 10.1093/bioinformatics/bti670 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 978VM UT WOS:000232901100016 PM 16159919 ER PT J AU Griffith, LM Pavletic, SZ Tyndall, A Bredeson, CN Bowen, JD Childs, RW Gratwohl, A van Laar, JM Mayes, MD Martin, R McSweeney, PA Muraro, PA Openshaw, H Saccardi, R Sandmaier, BM Forman, SJ Nash, RA AF Griffith, LM Pavletic, SZ Tyndall, A Bredeson, CN Bowen, JD Childs, RW Gratwohl, A van Laar, JM Mayes, MD Martin, R McSweeney, PA Muraro, PA Openshaw, H Saccardi, R Sandmaier, BM Forman, SJ Nash, RA CA Workshop Participants TI Feasibility of Allogeneic Hematopoietic Stem Cell Transplantation for Autoimmune Disease: Position Statement from a National Institute of Allergy and Infectious Diseases and National Cancer Institute-Sponsored International Workshop, Bethesda, MD, March 12 and 13, 2005 SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE allogeneic hematopoietic cell transplantation; autoimmune disease; clinical trial ID BONE-MARROW-TRANSPLANTATION; SYSTEMIC-LUPUS-ERYTHEMATOSUS; VERSUS-HOST-DISEASE; REFRACTORY RHEUMATOID-ARTHRITIS; CHRONIC MYELOID-LEUKEMIA; SEVERE APLASTIC-ANEMIA; LONG-TERM SURVIVAL; MULTIPLE-SCLEROSIS; REDUCED-INTENSITY; FOLLOW-UP C1 NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplant & Immunol Branch, NIH, Bethesda, MD 20892 USA. Dept Rheumatol, Basel, Switzerland. Med Coll Wisconsin, Ctr Int Blood & Marrow Transplantat Res, Milwaukee, WI 53226 USA. Univ Washington, Dept Neurol, Seattle, WA 98195 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Univ Basel, Dept Hematol, Kantonsspital, Basel, Switzerland. Univ Basel, Dept Internal Med, Kantonsspital, Basel, Switzerland. Leiden Univ, Med Ctr, Dept Rheumatol, Leiden, Netherlands. Univ Texas, Houston Hlth Sci Ctr, Dept Med, Div Rheumatol, Houston, TX USA. Natl Inst Neurol Disorders & Stroke, Neuroimmunol Branch, Rocky Mtn Canc Ctr, NIH, Bethesda, MD USA. City Hope Natl Med Ctr, Dept Neurol, Duarte, CA 91010 USA. Policlin Careggi, Bone Marrow Transplant Unit, Florence, Italy. Univ Washington, Seattle, WA 98195 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. City Hope Natl Med Ctr, Div Hematol & Hematopoiet Cell Transplantat, Duarte, CA 91010 USA. RP Pavletic, SZ (reprint author), NCI, Expt Transplant & Immunol Branch, WG Magnus Clin Ctr, 10 Ctr Dr,Room 4-3130, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov FU Intramural NIH HHS NR 58 TC 45 Z9 45 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD NOV PY 2005 VL 11 IS 11 BP 862 EP 870 DI 10.1016/j.bbmt.2005.07.009 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 987LU UT WOS:000233520200003 PM 16275589 ER PT J AU O'Connell, K AF O'Connell, K TI There's no place like WormBase: an indispensable resource for Caenorhabditis elegans researchers SO BIOLOGY OF THE CELL LA English DT Article DE Caenorhabditis elegans; database; genomics; Internet; WormBase AB The nematode Caenorhabditis elegans is used extensively by scientists to study a wide variety of biological processes and is one of the most thoroughly characterized animals. Over the years, the community of C. elegans researchers has generated a wealth of information on the genetics, development, behaviour, and cellular and molecular biology of the worm. This body of data has grown even larger with the recent application of high throughput screening methodology to study gene function, expression and interactions. WormBase (http://www.wormbase.org) is the primary online source of biological data on C. elegans and related nematodes. Equipped with an assortment of powerful search tools, WormBase allows users to quickly extract a variety of information, including data on individual genes, DNA sequence, cell lineage and literature citations. As the database is well maintained and the functionalities constantly modified in response to evolving researcher needs, WormBase has become a vital component of the laboratories studying the worm and a model for other biological databases. C1 NIH, NIDDK, Lab Biochem & Genet, Bethesda, MD 20892 USA. RP O'Connell, K (reprint author), NIH, NIDDK, Lab Biochem & Genet, Bethesda, MD 20892 USA. EM kevino@intra.niddk.nih.gov NR 0 TC 4 Z9 4 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0248-4900 J9 BIOL CELL JI Biol. Cell PD NOV PY 2005 VL 97 IS 11 BP 867 EP 872 DI 10.1042/BC20040155 PG 6 WC Cell Biology SC Cell Biology GA 986BT UT WOS:000233424600007 PM 16232125 ER PT J AU Paul, BD Lalani, S Bosy, T Jacobs, AJ Huestis, MA AF Paul, BD Lalani, S Bosy, T Jacobs, AJ Huestis, MA TI Concentration profiles of cocaine, pyrolytic methyl ecgonidine and thirteen metabolites in human blood and urine: determination by gas chromatography-mass spectrometry SO BIOMEDICAL CHROMATOGRAPHY LA English DT Article DE use of smoked cocaine and alcohol; metabolite concentrations; human blood and urine; gas chromatography-mass spectroscopy ID FREE-BASE COCAINE; METHYLECGONIDINE; INHALATION; SMOKING; PRODUCT; ABUSE AB When cocaine is smoked, a pyrolytic product, methyl ecgonidine (anhydroecgonine methyl ester), is also consumed with the cocaine. The amount of methyl ecgonidine formed depends on the pyrolytic conditions and composition of the illicit cocaine. This procedure describes detection of cocaine and 10 metabolites-cocaethylene, nor-cocaine, nor-coca ethylene, methyl ecgonine, ethyl ecgonine, benzoylecgonine, nor-benzoylecconine, m-hydroxybenzoylecgonine, p-hydroxybenzoylecgonine and ecgonine-in blood and urine. In addition, the detection of pyrolytic methyl ecgonidine and three metabolites-ecgonidine (anhydroecgonine), ethyl ecgonidine (anhydroecgonine ethyl ester) and nor-ecgonidine (nor-anhydroecgonine)-are included. The newly described metabolites, ethyl ecgonidine and nor-ecgonidine, were synthesized and characterized by gas chromatography-mass spectrometry (GC-MS). All 15 compounds were extracted from 3 mL of blood or urine by solid-phase extraction and identified by a GC-MS method. The overall recoveries were 49% for methyl ecgonine, 35% for ethyl ecgonine, 29% for ecgonine and more than 83% for all other drugs. The limits of detection were between 0.5 and 4.0 ng/mL except for ecgonine, which was 16 ng/ mL. Linearity for each analyte was established and in all cases correlation coefficients were 0.9985-1.0000. The procedure was applied to examine the concentration profiles of analytes of interest in post-mortem (PM) blood and urine, and in urine collected from living individuals (LV). These specimens previously were shown to be positive for the cocaine metabolite, benzoylecgonine. Ecgonidine, the major metabolite of methyl ecgonidine, was present in 77% of PM and 88% of the LV specimens, indicating smoking as the major route of cocaine administration. The new pyrolytic metabolites, ethyl ecgonidine and nor-ecgonidine, were present in smaller amounts. The urine concentrations of nor-ecgonidine were 0-163 ng/mL in LV and 0-75 ng/mL in PM specimens. Ethyl ecgonidine was found only in PM urine at concentrations 0-39 ng/mL. Ethanol-related cocaine metabolites, ethyl ecgonine or cocaethylene, were present in 69% of PM and 53% of cocaine-positive LV specimens, implying alcohol consumption with cocaine use. The four major metabolites of cocaine-benzoylecgonine, ecgonine, nor-benzoylecgonine and methyl ecgonine-constituted approximately 88 and 97% of all metabolites in PM and LV specimens, respectively. The concentrations of nor-cocaine and nor-cocaethylene were consistently the lowest of all cocaine metabolites. At benzoylecgonine concentrations below 100 ng/mL, ecgonine was present at the highest concentrations. In 20 urine specimens, benzoylecgonine and ecgonine median concentrations (range) were 54 (0-47) and 418 ng/mL (95-684), respectively. Therefore, detection of ecgonine is advantageous when benzoylecgonine concentrations are below 100 ng/mL. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Armed Forces Inst Pathol, Off Armed Forces Med Examiner, Div Forens Toxicol, Rockville, MD 20850 USA. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. RP Paul, BD (reprint author), Armed Forces Inst Pathol, Off Armed Forces Med Examiner, Div Forens Toxicol, 1413 Res Blvd, Rockville, MD 20850 USA. EM Buddha.Paul@afip.osd.mil NR 21 TC 36 Z9 36 U1 4 U2 23 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0269-3879 J9 BIOMED CHROMATOGR JI Biomed. Chromatogr. PD NOV PY 2005 VL 19 IS 9 BP 677 EP 688 DI 10.1002/bmc.495 PG 12 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Chemistry; Pharmacology & Pharmacy GA 984PO UT WOS:000233317000006 PM 15841503 ER PT J AU Torti, SV Ma, R Venditto, VJ Torti, FM Planalp, RP Brechbiel, MW AF Torti, SV Ma, R Venditto, VJ Torti, FM Planalp, RP Brechbiel, MW TI Preliminary evaluation of the cytotoxicity of a series of tris-2-aminoethylamine (Tren) based hexadentate heterocyclic donor agents SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID ANTICANCER IRON CHELATOR; TRANSFERRIN RECEPTOR; LIGAND OXIDATION; COMPLEXES; CIS,CIS-1,3,5-TRIAMINOCYCLOHEXANE; RADIOPHARMACEUTICALS; TACHPYRIDINE; DEFEROXAMINE; CARCINOMA; GROWTH AB Tachpyridine is a cytotoxic metal chelator with potential anti-tumor activity. The synthesis and evaluation of a set of derivatives of the related hexadentate heterocyclic donor agents tris-2-aminoethylamine (tren) and tris[N-(2-pyridylmethylene)-2-aminoethyl]amine (trenpyr) was performed to compare their cytotoxic activity to tachpyridine in HeLa tumor cells. Methyl groups were added to the pyridyl ring of trenpyr, and the effects of alkyl group substitution on cell survival were assessed. Profound cytotoxicity was observed and IC50 data were obtained in ascending order from those compounds substituted with a methyl group at the 3-, 4-, or 5-position and lastly by the 6-methyl derivative. These results suggest that analogous derivatives with substitution at the 3-position of the pyridyl ring deserve further exploration. Published by Elsevier Ltd. C1 NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Ctr Comprehens Canc, Dept Biochem, Winston Salem, NC 27109 USA. Wake Forest Univ, Sch Med, Ctr Comprehens Canc, Dept Canc Biol, Winston Salem, NC 27109 USA. Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. RP Brechbiel, MW (reprint author), NCI, Radiat Oncol Branch, NIH, 10 Ctr Dr,Bldg 10,Room B3B69, Bethesda, MD 20892 USA. EM martinwb@mail.nih.gov FU Intramural NIH HHS; NIDDK NIH HHS [DK 57781] NR 21 TC 6 Z9 6 U1 3 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD NOV 1 PY 2005 VL 13 IS 21 BP 5961 EP 5967 DI 10.1016/j.bmc.2005.07.007 PG 7 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 973JD UT WOS:000232517800008 PM 16115775 ER PT J AU Dijoux, MG Schnabel, PC Hallock, YF Boswell, JL Johnson, TR Wilson, JA Ireland, CM van Soest, R Boyd, MR Barrows, LR Cardellina, JH AF Dijoux, MG Schnabel, PC Hallock, YF Boswell, JL Johnson, TR Wilson, JA Ireland, CM van Soest, R Boyd, MR Barrows, LR Cardellina, JH TI Antitumor activity and distribution of pyrroloiminoquinones in the sponge genus Zyzzya SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE antitumor; pyrroloiminoquinone; topoisomerase II; DNA intercalation; DNA damage; Zyzzya ID MARINE NATURAL-PRODUCTS; PYRROLOQUINOLINE ALKALOIDS; PYRIDOACRIDINE ALKALOIDS; BATZELLA SP; MAKALUVAMINES; DISCORHABDIN; LATRUNCULIA; FULIGINOSA; DAMIRIA; GENERA AB A detailed analysis of four different collections of the sponge genus Zyzzya yielded nine pyrroloiminoquinones of the makaluvamine, batzelline, and isobatzelline/damirone classes. Dereplication analyses of additional Zyzzya extracts did not disclose more potent or additional new compounds. Comparative testing of these compounds in the National Cancer Institute's 60 cell line human tumor screen revealed varying levels of potency and differential cytotoxicity, apparently related to the unsaturation levels in and substitution patterns on the core ring system. Further studies on the topoisomerase II-mediated DNA cleavage were conducted. Reductive activation of the pyrroloiminoquinones led to DNA damage in vitro, which correlated with half wave potentials and reversibility parameters. DNA damage could be abrogated by ascorbate. Fluorescence displacement was used to measure intercalation with DNA; intercalation efficiency did not correlate with DNA-damaging proficiency. Makaluvamine H (5) emerged as the most potent and differential of our isolates, roughly comparable to makaluvamines C (in vitro) and I (in vivo). 3,7-Dimethyl guanine was isolated from one of the Zyzzya collections and from the sponge Latrunculia purpurea. (c) 2005 Elsevier Ltd. All rights reserved. C1 NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Frederick Canc Res & Dev Ct, Div Canc Treatment & Diagnosis, Frederick, MD 21702 USA. Univ Utah, Coll Pharm, Dept Pharmacol & Toxicol, Salt Lake City, UT 84112 USA. Univ Utah, Coll Pharm, Dept Med Chem, Salt Lake City, UT 84112 USA. Univ Amsterdam, Zool Museum, NL-1090 GT Amsterdam, Netherlands. RP Barrows, LR (reprint author), NCI, Lab Drug Discovery Res & Dev, Dev Therapeut Program,Frederick Canc Res & Dev Ct, Div Canc Treatment & Diagnosis, Bldg 1052,Room 121, Frederick, MD 21702 USA. EM lbarrows@deans.pharm.utah.edu; jcardellina@ncifcrf.gov NR 31 TC 18 Z9 19 U1 2 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD NOV 1 PY 2005 VL 13 IS 21 BP 6035 EP 6044 DI 10.1016/j.bme.2005.06.019 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 973JD UT WOS:000232517800017 PM 16009557 ER PT J AU Tangirala, RS Dixon, R Yang, DZ Ambrus, A Antony, S Agama, K Pommier, Y Curran, DP AF Tangirala, RS Dixon, R Yang, DZ Ambrus, A Antony, S Agama, K Pommier, Y Curran, DP TI Total and semisynthesis and in vitro studies of both enantiomers of 20-fluorocamptothecin SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE camptothecin; topoisomerase 1; isonitrile radical annulation ID HUMAN TOPOISOMERASE-I; SPECTRUM DEOXOFLUORINATING AGENT; ENHANCED THERMAL-STABILITY; TERNARY CLEAVABLE COMPLEX; BIS(2-METHOXYETHYL)AMINOSULFUR TRIFLUORIDE; ASYMMETRIC DIHYDROXYLATION; ANTITUMOR-ACTIVITY; LACTONE RING; CAMPTOTHECIN; DNA AB Both enantiomers of 20-fluorocamptothecin and the racemate have been prepared by total synthesis. The (R)-enantiomer is essentially inactive in a topoisomerase-I/DNA assay, while the (S)-enantiomer is much less active than (20S)-camptothecin. The lactone ring of 20-fluorocamptothecin hydrolyzes more rapidly than that of camptothecin in PBS. The results provide insight into the role of the 20-hydroxy group in the binding of camptothecin to topoisomerase-I and DNA. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. Univ Arizona, Coll Pharm, Tucson, AZ 85721 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. NCI, Canc Res Ctr, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Curran, DP (reprint author), Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA. EM curran@pitt.edu RI Yang, Danzhou/B-6228-2012; OI Ambrus, Attila/0000-0001-6014-3175 NR 44 TC 12 Z9 12 U1 0 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-894X J9 BIOORG MED CHEM LETT JI Bioorg. Med. Chem. Lett. PD NOV 1 PY 2005 VL 15 IS 21 BP 4736 EP 4740 DI 10.1016/j.bmcl.2005.07.074 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 972PO UT WOS:000232465900018 PM 16140529 ER PT J AU VanBuren, V Cassimeris, L Odde, DJ AF VanBuren, V Cassimeris, L Odde, DJ TI Mechanochemical model of microtubule structure and self-assembly kinetics SO BIOPHYSICAL JOURNAL LA English DT Article ID SLOWLY HYDROLYZABLE ANALOG; LATERAL CAP MODEL; DYNAMIC INSTABILITY; GTP HYDROLYSIS; PLUS-END; STABILIZE MICROTUBULES; THERMAL FLUCTUATIONS; XENOPUS EGGS; MONTE-CARLO; RIGIDITY AB Microtubule self-assembly is largely governed by the chemical kinetics and thermodynamics of tubulin-tubulin interactions. An important aspect of microtubule assembly is that hydrolysis of the beta-tubulin-associated GTP promotes proto. lament curling. Proto. lament curling presumably drives the transition from tip structures associated with growth (sheetlike projections and blunt ends) to those associated with shortening (rams' horns and frayed ends), and transitions between these structures have been proposed to be important for growth-shortening transitions. However, previous models for microtubule dynamic instability have not considered such structures or mechanics explicitly. Here we present a three-dimensional model that explicitly incorporates mechanical stress and strain within the microtubule lattice. First, we found that the model recapitulates three-dimensional tip structures and rates of assembly and disassembly for microtubules grown under standard conditions, and we propose that taxol may stabilize microtubule growth by reducing flexural rigidity. Second, in contrast to recent suggestions, it was determined that sheetlike tips are more likely to undergo catastrophe than blunt tips. Third, partial uncapping of the tubulin-GTP cap provides a possible mechanism for microtubule pause events. Finally, simulations of the binding and structural effects of XMAP215 produced the experimentally observed growth and shortening rates, and tip structure. C1 Lehigh Univ, Dept Biol Sci, Bethlehem, PA 18015 USA. Univ Minnesota, Dept Biomed Engn, Minneapolis, MN USA. RP Odde, DJ (reprint author), NIA, Genet Lab, NIH, 333 Cassell Dr,Suite 3000, Baltimore, MD 21224 USA. EM odde@mail.ahc.umn.edu RI Odde, David/H-4925-2011; OI Cassimeris, Lynne/0000-0003-1058-0734; Odde, David/0000-0001-7731-2799 NR 41 TC 129 Z9 132 U1 3 U2 26 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2005 VL 89 IS 5 BP 2911 EP 2926 DI 10.1529/biophysj.105.060913 PG 16 WC Biophysics SC Biophysics GA 979HP UT WOS:000232933300008 PM 15951387 ER PT J AU Sen, PN Basser, PJ AF Sen, PN Basser, PJ TI A model for diffusion in white matter in the brain SO BIOPHYSICAL JOURNAL LA English DT Article; Proceedings Paper CT 7th International Conference on Magnetic Resonance in Porous Media (MRPM7) CY JUL 04-08, 2004 CL Palaiseau, FRANCE ID BOVINE OPTIC-NERVE; MAGNETIC-RESONANCE; APPARENT DIFFUSION; RESTRICTED DIFFUSION; WATER DIFFUSION; BIOLOGICAL TISSUE; CELL-VOLUME; SPINAL-CORD; COEFFICIENT; ANISOTROPY AB Diffusion of molecules in brain and other tissues is important in a wide range of biological processes and measurements ranging from the delivery of drugs to diffusion-weighted magnetic resonance imaging. Diffusion tensor imaging is a powerful noninvasive method to characterize neuronal tissue in the human brain in vivo. As a first step toward understanding the relationship between the measured macroscopic apparent diffusion tensor and underlying microscopic compartmental geometry and physical properties, we treat a white matter fascicle as an array of identical thick-walled cylindrical tubes arranged periodically in a regular lattice and immersed in an outer medium. Both square and hexagonal arrays are considered. The diffusing molecules may have different diffusion coefficients and concentrations (or densities) in different domains, namely within the tubes' inner core, membrane, myelin sheath, and within the outer medium. Analytical results are used to explore the effects of a large range of microstructural and compositional parameters on the apparent diffusion tensor and the degree of diffusion anisotropy, allowing the characterization of diffusion in normal physiological conditions as well as changes occurring in development, disease, and aging. Implications for diffusion tensor imaging and for the possible in situ estimation of microstructural parameters from diffusion-weighted MR data are discussed in the context of this modeling framework. C1 NIH, Bethesda, MD 20892 USA. Schlumberger Doll Res Ctr, Ridgefield, CT 06877 USA. RP Sen, PN (reprint author), Schlumberger Doll Res Ctr, Old Quarry Rd, Ridgefield, CT 06877 USA. EM sen1@slb.com RI Basser, Peter/H-5477-2011 NR 31 TC 126 Z9 128 U1 1 U2 8 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD NOV PY 2005 VL 89 IS 5 BP 2927 EP 2938 DI 10.1529/biophysj.063016 PG 12 WC Biophysics SC Biophysics GA 979HP UT WOS:000232933300009 PM 16100258 ER PT J AU Conejero-Goldberg, C Wang, E Yi, CL Goldberg, TE Jones-Brando, L Marincola, FM Webster, MJ Torrey, EF AF Conejero-Goldberg, C Wang, E Yi, CL Goldberg, TE Jones-Brando, L Marincola, FM Webster, MJ Torrey, EF TI Infectious pathogen detection arrays: viral detection in cell lines and postmortem brain tissue SO BIOTECHNIQUES LA English DT Article ID HERPES-SIMPLEX-VIRUS; OLIGONUCLEOTIDE MICROARRAY HYBRIDIZATION; SARCOMA-ASSOCIATED HERPESVIRUS; DNA MICROARRAY; NUCLEOTIDE-SEQUENCE; TOXOPLASMA-GONDII; GENE-EXPRESSION; SCHIZOPHRENIA; AMPLIFICATION; INDIVIDUALS AB A unique array-based pathogen chip has been developed for the detection of viral RNA or DNA relevant to pathologies of the central nervous system. A total of 715 unique oligonucleotides (60-mer) representing approximately 100 pathogens were designed based on open reading frames (ORFs) from highly conserved and heterogenic regions within viral families. In addition, viral genes reflecting different stages of pathogen infection were also included to potentially define the stage of the viral infection. Viruses (double-stranded DNA, double- or single-stranded RNA, delta, retroid), parasites, and bacteria were included. Test samples labeled with Cy(TM)5 were examined by cohybridization with a reference RNA, labeled with Cy3, to the pathogen microarray chip. Good reproducibility of experiments was observed, based on data generated from duplicate hybridizations and duplicate spots on the microarray platform. A viral transcript detection sensitivity of 1 X 10(3) plaque-forming units (pfus) was achieved using selected cell lines and viruses. These findings suggest that the array-based platform described here is capable of detecting a broad spectrum of viruses in a single assay with relatively high sensitivity, specificity, and reproducibility. This method may be used to provide evidence of viral infection in postmortem tissue from psychiatric patients as well as a wide range of other diagnostic categories. C1 Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Brain Res Lab, NIH,Clin Ctr, Bethesda, MD 20814 USA. NIH, Ctr Clin, Dept Transfus Med, Bethesda, MD 20892 USA. NIH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Stanley Div Dev Neurovirol, Baltimore, MD USA. Stanley Med Res Inst, Bethesda, MD USA. RP Conejero-Goldberg, C (reprint author), Uniformed Serv Univ Hlth Sci, Dept Psychiat, Stanley Brain Res Lab, NIH,Clin Ctr, 4301 Jones Bridge Rd,Bldg 53,Room 13, Bethesda, MD 20814 USA. EM goldbergc@stanleyresearch.org NR 47 TC 21 Z9 22 U1 0 U2 0 PU BIOTECHNIQUES OFFICE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD NOV PY 2005 VL 39 IS 5 BP 741 EP 751 DI 10.2144/000112016 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 984IR UT WOS:000233297000015 PM 16312221 ER PT J AU Emery, SP Levine, RJ Qian, C Ewell, MG England, LJ Yu, KF Catalano, PM AF Emery, SP Levine, RJ Qian, C Ewell, MG England, LJ Yu, KF Catalano, PM CA CPEP Study Grp TI Twenty-four-hour urine insulin as a measure of hyperinsulinaemia/insulin resistance before onset of pre-eclampsia and gestational hypertension SO BJOG-AN INTERNATIONAL JOURNAL OF OBSTETRICS AND GYNAECOLOGY LA English DT Article ID PREGNANCY-INDUCED HYPERTENSION; ABNORMAL GLUCOSE-TOLERANCE; HEALTHY NULLIPAROUS WOMEN; DIABETES-MELLITUS; INTOLERANCE; CALCIUM; RISK; HYPERINSULINEMIA; COMPLICATIONS; METABOLISM AB Objective To evaluate levels of 24-hour urine insulin excretion before the onset of pre-eclampsia and gestational hypertension. Design Nested case-control study within the Calcium for Preeclampsia Prevention (CPEP) study cohort. Setting Five university medical centres in the United States. Sample Cases had developed pre-eclampsia (n= 70) or gestational hypertension (n= 142) in the absence of gestational diabetes. Controls (n= 429) had remained normotensive without gestational diabetes. Methods Subjects were required to have had an adequate baseline 24-hour urine collection prior to CPEP enrolment at 13-21 weeks. Controls were matched to cases by enrolment site and specimen storage time, without regard to gestational age or CPEP treatment. Adjusted mean 24-hour urine insulin excretion was, however, calculated using analysis of covariance, with adjustment models for pre-eclampsia considering body mass index, race and smoking status; and for gestational hypertension, gestational age at specimen collection, height, body mass index and smoking. Urine insulin was measured by radio-immunoassay. Main outcome measures Twenty-four-hour urine insulin excretion. Results Adjusted 24-hour urine insulin excretion at baseline (mean 17 weeks of gestation) was greater in women who developed pre-eclampsia than in normotensive controls (mean [SE]: 15.6 [1.5] vs 13.1 [1.2] x 10(3)mu IU/24 hour, P= 0.06), but not in women who developed gestational hypertension (14.7 [0.9] vs 15.0 [0.6] x 10(3)mu IU/24 hour, P= 0.79, in cases vs controls). Among women who developed pre-eclampsia, adjusted urine insulin excretion was greater than controls only in women with mild pre-eclampsia and not in severe pre-eclampsia (mild pre-eclampsia vs controls: 17.3 [2.0] vs 13.7 [1.6] x 10(3)mu IU/24 hour, P= 0.04; severe pre-eclampsia vs controls: 12.3 [2.2] vs 11.5 [1.2], P= 0.69). Conclusion The data suggest that early hyperinsulinaemia, a marker of insulin resistance, may predispose to mild pre-eclampsia. C1 NICHD, Epidemiol Branch, US Dept HHS, NIH, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Obstet & Gynecol, Cleveland, OH 44195 USA. Allied Technol Grp, Rockville, MD USA. Emmes Corp, Rockville, MD USA. NICHD, Biometry & Math Stat Branch, US Dept HHS, NIH, Bethesda, MD 20892 USA. Case Western Reserve Univ, Metrohlth Med Ctr, Dept Reprod Biol, Cleveland, OH USA. RP Levine, RJ (reprint author), NICHD, Epidemiol Branch, US Dept HHS, NIH, Bldg 6100,Room 7B03, Bethesda, MD 20892 USA. FU NICHD NIH HHS [N01-HD-1-3121, N01-HD-1-3122, N01-HD-1-3123, N01-HD-1-3124, N01-HD-1-3125, N01-HD-1-3126, N01-HD-2-3154, N01-HD-5-3246] NR 31 TC 20 Z9 21 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1470-0328 J9 BJOG-INT J OBSTET GY JI BJOG PD NOV PY 2005 VL 112 IS 11 BP 1479 EP 1485 DI 10.1111/j.1471-0528.2005.00720.x PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 975JE UT WOS:000232657200004 PM 16225566 ER PT J AU Sharifi, N Dahut, WL Steinberg, SM Figg, WD Tarassoff, C Arlen, P Gulley, JL AF Sharifi, N Dahut, WL Steinberg, SM Figg, WD Tarassoff, C Arlen, P Gulley, JL TI A retrospective study of the time to clinical endpoints for advanced prostate cancer SO BJU INTERNATIONAL LA English DT Article DE retrospective study; prostatic neoplasms; natural history; PSA; survival analysis ID NATURAL-HISTORY; ANDROGEN RECEPTOR; RADICAL PROSTATECTOMY; MITOXANTRONE; FLUTAMIDE; SURVIVAL; ANTIGEN; MEN; PROGRESSION; CASTRATION AB OBJECTIVE To determine the natural history of patients with prostate cancer who start initial androgen-deprivation therapy (ADT) for biochemical failure with no radiographic evidence of disease (D0) or with radiographic metastatic disease (D2), as the history is either not well-defined or is changing, and such data are critical for guiding therapy after prostate cancer recurrence. PATIENTS AND METHODS We retrospectively assessed the time to androgen-independence (AI), defined as the first sustained rise in prostate-specific antigen (PSA) level on ADT, time to metastatic disease and overall survival for 80 patients with metastatic prostate cancer in clinical trials at the National Cancer Institute. RESULTS ADT was initiated after metastatic disease in 37 patients and before metastatic disease in 43 patients; in these 43 patients, the median time to developing metastatic disease on ADT was 37.8 months. The median time to AI from the initiation of ADT was 19.3 and 13.1 months in D0 and D2 patients, respectively. The median overall survival from the start of ADT was 89.0 and 63.0 months, and the median overall survival from the time of AI was 63.1 and 44.2 months in D0 and D2 patients, respectively. These 80 patients, which included 43 who had no metastatic disease when starting ADT, had a median survival of 54.8 months after AI prostate cancer. CONCLUSIONS We describe the natural history of AI prostate cancer in D0 patients who eventually developed metastasis, and in D2 patients. The results suggest a longer than expected survival with AI prostate cancer, and to our knowledge this is the first study to report the time to metastatic disease for D0 patients from ADT and from AI. These results can be used to help design clinical trials in patients with D0 prostate cancer. C1 NCI, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Gulley, JL (reprint author), NCI, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, Ctr Canc Res, 10 Ctr Dr,8B07 MSC 1750, Bethesda, MD 20892 USA. EM gulleyj@mail.nih.gov RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 18 TC 37 Z9 39 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-4096 J9 BJU INT JI BJU Int. PD NOV PY 2005 VL 96 IS 7 BP 985 EP 989 DI 10.1111/j.1464-410X.2005.05798.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 973XZ UT WOS:000232557200011 PM 16225513 ER PT J AU Gladwin, MT AF Gladwin, MT TI Unraveling the hemolytic subphenotype of sickle cell disease SO BLOOD LA English DT Editorial Material ID HEMOGLOBIN SCAVENGER RECEPTOR; PULMONARY-HYPERTENSION; NITRIC-OXIDE; MECHANISM C1 NIH, Bethesda, MD 20892 USA. RP Gladwin, MT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. NR 12 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2005 VL 106 IS 9 BP 2925 EP 2926 DI 10.1182/blood-2005-08-3285 PG 2 WC Hematology SC Hematology GA 979BP UT WOS:000232917400001 ER PT J AU Bea, S Zettl, A Wright, G Salaverria, I Jehn, P Moreno, V Burek, C Ott, G Puig, X Yang, LM Lopez-Guillermo, A Chan, WC Greiner, TC Weisenburger, DD Armitage, JO Gascoyne, RD Connors, JM Grogan, TM Braziel, R Fisher, RI Smeland, EB Kvaloy, S Holte, H Delabie, J Simon, R Powell, J Wilson, WH Jaffe, ES Montserrat, E Muller-Hermelink, HK Staudt, LM Campo, E Rosenwald, A AF Bea, S Zettl, A Wright, G Salaverria, I Jehn, P Moreno, V Burek, C Ott, G Puig, X Yang, LM Lopez-Guillermo, A Chan, WC Greiner, TC Weisenburger, DD Armitage, JO Gascoyne, RD Connors, JM Grogan, TM Braziel, R Fisher, RI Smeland, EB Kvaloy, S Holte, H Delabie, J Simon, R Powell, J Wilson, WH Jaffe, ES Montserrat, E Muller-Hermelink, HK Staudt, LM Campo, E Rosenwald, A CA Lymphoma Leukemia Mol Profiling Pr TI Diffuse large B-cell lymphoma subgroups have distinct genetic profiles that influence tumor biology and improve gene-expression-based survival prediction SO BLOOD LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; CHROMOSOMAL IMBALANCES; CYTOGENETIC ANALYSIS; HODGKIN LYMPHOMA; BREAST-CANCER; AMPLIFICATION; PATTERNS; REVEALS; NUMBER; LEUKEMIA AB Gene-expression profiling has identified 3 major subgroups of diffuse large B-cell lymphoma (DLBCL): germinal center B-cell-like (GCB), activated B-cell-like (ABC), and primary mediastinal DLBCL (PMBCL). Using comparative genomic hybridization (CGH), we investigated the genetic alterations of 224 cases of untreated DLBCL (87 GCB-DLBCL, 77 ABC-DLBCL, 19 PMBCL, and 41 unclassified DLBCL) previously characterized by gene-expression profiling. The DLBCL subgroups differed significantly in the frequency of particular chromosomal aberrations. ABC-DLBCL had frequent trisomy 3, gains of 3q and 18q2l-q22, and losses of 6q21-q22, whereas GCB-DLBCL had frequent gains of 12q12, and PMBCL had gains of 9p21-pter and 2p14-p16. Parallel analysis of CGH alterations, locus-specific gene-expression profiles, and global gene-expression signatures revealed that DNA amplifications and gains had a substantial impact on the expression of genes in the involved chromosomal regions, and some genes were overexpressed in a DLBCL subgroup-specific fashion. Unexpectedly, specific chromosomal alterations were associated with significant changes in gene-expression signatures that reflect various aspects of lymphoma cell biology as well as the host response to the lymphoma. In addition, gains involving the chromosomal region 3p11-p12 provided prognostic information that was statistically independent of the previously defined gene-expresson-based survival model, thereby improving its predictive power. C1 Univ Barcelona, Hosp Clin, Hematopathol Sect,Dept Pathol & Hematol, Informat & Studies Serv,Catalan Dept Hlth, E-08036 Barcelona, Spain. Autonomous Univ Barcelona, Canc Epidemiol Serv, IDIBELL Catalan Inst Oncol, E-08193 Barcelona, Spain. Autonomous Univ Barcelona, Fac Med, Lab Estadist & Epidemiol, E-08193 Barcelona, Spain. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. NCI, Biometr Res Med Pathol & Metab Branch, Bethesda, MD 20892 USA. NIH, Bioinformat & Mol Anal Sect, Computat Biosci & Engn Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE USA. Univ Nebraska, Med Ctr, Dept Internal Med, Omaha, NE USA. British Columbia Canc Ctr, Dept Pathol, Vancouver, BC, Canada. Oregon Hlth & Sci Univ, Dept Pathol, Portland, OR USA. SW Oncol Grp, Portland, OR USA. Univ Arizona, Ctr Canc, Dept Pathol & Med, Tucson, AZ USA. Univ Rochester, Sch Med, James P Wilmot Canc Ctr, Rochester, NY 14627 USA. Norwegian Radium Hosp, Dept Immunol, Oslo, Norway. Norwegian Radium Hosp, Dept Oncol, Oslo, Norway. Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. RP Campo, E (reprint author), Univ Barcelona, Hosp Clin, Hematopathol Sect,Dept Pathol & Hematol, Informat & Studies Serv,Catalan Dept Hlth, Villarroel 170, E-08036 Barcelona, Spain. EM ecampo@clinic.ub.es RI Moreno, Victor/A-1697-2010; SALAVERRIA, ITZIAR/L-2246-2015; Bea, Silvia/K-7699-2014; OI Moreno, Victor/0000-0002-2818-5487; SALAVERRIA, ITZIAR/0000-0002-2427-9822; Delabie, Jan/0000-0001-5023-0689; Bea, Silvia/0000-0001-7192-2385; Campo, elias/0000-0001-9850-9793 FU NCI NIH HHS [UO1-CA84 967] NR 33 TC 221 Z9 226 U1 2 U2 5 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2005 VL 106 IS 9 BP 3183 EP 3190 DI 10.1182/blood-2005-04-1399 PG 8 WC Hematology SC Hematology GA 979BP UT WOS:000232917400046 PM 16046532 ER PT J AU Turner, J Koumenis, C Kute, TE Planalp, RP Brechbiel, MW Beardsley, D Cody, B Brown, KD Torti, FM Torti, SV AF Turner, J Koumenis, C Kute, TE Planalp, RP Brechbiel, MW Beardsley, D Cody, B Brown, KD Torti, FM Torti, SV TI Tachpyridine, a metal chelator, induces G(2) cell-cycle arrest, activates checkpoint kinases, and sensitizes cells to ionizing radiation SO BLOOD LA English DT Article ID PYRIDOXAL ISONICOTINOYL HYDRAZONE; EFFECTIVE ANTIPROLIFERATIVE AGENTS; DNA-DEPENDENT PROTEIN; MAMMALIAN RIBONUCLEOTIDE REDUCTASE; TRANSFERRIN RECEPTOR GENE; ANTICANCER IRON CHELATOR; DAMAGE CHECKPOINT; CHROMOSOMAL RADIOSENSITIVITY; LIPID-PEROXIDATION; GROWTH-INHIBITION AB Iron is critical for cell growth and proliferation. Iron chelators are being explored for a number of clinical applications, including the treatment of neurodegenerative disorders, heart disease, and cancer. To uncover mechanisms of action of tachpyridine, a chelator currently undergoing preclinical evaluation as an anticancer agent, cell-cycle analysis was performed. Tachpyridine arrested cells at G(2), a radiosensitive phase of the cell cycle, and enhanced the sensitivity of cancer cells but not nontransformed cells to ionizing radiation. G(2) arrest was p53 independent and was accompanied by activation of the checkpoint kinases CHK1 and CHK2. G(2) arrest was blocked by UCN-01, a CHK1 inhibitor, but proceeded in CHK2 knock-out cells, indicating a critical role for CHK1 in G(2) arrest. Tachpyridine-induced cell-cycle arrest was abrogated in cells treated with caffeine, an inhibitor of the ataxia-telangiectasia mutated/ ataxia-telanglectasia-mutated and Rad3-related (ATM/ATR) kinases. Further, G(2) arrest proceeded in ATM-deficient cells but was blocked in ATR-deficient cells, implicating ATR as the proximal kinase in tachpyridine-mediated G(2) arrest. Collectively, our results suggest that iron chelators may function as antitumor and radioenhancing agents and uncover a previously unexplored activity of iron chelators in activation of ATR and checkpoint kinases. C1 Wake Forest Univ Hlth Sci, Dept Biochem, Winston Salem, NC 27157 USA. Wake Forest Univ Hlth Sci, Dept Radiat Biol, Winston Salem, NC 27157 USA. Wake Forest Univ Hlth Sci, Dept Pathol, Winston Salem, NC 27157 USA. Univ New Hampshire, Dept Chem, Durham, NH 03824 USA. NCI, Bethesda, MD 20892 USA. Univ Florida, Coll Med, Dept Biochem & Mol Biol, Gainesville, FL 32610 USA. Wake Forest Univ Hlth Sci, Dept Canc Biol, Winston Salem, NC 27157 USA. Wake Forest Univ Hlth Sci, Ctr Comprehens Canc, Winston Salem, NC 27157 USA. RP Torti, SV (reprint author), Wake Forest Univ Hlth Sci, Dept Biochem, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM storti@wfubmc.edu RI Koumenis, Constantinos/B-2002-2008 FU NCI NIH HHS [CA102289]; NIDDK NIH HHS [DK 57781] NR 83 TC 44 Z9 46 U1 4 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 NOV 1 PY 2005 VL 106 IS 9 BP 3191 EP 3199 DI 10.1182/blood-2005-03-1263 PG 9 WC Hematology SC Hematology GA 979BP UT WOS:000232917400047 PM 16014567 ER PT J AU Rubio-Moscardo, F Blesa, D Mestre, C Siebert, R Balasas, T Benito, A Rosenwald, A Climent, J Martinez, JI Schilhabel, M Karran, EL Gesk, S Esteller, M deLeeuw, R Staudt, LM Fernandez-Luna, JL Pinkel, D Dyer, MJS Martinez-Climent, JA AF Rubio-Moscardo, F Blesa, D Mestre, C Siebert, R Balasas, T Benito, A Rosenwald, A Climent, J Martinez, JI Schilhabel, M Karran, EL Gesk, S Esteller, M deLeeuw, R Staudt, LM Fernandez-Luna, JL Pinkel, D Dyer, MJS Martinez-Climent, JA TI Characterization of 8p21.3 chromosomal deletions in B-cell lymphoma: TRAIL-R1 and TRAIL-R2 as candidate dosage-dependent tumor suppressor genes SO BLOOD LA English DT Article ID APOPTOSIS-INDUCING LIGAND; WILD-TYPE P53; COLORECTAL-CANCER; DECOY RECEPTORS; DEATH DOMAIN; BAND 8P21; MICE; EXPRESSION; BREAST; METASTASIS AB Deletions of chromosome 8p are a recurrent event in B-cell non-Hodgkin lymphoma (B-NHL), suggesting the presence of a tumor suppressor gene. We have characterized these deletions using comparative genomic hybridization to microarrays, fluorescence in situ hybridization (FISH) mapping, DNA sequencing, and functional studies. A minimal deleted region (MDR) of 600 kb was defined in chromosome 8p21.3, with one mantle cell lymphoma cell line (Z138) exhibiting monoallelic deletion of 650 kb. The MDR extended from bacterial artificial chromosome (BAC) clones RP11-382J24 and RP11-109B10 and included the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptor gene loci. Sequence analysis of the individual expressed genes within the MDR and DNA sequencing of the entire MDR in Z138 did not reveal any mutation. Gene expression analysis and quantitative reverse transcriptase-polymerase chain reaction (QRT-PCR) showed down-regulation of TRAIL-R1 and TRAIL-R2 receptor genes as a consistent event in B-NHL with 8p21.3 loss. Epigenetic inactivation was excluded via promoter methylation analysis. In vitro studies showed that TRAIL-induced apoptosis was dependent on TRAIL-R1 and/or -R2 dosage in most tumors. Resistance to apoptosis of cell lines with 8p21.3 deletion was reversed by restoration of TRAIL-R1 or TRAIL-R2 expression by gene transfection. Our data suggest that TRAIL-R1 and TRAIL-R2 act as dosage-dependent tumor suppressor genes whose monoallelic deletion can impair TRAIL-induced apoptosis in B-cell lymphoma. C1 Univ Navarra, Ctr Appl Med Res CIMA, Div Oncol, Oncol Mol Lab, Pamplona 31008, Spain. Univ Valencia, Hosp Clin, Dept Hematol & Med Oncol, Valencia, Spain. Inst Invest Citological Caja Ahorros Valencia, Valencia, Spain. Univ Hosp Schleswig Holstein, Inst Human Genet, Kiel, Germany. Univ Leicester, MRC, Toxicol Unit, Leicester LE1 7RH, Leics, England. Hosp Univ Univ Marques Valdecilla, Mol Genet Unit, Santander, Spain. Univ Wurzburg, Dept Pathol, D-97070 Wurzburg, Germany. Inst Mol Biotechnol, Jena, Germany. Ctr Nacl Invest Oncol, Madrid, Spain. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. NCI, Bethesda, MD 20892 USA. Univ Calif San Francisco, Canc Res Inst, San Francisco, CA 94143 USA. RP Martinez-Climent, JA (reprint author), Univ Navarra, Ctr Appl Med Res CIMA, Div Oncol, Oncol Mol Lab, Avda Pio XII,55, Pamplona 31008, Spain. EM jamcliment@unav.es RI Siebert, Reiner/A-8049-2010; Rubio Moscardo, Francisca/L-6247-2014; Martinez-Climent, Jose/I-9199-2012; Esteller, Manel/L-5956-2014; Dyer, Martin/F-2691-2014 OI Rubio Moscardo, Francisca/0000-0002-3609-9992; Martinez-Climent, Jose/0000-0002-7938-3950; Esteller, Manel/0000-0003-4490-6093; Dyer, Martin/0000-0002-5033-2236 NR 55 TC 66 Z9 69 U1 0 U2 11 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 NOV 1 PY 2005 VL 106 IS 9 BP 3214 EP 3222 DI 10.1182/blood-2005-05-2013 PG 9 WC Hematology SC Hematology GA 979BP UT WOS:000232917400050 PM 16051735 ER PT J AU Yamaoka, K Min, BK Zhou, YJ Paul, WE O'Shea, JJ AF Yamaoka, K Min, BK Zhou, YJ Paul, WE O'Shea, JJ TI Jak3 negatively regulates dendritic-cell cytokine production and survival SO BLOOD LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; MICE LACKING JAK3; COMMON MYELOID PROGENITOR; IL-10 GENE-EXPRESSION; RECEPTOR-GAMMA CHAIN; HUMAN MONOCYTES; LYMPHOID DEVELOPMENT; JANUS KINASE-3; T-CELLS; MOUSE AB Cytokines are critical in regulating the development and function of diverse cells. Janus kinase 3 (Jak3) is a tyrosine kinase expressed in hematopoietic cells that associates with the common gamma chain (gamma c) and is required for signaling for a family of cytokines including interleukin-2 (IL-2), IL-4, IL-7, IL-9, IL-15, and IL-21; deficiency of either Jak3 or gamma c results in severe combined immunodeficiency (SCID). While Jak3 is essential for lymphoid-cell development, the potential roles for Jak3 in regulating dendritic cells (DCs) were unclear. Herein, we show that although CD8(+)CD11c(+) splenic DCs are absent in Jak3(-/-) mice, bone marrow-derived DCs developed normally in vitro from Jak3(-/-) precursor cells. In fact, the survival of Jak3(-/-) DCs was enhanced, and they expressed lower levels of proapoptotic proteins. Jak3(-/-) DCs exhibited normal antigen uptake and up-regulation of costimulatory molecules. However, Jak3(-/-) DCs produced more IL-12 and IL-10 in response to Toll-like receptor ligands, which correlated with enhanced T helper 1 (Th1) differentiation in vivo. In summary, Jak3 is not essential for DC development but unexpectedly appears to be an important negative regulator. These results may be relevant clinically for patients with SCID who have undergone hematopoietic stem cell transplantation and for patients who might be treated with a Jak3 inhibitor. C1 NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Yamaoka, K (reprint author), NIAMSD, Mol Immunol & Inflammat Branch, NIH, Bldg 10,9N256,10 Ctr Dr, Bethesda, MD 20892 USA. EM yamaokak@mail.nih.gov NR 47 TC 37 Z9 38 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2005 VL 106 IS 9 BP 3227 EP 3233 DI 10.1182/blood-2005-02-0769 PG 7 WC Hematology SC Hematology GA 979BP UT WOS:000232917400052 PM 16020505 ER PT J AU Tang, DC Zhu, JQ Liu, WL Chin, K Sun, J Chen, L Hanover, JA Rodgers, GP AF Tang, DC Zhu, JQ Liu, WL Chin, K Sun, J Chen, L Hanover, JA Rodgers, GP TI The hydroxyurea-induced small GTP-binding protein SAR modulates gamma-globin gene expression in human erythroid cells SO BLOOD LA English DT Article ID HEMATOPOIETIC-CELLS; K562 CELLS; DIFFERENTIATION; INHIBITION; HBF; AUGMENTATION; PROGENITORS; HEMOGLOBIN; INDUCTION; PATHWAY AB Hydroxyurea (HU), a drug effective in the treatment of sickle cell disease, is thought to indirectly promote fetal hemoglobin (Hb F) production by perturbing the maturation of erythroid precursors. The molecular mechanisms involved in HU-mediated regulation of gamma-globin expression are currently unclear. We identified an HU-induced small guanosine triphosphate (GTP)-binding protein, secretion-associated and RAS-related (SAR) protein, in adult erythroid cells using differential display. Stable SAR expression in K562 cells increased gamma-globin mRNA expression and resulted in macrocytosis. The cells appeared immature. SAR-mediated induction of gamma-globin also inhibited K562 cell growth by causing arrest in G(1)/S, apoptosis, and delay of maturation, cellular changes consistent with the previously known effects of HU on erythroid cells. SAR also enhanced both gamma- and beta-globin transcription in primary bone marrow CD34(+) cells, with a greater effect on gamma-globin than on beta-globin. Although up-regulation of GATA-2 and p21 was observed both in SAR-expressing cells and HU-treated K562 cells, phosphatidylinositol 3 (PI3) kinase and phosphorylated ERK were inhibited specifically in SAR-expressing cells. These data reveal a novel role of SAR distinct from its previously known protein-trafficking function. We suggest that SAR may participate in both erythroid cell growth and gamma-globin production by regulating PI3 kinase/extracellular protein-related kinase (ERK) and GATA-2/p21-dependent signal transduction pathways. C1 NIDDKD, Mol & Clin Hematol Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Lab Cell Biochem & Biol, NIH, Bethesda, MD 20892 USA. RP Rodgers, GP (reprint author), NIDDKD, Mol & Clin Hematol Branch, NIH, Bldg 10,Rm 9N119, Bethesda, MD 20892 USA. EM gr5n@nih.gov NR 39 TC 27 Z9 27 U1 1 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2005 VL 106 IS 9 BP 3256 EP 3263 DI 10.1182/blood-2003-10-3458 PG 8 WC Hematology SC Hematology GA 979BP UT WOS:000232917400056 PM 15985540 ER PT J AU Ogasawara, Y Nakayama, K Tarnowka, M McCoy, JP Kajigaya, S Levin, BC Young, NS AF Ogasawara, Y Nakayama, K Tarnowka, M McCoy, JP Kajigaya, S Levin, BC Young, NS TI Mitochondrial DNA spectra of single human CD34(+) cells, T cells, B cells, and granulocytes SO BLOOD LA English DT Article ID MTDNA CONTROL REGION; MYELODYSPLASTIC SYNDROMES; SEQUENCE HETEROGENEITY; OXIDATIVE DAMAGE; POINT MUTATIONS; REPLICATION; FREQUENCY; DISEASE; ACCUMULATION; MECHANISMS AB Previously, we described the age-dependent accumulation of mitochondrial DNA (mtDNA) mutations, leading to a high degree of mtDNA heterogeneity among normal marrow and blood CD34(+) clones and in granulocytes. We established a method for sequence analysis of single cells. We show marked, distinct mtDNA heterogeneity from corresponding aggregate sequences in isolated cells of 5 healthy adult donors-37.9% +/- 3.6% heterogeneity in circulating CD34(+) cells, 36.4% +/- 14.1% in T cells, 36.0% +/- 10.7% in B cells, and 47.7% +/- 7.4% in granulocytes. Most heterogeneity was caused by poly-C tract variability; however, base substitutions were also prevalent, as follows: 14.7% +/- 5.7% in CD34(+) cells, 15.2% +/- 9.0% in T cells, 15.4% +/- 6.7% in B cells, and 32.3% +/- 2.4% in granulocytes. Many poly-C tract length differences and specific point mutations seen in these same donors but assayed 2 years earlier were still present in the new CD34(+) samples. Additionally, specific poly-C tract differences and point mutations were frequently shared among cells of the lymphoid and myeloid lineages. Secular stability and lineage sharing of mtDNA sequence variability suggest that mutations arise in the lymphohematopoietic stem cell compartment and that these changes may be used as a natural genetic marker to estimate the number of active stem cells. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Flow Cytometry Core Facil, NIH, Bethesda, MD 20892 USA. Natl Inst Stand & Technol, Div Biotechnol, Chem Sci & Technol Lab, Gaithersburg, MD 20899 USA. RP Young, NS (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10 CRC,3E-5140,9000 Rockville Pike, Bethesda, MD 20892 USA. EM youngns@mail.nih.gov NR 37 TC 12 Z9 12 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2005 VL 106 IS 9 BP 3271 EP 3284 DI 10.1182/blood-2005-01-0150 PG 14 WC Hematology SC Hematology GA 979BP UT WOS:000232917400059 PM 16020515 ER PT J AU Sun, K Wilkins, DEC Anver, MR Sayers, TJ Panoskaltsis-Mortari, A Blazar, BR Welniak, LA Murphy, WJ AF Sun, K Wilkins, DEC Anver, MR Sayers, TJ Panoskaltsis-Mortari, A Blazar, BR Welniak, LA Murphy, WJ TI Differential effects of proteasome inhibition by bortezomib on murine acute graft-versus-host disease (GVHD): delayed administration of bortezomib results in increased GVHD-dependent gastrointestinal toxicity SO BLOOD LA English DT Article ID NF-KAPPA-B; TUMOR-NECROSIS-FACTOR; ENTEROCYTE APOPTOSIS; MEDIATED APOPTOSIS; TNF; ACTIVATION; INDUCTION; PS-341; CELLS; MICE AB We have recently demonstrated that the proteasome inhibitor, bortezomib, administered immediately following murine allogeneic bone marrow transplantation (BMT) resulted in marked inhibition of acute graft-versus-host disease (GVHD) with retention of graft-versus-tumor effects. We now assessed the effects of delayed bortezomib administration (5 or more days after BMT) on GVHD. Recipient C57BL/6 (H2(b)) mice were lethally irradiated and given transplants of bone marrow cells and splenocytes from major histocompatibility complex (MHC)-disparate BALB/c (H2(d)) donors. In marked contrast to the effects of bortezomib on GVHD prevention when administered immediately after BMT, delayed bortezomib administration resulted in significant acceleration of GVHD-dependent morbidity. No toxicity was observed following delayed bortezomib administration in models where donor T cells were not coadministered, indicating that these deleterious effects were critically dependent on GVHD induction. The increase in GVHD susceptibility even occurred when late administration of bortezomlb was preceded by early administration. Pathologic assessment revealed that significant increases in gastrointestinal lesions occurred following delayed bortezomib administration during GVHD. This pathology correlated with significant increases of type 1 tumor necrosis factor alpha (TNF-alpha) receptor transcription in gastrointestinal cells and with significant increases of TNF-alpha, interleukin 1 beta (IL-1 beta), and IL-6 levels in the serum. These results indicate that the differential effects of proteasome inhibition with bortezomib on GVHD are critically dependent on the timing of bortezomib administration. C1 Univ Nevada, Sch Med, Dept Microbiol & Immunol, Reno, NV 89557 USA. Sci Applicat Int Corp, Pathol Histotechnol Lab, Frederick, MD USA. SAIC Frederick, Basic Sci Program, Expt Immunol Lab, Frederick, MD USA. NCI, Ctr Canc Res, Frederick, MD 21701 USA. Univ Minnesota, Ctr Canc, Minneapolis, MN USA. Univ Minnesota, Dept Pediat, Div Bone Marrow Transplantat, Minneapolis, MN 55455 USA. RP Murphy, WJ (reprint author), Univ Nevada, Sch Med, Dept Microbiol & Immunol, Mail Stop 199, Reno, NV 89557 USA. EM wmurphy@unr.edu FU NCI NIH HHS [R01 CA102282, N01-CO-12400, R01 CA102282-03]; NHLBI NIH HHS [R01 HL66308]; NIAID NIH HHS [R01 AI34495] NR 33 TC 80 Z9 89 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 NOV 1 PY 2005 VL 106 IS 9 BP 3293 EP 3299 DI 10.1182/blood-2004-11-4526 PG 7 WC Hematology SC Hematology GA 979BP UT WOS:000232917400061 PM 15961519 ER PT J AU Pavletic, SZ Carter, SL Kernan, NA Henslee-Downey, J Mendizabal, AM Papadopoulos, E Gingrich, R Casper, J Yanovich, S Weisdorf, D AF Pavletic, SZ Carter, SL Kernan, NA Henslee-Downey, J Mendizabal, AM Papadopoulos, E Gingrich, R Casper, J Yanovich, S Weisdorf, D CA Natl Heart Lung Blood Inst Unrelat TI Influence of T-cell depletion on chronic graft-versus-host disease: results of a multicenter randomized trial in unrelated marrow donor transplantation SO BLOOD LA English DT Article ID IDENTICAL SIBLING TRANSPLANTATION; TERM FOLLOW-UP; BONE-MARROW; SURVIVAL; LEUKEMIA; CYCLOSPORINE; PROPHYLAXIS; CD34; METHOTREXATE; ASSOCIATION AB Donor-derived T cells have been proposed to play a role in pathogenesis of chronic graft-versus-host disease (cGVHD). The impact of ex vivo T-cell depletion (TCD) on cGVHD was analyzed in a randomized multicenter trial involving unrelated donor marrow transplants. A total of 404 patients diagnosed with hematologic malignancies received a total body irradiation-based myeloablative conditioning regimen. GVHD prophylaxis included TCD plus cyclosporine (CSA) or unmodified grafts with CSA plus methotrexate (M/C). Median recipient age was 31.2 years (range, 0.5-55.6 years); median follow-up time since randomization was 4.2 years. The mean number of T cells infused was 1 log lower on the TCD arm. The incidence of cGVHD at 2 years was similar between the TCD and M/C arms, 29% versus 34% (P =.27), respectively. Survival at 3 years from diagnosis of cGVHD was also similar, (TCD 51% versus M/C 58%; P =.29). The proportion of patients with cGVHD who discontinued immunosuppression at 5 years was not different (TCD 72% versus M/C 63%; P =.27), and incidence of serious infections and leukemia relapse were similar on both treatment arms. In spite of a significant reduction of acute GVHD, TCD did not reduce the incidence of cGVHD or improve survival in patients who developed cGVHD. C1 Univ Nebraska, Med Ctr, Omaha, NE USA. EMMES Corp, Rockville, MD USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ S Carolina, Columbia, SC 29208 USA. Univ Iowa, Iowa City, IA USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Univ Minnesota, Minneapolis, MN USA. Virginia Commonwealth Univ, Med Coll Virginia, Richmond, VA 23298 USA. RP Pavletic, SZ (reprint author), NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, Bldg 10,Rm CRC 3-3330, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov OI Kernan, Nancy/0000-0003-1417-1823 FU NHLBI NIH HHS [N01-HB-47095, N01-HB-47097, N01-HB-47094, N01-HB-47098] NR 39 TC 62 Z9 64 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 1 PY 2005 VL 106 IS 9 BP 3308 EP 3313 DI 10.1182/blood-2005-04-1614 PG 6 WC Hematology SC Hematology GA 979BP UT WOS:000232917400063 PM 16046530 ER PT J AU Pomeroy, IM Matthews, PM Frank, JA Jordan, EK Esiri, MM AF Pomeroy, IM Matthews, PM Frank, JA Jordan, EK Esiri, MM TI Demyelinated neocortical lesions in marmoset autoimmune encephalomyelitis mimic those in multiple sclerosis SO BRAIN LA English DT Article DE multiple sclerosis; cortex; inflammation; experimental autoimmune encephalomyelitis; marmoset; Callithrix jacchus; immunohistochemistry; demyelination; myelin oligodendrocyte glycoprotein ID BRAIN ATROPHY; SERIAL MRI; DISABILITY; MS; LOAD AB The use of immunohistochemical methods has led to a new understanding of the prevalence and significance of cortical lesions in multiple sclerosis but these lesions have not yet been formally described in an animal model. In this study we have set out to use immunohistochemical techniques to identify and describe cortical lesions in marmosets with experimental autoimmune encephalomyelitis (EAE). Using antibodies to proteolipid protein (PLP), we found a total of 70 cortical lesions in 11 tissue blocks from 6 animals. These lesions were subdivided into leucocortical (40), intracortical (12) and subpial lesions (18). We quantified the density of inflammatory cells within lesions using a double labelling protocol which employed anti-PLP in addition to antibodies against markers of B-lymphocytes (CD20), T-lymphocytes (CD3), macrophages (MAC387) and MHC-II expressing cells (CR3/43). This analysis revealed that the large subpial lesions accounted for the majority of demyelinated cortex (88%) despite possessing the lowest density of inflammatory cells. This study has shown that lesions in this model share many of the major features of cortical lesions in multiple sclerosis both in terms of morphology and inflammatory cell content. We believe that this tool can be exploited in future studies to investigate the aetiology, development and clinical significance of cortical lesions in demyelinating disease. C1 Univ Oxford, Dept Clin Neurol, Oxford, England. NIH, Lab Diagnost Radiol Res, Bethesda, MD 20892 USA. RP Pomeroy, IM (reprint author), Radcliffe Infirm, Dept Neuropathol, Oxford OX2 6HE, England. EM ian.pomeroy@clneuro.ox.ac.uk OI Matthews, Paul M/0000-0002-1619-8328 FU Medical Research Council [G9409531]; Multiple Sclerosis Society [688] NR 26 TC 71 Z9 71 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD NOV PY 2005 VL 128 BP 2713 EP 2721 DI 10.1093/brain/awh626 PN 11 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 980UV UT WOS:000233044600021 PM 16150849 ER PT J AU Danforth, DN Zhu, YL AF Danforth, DN Zhu, YL TI Conversion of Fas-resistant to Fas-sensitive MCF-7 breast cancer cells by the synergistic interaction of interferon-gamma and all-trans retinoic acid SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Article DE apoptosis; Apo-1/CD95; Bcl-2; breast cancer; cell death; Fas; retinoids; interferon ID NECROSIS-FACTOR-ALPHA; SIGNALING PATHWAYS; INDUCED APOPTOSIS; GENE-EXPRESSION; TUMOR-CELLS; THIOREDOXIN REDUCTASE; MEDIATED APOPTOSIS; EPITHELIAL-CELLS; CARCINOMA CELLS; RECEPTOR-GAMMA AB The membrane receptor Fas (Apo-1/CD95) is an important initiator of programmed cell death induced by anti-Fas antibody or Fas ligand. MCF-7 human breast cancer cells have low levels of Fas receptor (FasR) and are resistant to anti-FasR antibody mediated apoptosis, however two naturally occurring substances, interferon and all-trans retinoic acid (AT), act synergistically to enhance antiproliferative processes in these cells, suggesting this combination may also be an effective means for enhancing FasR expression. When this was studied, it was found that IFN-gamma and AT in combination acted synergistically to induce expression of FasR mRNA and FasR protein in a time-dependent and dose-dependent manner. This induction required continuous protein synthesis, and STAT1 protein, but not PKR or TR1 protein, was induced in a manner quantitatively and temporally related to FasR protein induction, and consistent with STAT1 mediation of the synergistic effect of IFN-gamma and AT on FasR expression. FasR-induced cells were resistant to stimulation of apoptosis by anti-FasR antibody, however treatment with cycloheximide rendered these cells sensitive to antibody-induced apoptosis, suggesting endogenous blockade to signaling. These cells did not express caspase 3, or FLIPL, but strongly expressed the endogenous inhibitor of apoptosis Bcl-2, indicating a type II Fas signaling pathway. Expression of these proteins was not modulated by IFN/AT, however treatment of Fas-induced cells with Bcl-2 specific small interfering RNA (SiRNA) downregulated Bcl-2 protein expression and rendered these cells sensitive to the cytotoxic effects of anti-Fas antibody. These findings indicate that IFN-gamma+AT in combination modulate Fas signaling and provide a novel mechanism for the promotion of cell death in breast cancer cells. C1 NCI, Surg Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Danforth, DN (reprint author), NCI, Surg Branch, Ctr Canc Res, NIH, Bldg 10,Rm 4-5764, Bethesda, MD 20892 USA. EM David_Danforth@nih.gov NR 51 TC 9 Z9 11 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PD NOV PY 2005 VL 94 IS 1 BP 81 EP 91 DI 10.1007/s10549-005-7491-6 PG 11 WC Oncology SC Oncology GA 971SL UT WOS:000232404800010 PM 16136269 ER PT J AU Saif, MW Zujewski, J Hamilton, M AF Saif, MW Zujewski, J Hamilton, M TI Myasthenia gravis in a patient with breast cancer SO BREAST JOURNAL LA English DT Letter ID CARCINOMA C1 NCI, NIH, Bethesda, MD 20892 USA. RP Saif, MW (reprint author), NCI, NIH, Bethesda, MD 20892 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1075-122X J9 BREAST J JI Breast J. PD NOV-DEC PY 2005 VL 11 IS 6 BP 529 EP 530 DI 10.1111/j.1075-122X.2005.00171.x PG 2 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 014OQ UT WOS:000235489900053 PM 16297131 ER PT J AU Kaput, J Ordovas, JM Ferguson, L van Ommen, B Rodriguez, RL Allen, L Ames, BN Dawson, K German, B Krauss, R Malyj, W Archer, MC Barnes, S Bartholomew, A Birk, R van Bladeren, P Bradford, KJ Brown, KH Caetano, R Castle, D Chadwick, R Clarke, S Clement, K Cooney, CA Corella, D da Cruz, IBM Daniel, H Duster, T Ebbesson, SOE Elliott, R Fairweather-Tait, S Felton, J Fenech, M Finley, JW Fogg-Johnson, N Gill-Garrison, R Gibney, MJ Gillies, PJ Gustafsson, JA Hartmann, JL He, L Hwang, JK Jais, JP Jang, YS Joost, H Junien, C Kanter, M Kibbe, WA Koletzko, B Korf, BR Kornman, K Krempin, DW Langin, D Lauren, DR Lee, JH Leveille, GA Lin, SJ Mathers, J Mayne, M McNabb, W Milner, JA Morgan, P Muller, M Nikolsky, Y van der Ouderaa, F Park, T Pensel, N Perez-Jimenez, F Poutanen, K Roberts, M Saris, WHM Schuster, G Shelling, AN Simopoulos, AP Southon, S Tai, ES Towne, B Trayhurn, P Uauy, R Visek, WJ Warden, C Weiss, R Wiencke, J Winkler, J Wolff, GL Xi, ZW Zucker, JD AF Kaput, J Ordovas, JM Ferguson, L van Ommen, B Rodriguez, RL Allen, L Ames, BN Dawson, K German, B Krauss, R Malyj, W Archer, MC Barnes, S Bartholomew, A Birk, R van Bladeren, P Bradford, KJ Brown, KH Caetano, R Castle, D Chadwick, R Clarke, S Clement, K Cooney, CA Corella, D da Cruz, IBM Daniel, H Duster, T Ebbesson, SOE Elliott, R Fairweather-Tait, S Felton, J Fenech, M Finley, JW Fogg-Johnson, N Gill-Garrison, R Gibney, MJ Gillies, PJ Gustafsson, JA Hartmann, JL He, L Hwang, JK Jais, JP Jang, YS Joost, H Junien, C Kanter, M Kibbe, WA Koletzko, B Korf, BR Kornman, K Krempin, DW Langin, D Lauren, DR Lee, JH Leveille, GA Lin, SJ Mathers, J Mayne, M McNabb, W Milner, JA Morgan, P Muller, M Nikolsky, Y van der Ouderaa, F Park, T Pensel, N Perez-Jimenez, F Poutanen, K Roberts, M Saris, WHM Schuster, G Shelling, AN Simopoulos, AP Southon, S Tai, ES Towne, B Trayhurn, P Uauy, R Visek, WJ Warden, C Weiss, R Wiencke, J Winkler, J Wolff, GL Xi, ZW Zucker, JD TI The case for strategic international alliances to harness nutritional genomics for public and personal health SO BRITISH JOURNAL OF NUTRITION LA English DT Article DE strategic international alliances; nutrigenomics; gene-nutrient interactions; health diaparities ID DIABETES-RELATED TRAITS; CORONARY-HEART-DISEASE; GENETIC ASSOCIATION; POPULATION STRATIFICATION; CARBOHYDRATE INGESTION; COMPLEX DISEASES; IMMUNE FUNCTION; HAPMAP PROJECT; MESSENGER-RNA; DIETARY FIBER AB Nutrigenomics is the study of how constituents of the diet interact with genes, and their products, to alter phenotype and, conversely, how genes and their products metabolise these constituents into nutrients, antinutrients, and bioactive compounds. Results from molecular and genetic epidemiological studies indicate that dietary unbalance can alter gene-nutrient interactions in ways that increase the risk of developing chronic disease. The interplay of human genetic variation and environmental factors will make identifying causative genes and nutrients a formidable, but not intractable, challenge. We provide specific recommendations for how to best meet this challenge and discuss the need for new methodologies and the use of comprehensive analyses of nutrient-genotype interactions involving large and diverse populations. The objective of the present paper is to stimulate discourse and collaboration among nutrigenomic researchers and stakeholders, a process that will lead to an increase in global health and wellness by reducing health disparities in developed and developing countries. C1 Univ Calif Davis, Ctr Excellence Nutr Genom, Davis, CA 95616 USA. 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Univ Munich, Dr Von Hauner Childrens Hosp, D-80539 Munich, Germany. Interleukin Genet Inc, Waltham, MA 02452 USA. Nutrilite Div Access Business Grp LLC, Buena Pk, CA 90622 USA. Univ Toulouse 3, Obes Res Unit, Inst Louis Bugnard, French Inst Hlth & Med Res,INSERM,Toulouse Univ H, F-31059 Toulouse, France. HortRes Ltd, Hamilton, New Zealand. Yonsei Univ, Dept Food & Nutr, Seoul 120749, South Korea. Food Syst Design, Denville, NJ 07834 USA. Univ Calif Davis, Dept Microbiol, Div Biol Sci, Davis, CA 95616 USA. Univ Newcastle, Human Nutr Res Ctr, NuGO, Newcastle Upon Tyne, Tyne & Wear, England. Natl Res Council Canada, Inst Nutrisci & Hlth, Charlottetown, PE C1A 5T1, Canada. AgResearch, Grassland Res Ctr, Palmerston North, New Zealand. NCI, Nutr Sci Res Grp, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Rowett Res, Aberystwyth AB21 9SB, Dyfed, Wales. Univ Wageningen & Res Ctr, Wageningen Ctr Food Sci & Nutr, NuGO Dutch Innovat Cluster Nutrigenom, Wageningen, Netherlands. GeneGo Inc, St Joseph, MI 49085 USA. Unilever Corp Res, Sharnbrook MK44 1PY, Beds, England. Yonsei Univ, Dept Food & Nutr, Seoul 120749, South Korea. Inst Nacl Tecnol Agropecuaria, Inst Tecnol Alimentos, Buenos Aires, DF, Argentina. Hosp Univ Reina Sofia, Unidad Lipidos & Arteriosclerosis, Cordoba, Spain. Univ Kuopio, Food & Hlth Res Ctr, FIN-70211 Kuopio, Finland. Purina Nestle, St Louis, MO USA. Univ Maastricht, NuGO Nutr & Toxicol Res Inst NUTRIM, Maastricht, Netherlands. Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. Univ Auckland, Fac Med & Hlth Sci, Auckland 1, New Zealand. Ctr Genet Nutr & Hlth, Washington, DC 20009 USA. NuGO Inst Food Res, Norwich NR4 7UA, Norfolk, England. Singapore Gen Hosp, Dept Endocrinol, Singapore 169608, Singapore. Wright State Univ, Sch Med, Dept Community Hlth, Dayton, OH 45401 USA. Univ Liverpool, Sch Clin Sci, Liverpool Ctr Nutr Genom, Obes Biol Unit, Liverpool L69 3GA, Merseyside, England. Univ Chile, Inst Nutr & Tecnol Alimentos, Santiago 11, Chile. London Sch Hyg & Trop Med, London WC1, England. Univ Illinois, Coll Med, Dept Internal Med, Urbana, IL 61821 USA. Univ Calif Davis, Div Biol Sci, Neurobiol Physiol & Behav Sect, Davis, CA 95616 USA. Viocare Technol Inc, Princeton, NJ 08542 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Neuroepidemiol, San Francisco, CA 94143 USA. Food & Hlth Res, London N1 7AB, England. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. BioMarker Pharmaceut Inc, Campbell, CA 95008 USA. Univ Paris 13, EPML CNRS APuces, LIM&BIO, F-93017 Bobigny, France. RP Kaput, J (reprint author), Univ Calif Davis, Ctr Excellence Nutr Genom, Davis, CA 95616 USA. EM jkaput@uic.edu RI JAIS, Jean-Philippe/B-2993-2009; Shelling, Andrew/E-7496-2010; Joost, Hans-Georg/J-4462-2013; ZUCKER, Jean-Daniel /K-3008-2016; Dawson, Kenneth A./L-2540-2016; Kibbe, Warren/B-2106-2010; Ferguson, Lynnette/F-5989-2011; Jang, Yang Soo/D-4803-2012; Muller, Michael/B-5795-2008; Fairweather-Tait, Susan/K-4251-2012; da Cruz, Ivana/G-4329-2012; Daniel, Hannelore/B-8982-2009 OI Tai, E Shyong/0000-0003-2929-8966; Perez Jimenez, Francisco/0000-0001-9808-1280; Mathers, John/0000-0003-3406-3002; Cooney, Craig/0000-0003-4279-557X; Langin, Dominique/0000-0002-2669-7825; Shelling, Andrew/0000-0002-5300-1934; Ordovas, Jose/0000-0002-7581-5680; McNabb, Warren/0000-0003-2514-6551; JAIS, Jean-Philippe/0000-0002-0708-8776; Joost, Hans-Georg/0000-0002-5860-606X; ZUCKER, Jean-Daniel /0000-0002-5597-7922; Dawson, Kenneth A./0000-0002-0568-6588; Kibbe, Warren/0000-0001-5622-7659; Perez-Jimenez, Francisco/0000-0001-7499-7681; Muller, Michael/0000-0002-5930-9905; da Cruz, Ivana/0000-0003-3008-6899; FU NHLBI NIH HHS [HL 54776]; NIMHD NIH HHS [MD 00222] NR 83 TC 95 Z9 98 U1 1 U2 19 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA EDINBURGH BLDG, SHAFTESBURY RD, CB2 8RU CAMBRIDGE, ENGLAND SN 0007-1145 EI 1475-2662 J9 BRIT J NUTR JI Br. J. Nutr. PD NOV PY 2005 VL 94 IS 5 BP 623 EP 632 DI 10.1079/BJN20051585 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 981NZ UT WOS:000233096600002 PM 16277761 ER PT J AU Fee, E Brown, TM AF Fee, E Brown, TM TI The Public Health Act of 1848 SO BULLETIN OF THE WORLD HEALTH ORGANIZATION LA English DT Editorial Material AB This section looks back to some ground-breaking contributions to public health, reproducing them in their original form and adding a commentary on their significance from a modern-day perspective, Elizabeth Fee & Theodore Brown review measures to improve public health in England and Wales in the 19th century, with special reference to the Public Health Act of 1848, of which extracts are reproduced below. C1 Natl Lib Med, Hist Med Div, Bethesda, MD 20894 USA. Univ Rochester, Dept Hist, Rochester, NY 14642 USA. RP Fee, E (reprint author), Natl Lib Med, Hist Med Div, Bldg 38 1E21,8600 Rockville Pike, Bethesda, MD 20894 USA. EM elizabeth_fee@nlm.nih.gov NR 8 TC 8 Z9 8 U1 0 U2 4 PU WORLD HEALTH ORGANIZATION PI GENEVA 27 PA MARKETING AND DISSEMINATION, CH-1211 GENEVA 27, SWITZERLAND SN 0042-9686 J9 B WORLD HEALTH ORGAN JI Bull. World Health Organ. PD NOV PY 2005 VL 83 IS 11 BP 866 EP 872 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 982TS UT WOS:000233185100016 PM 16302044 ER PT J AU Goldberg, M Septier, D Rapoport, O Iozzo, RV Young, MF Ameye, LG AF Goldberg, M Septier, D Rapoport, O Iozzo, RV Young, MF Ameye, LG TI Targeted disruption of two small leucine-rich proteoglycans, biglycan and decorin, excerpts divergent effects on enamel and dentin formation SO CALCIFIED TISSUE INTERNATIONAL LA English DT Article DE biglycan; decorin; amelogenesis; amelogenin; dentinogenesis ID GROWTH-FACTOR RECEPTOR; RAT INCISOR; IN-VIVO; IMMUNOHISTOCHEMICAL LOCALIZATION; HYDROXYAPATITE FORMATION; EXTRACELLULAR-MATRIX; TOOTH DEVELOPMENT; DEFICIENT MICE; EXPRESSION; PROTEINS AB Small leucine-rich proteoglycans have been suggested to affect mineralization of dental hard tissues. To determine the functions of two of these small proteoglycans during the early stages of tooth formation, we characterized the dental phenotypes of biglycan (BGN KO) and decorin deficient (DCN KO) mice and compared them to that of wild type mice. Each targeted gene disruption resulted in specific effects on dentin and enamel formation. Dentin was hypomineralized in both knock out mice, although the effect was more prominent in the absence of decorin. Enamel formation was dramatically increased in newborn biglycan knockout mice but delayed in absence of decorin. Increased enamel formation in the former case resulted from an upregulation of amelogenin synthesis whereas delayed enamel formation in the later case was most probably an indirect consequence of the high porosity of the underlying dentin. Enamelin expression was unchanged in BGN KO, and reduced in DCN KO. Dentin sialoprotein (DSP), a member of the family of phosphorylated extracellular matrix proteins that play a role in dentinogenesis, was overexpressed in BGN-KO odontoblasts and in the sub-odontoblastic layer. In contrast, a decreased expression of DSP was detected in DCN KO. Dentin matrix protein-1 (DMP-1), bone sialoprotein (BSP) and osteopontin (OPN) were upregulated in BGN KO and downregulated in the DCN KO. Despite the strong effects induced by these deficiencies in newborn mice, no significant difference was detected between the three genotypes in adult mice, suggesting that the effects reported here in newborn mice are transient and subjected to self-repair. C1 Univ Paris 05, Grp Matrices Extracellulaires & Mineralisat, Fac Chirurg Dent, Lab Reparat & Remodelage Tissus Orofaciaux, F-92120 Montrouge, France. Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. NIDCR, Craniofacial & Skeletal Dis Branch, NIH, Bethesda, MD 20892 USA. Nestle Res Ctr, Dept Nutr & Hlth, CH-1000 Lausanne, Switzerland. Univ Paris 05, Fac Chirurg Dent, F-92120 Montrouge, France. RP Goldberg, M (reprint author), Univ Paris 05, Grp Matrices Extracellulaires & Mineralisat, Fac Chirurg Dent, Lab Reparat & Remodelage Tissus Orofaciaux, EA 2496, F-92120 Montrouge, France. EM mgoldod@aol.com OI Iozzo, Renato/0000-0002-5908-5112 NR 66 TC 36 Z9 39 U1 0 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD NOV PY 2005 VL 77 IS 5 BP 297 EP 310 DI 10.1007/s00223-005-0026-7 PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 987DP UT WOS:000233498900005 PM 16283572 ER PT J AU Gius, D Bradbury, CM Sun, LC Awwad, RT Huang, L Smart, DDK Bisht, KS Ho, AS Nguyen, P AF Gius, D Bradbury, CM Sun, LC Awwad, RT Huang, L Smart, DDK Bisht, KS Ho, AS Nguyen, P TI The epigenome as a molecular marker and target - Implications for cancer SO CANCER LA English DT Article DE epigenome; methylation; DNMT; molecular marker ID TUMOR-SUPPRESSOR GENE; RETINOBLASTOMA; METHYLATION; CELLS; HYPOMETHYLATION; TRANSFORMATION; TRANSCRIPTION; EPIGENETICS; DNMT1; FOS AB Tumor cell proliferation, de-differentiation, and progression depend on a complex combination of altered cell cycle regulation, excessive growth factor pathway activation, and decreased apoptosis. The understanding of these complex mechanisms Should lead to the identification of potential molecular markers, targets, and molecular profiles that Should eventually expand and improve therapeutic intervention. It now appears clear that methylation plays a central role in transformation, both in vitro and in vivo. However, the exact targets and mechanism(s) are not yet fully understood. This is partly due to the significant number of genes altered by changes in intracellular rnethyltransferase activity and the chemical agents used to modulate gene expression. The complex nature of methylation's role in regulating gene expression suggests that in addition to investigating individual genes, researchers Should develop more comprehensive methods to examine gene expression patterns and their predictive value as this will likely be necessary in the future. If methylation plays a role in transformation, then it seems logical that genes regulating intracellular methylation status may be used as molecular markers to profile tumors by any new methods currently being developed. Perhaps more noteworthy is that DNMT genes may be found to be novel molecular targets for new factor-specific anticancer agents. This idea will be addressed. C1 NCI, Mol Radiat Oncol Sect, Radiat Oncol Sci Program, Canc Res Ctr,NIH,Radiat Oncol Branch, Bethesda, MD 20892 USA. RP Gius, D (reprint author), NCI, Mol Radiat Oncol Sect, Radiat Oncol Sci Program, Canc Res Ctr,NIH,Radiat Oncol Branch, Bldg 10,Room B3B69,9000 Rockville Pike, Bethesda, MD 20892 USA. EM giusd@mail.nih.gov NR 20 TC 20 Z9 22 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2005 VL 104 IS 9 BP 1789 EP 1793 DI 10.1002/cncr.21395 PG 5 WC Oncology SC Oncology GA 976TE UT WOS:000232755500002 PM 16149092 ER PT J AU Warren, JL Weaver, DL Bocklage, T Key, CR Platz, CE Cronin, KA Ballard-Barbash, R Willey, SC Harlan, LC AF Warren, JL Weaver, DL Bocklage, T Key, CR Platz, CE Cronin, KA Ballard-Barbash, R Willey, SC Harlan, LC TI The frequency of ipsilateral second tumors after breast-conserving surgery for DCIS - A population-based analysis SO CANCER LA English DT Article DE ductal carcinoma in-situ; breast carcinoma; population-based study; outcomes study; breast-conserving surgery ID CARCINOMA IN-SITU; SURGICAL ADJUVANT BREAST; CANCER; WOMEN; RECURRENCE; TRIAL; MAMMOGRAPHY; THERAPY; SURVEILLANCE; RADIOTHERAPY AB BACKGROUND. The diagnosis of ductal carcinoma in situ (DCIS) is increasing, although to the authors' knowledge there is no consensus regarding optimal treatment. This analysis of women treated with breast-conserving surgery (BCS) evaluated the impact of radiation therapy (RT) in patient outcomes. METHODS. The current study included a population-based sample of 1103 women residing in selected Surveillance, Epidemiology, and End Results (SEER) registries who were diagnosed with DCIS between 1991-1992. Data were obtained from the registry, physician follow-up, and pathology reports. Physicians were contacted in 1999 to determine whether the patient had developed a second event in the ipsilateral breast. For second events, pathology reports were reviewed to determine the presence of in situ or invasive disease. Registry data through 2001 were used to assess death rates and cause of death. Cox proportional hazards and logistic regression models were used to evaluate the rates of second events and breast carcinoma deaths between women treated with and without RT. RESULTS. Over an average of 91 months, 13.2% of women developed a second event. Rates of second events were 11% for women treated with BCS and RT compared with 15% for women treated with BCS only (adjusted hazards ratio, 0.64; 95% confidence interval, 0.44-0.92). Women receiving RT were significantly less likely to develop invasive breast carcinoma in the ipsilateral breast (adjusted odds ratio, 0.40). By 200 1, the rate of death from breast carcinoma was 2.7%; in the group of women treated with BCS only compared with 0.8% in the group of women treated with BCS with RT. CONCLUSIONS. Among a population-based cohort, RT was found to significantly reduce the risk of second events in the ipsilateral breast, particularly invasive tumors, although not to the extent reported in clinical trials. C1 NCI, Div Canc Control & Populat Sci, Hlth Serv & Econ Branch, Appl Res Program, Bethesda, MD 20892 USA. Univ Vermont, Coll Med, Dept Pathol, Burlington, VT 05405 USA. Univ New Mexico, Hlth Sci Ctr, Dept Pathol, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, New Mexico Tumor Registry, Albuquerque, NM 87131 USA. Univ Iowa, Coll Med, Dept Pathol, Iowa City, IA 52242 USA. Georgetown Univ Hosp, Betty Lou Ourisman Breast Hlth Ctr, Dept Surg, Washington, DC 20007 USA. RP Warren, JL (reprint author), NCI, Div Canc Control & Populat Sci, Hlth Serv & Econ Branch, Appl Res Program, Execut Plaza N,Room 4005,6130 Execut Blvd,MSC 734, Bethesda, MD 20892 USA. EM joan_warren@nih.gov NR 28 TC 37 Z9 39 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD NOV 1 PY 2005 VL 104 IS 9 BP 1840 EP 1848 DI 10.1002/cncr.21406 PG 9 WC Oncology SC Oncology GA 976TE UT WOS:000232755500008 PM 16136599 ER PT J AU Kaneuchi, M Sasaki, M Tanaka, Y Shiina, H Yamada, H Yamamoto, R Sakuragi, N Enokida, H Verma, M Dahiya, R AF Kaneuchi, M Sasaki, M Tanaka, Y Shiina, H Yamada, H Yamamoto, R Sakuragi, N Enokida, H Verma, M Dahiya, R TI WT1 and WT1-AS genes are inactivated by promoter methylation in ovarian clear cell adenocarcinoma SO CANCER LA English DT Article DE Wilms tumor suppressor 1 gene; WT1; WT1 antisense; ovarian carcinoma; cancers of the ovary ID TUMOR SUPPRESSOR GENE; HUMAN BREAST CARCINOMAS; WILMS-TUMOR; CANCER; EXPRESSION; HYPERMETHYLATION; IDENTIFICATION; TRANSCRIPTION; REGION AB BACKGROUND. Ovarian clear cell adenocarcinoma is associated with one of the poorest prognoses among human epithelial ovarian cancers. The authors hypothesized that Wilms turner suppressor 1 gene (WT1) sense and antisense (WT1-AS) expression and their promoter methylation status Could characterize ovarian clear cell adenocarcinoma from ovarian serous adenocarcinoma. METHODS. To test this hypothesis, ovarian cancer cell lines and 42 cancer tissues (17 clear cell and 25 serous adenocarcinoma) were analyzed for expression and methylation of WT1 and WT1-AS genes. RESULTS. These experiments demonstrated that all serous adenocarcinoma tissues expressed both WT1 and WT1-AS genes, although expression of these genes was lacking in clear cell adenocarcinoma. The WT1 and WT1-AS promoter were significantly methylated in clear cell adenocarcinoma (88.2% and 88.2%, respectively) compared with serous adenocarcinoma (24.0% and 20.0%, respectively). Significant correlation between methylation and mRNA expression status was observed for each gene. Also in agreement with these data, WT1 and WT1-AS negative ovarian cancer cell lines reexpressed these genes after treatment with the demethylating agent, 5-aza-2'-deoxycytidine. CONCLUSIONS. The current study shows that CpG hypermethylation is an important mechanism of WT1 and WT1-AS gene inactivation in ovarian clear cell adenocarcinoma. This is the first report that has demonstrated differential expression and methylation of WTI -AS in ovarian clear cell and serous adenocarcinomas. This study presents new molecular characterizations between these two types of adenocarcinorna and may provide insight as to why clear cell adenocarcinorna has a poorer prognosis than serous adenocarcinoma of the ovary. C1 Univ Calif San Francisco, Urol Res Ctr 112F, Dept Urol, San Francisco, CA 94121 USA. Vet Affairs Med Ctr, San Francisco, CA 94121 USA. Hokkaido Univ, Sch Med, Dept Obstet & Gynecol, Sapporo, Hokkaido 060, Japan. Natl Canc Inst, Div Canc Prevent, Rockville, MD USA. RP Dahiya, R (reprint author), Univ Calif San Francisco, Urol Res Ctr 112F, Dept Urol, 4150 Clement St, San Francisco, CA 94121 USA. EM rdahiya@urol.ucsf.edu RI Sakuragi, Noriaki/D-6507-2012 FU NCI NIH HHS [R01CA101844]; NIA NIH HHS [R01AG21418]; NIDDK NIH HHS [T32DK07790] NR 20 TC 36 Z9 38 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 NOV 1 PY 2005 VL 104 IS 9 BP 1924 EP 1930 DI 10.1002/cncr.21397 PG 7 WC Oncology SC Oncology GA 976TE UT WOS:000232755500018 PM 16134181 ER PT J AU Packer, RJ Krailo, M Mehta, M Warren, K Allen, J Jakacki, R Villablanca, JG Chiba, A Reaman, G AF Packer, RJ Krailo, M Mehta, M Warren, K Allen, J Jakacki, R Villablanca, JG Chiba, A Reaman, G TI A phase I study of concurrent RMP-7 and carboplatin with radiation therapy for children with newly diagnosed brainstem gliomas SO CANCER LA English DT Article; Proceedings Paper CT Meeting of the Child-Neurology-Society CY OCT 15, 2004 CL Ottawa, CANADA SP Child Neurol Soc DE brainstem glioma; radiotherapy; radiosensitization; carboplatin ID BLOOD-BRAIN; BRADYKININ ANALOG; INTRACAROTID INFUSION; CANCER-GROUP; TUMORS; BARRIER; PERMEABILITY; RADIOTHERAPY; SURVIVAL; TRIAL AB BACKGROUND. Ninety percent of children with diffuse, intrinsic brainstem will die within 18 months of diagnosis. Radiotherapy is of transient benefit to children, and a potential way to improve its efficacy is to add Carboplatin is antineoplastic and radiosensitizing; however, its delivery to primary turner site is problematic. RMP-7 is a bradykinin analog that selective permeability of the blood-brain-tumor interface. The objective of Phase I study was to determine the toxicity and feasibility of delivering RMP-7 carboplatin for 5 successive days during radiotherapy to children with diagnosed, diffuse, intrinsic brainstem gliomas. METHODS. RMP-7 was given prior to the end of carboplatin infusion. Local therapy, in dose fractions of 180 centigrays (cGy) per day (to a total dose of cGy), was given within 4 hours of completion of drug delivery. Duration of ment was escalated in a stepwise, weekly fashion in cohorts of 3 patients, there was treatment-limiting toxicity or until radiotherapy was completed. teen patients were treated, and their median age was 7 years (age range, 3-12 yrs). RESULTS. One child died early during treatment of progressive disease and was assessable for toxicity. Treatment for 3 weeks, 4 weeks, and 5 weeks was well, with mild flushing, tachycardia, nausea, emesis, dizziness, and pain. One of 3 children treated at the full duration of therapy (33 doses over weeks) developed dose-limiting hepatotoxicity and neutropenia. The median survival was 328 days, and 1 patient remained free of disease for > 400 days after the initiation of treatment. CONCLUSIONS. The results of this study confirmed the feasibility of ivmg and carboplatin daily during radiotherapy to children with brainstem tumors. C1 Childrens Natl Med Ctr, Dept Neurol, Ctr Neurosci & Behav Med, Washington, DC 20010 USA. George Washington Univ, Dept Neurol, Washington, DC USA. George Washington Univ, Dept Pediat, Washington, DC 20052 USA. Univ So Calif, Keck Sch Med, Los Angeles, CA USA. Childrens Oncol Grp, Arcadia, CA USA. Univ Wisconsin, Med Ctr, Dept Radiat Oncol, Madison, WI 53706 USA. NCI, Bethesda, MD 20892 USA. NYU, Dept Neurol & Pediat, New York, NY USA. Childrens Hosp Pittsburgh, Dept Pediat, Pittsburgh, PA 15213 USA. Childrens Hosp Los Angeles, Dept Pediat, Los Angeles, CA 90027 USA. Childrens Natl Med Ctr, Div Hematol Oncol, Washington, DC 20010 USA. RP Packer, RJ (reprint author), Childrens Natl Med Ctr, Dept Neurol, Ctr Neurosci & Behav Med, 111 Michigan Ave,NW, Washington, DC 20010 USA. EM rpacker@cnmc.org OI mehta, minesh/0000-0002-4812-5713 NR 30 TC 26 Z9 26 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 NOV 1 PY 2005 VL 104 IS 9 BP 1968 EP 1974 DI 10.1002/cncr.21403 PG 7 WC Oncology SC Oncology GA 976TE UT WOS:000232755500024 PM 16177987 ER PT J AU Chau, CH Permenter, MG Steinberg, SM Retter, AS Dahut, WL Price, DK Figg, WD AF Chau, CH Permenter, MG Steinberg, SM Retter, AS Dahut, WL Price, DK Figg, WD TI Polymorphism in the hypoxia-inducible factor 1 alpha gene may confer susceptibility to androgen-independent prostate cancer SO CANCER BIOLOGY & THERAPY LA English DT Article DE HIF-1 alpha; single nucleotide polymorphism; androgen-independent prostate cancer ID RENAL-CELL CARCINOMA; HIF-ALPHA; FACTOR-1-ALPHA; HIF-1-ALPHA; VHL; IDENTIFICATION; HYDROXYLATION/; DESTRUCTION; DEGRADATION; COMPLEX AB The hypoxia-inducible factor 1 alpha ( HIF-1 alpha) plays a major role in cancer progression. The role of this transcription factor in prostate cancer development and its transition to a metastatic and androgen refractory state remains to be elucidated. Previous reports have identified the existence of single nucleotide polymorphisms ( SNPs) in the oxygen-dependent degradation domain of the HIF-1 alpha gene in renal cell carcinoma, head and neck squamous cell carcinoma, and androgen-independent prostate cancer ( AIPC). Studies in prostate cancer, however, are variable and limited in the number of cases assessed. Herein we further investigate these SNPs, specifically C1772T ( which results in an amino acid change from proline 582 to serine) and G1790A ( alanine 588 to threonine). The frequency of these polymorphisms was evaluated in a population of individuals with metastatic AIPC and compared to a set of healthy control subjects. The distribution of HIF-1 alpha genotypes for C1772T in 196 AIPC patients was 161 C/C ( 82.1%), 29 C/T ( 14.8%), and 6 T/T ( 3.1%). The genotype distribution in 196 controls was 179 C/C ( 91.3%), 14 C/T ( 7.1%), and 3 T/T ( 1.5%). Our results demonstrate a significant difference in genotype distribution between AIPC patients and control subjects only for the C1772T polymorphism ( p = 0.024). The association of the incidence of the polymorphism with overall survival was determined to be not statistically significant ( p = 0.93) by the Mantel-Haenszel ( log-rank) test. These results suggest that the C1772T polymorphism in HIF-1 alpha may confer susceptibility to AIPC and contribute to the progression or metastasis of this disease. C1 NCI, Mol Pharmacol Sect, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, Bethesda, MD 20892 USA. RP Figg, WD (reprint author), NCI, Mol Pharmacol Sect, Ctr Canc Res, 900 Rockville Pike,Bldg 10-Room 5A01, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Figg Sr, William/M-2411-2016 FU Intramural NIH HHS NR 22 TC 60 Z9 63 U1 1 U2 1 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD NOV PY 2005 VL 4 IS 11 BP 1222 EP 1225 DI 10.4161/cbt.4.11.2091 PG 4 WC Oncology SC Oncology GA 022GS UT WOS:000236044100017 PM 16205110 ER PT J AU Paskett, ED Reeves, KW Pineau, B Albert, PS Caan, B Hasson, M Iber, F Kikendall, JW Lance, P Shike, M Slattery, ML Weissfeld, J Kahle, L Schatzkin, A Lanza, E AF Paskett, ED Reeves, KW Pineau, B Albert, PS Caan, B Hasson, M Iber, F Kikendall, JW Lance, P Shike, M Slattery, ML Weissfeld, J Kahle, L Schatzkin, A Lanza, E CA Polyp Prevention Trial Study Grp TI The association between cigarette smoking and colorectal polyp recurrence (United States) SO CANCER CAUSES & CONTROL LA English DT Article DE colonic polyps; recurrence; smoking ID HYPERPLASTIC POLYPS; ADENOMATOUS POLYPS; RISK-FACTORS; FOLLOW-UP; ALCOHOL-CONSUMPTION; TOBACCO SMOKING; PROSPECTIVE COHORT; BRITISH DOCTORS; CANCER RISK; MORTALITY AB Objective: Although evidence exists linking smoking to precancerous colorectal adenomatous polyps, few studies have examined the association between cigarette smoking and recurrence of colorectal polyps. This association was investigated prospectively with data from the Polyp Prevention Trial. Methods: Cigarette smoking data were collected through baseline interviews. The study was completed by 1872 men and women with presence of adenomas at baseline colonoscopy. Multiple logistic regression analysis was used to examine the association between cigarette smoking and polyp recurrence (adenomatous and hyperplastic) up to four years from baseline. Results: Adenoma recurrence was not related to cigarette smoking. Current smokers had increased odds of hyperplastic polyps at follow-up compared to never smokers (OR 2.88, 95% CI 2.06-4.01). Current smoking was associated with subsequent distal (OR 3.44, 95% CI 2.38-4.95) and rectal (OR 3.53, 95% CI 2.15-5.78) hyperplastic polyps, but not subsequent proximal hyperplastic polyps. Cigarette smoking was associated with subsequent multiple and small size (4 mm) hyperplastic polyps. Significant linear trends were observed between development of subsequent hyperplastic polyps and all smoking variables. Conclusions: Although no association with recurrent adenomas was observed, cigarette smoking was significantly associated with hyperplastic polyp development, except for those in the proximal colon. This prospective study confirms that cigarette smoking has a significant effect on the development of hyperplastic colorectal polyps. C1 Ohio State Univ, Ctr Comprehens Canc, Div Populat Sci, Columbus, OH 43210 USA. First Coast Gastroenterol, St Augustine, FL USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. Kaiser Fdn Res Inst, Oakland, CA USA. WESTAT Corp, Rockville, MD 20850 USA. Edward Hines Jr Hosp, Vet Affairs Med Ctr, Hines, IL USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Utah, Salt Lake City, UT USA. Univ Pittsburgh, Pittsburgh, PA USA. Informat Management Serv Inc, Rockville, MD USA. NCI, Nutr Epidemiol Branch, Div Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Lab Canc Prevent, Ctr Canc Res, Bethesda, MD 20892 USA. RP Ohio State Univ, Ctr Comprehens Canc, Div Populat Sci, A357 Starling Loving Hall,320 W 10th Ave, Columbus, OH 43210 USA. EM paskett-1@medctr.osu.edu RI Lance, Peter/I-2196-2014 OI Lance, Peter/0000-0003-2944-1881 NR 68 TC 19 Z9 20 U1 1 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 EI 1573-7225 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2005 VL 16 IS 9 BP 1021 EP 1033 DI 10.1007/s10552-005-0298-2 PG 13 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 968CQ UT WOS:000232139900003 PM 16184467 ER PT J AU Wright, ME Michaud, DS Pietinen, P Taylor, PR Virtamo, J Albanes, D AF Wright, ME Michaud, DS Pietinen, P Taylor, PR Virtamo, J Albanes, D TI Estimated urine pH and bladder cancer risk in a cohort of male smokers (Finland) SO CANCER CAUSES & CONTROL LA English DT Article DE bladder neoplasms; body weight; cohort studies; diet; net acid excretion; urine pH ID NET ACID EXCRETION; N-GLUCURONIDATION; 4-AMINOBIPHENYL; ACETYLBENZIDINE; METABOLITES; CARCINOGEN; BENZIDINE; SMOKING; PROTEIN; LIVER AB Objective: Low urine pH may be an important risk factor for bladder cancer, although few studies have evaluated this association. We examined the relationship between estimated renal net acid excretion (NAE), an indirect measure of urine pH based on nutrient intake and anthropometry, and bladder cancer risk in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study. Methods: At baseline, 27,096 male smokers 50-69 years old completed a dietary questionnaire that assessed usual frequency of consumption and portion sizes for the previous 12 months, had height and weight measured, and provided a history of smoking. A total of 446 incident bladder cancer cases were identified during up to 17.4 years of follow-up. Results: In multivariate proportional hazards models, the relative risk (RR) for bladder cancer was 1.15 (95% confidence interval (CI)=0.86-1.55) for individuals in the highest (i.e., most acidic) versus the lowest (i.e., least acidic) NAE quintile (p=0.38). Among men who smoked for more than 45 years, there was a suggestion of increased risk with higher NAE levels (RR=1.72, 95% CI=0.96-3.10, p=0.08). Conclusions: These findings do not indicate that urine pH is a major risk factor for bladder cancer, although certain subsets of individuals may be at increased risk. C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20852 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. NCI, Canc Prevent Studies Branch, Ctr Canc Res, NIH,DHHS, Rockville, MD 20852 USA. RP Wright, ME (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 212D, Rockville, MD 20852 USA. EM wrighmar@mail.nih.gov RI Michaud, Dominique/I-5231-2014; Albanes, Demetrius/B-9749-2015 FU NCI NIH HHS [N01CN45035, N01CN45165] NR 27 TC 9 Z9 10 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0957-5243 J9 CANCER CAUSE CONTROL JI Cancer Causes Control PD NOV PY 2005 VL 16 IS 9 BP 1117 EP 1123 DI 10.1007/s10552-005-0348-9 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 968CQ UT WOS:000232139900014 PM 16184478 ER PT J AU Weiss, JM Weiss, NS Ulrich, CM Doherty, JA Voigt, LF Chen, C AF Weiss, JM Weiss, NS Ulrich, CM Doherty, JA Voigt, LF Chen, C TI Interindividual variation in nucleotide excision repair genes and risk of endometrial cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID PIGMENTOSUM GROUP-C; DNA-REPAIR; LUNG-CANCER; MICROSATELLITE INSTABILITY; ESTROGEN METABOLISM; CELL CARCINOMA; BREAST-CANCER; IN-VIVO; GROUP-A; POLYMORPHISMS AB Exposure to estrogens is a likely cause of endometrial cancer, but the means by which estrogens exert this effect are not entirely clear. One hypothesis is that certain estrogen metabolites bind to the DNA, forming bulky adducts that damage the DNA and initiate carcinogenesis. A woman's reduced capacity to repair such damage may increase her risk of endometrial cancer. We conducted a population-based case-control study in western Washington State to address the role of variation in nucleotide excision repair genes on the risk of endometrial cancer. Case women (n = 371), ages 50 to 69 years, were diagnosed with invasive endometrial cancer between 1994 and 1999. Control women (n = 420) were selected using random-digit dialing (ages 50-65 years) and by random selection from Health Care Financing Administration data files (ages 66-69 years). Genotyping assays were done for ERCC1, ERCC2 (XPD), ERCC4 (XPF), ERCC5 (XPG), XPA, and XPC. No appreciable differences between cases and controls were observed in the genotype distributions of ERCC1 (c8092a and c19007t), ERCC2 (D312N, K751Q, and c22541a), ERCC4 (R415Q and t30028c), or ERCC5 (D1104H). Carriage of at least one variant allele for XPA G23A was associated with decreased risk of endometrial cancer [odds ratio (OR), 0.70; 95% confidence interval (95% CI), 0.53-0.93]. Carriage of at least one XPC A499V variant allele was associated with a modest decrease in risk (OR, 0.79; 95% CI, 0.59-1.05). Women with variant alleles at both XPC A499V and K939Q had 58% of the risk of women with no XPC variant alleles (OR, 0.58; 95% CI, 0.35-0.96). Our data suggest that interindividual variation in XPA and XPC influences a woman's risk of endometrial cancer. C1 NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH, Rockville, MD 20852 USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Program Epidemiol, Div Publ Hlth Sci, Seattle, WA USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Dept Otolaryngol Head & Neck Surg, Seattle, WA USA. RP Weiss, JM (reprint author), NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH, 6120 Execut Blvd,EPS 8123,MSC 7240, Rockville, MD 20852 USA. EM weissjoc@mail.nih.gov FU NCI NIH HHS [K05 CA 92002, R01 CA 105212, R01 CA 75977, R03 CA 80636]; NICHD NIH HHS [N01 HD 23166] NR 53 TC 40 Z9 44 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 BP 2524 EP 2530 DI 10.1158/1055-9965.EPI-05-0414 PN 1 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BM UT WOS:000233351100011 PM 16284373 ER PT J AU Wang, SS Walker, JL Schiffman, M Solomon, D AF Wang, SS Walker, JL Schiffman, M Solomon, D CA Atypical Squamous Cell Undermined TI Evaluating the risk of cervical precancer with a combination of cytologic, virologic, and visual methods SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ASCUS-LSIL TRIAGE; HUMAN-PAPILLOMAVIRUS; WOMEN; CANCER; MANAGEMENT; CERVICOGRAPHY; PARTICIPANTS; STRATEGIES; NEOPLASIA; CELLS AB Several test modalities (cytologic, molecular, and visual) may be used for cervical cancer screening, triage, and follow-up. Although no currently available single test for cervical neoplasia can detect disease with both high sensitivity and specificity, combinations of available tests allow for improved risk prediction. We therefore evaluated the combination of liquid-based cytology (LBC), human papillomavirus (HPV) DNA testing, and visual inspection (cervicography), taken at a single point in time, to predict risk of subsequent cervical intraepithelial neoplasia 3 (CIN3) or cancer developing within 2 years in a triage population of 5,060 women referred for equivocal or mildly abnormal cytology. The concurrent administration of all three test modalities showed that combinations of these test modalities permitted clear and distinct risk stratification. Among HPV-positive women with high-grade LBC and high-grade cervicography results, 79.1% [95% confidence interval (95% CI), 64.0-90.0] were diagnosed with histologic CIN3 or cancer within 2 years, supporting a ''see-and-treat" clinical application. Conversely, only 1.4% (95% CI, 0.7-2.5) of women with a negative HPV, normal cervigram, and second normal cytology result developed CIN3 or cancer. Because this low absolute risk was largely attributable to the negative HPV test, our results suggest a lack of benefit for a secondary or tertiary test result given an HPV-negative test result. Within HPV-positive women, however, we observed a steadily increasing absolute risk for cervical precancer/cancer with increasing numbers and severity of abnormal test results. We conclude that the clear discrimination of cervical cancer risk provided by multiple test modalities is consistent with our understanding of cervical etiology related to HPV natural history. C1 NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA. RP Wang, SS (reprint author), NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS MSC 7234, Bethesda, MD 20892 USA. EM wangso@mail.nih.gov NR 14 TC 15 Z9 15 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 BP 2665 EP 2668 DI 10.1158/1055-9965.EPI-05-0151 PN 1 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BM UT WOS:000233351100032 PM 16284394 ER PT J AU Kovacic, MB Martin, M Gao, XJ Fuksenko, T Chen, CJ Cheng, YJ Chen, JY Apple, R Hildesheim, A Carrington, M AF Kovacic, MB Martin, M Gao, XJ Fuksenko, T Chen, CJ Cheng, YJ Chen, JY Apple, R Hildesheim, A Carrington, M TI Variation of the killer cell immunoglobulin-like receptors and HLA-C genes in nasopharyngeal carcinoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CLASS-II ALLELES; CERVICAL NEOPLASIA; FUNCTIONAL TRANSFER; DIRECT BINDING; UNITED-STATES; ANTIGEN; RISK; TAIWAN; ASSOCIATIONS; RECOGNITION AB Nasopharyngeal carcinoma (NPC) is an Epstein-Barrvirus (EBV)-associated malignancy. Previous studies have shown that NPC is associated with specific human leukocyte antigen (HLA) alleles which function in adaptive immunity to present viral and other antigens to the immune system. The role of innate immunity in NPC development is unknown. To determine whether innate immunity is associated with NPC, a case-control study was conducted among 295 Taiwanese NPC cases (99% EBV seropositive) and 252 community controls (29% EBV seropositive). Using high-resolution genotyping, we evaluated the variation of HLA class I alleles and killer cell immunoglobulin-like receptor (KIR) alleles. Located on the surface of natural killer (NK) cells and a subset of T cells, inhibitory KIRs diminish NK cytolysis of target cells upon binding to their HLA class I ligands and activating KIRs are thought to stimulate NK destruction of target cells. Our results suggest that an increasing number of activating KIRs may be associated with increasing NPC risk, particularly in individuals seropositive for anti-EBV antibodies known to be linked to NPC susceptibility (P-trend = 0.07). Among EBV-seropositive individuals, carriers of >= 5 activating KIRs had a 3.4-fold increased risk of disease (95% confidence interval, 0.74-15.7) compared with individuals with no functional activating KIRs. In contrast, there was no clear evidence of risk associated with increasing numbers of inhibitory KIRs. When evaluating HLA-Cw alleles, we observed that carriers of HLA-Cw*0401 alleles were at a significantly reduced NPC risk (odds ratio, 0.46; 95% confidence intervals, 0.23-0.92), an effect that could not be explained by linkage disequilibrium with other NPC-associated HLA alleles. Our results suggest that KIR-mediated activation may be associated with NPC risk. As this finding is consistent with a recent report examining cervical cancer, a malignancy caused by human papillomavirus, the data raises the possibility that KIRs, and more generally innate immunity, may be involved in the pathogenesis of viral-associated cancers. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD USA. NCI, Div Canc Prevent, NIH, Dept Hlth & Human Serv, Rockville, MD USA. Sci Applicat Int Corp, Basic Res Program, Frederick, MD USA. Natl Canc Inst, Lab Genom Divers, Frederick, MD USA. Natl Taiwan Univ, Coll Publ Hlth, Grad Inst Epidemiol, Taipei 10764, Taiwan. Natl Taiwan Univ, Coll Med, Dept Microbiol, Taipei 10764, Taiwan. Roche Mol Syst, Alameda, CA USA. RP Kovacic, MB (reprint author), Natl Canc Inst, Hormonal & Reprod Epidemiol Branch, 6120 Execut Blvd,Room 7101, Bethesda, MD 20853 USA. EM kovacicm@mail.nih.gov RI Chen, Chien-Jen/C-6976-2008; apple, raymond/I-4506-2012 OI apple, raymond/0000-0002-8007-0345 NR 32 TC 40 Z9 42 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 BP 2673 EP 2677 DI 10.1158/1055-9965.EPI-05-0229 PN 1 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BM UT WOS:000233351100034 ER PT J AU Faupel-Badger, JM Prindiville, SA Venzon, D Vonderhaar, BK Zujewski, JA Eng-Wong, J AF Faupel-Badger, JM Prindiville, SA Venzon, D Vonderhaar, BK Zujewski, JA Eng-Wong, J TI Effects of raloxifene on circulating prolactin and estradiol levels in premenopausal women at high risk for developing breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. RI Venzon, David/B-3078-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2682S EP 2682S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200009 ER PT J AU Abdullaev, Z Pack, S Pugacheva, E Loukinov, D Flanagan, PT Kwon, YW Vatolin, S Custer, M Risinger, JI Hong, J Schrump, DS Barrett, JC Lobanenkov, V AF Abdullaev, Z Pack, S Pugacheva, E Loukinov, D Flanagan, PT Kwon, YW Vatolin, S Custer, M Risinger, JI Hong, J Schrump, DS Barrett, JC Lobanenkov, V TI Epigenetic alterations initiated by switching of DNA occupancy from CTCF to BORIS SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NIAID, NIH, Rockville, MD USA. Lerner Res Inst, Cleveland, OH USA. NCI, NIH, Bethesda, MD 20892 USA. Novartis Inst Biomed Res, Cambridge, MA USA. RI Pack, Svetlana/C-2020-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2686S EP 2687S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200027 ER PT J AU Dawsey, SP Adams, L Roth, MJ Qiao, YL Wang, GQ Tayor, PR Dawsey, SM Woodson, K AF Dawsey, SP Adams, L Roth, MJ Qiao, YL Wang, GQ Tayor, PR Dawsey, SM Woodson, K TI COX2 (PTGS2) gene methylation in normal and dysplastic epithelium, early invasive squamous cell cancer, and associated subepithelial lymphocytes and stromal tissues SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2686S EP 2686S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200025 ER PT J AU Zhu, HM Theresa, GM Xi, SC Jiang, Q Chen, TP Li, E Muegge, K AF Zhu, HM Theresa, GM Xi, SC Jiang, Q Chen, TP Li, E Muegge, K TI Lsh is involved in de novo methylation of DNA SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, CCR, SAIC, Frederick, MD 21701 USA. Novartis, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2686S EP 2686S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200024 ER PT J AU Lubet, RA Yao, RS Grubbs, CJ You, M Wang, Y AF Lubet, RA Yao, RS Grubbs, CJ You, M Wang, Y TI Induction of phase II drug metabolizing enzymes in rat liver by various agents. Is there a coordinate response? Apparently not SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. Washington Univ, St Louis, MO USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2688S EP 2688S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200033 ER PT J AU Grubbs, CJ Muccio, DD Christov, KT Brouillette, WJ Lubet, RA AF Grubbs, CJ Muccio, DD Christov, KT Brouillette, WJ Lubet, RA TI Prevention of methylnitrosourea (MNU)-induced mammary cancers with new retinoids and correlations with short-term biomarkers SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Univ Alabama, Birmingham, AL USA. Univ Illinois, Chicago, IL USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2691S EP 2691S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200046 ER PT J AU Li, L Tao, LH Steele, V Lubet, R Pereira, M AF Li, L Tao, LH Steele, V Lubet, R Pereira, M TI DNA hypomethylation and excision of 5-methyl-2-deoxycytidine in vinyl carbamate-induced mouse lung tumor: Prevention by budesonide SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Med Univ Ohio, Toledo, OH USA. Ohio State Univ, Columbus, OH 43210 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2692S EP 2692S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200050 ER PT J AU Shen, Q Kim, HT Young, M Gunther, E Hilsenbeck, S Chodosh, L Colburn, N Brown, P AF Shen, Q Kim, HT Young, M Gunther, E Hilsenbeck, S Chodosh, L Colburn, N Brown, P TI AP-1 blockade in vivo suppresses development of mammary tumor in MMTV-erbB2 mice SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Baylor Coll Med, Houston, TX 77030 USA. NCI, Frederick, MD 21701 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2692S EP 2692S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200051 ER PT J AU Fabian, CJ Kimler, BF Anderson, JR Chamberlain, CS Mayo, MS Khan, SA Dooley, WC Krontiras, H Browne, D AF Fabian, CJ Kimler, BF Anderson, JR Chamberlain, CS Mayo, MS Khan, SA Dooley, WC Krontiras, H Browne, D TI Comparison of random periareolar fine needle aspiration versus ductal lavage for acquisition of breast tissue in meeting eligibility requirements for a phase II chemoprevention study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Univ Alabama, Birmingham, AL USA. NCI, Bethesda, MD 20892 USA. RI Dooley, William/E-7660-2013; Mayo, Matthew/E-3774-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2694S EP 2694S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200058 ER PT J AU Simoneau, AR Gerner, EW Nagle, R Ziogas, A Fujikawa-Brooks, S Lieberman, R Meyskens, FL AF Simoneau, AR Gerner, EW Nagle, R Ziogas, A Fujikawa-Brooks, S Lieberman, R Meyskens, FL TI Completed results of a phase IIa trial for prostate cancer chemoprevention using diflouromethylornithine [DFMO] SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Univ Calif Irvine, Long Beach, CA USA. Univ Arizona, Tucson, AZ USA. NCI, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2695S EP 2695S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200063 ER PT J AU Agurs-Collins, T Makambi, K Palmer, JR Rosenberg, L Adams-Campbell, LL AF Agurs-Collins, T Makambi, K Palmer, JR Rosenberg, L Adams-Campbell, LL TI Dietary patterns and breast cancer risk in women participating in the Black Womens Health Study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. Howard Univ, Ctr Canc, Washington, DC 20059 USA. Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2697S EP 2698S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200071 ER PT J AU Cross, AJ Gunter, MJ Wood, R Pietinen, P Taylor, PR Virtamo, J Albanes, D Sinha, R AF Cross, AJ Gunter, MJ Wood, R Pietinen, P Taylor, PR Virtamo, J Albanes, D Sinha, R TI Iron and colorectal cancer risk in the alpha-tocopherol, beta-carotene cancer prevention (ATBC) study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, DCEG, Rockville, MD USA. Tufts Univ, Boston, MA 02111 USA. Natl Publ Hlth Inst, Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015; Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2698S EP 2698S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200075 ER PT J AU Nicodemus, KK Berndt, SI AF Nicodemus, KK Berndt, SI TI Do polymorphisms in GSTM1, GSTT1, and GSTP1 influence the risk of prostate cancer? A meta-analysis of statistical epistasis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NIMH, Cognit & Psychosis Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2699S EP 2699S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200077 ER PT J AU Christo, DK Dorgan, JF Brinton, LA Hoffman, SC Comstock, GW Helzlsouer, KJ AF Christo, DK Dorgan, JF Brinton, LA Hoffman, SC Comstock, GW Helzlsouer, KJ TI C-reactive protein and risk of incident endometrial cancer in three US cohorts. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Johns Hopkins Sch Publ Hlth, Baltimore, MD USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2700S EP 2700S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200083 ER PT J AU Sansbury, LB Ratnasinghe, L Bergen, A Cantwell, MM Wanke, K Caporaso, N Lehman, T Kalindindi, A Modali, R Schatzkin, A Lanza, E AF Sansbury, LB Ratnasinghe, L Bergen, A Cantwell, MM Wanke, K Caporaso, N Lehman, T Kalindindi, A Modali, R Schatzkin, A Lanza, E TI Polymorphisms in ERCC2, ERCC4, OGG1, XRCC1, and XRCC3 genes and their role as effect modifiers of dietary antioxidant intake and risk of colorectal adenoma recurrence. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. US FDA, Ctr Struct Genom, Little Rock, AR USA. Univ Arkansas, Dept Epidemiol, Little Rock, AR 72204 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. BioServe Biotechnol Ltd, Laurel, MD USA. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2700S EP 2700S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200082 ER PT J AU Gunter, MJ Stolzenberg-Solomon, R Cross, AJ Leitzmann, MF Wood, R Virtamo, J Albanes, D Sinha, R AF Gunter, MJ Stolzenberg-Solomon, R Cross, AJ Leitzmann, MF Wood, R Virtamo, J Albanes, D Sinha, R TI C-reactive protein (CRP) and colorectal cancer incidence in a cohort of male smokers. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Rockville, MD USA. Tufts Univ, Boston, MA 02111 USA. Natl Publ Hlth Inst, Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015; Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2701S EP 2701S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200085 ER PT J AU Kamangar, F Qiao, YL Schiller, JT Dawsey, SM Fears, T Sun, XD Abnet, CC Zhao, P Taylor, PR Mark, SD AF Kamangar, F Qiao, YL Schiller, JT Dawsey, SM Fears, T Sun, XD Abnet, CC Zhao, P Taylor, PR Mark, SD TI Human papillomavirus serology and the risk of esophageal and gastric cancers: Results from a cohort in a high-risk region in China. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Beijing 100021, Peoples R China. RI Qiao, You-Lin/B-4139-2012 OI Qiao, You-Lin/0000-0001-6380-0871 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2702S EP 2702S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200090 ER PT J AU Trivers, K Gammon, M Abrahamson, P Lund, MJ Kaufman, J Moorman, P Cai, JW Porter, P Brinton, L Eley, JW AF Trivers, K Gammon, M Abrahamson, P Lund, MJ Kaufman, J Moorman, P Cai, JW Porter, P Brinton, L Eley, JW TI Reproductive factors and breast cancer survival in women less than 55 years of age. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Univ N Carolina, Chapel Hill, NC USA. Emory Univ, Atlanta, GA 30322 USA. Duke Univ, Med Ctr, Durham, NC USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2703S EP 2703S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200093 ER PT J AU Elmore, E Jain, A Brunier, A Kopelovitch, L Meyskens, FL Steele, VE Redpath, JL AF Elmore, E Jain, A Brunier, A Kopelovitch, L Meyskens, FL Steele, VE Redpath, JL TI Response of atorvastatin, alpha-TEA, and verapamil in the human melanoma prevention assay. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Univ Calif Irvine, Irvine, CA USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2704S EP 2705S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200100 ER PT J AU Liu, Y Alyaqoub, FS Tao, LH Steele, VE Lubet, RA Pereira, MA AF Liu, Y Alyaqoub, FS Tao, LH Steele, VE Lubet, RA Pereira, MA TI Effect of long and short-term treatment with targretin on DNA methylation and mRNA expression in vinyl carbamate-induced mouse lung tumors. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Ohio State Univ, Columbus, OH 43210 USA. Med Univ Ohio, Toledo, OH USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2704S EP 2704S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200099 ER PT J AU Marks, CL AF Marks, CL TI The use of genetically engineered mice in cancer prevention research. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2705S EP 2706S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200104 ER PT J AU Rader, JS Zhang, ZY Ma, D Gerhard, DS Nguyen, L Huettner, PC Smith, K Baty, J Mutch, DG Herzog, TJ Gibb, RK Powell, MA Massad, S Hernandez, E Judson, PL Swisher, EM Crowder, SE Borecki, IB AF Rader, JS Zhang, ZY Ma, D Gerhard, DS Nguyen, L Huettner, PC Smith, K Baty, J Mutch, DG Herzog, TJ Gibb, RK Powell, MA Massad, S Hernandez, E Judson, PL Swisher, EM Crowder, SE Borecki, IB TI Localization of a cervical cancer susceptibility locus to CD83 on 6p23 in a family-based association study. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Washington Univ, St Louis, MO USA. NIH, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. So Illinois Univ, Springfield, IL USA. Temple Univ, Philadelphia, PA 19122 USA. Univ Minnesota, Minneapolis, MN USA. Univ Washington, Seattle, WA 98195 USA. Univ Missouri, Columbia, MO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2705S EP 2705S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200102 ER PT J AU Bergen, AW Sansbury, LB Wanke, K Caporaso, N Ratnasinghe, L Lehman, TA Kalidinidi, A Modali, R Schatzkin, A Lanza, E AF Bergen, AW Sansbury, LB Wanke, K Caporaso, N Ratnasinghe, L Lehman, TA Kalidinidi, A Modali, R Schatzkin, A Lanza, E TI Obesity: gender, behavior and genetic polymorphisms in the Polyp Prevention Trial. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. Univ Arkansas, Sch Med, Little Rock, AR 72204 USA. BioServe Biotechnol Ltd, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2708S EP 2708S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200113 ER PT J AU Berrigan, D Potischman, N Dodd, K Graubard, B Hursting, SD Lavigne, J Barrett, JC Ballard-Barbash, R AF Berrigan, D Potischman, N Dodd, K Graubard, B Hursting, SD Lavigne, J Barrett, JC Ballard-Barbash, R TI Demographic and anthropometric correlates of serum levels of insulin-like growth factor 1 (IGF-1) and IGF binding protein-3 (IGFBP-3) in US adults. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, NIH, Bethesda, MD 20892 USA. UT Austin, Dept Nutr Sci, Austin, TX USA. Novartis Inst Biomed Res, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2712S EP 2712S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200129 ER PT J AU Jansen, AP Colburn, NH AF Jansen, AP Colburn, NH TI Epidermal expression of the translation inhibitor Pdcd4 suppresses tumorigenesis. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, CCR, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2714S EP 2715S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200140 ER PT J AU Fagundes, RB Abnet, CC Strickland, PT Kamangar, F Roth, MJ Taylor, PR Dawsey, SM AF Fagundes, RB Abnet, CC Strickland, PT Kamangar, F Roth, MJ Taylor, PR Dawsey, SM TI Higher urine 1-hydroxypyrene glucuronide (1-OHPG) is associated with tobacco smoke exposure and drinking mate in healthy subjects from Rio Grande do Sul, Brazil. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Univ Fed Santa Maria, BR-97119900 Santa Maria, RS, Brazil. NCI, Bethesda, MD 20892 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2717S EP 2717S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200149 ER PT J AU Lubet, RA McCormick, DL Christov, KT Steele, VE Crist, KA Grubbs, CJ AF Lubet, RA McCormick, DL Christov, KT Steele, VE Crist, KA Grubbs, CJ TI Limited chemopreventive efficacy of targretin in rat models of urinary bladder, prostate, and ovarian cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. IIT, Chicago, IL 60616 USA. Univ Illinois, Chicago, IL USA. Med Coll Ohio, Toledo, OH 43699 USA. Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2718S EP 2718S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200155 ER PT J AU Hudson, TS Nunez, N Green, J AF Hudson, TS Nunez, N Green, J TI Alternate chemopreventive mechanisms of action of resveratrol and muscadine grape skin powder extract in prostate cancer. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Univ Texas, Austin, TX 78712 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2720S EP 2721S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200166 ER PT J AU Jong, L Chao, WR Amin, K Yean, D Kapetanovic, IM Crowell, J AF Jong, L Chao, WR Amin, K Yean, D Kapetanovic, IM Crowell, J TI SR13668: A dietary indole analog inhibits PI3K/AKT signaling pathway and possesses potent oral anticancer activity in various murine xenograft models. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 SRI Int, Menlo Pk, CA 94025 USA. NCI, NIH, Div Canc Prevent, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2721S EP 2721S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200167 ER PT J AU Cantwell, MM Sansbury, L Ratnasinghe, L Bergen, A Wanke, K Caporaso, N Schatzkin, A Lehman, T Kalidindi, A Modali, R Lanza, E AF Cantwell, MM Sansbury, L Ratnasinghe, L Bergen, A Wanke, K Caporaso, N Schatzkin, A Lehman, T Kalidindi, A Modali, R Lanza, E TI Glutathione peroxidase (GPX) polymorphism and adenoma recurrence in the polyp prevention trial. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Rockville, MD USA. Univ Arkansas, Sch Med, Little Rock, AR 72204 USA. Bioserve Biotechnol Ltd, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2723S EP 2723S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200176 ER PT J AU Hance, KW Rogers, CJ Zaharoff, DA Schlom, J Greiner, JW AF Hance, KW Rogers, CJ Zaharoff, DA Schlom, J Greiner, JW TI Pancreatic cancer: Target for immune-based intervention? SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2723S EP 2723S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200177 ER PT J AU Chow, HHS Hakim, IA Vining, DR Crowell, JA Cordova, CA Hara, Y Alberts, DS AF Chow, HHS Hakim, IA Vining, DR Crowell, JA Cordova, CA Hara, Y Alberts, DS TI Effects of polyphenon E on drug and carcinogen metabolizing enzymes in healthy individuals. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ USA. NCI, Bethesda, MD 20892 USA. Mitsui Norin Co, Shizuoka, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2724S EP 2725S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200182 ER PT J AU McCray, QM Lin, Q Boushey, CJ Sinha, R Frankenfeld, C Mai, V AF McCray, QM Lin, Q Boushey, CJ Sinha, R Frankenfeld, C Mai, V TI Diet mediated differences in fecal microflora composition as a potential factor contributing to the observed high burden of CRC in African Americans. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 UMES, Princess Anne, MD USA. Univ Maryland, Baltimore, MD 21201 USA. Purdue Univ, W Lafayette, IN 47907 USA. NCI, Rockville, MD USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2726S EP 2726S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200186 ER PT J AU Lawson, KA Wright, ME Weinstein, SJ Pietinen, P Virtamo, J Taylor, PR Albanes, D AF Lawson, KA Wright, ME Weinstein, SJ Pietinen, P Virtamo, J Taylor, PR Albanes, D TI Dietary vitamin E and risk of colon and rectal cancer in a cohort of male smokers. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2727S EP 2727S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200190 ER PT J AU Mitrou, PN Albanes, D Weinstein, S Pietinen, P Taylor, P Virtamo, J Leitzmann, MF AF Mitrou, PN Albanes, D Weinstein, S Pietinen, P Taylor, P Virtamo, J Leitzmann, MF TI Intakes of calcium, dairy products, and prostate cancer risk in the ATBC study. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. RI Albanes, Demetrius/B-9749-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2727S EP 2727S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200191 ER PT J AU Wayne, SJ Neuhouser, ML Ulrich, CM Koprowski, C Baumgartner, K Baumgartner, RN McTiernan, A Bernstein, L Ballard-Barbash, R AF Wayne, SJ Neuhouser, ML Ulrich, CM Koprowski, C Baumgartner, K Baumgartner, RN McTiernan, A Bernstein, L Ballard-Barbash, R TI High intake of dietary fiber is associated with high levels of serum sex hormone-binding globulin in postmenopausal breast cancer survivors: The health, eating, activity, and lifestyle (HEAL) study. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 Univ New Mexico, Albuquerque, NM 87131 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ So Calif, Los Angeles, CA USA. Univ Louisville, Louisville, KY 40292 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2727S EP 2727S PN 2 PG 1 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200192 ER PT J AU Saydah, SH Graubard, B Ballard-Barbash, R Berrigan, D AF Saydah, SH Graubard, B Ballard-Barbash, R Berrigan, D TI Insulin-like growth factors and subsequent risk of cancer mortality in the United States. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 CDC, Natl Ctr Hlth Stat, Hyattsville, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2729S EP 2730S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200201 ER PT J AU Zahm, SH Morton, LM Wang, SS Hein, DW Rothman, N Colt, JS Davis, S Cerhan, JR Severson, RK Hartge, P Ross, RK AF Zahm, SH Morton, LM Wang, SS Hein, DW Rothman, N Colt, JS Davis, S Cerhan, JR Severson, RK Hartge, P Ross, RK TI Non-Hodgkin lymphoma, hair dyes, and genetic susceptibility. SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Meeting Abstract CT 4th Annual Conference on Frontiers in Cancer Prevention Research CY OCT 30-NOV 02, 2005 CL Baltimore, MD C1 NCI, Rockville, MD USA. Univ Louisville, Louisville, KY 40292 USA. Univ Washington, Seattle, WA 98195 USA. Mayo Clin, Rochester, MN USA. Wayne State Univ, Detroit, MI USA. Univ So Calif, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD NOV PY 2005 VL 14 IS 11 SU S BP 2730S EP 2731S PN 2 PG 2 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 985BN UT WOS:000233351200204 ER EF