FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Greenwald, P Anderson, D Nelson, SA Taylor, PR AF Greenwald, Peter Anderson, Darrell Nelson, Stefanie A. Taylor, Philip R. TI Clinical trials of vitamin and mineral supplements for cancer prevention' SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Conference on Multiviitamin/Mineral Supplements and Chronic Disease Prevention CY MAY 15-17, 2006 CL Natl Inst Hlth, Bethesda, MD HO Natl Inst Hlth DE multivitamin supplements; randomized clinical trials; cancer prevention; bioactive food components; nutrition ID BETA-CAROTENE SUPPLEMENTATION; BASE-LINE CHARACTERISTICS; DIETARY-FOLATE INTAKE; CARDIOVASCULAR-DISEASE; COLORECTAL-CANCER; RANDOMIZED-TRIAL; WOMENS HEALTH; LUNG-CANCER; RISK; MORTALITY AB Approximately 20-30% of Americans consume multivitamin supplements daily, indicating high public interest in the prevention of cancer and other chronic diseases through a nutrition-based approach. Although several bioactive food components, including vitamins and minerals, have been investigated for their ability to affect cancer risk, few large, randomized, placebo-controlled clinical trials of multivitamins with cancer as the primary endpoint have been performed. The results of most large-scale trials of multivitamin supplements (combinations of >= 2 vitamins and minerals) to prevent cancer have been mixed. The Linxian General Population and Dysplasia trials found a decreased risk of cancer, particularly stomach cancer, for participants taking a multivitamin supplement, but this was in a borderline-deficient population in China. Two trials, the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study and the,B-Carotene and Retinol Efficacy Trial, found an increased risk of lung cancer among male cigarette smokers or asbestos-exposed persons taking beta-carotene-a surprising result, considering that most epidemiologic studies have suggested that consumption of fruit and vegetables appears to lower cancer risk. To clarify the effects of multivitamin supplements, several large randomized clinical trials are underway, including the Physicians' Health Study II, the Selenium and Vitamin E Cancer Prevention Trial, and a European study, Supplementation en Vitamines et Mineraux Antioxydants (SU.VI.MAX). Because epidemiologic studies generally evaluate foods rather than specific bioactive food components, a systematic approach to determining how combinations of vitamins and minerals may interact to ameliorate cancer risk is necessary to further our understanding of the potential benefits and risks of supplement use. C1 NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Sci Consulting Grp Inc, Gaithersburg, MD USA. RP Greenwald, P (reprint author), NCI, Div Canc Prevent, NIH, 6130 Execut Blvd,Suite 2040, Bethesda, MD 20892 USA. EM pg37g@nih.gov FU Intramural NIH HHS NR 24 TC 49 Z9 51 U1 2 U2 11 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JAN PY 2007 VL 85 IS 1 BP 314S EP 317S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 125CP UT WOS:000243419400052 PM 17209217 ER PT J AU Boffetta, P van der Hel, O Norppa, H Fabianova, E Fucic, A Gundy, S Lazutka, J Cebulska-Wasilewska, A Puskailerova, D Znaor, A Kelecsenyi, Z Kurtinaitis, J Rachtan, J Forni, A Vermeulen, R Bonassi, S AF Boffetta, Paolo van der Hel, Olga Norppa, Hannu Fabianova, Eleonora Fucic, Aleksandra Gundy, Sarolta Lazutka, Juozas Cebulska-Wasilewska, Antonina Puskailerova, Daniela Znaor, Ariana Kelecsenyi, Zsolt Kurtinaitis, Juozas Rachtan, Jadwiga Forni, Alessandra Vermeulen, Roel Bonassi, Stefano TI Chromosomal aberrations and cancer risk: Results of a cohort study from central europe SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE chromosome aberrations; cohort studies; cytogenetics; Europe; neoplasms; risk ID LYMPHOCYTES; HUMANS AB A high level of chromosomal aberrations in peripheral blood lymphocytes may be an early marker of cancer risk, but data on risk of specific cancers and types of chromosomal aberrations (chromosome type and chromatid type) are limited. A total of 6,430 healthy individuals from nine laboratories in Croatia, Hungary, Lithuania, Poland, and Slovakia, included in chromosomal aberration surveys performed during 1978-2002, were followed up for cancer incidence or mortality for an average of 8.5 years; 200 cancer cases were observed. Compared with that for the low-tertile level of chromosomal aberrations, the relative risks of cancer for the medium and high tertiles were 1.78 (95% confidence interval: 1.19, 2.67) and 1.81 (95% confidence interval: 1.20, 2.73), respectively. The relative risk for chromosome-type aberrations above versus below the median was 1.50 (95% confidence interval: 1.12, 2.01), while that for chromatid-type aberrations was 0.97 (95% confidence interval: 0.72, 1.31). The analyses of risk of specific cancers were limited by small numbers, but the association was stronger for stomach cancer. This study confirms the previously reported association between level of chromosomal aberrations and cancer risk and provides novel information on the type of aberrations more strongly predictive of cancer risk and on the types of cancer more strongly predicted by chromosomal aberrations. C1 Int Agcy Res Canc, F-69008 Lyon, France. Finnish Inst Occupat Hlth, Helsinki, Finland. Reg Publ Hlth Author, Banska Bystrica, Slovakia. Inst Med Res & Occupat Hlth, Zagreb, Croatia. Natl Inst Oncol, Budapest, Hungary. Vilnius Univ, Vilnius, Lithuania. Jagiellonian Univ, Coll Med, Dept Epidemiol, Krakow, Poland. Polish Acad Sci, Inst Nucl Phys, Krakow, Poland. Croatian Natl Canc Registry, Zagreb, Croatia. Vilnius Univ, Inst Oncol, Lithuanian Canc Register, Vilnius, Lithuania. Inst Oncol, Dept Canc Epidemiol, Krakow Branch, Krakow, Poland. Univ Milan, Dept Environm & Occupat Hlth, Milan, Italy. NCI, Bethesda, MD 20892 USA. Natl Inst Canc Res, Unit Mol Epidemiol, Genoa, Italy. RP Boffetta, P (reprint author), Int Agcy Res Canc, 150 Cours Albert Thomas, F-69008 Lyon, France. EM boffetta@iarc.fr RI Vermeulen, Roel/F-8037-2011; OI Vermeulen, Roel/0000-0003-4082-8163; bonassi, stefano/0000-0003-3833-6717 NR 27 TC 90 Z9 99 U1 1 U2 8 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 JAN 1 PY 2007 VL 165 IS 1 BP 36 EP 43 DI 10.1093/aje/kwj367 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 120BW UT WOS:000243059500005 PM 17071846 ER PT J AU Bluhm, EC Zahm, SH Fine, HA Black, PM Loeffler, JS Shapiro, WR Selker, RG Inskip, PD AF Bluhm, Elizabeth C. Zahm, Shelia Hoar Fine, Howard A. Black, Peter M. Loeffler, Jay S. Shapiro, William R. Selker, Robert G. Inskip, Peter D. TI Personal hair dye use and risks of glioma, meningioma, and acoustic neuroma among adults SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE glioma; hair dyes; meningioma; neuroma; acoustic ID NON-HODGKINS-LYMPHOMA; BLADDER-CANCER RISK; CHILDHOOD BRAIN-TUMORS; BREAST-CANCER; COLORING PRODUCTS; UNITED-STATES; MULTIPLE-MYELOMA; LEUKEMIA; WOMEN; CARCINOGENICITY AB Previous studies have suggested an association of personal hair dye use with bladder and hematopoietic cancers. Risks for brain tumors are not well understood. The authors investigated associations between use of synthetic hair dyes and risk of brain tumors in a hospital-based case-control study. The study included adults newly diagnosed with glioma (n = 489), meningioma (n = 197), or acoustic neuroma (n = 96) between 1994 and 1998 at three urban US hospitals and 799 controls. Odds ratios were estimated and 95% confidence intervals were calculated using unconditional logistic regression. Detailed exposure histories were obtained by interview. There was no consistent pattern of elevated odds ratios for glioma, meningioma, or acoustic neuroma with use or prolonged use of permanent, semipermanent, temporary, or gradual hair dyes. Although use of permanent brown hair dye for 20 or more years was associated with glioma among women, the estimate was imprecise (odds ratio = 3.8, 95% confidence interval: 1.2, 12.5) and was based on just 13 exposed cases; thus, this could be a chance finding. Overall, there was little consistent evidence for an association of synthetic hair dye use with glioma, meningioma, or acoustic neuroma. However, prolonged use of dark-colored permanent dyes warrants further investigation given the high prevalence of hair dyeing. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Div Canc Prevent, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02115 USA. St Josephs Hosp, Barrow Neurol Inst, Phoenix, AZ USA. Western Penn Hosp, Div Neurosurg, Pittsburgh, PA 15224 USA. RP Bluhm, EC (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,MSC 7238, Bethesda, MD 20892 USA. EM bluhme@mail.nih.gov RI Zahm, Shelia/B-5025-2015 FU Intramural NIH HHS NR 53 TC 9 Z9 10 U1 3 U2 7 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 JAN 1 PY 2007 VL 165 IS 1 BP 63 EP 71 DI 10.1093/aje/kwk002 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 120BW UT WOS:000243059500008 PM 17079691 ER PT J AU Longstreth, WT Larsen, EKM Klein, R Wong, TY Sharrett, AR Lefkowitz, D Manolio, TA AF Longstreth, W. T., Jr. Larsen, Emily K. Marino Klein, Ronald Wong, Tien Yin Sharrett, A. Richey Lefkowitz, David Manolio, Teri A. TI Associations between findings on cranial magnetic resonance imaging and retinal photography in the elderly - The cardiovascular health study SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE arteriosclerosis; brain infarction; leukoaraiosis; magnetic resonance imaging; microcirculation; retinal artery; retinal vein ID MICROVASCULAR ABNORMALITIES; ATHEROSCLEROSIS RISK; WHITE-MATTER; CLINICAL STROKE; BLOOD-PRESSURE; COMMUNITIES; PEOPLE; MANIFESTATIONS; PREDICTORS; INFARCTION AB Associations between findings on cranial magnetic resonance imaging (MRI) and retinal photographs have been described mostly in middle-aged people. In the Cardiovascular Health Study, 1,717 elderly participants underwent MRI and retinal photography between 1991 and 1999. Associations were sought between MRI findings and four findings of retinal microvascular disease: retinopathy, focal arteriolar narrowing, arteriovenous nicking, and the arteriovenous ratio-the last based upon semiautomated measurements of arterioles and venules. After controlling for age and gender, the authors found associations between MRI findings and the smaller arteriovenous ratio (per standard deviation decrease): prevalent infarcts (odds ratio = 1.18, 95% confidence interval: 1.05, 1.34; p = 0.007), white matter grade (regression coefficient, 0.093; p = 0.011), incident infarct (odds ratio = 1.26, 95% confidence interval: 1.09, 1.46; p = 0.002), and worsening white matter grade (odds ratio = 1.12, 95% confidence interval: 0.98, 1.29; p = 0.09). Arteriovenous nicking was also associated with prevalent (odds ratio = 1.84, 95% confidence interval: 1.23, 2.76; p = 0.003) and incident (odds ratio = 1.84, 95% confidence interval: 1.15, 2.94; p = 0.011) infarcts. Adjustment for hypertension and diabetes had minimal effect. Evidence of small vessel disease in the retina increases the likelihood of finding it in the brain. Associations were less prominent in this elderly population than have been described in middle-aged people. C1 Univ Washington, Harborview Med Ctr, Dept Neurol, Seattle, WA 98104 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98104 USA. Univ Washington, Dept Biostat, Seattle, WA 98104 USA. Univ Wisconsin, Dept Ophthalmol, Madison, WI USA. Univ Melbourne, Ctr Eye Res Australia, Melbourne, Vic, Australia. Natl Univ Singapore, Singapore Eye Res Inst, Singapore 117548, Singapore. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. Wake Forest Univ, Dept Neurol, Winston Salem, NC 27109 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Longstreth, WT (reprint author), Univ Washington, Harborview Med Ctr, Dept Neurol, Box 359775,325 9Th Ave, Seattle, WA 98104 USA. EM wl@u.washington.edu FU NHLBI NIH HHS [N01-HC-35129, N01-HC-15103, N01-HC-85079, N01-HC-85086] NR 20 TC 59 Z9 60 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JAN 1 PY 2007 VL 165 IS 1 BP 78 EP 84 DI 10.1093/aje/kwj350 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 120BW UT WOS:000243059500010 PM 17041135 ER PT J AU Nicodemus, KK Luna, A Shugart, YY AF Nicodemus, Kristin K. Luna, Augustin Shugart, Yin Yao TI An evaluation of power and type I error of single-nucleotide polymorphism transmission/disequilibrium-based statistical methods under different family structures, missing parental data, and population stratification SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CASE-CONTROL ASSOCIATION; COMMON GENETIC-VARIANTS; LARGE-SCALE; LINKAGE; BIAS; DISEQUILIBRIUM; DESIGNS; CANCER; QUANTIFICATION; TRANSMISSION AB Researchers conducting family-based association studies have a wide variety of transmission/ disequilibrium (TD)-based methods to choose from, but few guidelines exist in the selection of a particular method to apply to available data. Using a simulation study design, we compared the power and type I error of eight popular TD-based methods under different family structures, frequencies of missing parental data, genetic models, and population stratifications. No method was uniformly most powerful under all conditions, but type I error was appropriate for nearly every test statistic under all conditions. Power varied widely across methods, with a 46.5% difference in power observed between the most powerful and the least powerful method when 50% of families consisted of an affected sib pair and one parent genotyped under an additive genetic model and a 35.2% difference when 50% of families consisted of a single affection-discordant sibling pair without parental genotypes available under an additive genetic model. Methods were generally robust to population stratification, although some slightly less so than others. The choice of a TD-based test statistic should be dependent on the predominant family structure ascertained, the frequency of missing parental genotypes, and the assumed genetic model. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Biostat, Baltimore, MD 21218 USA. NIMH, Genes Cognit & Psychosis Program, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Shugart, YY (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St,E 6516, Baltimore, MD 21205 USA. EM yyao@jhsph.edu FU NCI NIH HHS [R03CA123620-01, R03 CA123620] NR 27 TC 14 Z9 14 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JAN PY 2007 VL 80 IS 1 BP 178 EP 185 DI 10.1086/510498 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 120RG UT WOS:000243102500017 PM 17160905 ER PT J AU Hyre, AD Fox, CS Astor, BC Cohen, AJ Muntner, P AF Hyre, Amanda D. Fox, Caroline S. Astor, Brad C. Cohen, Andrew J. Muntner, Paul TI The impact of reclassifying moderate CKD as a coronary heart disease risk equivalent on the number of US adults recommended lipid-lowering treatment SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE chronic kidney disease (CKD); coronary heart disease; Third National Cholesterol Education Program Adult Treatment Panel (ATP-III); low-density lipoprotein (LDL) cholesterol ID CHRONIC KIDNEY-DISEASE; PRIOR MYOCARDIAL-INFARCTION; GLOMERULAR-FILTRATION-RATE; TREATMENT PANEL-III; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; SERUM CREATININE; RENAL-DISEASE; UNITED-STATES; FOLLOW-UP AB Background: The Third National Cholesterol Education Program Adult Treatment Panel (ATP-III) guidelines recommend consideration of lipid-lowering therapy at lower low-density lipoprotein cholesterol levels (>= 100 mg/dL [>= 2.59 mmol/L]) for adults with coronary heart disease risk equivalents. Chronic kidney disease is associated with increased coronary heart disease risk but is not included as a risk equivalent in these guidelines. Methods: The impact of including moderate chronic kidney disease (estimated glomerular filtration rate, 30 to 59 mL/min/1.73 m(2) [0.50 to 0.98 mL/s]) as a coronary heart disease risk equivalent on the percentage and number of US adults with chronic kidney disease recommended lipid-lowering therapy was estimated by using data from the Third National Health and Nutrition Examination Survey. Results: Of adults with moderate chronic kidney disease, 53.0% had a history of coronary heart disease or a risk equivalent, 24.7% reported a history of myocardial infarction or stroke, 17.7% had diabetes, 9.6% had angina, and 26.9% had a 10-year coronary heart disease risk greater than 20%. Using current ATP-III guidelines, lipid-lowering therapy is recommended for 61.4% of adults with moderate chronic kidney disease. If moderate chronic kidney disease was reclassified as a coronary heart disease risk equivalent, this percentage would increase to 87.7%, representing an increase in number of adults with moderate chronic kidney disease recommended lipid-lowering treatment from 4.5 to 6.5 million adults. Conclusion: This analysis shows that a majority of adults with moderate chronic kidney disease have coronary heart disease or risk equivalents. Nonetheless, a substantially greater proportion of US adults with moderate chronic kidney disease would be recommended lipid-lowering therapy through its reclassification as a coronary heart disease risk equivalent. C1 Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, New Orleans, LA 70112 USA. Ochsner Hlth Syst, Dept Nephrol, New Orleans, LA USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Endocrinol Diab & Hpertens, Boston, MA USA. NHLBI, Natl Inst Hlth, Bethesda, MD USA. Johns Hopkins Univ, Dept Epidemiol & Med, Baltimore, MD USA. RP Muntner, P (reprint author), Tulane Univ, Sch Publ Hlth & Trop Med, Dept Epidemiol, 1440 Canal St,Sl-18, New Orleans, LA 70112 USA. EM pmuntner@tulane.edu NR 39 TC 34 Z9 35 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2007 VL 49 IS 1 BP 37 EP 45 DI 10.1053/j.ajkd.2006.09.017 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 197PD UT WOS:000248566900006 PM 17185144 ER PT J AU Zhang, L Kao, WHL Berthier-Schaad, Y Plantinga, L Fink, N Smith, MW Coresh, J AF Zhang, Lin Kao, W. H. Linda Berthier-Schaad, Yvette Plantinga, Laura Fink, Nancy Smith, Michael W. Coresh, Josef TI C-reactive protein haplotype predicts serum C-reactive protein levels but not cardiovascular disease risk in a dialysis cohort SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE C-reactive protein (CRP) gene; serum C-reactive protein (CRP) level; haplotype; cardiovascular disease (CVD); end-stage renal disease (ESRD) ID SINGLE-NUCLEOTIDE POLYMORPHISMS; PLASMA CRP LEVELS; HEMODIALYSIS-PATIENTS; GENE POLYMORPHISMS; PROMOTER REGION; LINKAGE PHASE; INFLAMMATION; POPULATION; ASSOCIATION; MORTALITY AB Background: C-Reactive protein (CRP) gene variation has been associated with serum CRP levels in the general population. We examined the associations of CRP gene variation with longitudinal CRP measurements and incident cardiovascular disease (CVD) risk in a cohort of 504 white and 244 African-American incident dialysis patients. Methods: Seven tagging single-nucleotide polymorphisms in the CRP gene were selected by using the Carlson method (r(2) > 0.65). High-sensitivity CRP was measured every 6 months (mean, 4.6 months). Haplo.glm was used to determine the association of haplotypes with serum CRP levels and CVD risk. Global tests from Haplo.score were conducted to determine statistical significance. Results: Compared with the most common haplotype, 1 haplotype was associated with a 52% lower CRP level at baseline among African Americans (ratio, 0.48; 95% confidence interval [Cl], 0.28 to 0.82; global P-value = 0.0005). Furthermore, this haplotype was associated significantly with lower serum CRP levels during 36 months of follow-up. Among whites, this haplotype was associated with an 18% (ratio, 0.82; 95% Cl, 0.56 to 1.22; n = 6 carriers) lower CRP level compared with the most common haplotype with a frequency of 1% (global P-value = 0.048). No association was detected between CRP gene variation and CVD risk in either whites or African Americans. Conclusion: Compared with the most common haplotype of the CRP gene, 1 haplotype predicts a lower serum CRP level over time, but no association exists between haplotype of CRP gene and incident CVD in this incident dialysis population. Serum CRP level might be a biomarker, rather than a causal factor, in CVD development. CRP variation may lead to susceptibility to inflammation, but not risk for CVD; however, replication in multiple settings is necessary. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. Johns Hopkins Sch Med, Dept Med, Baltimore, MD USA. SAIC, Lab Genom Divers & Basic Res Program, Frederick, MD USA. NCI, Frederick, MD 21701 USA. RP Coresh, J (reprint author), Johns Hopkins Univ, 2024 E Monument,Ste 2-600, Baltimore, MD 21205 USA. EM jcoresh@jhsph.edu RI Smith, Michael/B-5341-2012 FU AHRQ HHS [R01-HS-08365]; Intramural NIH HHS; NCI NIH HHS [N01-CO-12400]; NHLBI NIH HHS [R01-HL-62985]; NIDDK NIH HHS [R01-DK-59616] NR 31 TC 24 Z9 26 U1 1 U2 3 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-6386 EI 1523-6838 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JAN PY 2007 VL 49 IS 1 BP 118 EP 126 DI 10.1053/j.ajkd.2006.10.008 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 197PD UT WOS:000248566900014 PM 17185152 ER PT J AU Butman, JA Floeter, MK AF Butman, J. A. Floeter, M. K. TI Decreased thickness of primary motor cortex in primary lateral sclerosis SO AMERICAN JOURNAL OF NEURORADIOLOGY LA English DT Article ID TRANSCRANIAL MAGNETIC STIMULATION; CORTICOSPINAL TRACT DEGENERATION; CEREBRAL-CORTEX; NEURON; ALS; MR; SPECTROSCOPY; BRAIN; FEATURES; CRITERIA AB BACKGROUND AND PURPOSE: Primary lateral sclerosis (PLS) is a rare form of motor neuron disease characterized by upper motor neuron dysfunction. Because pathologic examination has revealed a loss of neurons in the motor cortex of patients with PLS, we sought to confirm and extend this finding by using MR imaging to measure cortical thickness. METHODS: Seven patients with PLS and 7 age-matched neurologically normal control subjects were examined with heavily T1-weighted short-tau inversion recovery (STIR) MR imaging performed at 3T. Cortical thickness in the anterior and posterior banks of both the central and precentral sulci were measured. RESULTS: Primary motor cortex (M1) was significantly thinner in patients with PLS than M1 in healthy control subjects, measuring 2.32 +/- 0.21 mm compared with 2.79 +/- 0.18 mm (P =.0008). Cortical thickness did not differ between the 2 groups for primary sensory cortex or for the anterior or posterior banks of the precentral sulcus. Therefore, loss of gray matter was specific to motor cortex. Although this difference was modest, cortical thickness discriminated between the 2 groups; only I PLS case was within the range of normal measurements. CONCLUSION: Decreased thickness of M1 on the anterior bank of the precentral sulcus in patients with PLS, demonstrable by MR imaging, indicates a selective loss of upper motor neurons in this disease. Measurements of cortical thickness by MR imaging may provide a useful biomarker for diagnosis and study of upper motor neuron diseases. C1 Natl Inst Hlth, Dept Diagnost Radiol, Imaging Sci Program, Ctr Clin, Bethesda, MD USA. NINDS, EMG Sect, NIH, Bethesda, MD 20892 USA. RP Butman, JA (reprint author), Bldg 10,Rm 1C660,900 Rockville Pike, Bethesda, MD 20892 USA. EM jbutman@nih.gov RI Butman, John/A-2694-2008; OI Butman, John/0000-0002-1547-9195 FU Intramural NIH HHS NR 38 TC 25 Z9 26 U1 0 U2 1 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 JAN PY 2007 VL 28 IS 1 BP 87 EP 91 PG 5 WC Clinical Neurology; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 127PK UT WOS:000243598600020 PM 17213431 ER PT J AU Davis, AR Hendlish, SK Westhoff, C Frederick, MM Zhang, J Gilles, JM Barnhart, K Creinin, MD AF Davis, Anne R. Hendlish, Sarah K. Westhoff, Carolyn Frederick, Margaret M. Zhang, Jun Gilles, Jerry M. Barnhart, Kurt Creinin, Mitchell D. CA Natl Inst Child Hlth Human Dev Man TI Bleeding patterns after misoprostol vs surgical treatment of early pregnancy failure: results from a randomized trial SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article AB Misoprostol is an acceptable alternative to curettage for treatment of early pregnancy failure. Although bleeding is heavier and more prolonged after medical treatment of early pregnancy failure with misoprostol compared with curettage, bleeding with misoprostol rarely requires intervention. C1 Columbia Univ, New York, NY 10027 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. NICHHD, NIH, Div Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Miami, Miami, FL 33152 USA. Univ Penn, Penn Fertil Care, Philadelphia, PA 19104 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. McGee Womens Res Inst, Pittsburgh, PA USA. RP Davis, AR (reprint author), Columbia Univ, New York, NY 10027 USA. NR 0 TC 14 Z9 14 U1 1 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JAN PY 2007 VL 196 IS 1 BP 31 EP 33 DI 10.1016/j.ajog.2006.07.053 PG 3 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 127GA UT WOS:000243572100008 ER PT J AU Cordeiro, JR Camelier, A Oakley, F Jardim, JR AF Cordeiro, Junia R. Camelier, Aquiles Oakley, Frances Jardim, Jose R. TI Cross-cultural reproducibility of the Brazilian Portuguese version of the role checklist for persons with chronic obstructive pulmonary disease SO AMERICAN JOURNAL OF OCCUPATIONAL THERAPY LA English DT Article DE chronic obstructive pulmonary disease (COPD); culture; role ID TRAUMATIC BRAIN-INJURY; QUALITY-OF-LIFE; OCCUPATIONAL-THERAPY; TRANSLATION; RELIABILITY; ADAPTATION; AGREEMENT; DISORDER; PATIENT; COPD AB OBJECTIVE. This article presents the results of a cross-cultural reproducibility and test-retest reliability study of a Brazilian version of the Role Checklist, in a population with chronic obstructive pulmonary disease (COPD). METHODS. The English version was translated and culturally adapted into Brazilian Portuguese, then administered twice at a 2-week interval to a group of 25 clinically stable individuals with COPD. RESULTS. Cross-cultural adaptation led to adjustments in some terms used in the checklist. Values obtained for kappa suggested mode rate-to-substantial agreement for Part I and Part II. No statistically significant correlations were found between agreement and variables of gender, occupation, marital status, level of education, level of depression, or severity of bronchial obstruction. CONCLUSION. The Brazilian Portuguese version of the Role Checklist was found content valid and reliable for persons with COPD and probably for the Brazilian population in general. C1 UNIFESP, Brazil Resp Div, Lar Escola Sao Francisco, BR-04023062 Sao Paulo, Brazil. UNIFESP, Rehabil Pulm Ctr, Lar Escola Sao Francisco, BR-04023062 Sao Paulo, Brazil. Hosp Israelita Albert Einstein, Occupat Therapy Sect, Sao Paulo, Brazil. NIH, Occupat Therapy Sect, Bethesda, MD 20892 USA. RP Cordeiro, JR (reprint author), UNIFESP, Brazil Resp Div, Lar Escola Sao Francisco, Rua Botucatu 740,3o Andar, BR-04023062 Sao Paulo, Brazil. EM juniacordeiro@terra.com.br; joserjardim@yahoo.com.br NR 53 TC 3 Z9 3 U1 1 U2 3 PU AMER OCCUPATIONAL THERAPY ASSOC, INC PI BETHESDA PA 4720 MONTGOMERY LANE, BETHESDA, MD 20814-3425 USA SN 0272-9490 J9 AM J OCCUP THER JI Am. J. Occup. Ther. PD JAN-FEB PY 2007 VL 61 IS 1 BP 33 EP 40 PG 8 WC Rehabilitation SC Rehabilitation GA 130EM UT WOS:000243782300004 PM 17302103 ER PT J AU Chua, F Dunsmore, SE Clingen, PH Mutsaers, SE Shapiro, SD Segal, AW Roes, J Laurent, GJ AF Chua, Felix Dunsmore, Sarah E. Clingen, Peter H. Mutsaers, Steven E. Shapiro, Steven D. Segal, Anthony W. Roes, Jurgen Laurent, Geoffrey J. TI Mice lacking neutrophil elastase are resistant to bleomycin-induced pulmonary fibrosis SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID GROWTH-FACTOR-BETA; INTERSTITIAL LUNG-DISEASE; LOWER RESPIRATORY-TRACT; BRONCHOALVEOLAR LAVAGE; TRANSFORMING GROWTH-FACTOR-BETA-1; IMMUNOHISTOCHEMICAL LOCALIZATION; CHRONIC INFLAMMATION; COLLAGEN PRODUCTION; TISSUE FIBROSIS; GENE-EXPRESSION AB Neutrophil elastase is a serine protease stored in the azurophilic granules of leukocytes. It has been implicated in the pathology of several lung diseases and is generally presumed to contribute to the tissue destruction and extracellular matrix damage associated with these conditions. To delineate the role of neutrophil elastase in pulmonary inflammation and fibrosis, neutrophil elastase-null mice were intratracheally instilled with bleomycin. In neutrophil elastase-null mice, biochemical and morphological characteristics of pulmonary fibrosis were attenuated for at least 60 days after bleomycin administration despite a typical response to bleomycin as evidenced by assessment of indices of DNA and cell damage. Neutrophil burden of bleomycin-treated wild-type and neutrophil elastase-null mice was comparable, and marked neutrophilic alveolitis was manifest in bleomycin-treated neutrophil elastase-null mice. An absence of immunostaining for active transforming growth factor (TGF)-beta in lung tissue from bleomycin-treated neutrophil elastase-null mice suggested a defect in TGF-beta activation, which was confirmed by biochemical assessment of TGF-beta levels in bronchoalveolar lavage fluid and lung tissue. These data point to novel and unexpected fibrogenic consequences of neutrophil elastase activity in the inflamed lung. C1 UCL Royal Free & Univ Coll Med Sch, Dept Med, London, England. UCL Royal Free & Univ Coll Med Sch, Dept Oncol, London, England. UCL Royal Free & Univ Coll Med Sch, Dept Immunol & Mol Pathol, London, England. Brigham & Womens Hosp, Dept Med Pulm, Boston, MA 02115 USA. RP Dunsmore, SE (reprint author), NIGMS, 45 Ctr Dr, Bethesda, MD 20892 USA. EM sdunsmore_uk@yahoo.com OI Segal, Anthony/0000-0001-7602-9043 FU Wellcome Trust [061554] NR 50 TC 58 Z9 59 U1 0 U2 3 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 JAN PY 2007 VL 170 IS 1 BP 65 EP 74 DI 10.2353/ajpath.2007.060352 PG 10 WC Pathology SC Pathology GA 122RA UT WOS:000243242900007 PM 17200183 ER PT J AU Gelderblom, H Schmidt, J Londono, D Bai, YH Quandt, J Hornung, R Marques, A Martin, R Cadavid, D AF Gelderblom, Harald Schmidt, Jens Londono, Diana Bai, Yunhong Quandt, Jacqueline Hornung, Ron Marques, Adriana Martin, Roland Cadavid, Diego TI Role of interleukin 10 during persistent infection with the relapsing fever spirochete Borrelia turicatae SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; JARISCH-HERXHEIMER REACTION; BURGDORFERI LIPOPROTEINS; LYME BORRELIOSIS; GENE-EXPRESSION; SURFACE PROTEIN; CYTOKINE; ANTIBODIES; ARTHRITIS; DISEASE AB Relapsing fever is an infection characterized by peaks of spirochetemia attributable to antibody selection against variable serotypes. in the absence of B cells, serotypes cannot be cleared, resulting in persistent infection. We previously identified differences in spirochetemia and disease severity during persistent infection of severe combined immunodeficiency mice with isogenic serotypes 1 (Bt1) or 2 (Bt2) of Borrelia turicatae. To investigate this further, we studied pathogen load, clinical disease, cytokine/chemokine production, and inflammation in mice deficient in B (Igh6(-/-)) or B and T (Rag1(-/-)) cells persistently infected with Bt1 or Bt2. The results showed that Igh6-/- mice, despite lower spirochetemia, had a significantly aggravated disease course compared with Rag1(-/-) mice. Measurement of cytokines revealed a significant positive correlation between pathogen load and interleukin (IL)-10 in blood, brain, and heart. Bt2-infected Rag1(-/-) mice harbored the highest spirochetemia and, at the same time, displayed the highest IL-10 plasma levels. In the brain, Bt1, which was five times more neurotropic than Bt2, caused higher IL-10 production. Activated microglia were the main source of IL-10 in brain. IL-10 injected systemically reduced disease and spirochetemia. The results suggest IL-10 plays a protective role as a down-regulator of inflammation and pathogen load during infection with relapsing fever spirochetes. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurosci, Newark, NJ 07103 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Ctr Emerging Pathogens, Newark, NJ 07103 USA. NIAID, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. NIAID, Natl Inst Neurol Disorders & Stroke, Clin Studies Unit, NIH, Bethesda, MD 20892 USA. SAIC Frederick Inc, Clin Serv Program, Natl Canc Inst Frederick, Frederick, MD USA. RP Cadavid, D (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Neurosci, 185 S Orange Ave,MSB H506, Newark, NJ 07103 USA. EM cadavidi@umdnj.edu RI Schmidt, Jens/B-5791-2013 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 37 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JAN PY 2007 VL 170 IS 1 BP 251 EP 262 DI 10.2353/ajpath.2007.060407 PG 12 WC Pathology SC Pathology GA 122RA UT WOS:000243242900022 PM 17200198 ER PT J AU Tishkoff, SA Reed, FA Froment, A Smith, MW Williams, SM Omar, SA Kotze, MJ Pretorius, GS Ibrahim, M Doumbo, O Thera, M Wambebe, C Dobrin, SE Weber, JL AF Tishkoff, S. A. Reed, F. A. Froment, A. Smith, M. W. Williams, S. M. Omar, S. A. Kotze, M. J. Pretorius, G. S. Ibrahim, M. Doumbo, O. Thera, M. Wambebe, C. Dobrin, S. E. Weber, J. L. TI Ancient population structure and migration in Africa inferred from genome-wide genetic markers SO AMERICAN JOURNAL OF PHYSICAL ANTHROPOLOGY LA English DT Meeting Abstract C1 Univ Maryland, Dept Biol, College Pk, MD 20742 USA. IRD, UR 092, Orleans, France. NCI, Lab Genom Diversity, SAIC, Frederick, MD 21701 USA. Vanderbilt Univ, Ctr Hum Genet Res, Nashville, TN USA. KEMRI, Nairobi, Kenya. Univ Stellenbosch, Div Human Genet, ZA-7505 Tygerberg, South Africa. Univ Khartoum, Dept Mol Biol, Khartoum, Sudan. Univ Bamako, Malaria Res & Training Ctr, Bamako, Mali. Inst Biomed Res, Abuja, Nigeria. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI USA. RI Smith, Michael/B-5341-2012 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0002-9483 J9 AM J PHYS ANTHROPOL JI Am. J. Phys. Anthropol. PY 2007 SU 44 BP 232 EP 232 PG 1 WC Anthropology; Evolutionary Biology SC Anthropology; Evolutionary Biology GA 142NK UT WOS:000244656500746 ER PT J AU Weinrich, M Rosen, BG AF Weinrich, Michael Rosen, Barbara G. TI Musculoskeletal Research Conference Summary Report SO AMERICAN JOURNAL OF PHYSICAL MEDICINE & REHABILITATION LA English DT Editorial Material DE musculoskeletal; research; disabilities; rehabilitation issues C1 NICHHD, Natl Ctr Med Rehabil Res, NIH, Bethesda, MD 20892 USA. CESSI, Interagcy Comm Disabil Res, Mclean, VA USA. RP Weinrich, M (reprint author), NICHHD, Natl Ctr Med Rehabil Res, NIH, 6100 Execut Blvd,Room 2A03,MSC7510, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 1 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0894-9115 J9 AM J PHYS MED REHAB JI Am. J. Phys. Med. Rehabil. PD JAN PY 2007 VL 86 IS 1 SU S BP S1 EP S18 DI 10.1097/PHM.0b013e31802ba3b4 PG 18 WC Rehabilitation; Sport Sciences SC Rehabilitation; Sport Sciences GA 123XV UT WOS:000243331300001 PM 17370368 ER PT J AU Balasubramanyam, A Mersmann, H Jahoor, F Phillips, TM Sekhar, RV Schubert, U Brar, B Iyer, D Smith, EO Takahashi, H Lu, HY Anderson, P Kino, T Henklein, P Kopp, JB AF Balasubramanyam, Ashok Mersmann, Harry Jahoor, Farook Phillips, Terry M. Sekhar, Rajagopal V. Schubert, Ulrich Brar, Baljinder Iyer, Dinakar Smith, E. O'Brian Takahashi, Hideko Lu, Huiyan Anderson, Peter Kino, Tomoshige Henklein, Peter Kopp, Jeffrey B. TI Effects of transgenic expression of HIV-1 Vpr on lipid and energy metabolism in mice SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE human immunodeficiency virus lipodystrophy; glucose; triglycerides; cholesterol; energy expenditure; fat oxidation ID VIRAL PROTEIN-R; IMMUNOAFFINITY CAPILLARY-ELECTROPHORESIS; IMMUNODEFICIENCY-VIRUS INFECTION; CELL-CYCLE ARREST; LIPODYSTROPHY SYNDROME; INHIBITORS; DIFFERENTIATION; PATHOGENESIS; EXPENDITURE; APOPTOSIS AB HIV infection is associated with abnormal lipid metabolism, body fat redistribution, and altered energy expenditure. The pathogenesis of these complex abnormalities is unclear. Viral protein R ( Vpr), an HIV-1 accessory protein, can regulate gene transcription mediated by the glucocorticoid receptor and peroxisome proliferator-activated receptor-gamma and affect mitochondrial function in vitro. To test the hypothesis that expression of Vpr in liver and adipocytes can alter lipid metabolism in vivo, we engineered mice to express Vpr under control of the phosphoenolpyruvate carboxykinase promoter in a tissue-specific and inducible manner and investigated the effects of dietary fat, indinavir, and dexamethasone on energy metabolism and body composition. The transgenic mice expressed Vpr mRNA in white and brown adipose tissues and liver and immunoaffinity capillary electrophoresis revealed that they had free Vpr protein in the plasma. Compared with wild-type ( WT) animals, Vpr mice had lower plasma triglyceride levels after 6 wk ( P < 0.05) but not after 10 wk of a high-fat diet and lower plasma cholesterol levels after 10 wk of high-fat diet ( P < 0.05). Treatment with dexamethasone obviated group differences, whereas indinavir had no significant independent effect on lipids. In the fasted state, Vpr mice had a higher respiratory quotient than WT mice ( P < 0.05). These data provide the first in vivo evidence that HIV-1 Vpr expressed at low levels in adipose tissues and liver can 1) circulate in the blood, 2) regulate lipid and fatty acid metabolism, and 3) alter fuel selection for oxidation in the fasted state. C1 Baylor Coll Med, Translat Metab Unit, Div Endocrinol Diabet & Metab, Dept Med, Houston, TX 77030 USA. Baylor Coll Med, USDA ARS, Childrens Nutr Res Ctr, Dept Pediat, Houston, TX 77030 USA. Ben Taub Gen Hosp, Endocrine Serv, Houston, TX 77030 USA. NIDDKD, Div Engn & Phys Sci, Off Res Sci, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NICHHD, Reprod Biol & Med Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. Univ Erlangen Nurnberg, Inst Clin & Mol Virol, Erlangen, Bavaria, Germany. Humboldt Univ, Inst Biochem, Berlin, Germany. RP Balasubramanyam, A (reprint author), Baylor Coll Med, Translat Metab Unit, Div Endocrinol Diabet & Metab, Dept Med, BCM 700B, Houston, TX 77030 USA. EM ashokb@bcm.tmc.edu OI Kopp, Jeffrey/0000-0001-9052-186X FU Intramural NIH HHS; NIDDK NIH HHS [R01-DK-59537, R01 DK059537] NR 39 TC 16 Z9 16 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 2007 VL 292 IS 1 BP E40 EP E48 DI 10.1152/ajpendo.00163.2006 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 122UZ UT WOS:000243253900006 PM 16882932 ER PT J AU Maggio, M Lauretani, F Ceda, GP Bandinelli, S Basaria, S Paolisso, G Ble, A Egan, JM Metter, EJ Abbatecola, AM Zuliani, G Ruggiero, C Valenti, G Guralnik, JM Ferrucci, L AF Maggio, Marcello Lauretani, Fulvio Ceda, Gian Paolo Bandinelli, Stefania Basaria, Shehzad Paolisso, Giuseppe Ble, Alessandro Egan, Josephine M. Metter, E. Jeffrey Abbatecola, Angela M. Zuliani, Giovanni Ruggiero, Carmelinda Valenti, Giorgio Guralnik, Jack M. Ferrucci, Luigi TI Association of hormonal dysregulation with metabolic syndrome in older women: data from the InCHIANTI study SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE sex hormone-binding globulin; hormonal dysregulation; insulin-like growth factor I; androgens ID POLYCYSTIC-OVARY-SYNDROME; HOMEOSTASIS MODEL ASSESSMENT; BINDING GLOBULIN LEVELS; INSULIN SENSITIVITY; POSTMENOPAUSAL WOMEN; GLUCOSE-TOLERANCE; SERUM; RISK; PREVALENCE; RESISTANCE AB Association of hormonal dysregulation with metabolic syndrome in older women: data from the InCHIANTI study. Am J Physiol Endocrinol Metab 292:E353-E358, 2007. First published September 12, 2006; doi:10.1152/ajpendo.00339.2006. Metabolic syndrome (MetS) is a strong risk factor for type 2 diabetes and cardiovascular disease. Conditions associated with hyperandrogenism are often associated with glucose intolerance and other features of MetS in young women. As the prevalence of MetS increases with age and is probably multifactorial, it is reasonable to hypothesize that age-related changes in androgens and other hormones might contribute to the development of MetS in older persons. However, this hypothesis has never been tested in older women. We hypothesized that high levels of testosterone, dehydroepiandrosterone sulfate (DHEA-S), and cortisol and low levels of sex hormone-binding globulin (SHBG) and IGF-I would be associated with MetS in a representative cohort of older Italian women independently of confounders (including inflammatory markers). After exclusion of participants on hormone replacement therapy and those with a history of bilateral oophorectomy, 512 women (>= 65 yr) had complete data on testosterone, cortisol, DHEA-S, SHBG, fasting insulin, total and free IGF-I, IL-6, and C-reactive protein (CRP). MetS was defined according to ATP-III criteria. Insulin resistance was calculated according to HOMA. MetS was found in 145 women (28.3%). Participants with vs. those without MetS had higher age-adjusted levels of bioavailable testosterone (P < 0.001), IL-6 (P < 0.001), CRP (P < 0.001), and HOMA (P < 0.001) and lower levels of SHBG (P < 0.001). After adjustment for potential confounders, participants with decreased SHBG had an increased risk of MetS (P < 0.0001) vs. those with low SHBG. In a further model including all hormones and confounders, log SHBG was the only independent factor associated with MetS (OR: 0.44, 95% CI 0.21-0.91, P = 0.027). In older women, SHBG is negatively associated with MetS independently of confounders, including inflammatory markers and insulin resistance. Further studies are needed to support the notion that raising SHBG is a potential therapeutic target for prevention and treatment of MetS. C1 Harbor Hosp, NIA ASTRA Unit, Natl Inst Aging, NIH, Baltimore, MD 21225 USA. NIA, Clin Res Branch, NIH, Baltimore, MD USA. Univ Parma, Sch Endocrinol, Sect Geriatr, Dept Internal Med & Biomed Sci, I-43100 Parma, Italy. Johns Hopkins Univ, Sch Med, Bayview Med Ctr, Div Endocriniol,Dept Med, Baltimore, MD USA. Univ Ferrara, Sect Internal Med Gerontol & Geriatr, Dept Clin & Expt med, Ferrara, Italy. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD USA. RP Ferrucci, L (reprint author), Harbor Hosp, NIA ASTRA Unit, Natl Inst Aging, NIH, 3001 S Hanover St, Baltimore, MD 21225 USA. EM ferruccilu@grc.nia.nih.gov RI Perez , Claudio Alejandro/F-8310-2010; Lauretani, Fulvio/K-5115-2016; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Paolisso, Giuseppe/0000-0002-2137-455X; Lauretani, Fulvio/0000-0002-5287-9972; Ceda, Gian Paolo/0000-0002-9648-8295 FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [N01-AG-916413, N01-AG-821336]; NIMHD NIH HHS [R01 MD009164] NR 39 TC 35 Z9 40 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 2007 VL 292 IS 1 BP E353 EP E358 DI 10.1152/ajpendo.00339.2006 PG 6 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 122UZ UT WOS:000243253900046 PM 16968811 ER PT J AU Vgontzas, AN Pejovic, S Zoumakis, E Lin, HM Bixler, EO Basta, M Fang, J Sarrigiannidis, A Chrousos, GP AF Vgontzas, A. N. Pejovic, S. Zoumakis, E. Lin, H. M. Bixler, E. O. Basta, M. Fang, J. Sarrigiannidis, A. Chrousos, G. P. TI Daytime napping after a night of sleep loss decreases sleepiness, improves performance, and causes beneficial changes in cortisol and interleukin-6 secretion SO AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM LA English DT Article DE alertness; sleep deprivation; proinflammatory cytokines; hypothalamic-pituitary-adrenal axis; daytime sleep ID CYTOKINES; DEPRIVATION; RESTRICTION; DISORDERS; ELEVATION; PATTERNS; OBESITY; HUMANS; IL-6; EEG AB Daytime napping after a night of sleep loss decreases sleepiness, improves performance, and causes beneficial changes in cortisol and interleukin-6 secretion. Am J Physiol Endocrinol Metab 292:E253-E261, 2007. First published August 29, 2006; doi:10.1152/ajpendo.00651.2005.- Sleep loss has been associated with increased sleepiness, decreased performance, elevations in inflammatory cytokines, and insulin resistance. Daytime napping has been promoted as a countermeasure to sleep loss. To assess the effects of a 2-h midafternoon nap following a night of sleep loss on postnap sleepiness, performance, cortisol, and IL-6, 41 young healthy individuals (20 men, 21 women) participated in a 7-day sleep deprivation experiment (4 consecutive nights followed by a night of sleep loss and 2 recovery nights). One-half of the subjects were randomly assigned to take a midafternoon nap (1400-1600) the day following the night of total sleep loss. Serial 24-h blood sampling, multiple sleep latency test (MSLT), subjective levels of sleepiness, and psychomotor vigilance task (PVT) were completed on the fourth (predeprivation) and sixth days (postdeprivation). During the nap, subjects had a significant drop in cortisol and IL-6 levels (P < 0.05). After the nap they experienced significantly less sleepiness (MSLT and subjective, P < 0.05) and a smaller improvement on the PVT (P < 0.1). At that time, they had a significant transient increase in their cortisol levels (P < 0.05). In contrast, the levels of IL-6 tended to remain decreased for similar to 8 h (P = 0.1). We conclude that a 2-h midafternoon nap improves alertness, and to a lesser degree performance, and reverses the effects of one night of sleep loss on cortisol and IL-6. The redistribution of cortisol secretion and the prolonged suppression of IL-6 secretion are beneficial, as they improve alertness and performance. C1 Penn State Univ, Coll Med, Dept Psychiat H073, Sleep Res & Treatment Ctr, Hershey, PA 17033 USA. Penn State Univ, Coll Med, Hlth Evaluat Sci, Hershey, PA 17033 USA. NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. Univ Athens, Sch Med, Dept Pediat 1, GR-11527 Athens, Greece. Univ Athens, Sch Med, Unit Endocrinol Metab & Diabet, GR-11527 Athens, Greece. RP Vgontzas, AN (reprint author), Penn State Univ, Coll Med, Dept Psychiat H073, Sleep Res & Treatment Ctr, 500 Univ Dr, Hershey, PA 17033 USA. EM axv3@psu.edu FU NCRR NIH HHS [RR-010732, RR-016499]; NHLBI NIH HHS [HL-64415] NR 40 TC 60 Z9 62 U1 2 U2 10 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1849 J9 AM J PHYSIOL-ENDOC M JI Am. J. Physiol.-Endocrinol. Metab. PD JAN PY 2007 VL 292 IS 1 BP E253 EP E261 DI 10.1152/ajpendo.00651.2005 PG 9 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 122UZ UT WOS:000243253900033 PM 16940468 ER PT J AU Chen, ZG Eggerman, TL Patterson, AP AF Chen, Zhigang Eggerman, Thomas L. Patterson, Amy P. TI ApoB mRNA editing is mediated by a coordinated modulation of multiple apoB mRNA editing enzyme components SO AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY LA English DT Article DE apolipoprotein; development; apolipoprotein B mRNA editing enzyme; apolipoprotein B mRNA editing enzyme-1 complementation; factor; CUG binding protein-2 ID APOBEC-1 COMPLEMENTATION FACTOR; POLYMERASE CHAIN-REACTION; APOLIPOPROTEIN-B; BINDING PROTEIN; MOLECULAR-CLONING; DEVELOPMENTAL REGULATION; CATALYTIC SUBUNIT; MOORING SEQUENCE; SMALL-INTESTINE; GRY-RBP AB Apolipoprotein (apo) B mRNA editing is accomplished by a large multiprotein complex. How these proteins interact to achieve the precise single-nucleotide change induced by this complex remains unclear. We investigated the relationship between altered apoB mRNA editing and changes in editing enzyme components to evaluate their roles in editing regulation. In the mouse fetal small intestine, we found that the dramatic developmental upregulation of apoB mRNA editing from similar to 3% to 88% begins with decreased levels of inhibitory CUG binding protein 2 (CUGBP2) expression followed by increased levels of apoB mRNA editing enzyme (apobec)-1 and apobec-1 complementation factor (ACF) (4 and 8-fold) and then by decreased levels of the inhibitory components glycine-arginine-tyrosine-rich RNA binding protein (GRY-RBP) and heterogeneous nuclear ribonucleoprotein (hnRNP)-C1 (75% and 56%). In contrast, the expression of KH-type splicing regulatory protein (KSRP), apobec-1 binding protein (ABBP) 1, ABBP2, and Bcl-2-associated athanogene 4 (BAG4) were unaltered. In the human intestinal cell line Caco-2, the increase of apoB mRNA editing from similar to 1.7% to similar to 23% was associated with 6- and 3.2-fold increases of apobec-1 and CUGBP2, respectively. In the mouse large intestine, the editing was 48% and had a 2.7- fold relatively greater CUGBP2 level. Caco-2 and the large intestine thus have increased instead of decreased CUGBP2 and a lower level of editing, suggesting that inhibitory CUGBP2 may play a critical role in the magnitude of editing regulation. Short interfering RNA-mediated gene-specific knockdown of CUGBP2, GRY-RBP, and hnRNP-C1 resulted in increased editing in Caco-2 cells, consistent with their known inhibitory function. These data suggest that a coordinated expression of editing components determines the magnitude and specificity of apoB mRNA editing. C1 NIH, Off Biotechnol Act, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIDDKD, Div Diabet Endocrinol & Metab Dis, Bethesda, MD 20892 USA. NHLBI, Bethesda, MD 20892 USA. RP Patterson, AP (reprint author), NIH, Off Biotechnol Act, 6705 Rockledge Dr,Suite 750, Bethesda, MD 20892 USA. EM pattersa@od.nih.gov NR 40 TC 12 Z9 13 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0193-1857 J9 AM J PHYSIOL-GASTR L JI Am. J. Physiol.-Gastroint. Liver Physiol. PD JAN PY 2007 VL 292 IS 1 BP G53 EP G65 DI 10.1152/ajpgi.00118.2006 PG 13 WC Gastroenterology & Hepatology; Physiology SC Gastroenterology & Hepatology; Physiology GA 124VW UT WOS:000243399800007 PM 16920700 ER PT J AU Ghio, AJ Turi, JL Madden, MC Dailey, LA Richards, JD Stonehuerner, JG Morgan, DL Singleton, S Garrick, LM Garrick, MD AF Ghio, Andrew J. Turi, Jennifer L. Madden, Michael C. Dailey, Lisa A. Richards, Judy D. Stonehuerner, Jacqueline G. Morgan, Daniel L. Singleton, Steven Garrick, Laura M. Garrick, Michael D. TI Lung injury after ozone exposure is iron dependent SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE air pollution; lung diseases; ferritin; oxidants; free radicals ID INDUCED AIRWAY HYPERRESPONSIVENESS; BRONCHIAL EPITHELIAL-CELLS; HYDROGEN-PEROXIDE; INFLAMMATION; TOXICITY; RADICALS; RAT; SUPPLEMENTATION; RESPONSIVENESS; NONSMOKERS AB We tested the hypothesis that oxidative stress and biological effect after ozone (O-3) exposure are dependent on changes in iron homeostasis. After O-3 exposure, healthy volunteers demonstrated increased lavage concentrations of iron, transferrin, lactoferrin, and ferritin. In normal rats, alterations of iron metabolism after O-3 exposure were immediate and preceded the inflammatory influx. To test for participation of this disruption in iron homeostasis in lung injury following O-3 inhalation, we exposed Belgrade rats, which are functionally deficient in divalent metal transporter 1 (DMT1) as a means of iron uptake, and controls to O-3. Iron homeostasis was disrupted to a greater extent and the extent of injury was greater in Belgrade rats than in control rats. Nonheme iron and ferritin concentrations were higher in human bronchial epithelial (HBE) cells exposed to O-3 than in HBE cells exposed to filtered air. Aldehyde generation and IL-8 release by the HBE cells was also elevated following O-3 exposure. Human embryonic kidney (HEK 293) cells with elevated expression of a DMT1 construct were exposed to filtered air and O-3. With exposure to O-3, elevated DMT1 expression diminished oxidative stress (i.e., aldehyde generation) and IL-8 release. We conclude that iron participates critically in the oxidative stress and biological effects after O3 exposure. C1 US EPA, Human Studies Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Chapel Hill, NC 27599 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. Natl Toxicol Program, Res Triangle Pk, NC USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27706 USA. SUNY Buffalo, Dept Biochem, Buffalo, NY 14260 USA. RP Ghio, AJ (reprint author), US EPA, Human Studies Div, Natl Hlth & Environm Effects Res Lab, Off Res & Dev, Campus Box 7315,104 Mason Farm Rd, Chapel Hill, NC 27599 USA. EM ghio.andy@epa.gov FU NICHD NIH HHS [K12 HD043494] NR 30 TC 31 Z9 31 U1 0 U2 6 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JAN PY 2007 VL 292 IS 1 BP L134 EP L143 DI 10.1152/ajplung.00534.2005 PG 10 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 124VX UT WOS:000243399900019 PM 16905637 ER PT J AU Simon, A van der Meer, JWM AF Simon, Anna van der Meer, Jos W. M. TI Pathogenesis of familial periodic fever syndromes or hereditary autoinflammatory syndromes SO AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY LA English DT Review DE inflammasome; interleukin-1 beta; nucleotide-binding oligomerization domain-leucine rich repeat proteins; tumor necrosis factor receptor; isoprenoid pathway ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; MEVALONATE KINASE-DEFICIENCY; MULTISYSTEM INFLAMMATORY DISEASE; INTERLEUKIN-1 RECEPTOR ANTAGONIST; BACTERIAL MURAMYL DIPEPTIDE; INTESTINAL EPITHELIAL-CELLS; ALDRICH-SYNDROME PROTEIN; BLOOD MONONUCLEAR-CELLS; INNATE IMMUNE-SYSTEM AB Familial periodic fever syndromes, otherwise known as hereditary autoinflammatory syndromes, are inherited disorders characterized by recurrent episodes of fever and inflammation. The general hypothesis is that the innate immune response in these patients is wrongly tuned, being either too sensitive to very minor stimuli or turned off too late. The genetic background of the major familial periodic fever syndromes has been unraveled, and through research into the pathophysiology, a clearer picture of the innate immune system is emerging. After an introduction on fever, interleukin-1 beta and inflammasomes, which are involved in the majority of these diseases, this manuscript offers a detailed review of the pathophysiology of the cryopyrin-associated periodic syndromes, familial Mediterranean fever, the syndrome of pyogenic arthritis, pyoderma gangrenosum and acne, Blau syndrome, TNF-receptor-associated periodic syndrome and hyper-IgD and periodic fever syndrome. Despite recent major advances, there are still many questions to be answered regarding the pathogenesis of these disorders. C1 NIAMSD, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA. Radboud Univ Nijmegen, Med Ctr, Dept Gen Internal Med, Nijmegen, Netherlands. RP Simon, A (reprint author), NIAMSD, Genet & Genom Branch, NIH, Bldg 10,Rm 9N214 MSC 1820 10 Ctr Dr, Bethesda, MD 20892 USA. EM simona2@mail.nih.gov RI Simon, Anna/D-3757-2009; van der Meer, Jos/C-8521-2013 OI Simon, Anna/0000-0002-6141-7921; van der Meer, Jos/0000-0001-5120-3690 NR 154 TC 63 Z9 64 U1 0 U2 3 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 JAN PY 2007 VL 292 IS 1 BP R86 EP R98 DI 10.1152/ajpregu.00504.2006 PG 13 WC Physiology SC Physiology GA 121QK UT WOS:000243171900007 PM 16931648 ER PT J AU Chen, LM Kim, SM Oppermann, M Faulhaber-Walter, R Huang, YN Mizel, D Chen, M Lopez, MLS Weinstein, LS Gomez, RA Briggs, JP Schnermann, J AF Chen, Limeng Kim, Soo Mi Oppermann, Mona Faulhaber-Walter, Robert Huang, Yuning Mizel, Diane Chen, Min Sequeira Lopez, Maria Luisa Weinstein, Lee S. Gomez, R. Ariel Briggs, Josie P. Schnermann, Jurgen TI Regulation of renin in mice with Cre recombinase-mediated deletion of G protein Gs alpha in juxtaglomerular cells SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE juxtaglomerular granular cell culture; furosemide; hydralazine; aldosterone; cyclooxygenase 2; urine concentration ID MESSENGER-RNA STABILITY; CYCLOOXYGENASE-2 EXPRESSION; ANGIOTENSIN SYSTEM; KNOCKOUT MICE; MACULA DENSA; SECRETION; GENE; INHIBITION; RECEPTOR; CAMP AB By crossing mice with expression of Cre recombinase under control of the endogenous renin promoter (Sequeira Lopez ML, Pentz ES, Nomasa T, Smithies O, Gomez RA. Dev Cell 6: 719 - 728, 2004) with mice in which exon 1 of the Gnas gene was flanked by loxP sites (Chen M, Gavrilova O, Liu J, Xie T, Deng C, Nguyen AT, Nackers LM, Lorenzo J, Shen L, Weinstein LS. Proc Natl Acad Sci USA), we generated animals with preferential and nearly complete excision of Gs alpha in juxtaglomerular granular (JG) cells. Compared with wild-type animals, mice with conditional Gs alpha deficiency had markedly reduced basal levels of renin expression and very low plasma renin concentrations. Furthermore, the acute release responses to furosemide, hydralazine, and isoproterenol were virtually abolished. Consistent with a state of primary renin depletion, Gs alpha-deficient mice had reduced arterial blood pressure, reduced levels of aldosterone, and a low glomerular filtration rate. Renin content and renin secretion of JG cells in primary culture were drastically reduced, and the stimulatory response to the addition of PGE2 or isoproterenol was eliminated. Unexpectedly, Gs alpha recombination was also observed in the renal medulla, and this was associated with a vasopressin-resistant concentrating defect. Our study shows that Cre recombinase under control of the renin promoter can be used for the excision of floxed targets from JG cells. We conclude that Gs alpha-mediated signal transduction is essential and nonredundant in the control of renin synthesis and release. C1 NIDDK, NIH, Bethesda, MD 20892 USA. Univ Virginia, Charlottesville, VA 22903 USA. RP Schnermann, J (reprint author), NIDDK, NIH, Bldg 10,Room 4 D51,10 Ctr Dr,MSC-1370, Bethesda, MD 20892 USA. EM jurgens@intra.niddk.nih.gov RI Briggs, Josephine/B-9394-2009 OI Briggs, Josephine/0000-0003-0798-1190 FU Intramural NIH HHS; NHLBI NIH HHS [HL-66242] NR 36 TC 53 Z9 56 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 JAN PY 2007 VL 292 IS 1 BP F27 EP F37 DI 10.1152/ajprenal.00193.2006 PG 11 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 124DB UT WOS:000243346300005 PM 16822937 ER PT J AU Curthoys, NP Taylor, L Hoffert, JD Knepper, MA AF Curthoys, Norman P. Taylor, Lynn Hoffert, Jason D. Knepper, Mark A. TI Proteomic analysis of the adaptive response of rat renal proximal tubules to metabolic acidosis SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE difference gel electrophoresis; mass spectrometry; phosphoenolpyruvate carboxykinase; glutaminase; mRNA stabilization ID PHOSPHATE-DEPENDENT GLUTAMINASE; CARBOXYKINASE MESSENGER-RNA; GENE-EXPRESSION; BASE-BALANCE; ARTERIOVENOUS DIFFERENCES; BINDING PROTEINS; KIDNEY; DEHYDROGENASE; IDENTIFICATION; ACTIVATION AB Proximal tubules were isolated from control and acidotic rats by collagenase digestion and Percoll density gradient centrifugation. Western blot analysis indicated that the tubules were similar to 95% pure. The samples were analyzed by two-dimensional difference gel electrophoresis (DIGE) and DeCyder software was used to quantify the temporal changes in proteins that exhibit enhanced or reduced expression. The mass-to-charge ratios and the amino acid sequences of the recovered tryptic peptides were determined by MALDI-TOF/TOF mass spectrometry and the proteins were identified using Mascot software. This analysis confirmed the well-characterized adaptive responses in glutaminase (GA), glutamate dehydrogenase (GDH), and phosphoenolpyruvate carboxykinase (PEPCK). This approach also identified 17 previously unrecognized proteins that are increased with ratios of 1.5 to 5.6 and 16 proteins that are decreased with ratios of 0.67 to 0.03 when tubules from 7-day acidotic vs. control rats were compared. Some of these changes were confirmed by Western blot analysis. Temporal studies identified proteins that were induced either with rapid kinetics similar to PEPCK or with more gradual profiles similar to GA and GDH. All of the mRNAs that encode the latter proteins contain an AU sequence that is homologous to the pH response element found in GA mRNA. Thus selective mRNA stabilization may be a predominant mechanism by which protein expression is increased in response to acidosis. C1 Colorado State Univ, Dept Biochem & Mol Biol, Ft Collins, CO 80523 USA. NHLBI, Lab Kidney & Electrolyte Metab, NIH, Bethesda, MD 20892 USA. RP Curthoys, NP (reprint author), Colorado State Univ, Dept Biochem & Mol Biol, Campus Delivery 1870, Ft Collins, CO 80523 USA. EM Norman.Curthoys@ColoState.edu FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999]; NHLBI NIH HHS [ZO1-HL-01282-KE]; NIDDK NIH HHS [DK-43704, DK-37124] NR 45 TC 40 Z9 40 U1 0 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X EI 1522-1466 J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2007 VL 292 IS 1 BP F140 EP F147 DI 10.1152/ajprenal.00217.2006 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 124DB UT WOS:000243346300018 PM 16896179 ER PT J AU Kim, SM Chen, LM Mizel, D Huang, YG Briggs, JP Schnermann, J AF Kim, Soo Mi Chen, Limeng Mizel, Diane Huang, Yuning G. Briggs, Josie P. Schnermann, Jurgen TI Low plasma renin and reduced renin secretory responses to acute stimuli in conscious COX-2-deficient mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE furosemide; hydralazine; isoproterenol; quinaprilate; candesartan; genetic background; cyclooxygenase-2 ID MACULA DENSA; INHIBITION; EXPRESSION; CYCLOOXYGENASE-2; HYPERTENSION; RELEASE; LACKING; SYSTEM; DIETS; RAT AB Low plasma renin and reduced renin secretory responses to acute stimuli in conscious COX-2-deficient mice. Am J Physiol Renal Physiol 292: F415-F422, 2007. First published September 5, 2006; doi:10.1152/ajprenal.00317.2006.-In the current experiments, we determined the response of plasma renin concentration (PRC) to acute intraperitoneal administration of furosemide (40 mg/kg), hydralazine (2 mg/kg), isoproterenol (10 mg/kg), candesartan (50 mu g), or quinaprilate (50 mu g) in conscious wild-type (WT) and cyclooxygenase (COX)-2-/- mice on three different genetic backgrounds (mixed, C57BL/6, 129J). PRC was measured in plasma obtained by tail vein puncture. Basal PRC was significantly lower in COX-2-/- than WT mice independent of genetic background (51, 10, and 17% of WT in mixed, 129J, and C57BL/6). All five acute interventions caused significant increases of PRC in both COX-2-/- and -/- mice, but the response was consistently less in COX-2-deficient mice (e.g., Delta PRC in ng ANG I center dot ml(-1)center dot h(-1) caused by furosemide, isoproterenol, hydralazine, quinaprilate, or candesartan 4,699 +/- 544, 3,534 +/- 957, 2,522 +/- 369, 9,453 +/- 1,705, 66,455 +/- 21,938 in 129J WT, and 201 +/- 78, 869 +/- 275, 140 +/- 71, 902 +/- 304, 2,660 +/- 954 in 129J COX-2-/-). A low-NaCl diet and enalapril for 1 wk caused a 14-fold elevation of PRC in COX-2-/- mice and was associated with a greatly increased PRC response to acute furosemide (Delta PRC 201 +/- 78 before and 15,984 +/- 2,397 after low Na/enalapril). As measured by radiotelemetry, blood pressure and heart rate responses to furosemide, hydralazine, isoproterenol, candesartan, or quinaprilate were not different between COX-2 genotypes. In conclusion, chronic absence of COX-2 reduces renin expression, release, and PRC and is associated with a reduced ability to alter PRC during acute stimulation regardless of the nature of the stimulus. COX-2 activity does not appear to be a mandatory and specific requirement for furosemide-stimulated renin secretion. C1 Natl Inst Diab & Digest & Kidney Dis, NIH, Bethesda, MD 20892 USA. RP Schnermann, J (reprint author), Natl Inst Diab & Digest & Kidney Dis, NIH, Bldg 10,Rm 4D51,10 Ctr Dr MSC 1370, Bethesda, MD 20892 USA. EM jurgens@intra.niddk.nih.gov FU Intramural NIH HHS NR 24 TC 40 Z9 45 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2007 VL 292 IS 1 BP F415 EP F422 DI 10.1152/ajprenal.00317.2006 PG 8 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 124DB UT WOS:000243346300047 PM 16954340 ER PT J AU Nielsen, J Kwon, TH Frokiaer, J Knepper, MA Nielsen, S AF Nielsen, Jakob Kwon, Tae-Hwan Frokiaer, Jorgen Knepper, Mark A. Nielsen, Soren TI Maintained ENaC trafficking in aldosterone-infused rats during mineralocorticoid and glucocorticoid receptor blockade SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE epithelial sodium channel; mineralocorticoid receptor ID EPITHELIAL SODIUM-CHANNEL; NA-CL COTRANSPORTER; ANGIOTENSIN-II; COLLECTING DUCT; INDUCED PROTEIN; KNOCKOUT MICE; GAMMA-SUBUNIT; K-ATPASE; EXPRESSION; KIDNEY AB Maintained ENaC trafficking in aldosterone-infused rats during mineralocorticoid and glucocorticoid receptor blockade. Am J Physiol Renal Physiol 292: F382-F394, 2007. First published August 15, 2006; doi:10.1152/ajprenal.00212.2005.-Aldosterone induces redistribution of epithelial sodium channel ( ENaC) to the apical plasma membrane from intracellular vesicles in renal connecting tubule (CNT) and cortical collecting duct (CCD). The role of the classical mineralocorticoid receptor (MR) in ENaC trafficking is still debated. We examined whether the MR antagonist spironolactone affects ENaC regulation in the kidney cortex of aldosterone-infused rats. Aldosterone infusion for 7 days resulted in a plasma aldosterone concentration in the high physiological range (3 to 4 nM). Aldosterone infusion decreased plasma K(+) concentration compared with untreated control rats. Cotreatment with spironolactone completely blocked the aldosterone-induced decrease in plasma K(+). Immunoblotting and immunohistochemistry showed increased protein abundance of Na-K-ATPase alpha(1)-subunit and NCC in the kidney cortex, in response to aldosterone infusion that was blocked by spironolactone. In contrast, aldosterone-induced redistribution of ENaC subunits from the cytoplasm to the apical plasma membrane domain in CNT and CCD was unaffected by spironolactone. Immunoblotting of alpha ENaC showed increased protein abundance in aldosterone-infused rats that was not blocked by spironolactone treatment. To exclude possible glucocorticoid receptor (GR)-mediated effects of aldosterone, we treated aldosterone-infused rats with both spironolactone and the GR antagonist RU486. Combined MR and GR blockade prevented neither ENaC trafficking nor the upregulation of alpha ENaC protein abundance in aldosterone-infused rats. We provide new evidence for ENaC trafficking occurring independent of MR and GR activation in aldosterone-infused rats. C1 Univ Aarhus, Inst Anat, Water & Salt Res Ctr, DK-8000 Aarhus, Denmark. Univ Aarhus, Inst Anat, Aarhus, Denmark. Univ Aarhus, Inst Clin Med, Aarhus, Denmark. Kyungpook Natl Univ, Sch Med, Dept Biochem & Cell Biol, Taegu, South Korea. Nalt Heart Lung & Blood Inst, Lab Kidney & Electrolyte Metab, NIH, Bethesda, MD USA. RP Nielsen, S (reprint author), Univ Aarhus, Inst Anat, Water & Salt Res Ctr, Bldg 233, DK-8000 Aarhus, Denmark. EM sn@ana.au.dk FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 44 TC 25 Z9 26 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JAN PY 2007 VL 292 IS 1 BP F382 EP F394 DI 10.1152/ajprenal.00212.2005 PG 13 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 124DB UT WOS:000243346300044 PM 16912064 ER PT J AU Wever, KE Masereeuw, R Miller, DS Hang, XM Flik, G AF Wever, Kim E. Masereeuw, Rosalinde Miller, David S. Hang, Xiao M. Flik, Gert TI Endothelin and calciotropic hormones share regulatory pathways in multidrug resistance protein 2-mediated transport SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE parathyroid hormone; parathyroid hormone-related protein; stanniocalcin; xenobiotic transport; fluorescein-methotrexate; Sparus auratus; gilthead sea bream; Fundulus heteroclitus; killifish ID RENAL PROXIMAL TUBULE; CONJUGATE EXPORT PUMP; ORGANIC ANION SECRETION; PARATHYROID-HORMONE; CALCIUM LEVELS; DRUG EFFLUX; OREOCHROMIS-MOSSAMBICUS; MRP2-MEDIATED TRANSPORT; GADUS-MORHUA; FRESH-WATER AB The kidney of vertebrates plays a key role in excretion of endogenous waste products and xenobiotics. Active secretion in the proximal nephron is at the basis of this excretion, mediated by carrier proteins including multidrug resistance protein 2 (Mrp2). We previously showed that Mrp2 function is reduced by endothelin-1 (ET-1) through a basolateral B-type receptor, nitric oxide (NO), cGMP, and PKC (Notenboom S, Miller DS, Smits P, Russel FGM, Masereeuw R. Am J Physiol Renal Physiol 282: F458 - F464, 2002; Notenboom S, Miller DS, Smits P, Russel FG, Masereeuw R. Am J Physiol Renal Physiol 287: F33 - F38, 2004). This pathway was rapidly activated by several nephrotoxicants and appeared to be calcium dependent. In the present study, we studied the effect of the calciotropic hormones parathyroid hormone (PTH), PTH-related protein (PTHrP), and stanniocalcin (STC) to interfere with ET-regulated Mrp2 transport. Like ET-1, PTH reduces Mrp-2-mediated transport by 40% in killifish renal proximal tubules. When given in combination, an additive effect was seen, which is partially reversed by the PKC inhibitor calphostin C. Recombinant PTHrP shows a comparable inhibitory effect, which is concentration dependent and additive to the inhibition by ET. STC fully reverses PTHrP-inhibited transport as does a guanylyl cyclase inhibitor. Finally, to confirm PTHrP bioactivity in a homologous assay, we performed immunolocalization and transport studies in sea bream kidney tubules. Mrp2 immunoreactivity was observed in similar to 40% of the tubules and is associated with the brush-border and apical plasma membrane of cells. Both proximal tubules and distal (collecting) tubules express the antigen. A highly significant 40% inhibition of Mrp2-mediated transport was observed with PTHrP in sea bream tubules. In conclusion, ET-regulated Mrp2 transport is influenced by calciotropic hormones and involves PKC and cGMP signaling. C1 Radboud Univ Nijmegen, Fac Sci, Inst Neurosci, Dept Anim Physiol, NL-6525 ED Nijmegen, Netherlands. Nijmegen Ctr Mol Life, Dept Pharmacol & Toxicol, NL-6525 ED Nijmegen, Netherlands. Radboud Univ Nijmegen, Dept Pharmacol & Toxicol, Med Ctr, NL-6525 ED Nijmegen, Netherlands. Mt Desert Isl Biol Lab, Salsbury Cove, ME USA. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC USA. Univ Manchester, Fac Life Sci, Manchester M13 9PL, Lancs, England. Dalian Maritime Univ, Inst Environm Syst Biol, Dalian, Peoples R China. RP Flik, G (reprint author), Radboud Univ Nijmegen, Fac Sci, Inst Neurosci, Dept Anim Physiol, Toernooiveld 1, NL-6525 ED Nijmegen, Netherlands. EM G.Flik@science.ru.nl RI Flik, Gert/C-8229-2011; Masereeuw, Roos/N-3582-2014; Wever, Kimberley/D-9705-2016 OI Flik, Gert/0000-0001-9285-7957; Wever, Kimberley/0000-0003-3635-3660 NR 58 TC 8 Z9 9 U1 2 U2 4 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 JAN PY 2007 VL 292 IS 1 BP F38 EP F46 DI 10.1152/ajprenal.00479.2005 PG 9 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 124DB UT WOS:000243346300006 PM 16912062 ER PT J AU Fuemmeler, BF Baffi, C Masse, LC Atienza, AA Evans, WD AF Fuemmeler, Bernard F. Baffi, Charlie Masse, Louise C. Atienza, Audie A. Evans, W. Doug TI Employer and healthcare policy interventions aimed at adult obesity SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID CHILDHOOD OBESITY; UNITED-STATES; PERCEPTIONS; SELECTION; COST; LIFE AB Background: Increasing rates of obesity in the population have made prevention a high public health priority. Policy strategies for curtailing obesity have been recommended, yet there has been little research on the degree of public support for policy-level interventions. Methods: Participants for this study included 1139 respondents who were surveyed as part of the Research Triangle Institute Obesity Telephone Survey conducted in September 2004. Participants were asked to indicate to what degree they favor specific healthcare and work policy strategies for treating and preventing adult obesity. Participants were also asked about their beliefs regarding the causes of obesity. Results: A majority (85%) favored a policy change strategy that offered employers tax breaks if they provided adequate exercise facilities in the workplace. Seventy-three percent favored a move by healthcare companies to require obesity treatment and prevention. The same proportion (72%) favored beneficiary discounts by employers or healthcare companies to motivate individuals to maintain or move toward a healthy weight. Majorities endorsed a lack of willpower and the cost of healthy food as causes. Nearly two thirds did not believe genes or lack of knowledge was related to obesity in society, and the sample was split with regard to the belief that obesity is caused by society. Conclusions: The findings suggest that there is strong support for healthcare and employment policies in obesity prevention and treatment. These findings may be important to policymakers in developing population-based strategies to prevent obesity. C1 NCI, Bethesda, MD 20892 USA. Res Triangle Inst, Washington, DC USA. RP Fuemmeler, BF (reprint author), Duke Univ, Med Ctr, Dept Community & Family Med, DUMC 2914, Durham, NC 27710 USA. EM bernard.fuemmeler@duke.edu NR 20 TC 12 Z9 12 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JAN PY 2007 VL 32 IS 1 BP 44 EP 51 DI 10.1016/j.amepre.2006.09.003 PG 8 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 130DZ UT WOS:000243780900007 PM 17218190 ER PT J AU Wang, PS Sherrill, J Vitiello, B AF Wang, Philip S. Sherrill, Joel Vitiello, Benedetto TI Unmet need for services and interventions among adolescents with mental disorders SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Editorial Material ID PSYCHIATRIC-DISORDERS; SOCIAL-CONSEQUENCES C1 NIMH, Div Serv & Intervent Res, Rockville, MD 20852 USA. RP Wang, PS (reprint author), NIMH, Div Serv & Intervent Res, 6001 Execut Blvd,Room 7141 MSC 9629, Rockville, MD 20852 USA. EM wangphi@mail.nih.gov NR 9 TC 26 Z9 26 U1 2 U2 3 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 JAN PY 2007 VL 164 IS 1 BP 1 EP 3 DI 10.1176/appi.ajp.164.1.1 PG 3 WC Psychiatry SC Psychiatry GA 122VX UT WOS:000243256400001 PM 17202533 ER PT J AU Goldstein, RZ Alia-Klein, N Tomasi, D Zhang, L Cottone, LA Maloney, T Telang, F Caparelli, EC Chang, L Ernst, T Samaras, D Squires, NK Volkow, ND AF Goldstein, Rita Z. Alia-Klein, Nelly Tomasi, Dardo Zhang, Lei Cottone, Lisa A. Maloney, Thomas Telang, Frank Caparelli, Elisabeth C. Chang, Linda Ernst, Thomas Samaras, Dimitris Squires, Nancy K. Volkow, Nora D. TI Is decreased prefrontal cortical sensitivity to monetary reward associated with impaired motivation and self-control in cocaine addiction? SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the American-College-Neuropsychopharmacology CY DEC 11-15, 2005 CL Waikoloa, HI SP Vanderbilt Univ, Sch Med, Dept Psychiat ID HUMAN ORBITOFRONTAL CORTEX; WHITE-MATTER INTEGRITY; HUMAN BRAIN; ACTIVATION; INVOLVEMENT; FMRI; METHYLPHENIDATE; EXPERIENCE; DEPENDENCE; RESPONSES AB Objective: This study attempted to examine the brain's sensitivity to monetary rewards of different magnitudes in cocaine abusers and to study its association with motivation and self-control. Method: Sixteen cocaine abusers and 13 matched healthy comparison subjects performed a forced-choice task under three monetary value conditions while brain activation was measured with functional magnetic resonance imaging. Objective measures of state motivation were assessed by reaction time and accuracy, and subjective measures were assessed by self-reports of task engagement. Measures of trait motivation and self-control were assessed with the Multidimensional Personality Questionnaire. Results: The cocaine abusers demonstrated an overall reduced regional brain responsivity to differences between the monetary value conditions. Also, in comparison subjects but not in cocaine abusers, reward-induced improvements in performance were associated with self-reports of task engagement, and money-induced activations in the lateral prefrontal cortex were associated with parallel activations in the orbitofrontal cortex. For cocaine abusers, prefrontal cortex sensitivity to money was instead associated with motivation and self-control. Conclusions: These findings suggest that in cocaine addiction 1) activation of the corticolimbic reward circuit to gradations of money is altered; 2) the lack of a correlation between objective and subjective measures of state motivation may be indicative of disrupted perception of motivational drive, which could contribute to impairments in self-control; and 3) the lateral prefrontal cortex modulates trait motivation and deficits in self-control, and a possible underlying mechanism may encompass a breakdown in prefrontal-orbitofrontal cortical communication. C1 Brookhaven Natl Lab, Upton, NY 11973 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Univ Hawaii, John A Burns Sch Med, Honolulu, HI 96822 USA. NIDA, Bethesda, MD 20892 USA. RP Goldstein, RZ (reprint author), Brookhaven Natl Lab, POB 5000, Upton, NY 11973 USA. EM rgoldstein@bnl.gov RI Tomasi, Dardo/J-2127-2015 FU NCRR NIH HHS [5-M01-RR-10710, M01 RR010710, M01 RR010710-070110]; NIAAA NIH HHS [AA/OD09481-04, R01 AA009481-06]; NIDA NIH HHS [1K23-DA-15517-01, DA-06891-06, K02-DA-16991, K23 DA015517, K23 DA015517-01, K24-DA-16170, R01 DA006891, R01 DA006891-03, R03 DA017070, R03 DA017070-01, R03-DA-017070-01] NR 41 TC 141 Z9 144 U1 2 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 JAN PY 2007 VL 164 IS 1 BP 43 EP 51 DI 10.1176/appi.ajp.164.1.43 PG 9 WC Psychiatry SC Psychiatry GA 122VX UT WOS:000243256400012 PM 17202543 ER PT J AU Leibenluft, E Rich, BA Vinton, DT Nelson, EE Fromm, SJ Berghorst, LH Joshi, P Robb, A Schachar, RJ Dickstein, DP McClure, EB Pine, DS AF Leibenluft, Ellen Rich, Brendan A. Vinton, Deborah T. Nelson, Eric E. Fromm, Stephen J. Berghorst, Lisa H. Joshi, Paramjit Robb, Adelaide Schachar, Russell J. Dickstein, Daniel P. McClure, Erin B. Pine, Daniel S. TI Neural circuitry engaged during unsuccessful motor inhibition in pediatric bipolar disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; FACIAL EXPRESSIONS; PREFRONTAL CORTEX; BRAIN ACTIVATION; ERROR-DETECTION; ADOLESCENTS; MANIA; FMRI; SCHIZOPHRENIA; ABNORMALITIES AB Objective: Deficits in motor inhibition may contribute to impulsivity and irritability in children with bipolar disorder. Studies of the neural circuitry engaged during failed motor inhibition in pediatric bipolar disorder may increase our understanding of the pathophysiology of the illness. The authors tested the hypothesis that children with bipolar disorder and comparison subjects would differ in ventral prefrontal cortex, striatal, and anterior cingulate activation during unsuccessful motor inhibition. They also compared activation in medicated versus unmedicated children with bipolar disorder and in children with bipolar disorder and attention deficit hyperactivity disorder ( ADHD) versus those with bipolar disorder without ADHD. Method: The authors conducted an event-related functional magnetic resonance imaging study comparing neural activation in children with bipolar disorder and healthy comparison subjects while they performed a motor inhibition task. The study group included 26 children with bipolar disorder ( 13 unmedicated and 15 with ADHD) and 17 comparison subjects matched by age, gender, and IQ. Results: On failed inhibitory trials, comparison subjects showed greater bilateral striatal and right ventral prefrontal cortex activation than did patients. These deficits were present in unmedicated patients, but the role of ADHD in mediating them was unclear. Conclusions: In relation to comparison subjects, children with bipolar disorder may have deficits in their ability to engage striatal structures and the right ventral prefrontal cortex during unsuccessful inhibition. Further research should ascertain the contribution of ADHD to these deficits and the role that such deficits may play in the emotional and behavioral dysregulation characteristic of bipolar disorder. C1 NIMH, Emot & Dev Branch, Mood & Anxiety Disorders Program, NIH,Hlth & Human Serv, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, Dept Psychol, Boston, MA 02115 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Univ Toronto, Dept Psychiat, Toronto, ON, Canada. Hosp Sick Children, Res Inst, Toronto, ON M5G 1X8, Canada. Georgia State Univ, Dept Psychol, Atlanta, GA 30303 USA. RP Leibenluft, E (reprint author), NIMH, Emot & Dev Branch, Mood & Anxiety Disorders Program, NIH,Hlth & Human Serv, Bldg 15K,MSC 2670, Bethesda, MD 20892 USA. EM leibs@mail.nih.gov RI Nelson, Eric/B-8980-2008; Dickstein, Daniel/L-3210-2016; OI Nelson, Eric/0000-0002-3376-2453; Dickstein, Daniel/0000-0003-1647-5329; Schachar, Russell/0000-0002-2015-4395 NR 40 TC 106 Z9 108 U1 1 U2 6 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 JAN PY 2007 VL 164 IS 1 BP 52 EP 60 DI 10.1176/appi.ajp.164.1.52 PG 9 WC Psychiatry SC Psychiatry GA 122VX UT WOS:000243256400013 PM 17202544 ER PT J AU Barnett, JH Heron, J Ring, SM Golding, J Goldman, D Xu, K Jones, PB AF Barnett, Jennifer H. Heron, Jon Ring, Susan M. Golding, Jean Goldman, David Xu, Ke Jones, Peter B. TI Gender-specific effects of the catechol-O-methyltransferase Val(108)/(158)Met polymorphism on cognitive function in children SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID GENE POLYMORPHISM; BRAIN-DEVELOPMENT; ADOLESCENT BRAIN; MET GENOTYPE; COMT GENE; SCHIZOPHRENIA; ASSOCIATION; PERFORMANCE; ABILITY; MEMORY AB Objective: The study aimed to determine the cognitive effect of the Val(108)/(158)Met polymorphism in the catechol-O-methyltransferase ( COMT) gene in children before and during puberty. This polymorphism affects cognitive function in healthy adults and may contribute to risk for schizophrenia. Method: COMT genotype was determined for 8,707 children from the Avon Longitudinal Study of Parents and Children ( ALSPAC), a geographically defined general population cohort of children born between April 1, 1991, and Dec. 31, 1992, in the southwest of England. Fourteen measures of cognitive function-including working memory, verbal and motor inhibition, attentional control, and IQ-were assessed at ages 8 and 10 years. Any pubertal development at age 9 years was reported by parents. Effects of COMT genotype on cognition and interactions with gender and puberty were assessed using general linear models. Results: In boys, genotype significantly affected executive function and explained up to 10 points normal variation in verbal IQ. The effects on IQ were significantly greater in pubertal than in prepubertal boys. In girls, there were no significant effects of genotype on cognition. Conclusions: This common polymorphism may be one of the genes of small effect that contribute to normal variation in IQ. The gender-specific nature of the effect and its possible interaction with puberty may be relevant to both normal cognitive and brain development and to abnormal development in disorders such as schizophrenia. C1 Univ Cambridge, Dept Psychiat, Cambridge CB2 2QQ, England. Univ Bristol, Div Child Hlth, Unit Pediat & Perinatal Epidemiol, Bristol BS8 1TH, Avon, England. NIAAA, Neurogenet Lab, Bethesda, MD USA. RP Barnett, JH (reprint author), Univ Cambridge, Addenbrookes Hosp, Dept Psychiat, Box 189, Cambridge CB2 2QQ, England. EM jhb32@cam.ac.uk RI Heron, Jon/D-5884-2011; Goldman, David/F-9772-2010; OI Heron, Jon/0000-0001-6199-5644; Goldman, David/0000-0002-1724-5405; Jones, Peter/0000-0002-0387-880X FU Intramural NIH HHS; Medical Research Council [G9815508]; Wellcome Trust NR 45 TC 83 Z9 88 U1 3 U2 6 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 JAN PY 2007 VL 164 IS 1 BP 142 EP 149 DI 10.1176/appi.ajp.164.1.142 PG 8 WC Psychiatry SC Psychiatry GA 122VX UT WOS:000243256400025 PM 17202556 ER PT J AU Volkow, ND Wang, GJ Fowler, JS Telang, F Jayne, M Wong, C AF Volkow, Nora D. Wang, Gene-Jack Fowler, Joanna S. Telang, Frank Jayne, Millard Wong, Christopher TI Stimulant-induced enhanced sexual desire as a potential contributing factor in HIV transmission SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article ID HUMAN BRAIN; DOPAMINE; BEHAVIOR; METHYLPHENIDATE; METHAMPHETAMINE; COCAINE; AMPHETAMINE; USERS; MEN AB Objective: Stimulant abuse is associated with an increased risk of contracting human immunodeficiency virus ( HIV). Although sharing of contaminated needles is one of the routes by which HIV is spread, noninjection abusers are also at high risk. The authors investigated the effect of the stimulant drug methylphenidate ( given intravenously) on sexual desire as a possible contributing factor to risky sexual behavior associated with the contraction of HIV. Method: The effects of intravenous methylphenidate ( 0.5 mg/kg) on self-reports of sexual desire ( rated from 0-10) were evaluated in 39 comparison subjects and 39 cocaine abusers. Results: Intravenous methylphenidate significantly increased self-reports of sexual desire in comparison subjects ( 1.4 versus 3.7) and cocaine abusers ( 2.8 versus 4.8). Conclusions: Stimulant-induced enhancement of sexual desire could be one mechanism by which stimulant drugs such as cocaine and methamphetamine increase the risk for HIV transmission even when they are not injected. C1 NIDA, Bethesda, MD 20892 USA. NIAAA, Lab Neuroimaging, Bethesda, MD USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. Brookhaven Natl Lab, Dept Chem, Upton, NY 11973 USA. RP Volkow, ND (reprint author), NIDA, 6001 Execut Blvd,Rm 5274, Bethesda, MD 20892 USA. EM nvolkow@nida.nih.gov FU Intramural NIH HHS NR 17 TC 70 Z9 70 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 JAN PY 2007 VL 164 IS 1 BP 157 EP U7 DI 10.1176/appi.ajp.164.1.157 PG 4 WC Psychiatry SC Psychiatry GA 122VX UT WOS:000243256400028 PM 17202559 ER PT J AU Boyce, CA Cain, VS AF Boyce, Cheryl A. Cain, Virginia S. TI Disentangling health disparities through national surveys SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Editorial Material C1 NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Dept Hlth & Human Serv, Atlanta, GA USA. RP Boyce, CA (reprint author), NIMH, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. NR 0 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 JAN PY 2007 VL 97 IS 1 BP 10 EP 10 DI 10.2105/AJPH.2006.103960 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 123QO UT WOS:000243310600003 ER PT J AU Fest, S Aldo, PB Abrahams, VM Visintin, I Alvero, A Chen, R Chavez, SL Romero, R Mor, G AF Fest, Stefan Aldo, Paulomi B. Abrahams, V. M. Visintin, I. Alvero, A. Chen, R. Chavez, S. L. Romero, R. Mor, G. TI Trophoblast-macrophage interactions: a regulatory network for the protection of pregnancy SO AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY LA English DT Article DE chemokines; cytokines; implantation; lipopolysaccharide; monocytes; Toll-like receptor-4 ID TOLL-LIKE RECEPTORS; T-CELLS; ACTIVATED LYMPHOCYTES; EPITHELIAL-CELLS; HUMAN DECIDUA; EXPRESSION; TOLERANCE; RANTES; IMPLANTATION; RECRUITMENT AB Problem Macrophages are one of the first immune cells observed at the implantation site. Their presence has been explained as the result of an immune response toward paternal antigens. The mechanisms regulating monocyte migration and differentiation at the implantation site are largely unknown. In the present study, we demonstrate that trophoblast cells regulate monocyte migration and differentiation. We propose that trophoblast cells 'educate' monocytes/macrophages to create an adequate environment that promote trophoblast survival. Method of Study CD14(+) monocytes were isolated from peripheral blood using magnetic beads. Co-culture experiments were conducted using a two-chamber system. Monocytes were stimulated with lipopolysaccharide (LPS) and cytokine levels were determined using multiplex cytokine detecting assay. Results Trophoblast cells increase monocyte migration and induce a significant increase in the secretion and production of the pro-inflammatory cytokines [interleukin-6 (IL-6), IL-8, tumor necrosis factor-alpha] and chemokines (growth-related oncogen-alpha, monocyte chemoattractant protein-1, macrophage inflammatory protein-1 beta, RANTES). Furthermore, the response of monocytes to LPS was different in monocytes pre-exposed to trophoblast cells. Conclusions The results of this study suggest that trophoblast cells are able to recruit and successfully educate monocytes to produce and secrete a pro-inflammatory cytokine and chemokine profile supporting its growth and survival. Furthermore we demonstrate that trophoblast cells can modulate monocytes response to bacterial stimuli. C1 Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, New Haven, CT 06520 USA. Univ Med Berlin, Charite, Dept Paediat, Berlin, Germany. NICHHD, Perinatol Res Branch, Detroit, MI USA. RP Mor, G (reprint author), Yale Univ, Sch Med, Dept Obstet Gynecol & Reprod Sci, Reprod Immunol Unit, 333 Cedar St,FMB 301, New Haven, CT 06520 USA. EM gil.mor@yale.edu FU Intramural NIH HHS; NICHD NIH HHS [2 N01 HD23342, R01 HD049446-01] NR 38 TC 110 Z9 119 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1046-7408 J9 AM J REPROD IMMUNOL JI Am. J. Reprod. Immunol. PD JAN PY 2007 VL 57 IS 1 BP 55 EP 66 DI 10.1111/j.1600-0897.2006.00446.x PG 12 WC Immunology; Reproductive Biology SC Immunology; Reproductive Biology GA 117QU UT WOS:000242888800008 PM 17156192 ER PT J AU Yang, IV Burch, LH Steele, MP Savov, JD Hollingsworth, JW McElvania-Tekippe, E Berman, KG Speer, MC Sporn, TA Brown, KK Schwarz, MI Schwartz, DA AF Yang, Ivana V. Burch, Lauranell H. Steele, Mark P. Savov, Jordan D. Hollingsworth, John W. McElvania-Tekippe, Erin Berman, Katherine G. Speer, Marcy C. Sporn, Thomas A. Brown, Kevin K. Schwarz, Marvin I. Schwartz, David A. TI Gene expression profiling of familial and sporadic interstitial pneumonia SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE familial interstitial pneumonia; global transcription analysis; interstitial lung disease; lung fibrosis; microarrays ID IDIOPATHIC PULMONARY-FIBROSIS; INDUCED LUNG INJURY; HISTOLOGIC PATTERN; DISEASE; SUSCEPTIBILITY; MICE; INFLAMMATION; INVOLVEMENT; INHIBITION; ALVEOLITIS AB Rationale: Idiopathic interstitial pneumonia (IIP) and its familial variants are progressive and largely untreatable disorders with poorly understood molecular mechanisms. Both the genetics and the histologic type of IIP play a role in the etiology and pathogenesis of interstitial lung disease, but transcriptional signatures of these sub-types are unknown. Objectives: To evaluate gene expression in the lung tissue of patients with usual interstitial pneumonia or nonspecific interstitial pneumonia that was either familial or nonfamilial in origin, and to compare it with gene expression in normal lung parenchyma. Methods: We profiled RNA from the lungs of 16 patients with sporadic IIP, 10 with familial HIP, and 9 normal control subjects on a whole human genome oligonucleotide microarray. Results: Significant transcriptional differences exist in familial and sporadic lips. The genes distinguishing the genetic subtypes belong to the same functional categories as transcripts that distinguish lip from normal samples. Relevant categories include chemokines and growth factors and their receptors, complement components, genes associated with cell proliferation and death, and genes in the Wnt pathway. The role of the chemokine CXCL12 in disease pathogenesis was confirmed in the murine bleomycin model of lung injury, with C57BL/6(CXCR4+/-) mice demonstrating significantly less Collagen deposition than C57BL/(6XCR4+/+) mice. Whereas substantial differences exist between familial and sporadic IIPs, we identified only minor gene expression changes between usual interstitial pneumonia and nonspecific interstitial pneumonia . Conclusions: Taken together, our findings indicate that differences in gene expression profiles between familial and sporadic UPS may provide clues to the etiology and pathogenesis of IIP. C1 Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC 27909 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Univ Colorado, Denver, CO 80202 USA. Ctr Hlth Sci, Denver, CO USA. RP Yang, IV (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, POB 12233,MD B3-08, Res Triangle Pk, NC 27909 USA. EM yangi@niehs.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [HL67467]; NIEHS NIH HHS [ES011961, ES11375] NR 44 TC 87 Z9 89 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 1 PY 2007 VL 175 IS 1 BP 45 EP 54 DI 10.1164/rccm.200601-062OC PG 10 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 123IO UT WOS:000243289800011 PM 16998095 ER PT J AU Wood, R Middelkoop, K Myer, L Grant, AD Whitelaw, A Lawn, SD Kaplan, G Huebner, R McIntyre, J Bekker, LG AF Wood, Robin Middelkoop, Keren Myer, Landon Grant, Alison D. Whitelaw, Andrew Lawn, Stephen D. Kaplan, Gilla Huebner, Robin McIntyre, James Bekker, Linda-Gail TI Undiagnosed tuberculosis in a community with high HIV prevalence - Implications for tuberculosis control SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE African community; case finding; HIV infection; incidence and prevalence; pulmonary tuberculosis ID SUB-SAHARAN AFRICA; PULMONARY TUBERCULOSIS; SOUTH-AFRICA; MYCOBACTERIUM-TUBERCULOSIS; ANTIRETROVIRAL TREATMENT; HIGH-RATES; INFECTION; MALAWI; IMPACT; EPIDEMIOLOGY AB Background: Although failure of tuberculosis (TB) control in sub-Saharan Africa is attributed to the HIV epidemic, it is unclear why the directly observed therapy short-course (DOTS) strategy is insufficient in this setting. We conducted a cross-sectional survey of pulmonary TB (PTB) and HIV infection in a community of 13,000 with high HIV prevalence and high TB notification rate and a well-functioning DOTS TB control program. Methods: Active case finding for PTB was performed in 762 adults using sputum microscopy and Mycobacterium tuberculosis culture, testing for HIV, and a symptom and risk factor questionnaire. Survey findings were correlated with notification data extracted from the TB treatment register. Results: Of those surveyed, 174 (23%) tested HIV positive, 11 (7 HIV positive) were receiving TB therapy, 6 (5 HIV positive) had previously undiagnosed smear-positive PTB, and 6 (4 HIV positive) had smear-negative/culture-positive PTB. Symptoms were not a useful screen for PTB. Among HIV-positive and -negative individuals, prevalence of notified smear-positive PTB was 1,563/100,000 and 352/100,000, undiagnosed smear-positive PTB prevalence was 2,837/100,000 and 175/100,000, and case-finding proportions were 37 and 67%, respectively. Estimated duration of infectiousness was similar for HIV-positive and HIV-negative individuals. However, 87% of total person-years of undiagnosed smear-positive TB in the community were among HIV-infected individuals. Conclusions: PTB was identified in 9% of HIV-infected individuals, with 5% being previously undiagnosed. Lack of symptoms suggestive of PTB may contribute to low case-finding rates. DOTS strategy based on passive case finding should be supplemented by active case finding targeting HIV-infected individuals. C1 UCT, Fac Hlth Sci, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med,Sch Publ Hlth & Family, ZA-7925 Cape Town, South Africa. Univ Cape Town, Dept Med, ZA-7700 Rondebosch, South Africa. Groote Schuur Hosp, Natl Hlth Lab Serv, ZA-7925 Cape Town, South Africa. Univ Witwatersrand, Perinatal Hlth Res Unit, ZA-2050 Johannesburg, South Africa. Columbia Univ, Mailman Sch Publ Hlth, Dept Epidemiol, New York, NY 10027 USA. Univ London London Sch Hyg & Trop Med, Clin Res Unit, Dept Infect & Trop Dis, London WC1E 7HT, England. Publ Hlth Res Inst, Lab Mycobacterial Immun & Pathogenesis, Newark, NJ USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. RP Bekker, LG (reprint author), UCT, Fac Hlth Sci, Desmond Tutu HIV Ctr, Inst Infect Dis & Mol Med,Sch Publ Hlth & Family, ZA-7925 Cape Town, South Africa. EM linda-gail.bekker@hiv-research.org.za RI Wood, Robin/G-8509-2011 FU NIAID NIH HHS [U19 AI053217, 1 U19AI53217-01, R01 AI054361, R01 AI058736]; PHS HHS [R01 54361, R01 A1058736-01A1]; Wellcome Trust [074641/Z/04/Z] NR 39 TC 160 Z9 163 U1 0 U2 9 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 1 PY 2007 VL 175 IS 1 BP 87 EP 93 DI 10.1164/rccm.200606-759OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 123IO UT WOS:000243289800017 PM 16973982 ER PT J AU Brown, JM Swindle, EJ Kushnir-Sukhov, NM Holian, A Metcalfe, DD AF Brown, Jared M. Swindle, Emily J. Kushnir-Sukhov, Nataliya M. Holian, Andrij Metcalfe, Dean D. TI Silica-directed mast cell activation is enhanced by scavenger receptors SO AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY LA English DT Article DE B6.Cg-Kit(W-sh) sash mouse; CD204; macrophage receptor with collagenous structure; mast cell silicosis; SR-A ID INDUCED PULMONARY-FIBROSIS; SYSTEMIC AUTOIMMUNE-DISEASE; MOUSE ALVEOLAR MACROPHAGES; TUMOR-NECROSIS-FACTOR; ZEALAND MIXED MICE; INDUCED APOPTOSIS; GROWTH-FACTOR; I COLLAGEN; LUNG; INFLAMMATION AB Inhalation of crystalline silica results in pulmonary fibrosis and silicosis. It has been suggested that mast cells play a role in these conditions. How mast cells would influence pathology is unknown. We thus explored mast cell interactions with silica in vitro and in B6.Cg-Kit(W-sh) mast cell-deficient mice. B6.Cg-Kit(W-sh) mice did not develop inflammation or significant Collagen deposition after instillation of silica, while C57BI/6 wild-type mice did have these findings. Given this supporting evidence of a role for mast cells in the development of silicosis, we examined the ability of silica to activate mouse bone marrow-derived mast cells'(BMMC), including degranulation (P-hexosaminidase release); production of reactive oxygen species (ROS) and inflammatory mediators; and the effects of silica on Fc epsilon RI-dependent activation. Silica did not induce mast cell degranulation. However, TNF-alpha, IL-13, monocyte chemotactic protein-1, protease activity, and production of ROS were dose-dependently increased after silica exposure, and production was enhanced after FC epsilon RI stimulation. This mast cell activation was inhibited by anti-inflammatory compounds. As silica mediates some effects in macrophages through scavenger receptors (SRs), we first determined that mast cells express scavenger receptors; then explored the involvement of SR-A and macrophage receptor with colleagenous structure (MARCO). Silica-induced ROS formation, apoptosis, and TNF-alpha production were reduced in BMMC obtained from SR-A, MARCO, and SR-A/MARCO knockout mice. These findings demonstrate that silica directs mast cell production of inflammatory mediators, in part through SRs, providing insight into critical events in the pathogenesis and potential therapeutic targets in silicosis. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Univ Montana, Ctr Environm Hlth Sci, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA. RP Brown, JM (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C209,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. EM jmbrown@niaid.nih.gov FU Intramural NIH HHS; NCRR NIH HHS [P20 RR01760]; NIEHS NIH HHS [R01 ES04804] NR 50 TC 53 Z9 54 U1 1 U2 5 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 JAN PY 2007 VL 36 IS 1 BP 43 EP 52 DI 10.1165/rcmb.2006-0197OC PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Respiratory System SC Biochemistry & Molecular Biology; Cell Biology; Respiratory System GA 123OY UT WOS:000243306400006 PM 16902192 ER PT J AU Yabroff, KR Ashbeck, E Rosenberg, R AF Yabroff, K. Robin Ashbeck, Erin Rosenberg, Robert TI Trends in time to completion of mammographic screening and follow-up services SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE breast cancer; breast neoplasms; mammography; mass screening; prevention; trend study ID UNITED-STATES; BREAST; BIOPSY; CARCINOMA; DIAGNOSIS; PROGRESS; WOMEN AB OBJECTIVE. The popular press has raised questions about mammographic capacity in the United States, but mammographic utilization data have not been used to inform these concerns. We used data for the period 1995-2002 from the New Mexico Mammography Project to assess trends in time to completion of mammographic screening and follow-up services. CONCLUSION. The median time to return mammographic screening changed little over time, but trends in the time required to complete recommended follow-up services varied by type of service and urban or rural residence. Further monitoring of time required to complete screening and follow-up services in other regions can inform debates on mammographic capacity. C1 Natl Canc Inst, Div Canc Control & Populat Sci, Bethesda, MD USA. Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87131 USA. RP Yabroff, KR (reprint author), Natl Canc Inst, Div Canc Control & Populat Sci, Execut Plaza N,Rm 4005,6130 Execut Blvd,MSC, Bethesda, MD USA. OI Yabroff, K. Robin/0000-0003-0644-5572 NR 21 TC 3 Z9 3 U1 0 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JAN PY 2007 VL 188 IS 1 BP 242 EP 245 DI 10.2214/AJR.04.1730 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 156KX UT WOS:000245647900039 PM 17179373 ER PT J AU Bagot, KS Berarducci, JM Franken, FH Frazier, MJ Ernst, M Moolchan, ET AF Bagot, Kara S. Berarducci, Jennifer M. Franken, Frederick H. Frazier, Matthew J. Ernst, Monique Moolchan, Eric T. TI Adolescents with conduct disorder: Early smoking and treatment requests SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID DEFICIT HYPERACTIVITY DISORDER; SUBSTANCE USE DISORDERS; CIGARETTE-SMOKING; NICOTINE DEPENDENCE; PSYCHIATRIC COMORBIDITY; TOBACCO USE; HIGH-RISK; BEHAVIORS; CHILDREN; TRAJECTORIES AB This study explored the relationship of a diagnosis of conduct disorder (CD) with the developmental smoking trajectory among 117 adolescent volunteers. Logistic regression analyses revealed that adolescents with CD smoked their first whole cigarette earlier (p = 0.03) and sought cessation treatment earlier (p = .01) compared to non-CD adolescents. Additionally, adolescents who smoked their first whole cigarette before the age of nine were eight times more likely to have CD. These findings suggest that in addition to addressing disruptive behaviors, early prevention and access to interventions for tobacco use are needed for youths with CD. C1 Natl Inst Drug Abuse, Teen Tobacco Addict Treatment Res Clin, Intramural Res Program, Baltimore, MD 21224 USA. NIMH, Intramural Res Program, Baltimore, MD USA. RP Moolchan, ET (reprint author), Natl Inst Drug Abuse, Teen Tobacco Addict Treatment Res Clin, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM emoolcha@intra.nida.nih.gov FU Intramural NIH HHS NR 38 TC 3 Z9 3 U1 7 U2 7 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PD JAN-FEB PY 2007 VL 16 IS 1 BP 62 EP 66 DI 10.1080/10550490601080100 PG 5 WC Substance Abuse SC Substance Abuse GA 138FP UT WOS:000244348800010 PM 17364424 ER PT J AU Suarez-Morales, L Matthews, J Martino, S Ball, SA Rosa, C Farentinos, C Szapocznik, J Carroll, KM AF Suarez-Morales, Lourdes Matthews, Julie Martino, Steve Ball, Samuel A. Rosa, Carmen Farentinos, Christine Szapocznik, Jose Carroll, Kathleen M. TI Issues in designing and implementing a Spanish-language multi-site clinical trial SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID SUBSTANCE-ABUSE; DRUG-ABUSE; FOLLOW-UP; ALCOHOLISM; DISORDERS; HISPANICS; SERVICES; RISK; NEED; CARE AB To address at least in part health disparities in Hispanic populations, the NIDA Clinical Trials Network implemented the first multi-site randomized clinical trial of substance abuse treatment conducted entirely in Spanish. This trial was intended to evaluate the effectiveness of Motivational Enhancement Therapy in a diverse population of Hispanics. In the conduct of this trial, several barriers to the successful implementation of a Spanish-language multi-site trial had to be addressed, including the appropriate translation of assessment instruments, shortage of appropriately trained Spanish-speaking clinical staff, and barriers to recruitment and retention of this population. To encourage similar research, strategies are described that were developed by the study team to meet these challenges. C1 Univ Miami, Miller Sch Med, Ctr Studies Family, Miami, FL 33136 USA. Adv Behav Hlth, Middletown, CT USA. Yale Univ, Connecticut VA Healthcare Ctr, Dept Psychiat, New Haven, CT 06520 USA. NIDA, Ctr Clin Trials Network, Bethesda, MD 20892 USA. ChangePoint Inc, Portland, OR USA. RP Suarez-Morales, L (reprint author), Univ Miami, Miller Sch Med, Ctr Studies Family, 1425 NW 10th Ave, Miami, FL 33136 USA. EM LSuarez@med.miami.edu RI Carroll, Kathleen/A-7526-2009; OI Carroll, Kathleen/0000-0003-3263-3374 FU NIDA NIH HHS [K05 DA000457, K05 DA00457, U10 DA013038, U10 DA013720, U10 DA13038, U10 DA13720] NR 38 TC 14 Z9 14 U1 0 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2007 VL 16 IS 3 BP 206 EP 215 DI 10.1080/10550490701375707 PG 10 WC Substance Abuse SC Substance Abuse GA 181QK UT WOS:000247451000009 PM 17612825 ER PT J AU Boyer, EW Babu, KM Macalino, GE Compton, W AF Boyer, Edward W. Babu, Kavita M. Macalino, Grace E. Compton, Wilson TI Self-treatment of opioid withdrawal with a dietary supplement, Kratom SO AMERICAN JOURNAL ON ADDICTIONS LA English DT Article ID UNITED-STATES; MITRAGYNA-SPECIOSA; MEDICINE; ALKALOIDS; ABUSE AB We examined the use of Kratom ( Mitragyna sp.), a dietary supplement with mu- opioid agonist activity, by members of a cybercommunity who self- treat chronic pain with opioid analgesics from Internet pharmacies. Within one year, an increase in the number of mentions on Drugbuyers.com, a Web site that facilitates the online purchase of opioid analgesics, suggested that members began managing opioid withdrawal with Kratom. This study demonstrates the rapidity with which information on psychoactive substances disseminates through online communities and suggests that online surveillance may be important to the generation of effective opioid analgesic abuse prevention strategies. C1 Univ Massachusetts, Sch Med, Div Med Toxicol, Dept Emergency Med, Worcester, MA 01655 USA. Tufts Univ New England Med Ctr, Boston, MA USA. Natl Inst Drug Abuse, Rockville, MD USA. RP Boyer, EW (reprint author), Univ Massachusetts, Sch Med, Div Med Toxicol, Dept Emergency Med, 55 Lake Ave N, Worcester, MA 01655 USA. EM edward.boyer@childrens.harvard.edu NR 16 TC 4 Z9 4 U1 1 U2 1 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 1055-0496 J9 AM J ADDICTION JI Am. J. Addict. PY 2007 VL 16 IS 5 DI 10.1080/10550490701525368 PG 5 WC Substance Abuse SC Substance Abuse GA 222YH UT WOS:000250333900004 ER PT J AU Ranganathan, S Nicholl, GCB Henry, S Lutka, F Sathanoori, R Lacomis, D Bowser, R AF Ranganathan, Srikanth Nicholl, Georgina C. B. Henry, Sarah Lutka, Fran Sathanoori, Ramasri Lacomis, David Bowser, Robert TI Comparative proteomic profiling of cerebrospinal fluid between living and post mortem ALS and control subjects SO AMYOTROPHIC LATERAL SCLEROSIS LA English DT Article DE cerebrospinal fluid; proteomics; mass spectrometry; biomarkers ID AMYOTROPHIC-LATERAL-SCLEROSIS; ALZHEIMERS-DISEASE; POTENTIAL BIOMARKERS; IDENTIFICATION; TRANSTHYRETIN; DIAGNOSIS; MARKERS; DAMAGE AB Neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS), lack definitive diagnostic tests or biomarkers of disease progression. Most studies that investigate protein abnormalities in ALS have used biofluids such as blood or cerebrospinal fluid (CSF), while some have used post mortem tissue or CSF samples. Since ALS disease progression and post mortem effects probably induce significant alterations to protein modifications or proteolysis, we directly examined the CSF proteome from ALS subjects at various lengths of time from symptom onset and at autopsy by mass spectrometry based proteomics. CSF was also obtained from both healthy age-matched control subjects and at autopsy from healthy and Alzheimer's disease (AD) controls. We identified significant differences in the CSF proteome between living and post mortem ALS subjects, as well as living and post mortem control subjects. We also noted differences in the CSF proteome of ALS subjects that have exhibited symptoms for varying lengths of time and between ALS and AD subjects at end-stage of disease. This is the first study describing differences in the CSF proteome from post mortem and living ALS subjects using a mass spectrometric approach. These differences highlight the importance of utilizing CSF from living ALS subjects near the time of symptom onset for the identification of early protein biomarkers, although some protein alterations that occur early in the disease process are maintained throughout the course of disease and in post mortem samples. C1 Univ Pittsburgh, Sch Med, Dept Pathol, Pittsburgh, PA 15261 USA. Natl Inst Neurol Disorders & Stroke, Neurogenet Branch, NIH, Bethesda, MD USA. Lofstrand Labs Ltd, Gaithersburg, MD USA. RP Bowser, R (reprint author), Univ Pittsburgh, Sch Med, Dept Pathol, BST S-420200 Lothrop St, Pittsburgh, PA 15261 USA. EM bowserrp@upmc.edu FU NIEHS NIH HHS [R21 ES013469-02, R21 ES013469, ES013469] NR 18 TC 9 Z9 9 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1748-2968 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. PY 2007 VL 8 IS 6 BP 373 EP 379 DI 10.1080/17482960701549681 PG 7 WC Clinical Neurology SC Neurosciences & Neurology GA 234GK UT WOS:000251148500009 PM 17852009 ER PT S AU Anderson, D Luke, RH Keller, JM AF Anderson, Derek Luke, Robert H. Keller, James M. BE Melin, P Castillo, O Ramirez, EG Kacprzyk, J Pedrycz, W TI Incorporation of non-euclidean distance metrics into fuzzy clustering on graphics processing units SO ANALYSIS AND DESIGN OF INTELLIGENT SYSTEMS USING SOFT COMPUTING TECHNIQUES SE ADVANCES IN SOFT COMPUTING LA English DT Proceedings Paper CT IFSA 2007 World Congress CY JUN 18-21, 2007 CL Cancun, MEXICO SP Int Fuzzy Syst Assoc, Hispan Amer Fuzzy Syst Assoc, Tijuana Inst Technol, Div Grad Studies AB Computational tractability of clustering algorithms becomes a problem as the number of data points, feature dimensionality, and number of clusters increase. Graphics Processing Units (GPUs) are low cost, high performance stream processing architectures used currently by the gaming, movie, and computer aided design industries. Fuzzy clustering is a pattern recognition algorithm that has a great amount of inherent parallelism that allows it to be sped up through stream processing on a GPU. We previously presented a method for offloading fuzzy clustering to a GPU, while maintaining full control over the various clustering parameters. In this work we extend that research and show how to incorporate non-Euclidean distance metrics. Our results show a speed increase of one to almost two orders of magnitude for particular cluster configurations. This methodology is particularly important for real time applications such as segmentation of video streams and high throughput problems. C1 [Anderson, Derek; Luke, Robert H.; Keller, James M.] Univ Missouri, Dept Elect & Comp Engn, Columbia, MO 65211 USA. [Anderson, Derek; Luke, Robert H.] Natl Lib Med, Biomed & Hlth Informat Res Training Program, Columbia, MO USA. RP Anderson, D (reprint author), Univ Missouri, Dept Elect & Comp Engn, Columbia, MO 65211 USA. EM dtaxtd@missouri.edu; rh13db@missouri.edu; kellerj@missouri.edu FU National Library of Medicine [T15 LM07089] FX D. Anderson and R. Luke are pre-doctoral biomedical informatics research fellows funded by the National Library of Medicine (T15 LM07089). NR 10 TC 6 Z9 6 U1 0 U2 1 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 1615-3871 BN 978-3-540-72431-5 J9 ADV SOFT COMP PY 2007 VL 41 BP 128 EP + DI 10.1007/978-3-540-72432-2_14 PG 2 WC Computer Science, Artificial Intelligence SC Computer Science GA BGQ85 UT WOS:000249852400014 ER PT J AU Mauck, RL Martinez-Diaz, GJ Yuan, XN Tuan, RS AF Mauck, Robert L. Martinez-Diaz, Gabriel J. Yuan, Xiaoning Tuan, Rocky S. TI Regional multilineage differentiation potential of meniscal fibrochondrocytes: Implications for meniscus repair SO ANATOMICAL RECORD-ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY LA English DT Article DE meniscus; fibrochondrocyte; multipotential mesenchymal stem cells; adipogenesis; osteogenesis; chondrogenesis ID MESENCHYMAL STEM-CELLS; HUMAN ARTICULAR CHONDROCYTES; EXOGENOUS FIBRIN CLOT; HUMAN TRABECULAR BONE; ORGAN-CULTURE MODEL; KNEE-JOINT MENISCUS; STROMAL CELLS; SEMILUNAR CARTILAGES; SKELETAL-MUSCLE; OSTEOARTHRITIS DEVELOPMENT AB The knee menisci are wedge-shaped semilunar fibrocartilaginous structures that reside between the femur and tibia and function to transmit and distribute load. These structures have characteristics of both fibrous and cartilaginous tissues. The cartilage-like inner region and the fibrous vascularized outer region each has a distinct extracellular matrix, and resident meniscal fibrochondrocytes (MFCs) with distinct morphologies dependent on their location. Damage to the meniscus is common, and disruption of tissue structure and function result in erosion of the underlying articular cartilage. It has been observed that damage in the vascular periphery undergoes spontaneous repair, whereas damage of the inner region does not heal. While vascularity of the peripheral region plays a role in healing, recent findings have also suggested that local cellular composition influences local healing capacity. This study examined the variation in multipotential characteristics of cell populations isolated from different regions of the bovine meniscus. MFCs were isolated from the outer (vascular), inner (avascular), and horn (mixed) regions and induced toward chondrogenic, adipogenic, and osteogenic lineages. The results of this study suggest that MFCs from all regions of the meniscus possess a multilineage differentiation capability, particularly toward chondrogenesis and adipogenesis. MFCs from the outer region were most plastic, differentiating along all three mesenchymal lineages. These findings may underlie the experimental observation of improved integration of meniscus grafts from the outer zone and may have implications for developing strategies of cell-based meniscus repair. Anat Rec, 290:48-58, 2007. (c) 2006 Wiley-Liss, Inc. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Yuan, XN (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, 50 S Dr,MSC 8022,Bldg 50,Room 1503, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU Intramural NIH HHS; NIAMS NIH HHS [Z01 AR41113] NR 88 TC 39 Z9 41 U1 0 U2 8 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA J9 ANAT REC JI Anat. Rec. PD JAN PY 2007 VL 290 IS 1 BP 48 EP 58 DI 10.1002/ar.a.20419 PG 11 WC Anatomy & Morphology SC Anatomy & Morphology GA 139VT UT WOS:000244461400003 PM 17441197 ER PT J AU Englund, EA Appella, DH AF Englund, Ethan A. Appella, Daniel H. TI gamma-substituted peptide nucleic acids constructed from L-lysine are a versatile scaffold for multifunctional display SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE binding studies; chiral backbone; DNA structures; nucleic acids; peptide nucleic acids ID LIGHT-UP PROBES; THIAZOLE ORANGE; CELLULAR UPTAKE; PNA ANALOGS; DNA-BINDING; CHIRAL PNA; RECOGNITION; BACKBONE; DUPLEX; FLUORESCENCE C1 NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. NIDDK, NIH, DHHS, Bethesda, MD 20892 USA. Northwestern Univ, Evanston, IL 60208 USA. RP Appella, DH (reprint author), NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. EM appellad@niddk.nih.gov FU Intramural NIH HHS NR 46 TC 58 Z9 58 U1 0 U2 12 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2007 VL 46 IS 9 BP 1414 EP 1418 DI 10.1002/anie.200603483 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 140LQ UT WOS:000244507100006 PM 17133633 ER PT J AU Chen, K Liu, Z Zhou, C Bracken, WC Kallenbach, NR AF Chen, Kang Liu, Zhigang Zhou, Chunhui Bracken, W. Clay Kallenbach, Neville R. TI Spin relaxation enhancement confirms dominance of extended conformations in short alanine peptides SO ANGEWANDTE CHEMIE-INTERNATIONAL EDITION LA English DT Article DE intramolecular distances; NMR spectroscopy; pepticles; protein folding ID POLYPROLINE-II CONFORMATION; UNFOLDED PROTEINS; SPECTROSCOPIC RULER; POLYPEPTIDE-CHAINS; SINGLE-MOLECULE; DENATURED STATE; HELIX FORMATION; RANDOM-COIL; BACKBONE; MODEL C1 [Chen, Kang] NIH, NHLBI, Lab Mol Biophys, Bethesda, MD 20892 USA. [Liu, Zhigang; Zhou, Chunhui; Kallenbach, Neville R.] NYU, Dept Chem, New York, NY 10003 USA. [Bracken, W. Clay] Cornell Univ, Weill Med Coll, Dept Biochem, New York, NY 10021 USA. RP Chen, K (reprint author), NIH, NHLBI, Lab Mol Biophys, 50 S Dr, Bethesda, MD 20892 USA. EM chenk2@mail.nih.gov; nrkl@nyu.edu RI Bracken, Clay/A-7811-2009 FU NCRR NIH HHS [C06 RR-16572] NR 31 TC 25 Z9 25 U1 0 U2 7 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1433-7851 J9 ANGEW CHEM INT EDIT JI Angew. Chem.-Int. Edit. PY 2007 VL 46 IS 47 BP 9036 EP 9039 DI 10.1002/anie.200703376 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 240GV UT WOS:000251576400021 PM 17943945 ER PT J AU Brewer, NT Cuite, CL Herrington, JE Weinstein, ND AF Brewer, Noel T. Cuite, Cara L. Herrington, James E. Weinstein, Neil D. TI Risk compensation and vaccination: Can getting vaccinated cause people to engage in risky behaviors? SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID HUMAN-PAPILLOMAVIRUS TYPE-16; CONTROLLED-TRIAL; BELT USE; WOMEN AB Background. Some believe that vaccinating young women against human papillomavirus (HPV) will increase their risky behavior. In more formal terms, vaccination lowers risk perception, and people compensate for their lower perceived risk by reducing other preventive behaviors. Purpose: We test several predictions from the risk compensation hypothesis in the context of vaccination behavior. Methods: We obtained a random sample of adults (N = 705), interviewing them by phone just as the Lyme disease vaccine first became available to the public and again 18 months later. Analyses controlled for age, sex, education, and race. Results: Vaccinated respondents were less likely to continue engaging in two of five protective behaviors after vaccination. The frequency of these protective behaviors did not dip below that among the unvaccinated respondents. Conclusions: We found some evidence of regression (protective behaviors dropping, after vaccination, to levels reported by the unvaccinated cohort). However, we did not find disinhibition (exceeding the risk taking of the unvaccinated cohort), the greater threat to public health. Although we will not know for several years what effect HP V vaccination has on other behaviors, if any, data on other vaccinations can offer critically important information in the interim. C1 UNC, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, Chapel Hill, NC 27516 USA. Rutgers State Univ, Piscataway, NJ 08855 USA. Natl Inst Hlth, Bethesda, MD 20892 USA. RP Brewer, NT (reprint author), UNC, Sch Publ Hlth, Dept Hlth Behav & Hlth Educ, 306 Rosenau Hall CB 7440, Chapel Hill, NC 27516 USA. EM ntbl@unc.edu RI Brewer, Noel/C-4375-2008 NR 18 TC 40 Z9 40 U1 0 U2 6 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PY 2007 VL 34 IS 1 BP 95 EP 99 DI 10.1007/BF02879925 PG 5 WC Psychology, Multidisciplinary SC Psychology GA 213JT UT WOS:000249663800011 PM 17688401 ER PT J AU Bellizzi, KM Miller, MF Arora, NK Rowland, JH AF Bellizzi, Keith M. Miller, Melissa Farmer Arora, Neeraj K. Rowland, Julia H. TI Positive and negative life changes experienced by survivors, of non-Hodgkin's Lymphoma SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Article ID BREAST-CANCER SURVIVORS; STRESS-RELATED GROWTH; QUALITY-OF-LIFE; BONE-MARROW TRANSPLANTATION; POSTTRAUMATIC GROWTH; LONG-TERM; PSYCHOLOGICAL ADJUSTMENT; PROSTATE-CANCER; SEXUAL ASSAULT; SELF-ESTEEM AB Background. The impact of cancer on adult survivors of aggressive non-Hodgkin's Lymphoma (NHL) is understudied. Purpose: We examined positive and negative life changes (health behaviors, relationships, financial situation) experienced by survivors of NHL and their association with physical and mental function. Methods: Using the Los Angeles County Cancer Surveillance Program, 744 questionnaires were mailed to adult survivors of NHL: 308 provided complete data for analyses (M age = 59.8, SD = 14.9). Results: Perceptions of positive and negative life changes were common in our sample, with 77.9% of NHL survivors reporting at least one positive change and 78.6% reporting at least one negative change. Cancer had the greatest positive change on relationships and the most negative change on survivors' financial situation. There was an equal distribution of survivors classified as having experienced positive change and negative change on health behaviors. Regardless of whether positive and negative life change were entered into separate regression models or the same model, an increase in negative life change in each of the domains was significantly associated with a decrease in physical and mental functioning. Positive change was significantly associated only with physical functioning when examining overall change (p =.018) and health behaviors (p =.013), and the inclusion of negative change attenuated these associations. Conclusions: In designing interventions to improve the mental and physical function of NHL survivors, the greatest benefit may likely be achieved by reducing the negative effects of cancer. Perhaps positive life changes are related in more specific ways to other indexes of adjustment, but our findings failed to show a positive relationship with mental and physical function. C1 NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. Natl Canc Inst, Outcomes Res Branch, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD USA. RP Bellizzi, KM (reprint author), NCI, Off Canc Survivorship, Div Canc Control & Populat Sci, 6116 Execut Blvd,Suite 404,MSC 8336, Bethesda, MD 20892 USA. EM bellizzk@mail.nih.gov FU NCI NIH HHS [N01-PC-35139, N02-PC-15105]; PHS HHS [U55/CCR 921930-02] NR 54 TC 51 Z9 52 U1 1 U2 5 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PY 2007 VL 34 IS 2 BP 188 EP 199 DI 10.1007/BF02872673 PG 12 WC Psychology, Multidisciplinary SC Psychology GA 217EK UT WOS:000249931000008 PM 17927557 ER PT J AU Kreuter, MW Green, MC Cappella, JN Slater, MD Wise, ME Storey, D Clark, EM O'Keefe, DJ Erwin, DO Holmes, K Hinyard, LJ Houston, T Woolley, S AF Kreuter, Matthew W. Green, Melanie C. Cappella, Joseph N. Slater, Michael D. Wise, Meg E. Storey, Doug Clark, Eddie M. O'Keefe, Daniel J. Erwin, Deborah O. Holmes, Kathleen Hinyard, Leslie J. Houston, Thomas Woolley, Sabra TI Narrative communication in cancer prevention and control: A framework to guide research and application SO ANNALS OF BEHAVIORAL MEDICINE LA English DT Review ID BREAST SELF-EXAMINATION; OF-THE-LITERATURE; SOCIAL SUPPORT; PUBLIC-HEALTH; EFFICACY EXPECTATIONS; MEDIA COVERAGE; MESSAGES; WOMEN; CARE; PERFORM AB Narrative forms of communication-including entertainment education, journalism, literature, testimonials, and storytelling-are emerging as important tools for cancer prevention and control. To stimulate critical thinking about the role of narrative in cancer communication and promote a more focused and systematic program of research to understand its effects, we propose a typology of narrative application in cancer control. We assert that narrative has four distinctive capabilities: overcoming resistance, facilitating information processing, providing surrogate social connections, and addressing emotional and existential issues. We further assert that different capabilities are applicable to different outcomes across the cancer control continuum (e.g., prevention, detection, diagnosis, treatment, survivorship). This article describes the empirical evidence and theoretical rationale supporting propositions in the typology, identifies variables likely to moderate narrative effects, raises ethical issues to be addressed when using narrative communication in cancer prevention and control efforts, and discusses potential limitations of using narrative in this way. Future research needs based on these propositions are outlined and encouraged. C1 St Louis Univ, Sch Publ Hlth, Dept Community Hlth, Hlth Commun Res Lab, St Louis, MO 63104 USA. Univ N Carolina, Dept Psychol, Chapel Hill, NC USA. Univ Penn, Annenberg Sch Commun, Philadelphia, PA 19104 USA. Univ Penn, Abrams Canc Ctr, Philadelphia, PA 19104 USA. Ohio State Univ, Sch Commun, Columbus, OH 43210 USA. Univ Wisconsin, Ctr Hlth Syst Res & Anal, Madison, WI USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Ctr Commun Programs, Baltimore, MD USA. St Louis Univ, Dept Psychol, St Louis, MO 63103 USA. Northwestern Univ, Dept Commun Studies, Evanston, IL 60208 USA. Univ Alabama, Ctr Outcomes & Effectiveness Res & Educ, Birmingham, AL USA. Vet Affairs Med Ctr, Deep S Ctr Effectiveness Res, Birmingham, AL USA. NCI, Hlth Commun & Informat Res Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Kreuter, MW (reprint author), St Louis Univ, Sch Publ Hlth, Dept Community Hlth, Hlth Commun Res Lab, 3545 Layayette Ave, St Louis, MO 63104 USA. EM kreuter@slu.edu RI Slater, Michael/A-5450-2011; Ho, Rainbow Tin Hung/A-8705-2012 OI Slater, Michael/0000-0003-4279-346X; Ho, Rainbow Tin Hung/0000-0002-6173-621X NR 103 TC 211 Z9 216 U1 4 U2 49 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0883-6612 J9 ANN BEHAV MED JI Ann. Behav. Med. PY 2007 VL 33 IS 3 BP 221 EP 235 DI 10.1007/BF02879904 PG 15 WC Psychology, Multidisciplinary SC Psychology GA 186CQ UT WOS:000247757100001 PM 17600449 ER PT J AU Catov, JM Newman, AB Roberts, JM Sutton-Tyrrell, KC Kelsey, SF Harris, T Jackson, R Colbert, LH Satterfield, S Ayonayon, HN Ness, RB AF Catov, Janet M. Newman, Anne B. Roberts, James M. Sutton-Tyrrell, Kim C. Kelsey, Sheryl F. Harris, Tamara Jackson, Rebecca Colbert, Lisa H. Satterfield, Suzanne Ayonayon, Hilsa N. Ness, Roberta B. TI Association between infant birth weight and maternal cardiovascular risk factors in the health, aging, and body composition study SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE pregnancy; women; heart disease; risk factors ID FOR-GESTATIONAL-AGE; C-REACTIVE PROTEIN; ADIPOSE-TISSUE DISTRIBUTION; AMBULATORY BLOOD-PRESSURE; INSULIN-RESISTANCE; PREGNANCY COMPLICATIONS; PRETERM DELIVERY; METABOLICALLY-OBESE; GROWTH-RETARDATION; GLUCOSE-TOLERANCE AB PURPOSE: Mothers who deliver a low-birth-weight (LBW) infant may themselves be at excess risk for cardiovascular disease. We investigated whether older women who bore LBW infants had higher blood pressure, lipid, glucose, insulin, interleukin 6 (IL-6), and C-reactive protein concentrations, and pulse wave velocity compared to women with normal-weight births. METHODS: Participants were 446 women with a mean age of 80 years and 47% black. Women reported birth weight and complications for each pregnancy. Analysis was limited to first births not complicated by hypertension or preeclampsia. RESULTS: Women who had delivered a first-birth infant weighing less than 2500 g had a lower body mass index (BMI) compared with women with a normal-weight (;2500 g) infant (26.7 versus 28.4 kg/m; p = 0.02), but they had a larger abdominal circumference for BMI (97.9 versus 95.5 cm; p = 0.05). They also were marginally more likely to be administered antihypertensive medication (p = 0.06). After adjustment for BMI, race, and age, women with a history of a small infant had elevations in systolic blood pressure (p = 0.05) and greater IL-6 levels (p = 0.02) and were more insulin resistant (p = 0.05) compared with women with a normal-weight infant. CONCLUSIONS: These findings suggest that a history of LBW delivery identifies women with elevated cardiovascular risk factors. C1 Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Magee Womens Res Inst, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Dept OB GYN & Reprod Sci, Pittsburgh, PA 15260 USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Obstet & Gynecol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Wisconsin, Dept Kinesiol, Madison, WI USA. Univ Tennessee, Memphis, TN USA. RP Catov, JM (reprint author), Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, 130 DeSoto St, Pittsburgh, PA 15261 USA. EM jmcst43@pitt.edu RI Newman, Anne/C-6408-2013 OI Newman, Anne/0000-0002-0106-1150 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 52 TC 25 Z9 26 U1 0 U2 3 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 JAN PY 2007 VL 17 IS 1 BP 36 EP 43 DI 10.1016/j.annepidem.2006.02.007 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 123FI UT WOS:000243281300005 PM 16843009 ER PT J AU Yu, K Martin, R Rothman, N Zheng, T Lan, Q AF Yu, K. Martin, R. Rothman, N. Zheng, T. Lan, Q. TI Two-sample comparison based on prediction error, with applications to candidate gene association studies SO ANNALS OF HUMAN GENETICS LA English DT Article DE classification tree; haplotype; candidate gene association studies; prediction error; bootstrap ID MAXIMUM-LIKELIHOOD-ESTIMATION; FAMILY-BASED TESTS; TRANSMISSION/DISEQUILIBRIUM TEST; HAPLOTYPE FREQUENCIES; LINKAGE DISEQUILIBRIUM; FOUNDER HETEROGENEITY; CROSS-VALIDATION; CLASSIFICATION; SUSCEPTIBILITY; POPULATION AB To take advantage of the increasingly available high-density SNP maps across the genome, various tests that compare multilocus genotypes or estimated haplotypes between cases and controls have been developed for candidate gene association studies. Here we view this two-sample testing problem from the perspective of supervised machine learning and propose a new association test. The approach adopts the flexible and easy-to-understand classification tree model as the learning machine, and uses the estimated prediction error of the resulting prediction rule as the test statistic. This procedure not only provides an association test but also generates a prediction rule that can be useful in understanding the mechanisms underlying complex disease. Under the set-up of a haplotype-based transmission/disequilibrium test (TDT) type of analysis, we find through simulation studies that the proposed procedure has the correct type I error rates and is robust to population stratification. The power of the proposed procedure is sensitive to the chosen prediction error estimator. Among commonly used prediction error estimators, the .632+ estimator results in a test that has the best overall performance. We also find that the test using the .632+ estimator is more powerful than the standard single-point TDT analysis, the Pearson's goodness-of-fit test based on estimated haplotype frequencies, and two haplotype-based global tests implemented in the genetic analysis package FBAT. To illustrate the application of the proposed method in population-based association studies, we use the procedure to study the association between non-Hodgkin lymphoma and the IL10 gene. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Millennium Pharmaceut, Cambridge, MA 02139 USA. Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. RP Yu, K (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. EM yuka@mail.nih.gov FU Intramural NIH HHS NR 39 TC 3 Z9 3 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0003-4800 J9 ANN HUM GENET JI Ann. Hum. Genet. PD JAN PY 2007 VL 71 BP 107 EP 118 DI 10.1111/j.1469-1809.2006.00306.x PN 1 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 113YL UT WOS:000242633800011 PM 17227481 ER PT J AU Craig, D Blackstone, MD AF Craig, D. Blackstone, M. D. TI Functional characterization of a family of proteins related to the SPG3A protein atlastin SO ANNALS OF NEUROLOGY LA English DT Meeting Abstract CT 132nd Annual Meeting of the American-Neurological-Association CY OCT 07-10, 2007 CL Washington, DC SP Amer Neurol Assoc C1 [Craig, D.; Blackstone, M. D.] Natl Inst Neurol Disorder & Stroke, Bethesda, MD USA. NR 0 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 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PY 2007 VL 62 SU 11 BP S1 EP S1 PG 1 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 217EG UT WOS:000249930600002 ER PT J AU Jett, DA AF Jett, David A. TI Neurological aspects of chemical terrorism SO ANNALS OF NEUROLOGY LA English DT Editorial Material ID AGENT-INDUCED SEIZURES; INDUCED NEUROPATHOLOGY; PATHOLOGY; EXPOSURE; BRAIN; RATS C1 NINDS, Off Technol Dev, NIH, Bethesda, MD 20892 USA. RP Jett, DA (reprint author), NINDS, Off Technol Dev, NIH, 6001 Execut Blvd,NSC,Room 2177,MSC 9527, Bethesda, MD 20892 USA. EM jettd@ninds.nih.gov NR 25 TC 9 Z9 9 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JAN PY 2007 VL 61 IS 1 BP 9 EP 13 DI 10.1002/ana.21072 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 133QR UT WOS:000244028000006 PM 17262854 ER PT J AU Balakrishna, N Arlappa, N Laxmaiah, A Galreddy, CH Brahmam, GNV AF Balakrishna, N. Arlappa, N. Laxmaiah, A. Galreddy, C. H. Brahmam, G. N. V. TI Association between anthropometric measurements and hypertension: A study among rural elderly, in India SO ANNALS OF NUTRITION AND METABOLISM LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0250-6807 J9 ANN NUTR METAB JI Ann. Nutr. Metab. PY 2007 VL 51 SU 1 BP 116 EP 116 PG 1 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 192FE UT WOS:000248185400260 ER PT J AU Curwin, BD Hein, MJ Sanderson, WT Striley, C Heederik, D Kromhout, H Reynolds, SJ Alavanja, MC AF Curwin, Brian D. Hein, Misty J. Sanderson, Wayne T. Striley, Cynthia Heederik, Dick Kromhout, Hans Reynolds, Stephen J. Alavanja, Michael C. TI Urinary pesticide concentrations among children, mothers and fathers living in farm and non-farm households in Iowa SO ANNALS OF OCCUPATIONAL HYGIENE LA English DT Article DE biological monitoring; herbicides; insecticides; pesticides; pesticide exposure; take-home; urine ID CENTRAL WASHINGTON-STATE; ORGANOPHOSPHORUS PESTICIDES; METOLACHLOR MERCAPTURATE; AGRICULTURAL COMMUNITY; EXPOSURE PATHWAYS; LAWN APPLICATIONS; CANCER-RISK; CHLORPYRIFOS; APPLICATORS; HEALTH AB In the spring and summer of 2001, 47 fathers, 48 mothers and 117 children of Iowa farm and non-farm households were recruited to participate in a study investigating take-home pesticide exposure. On two occasions similar to 1 month apart, urine samples from each participant and dust samples from various rooms were collected from each household and were analyzed for atrazine, metolachlor, glyphosate and chlorpyrifos or their metabolites. The adjusted geometric mean (GM) level of the urine metabolite of atrazine was significantly higher in fathers, mothers and children from farm households compared with those from non-farm households (P <= 0.0001). Urine metabolites of chlorpyrifos were significantly higher in farm fathers (P = 0.02) and marginally higher in farm mothers (P = 0.05) when compared with non-farm fathers and mothers, but metolachlor and glyphosate levels were similar between the two groups. GM levels of the urinary metabolites for chlorpyrifos, metolachlor and glyphosate were not significantly different between farm children and non-farm children. Farm children had significantly higher urinary atrazine and chlorpyrifos levels (P = 0.03 and P = 0.03 respectively) when these pesticides were applied by their fathers prior to sample collection than those of farm children where these pesticides were not recently applied. Urinary metabolite concentration was positively associated with pesticide dust concentration in the homes for all pesticides except atrazine in farm mothers; however, the associations were generally not significant. There were generally good correlations for urinary metabolite levels among members of the same family. C1 NIOSH, Div Surveillance Hazard Evalutat & Field Studies, Cincinnati, OH USA. Univ Iowa, Dept Environm & Occupat Hlth, Iowa City, IA USA. NIOSH, Div Appl Res & Technol, Cincinnati, OH 45226 USA. Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Curwin, BD (reprint author), NIOSH, Div Surveillance Hazard Evalutat & Field Studies, Cincinnati, OH USA. EM bcurwin@cdc.gov RI Kromhout, Hans/A-9159-2008 NR 51 TC 80 Z9 84 U1 3 U2 27 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 JAN PY 2007 VL 51 IS 1 BP 53 EP 65 DI 10.1093/annhug/mel062 PG 13 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 126EV UT WOS:000243495900007 PM 16984946 ER PT J AU Sherry, RM Rosenberg, SA AF Sherry, R. M. Rosenberg, S. A. TI The development of effective cell transfer immunotherapy for patients with cancer SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 5th International Symposium onTargeted Anticancer Therapies CY MAR 08-10, 2007 CL Amsterdam, NETHERLANDS SP Novartis, Astellas, Genentech, MSD, AstraZeneca, Johnson & Johnson, OSI Oncol, Bayer HealthCare, Merck Serono, Pfizer C1 NCI, Tumor Immunol Sect, Surg Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2007 VL 18 SU 4 BP 17 EP 17 PG 1 WC Oncology SC Oncology GA 207VZ UT WOS:000249280500003 ER PT J AU Bates, SE Piekarz, R Wright, J Fojo, T AF Bates, S. E. Piekarz, R. Wright, J. Fojo, T. TI Histone deacetylase inhibitors in T cell lymphomas as a paradigm in cancer therapy SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 5th International Symposium onTargeted Anticancer Therapies CY MAR 08-10, 2007 CL Amsterdam, NETHERLANDS SP Novartis, Astellas, Genentech, MSD, AstraZeneca, Johnson & Johnson, OSI Oncol, Bayer HealthCare, Merck Serono, Pfizer C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2007 VL 18 SU 4 BP 23 EP 23 PG 1 WC Oncology SC Oncology GA 207VZ UT WOS:000249280500021 ER PT J AU Fojo, T AF Fojo, T. TI Cancer stem cell hypothesis: An inadequate explanation for drug resistance SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 5th International Symposium onTargeted Anticancer Therapies CY MAR 08-10, 2007 CL Amsterdam, NETHERLANDS SP Novartis, Astellas, Genentech, MSD, AstraZeneca, Johnson & Johnson, OSI Oncol, Bayer HealthCare, Merck Serono, Pfizer C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2007 VL 18 SU 4 BP 26 EP 26 PG 1 WC Oncology SC Oncology GA 207VZ UT WOS:000249280500026 ER PT J AU Hassan, R Pastan, I AF Hassan, R. Pastan, I. TI Antibody-based therapies targeting the tumor antigen mesothelin SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 5th International Symposium onTargeted Anticancer Therapies CY MAR 08-10, 2007 CL Amsterdam, NETHERLANDS SP Novartis, Astellas, Genentech, MSD, AstraZeneca, Johnson & Johnson, OSI Oncol, Bayer HealthCare, Merck Serono, Pfizer C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2007 VL 18 SU 4 BP 26 EP 26 PG 1 WC Oncology SC Oncology GA 207VZ UT WOS:000249280500028 ER PT J AU Doroshow, J AF Doroshow, J. TI Phase 'O' trials SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 5th International Symposium onTargeted Anticancer Therapies CY MAR 08-10, 2007 CL Amsterdam, NETHERLANDS SP Novartis, Astellas, Genentech, MSD, AstraZeneca, Johnson & Johnson, OSI Oncol, Bayer HealthCare, Merck Serono, Pfizer C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2007 VL 18 SU 4 BP 28 EP 28 PG 1 WC Oncology SC Oncology GA 207VZ UT WOS:000249280500032 ER PT J AU Belch, A Kouroukis, CT Crump, M Sehn, L Gascoyne, RD Klasa, R Powers, J Wright, J Eisenhauer, EA AF Belch, A. Kouroukis, C. T. Crump, M. Sehn, L. Gascoyne, R. D. Klasa, R. Powers, J. Wright, J. Eisenhauer, E. A. TI A phase II study of bortezomib in mantle cell lymphoma: The National Cancer Institute of Canada Clinical Trials Group trial IND.150 SO ANNALS OF ONCOLOGY LA English DT Article DE bortezomib; mantle cell lymphoma ID NON-HODGKINS-LYMPHOMA; RESPONSE CRITERIA; ONCOLOGY-GROUP; MYELOMA AB Background: We evaluated the activity and toxic effects of bortezomib in patients with mantle cell lymphoma. Patients and methods: Thirty patients, including 29 eligible patients, were enrolled; 13 had received no prior chemotherapy. The dose of bortezomib was 1.3 mg/m(2) given on days 1, 4, 8 and 11 every 21 days. Response was assessed according to the International Workshop Criteria for non-Hodgkin's lymphoma and toxicity graded using the National Cancer Institute Common Toxicity Criteria version 2.0. Results: There were 13 responding patients (46.4%; 95% confidence interval = 27.5% to 66.1%), including one unconfirmed complete remission. The median response duration was 10 months. Response rates were similar in previously untreated (46.2%) and treated (46.7%) patients. Neurological toxicity and myalgia led to treatment discontinuation in 10 patients after two to seven treatment cycles. Five serious adverse events (including two deaths) associated with fluid retention were observed in the first 12 patients. We subsequently excluded patients with baseline effusions, dyspnea or edema; no further events were seen. Conclusions: Bortezomib is active in treating patients with mantle cell lymphoma. While cumulative neuromuscular toxic effects limited therapy duration and specific issues related to fluid retention require further evaluation, continued study of this drug in combination regimens is warranted. C1 Queens Univ, Natl Canc Inst Canada Clin Trials Grp, IND Program, Kingston, ON K7L 3N6, Canada. Cross Canc Inst, Dept Med Oncol, Edmonton, AB T6G 1Z2, Canada. Juravinski Canc Ctr, Hamilton, ON, Canada. Princess Margaret Hosp, Univ Hlth Network, Toronto, ON M4X 1K9, Canada. British Columbia Canc Agcy, Vancouver Clin, Vancouver, BC V5Z 4E6, Canada. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Eisenhauer, EA (reprint author), Queens Univ, Natl Canc Inst Canada Clin Trials Grp, IND Program, 10 Stuart St, Kingston, ON K7L 3N6, Canada. EM eeisenhauer@ctg.queensu.ca NR 18 TC 112 Z9 114 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2007 VL 18 IS 1 BP 116 EP 121 PG 6 WC Oncology SC Oncology GA 127NR UT WOS:000243593700021 PM 16971665 ER PT J AU Mani, S McDaid, HM Grossman, A Muggia, F Goel, S Griffin, T Colevas, D Horwitz, SB Egorin, MJ AF Mani, S. McDaid, H. M. Grossman, A. Muggia, F. Goel, S. Griffin, T. Colevas, D. Horwitz, S. B. Egorin, M. J. TI Peripheral blood mononuclear and tumor cell pharmacodynamics of the novel epothilone B analogue, ixabepilone SO ANNALS OF ONCOLOGY LA English DT Article DE neuropathy; neutropenia; pharmacodynamics; tubulin ID APO-2L/TRAIL-INDUCED APOPTOSIS; BREAST-CANCER; SOLID TUMORS; BMS-247550; MICROTUBULE; PACLITAXEL AB Background: We previously demonstrated that peak microtubule bundle formation (MBF) in peripheral blood mononuclear cells (PBMCs) occurs at the end of drug infusion and correlates with drug pharmacokinetics (PK). In the current study, a new expanded evaluation of drug target effect was undertaken. Patients and methods: Patients with advanced solid malignancies were treated with ixabepilone 40 mg/m(2) administered as a 1-h i.v. infusion every 3 weeks. Blood, plasma, and tumor tissue sampling was carried out to characterize pharmacodynamics and PK. Results: Forty-seven patients were treated with 141 cycles of ixabepilone. In both PBMCs (n = 27) and tumor cells (n = 9), peak MBF occurred at the end of infusion; however, at 24-72 h after drug infusion, the number of cells with MBF was significantly greater in tumor cells, relative to PBMCs. A Hill model (EC50 = 109.65 ng/ml; r(2) = 0.94) was fitted, which demonstrated a relationship between percentage of PBMCs with MBF and plasma ixabepilone concentration. The percentage of PBMCs with MBF at the end of infusion also correlated with severity of neutropenia (P = 0.050). Conclusions: Plasma ixabepilone concentration and severity of neutropenia correlate with the level of MBF in PBMCs. Therefore, this technically straightforward assay should be considered as a complement to the clinical development of novel microtubule-binding agents. C1 Albert Einstein Coll Med, Albert Einstein Comprehens Canc Ctr, New York, NY USA. Albert Einstein Coll Med, Dept Mol Genet, New York, NY USA. Albert Einstein Coll Med, Dept Mol Pharmacol, New York, NY USA. NYU, Sch Med, Ctr Comprehens Canc, New York, NY USA. Bristol Myers Squibb Co, Wallingford, CT 06492 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. RP Mani, S (reprint author), Yeshiva Univ Albert Einstein Coll Med, Jack D Weiler Hosp, Dept Oncol, Room 2S-49,1825 Eastchester Rd, Bronx, NY 10461 USA. EM smani@montefiore.org OI Muggia, Franco/0000-0003-0703-9146 FU NCI NIH HHS [CA 39821, CA 13330-30, R03 CA 86807, U01 CA76642-01, CA 77263]; NCRR NIH HHS [M01-RR12248, M01 RR00096] NR 17 TC 11 Z9 12 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2007 VL 18 IS 1 BP 190 EP 195 DI 10.1093/annonc/mdl315 PG 6 WC Oncology SC Oncology GA 127NR UT WOS:000243593700032 PM 17018704 ER PT J AU Fojo, T Menefee, M AF Fojo, T. Menefee, M. TI Mechanisms of multidrug resistance: the potential role of microtubule-stabilizing agents SO ANNALS OF ONCOLOGY LA English DT Article; Proceedings Paper CT 31st Congress of the European-Society-for-Medical-Oncology CY SEP 29-OCT 03, 2006 CL Istanbul, TURKEY SP European Soc Med Oncol DE epothilones; microtubulin; paclitaxel; P-glycoprotein; taxanes; tubulin ID PREPROPHASE BAND FORMATION; DYNAMIC INSTABILITY; DESOXYEPOTHILONE-B; ANTITUMOR EFFICACY; PURIFIED TUBULIN; PACLITAXEL TAXOL; DRUG-RESISTANCE; EPOTHILONE-A; CELL LINES; DISCODERMOLIDE AB Antimitotic agents that target the dynamic equilibrium between the microtubule polymer and tubulin heteroclimers are key components of chemotherapeutic regimens for various solid tumors. These agents can be divided into two major classes based on their effect on microtubule polymerization and the mass of microtubule polymers: those that inhibit polymerization, such as the vinca alkaloids and those that stabilize microtubules, such as the taxanes and epothilones. The taxanes paclitaxel (Taxol) and docetaxel (Taxotere) were the first antimicrotubule agents approved for use in solid tumors, but their usefulness is often limited by development of drug resistance. The epothilones are distinguished from the taxanes structurally and functionally and have been shown in vitro and in preclinical models to have superior potency to the taxanes. The epothilones are not susceptible to P-glycoprotein-mediated efflux and have shown activity against taxane-resistant tumors. Other natural-product microtubule-stabilizing agents also have promising pharmacologic profiles. This article discusses mechanisms of drug resistance and summarizes scientific and clinical data supporting the potential of novel microtubule-stabilizing agents for achieving broad antitumor efficacy without the emergence of drug resistance. The ability to reduce the development of resistance with the epothilones and other microtubule-stabilizing agents may provide additional treatment options at the time of presentation and in the setting of taxane resistance. C1 NCI, Bethesda, MD 20892 USA. Mayo Clin, Div Med Oncol, Rochester, MN USA. RP Fojo, T (reprint author), NCI, Bldg 10 Room 12C103,10 Ctr Dr, Bethesda, MD 20892 USA. EM tfojo@helix.nih.gov NR 52 TC 77 Z9 82 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2007 VL 18 SU 5 BP V3 EP V8 DI 10.1093/annonc/mdm172 PG 6 WC Oncology SC Oncology GA 213TE UT WOS:000249689200002 PM 17656560 ER PT J AU Hoyo, C Schildkraut, J Murphy, S Chow, W Vaughan, T Risch, H Artle, R Mayne, S Fraumeni, J Gammon, M AF Hoyo, C. Schildkraut, J. Murphy, S. Chow, W. Vaughan, T. Risch, H. Artle, R. Mayne, S. Fraumeni, J., Jr. Gammon, M. TI IGF2R polymorphisms and esophageal and gastric cardia adenocarcinomas SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract CT 9th World Congress on Gastrointestinal Cancer CY JUN 28-JUL 01, 2007 CL Barcelona, SPAIN C1 Duke Univ, Med Ctr, Durham, NC USA. NCI, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Yale Univ, New Haven, CT 06520 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 2007 VL 18 SU 7 BP VII12 EP VII12 PG 1 WC Oncology SC Oncology GA 207WC UT WOS:000249280800006 ER PT J AU Esquivel, J Sticca, R Sugarbaker, P Levine, E Yan, TD Alexander, R Baratti, D Bartlett, D Barone, R Barrios, P Bieligk, S Bretcha-Boix, P Chang, CK Chu, F Chu, Q Daniel, S Debree, E Deraco, M Dominguez-Parra, L Elias, D Flynn, R Foster, J Garofalo, A Gilly, FN Glehen, O Gomez-Portilla, A Gonzalez-Bayon, L Gonzalez-Moreno, S Goodman, M Gushchin, V Hanna, N Hartmann, J Harrison, L Hoefer, R Kane, J Kecmanovic, D Kelley, S Kuhn, J LaMont, J Lange, J Li, B Loggie, B Mahteme, H Mann, G Martin, R Misih, RA Moran, B Morris, D Onate-Ocana, L Petrelli, N Philippe, G Pingpank, J Pitroff, A Piso, P Quinones, M Riley, L Rutstein, L Saha, S Alrawi, S Sardi, A Schneebaum, S Shen, P Shibata, D Spellman, J Stojadinovic, A Stewart, J Torres-Melero, J Tuttle, T Verwaal, V Villar, J Wilkinson, N Younan, R Zeh, H Zoetmulder, F Sebbag, G AF Esquivel, J. Sticca, R. Sugarbaker, P. Levine, E. Yan, T. D. Alexander, R. Baratti, D. Bartlett, D. Barone, R. Barrios, P. Bieligk, S. Bretcha-Boix, P. Chang, C. K. Chu, F. Chu, Q. Daniel, S. deBree, E. Deraco, M. Dominguez-Parra, L. Elias, D. Flynn, R. Foster, J. Garofalo, A. Gilly, F. N. Glehen, O. Gomez-Portilla, A. Gonzalez-Bayon, L. Gonzalez-Moreno, S. Goodman, M. Gushchin, V. Hanna, N. Hartmann, J. Harrison, L. Hoefer, R. Kane, J. Kecmanovic, D. Kelley, S. Kuhn, J. LaMont, J. Lange, J. Li, B. Loggie, B. Mahteme, H. Mann, G. Martin, R. Misih, R. A. Moran, B. Morris, D. Onate-Ocana, L. Petrelli, N. Philippe, G. Pingpank, J. Pitroff, A. Piso, P. Quinones, M. Riley, L. Rutstein, L. Saha, S. Alrawi, S. Sardi, A. Schneebaum, S. Shen, P. Shibata, D. Spellman, J. Stojadinovic, A. Stewart, J. Torres-Melero, J. Tuttle, T. Verwaal, V. Villar, J. Wilkinson, N. Younan, R. Zeh, H. Zoetmulder, F. Sebbag, G. TI Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the management of peritoneal surface malignancies of colonic origin: A consensus statement SO ANNALS OF SURGICAL ONCOLOGY LA English DT Article ID COLORECTAL-CANCER; CARCINOMATOSIS C1 St Agnes Hosp, Baltimore, MD USA. Univ N Dakota, Altru Hosp, Grand Forks, ND 58201 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Univ Maryland, Baltimore, MD 21201 USA. Natl Canc Inst, I-20133 Milan, Italy. Univ Pittsburgh, Med Ctr, Pittsburgh, PA USA. Sharp HealthCare, San Diego, CA USA. Hosp San Pablo, Barcelona, Spain. Baltimore Washington Med Ctr, Glen Burnie, MD USA. Hosp San Jaime, Torrevieja, Spain. Walnut Creek Kaiser Permanente, Walnut Creek, CA USA. St George Hosp, Sydney, NSW, Australia. Louisiana State Univ, Shreveport, LA 71105 USA. Crete Univ Hosp, Sch Med, Iraklion, Greece. Inst Nacl Cancerl, Mexico City, DF, Mexico. Inst Gustave Roussy, Villejuif, France. Creighton Univ, Sch Med, Omaha, NE USA. Osped S Camillo Forlanini, Rome, Italy. Univ Lyon, Lyon, France. Policlin San Jose, Vitoria, Spain. Hosp Gen Univ Gregorio Maranon, Madrid, Spain. MD Anderson Espana, Madrid, Spain. Dorothy E Schneider Canc Ctr, San Mateo, CA USA. Mercy Med Ctr, Baltimore, MD USA. Univ Med & Dent New Jersey, Newark, NJ 07103 USA. Surg Oncol Associates, Newport News, VA USA. Roswell Pk Canc Ctr, Buffalo, NY USA. First Surg Univ Hosp, Belgrade, Serbia. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Baylor Univ, Med Ctr, Dallas, TX USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. Akad Univ Hosp, Uppsala, Sweden. Univ Washington, Seattle, WA 98195 USA. Univ Louisville, Louisville, KY 40292 USA. Helen F Graham Canc Ctr, Newark, DE USA. N Hampshire Hosp, Basingstoke, Hants, England. Hosp Med Sur, Tlalpan, Mexico. Kantonsspital, Dept Surg, St Gallen, Switzerland. NCI, Bethesda, MD 20892 USA. Univ Regensburg, D-8400 Regensburg, Germany. Dekalb Med Ctr, Decatur, GA USA. St Lukes Hosp, Bethlehem, PA USA. Maine Med Ctr, Portland, ME 04102 USA. Miami Valley Hosp, Xenia, OH USA. Tel Aviv Sourasky Med Ctr, Tel Aviv, Israel. Beebe Med Christiana Care, Lewes, DE USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Hosp Torrecardenas, Almeria, Spain. Fairview Univ, Med Ctr, Minneapolis, MN USA. Netherlands Canc Inst, Amsterdam, Netherlands. Hosp Virgen Las Nieves, Granada, Spain. Univ Iowa, Iowa City, IA USA. Soroka Univ, Med Ctr, Beer Sheva, Israel. RP Esquivel, J (reprint author), St Agnes Hosp, Baltimore, MD USA. EM jesusesquivel@yahoo.com RI Baratti, Dario/E-5502-2017 OI Baratti, Dario/0000-0002-5442-2642 NR 11 TC 223 Z9 234 U1 0 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD JAN PY 2007 VL 14 IS 1 BP 128 EP 133 DI 10.1245/s10434-006-9185-7 PG 6 WC Oncology; Surgery SC Oncology; Surgery GA 117CL UT WOS:000242850200016 PM 17072675 ER PT S AU Kessler, RC Merikangas, KR Wang, PS AF Kessler, Ronald C. Merikangas, Kathleen R. Wang, Philip S. TI Prevalence, comorbidity, and service utilization for mood disorders in the United States at the beginning of the twenty-first century SO ANNUAL REVIEW OF CLINICAL PSYCHOLOGY SE Annual Review of Clinical Psychology LA English DT Review; Book Chapter DE bipolar disorder; depression; manic-depression; major depressive disorder ID MAJOR DEPRESSIVE DISORDER; WORLD-HEALTH-ORGANIZATION; NATIONAL EPIDEMIOLOGIC SURVEY; PERFORMANCE QUESTIONNAIRE HPQ; DIAGNOSTIC INTERVIEW CIDI; IMPULSE-CONTROL DISORDERS; PRIMARY-CARE PHYSICIANS; BIPOLAR-I DISORDER; REPLICATION NCS-R; ANXIETY DISORDERS AB The results of recent community epidemiological research are reviewed, documenting that major depressive disorder (MDD) is a highly prevalent, persistent, and often seriously impairing disorder, and that bipolar disorder (BPD) is less prevalent but more persistent and more impairing than MDD. The higher persistence and severity of BPD results in a substantial proportion of all seriously impairing depressive episodes being due to threshold or subthreshold BPD rather than to MDD. Although the percentage of people with mood disorders in treatment has increased substantially since the early 1990s, a majority of cases remain either untreated or under-treated. An especially serious concern is the misdiagnosis of depressive episodes due to BPD as due to MDD because the majority of depression treatment involves medication provided by primary care doctors in the absence of psychotherapy. The article closes with a discussion of future directions for research. C1 [Kessler, Ronald C.] Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. [Merikangas, Kathleen R.] NIMH, Sect Dev Genet Epidemiol, Intramural Res Program, Bethesda, MD 20892 USA. [Wang, Philip S.] NIMH, Div Serv & Intervent Res, Bethesda, MD 20892 USA. RP Kessler, RC (reprint author), Harvard Univ, Sch Med, Dept Hlth Care Policy, Boston, MA 02115 USA. EM Kessier@hcp.med.harvard.edu FU NIDA NIH HHS [R01 DA016558]; NIMH NIH HHS [1 R13 MH066849, R01 MH069864, U01 MH60220] NR 140 TC 190 Z9 193 U1 7 U2 32 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1548-5943 BN 978-0-8243-3903-6 J9 ANNU REV CLIN PSYCHO JI Annu. Rev. Clin. Psychol. PY 2007 VL 3 BP 137 EP 158 DI 10.1146/annurev.clinpsy.3.022806.091444 PG 22 WC Psychology, Clinical; Psychology SC Psychology GA 295QK UT WOS:000255488800007 PM 17716051 ER PT S AU Klar, AJS AF Klar, Amar J. S. TI Lessons learned from studies of fission yeast mating-type switching and silencing SO ANNUAL REVIEW OF GENETICS SE Annual Review of Genetics LA English DT Review; Book Chapter DE fission yeast; cellular differentiation ID H3 LYSINE-9 METHYLATION; CHROMO-DOMAIN PROTEINS; DNA-POLYMERASE-ALPHA; SCHIZOSACCHAROMYCES-POMBE; RNA INTERFERENCE; SACCHAROMYCES-CEREVISIAE; HISTONE DEACETYLASE; EPIGENETIC CONTROL; MEIOTIC RECOMBINATION; S-POMBE AB Stably maintaining specific states of gene expression during cell division is crucial for cellular differentiation. In fission yeast, such patterns result from directed gene rearrangements and chromosomally inherited epigenetic gene control mechanisms that control mating cell type. Recent advances have shown that a specific DNA strand at the mat1 locus is "differentiated" by a novel strand-specific imprint so that nonequivalent sister chromatids are produced. Therefore, cellular differentiation is a natural consequence of the fact that DNA strands are complementary and nonequivalent. Another epigenetic control that "silences" library copies of mat-information is due to heterochromatin organization. This is a clear case where Mendel's gene is composed of DNA plus the associated epigenetic moiety. Following up on initial genetic studies with more recent molecular investigations, this system has become one of the prominent models to understand mechanisms of gene regulation, genome integrity, and cellular differentiation. By applying lessons learned from these studies, such epigenetic gene control mechanisms, which must be installed in somatic cells, might explain mechanisms of cellular differentiation and development in higher eukaryotes. C1 NIH, Gene Regulat & Chromosome Biol, Natl Canc Inst Frederick, Frederick, MD 21702 USA. RP Klar, AJS (reprint author), NIH, Gene Regulat & Chromosome Biol, Natl Canc Inst Frederick, Frederick, MD 21702 USA. EM klar@ncifcrf.gov FU Intramural NIH HHS NR 129 TC 61 Z9 61 U1 3 U2 12 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4197 BN 978-0-8243-1241-1 J9 ANNU REV GENET JI Annu. Rev. Genet. PY 2007 VL 41 BP 213 EP 236 DI 10.1146/annurev.genet.39.073103.094316 PG 24 WC Genetics & Heredity SC Genetics & Heredity GA 251GD UT WOS:000252359500011 PM 17614787 ER PT S AU Martin, SE Caplen, NJ AF Martin, Scott E. Caplen, Natasha J. TI Applications of RNA interference in mammalian systems SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE siRNA; shRNA; screen; gene expression; gene function; gene silencing; RNAi ID DOUBLE-STRANDED RNAS; ADULT-MOUSE BRAIN; HEPATITIS-B-VIRUS; SHORT HAIRPIN RNA; GROWTH IN-VITRO; GENE-EXPRESSION; HUMAN-CELLS; TRANSGENIC MICE; CANCER-CELLS; DEPENDENT STIMULATION AB RNA interference (RNAi) can mediate the long- or short-term silencing of gene expression at the DNA, RNA, and/or protein level. Although several triggers of RNAi have been identified, the best characterized of these are small interfering RNAs (siRNAs), which can decrease gene expression through mRNA transcript cleavage, and endogenous microRNAs (miRNAs), which primarily inhibit protein translation. An improved understanding of RNAi has provided new, powerful tools for conducting functional studies in a gene-specific manner. In various applications, RNAi has been used to create model systems, to identify novel molecular targets, to study gene function in a genome-wide fashion, and to create new avenues for clinical therapeutics. Here, we review many of the ongoing applications of RNAi in mammalian and human systems, and discuss how advances in our knowledge of the RNAi machinery have enhanced the use of these technologies. C1 Natl Inst Hlth, Natl Canc Ctr, Genet Branch, Gene Silencing Sect, Bethesda, MD 20892 USA. RP Martin, SE (reprint author), Natl Inst Hlth, Natl Canc Ctr, Genet Branch, Gene Silencing Sect, Bethesda, MD 20892 USA. EM martinsc@mail.mail.gov; ncaplen@mail.nih.gov RI Caplen, Natasha/H-2768-2016 OI Caplen, Natasha/0000-0002-0001-9460 FU Intramural NIH HHS NR 160 TC 83 Z9 92 U1 2 U2 12 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1527-8204 BN 978-0-8243-3708-7 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2007 VL 8 BP 81 EP 108 DI 10.1146/annurev.genom.8.080706.092424 PG 28 WC Genetics & Heredity SC Genetics & Heredity GA 221MY UT WOS:000250233200005 PM 17477824 ER PT S AU Elston, RC Lin, D Zheng, G AF Elston, Robert C. Lin, Danyu Zheng, Gang TI Multistage sampling for genetic studies SO ANNUAL REVIEW OF GENOMICS AND HUMAN GENETICS SE Annual Review of Genomics and Human Genetics LA English DT Review; Book Chapter DE association; DNA pooling; linkage analysis; genome-wide; segregation analysis; self-replication ID CASE-CONTROL ASSOCIATION; GENOME-WIDE ASSOCIATION; HARDY-WEINBERG DISEQUILIBRIUM; POOLED DNA SAMPLES; POPULATION STRATIFICATION; DISEASE ASSOCIATION; LINKAGE ANALYSIS; 2-STAGE DESIGNS; LOGISTIC-REGRESSION; PAIR LINKAGE AB In the past, to study Mendelian diseases, segregating families have been carefully ascertained for segregation analysis, followed by collecting extended multiplex families for linkage analysis. This would then be followed by association studies, using independent case-control samples and/or additional family data. Recently, for complex diseases, the initial sampling has been for a genome-wide linkage analysis, often using independent sib-pairs or nuclear families, to identify candidate regions for follow-up with association studies, again using case-control samples and/or additional family data. We now have the ability to conduct genome-wide association studies using 100,000-500,000 diallelic genetic markers. For such studies we focus especially on efficient two-stage association sampling designs, which can retain nearly optimal statistical power at about half the genotyping cost. Similarly, beginning an association study by genotyping pooled samples may also be a viable option if the cost of accurately pooling DNA samples outweighs genotyping costs. Finally, we note that the sampling of family data for linkage analysis is not a practice that should be automatically discontinued. C1 Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Elston, RC (reprint author), Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44106 USA. EM rce@darwin.case.edu; lin@bios.une.edu; zhengg@nhlbi.nih.gov FU NCI NIH HHS [CA82659]; NCRR NIH HHS [RR03655]; NIGMS NIH HHS [GM-28356]; PHS HHS [P30CAD43703] NR 74 TC 19 Z9 20 U1 1 U2 5 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1527-8204 BN 978-0-8243-3708-7 J9 ANNU REV GENOM HUM G JI Annu. Rev. Genomics Hum. Genet. PY 2007 VL 8 BP 327 EP 342 DI 10.1146/annurev.genom.8.080706.092357 PG 16 WC Genetics & Heredity SC Genetics & Heredity GA 221MY UT WOS:000250233200015 PM 17506660 ER PT S AU Chen, J Subbarao, K AF Chen, Jun Subbarao, Kanta TI The immunobiology of SARS SO ANNUAL REVIEW OF IMMUNOLOGY SE Annual Review of Immunology LA English DT Review; Book Chapter DE SARS-CoV; ACE2; immune response; chemokines; cytokines ID ACUTE-RESPIRATORY-SYNDROME; SYNDROME-ASSOCIATED CORONAVIRUS; INFLUENZA-A H5N1; ANGIOTENSIN-CONVERTING ENZYME-2; HUMAN MONOCLONAL-ANTIBODY; ACTIVATED PROTEIN-KINASE; IN-SITU HYBRIDIZATION; HUMAN DENDRITIC CELLS; DC-SIGN CD209; SPIKE PROTEIN AB Severe acute respiratory syndrome (SARS) presented as an atypical pneumonia that progressed to acute respiratory distress syndrome in similar to 20% of cases and was associated with a mortality of about 10%. The etiological agent was a novel coronavirus (CoV). Angiotensin-converting enzyme 2 is the functional receptor for SARS-CoV; DC-SIGN and CD209L (L-SIGN) can enhance viral entry. Although the virus infects the lungs, gastrointestinal tract, liver, and kidneys, the disease is limited to the lungs, where diffuse alveolar damage is accompanied by a disproportionately sparse inflammatory infiltrate. Pro-inflammatory cytokines and chemokines, particularly IP-10, IL-8, and MCP-1, are elevated in the lungs and peripheral blood, but there is an unusual lack of an antiviral interferon (IFN) response. The virus is susceptible to exogenous type I IFN but suppresses the induction of IFN. Innate immunity is important for viral clearance in the mouse model. Virus-specific neutralizing antibodies that develop during convalescence prevent reinfection in animal models. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Chen, J (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM chenju@niaid.nih.gov; KSubbarao@niaid.nih.gov FU Intramural NIH HHS NR 173 TC 61 Z9 67 U1 3 U2 13 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0732-0582 BN 978-0-8243-3025-5 J9 ANNU REV IMMUNOL JI Annu. Rev. Immunol. PY 2007 VL 25 BP 443 EP 472 DI 10.1146/annurev.immunol.25.022106.141706 PG 30 WC Immunology SC Immunology GA 167FP UT WOS:000246437100016 PM 17243893 ER PT J AU Neuman, KC Lionnet, T Allemand, JF AF Neuman, K. C. Lionnet, T. Allemand, J.-F TI Single-molecule micromanipulation techniques SO ANNUAL REVIEW OF MATERIALS RESEARCH SE Annual Review of Materials Research LA English DT Review; Book Chapter DE optical tweezers; magnetic tweezers; polymer elasticity; microrheology; biophysics; soft condensed matter physics ID ATOMIC-FORCE MICROSCOPY; OPTICAL TWEEZERS; RNA-POLYMERASE; STRUCTURAL TRANSITIONS; DIELECTRIC PARTICLES; MAGNETIC TWEEZERS; LASER TWEEZERS; LOCAL VISCOELASTICITY; GOLD NANOPARTICLES; MECHANICAL FORCE AB Single-molecule micrornanipulation techniques traditionally have been developed for biophysical applications, but they are being increasingly employed in materials science applications such as theology and polymer dynamics. Continuing developments and improvements in single-molecule manipulation techniques afford new opportunities in a broad range of fields. In this review we present an overview of current single-molecule manipulation techniques, with an emphasis on optical and magnetic tweezers, followed by a description of the elastic properties of single biopolymers. We then review die use of micrornanipulation techniques to locally probe material properties. To provide some insight into biophysical questions addressed by these techniques, we describe two applications, which further serve to illustrate the power and versatility of single-molecule micromanipulation techniques. We conclude with a brief discussion of emerging applications and techniques. C1 NHLBI, Lab Mol Biophys, NIH, Bethesda, MD 20892 USA. Ecole Normale Super, Phys Stat Lab, F-75005 Paris, France. Ecole Normale Super, Dept Biol, F-75005 Paris, France. Ecole Normale Super, Dept Chim, Lab Pasteur, F-75005 Paris, France. CNRS, UMR Associe 8550, Paris, France. Univ Paris 06, Paris, France. Univ Paris 07, Paris, France. RP Neuman, KC (reprint author), NHLBI, Lab Mol Biophys, NIH, Bldg 10, Bethesda, MD 20892 USA. EM neumankc@mail.nih.gov; lionnet@lps.ens.fr; allemand@lps.ens.fr RI Neuman, Keir/F-7400-2011 OI Neuman, Keir/0000-0002-0863-5671 NR 137 TC 73 Z9 73 U1 4 U2 40 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 1531-7331 J9 ANNU REV MATER RES JI Ann. Rev. Mater. Res. PY 2007 VL 37 BP 33 EP 67 DI 10.1146/annurev.matsci.37.052506.084336 PG 35 WC Materials Science, Multidisciplinary SC Materials Science GA 200IY UT WOS:000248758300003 ER PT S AU Pastan, I Hassan, R FitzGerald, DJ Kreitman, RJ AF Pastan, Ira Hassan, Raffit FitzGerald, David J. Kreitman, Robert J. TI Immunotoxin treatment of cancer SO ANNUAL REVIEW OF MEDICINE SE Annual Review of Medicine LA English DT Review; Book Chapter DE Pseudomonas toxin; diphtheria toxin; monoclonal antibody; recombinant immunotoxin ID PHASE-I TRIAL; NON-HODGKINS-LYMPHOMA; HAIRY-CELL LEUKEMIA; A-CHAIN IMMUNOTOXIN; ADVANCED SOLID TUMORS; BONE-MARROW-TRANSPLANTATION; INTERLEUKIN-2 FUSION TOXIN; DENILEUKIN DIFTITOX ONTAK; METASTATIC COLON-CANCER; ACUTE MYELOID-LEUKEMIA AB Immunotoxms are proteins used to treat cancer that are composed of an antibody fragment linked to a toxin. The immunotoxin binds to a surface antigen on a cancer cell, enters the cell by endocytosis, and kills it. The most potent immunotoxins are made from bacterial and plant toxins. Refinements over many years have produced recombinant immunotoxins; these therapeutic proteins are made using protein engineering. Individual immunotoxins are designed to treat specific cancers. To date, most success has been achieved treating hematologic tumors. Obstacles to successful treatment of solid tumors include poor penetration into tumor masses and the immune response to the toxin component of the immunotoxin, which limits the number of cycles that can be given. Strategies to overcome these limitations are being pursued. C1 NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Pastan, I (reprint author), NCI, Mol Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. EM pastani@mail.nih.gov NR 100 TC 234 Z9 245 U1 3 U2 24 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4219 BN 978-0-8243-0558-1 J9 ANNU REV MED JI Annu. Rev. Med. PY 2007 VL 58 BP 221 EP 237 DI 10.1146/annurev.med.58.070605.115320 PG 21 WC Medicine, General & Internal SC General & Internal Medicine GA 139VU UT WOS:000244461500015 PM 17059365 ER PT S AU Dautin, N Bernstein, HD AF Dautin, Nathalie Bernstein, Harris D. TI Protein secretion in gram-negative bacteria via the autotransporter pathway SO ANNUAL REVIEW OF MICROBIOLOGY SE Annual Review of Microbiology LA English DT Review; Book Chapter DE bacterial pathogenesis; beta barrel; beta helix; outer membrane proteins; protein translocation ID ENTEROTOXIGENIC ESCHERICHIA-COLI; OUTER-MEMBRANE PROTEIN; SIGNAL RECOGNITION PARTICLE; INFLUENZAE HAP AUTOTRANSPORTER; TOXIN-B-SUBUNIT; HELICOBACTER-PYLORI; VACUOLATING TOXIN; AIDA-I; SHIGELLA-FLEXNERI; NEISSERIA-MENINGITIDIS AB Autotransporters are a large and diverse superfamily of proteins produced by pathogenic gram-negative bacteria that are composed of an N-terminal passenger domain, which typically harbors a virulence function, and a C-terminal beta domain. It has long been known that the beta domain anchors the protein to the outer membrane and facilitates transport of the passenger domain into the extracellular space. Despite the apparent simplicity of the autotransporter pathway, several aspects of autotransporter biogenesis remain poorly understood, most notably the mechanism by which the passenger domain is translocated across the outer membrane. Here we review recent evidence that the enormous sequence diversity of both passenger and beta domains belies a remarkable conservation of structure. We also discuss insights into each stage of autotransporter biogenesis that have emerged from recent structural, biochemical, and imaging studies. C1 NIH, NIDDK, Genet & Biochem Branch, Bethesda, MD 20892 USA. RP Dautin, N (reprint author), NIH, NIDDK, Genet & Biochem Branch, Bethesda, MD 20892 USA. EM nathalied@niddk.nih.gov; harris_bernstein@nih.gov FU Intramural NIH HHS NR 97 TC 184 Z9 188 U1 3 U2 30 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4227 BN 978-0-8243-1161-2 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2007 VL 61 BP 89 EP 112 DI 10.1146/annurev.micro.61.080706.093233 PG 24 WC Microbiology SC Microbiology GA 231RB UT WOS:000250965600007 PM 17506669 ER PT S AU Anantharaman, V Iyer, LM Aravind, L AF Anantharaman, Vivek Iyer, Lakshminarayan M. Aravind, L. TI Comparative genomics of protists: New insights into the evolution of eukaryotic signal transduction and gene regulation SO ANNUAL REVIEW OF MICROBIOLOGY SE Annual Review of Microbiology LA English DT Review; Book Chapter DE Apicomplexa; amoebozoa; kinases; ubiquitin; GTPases; cyclic nucleotides ID PLASMODIUM-FALCIPARUM; PROTOZOAN PARASITES; RNA INTERFERENCE; SMALL GTPASES; HISTONE H3; PROTEIN; DOMAINS; DICTYOSTELIUM; TRANSCRIPTION; APICOMPLEXA AB Data from protist genomes suggest that eukaryotes show enormous variability in their gene complements, especially of genes coding regulatory proteins. Overall counts of eukaryotic signaling proteins show weak nonlinear scaling with proteome size, but individual superfamilies of signaling domains might show vast expansions in certain protists. Alteration of domain architectural complexity of signaling proteins and repeated lineage-specific reshaping of architectures might have played a major role in the emergence of new signaling interactions in different eukaryotes. Lateral transfer of various signaling domains from bacteria or from hosts, in parasites such as apicomplexans, appears to also have played a major role in the origin of new functional networks. Lineage-specific expansion of regulatory proteins, particularly of transcription factors, has played a critical role in the adaptive radiation of different protist lineages. Comparativc genomics allows objective reconstruction of the ancestral conditions and subsequent diversification of several regulatory systems involved in phosphorylation, cyclic nucleotide signaling, Ubiquitin conjugation, chromatin remodeling, and posttranscriptional gene silencing. C1 Natl Lib Med, Natl Inst Hlth, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Aravind, L (reprint author), Natl Lib Med, Natl Inst Hlth, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. EM aravind@mail.nih.gov OI Anantharaman, Vivek/0000-0001-8395-0009 FU Intramural NIH HHS NR 73 TC 38 Z9 38 U1 0 U2 6 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4227 BN 978-0-8243-1161-2 J9 ANNU REV MICROBIOL JI Annu. Rev. Microbiol. PY 2007 VL 61 BP 453 EP 475 DI 10.1146/annurev.micro.61.080706.093309 PG 23 WC Microbiology SC Microbiology GA 231RB UT WOS:000250965600023 PM 17506670 ER PT S AU Murray, EA Bussey, TJ Saksida, LM AF Murray, Elisabeth A. Bussey, Timothy J. Saksida, Lisa M. TI Visual perception and memory: A new view of medial temporal lobe function in primates and rodents SO ANNUAL REVIEW OF NEUROSCIENCE SE Annual Review of Neuroscience LA English DT Review; Book Chapter DE declarative memory; object perception; object recognition; spatial memory; feature conjunctions; configural learning ID PERIRHINAL CORTEX LESIONS; NONMATCHING-TO-SAMPLE; SELECTIVE HIPPOCAMPAL DAMAGE; OBJECT RECOGNITION MEMORY; SPATIAL MEMORY; DOUBLE DISSOCIATION; EXCITOTOXIC LESIONS; LOCATION MEMORY; RHESUS-MONKEYS; RHINAL CORTEX AB The prevailing view of medial temporal lobe (MTL) function has two principal elements: first, that the MTL subserves memory but not perception, and second, that the many anatomically distinctive parts of the MTL function together in the service of declarative memory. Recent neuropsychological studies have, however, challenged both opinions. First, studies in rodents, nonhuman primates, and humans suggest that the perirhinal cortex represents information about objects for both mnemonic and perceptual purposes. Second, the idea that MTL components contribute to declarative memory in similar ways has also been contradicted. Whereas the perirhinal cortex plays an essential role in familiarity-based object recognition, the hippocampus contributes little, if at all, to this function. In both primates and rodents, the hippocampus contributes to the memory and perception of places and paths, whereas the perirhinal cortex does so for objects and the contents of scenes. C1 NIMH, NIH, Neuropsychol Lab, Sect Neurobiol Learning & Memory, Bethesda, MD 20892 USA. Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. Univ Cambridge, MRC, Cambridge CB2 3EB, England. Univ Cambridge, Wellcome Trust Behav & Clin Neurosci Inst, Cambridge CB2 3EB, England. RP Murray, EA (reprint author), NIMH, NIH, Neuropsychol Lab, Sect Neurobiol Learning & Memory, Bethesda, MD 20892 USA. EM murraye@mail.nih.gov; tjb1000@cam.ac.uk; lms42@cam.ac.uk RI Bussey, Timothy/M-2758-2016; Saksida, Lisa/M-2753-2016; OI Bussey, Timothy/0000-0001-7518-4041; Saksida, Lisa/0000-0002-8416-8171; Murray, Elisabeth/0000-0003-1450-1642 FU Medical Research Council [G0001354] NR 96 TC 218 Z9 219 U1 5 U2 35 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0147-006X BN 978-0-8243-2430-8 J9 ANNU REV NEUROSCI JI Annu. Rev. Neurosci. PY 2007 VL 30 BP 99 EP 122 DI 10.1146/annurev.neuro.29.051605.113046 PG 24 WC Neurosciences SC Neurosciences & Neurology GA 200AD UT WOS:000248735400005 PM 17417938 ER PT S AU Lei, XG Cheng, WH McClung, JP AF Lei, Xin Gen Cheng, Wen-Hsing McClung, James P. TI Metabolic regulation and function of glutathione peroxidase-1 SO ANNUAL REVIEW OF NUTRITION SE Annual Review of Nutrition LA English DT Review; Book Chapter DE selenium; reactive oxygen species; reactive nitrogen species; signaling; chronic disease ID NF-KAPPA-B; BREAST-CANCER RISK; MITOCHONDRIAL OXIDATIVE STRESS; ISCHEMIA-REPERFUSION INJURY; DEPENDENT DIABETES-MELLITUS; BETA-MEDIATED NEUROTOXICITY; SELENOCYSTEINE TRANSFER-RNA; SELENIUM DEFICIENCY; NITRIC-OXIDE; SUPEROXIDE-DISMUTASE AB Glutathione peroxidase-1 (GPX1) represents the first identified mammalian selenoprotein, and our understanding in the metabolic regulation and function of this abundant selenoenzyme has greatly advanced during the past decade. Selenocysteine insertion sequence associating factors, adenosine, and Abl and Arg tyrosine kinases are potent, Se-independent regulators of GPX1 gene, protein, and activity. Overwhelming evidences have been generated using the GPX1 knockout and transgenic mice for the in vivo protective role of GPX1 in coping with oxidative injury and death mediated by reactive oxygen species. However, GPX1 exerts an intriguing dual role in reactive nitrogen species (RNS)-related oxidative stress. Strikingly, knockout of GPX1 rendered mice resistant to toxicities of drugs including acetaminophen and kainic acid, known as RNS inducers. Intracellular and tissue levels of GPX1 activity affect apoptotic signaling pathway, protein kinase phosphorylation, and oxidant-mediated activation of NF kappa B. Data are accumulating to link alteration or abnormality of GPX1 expression to etiology of cancer, cardiovascular disease, neurodegeneration, autoimmune disease, and diabetes. Future research should focus on the mechanism of GPX1 in the pathogeneses and potential applications of GPX1 manipulation in the treatment of these disorders. C1 Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. USA, Environm Med Res Inst, Mil Nutr Div, Natick, MA 01760 USA. RP Lei, XG (reprint author), Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. EM XL20@Cornell.edu RI McClung, James/A-1989-2009 FU Intramural NIH HHS; NIDDK NIH HHS [DK 53018, R01 DK053018] NR 151 TC 111 Z9 120 U1 5 U2 19 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0199-9885 BN 978-0-8243-2827-6 J9 ANNU REV NUTR JI Annu. Rev. Nutr. PY 2007 VL 27 BP 41 EP 61 DI 10.1146/-annurev.nutr.27.061406.093716 PG 23 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 236CK UT WOS:000251280400004 PM 17465855 ER PT S AU Murphy, E Steenbergen, C AF Murphy, Elizabeth Steenbergen, Charles TI Preconditioning: The mitochondrial connection SO ANNUAL REVIEW OF PHYSIOLOGY SE Annual Review of Physiology LA English DT Review; Book Chapter DE mitochondrial permeability transition; glycogen synthase kinase; protein kinase C; voltage-dependent anion channel ID PERMEABILITY TRANSITION PORE; DEPENDENT ANION CHANNEL; PROTEIN-KINASE-C; GLYCOGEN-SYNTHASE KINASE-3-BETA; SENSITIVE K+ CHANNEL; INDUCED CARDIOPROTECTION; POTASSIUM CHANNELS; NITRIC-OXIDE; CELL-DEATH; RAT HEARTS AB Over the past decade there has been considerable progress in elucidating the signaling pathways involved in cardioprotection. siderable recent data suggest that many of these signaling pathways converge on the mitochondria, where such pathways alter the activity of key mitochondrial proteins, leading to reduced apoptosis and necrosis. Inhibition of the mitochondrial permeability transition pore is emerging as a central mechanism in cardioprotection. This review focuses on mechanisms by which cardioprotection alters mitochondrial proteins and channels that regulate cell death and survival. C1 Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21205 USA. RP Murphy, E (reprint author), Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. EM murphy1@niehs.nih.gov; csteenb1@jhmi.edu FU NHLBI NIH HHS [R01 HL039752] NR 93 TC 141 Z9 144 U1 0 U2 2 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4278 BN 978-0-8243-0369-3 J9 ANNU REV PHYSIOL JI Annu. Rev. Physiol. PY 2007 VL 69 BP 51 EP 67 DI 10.1146/annurev.physiol.69.031905.163645 PG 17 WC Physiology SC Physiology GA 152BB UT WOS:000245334100006 PM 17007587 ER PT S AU Martin, A AF Martin, Alex TI The representation of object concepts in the brain SO ANNUAL REVIEW OF PSYCHOLOGY SE Annual Review of Psychology LA English DT Review; Book Chapter DE semantic memory; fnsiform gyrus; temporal lobes; category specificity ID HUMAN VISUAL-CORTEX; CATEGORY-SPECIFIC DEFICITS; RESONANCE-IMAGING EVIDENCE; TEMPORAL-LOBE ATROPHY; FUSIFORM FACE AREA; BIOLOGICAL MOTION; CORTICAL ACTIVITY; SEMANTIC MEMORY; MANIPULATABLE OBJECTS; NEURAL MECHANISMS AB Evidence from functional neutoimaging of the human brain indicates that information about salient properties of an object-such as what it looks like, how it moves, and how it is used-is stored in sensory and motor systems active when that information was acquired. As a result, object concepts belonging to different categories like animals and tools are represented in partially distinct, sensory- and motor property-based neural networks. This suggests that object concepts are not explicitly represented, but rather emerge from weighted activity within property-based brain regions. However, some property-based regions seem to show a categorical organization, thus providing evidence consistent with category-based, domain-specific formulations as well. C1 NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Martin, A (reprint author), NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. EM alexmartin@mail.nih.gov RI martin, alex/B-6176-2009 FU Intramural NIH HHS NR 137 TC 742 Z9 755 U1 14 U2 106 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0066-4308 BN 978-0-8243-0258-0 J9 ANNU REV PSYCHOL JI Annu. Rev. Psychol. PY 2007 VL 58 BP 25 EP 45 DI 10.1146/annurev.psych.57.102904.190143 PG 25 WC Psychology; Psychology, Multidisciplinary SC Psychology GA 131VX UT WOS:000243900200002 PM 16968210 ER PT J AU Bornstein, MH AF Bornstein, Marc H. BE MacLaury, RE Paramei, GV Dedrick, D TI Hue categorization and color naming Cognition to language to culture SO ANTHROPOLOGY OF COLOR: INTERDISCIPLINARY MULTILEVEL MODELING LA English DT Article; Book Chapter ID CATEGORICAL PERCEPTION; NONTRIVIAL CONSTRAINTS; CHROMATIC ABERRATION; SPECTRAL SENSITIVITY; YOUNG-CHILDREN; VISION; DISCRIMINATION; TERMS; EYE; AGE C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Bornstein, MH (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. NR 133 TC 3 Z9 3 U1 0 U2 3 PU JOHN BENJAMINS B V PUBL PI AMSTERDAM ME PA PO BOX 36224, 1020 AMSTERDAM ME, NETHERLANDS BN 978-90-272-9170-7 PY 2007 BP 3 EP 27 PG 25 WC Anthropology; Linguistics SC Anthropology; Linguistics GA BBI46 UT WOS:000306965700003 ER PT J AU Ware, JH Zhou, ZZ Guan, J Kennedy, AR Kopelovich, L AF Ware, Jeffrey H. Zhou, Zhaczong Guan, Jun Kennedy, Ann R. Kopelovich, Levy TI Establishment of human cancer cell clones with different characteristics: A model for screening chemopreventive agents SO ANTICANCER RESEARCH LA English DT Article DE parental population; human cancer cell clones; limiting dilution ID PROSTATE-SPECIFIC ANTIGEN; BREAST-CANCER; SUPEROXIDE-DISMUTASE; COLON-CANCER; NUDE-MICE; MULTISTAGE CARCINOGENESIS; ANDROGEN DEPRIVATION; INDEPENDENT GROWTH; URINARY-BLADDER; GENE-EXPRESSION AB Background: The present study was undertaken in order to establish phenotypically different cell clones from 10 parental lines of human breast (MCF-7 and T-47D), prostate (PC-3 and DU145), lung (A549 and A427), colon (HCT-116 and HT-29) and bladder (TCCSUP and T24) cancer cells. Materials and Methods: Sublines were established from each of the parental lines by the limiting dilution method. The derived clones were characterized in terms of plating efficiency, cell proliferation rate, saturation density and colony formation efficiency in soft agar. Results: Phenotypically different cell clones were derived from each parental human cancer cell line, with many clones having more 'normal' characteristics than the parental line from which they were derived. Conclusion: Phenotypically normal clones obtained through clonal selection from human cancer cell populations are expected to be a useful tool for the screening of cancer chemopreventive agents and the study of tumor progression. C1 Univ Penn, Sch Med, Dept Radiat Oncol, Div Oncol Res, Philadelphia, PA 19104 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Ware, JH (reprint author), Univ Penn, Sch Med, Dept Radiat Oncol, Div Oncol Res, 195 John Morgan Bldg,3620 Hamilton Walk, Philadelphia, PA 19104 USA. EM jhware@mail.med.upenn.edu FU NCI NIH HHS [N01-CN-25107] NR 53 TC 5 Z9 5 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 JAN-FEB PY 2007 VL 27 IS 1A BP 1 EP 16 PG 16 WC Oncology SC Oncology GA 140ZJ UT WOS:000244545200001 PM 17352209 ER PT J AU Weecharangsan, W Opanasopit, P Lee, RJ AF Weecharangsan, Wanlop Opanasopit, Praneet Lee, Robert J. TI In vitro gene transfer using cationic vectors, electroporation and their combination SO ANTICANCER RESEARCH LA English DT Article DE gene transfer; transfection; polyethylenimine; lipofectamine; electroporation ID DELIVERY; POLYETHYLENIMINE; CELLS; VIVO; LIPOSOMES AB Background: The aim of this study was to investigate the transfection efficiency of cationic vectors (polyethylenimine; PEI25K and lipofectamine (TM)), electroporation and their combination in the human cancer cell lines, Raji human lymphoma and KB human oral carcinoma. Materials and Methods: Raji human lymphoma and KB human oral carcinoma cell lines were transfected with pcDNA3-CMV-Luc at various NIP ratios of cationic vectors and voltages of electroporation, as well as with a combination of the cationic vectors and electroporation. Results: The major findings were: (a) cationic vectors or electroporation alone increased transfection efficiency; (b) cationic vectors inhibited the transfection efficiency by electroporation. Conclusion: Our results demonstrate that cationic vectors and electroporation are feasible and efficient in transfecting human cancer cell lines. However, a combination of cationic vectors and electroporation is ineffective. C1 Ohio State Univ, Coll Pharm, NCI,NSEC CANPBD, Ctr Comprehens Canc,Div Pharmaceut, Columbus, OH 43210 USA. Silpakorn Univ, Dept Pharmaceut Technol, Nakhon Pathom, Thailand. RP Lee, RJ (reprint author), Ohio State Univ, Coll Pharm, NCI,NSEC CANPBD, Ctr Comprehens Canc,Div Pharmaceut, 542 LM Parks Hall,500 W 12th Ave, Columbus, OH 43210 USA. EM lee.1339@osu.edu NR 12 TC 10 Z9 10 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 JAN-FEB PY 2007 VL 27 IS 1A BP 309 EP 313 PG 5 WC Oncology SC Oncology GA 140ZJ UT WOS:000244545200040 PM 17354325 ER PT J AU Hope, WW Drusano, GL Moore, CB Sharp, A Louie, A Walsh, TJ Denning, DW Warn, PA AF Hope, William W. Drusano, George L. Moore, Caroline B. Sharp, Andrew Louie, Arnold Walsh, Thomas J. Denning, David W. Warn, Peter A. TI Effect of neutropenia and treatment delay on the response to antifungal agents in experimental disseminated candidiasis SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID COLONY-STIMULATING FACTOR; BLOOD-STREAM INFECTIONS; BREAKTHROUGH CANDIDEMIA; ATTRIBUTABLE MORTALITY; SYSTEMIC CANDIDIASIS; INTERFERON-GAMMA; ACUTE-LEUKEMIA; MURINE MODEL; RISK-FACTORS; ALBICANS AB Disseminated candidiasis is associated with a high rate of morbidity and mortality. The presence of neutrophills and the timely administration of antifungall agents are likely to be critical factors for a favorable therapeutic outcome of this syndrome. The effect of neutropenia on the temporal profile of the burden of Candida albicans in untreated mice and those treated with amphotericin B was determined using a pharmacodynamic model of disseminated candidiasis. A mathematical model was developed to describe the rate and extent of the C albicans killing attributable to neutrophils and to amphotericin B. The consequences of a delay in the administration of amphotericin B, flucytosine, or micafungin were studied by defining dose-response relationships. Neutrophils caused a logarithmic decline in fungal burden in treated and untreated mice. The combination of amphotericin B and neutrophils resulted in a high rate of Candida killing and a sustained anti-C. albicans effect. In neutropenic mice, 5 mg/kg of body weight of amphotericin B was required to prevent progressive logarithmic growth. An increased delay in drug administration resulted in a reduction in the maximum effect to a point at which no drug effect could be observed. Neutrophills and the timely initiation of antifungal agents are critical determinants in the treatment of experimental disseminated candidiasis. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. Univ Manchester, Sch Med, Manchester M13 9PT, Lancs, England. Ordway Res Inst, Emerging Infect & Host Def Sect, Albany, NY 12208 USA. Wythenshawe Hosp, Manchester M23 9LT, Lancs, England. RP Hope, WW (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, CRC Room 1-5750,10 Ctr Dr,MSC 1100, Bethesda, MD 20892 USA. EM hopew@mail.nih.gov OI Denning, David/0000-0001-5626-2251; Hope, William/0000-0001-6187-878X NR 32 TC 25 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD JAN PY 2007 VL 51 IS 1 BP 285 EP 295 DI 10.1128/AAC.00601-06 PG 11 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 122GR UT WOS:000243214200037 PM 17088486 ER PT J AU Larder, B Wang, DC Revell, A Montaner, J Harrigan, R De Wolf, F Lange, J Wegner, S Ruiz, L Perez-Elias, MJ Emery, S Gatell, J Monforte, AD Torti, C Zazzi, M Lane, C AF Larder, Brendan Wang, Dechao Revell, Andrew Montaner, Julio Harrigan, Richard De Wolf, Frank Lange, Joep Wegner, Scott Ruiz, Lidia Perez-Elias, Maria Jesus Emery, Sean Gatell, Jose Monforte, Antonello D'Arminio Torti, Carlo Zazzi, Maurizio Lane, Clifford TI The development of artificial neural networks to predict virological response to combination HIV therapy SO ANTIVIRAL THERAPY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; DRUG-RESISTANCE; VIRTUAL PHENOTYPE; GENOTYPE; RECOMMENDATIONS; SUSCEPTIBILITY; MANAGEMENT; LOPINAVIR; PROTEASE; SYSTEMS AB Introduction: When used in combination, antiretroviral drugs are highly effective for suppressing HIV replication. Nevertheless, treatment failure commonly occurs and is generally associated with viral drug resistance. The choice of an alternative regimen may be guided by a drug-resistance test. However, interpretation of resistance from genotypic data poses a major challenge. Methods: As an alternative to current interpretation systems, we have developed artificial neural network (ANN) models to predict virological response to combination therapy from HIV genotype and other clinical information. Results: ANN models trained with genotype, baseline viral load and time to follow-up viral load (1,154 treatment change episodes from multiple clinics), produced predictions of virological response that were highly significantly correlated with actual responses (r(2)=0.53; P < 0.00001) using independent test data from clinics that contributed training data. Augmented models, trained with the additional variables of baseline CD4(+) T-cell count and four treatment history variables, were more accurate, explaining 69% of the variance in virological response. Models trained with the full input dataset, but only those data involving highly active antiretroviral therapy (three or more full-dose antiretroviral drugs in combination), performed at an intermediate level, explaining 61% of the variance. The augmented models performed less well when tested with data from unfamiliar clinics that had not contributed data to the training dataset, explaining 46% of the variance in response. Conclusion: These data indicate that ANN models can be quite accurate predictors of virological response to HIV therapy even for patients from unfamiliar clinics. ANN models therefore warrant further development as a potential tool to aid treatment selection. C1 HIV Resistance Response Database Initiat, London, England. BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. Netherlands HIV Monitoring Fdn, Amsterdam, Netherlands. Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Fundacio IrsiCaixa, Badalona, Spain. Ramon & Cajal Hosp, Madrid, Spain. Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. Hosp Clin Barcelona, Barcelona, Spain. Univ Milan, Milan, Italy. Univ Brescia, Inst Infect & Trop Dis, Brescia, Italy. Univ Siena, I-53100 Siena, Italy. NIAID, Bethesda, MD 20892 USA. RP Larder, B (reprint author), HIV Resistance Response Database Initiat, London, England. EM brendanlarder@hivrdi.org NR 41 TC 39 Z9 40 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 1 BP 15 EP 24 PG 10 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 176UU UT WOS:000247111200003 PM 17503743 ER PT J AU Modi, AA Wright, EC Seeff, LB AF Modi, Apurva A. Wright, Elizabeth C. Seeff, Leonard B. TI Complementary and alternative medicine (CAM) for the treatment of chronic hepatitis B and C: a review SO ANTIVIRAL THERAPY LA English DT Review ID SHO-SAIKO-TO; RANDOMIZED CONTROLLED-TRIALS; JAPANESE HERBAL MEDICINES; PLACEBO-CONTROLLED TRIAL; BLOOD MONONUCLEAR-CELLS; PREVENTS LIVER FIBROSIS; HEPATOCELLULAR-CARCINOMA; PHYLLANTHUS-AMARUS; CONSORT STATEMENT; VIRUS-INFECTION AB Complementary and alternative medicine (CAM) has been used for centuries in China and Japan to treat various illnesses, including viral hepatitis. Several therapeutic approaches constitute CAM, the most relevant for this review being the use of herbals. However, profound disagreements exist between conventional and alternative medicine practitioners regarding their value. Western medical advocates cite deep concerns about the purity of most herbals because of lack of standardized production, the paucity of pharmacokinetic data, the fact that few well-designed randomized, controlled trials of these products have been performed and the evidence that some herbals have been responsible for severe adverse effects. Nevertheless, many in the public, even in western countries, turn to the use of herbals, believing that they must be safe and effective because they are 'natural' and have been used for centuries, and because of dissatisfaction with conventional medicine. Accordingly, their use in western countries and the costs incurred have increased each year. While there is evidence that some herbals have physiological effects, there still is insufficient evidence to recommend their use. This paper reviews the classification, epidemiology and philosophy of CAM, and the reasons advanced for herbal use to treat viral hepatitis. The criteria necessary to develop a potential pharmacological agent are presented, as well as the requirements for conducting a scientifically valid treatment trial of herbals. Five herbals used in the past to treat viral hepatitis are reviewed and evaluated for the quality of their studies and mention is made of herbals known to have adverse effects. C1 NIH, NIDDK, Bethesda, MD 20892 USA. RP Seeff, LB (reprint author), NIH, NIDDK, Bldg 10, Bethesda, MD 20892 USA. EM seeffl@extra.niddk.nih.gov NR 101 TC 16 Z9 17 U1 3 U2 5 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 3 BP 285 EP 295 PG 11 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 176UY UT WOS:000247111600001 PM 17591018 ER PT J AU Taubenberger, JK Hultin, JV Morens, DM AF Taubenberger, Jeffery K. Hultin, Johan V. Morens, David M. TI Discovery and characterization of the 1918 pandemic influenza virus in historical context SO ANTIVIRAL THERAPY LA English DT Review ID FILTER-PASSING VIRUS; EPIDEMIC INFLUENZA; AVIAN INFLUENZA; A VIRUSES; HEMAGGLUTININ GENE; HOST IMMUNE; ETIOLOGY; ORIGIN; CULTIVATION; PATHOGENICITY AB The 2005 completion of the entire genome sequence of the 1918 H1N1 pandernic influenza virus represents both a beginning and an end. Investigators have already begun to study the virus in vitro and in vivo to better understand its properties, pathogenicity, transmissibility and elicitation of host responses. Although this is an exciting new beginning, characterization of the 1918 virus also represents the culmination of over a century of scientific research aiming to understand the causes of pandemic influenza. In this brief review we attempt to place in historical context the identification and sequencing of the 1918 virus, including the alleged discovery of a bacterial cause of influenza during the 1889-1893 pandemic, the controversial detection of 'filter-passing agents' during the 1918-1919 pandernic, and subsequent breakthroughs in the 1930s that led to isolation of human and swine influenza viruses, greatly influencing the development of modern virology. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Taubenberger, JK (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM taubenbergerj@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000995-01] NR 105 TC 52 Z9 58 U1 0 U2 11 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 4 BP 581 EP 591 PN B PG 11 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 197IA UT WOS:000248546600002 PM 17944266 ER PT J AU Loomba, R Liang, TJ AF Loomba, Rohit Liang, T. Jake TI Treatment of chronic hepatitis B SO ANTIVIRAL THERAPY LA English DT Review ID HBEAG(+) CHRONIC HEPATITIS; E-ANTIGEN SEROCONVERSION; LDT VS. LAMIVUDINE; LONG-TERM THERAPY; ADEFOVIR DIPIVOXIL; VIRUS-INFECTION; INTERFERON-ALPHA; NATURAL-HISTORY; UNITED-STATES; GLOBE TRIAL AB Hepatitis B virus (HBV) infection is the leading cause of chronic liver disease and hepatocellular carcinoma worldwide. Approximately 350 million individuals are infected with HBV and >500,000 deaths per year can be attributed to HBV. Although universal vaccination has reduced HBV incidence in many countries, it still remains a major public health problem, especially in parts of Asia and Africa. Improved understanding of HBV virology and virus-host interactions has revolutionized chronic hepatitis B therapy in the past two decades. Development of oral nucleoside/mucleotide analogues heralds a new era of safe and effective treatment of this disease. On the basis of these advances, new guidelines for the treatment of chronic hepatitis B have been issued. Successful long-term treatment of chronic hepatitis B may rest on combination therapy that is based on molecular approaches targeting various stages of the HBV life-cycle. In this review, we summarize the current modalities and highlight important issues in the treatment of chronic hepatitis B monoinfection. C1 [Loomba, Rohit; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. RP Loomba, R (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. EM roloomba@ucsd.edu; jliang@nih.gov NR 57 TC 12 Z9 14 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 SU 3 BP H33 EP H41 PG 9 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 248HR UT WOS:000252144200005 PM 18284181 ER PT J AU Aldrovandi, GM Lindsey, JC Jacobson, D Heckman, B Zadzilka, A Sheeran, E Moye, J Borum, P Meyer, WA Hardin, D DeCarlo, E Mulligan, K AF Aldrovandi, G. M. Lindsey, J. C. Jacobson, D. Heckman, B. Zadzilka, A. Sheeran, E. Moye, J. Borum, P. Meyer, W. A., III Hardin, D. DeCarlo, E. Mulligan, K. TI Dyslipidaemia in vertically infected children and youth on protease inhibitor (PI)-containing antiretroviral therapy (ART): preliminary results of PACTG 1045 SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 9th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV CY JUL 19-21, 2007 CL Sydney, AUSTRALIA C1 Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Frontier Sci & Technol Res Fdn Inc, Amherst, NY USA. Social & Sci Syst Inc, Silver Spring, MD USA. NICHHD, NIH, Bethesda, MD 20892 USA. Univ Florida, Gainesville, FL USA. Quest Diagnost Inc, Baltimore, MD USA. Ohio State Univ, Columbus, OH 43210 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 6 BP L6 EP L7 PG 2 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 214YD UT WOS:000249773400026 ER PT J AU Archin, NM Eron, J Palmer, S Ngo, L Duff, H Bandarenko, N Schmitz, J Wiegand Coffin, JM Landay, AL Bosch, RJ Cohen, MS Margolis, DM AF Archin, N. M. Eron, J. Palmer, S. Ngo, L. Duff, Hartmann Bandarenko, N. Schmitz, J. Wiegand, A. Coffin, J. M. Landay, A. L. Bosch, R. J. Cohen, M. S. Margolis, D. M. TI Standard ART and valproic acid have limited impact on persistent HIV infection of resting CD4(+) T-cells SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 [Archin, N. M.; Eron, J.; Ngo, L.; Duff, Hartmann; Bandarenko, N.; Schmitz, J.; Cohen, M. S.; Margolis, D. M.] Univ N Carolina, Chapel Hill, NC 27515 USA. [Palmer, S.; Wiegand, A.; Coffin, J. M.] NIH, NCI, HIV Drug Resistance Program, Frederick, MD USA. [Landay, A. L.] Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. [Bosch, R. J.] Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 SU 1 BP S107 EP S107 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 256AL UT WOS:000252700000096 ER PT J AU Archin, NM Eron, J Palmer, S Ngo, L Duff, AH Bandarenko, N Schmitz, J Wiegand, A Coffin, JM Landay, AL Bosch, RJ Cohen, MS Margolis, DM AF Archin, N. M. Eron, J. Palmer, S. Ngo, L. Duff, A. Hartmann Bandarenko, N. Schmitz, J. Wiegand, A. Coffin, J. M. Landay, A. L. Bosch, R. J. Cohen, M. S. Margolis, D. M. TI Standard ART and valproic acid have limited impact on persistent HIV infection of resting CD4(+) T-cells SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 Univ N Carolina, Chapel Hill, NC USA. NCI, NIH, HIV Drug Resistance Program, Frederick, MD 21701 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 5 BP S107 EP S107 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 197IC UT WOS:000248546900115 ER PT J AU Beilhartz, G Tchesnokov, E Bermingham, A O'Keefe, B Beutler, J LeGrice, S Gotte, M AF Beilhartz, G. Tchesnokov, E. Bermingham, A. O'Keefe, B. Beutler, J. LeGrice, S. Goette, M. TI Competition with the nucleic acid substrate can present an obstacle in the development of RNase H active site inhibitors SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 [Beilhartz, G.; Tchesnokov, E.; Goette, M.] McGill Univ, Montreal, PQ H3A 2T5, Canada. [O'Keefe, B.; Beutler, J.; LeGrice, S.] Natl Canc Inst, Frederick, MD USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 SU 1 BP S123 EP S123 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 256AL UT WOS:000252700000110 ER PT J AU Beilhartz, G Tchesnokov, E Bermingham, A O'Keefe, B Beutler, J LeGrice, S Gotte, M AF Beilhartz, G. Tchesnokov, E. Bermingham, A. O'Keefe, B. Beutler, J. LeGrice, S. Gotte, M. TI Competition with the nucleic acid substrate can present an obstacle in the development of RNase H active site inhibitors SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 McGill Univ, Montreal, PQ, Canada. NCI, Frederick, MD 21701 USA. RI Beutler, John/B-1141-2009 OI Beutler, John/0000-0002-4646-1924 NR 0 TC 2 Z9 2 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 5 BP S123 EP S123 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 197IC UT WOS:000248546900129 ER PT J AU Das, K Bauman, JD Baweja, M Clark, AD Boyer, PL Shatkin, AJ Lewi, PJ Hughes, SH Arnold, E AF Das, K. Bauman, J. D. Baweja, M. Clark, A. D., Jr. Boyer, P. L. Shatkin, A. J. Lewi, P. J. Hughes, S. H. Arnold, E. TI Strategic flexibility of the nonnucleoside RT inhibitor TMC278 explains its potency against drug-resistant mutants SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 [Das, K.; Bauman, J. D.; Baweja, M.; Clark, A. D., Jr.; Arnold, E.] Rutgers State Univ, Ctr Adv Biotechnol & Med, Piscataway, NJ 08855 USA. [Boyer, P. L.; Hughes, S. H.] NCI, Frederick, MD USA. [Lewi, P. J.] Katholieke Univ Leuven, Dept Transgene Technol & Gene Therapy, B-3000 Louvain, Belgium. NR 0 TC 1 Z9 1 U1 0 U2 4 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 SU 1 BP S33 EP S33 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 256AL UT WOS:000252700000032 ER PT J AU Delviks-Frankenberry, KA Nikolenko, GN Barr, R Pathak, VK AF Delviks-Frankenberry, K. A. Nikolenko, G. N. Barr, R. Pathak, V. K. TI Probing the mechanism by which connection domain mutations enhance AZT resistance: mutational analysis of the RNase H primer grip SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 [Delviks-Frankenberry, K. A.; Nikolenko, G. N.; Barr, R.; Pathak, V. K.] NCI, HIV Drug Resistance Program, Frederick, MD USA. RI Delviks-Frankenberry, Krista/M-4822-2013 NR 0 TC 2 Z9 2 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 SU 1 BP S125 EP S125 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 256AL UT WOS:000252700000112 ER PT J AU Delviks-Frankenberry, KA Nikolenko, GN Barr, R Pathak, VK AF Delviks-Frankenberry, K. A. Nikolenko, G. N. Barr, R. Pathak, V. K. TI Probing the mechanism by which connection domain mutations enhance AZT resistance: mutational analysis of the RNase H primer grip SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 NCI, HIV Drug Resistance Program, Frederick, MD 21701 USA. RI Delviks-Frankenberry, Krista/M-4822-2013 NR 0 TC 2 Z9 2 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 5 BP S125 EP S125 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 197IC UT WOS:000248546900131 ER PT J AU Haubrich, RH Riddler, SA DiRienzo, AG Peeples, L Klingman, KL Garren, KW George, T Rooney, JF Brizz, B Havlir, D Mellors, JW AF Haubrich, R. H. Riddler, S. A. DiRienzo, A. G. Peeples, L. Klingman, K. L. Garren, K. W. George, T. Rooney, J. F. Brizz, B. Havlir, D. Mellors, J. W. CA AIDS CTG 5142 Study Team TI Drug resistance at virological failure in a randomized, phase III trial of NRTI-, PI- and NNRTI-sparing regimens for initial treatment of HIV-1 infection (ACTG 5142) SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 [Haubrich, R. H.] Univ Calif San Diego, San Diego, CA 92103 USA. [Riddler, S. A.; Mellors, J. W.] Univ Pittsburgh, Pittsburgh, PA USA. [DiRienzo, A. G.; Peeples, L.] Harvard Univ, Stat & Data Anal Ctr, Sch Publ Hlth, Boston, MA 02115 USA. [Klingman, K. L.] NIAID, Div AIDS, Bethesda, MD 20892 USA. [Garren, K. W.] Abbott Labs, Abbott Pk, IL 60064 USA. [George, T.] Bristol Myers Squibb Co, Plainsboro, NJ USA. [Rooney, J. F.] Gilead Sci, Foster City, CA USA. [Brizz, B.] Social & Sci Syst Inc, Silver Spring, MD USA. [Havlir, D.] Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 SU 1 BP S66 EP S66 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 256AL UT WOS:000252700000058 ER PT J AU Haubrich, RH Riddler, SA DiRienzo, AG Peeples, L Klingman, KL Garren, KW George, T Rooney, JF Brizz, B Havlir, D Mellors, JW AF Haubrich, R. H. Riddler, S. A. DiRienzo, A. G. Peeples, L. Klingman, K. L. Garren, K. W. George, T. Rooney, J. F. Brizz, B. Havlir, D. Mellors, J. W. CA AIDS Clin Trials Grp TI Drug resistance at virological failure in a randomized, Phase III trial of NRTI-, PI- and NNRTI-sparing regimens for initial treatment of HIV-1 infection (ACTG 5142) SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 Univ Calif San Diego, San Diego, CA 92103 USA. Univ Pittsburgh, Pittsburgh, PA USA. Harvard Univ, Sch Publ Hlth, Data Anal Ctr, Boston, MA 02115 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. Abbott Labs, Abbott Pk, IL 60064 USA. Bristol Myers Squibb Co, Plainsboro, NJ USA. Gilead Sci Inc, Foster City, CA 94404 USA. Social & Sci Syst Inc, Silver Spring, MD USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 5 BP S66 EP S66 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 197IC UT WOS:000248546900076 ER PT J AU Kearney, M Shao, W Maldarelli, F Margolick, J Daar, E Mellors, J Rao, V Coffin, J Palmer, S AF Kearney, M. Shao, W. Maldarelli, F. Margolick, J. Daar, E. Mellors, J. Rao, V. Coffin, J. Palmer, S. TI Evolution and persistence of CTL-associated mutations in newly HIV-1-infected individuals SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 [Kearney, M.; Shao, W.; Maldarelli, F.; Coffin, J.; Palmer, S.] NCI, NIH, HIV Drug Resistance Program, Bethesda, MD 20892 USA. [Kearney, M.; Rao, V.] Catholic Univ Amer, Washington, DC 20064 USA. [Margolick, J.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Daar, E.] Univ Calif Los Angeles, Med Ctr, Div HIV Med Harbor, Los Angeles, CA USA. [Mellors, J.] Univ Pittsburgh, Dept Infect Dis, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 SU 1 BP S100 EP S100 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 256AL UT WOS:000252700000089 ER PT J AU Kearney, M Shao, W Maldarelli, F Margolick, J Daar, E Mellors, J Rao, V Coffin, J Palmer, S AF Kearney, M. Shao, W. Maldarelli, F. Margolick, J. Daar, E. Mellors, J. Rao, V. Coffin, J. Palmer, S. TI Evolution and persistence of CTL-associated mutations in newly HIV-1-infected individuals SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 NCI, NIH, HIV Drug Resistance Program, Bethesda, MD 20892 USA. Catholic Univ Amer, Washington, DC 20064 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD USA. Univ Calif Los Angeles, Med Ctr, Div HIV Med, Los Angeles, CA USA. Univ Pittsburgh, Dept Infect Dis, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 5 BP S100 EP S100 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 197IC UT WOS:000248546900108 ER PT J AU Larder, BA Wang, D Revell, A Montaner, J Harrigan, R Wegner, S Lane, HC AF Larder, B. A. Wang, D. Revell, A. Montaner, J. Harrigan, R. Wegner, S. Lane, H. C. TI Development of computational models for prediction of virological response in a prospective clinical study SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 [Larder, B. A.; Wang, D.; Revell, A.] HIV Resistance response Database Initiat, London, England. [Montaner, J.; Harrigan, R.] BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. [Wegner, S.] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Lane, H. C.] NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 SU 1 BP S167 EP S167 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 256AL UT WOS:000252700000152 ER PT J AU Larder, BA Wang, D Revell, A Montaner, J Harrigan, R Wegner, S Lane, HC AF Larder, B. A. Wang, D. Revell, A. Montaner, J. Harrigan, R. Wegner, S. Lane, H. C. TI Development of computational models for prediction of virological response in a prospective clinical study SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 HIV Resistance Response Database Initiat, London, England. BC Ctr Excellence HIV AIDS, Vancouver, BC, Canada. Uniformed Serv Univ Hlth Sci, Bethesda, MD USA. NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 5 BP S167 EP S167 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 197IC UT WOS:000248546900171 ER PT J AU Maldarelli, F Kearney, M Palmer, S Danley, K Mican, J Rock, D Shao, W Mellors, J Coffin, J AF Maldarelli, F. Kearney, M. Palmer, S. Danley, K. Mican, J. Rock, D. Shao, W. Mellors, J. Coffin, J. TI Similar diversity of HTV-1 pro-pol before and after initiation of suppressive antiretroviral therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 [Maldarelli, F.; Kearney, M.; Palmer, S.; Danley, K.; Coffin, J.] NIH, NCI, HIV Drug Resistance Program, Frederick, MD USA. [Mican, J.] NIAID, NIH, Immunoregulat Lab, Bethesda, MD 20892 USA. [Shao, W.] SAIC, Bethesda, MD USA. [Mellors, J.] Univ Pittsburgh, Dept Infect Dis, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 SU 1 BP S105 EP S105 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 256AL UT WOS:000252700000094 ER PT J AU Maldarelli, F Kearney, M Palmer, S Danley, K Mican, J Rock, D Shao, W Mellors, J Coffin, J AF Maldarelli, F. Kearney, M. Palmer, S. Danley, K. Mican, J. Rock, D. Shao, W. Mellors, J. Coffin, J. TI Similar diversity of HIV-1 pro-pol before and after initiation of suppressive antiretroviral therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 NCI, NIH, HIV Drug Resistance Program, Frederick, MD 21701 USA. NIAID, NIH, Immunoregulat Lab, Bethesda, MD 20892 USA. NIAID, NIH, CCMD Clin, Bethesda, MD 20892 USA. SAIC, Frederick, MD USA. Univ Pittsburgh, Dept Infect Dis, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 5 BP S105 EP S105 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 197IC UT WOS:000248546900113 ER PT J AU Moore, MD Fu, W Nikolaitchik, O Chen, J Ptak, RG Hu, WS AF Moore, M. D. Fu, W. Nikolaitchik, O. Chen, J. Ptak, R. G. Hu, W-S TI How HIV-1 selects copackaged RNAs: implication for antiviral strategies targeting RNA dimerization initiation signal SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 [Moore, M. D.; Nikolaitchik, O.; Chen, J.; Hu, W-S] Natl Canc Inst, HIV Drug Resistance Program, Frederick, MD USA. [Fu, W.; Ptak, R. G.] So Res Inst, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 SU 1 BP S95 EP S95 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 256AL UT WOS:000252700000084 ER PT J AU Moore, MD Fu, W Nikolaitchik, O Chen, J Ptak, RG Hu, WS AF Moore, M. D. Fu, W. Nikolaitchik, O. Chen, J. Ptak, R. G. Hu, W-S TI How HIV-1 selects copackaged RNAs: implication for antiviral strategies targeting RNA dimerization initiation signal SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 Natl Canc Inst, HIV Drug Resistance Program, Frederick, MD USA. So Res Inst, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 5 BP S95 EP S95 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 197IC UT WOS:000248546900103 ER PT J AU Nisslev, DV Shenk, JL Ambrose, Z Strathern, JN Sluis-Cremer, N AF Nisslev, D. V. Shenk, J. L. Ambrose, Z. Strathern, J. N. Sluis-Cremer, N. TI The fidelity of HIV-1 reverse transcriptase: identification of variants with increased levels of mutation during reverse transcription SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 SAIC Frederick Inc, NCI, BRP, Frederick, MD USA. NCI, GRCBL, Frederick, MD 21701 USA. NCI, HIV DRP, Frederick, MD 21701 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 5 BP S109 EP S109 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 197IC UT WOS:000248546900117 ER PT J AU Nissley, DV Shenk, JL Ambrose, Z Strathern, JN Sluis-Cremer, N AF Nissley, D. V. Shenk, J. L. Ambrose, Z. Strathern, J. N. Sluis-Cremer, N. TI The fidelity of HIV-1 reverse transcriptase: identification of variants with increased levels of mutation during reverse transcription SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 [Nissley, D. V.] SAIC Frederick Inc, NCI, BRP, Frederick, MD USA. [Nissley, D. V.; Shenk, J. L.; Strathern, J. N.] NCI Frederick, GRCBL, Frederick, MD USA. [Ambrose, Z.] NCI Frederick, HIV DRP, Frederick, MD USA. [Sluis-Cremer, N.] Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 SU 1 BP S109 EP S109 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 256AL UT WOS:000252700000098 ER PT J AU Palmer, S Wiegand, A Miura, T Block, B Pereyra, F Maldarelli, F King, M Bernstein, B Hanna, G Mellors, J Walker, B Coffin, J AF Palmer, S. Wiegand, A. Miura, T. Block, B. Pereyra, F. Maldarelli, F. King, M. Bernstein, B. Hanna, G. Mellors, J. Walker, B. Coffin, J. TI Low-level viraemia in HIV-1-infected patients classified as 'elite controllers' compared to patients on suppressive antiretroviral therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 [Palmer, S.; Wiegand, A.; Maldarelli, F.; Coffin, J.] NIH, NCI, HIV Drug Resistance Program, Frederick, MD USA. [Miura, T.; Block, B.; Pereyra, F.; Walker, B.] Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. [Bernstein, B.; Hanna, G.] Abbott Labs, Abbott Pk, IL 60064 USA. [Mellors, J.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 SU 1 BP S103 EP S103 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 256AL UT WOS:000252700000092 ER PT J AU Palmer, S Wiegand, A Miura, T Block, B Pereyra, F Maldarelli, F King, M Bernstein, B Hanna, G Mellors, J Walker, B Coffin, J AF Palmer, S. Wiegand, A. Miura, T. Block, B. Pereyra, F. Maldarelli, F. King, M. Bernstein, B. Hanna, G. Mellors, J. Walker, B. Coffin, J. TI Low-level viraemia in HIV-1-infected patients classified as 'elite controllers' compared to patients on suppressive antiretroviral therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 NCI, NIH, HIV Drug Resistance Program, Frederick, MD 21701 USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Boston, MA 02114 USA. Abbott Labs, Abbott Pk, IL 60064 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 5 BP S103 EP S103 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 197IC UT WOS:000248546900111 ER PT J AU Palmer, S Ambrose, Z Kearney, M Shao, W Boltz, V Kimata, J Maldarelli, F Mellors, JW Hu, SL Lifson, JD KewalRamani, VN Coffin, JM AF Palmer, S. Ambrose, Z. Kearney, M. Shao, W. Boltz, V. Kimata, J. Maldarelli, F. Mellors, J. W. Hu, S-L Lifson, J. D. KewalRamani, V. N. Coffin, J. M. TI Dynamics of virus replication and antiviral drug resistance in a new RT-SHIV macaque model of antiviral therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 [Ambrose, Z.; Kearney, M.; Shao, W.; Boltz, V.; Maldarelli, F.; KewalRamani, V. N.; Coffin, J. M.] Natl Canc Inst, HIV Drug Resistance Program, Frederick, MD USA. [Kimata, J.] Baylor Coll Med, Houston, TX 77030 USA. [Mellors, J. W.] Univ Pittsburgh, Dept Med, Pittsburgh, PA 15260 USA. [Hu, S-L] Washington Natl Primate Res Ctr, Seattle, WA USA. [Lifson, J. D.] Natl Canc Inst, AIDS Vaccine Program, SAIC Frederick, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 SU 1 BP S98 EP S98 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 256AL UT WOS:000252700000087 ER PT J AU Palmer, S Ambrose, Z Kearney, M Shao, W Boltz, V Kimata, J Maldarelli, F Mellors, JW Hu, SL Lifson, JD KewalRamani, VN Coffin, JM AF Palmer, S. Ambrose, Z. Kearney, M. Shao, W. Boltz, V. Kimata, J. Maldarelli, F. Mellors, J. W. Hu, S-L Lifson, J. D. KewalRamani, V. N. Coffin, J. M. TI Dynamics of virus replication and antiviral drug resistance in a new RT-SHIV macaque model of antiviral therapy SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 16th International HIV Drug Resistance Workshop CY JUN 12-16, 2007 CL BARBADOS C1 Natl Canc Inst, HIV Drug Resistance Program, Frederick, MD USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Washington Natl Primate Res Ctr, Seattle, WA USA. Natl Canc Inst, SAIC Frederick, AIDS Vaccine Program, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2007 VL 12 IS 5 BP S98 EP S98 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 197IC UT WOS:000248546900106 ER PT J AU Reddy, RM Yeow, WS Chua, A Nguyen, DM Baras, A Ziauddin, MF Shamimi-Noori, SM Maxhimer, JB Schrump, DS Nguyen, DM AF Reddy, Rishindra M. Yeow, Wen-Shuz Chua, Alex Nguyen, Duc M. Baras, Aris Ziauddin, M. Firdos Shamimi-Noori, Susan M. Maxhimer, Justin B. Schrump, David S. Nguyen, Dao M. TI Rapid and profound potentiation of Apo2L/TRAIL-mediated cytotoxicity and apoptosis in thoracic cancer cells by the histone deacetylase inhibitor Trichostatin A: the essential role of the mitochondria-mediated caspase activation cascade SO APOPTOSIS LA English DT Article DE histone deacetylase inhibitor; Apo2L; TRAIL; type II pathway; apoptosis; caspases; mitochondria ID TRAIL-INDUCED APOPTOSIS; NF-KAPPA-B; DEATH RECEPTOR; CYTOCHROME-C; LUNG-CANCER; IN-VIVO; TRAIL/APO2L-INDUCED APOPTOSIS; SUBERIC BISHYDROXAMATE; DEPSIPEPTIDE FR901228; BCL-2 OVEREXPRESSION AB Apo2L/TRAIL is actively investigated as a novel targeted agent to directly induce apoptosis of susceptible cancer cells. Apo2L/TRAIL-refractory cells can be sensitized to the cytotoxic effect of this ligand by cytotoxic chemotherapeutics. The aim of this study was to evaluate the in vitro tumoricidal activity of the Apo2L/TRAIL + Trichostatin A in cultured thoracic cancer cells and to elucidate the molecular basis of the synergistic cytotoxicity of this combination. Concurrent exposure of cultured cancer cells to sublethal concentrations of Apo2L/TRAIL and Trichostatin A resulted in profound enhancement of Apo2L/TRAIL-mediated cytotoxicity in all cell lines regardless of their intrinsic susceptibility to this ligand. This combination was not toxic to primary normal cells. While Apo2L/TRAIL alone or Trichostatin A alone mediated < 20% cell death, 60 to 90% of cancer cells were apoptotic following treatment with TSA + Apo2L/TRAIL combinations. Complete translocation of Bax from the cytosol to the mitochondria compartment was mainly observed in combination-treated cells and this was correlated with robust elevation of caspase 9 proteolytic activity indicative of activation of the mitochondria apoptogenic effect. Profound TSA + Apo2L/TRAIL-mediated cytotoxicity and apoptosis were completely abrogated by either Bcl2 over-expression or by the selective caspase 9 inhibitor, highlighting the essential role of mitochondria-dependent apoptosis signaling cascade in this process. Moreover, increased caspase 8 activity observed in cells treated with the TSA + Apo2L/TRAIL combination was completely suppressed by Bcl-2 over-expression or by the selective caspase 9 inhibitor indicating that the elevated caspase 8 activity in combination-treated cells was secondary to a mitochondria-mediated amplification feedback loop of caspase activation. These finding form the basis for further development of HDAC inhibitors + Apo2L/TRAIL combination as novel targeted therapy for thoracic malignancies. C1 Clin Res Ctr, Bethesda, MD 20892 USA. NCI, Sect Thorac Oncol, Surg Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Canc Res Training Award, NIH, Bethesda, MD 20892 USA. RP Nguyen, DM (reprint author), Clin Res Ctr, Room 4W-4-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM Dao_Nguyen@nigh.gov FU Intramural NIH HHS NR 68 TC 25 Z9 29 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD JAN PY 2007 VL 12 IS 1 BP 55 EP 71 DI 10.1007/s10495-006-0484-z PG 17 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 118UO UT WOS:000242968200005 PM 17136498 ER PT J AU Sadarangani, A Kato, S Espinoza, N Lange, S Llados, C Espinosa, M Villalon, M Lipkowitz, S Cuello, M Owen, GI AF Sadarangani, Anil Kato, Sumie Espinoza, Natalia Lange, Soledad Llados, Carmen Espinosa, Marisol Villalon, Manuel Lipkowitz, Stanley Cuello, Mauricio Owen, Gareth I. TI TRAIL mediates apoptosis in cancerous but not normal primary cultured cells of the human reproductive tract SO APOPTOSIS LA English DT Article DE endometrium; cervix; fallopian; ovarian cancer ID HUMAN ENDOMETRIAL CARCINOMA; EPIDERMAL-GROWTH-FACTOR; OVARIAN-CANCER; DEATH RECEPTORS; BREAST-CANCER; APO2 LIGAND; NECROSIS; LINES; ACTIVATION; EXPRESSION AB Cancer of the reproductive tract encompasses malignancies of the uterine corpus, cervix, ovary, Fallopian tube, among others and accounts for 15% of female cancer mortalities. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) mediates apoptosis by binding to death receptors and offers a promising cancer treatment. The goal of this study was to investigate and characterize the effect of TRAIL in endometrial cancer cell lines and normal (non-cancerous) epithelial cells of endometrial origin. We also examined the effect of TRAIL in other primary cultured cancers and normal cells of the human female reproductive tract and evaluated if TRAIL mediated apoptosis correlated with death receptors and decoy receptors 1 and 2. Herein, we demonstrate that TRAIL at concentrations which kill cancerous cells, does not mediate apoptosis or alter cell viability in normal human endometrium, ovary, cervix or Fallopian tube. The partial inhibition by a caspase 9 inhibitor and the total inhibition by a caspase 8 inhibitor demonstrates the dependency on the extrinsic apoptotic pathway. The selective mortality does not correlate with the presence of death or decoy receptors. These results suggest that TRAIL may be an effective treatment for endometrial cancer and other female reproductive cancers, with minimal secondary effects on healthy tissue. C1 Pontificia Univ Catolica Chile, Fac Biol Sci, Dept Physiol, Santiago, Chile. Pontificia Univ Catolica Chile, Fac Med, Dept Obstet & Gynecol, Santiago, Chile. NCI, Cellular & Mol Biol Lab, Canc Res Ctr, Bethesda, MD 20892 USA. RP Owen, GI (reprint author), Pontificia Univ Catolica Chile, Fac Biol Sci, Dept Physiol, Alameda 340, Santiago, Chile. EM gowen@bio.puc.cl FU Wellcome Trust [GR071469] NR 49 TC 29 Z9 30 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1360-8185 J9 APOPTOSIS JI Apoptosis PD JAN PY 2007 VL 12 IS 1 BP 73 EP 85 DI 10.1007/s10495-006-0492-z PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 118UO UT WOS:000242968200006 PM 17136491 ER PT J AU Chalmers, NI Palmer, RJ Du-Thumm, L Sullivan, R Shi, WY Kolenbrander, PE AF Chalmers, Natalia I. Palmer, Robert J. Du-Thumm, Laurence Sullivan, Richard Shi, Wenyuan Kolenbrander, Paul E. TI Use of quantum dot luminescent probes to achieve single-cell resolution of human oral bacteria in biofilms SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; SALMONELLA-TYPHIMURIUM; CRYPTOSPORIDIUM-PARVUM; QUANTITATIVE DETECTION; STREPTOCOCCUS-MUTANS; DENTAL PLAQUE; IN-VIVO; LABELS; COLONIZATION; NANOCRYSTALS AB Oral biofilms are multispecies communities, and in their nascent stages of development, numerous bacterial species engage in interspecies interactions. Better insight into the spatial relationship between different species and how species diversity increases over time can guide our understanding of the role of interspecies interactions in the development of the biofilms. Quantum dots (QD) are semiconductor nanocrystals and have emerged as a promising tool for labeling and detection of bacteria. We sought to apply QD-based primary immunofluorescence for labeling of bacterial cells with in vitro and in vivo biofilms and to compare this approach with the fluorophore-based primary immunofluorescence approach we have used previously. To investigate QD-based primary immunofluorescence as the means to detect distinct targets with single-cell resolution, we conjugated polyclonal and monoclonal antibodies to the QD surface. We also conducted simultaneous QD conjugate-based and fluorophore conjugate-based immunofluorescence and showed that these conjugates were complementary tools in immunofluorescence applications. Planktonic and biofilm cells were labeled effectively by considering two factors: the final nanomolar concentration of QD conjugate and the amount of antibody conjugated to the QD, which we define as the degree of labeling. These advances in the application of QD-based immunofluorescence for the study of biofilms in vitro and in vivo will help to define bacterial community architecture and to facilitate investigations of interactions between bacterial species in these communities. C1 NIDCR, NIH, Bethesda, MD 20892 USA. Univ Maryland, Sch Dent, Dept Biomed Sci, Baltimore, MD 21201 USA. Colgate Palmol Co, Piscataway, NJ 08855 USA. Univ Calif Los Angeles, Sch Dent, Dept Oral Biol & Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Inst Mol Biol, Los Angeles, CA 90025 USA. RP Kolenbrander, PE (reprint author), NIDCR, NIH, Bldg 30,Room 310,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA. EM pkolenbrander@dir.nidcr.nih.gov FU Intramural NIH HHS NR 42 TC 56 Z9 57 U1 2 U2 17 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JAN PY 2007 VL 73 IS 2 BP 630 EP 636 DI 10.1128/AEM.02164-06 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 136BK UT WOS:000244197400031 PM 17114321 ER PT J AU La Rooy, D Pipe, ME Murray, JE AF La Rooy, David Pipe, Margaret-Ellen Murray, Janice E. TI Enhancing children's event recall after long delays SO APPLIED COGNITIVE PSYCHOLOGY LA English DT Article ID COGNITIVE INTERVIEW; EYEWITNESS MEMORY; HYPERMNESIA; PROPS; REAL; CUES; ORGANIZATION; REMINISCENCE; RETRIEVAL; PICTURES AB The effects of context reinstatement as means of enhancing 5- and 6-year-old children's event memory in repeated interviews after a 6-month delay were examined. Children were interviewed immediately after the event (baseline interview) and twice at a 6-month delay, with 24 hours between interviews. The first 6-month interview was conducted in a perfect-context reinstatement (n = 15), imperfect-context reinstatement (n = 16), or no-context reinstatement (n - 15) condition. The second 6-month interview was conducted 24 hours later with no-context reinstatement for all children. Context reinstatement attenuated the effects of delay on recall. The accuracy of the details reported was greater in the perfect-context compared to the imperfect-context and no-context conditions. Details repeated between the immediate-baseline interview and in the first 6-month interview were more accurate than details repeated between the first and second 6-month interview. There was no increase in recall (hypermnesia) across the first and second 6-month interviews in any condition. Practical implications of these findings are discussed. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 NICHHD, Sect Social & Emot Dev, Bethesda, MD USA. Univ Otago, Dept Psychol, Dunedin, New Zealand. RP La Rooy, D (reprint author), Kingston Univ, Fac Arts & Social Sci, Penrhyn Rd, Kingston upon Thames KT1 2EE, Surrey, England. EM david@larooy.net RI la rooy, david/A-2104-2009 NR 50 TC 17 Z9 18 U1 0 U2 8 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0888-4080 J9 APPL COGNITIVE PSYCH JI Appl. Cogn. Psychol. PD JAN PY 2007 VL 21 IS 1 BP 1 EP 17 DI 10.1002/acp.1272 PG 17 WC Psychology, Experimental SC Psychology GA 126GM UT WOS:000243500700001 ER PT J AU Hendricks, C Bornstein, MH AF Hendricks, Charlene Bornstein, Marc H. TI Ecological analysis of early adolescents' stress responses to 9/11 in the Washington, DC, area SO APPLIED DEVELOPMENTAL SCIENCE LA English DT Review ID SEPTEMBER-11 TERRORIST ATTACKS; POSTTRAUMATIC-STRESS; EVENT SCALE; COPING STRATEGIES; PSYCHOLOGICAL SYMPTOMS; PERSONALITY STRUCTURE; CAUSAL ATTRIBUTIONS; CHILDRENS RESPONSES; GENERAL-POPULATION; PROTECTIVE FACTORS AB This study uses an ecological perspective to explore the unique associations of maternal personal characteristics, parenting behaviors, and adolescents' own characteristics to posttraumatic distress and symptoms of arousal, avoidance, and intrusions, in 97 early adolescents and mothers from the Washington, DC, area to the events of September 11, 2001. Maternal characteristics and/or adolescents' perceptions of parenting behaviors were uniquely related to adolescents' responses, controlling for adolescents' own characteristics. Maternal responses and parenting behaviors play key roles in adolescents' continuing responses to the traumatic events of September 11. C1 [Hendricks, Charlene; Bornstein, Marc H.] NICHHD, Natl Inst Hlth, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Hendricks, C (reprint author), NICHHD, Natl Inst Hlth, Dept Hlth & Human Serv, Suite 8030,6705 Rockledge Dr, Bethesda, MD 20892 USA. EM hendricc@mail.nih.gov NR 135 TC 7 Z9 7 U1 2 U2 2 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 1088-8691 J9 APPL DEV SCI JI Appl. Dev. Sci. PY 2007 VL 11 IS 2 BP 71 EP 88 PG 18 WC Psychology, Developmental SC Psychology GA 248HZ UT WOS:000252145000002 ER PT J AU McClure, EB Monk, CS Nelson, EE Parrish, JM Adler, A Blair, RJR Fromm, S Charney, DS Leibenluft, E Ernst, M Pine, DS AF McClure, Erin B. Monk, Christopher S. Nelson, Eric E. Parrish, Jessica M. Adler, Abby Blair, R. James R. Fromm, Stephen Charney, Dennis S. Leibenluft, Ellen Ernst, Monique Pine, Daniel S. TI Abnormal attention modulation of fear circuit function in pediatric generalized anxiety disorder SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID OBSESSIVE-COMPULSIVE DISORDER; THREAT-RELATED STIMULI; AMYGDALA RESPONSE; MAJOR DEPRESSION; ANTIDEPRESSANT TREATMENT; FACIAL EXPRESSIONS; EMOTIONAL FACES; NEURAL RESPONSE; SOCIAL PHOBIA; ADOLESCENTS AB Context: Considerable work implicates abnormal neural activation and disrupted attention to facial-threat cues in adult anxiety disorders. However, in pediatric anxiety, no research has examined attention modulation of neural response to threat cues. Objective: To determine whether attention modulates amygdala and cortical responses to facial-threat cues differentially in adolescents with generalized anxiety disorder and in healthy adolescents. Design: Case-control study. Setting: Government clinical research institute. Participants: Fifteen adolescents with generalized anxiety disorder and 20 controls. Main Outcome Measures: Blood oxygenation level dependent signal as measured via functional magnetic resonance imaging. During imaging, participants completed a face-emotion rating task that systematically manipulated attention. Results: While attending to their own subjective fear, patients, but not controls, showed greater activation to fearful faces than to happy faces in a distributed network including the amygdala, ventral prefrontal cortex, and anterior cingulate cortex ( P < .05, small-volume corrected, for all). Right amygdala findings appeared particularly strong. Functional connectivity analyses demonstrated positive correlations among the amygdala, ventral prefrontal cortex, and anterior cingulate cortex. Conclusions: This is the first evidence in juveniles that generalized anxiety disorder-associated patterns of pathologic fear circuit activation are particularly evident during certain attention states. Specifically, fear circuit hyperactivation occurred in an attention state involving focus on subjectively experienced fear. These findings underscore the importance of attention and its interaction with emotion in shaping the function of the adolescent human fear circuit. C1 Georgia State Univ, Dept Psychol, Atlanta, GA 30302 USA. NIMH, Emot Dev & Affect Neurosci Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIMH, Unit Affect Disorders, Pediat & Dev Neuropsychiat Branch, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Michigan, Dept Psychol, Ann Arbor, MI 48109 USA. Univ Michigan, Ctr Human Growth & Dev, Ann Arbor, MI 48109 USA. Mt Sinai Sch Med, Dept Psychiat, New York, NY USA. Mt Sinai Sch Med, Dept Neurosci, New York, NY USA. Mt Sinai Sch Med, Dept Pharmacol & Biol Chem, New York, NY USA. RP McClure, EB (reprint author), Georgia State Univ, Dept Psychol, POB 4010, Atlanta, GA 30302 USA. EM emcclure@gsu.edu RI Nelson, Eric/B-8980-2008; Monk, Christopher/J-1805-2014 OI Nelson, Eric/0000-0002-3376-2453; FU Intramural NIH HHS NR 50 TC 211 Z9 216 U1 3 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JAN PY 2007 VL 64 IS 1 BP 97 EP 106 DI 10.1001/archpsyc.64.1.97 PG 10 WC Psychiatry SC Psychiatry GA 123CF UT WOS:000243273200011 PM 17199059 ER PT J AU Kamangar, F Malekzadeh, R Dawsey, SM Saidi, F AF Kamangar, Farin Malekzadeh, Reza Dawsey, Sanford M. Saidi, Farrokh TI Esophageal cancer in northeastern Iran: A review SO ARCHIVES OF IRANIAN MEDICINE LA English DT Review DE esophageal cancer; Iran ID N-NITROSO COMPOUNDS; POLYCYCLIC AROMATIC-HYDROCARBONS; PAPILLOMAVIRUS TYPE-16 INFECTION; SQUAMOUS-CELL CARCINOMA; NESTED CASE-CONTROL; HIGH-RISK REGION; GASTRIC CANCERS; MATE DRINKING; SERUM SELENIUM; TOOTH LOSS AB Golestan Province in northeastern Iran has one of the highest rates of esophageal squamous cell cancer in the world. This article reviews the studies conducted on esophageal squamous cell cancer in this area and summarizes the data on epidemiologic patterns, incidence trends, and etiology of esophageal squamous cell cancer in this province. C1 [Kamangar, Farin; Dawsey, Sanford M.] Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. [Malekzadeh, Reza] Univ Tehran Med Sci, Digest Dis Res Ctr, Tehran, Iran. [Saidi, Farrokh] Shaheed Beheshti Univ Med Sci, Modarress Hosp, Dept Surg, Tehran, Iran. RP Kamangar, F (reprint author), Natl Canc Inst, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM kamangaf@mail.nih.gov; malek@ams.ac.ir OI Malekzadeh, Reza/0000-0003-1043-3814 NR 112 TC 90 Z9 92 U1 3 U2 6 PU ACAD MEDICAL SCIENCES I R IRAN PI TEHRAN PA PO BOX 19395-5655, TEHRAN, 00000, IRAN SN 1029-2977 J9 ARCH IRAN MED JI Arch. Iran. Med. PD JAN PY 2007 VL 10 IS 1 BP 70 EP 82 PG 13 WC Medicine, General & Internal SC General & Internal Medicine GA 272NT UT WOS:000253866800014 PM 17198458 ER PT J AU Weisinger, HS Salem, N Makino, KK Hibbeln, JR Sinclair, AJ Weisinger, RS DePetrillo, PB AF Weisinger, Harrison S. Salem, Norman, Jr. Makino, Kevin K. Hibbeln, Joseph R. Sinclair, Andrew J. Weisinger, Richard S. DePetrillo, Paolo B. TI Effect of dietary omega-3 on heart rate variability in fatty acid deficiency hooded rats SO ARCHIVES OF MEDICAL SCIENCE LA English DT Article DE omega-3 fatty acids; heart rate variability (HRV); Hurst exponent ID ACUTE MYOCARDIAL-INFARCTION; ISOFLURANE ANESTHESIA; SPECTRAL-ANALYSIS; CELL-MEMBRANES; CARDIAC DEATH; TIME-SERIES; GUINEA-PIGS; BRAIN; SURVIVORS; DISEASE AB Introduction: Recent reports in adult humans suggest that heart rate variability is modulated by the concentration of omega-3 polyunsaturated fatty acids (PUFA) contained in blood cell membranes. Material and methods: Hurst analysis of ECG data was conducted on 12 male adult hooded (Long-Evans) rats, representing the 3(rd) generation to be fed diets that were either deficient in, or supplemented with, omega-3 PUFA. ECG data were obtained from surface electrodes and 4000 beats were analyzed for each animal. Results: Dietary manipulation, despite leading to large changes in tissue omega-3 PUFA levels, did not significantly affect the complexity of heart rate dynamics, with Hurst exponent (H) values of 0.15 +/- 0.02 and 0.12 +/- 0.03, for animals fed omega-3 fatty acid-adequate and -deficient diets, respectively. Mean heart rate was also unaffected by the diets. A power calculation revealed that about one hundred animals per group would have been required to avoid a type II1 error. Conclusions: According to this model of dietary PUFA manipulation, omega-3 fatty acids are unlikely to exert a large effect on the autonomic functions that control heart rate variability. Prospective studies into the effect of omega-3 fatty acids on HRV should consider the need for large sample size as estimated by the results contained in this report. C1 [Weisinger, Harrison S.] St Vincents Hosp, Dept Med, Fitzroy, Vic 3065, Australia. [Weisinger, Harrison S.; Salem, Norman, Jr.; Makino, Kevin K.] NIAAA, Lab Membrane Biochem & Biophys, NIH, Rockville, MD 20852 USA. [Sinclair, Andrew J.] La Trobe Univ, Sch Psychol Sci, Bundoora, Vic 3086, Australia. [Sinclair, Andrew J.] Deakin Univ, Sch Exercise & Nutr Sci, Geelong, Vic 3125, Australia. [DePetrillo, Paolo B.] NIAAA, NIH, Clin Sci Lab, Rockville, MD 20852 USA. RP Weisinger, HS (reprint author), St Vincents Hosp, Dept Med, Fitzroy, Vic 3065, Australia. EM weisinger@mac.com NR 42 TC 3 Z9 3 U1 0 U2 0 PU TERMEDIA PUBLISHING HOUSE LTD PI POZNAN PA WENEDOW ST 9-1, POZNAN, 61-614, POLAND SN 1896-9151 J9 ARCH MED SCI JI Arch. Med. Sci. PY 2007 VL 3 IS 3 BP 208 EP 214 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 276VE UT WOS:000254170900004 ER PT J AU Stewart, R White, LR Xue, QL Launer, LJ AF Stewart, Robert White, Lon R. Xue, Qian-Li Launer, Lenore J. TI Twenty-six-year change in total cholesterol levels and incident dementia - The Honolulu-Asia Aging Study SO ARCHIVES OF NEUROLOGY LA English DT Article ID E EPSILON-4 ALLELE; ALZHEIMERS-DISEASE; VASCULAR DEMENTIA; BLOOD-PRESSURE; OLDER PERSONS; PLASMA-LIPIDS; RISK; ASSOCIATION; DIAGNOSIS; STATE AB Background: The relationship between total cholesterol levels and dementia is unclear. Objective: To compare the natural history of change in total cholesterol across 26 years between men who did and did not develop dementia 3 years after the last measurement. Design, Setting, and Participants: In the Honolulu-Asia Aging Study, 1027 Japanese American men had total cholesterol levels assayed on 5 occasions between 1965 and 1993 and were screened for dementia on 2 occasions between 1991 and 1996. Main Outcome Measure: The slope of 26-year change in serum total cholesterol levels was estimated by a repeated-measures analysis and was compared between men with incident dementia (n=56) and those without dementia (n=971) at the end of the follow-up period. Results: Cholesterol levels in men with dementia and, in particular, those with Alzheimer disease had declined at least 15 years before the diagnosis and remained lower than cholesterol levels in men without dementia throughout that period. The difference in slopes was robust to adjustment for potential confounding factors, including vascular risk factors, weight change, alcohol intake, and use of lipid-lowering agents. Conclusion: A decline in serum total cholesterol levels may be associated with early stages in the development of dementia. C1 Kings Coll London, Inst Psychiat, Epidemiol Sect, London SE5 8AF, England. Pacific Hlth Res Inst, Honolulu, HI USA. John Hopkins Ctr Aging & Hlth, Baltimore, MD USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Baltimore, MD 21224 USA. RP Stewart, R (reprint author), Kings Coll London, Inst Psychiat, Epidemiol Sect, Campus Box 60,De Crespigny Pk, London SE5 8AF, England. EM r.stewart@iop.kcl.ac.uk OI Stewart, Robert/0000-0002-4435-6397 FU Intramural NIH HHS; NHLBI NIH HHS [N01-HC-05102]; NIA NIH HHS [5U01-AG019349, N01-AG-4-2149] NR 16 TC 97 Z9 99 U1 1 U2 4 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 JAN PY 2007 VL 64 IS 1 BP 103 EP 107 DI 10.1001/archneur.64.1.103 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 123ZN UT WOS:000243336500015 PM 17210816 ER PT J AU Duggal, P Klein, AP Lee, KE Klein, R Klein, BEK Bailey-Wilson, JE AF Duggal, Priya Klein, Alison P. Lee, Kristine E. Klein, Ronald Klein, Barbara E. K. Bailey-Wilson, Joan E. TI Identification of novel genetic loci for intraocular pressure - A genomewide scan of the Beaver Dam Eye Study SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID OPEN-ANGLE GLAUCOMA; WIDE LINKAGE ANALYSIS; BLOOD-PRESSURE; COMPLEX TRAITS; PULSE PRESSURE; FAMILY; REGION; MAPS; LOCALIZATION; 2CEN-Q13 AB Objective: To identify genetic loci that control intraocular pressure (IOP). Methods: We performed a genomewide scan of IOP, using 486 pedigrees ascertained through a population-based cohort, the Beaver Dam Eye Study. Linkage analysis was performed using the modified Haseman-Elston regression models and variance components linkage analysis. Results: Seven regions of interest were identified on chromosomes 2, 5, 6, 7, 12, 15, and 19. The novel linkage region on chromosome 19p had an empirical multipoint P value of 6.1 X 10(-5). Two of the regions (2 and 19) were especially interesting since each has been identified as a potential linkage region for blood pressure. Conclusions: The results of this genomewide scan provide evidence that a quantitative trait locus may influence elevated IOP and may colocalize with blood pressure loci. These loci may control systemic pressure reflected in the eye and vascular system. Clinical Relevance: Glaucoma is a leading cause of blindness in the world, and the identification of genes that contribute to this disease is essential. Elevated IOP is a principal risk factor for primary open-angle glaucoma and an intriguing quantitative trait that may strongly influence the development of disease. C1 NHGRI, Stat Genet Sect, Inherited Dis Res Branch, NIH, Baltimore, MD 21210 USA. Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. Univ Wisconsin, Dept Ophthalmol & Visual Sci, Madison, WI USA. RP Duggal, P (reprint author), NHGRI, Stat Genet Sect, Inherited Dis Res Branch, NIH, 333 Cassell Dr,Suite 1200, Baltimore, MD 21210 USA. EM pduggal@mail.nih.gov OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU Intramural NIH HHS [Z01 HG200327-03]; NCRR NIH HHS [P41 RR003655, P41 RR003655-16, RR03665]; NEI NIH HHS [U10 EY006594-13, R01 EY010605, R01 EY010605-04, R01 EY015286, R01 EY015286-02, U10 EY006594, U10 EY06594] NR 31 TC 36 Z9 36 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 2007 VL 125 IS 1 BP 74 EP 79 DI 10.1001/archopht.125.1.74 PG 6 WC Ophthalmology SC Ophthalmology GA 123ZQ UT WOS:000243336800010 PM 17210855 ER PT J AU Klein, AP Duggal, P Lee, KE Klein, R Bailey-Wilson, JE Klein, BEK AF Klein, Alison P. Duggal, Priya Lee, Kristine E. Klein, Ronald Bailey-Wilson, Joan E. Klein, Barbara E. K. TI Confirmation of linkage to ocular refraction on chromosome 22q and identification of a novel linkage region on 1q SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID BEAVER DAM EYE; FAMILIAL HIGH MYOPIA; CONE DYSFUNCTION; GENOMEWIDE SCAN; ERROR; LOCUS; POPULATION; MAPS AB Objective: To localize genes influencing ocular refraction in subjects in the Beaver Dam Eye Study. Previous studies establish that myopia clusters within families and linkage to myopia has been demonstrated on 2q, 4q, 12q, 17q, 18q, 22q, and Xq. Few studies have examined genetic effects across the entire range of refraction, though linkages to 1p, 3q, 4q, 8p, and 11p have been reported, and our previous analysis of the Beaver Dam Eye Study demonstrated substantial heritability for refraction (68%). Methods: We conducted nonparametric sibling-pair and genome-wide linkage analyses on spherical equivalent adjusting for age, education, and nuclear sclerosis, in 834 sibling pairs in 486 extended pedigrees. Results: We identified a novel region of suggestive linkage on 1q (multipoint, P < .00019) and replicated the 22q region (multipoint, P = .0033) previously linked to myopia. Additionally, there was some evidence of linkage to 7p (multipoint, P = .0023). Conclusion: Refraction is a complex trait influenced by both genes and environment. Our work confirms a previously reported linkage region on 22q and identifies 2 novel regions of linkage on 1q and 7p. Clinical Relevance: Further, genetic research is needed to finemap this trait to identify the causative gene. Modifying the actions of such a gene might lead to a reduction in the risk of refractive error. C1 Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Dept Oncol, Baltimore, MD 21231 USA. Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Dept Pathol, Baltimore, MD 21231 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21231 USA. NHGRI, Stat Genet Sect, Inherited Dis Res Branch, Baltimore, MD USA. Univ Wisconsin, Sch Med, Dept Ophthalmol & Visual Sci, Madison, WI USA. RP Klein, AP (reprint author), Johns Hopkins Univ, Sidney Kimmel Comprehens Canc Ctr, Sch Med, Dept Oncol, 1550 Orleans St, Baltimore, MD 21231 USA. OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU Intramural NIH HHS; NEI NIH HHS [EY015286, EY06594] NR 34 TC 32 Z9 32 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JAN PY 2007 VL 125 IS 1 BP 80 EP 85 DI 10.1001/archopht.125.1.80 PG 6 WC Ophthalmology SC Ophthalmology GA 123ZQ UT WOS:000243336800011 PM 17210856 ER PT B AU Walker, FL Gallagher, ME Thoma, GR AF Walker, Frank L. Gallagher, Marie E. Thoma, George R. GP SIS&T TI PDF file migration to PDF/A: Technical considerations SO Archiving 2007, Final Program and Proceedings LA English DT Proceedings Paper CT 4th IS&T Archiving Conference CY MAY 21-24, 2007 CL Arlington, VA SP Soc Imaging Sci & Technol, ALA ALCTS Assoc Lib Collect & Tech Serv, CNI, DLF, DPC, ECPA, ISCC, MCN, OCLC, SAA AB The PDF/A specification for long-term preservation of electronic documents became an international standard in 2005. This standard seeks to guarantee the long-term visual appearance of an electronic document. For collections to be archived as PDF files, it makes sense to select the PDF/A file format, because this particular type of PDF file makes it easier to migrate to future file formats. However, in the years before the PDF/A specification became a standard, many organizations began creating archives of collections in PDF, but in formats not necessarily compatible with PDF/A. Because of its value to preservation that PDF/A offers, there is an advantage to migrating collections to PDF/A. Commercial software tools are becoming available, both for creating PDF/A files and for evaluating their compatibility with the PDF/A standard. One such tool was used to study PDF files culled from the Internet as well as from an in-house collection to determine the chances of success for migrating an archived collection of PDF documents to PDF/A. This study explores the types of problems posed by such a migration, and determines the circumstances in which a migration would be successful. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. NR 6 TC 0 Z9 0 U1 0 U2 3 PU SOC IMAGING SCIENCE & TECHNOLOGY PI SPRINGFIELD PA 7003 KILWORTH LANE, SPRINGFIELD, VA 22151 USA BN 978-0-89208-270-4 PY 2007 BP 6 EP 11 PG 6 WC Information Science & Library Science; Imaging Science & Photographic Technology SC Information Science & Library Science; Imaging Science & Photographic Technology GA BGX58 UT WOS:000251160200003 ER PT B AU Gallagher, ME AF Gallagher, Marie E. GP SIS&T TI Keeping the promises associated with your digital assets: Is it possible SO Archiving 2007, Final Program and Proceedings LA English DT Proceedings Paper CT 4th IS&T Archiving Conference CY MAY 21-24, 2007 CL Arlington, VA SP Soc Imaging Sci & Technol, ALA ALCTS Assoc Lib Collect & Tech Serv, CNI, DLF, DPC, ECPA, ISCC, MCN, OCLC, SAA AB The Profiles in Science (R) Web site [1] features digital reproductions of historical papers, photographs, audios and videos selected from the archival collections of the National Library of Medicine as well as collaborating institutions. The Web site's digital items are derivatives of high quality digital masters residing in a repository designed for long term survival. The need for significant infrastructure to guarantee the persistence of these digital files was expected, and our desire to ensure their persistence influenced our choices and system design decisions from the start. Choosing file formats carefully, making certain that our digital assets were not lost due to media degradation or obsolescence, and planning for maximum flexibility in order to take advantage of rapidly changing technology were among the strategies we employed from the beginning [2]. However, the items selected for Profiles in Science include both public domain materials and materials restricted for copyright or other reasons. The need for additional infrastructure to keep copyright and restriction-related promises associated with individual digital assets became apparent. Situations that called for sharing items from our repository required different strategies for different cases depending on the recipients and their intended use of the items. In all cases, we decided to prominently associate the property rights information with the digital artifacts in order to protect all stakeholders. Rights information embedded in digital items can be overlooked or ignored. Rights information stored separately from digital items can be forgotten or lost. In this paper we share our experiences and examine linking property rights information with digital items. C1 Natl Lib Med, Lister Hill Natl Ctr Biomed Commun, Bethesda, MD USA. NR 13 TC 0 Z9 0 U1 0 U2 1 PU SOC IMAGING SCIENCE & TECHNOLOGY PI SPRINGFIELD PA 7003 KILWORTH LANE, SPRINGFIELD, VA 22151 USA BN 978-0-89208-270-4 PY 2007 BP 146 EP 149 PG 4 WC Information Science & Library Science; Imaging Science & Photographic Technology SC Information Science & Library Science; Imaging Science & Photographic Technology GA BGX58 UT WOS:000251160200034 ER PT J AU Lee, DS Evans, JC Robins, SJ Wilson, PW Albano, I Fox, CS Wang, TJ Benjamin, EJ D'Agostino, RB Vasan, RS AF Lee, Douglas S. Evans, Jane C. Robins, Sander J. Wilson, Peter W. Albano, Irene Fox, Caroline S. Wang, Thomas J. Benjamin, Emelia J. D'Agostino, Ralph B. Vasan, Ramachandran S. TI Gamma glutamyl transferase and metabolic syndrome, cardiovascular disease, and mortality risk - The Framingham Heart Study SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Article DE biomarkers; gamma glutamyl transferase; risk factor; cardiovascular disease; metabolic syndrome; mortality ID YOUNG-ADULTS CARDIA; C-REACTIVE PROTEIN; PROGNOSTIC VALUE; BLOOD-PRESSURE; LIVER-ENZYMES; TRANSPEPTIDASE; ASSOCIATION; DETERMINANTS; HYPERTENSION; CELLS AB Objective - To determine whether serum gamma-glutamyl transferase (GGT) predicts cardiovascular disease (CVD) morbidity and mortality, accounting for temporal changes in known CVD risk factors and C-reactive protein (CRP). Methods and Results - In 3451 Framingham Study participants (mean age 44 years, 52% women) we examined the relations of GGT with CVD risk factors, and prospectively determined the risk of new-onset metabolic syndrome, incident CVD, and death. GGT was positively associated with body mass index, blood pressure, LDL cholesterol, triglycerides, and blood glucose in cross-sectional analysis (P < 0.005). On follow-up (mean 19 years), 968 participants developed metabolic syndrome, 535 developed incident CVD, and 362 died. The risk of metabolic syndrome increased with higher GGT (multivariable-adjusted hazard ratio [HR] per SD increment log-GGT, 1.26 [95% CI; 1.18 to 1.35]). Adjusting for established CVD risk factors (as time-dependent covariates updated quadriennially) and baseline CRP, a 1-SD increase in log-GGT conferred a 13% increase in CVD risk (P = 0.007) and 26% increased risk of death (P < 0.001). Individuals in the highest GGT quartile experienced a 67% increase in CVD incidence (multivariable-adjusted HR 1.67, 95% CI; 1.25 to 2.22). Conclusion - An increase in serum GGT predicts onset of metabolic syndrome, incident CVD, and death suggesting that GGT is a marker of metabolic and cardiovascular risk. C1 Univ Toronto, Hlth Network, Div Cardiol, Inst Clin Evaluat Sci, Toronto, ON M4N 3M5, Canada. NHLBI, Framingham Heart Study, Framingham, MA USA. Univ Padua, Endocrine Metab Lab, Dept Med & Surg Sci, Padua, Italy. Med Univ S Carolina, Dept Med, Charleston, SC 29425 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Epidemiol & Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Cardiol Sect, Boston, MA 02215 USA. RP Lee, DS (reprint author), Univ Toronto, Hlth Network, Div Cardiol, Inst Clin Evaluat Sci, Rm G-106,2075 Bayview Ave, Toronto, ON M4N 3M5, Canada. EM dlee@ices.on.ca RI Lee, Douglas/J-4315-2014; OI Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [N01HV28178, 2K24HL04334, K23HL074077, N01-HC-25195, R01HL073272, R01HL076784, R01HL67288, R01HL71039] NR 41 TC 268 Z9 290 U1 1 U2 29 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JAN PY 2007 VL 27 IS 1 BP 127 EP 133 DI 10.1161/01.ATV.0000251993.20372.40 PG 7 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 127FZ UT WOS:000243572000021 PM 17095717 ER PT J AU Blackman, MR Muniyappa, R Wilson, M Moquin, BE Baldwin, HL Wong, KA Snyder, C Magalnick, M Alli, S Reynolds, J Steinberg, SM Goldbach-Mansky, R AF Blackman, Marc R. Muniyappa, Ranganath Wilson, Mildred Moquin, Barbara E. Baldwin, Howard L. Wong, Kelli A. Snyder, Christopher Magalnick, Michael Alli, Shaan Reynolds, James Steinberg, Seth M. Goldbach-Mansky, Raphaela TI Diurnal secretion of growth hormone, cortisol, and dehydroepiandrosterone in pre- and perimenopausal women with active rheumatoid arthritis: a pilot case-control study SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID PITUITARY-ADRENAL AXIS; TUMOR-NECROSIS-FACTOR; SYSTEMIC-LUPUS-ERYTHEMATOSUS; SERUM-LEVELS; FACTOR-I; CHRONIC INFLAMMATION; FACTOR-ALPHA; TNF-ALPHA; IGF-I; INTERLEUKIN-6 AB Rheumatoid arthritis ( RA) is associated with neuroendocrine and immunologic dysfunction leading to rheumatoid cachexia. Although excess proinflammatory cytokines can decrease somatotropic axis activity, little is known about the effects of RA on growth hormone/insulin-like growth factor-1 (GH/IGF-I) axis function. We tested the hypothesis that patients with active RA exhibit decreased GH/IGF-I axis activity. To do so, we conducted a pilot case-control study at a clinical research center in 7 pre-and perimenopausal women with active RA and 10 age-and body mass index-matched healthy women. Participants underwent blood sampling every 20 minutes for 24 hours ( 8 a. m. to 8 a. m.), and sera were assayed for GH, cortisol, and dehydroepiandrosterone ( DHEA). Sera obtained after overnight fasting were assayed for IGF-I, IGF-binding protein (IGFBP)-1, IGFBP-3, C-reactive protein (CRP), interleukin- 6 (IL-6), glucose, insulin, and lipids. Body composition and bone mineral density were evaluated by DEXA (dual emission x-ray absorptiometry) scans. In patients with RA, mean disease duration was 7.6 +/- 6.8 years, and erythrocyte sedimentation rate, CRP, and IL-6 were elevated. GH half-life was shorter than in control subjects (p = 0.0037), with no other significant group differences in GH deconvolution parameters or approximate entropy scores. IGF-I (p = 0.05) and IGFBP- 3 (p = 0.058) were lower, whereas IGFBP-1 tended to be higher (p = 0.066), in patients with RA, with nonsignificantly increased 24-hour total GH production rates. There were no significant group differences in cortisol or DHEA secretion. Lean body mass was lower in patients with RA (p = 0.019), particularly in the legs (p = 0.01). Women with active RA exhibit a trend toward GH insensitivity and relatively diminished diurnal cortisol and DHEA secretion for their state of inflammation. Whether these changes contribute to rheumatoid cachexia remains to be determined. C1 Natl Ctr Complementary & Alternat Med, Natl Inst Hlth, Clin Invest Lab, Endocrine Sect, Bethesda, MD 20892 USA. NIAMSD, NIH, Off Clin Director, Bethesda, MD 20892 USA. NIH, Warren Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. NCI, NIH, Canc Res Ctr, Biostat & Data Management Sect, Bethesda, MD 20892 USA. RP Blackman, MR (reprint author), Natl Ctr Complementary & Alternat Med, Natl Inst Hlth, Clin Invest Lab, Endocrine Sect, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM Marc.Blackman@va.gov FU Intramural NIH HHS NR 42 TC 7 Z9 7 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2007 VL 9 IS 4 AR R73 DI 10.1186/ar2271 PG 9 WC Rheumatology SC Rheumatology GA 222ZV UT WOS:000250339700020 PM 17662149 ER PT J AU Csako, G Costello, R Shamim, EA O'Hanlon, TP Tran, A Clauw, DJ Williams, HJ Miller, FW AF Csako, Gyorgy Costello, Rene Shamim, Ejaz A. O'Hanlon, Terrance P. Tran, Anthony Clauw, Daniel J. Williams, H. James Miller, Frederick W. TI Serum proteins and paraproteins in women with silicone implants and connective tissue disease: a case-control study SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID MONOCLONAL GAMMOPATHY; BREAST IMPLANTS; UNDETERMINED SIGNIFICANCE; MULTIPLE-MYELOMA; SCLEROSIS SCLERODERMA; SYSTEMIC-SCLEROSIS; ADULT-POPULATION; PLASMA-CELLS; RISK; GEL AB Prior studies have suggested abnormalities of serum proteins, including paraproteins, in women with silicone implants but did not control for the presence of connective-tissue disease (CTD). This retrospective case-control study, performed in tertiary-care academic centers, assessed possible alterations of serum proteins, including paraproteins, in such a population. Seventy-four women with silicone implants who subsequently developed CTD, and 74 age-matched and CTD-matched women without silicone implants, were assessed in the primary study; other groups were used for additional comparisons. Routine serum protein determinations and high-sensitivity protein electrophoresis and immunofixation electrophoresis were performed for detection of paraproteins. Women with silicone implants, either with or without CTD, had significantly lower serum total protein and alpha(1)-globulin, alpha(2)-globulin, beta-globulin,gamma-globulin, and IgG levels compared with those without silicone implants. There was no significant difference, however, in the frequency of paraproteinemia between women with silicone implants and CTD (9.5%) and age-matched and CTD-matched women without silicone implants (5.4%) (odds ratio, 1.82; 95% confidence interval, 0.51-6.45). Paraprotein isotypes were similar in the two groups, and the clinical characteristics of the 13 women with paraproteinemia were comparable with an independent population of 10 women with silicone breast implants, CTD, and previously diagnosed monoclonal gammopathies. In summary, this first comprehensive study of serum proteins in women with silicone implants and CTD found no substantially increased risk of monoclonal gammopathy. Women with silicone implants, however, had unexpectedly low serum globulin and immunoglobulin levels, with or without the subsequent development of CTD. The causes and clinical implications of these findings require further investigation. C1 [Csako, Gyorgy; Costello, Rene; Tran, Anthony] DHHS, NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. [Shamim, Ejaz A.; O'Hanlon, Terrance P.; Miller, Frederick W.] DHHS, NIH, Natl Inst Environm Hlth Sci, Environm Autoimmun Grp, Bethesda, MD 20892 USA. [Tran, Anthony] Associat Publ Hlth Labs, Silver Spring, MD 20910 USA. [Clauw, Daniel J.] Univ Michigan, Sch Med, Dept Med, Div Rheumatol, Ann Arbor, MI 48109 USA. [Williams, H. James] Univ Utah, Med Ctr, Dept Internal Med, Div Rheumatol, Salt Lake City, UT 84132 USA. RP Csako, G (reprint author), DHHS, NIH, Ctr Clin, Dept Lab Med, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM gcsako@nih.gov OI Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS NR 48 TC 3 Z9 4 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2007 VL 9 IS 5 AR R95 DI 10.1186/ar2295 PG 10 WC Rheumatology SC Rheumatology GA 252TB UT WOS:000252468400018 PM 17875216 ER PT J AU Ettinger, R Kuchen, S Sims, GP Robbins, R Withers, D Fischer, RT Lipsky, PE AF Ettinger, Rachel Kuchen, Stefan Sims, Gary P. Robbins, Rachel Withers, David Fischer, Randy T. Lipsky, Peter E. TI IL-21 and BAFF/BLyS synergize in stimulating plasma cell differentiation from human marginal zone B cells as well as from circulating peripheral blood B cells from autoimmune patients SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract CT 6th Global Arthritis Research Network Meeting (GARN) CY MAY 10-13, 2007 CL Zurich, SWITZERLAND C1 [Ettinger, Rachel; Kuchen, Stefan; Sims, Gary P.; Robbins, Rachel; Withers, David; Fischer, Randy T.; Lipsky, Peter E.] NIAMS, Autoimmun Branch, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2007 VL 9 SU 3 AR P8 DI 10.1186/ar2234 PG 1 WC Rheumatology SC Rheumatology GA 285YA UT WOS:000254810900009 ER PT J AU Hansen, A Lipsky, PE Dorner, T AF Hansen, Arne Lipsky, Peter E. Doerner, Thomas TI B cells in Sjogren's syndrome: indications for disturbed selection and differentiation in ectopic lymphoid tissue SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GLAND EPITHELIAL-CELLS; LABIAL SALIVARY-GLANDS; EPSTEIN-BARR-VIRUS; PERIPHERAL-BLOOD; GERMINAL CENTER; T-CELLS; AUTOANTIBODY PRODUCTION; RHEUMATOID-ARTHRITIS; CHAIN REARRANGEMENTS AB Primary Sjogren's syndrome ( pSS) is an autoimmune disorder characterized by specific pathological features. A hallmark of pSS is B- cell hyperactivity as manifested by the production of autoantibodies, hypergammaglobulinemia, formation of ectopic lymphoid structures within the inflamed tissues, and enhanced risk of B- cell lymphoma. Changes in the distribution of peripheral B- cell subsets and differences in post- recombination processes of immunoglobulin variable region ( IgV) gene usage are also characteristic features of pSS. Comparison of B cells from the peripheral blood and salivary glands of patients with pSS with regard to their expression of the chemokine receptors CXCR4 and CXCR5, and their migratory capacity towards the corresponding ligands, CXCL12 and CXCL13, provide a mechanism for the prominent accumulation of CXCR4+ CXCR5+ memory B cells in the inflamed glands. Glandular B cells expressing distinct features of IgV light and heavy chain rearrangements, ( re) circulating B cells with increased mutations of c transcripts in both CD27 - and CD27+ memory B- cell subsets, and enhanced frequencies of individual peripheral B cells containing IgV heavy chain transcripts of multiple isotypes indicate disordered selection and incomplete differentiation processes of B cells in the inflamed tissues in pSS. This may possibly be related to a lack of appropriate censoring mechanisms or different B- cell activation pathways within the ectopic lymphoid structures of the inflamed tissues. These findings add to our understanding of the pathogenesis of this autoimmune inflammatory disorder and may result in new therapeutic approaches. C1 Charite Univ Med Berlin, Dept Med, Charite Ctr CC 12, D-10098 Berlin, Germany. Charite Univ Med Berlin, Dept Med, Charite Ctr CC 14, D-10098 Berlin, Germany. Charite Univ Med Berlin, Dept Transfus Med, D-10098 Berlin, Germany. NIAMSD, NIH, Autoimmun Branch, Bethesda, MD 20892 USA. RP Hansen, A (reprint author), Charite Univ Med Berlin, Dept Med, Charite Ctr CC 12, Clara Zetkin Str 94, D-10098 Berlin, Germany. EM arne.hansen@charite.de NR 117 TC 68 Z9 73 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2007 VL 9 IS 4 AR 218 DI 10.1186/ar2210 PG 12 WC Rheumatology SC Rheumatology GA 222ZV UT WOS:000250339700007 PM 17697366 ER PT J AU Kimberley, FC Lobito, AA Siegel, RM Screaton, GR AF Kimberley, Fiona C. Lobito, Adrian A. Siegel, Richard M. Screaton, Gavin R. TI Falling into TRAPS - receptor misfolding in the TNF receptor 1-associated periodic fever syndrome SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID NECROSIS-FACTOR-RECEPTOR; FAMILIAL HIBERNIAN FEVER; NF-KAPPA-B; ENCODING MEVALONATE KINASE; TNFRSF1A MUTATIONS; AUTOINFLAMMATORY SYNDROMES; MEDITERRANEAN FEVER; ACTIVATION; GENE; DOMAIN AB TNF receptor-associated periodic syndrome (TRAPS) is a dominantly inherited disease caused by missense mutations in the TNF receptor 1 ( TNFR1) gene. Patients suffer from periodic bouts of severe abdominal pain, localised inflammation, migratory rashes, and fever. More than 40 individual mutations have been identified, all of which occur in the extracellular domain of TNFR1. In the present review we discuss new findings describing aberrant trafficking and function of TNFR1 harbouring TRAPS mutations, challenging the hypothesis that TRAPS pathology is driven by defective receptor shedding, and we suggest that TNFR1 might acquire novel functions in the endoplasmic reticulum, distinct from its role as a cell surface receptor. We also describe the clinical manifestations of TRAPS, current treatment regimens, and the widening array of patient mutations. C1 Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London W12 0NN, England. Univ Amsterdam, Acad Med Ctr, Lab Expt Oncol & Radiobiol, NL-1105 AZ Amsterdam, Netherlands. Genetech, San Francisco, CA 94080 USA. NIAMS, NIH, Autoimmun Branch, Immunoregulat Unit, Bethesda, MD 20892 USA. RP Screaton, GR (reprint author), Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Du Cane Rd, London W12 0NN, England. EM g.screaton@imperial.ac.uk RI Siegel, Richard/C-7592-2009; OI Siegel, Richard/0000-0001-5953-9893; Screaton, Gavin/0000-0002-3549-4309 FU Medical Research Council [G0400720] NR 64 TC 39 Z9 39 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2007 VL 9 IS 4 AR 217 DI 10.1186/ar2197 PG 8 WC Rheumatology SC Rheumatology GA 222ZV UT WOS:000250339700006 PM 17666110 ER PT J AU Kolf, CM Cho, E Tuan, RS AF Kolf, Catherine M. Cho, Elizabeth Tuan, Rocky S. TI Mesenchymal stromal cells - Biology of adult mesenchymal stem cells: regulation of niche, self-renewal and differentiation SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID HUMAN BONE-MARROW; GROWTH-FACTOR-BETA; HUMAN ADIPOSE-TISSUE; CHICK LIMB-BUD; PROGENITOR CELLS; IN-VITRO; OSTEOGENIC DIFFERENTIATION; MORPHOGENETIC PROTEIN-2; FUNCTIONAL-ANALYSIS; GENE-EXPRESSION AB Recent advances in understanding the cellular and molecular signaling pathways and global transcriptional regulators of adult mesenchymal stem cells have provided new insights into their biology and potential clinical applications, particularly for tissue repair and regeneration. This review focuses on these advances, specifically in the context of self-renewal and regulation of lineage-specific differentiation of mesenchymal stem cells. In addition we review recent research on the concept of stem cell niche, and its relevance to adult mesenchymal stem cells. C1 NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Cartilage Biol & Orthopaed Branch, NIH, US Dept HHS, 50 South Dr, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU Intramural NIH HHS; NIAMS NIH HHS [Z01 AR041131] NR 90 TC 408 Z9 455 U1 10 U2 80 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2007 VL 9 IS 1 AR 204 DI 10.1186/ar2116 PG 10 WC Rheumatology SC Rheumatology GA 164RD UT WOS:000246250800005 PM 17316462 ER PT J AU Longo, NS Satorius, C Durandy, A Lipsky, PE AF Longo, Nancy S. Satorius, Colleen Durandy, Anne Lipsky, Peter E. TI Characterization of immunoglobulin mutations in humans with activation-induced cytidine deaminase deficiency SO ARTHRITIS RESEARCH & THERAPY LA English DT Meeting Abstract CT 6th Global Arthritis Research Network Meeting (GARN) CY MAY 10-13, 2007 CL Zurich, SWITZERLAND C1 [Longo, Nancy S.; Satorius, Colleen; Lipsky, Peter E.] NIAMSD, Autoimmun Branch, Bethesda, MD 20892 USA. [Durandy, Anne] Hop Necker Enfants Malad, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2007 VL 9 SU 3 AR P14 DI 10.1186/ar2240 PG 2 WC Rheumatology SC Rheumatology GA 285YA UT WOS:000254810900015 ER PT J AU Ochi, T Yoshikawa, H Toyosaki-Maeda, T Lipsky, PE AF Ochi, Takahiro Yoshikawa, Hideki Toyosaki-Maeda, Tomoko Lipsky, Peter E. TI Mesenchymal stromal cells - Nurse-like cells reside in the synovial tissue and bone marrow in rheumatoid arthritis SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID FIBROBLAST-LIKE SYNOVIOCYTES; CHRONIC LYMPHOCYTIC-LEUKEMIA; SOLUBLE FAS LIGAND; B-CELLS; PHENOTYPIC CHARACTERIZATION; PROMOTE SURVIVAL; EXPRESSION; SUPPORT; LINES; DIFFERENTIATION AB A major question concerning the immunopathology of rheumatoid arthritis is why the disease is localized to particular joints. A possible explanation could be the presence within the synovium of cells that foster inflammation or easy accessibility of the synovium to migratory disease enhancing cells. Within both the bone marrow and the synovium, fibroblastic stromal cells play an important role in supporting the differentiation and survival of normal cells, and also contribute to the pathologic processes. Among fibroblastic stromal cells in synovial tissue and bone marrow, nurse-like cells are a unique population having the specific capacity to promote pseudoemperipolesis ( adhesion and holding beneath) of lymphocytes, and also the ability to promote the growth and function of some populations of lymphocytes and monocytes. Nurse-like cells could therefore contribute to the immunopathogenesis of rheumatoid arthritis, and may contribute to the localization of inflammation within specific joints. The present review considers the evidence that supports these possibilities. C1 Sagamihara Natl Hosp, Kanagawa, Japan. Osaka Univ, Sch Med, Dept Orthopaed Surg, Osaka 553, Japan. Shionogi & Co Ltd, Shionogi Res Labs, Dept Immunol, Osaka 553, Japan. NIAMSD, Bethesda, MD 20892 USA. RP Ochi, T (reprint author), Sagamihara Natl Hosp, Kanagawa, Japan. EM t-ochi@sagamihara-hosp.gr.jp NR 38 TC 8 Z9 8 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2007 VL 9 IS 1 AR 201 DI 10.1186/ar2105 PG 6 WC Rheumatology SC Rheumatology GA 164RD UT WOS:000246250800002 PM 17306036 ER PT J AU Steinert, AF Ghivizzani, SC Rethwilm, A Tuan, RS Evans, CH Noth, U AF Steinert, Andre F. Ghivizzani, Steven C. Rethwilm, Axel Tuan, Rocky S. Evans, Christopher H. Noeth, Ulrich TI Major biological obstacles for persistent cell-based regeneration of articular cartilage SO ARTHRITIS RESEARCH & THERAPY LA English DT Review ID MESENCHYMAL STEM-CELLS; AUTOLOGOUS CHONDROCYTE IMPLANTATION; TISSUE-ENGINEERED CARTILAGE; MARROW STROMAL CELLS; FULL-THICKNESS DEFECTS; MEDIATED GENE-TRANSFER; GROWTH-FACTOR-I; X COLLAGEN EXPRESSION; BONE-MARROW; CHONDROGENIC DIFFERENTIATION AB Hyaline articular cartilage, the load-bearing tissue of the joint, has very limited repair and regeneration capacities. The lack of efficient treatment modalities for large chondral defects has motivated attempts to engineer cartilage constructs in vitro by combining cells, scaffold materials and environmental factors, including growth factors, signaling molecules, and physical influences. Despite promising experimental approaches, however, none of the current cartilage repair strategies has generated long lasting hyaline cartilage replacement tissue that meets the functional demands placed upon this tissue in vivo. The reasons for this are diverse and can ultimately result in matrix degradation, differentiation or integration insufficiencies, or loss of the transplanted cells and tissues. This article aims to systematically review the different causes that lead to these impairments, including the lack of appropriate differentiation factors, hypertrophy, senescence, apoptosis, necrosis, inflammation, and mechanical stress. The current conceptual basis of the major biological obstacles for persistent cell-based regeneration of articular cartilage is discussed, as well as future trends to overcome these limitations. C1 Univ Wurzburg, Orthopaed Ctr Musculoskeletal Res, Konig Ludwig Haus, Wurzburg, Germany. Univ Florida, Dept Orthopaed & Rehabil, Gainesville, FL USA. Univ Wurzburg, Inst Virol & Immunbiol, D-8700 Wurzburg, Germany. NIAMSD, Cartilage Biol & Orthopaed Branch, Dept Hlth & Human Serv, NIH, Bethesda, MD USA. Harvard Univ, Sch Med, Ctr Mol Orthopaed, Boston, MA USA. RP Steinert, AF (reprint author), Univ Wurzburg, Orthopaed Ctr Musculoskeletal Res, Konig Ludwig Haus, Wurzburg, Germany. EM a-steinert.klh@mail.uni-wuerzburg.de RI Steinert, Prof. Dr. , Andre/P-4559-2015 OI Steinert, Prof. Dr. , Andre/0000-0002-4397-8434 FU NIAMS NIH HHS [AR48566, AR50249, R01 AR048566, R01 AR050249, Z01 AR041131] NR 205 TC 147 Z9 158 U1 3 U2 33 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2007 VL 9 IS 3 AR 213 DI 10.1186/ar2195 PG 15 WC Rheumatology SC Rheumatology GA 201CO UT WOS:000248809300005 PM 17561986 ER PT J AU Tuan, RS AF Tuan, Rocky S. TI A second-generation autologous chondrocyte implantation approach to the treatment of focal articular cartilage defects SO ARTHRITIS RESEARCH & THERAPY LA English DT Article ID PERFUSION CULTURE; CHONDRAL DEFECTS; STEM-CELLS; REPAIR; KNEE; TRANSPLANTATION; REGENERATION; GRAFTS AB Autologous chondrocyte implantation (ACI) is the most widely used cell-based surgical procedure for the repair of articular cartilage defects. Challenges to successful ACI outcomes include limitation in defect size and geometry as well as inefficient cell retention. Second-generation ACI procedures have thus focused on developing three-dimensional constructs using native and synthetic biomaterials. Clinically significant and satisfactory results from applying autologous chondrocytes seeded in fibrin within a biodegradable polymeric material were recently reported. In the future, third-generation cell-based articular cartilage repair should focus on the use of chondroprogenitor cells and biofunctionalized biomaterials for more extensive and permanent repair. C1 NIAMSD, Natl Inst Hlth, Dept Hlth & Human Serv, Cartilage Biol & Orthopaed Branch, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, Natl Inst Hlth, Dept Hlth & Human Serv, Cartilage Biol & Orthopaed Branch, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU Intramural NIH HHS NR 27 TC 35 Z9 36 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1478-6354 J9 ARTHRITIS RES THER JI Arthritis Res. Ther. PY 2007 VL 9 IS 5 AR 109 DI 10.1186/ar2310 PG 4 WC Rheumatology SC Rheumatology GA 252TB UT WOS:000252468400002 PM 18021426 ER PT J AU Almond, CSD Chen, EA Berman, MR Less, JR Baldwin, JT Linde-Feucht, SR Hoke, TR Pearson, GD Jenkins, K Duncan, BW Zuckerman, BD AF Almond, Christopher S. D. Chen, Eric A. Berman, Michael R. Less, Joanne R. Baldwin, J. Timothy Linde-Feucht, Sarah R. Hoke, Tracey R. Pearson, Gail D. Jenkins, Kathy Duncan, Brian W. Zuckerman, Bram D. TI High-risk medical devices, children and the FDA: Regulatory challenges facing pediatric mechanical circulatory support devices SO ASAIO JOURNAL LA English DT Article; Proceedings Paper CT 2nd International Conference on Pediatric Mechanical Circulatory Support Systems/Pediatric Cardiopulmonary Perfusion CY MAY 18-20, 2006 CL Toronto, CANADA ID EXTRACORPOREAL MEMBRANE-OXYGENATION; CARDIAC TRANSPLANTATION; ASSIST DEVICES; LIFE-SUPPORT; INFANTS; BRIDGE; HEART; ECMO AB Pediatric mechanical circulatory support is a critical unmet need in the United States. Infant- and child-sized ventricular assist devices are currently being developed largely through federal contracts and grants through the National Heart, Lung, and Blood Institute (NHLBI). Human testing and marketing of high-risk devices for children raises epidemiologic and regulatory issues that will need to be addressed. Leaders from the US Food and Drug Administration (FDA), NHLBI, academic pediatric community, and industry convened in January 2006 for the first FDA Workshop on the Regulatory Process for Pediatric Mechanical Circulatory Support Devices. The purpose was to provide the pediatric community with an overview of the federal regulatory process for high-risk medical devices and to review the challenges specific to the development and regulation of pediatric mechanical circulatory support devices. Pediatric mechanical circulatory support present significant epidemiologic, logistic, and financial challenges to industry, federal regulators, and the pediatric community. Early interactions with the FDA, shared appreciation of challenges, and careful planning will be critical to avoid unnecessary delays in making potentially life-saving devices available for children. Collaborative efforts to address these challenges are warranted. C1 Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Cardiol, Boston, MA 02115 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NHLBI, NIH, Bethesda, MD 20892 USA. US FDA, Off Orphan Prod Dev, Rockville, MD 20857 USA. Cleveland Clin Fdn, Childrens Hosp, Dept Cardiac Surg, Cleveland, OH 44195 USA. RP Almond, CSD (reprint author), Harvard Univ, Childrens Hosp Boston, Sch Med, Dept Cardiol, 300 Longwood Ave, Boston, MA 02115 USA. NR 21 TC 14 Z9 14 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1058-2916 J9 ASAIO J JI Asaio J. PD JAN-FEB PY 2007 VL 53 IS 1 BP 4 EP 7 DI 10.1097/01.mat.0000247958.84788.3a PG 4 WC Engineering, Biomedical; Transplantation SC Engineering; Transplantation GA 128XE UT WOS:000243692200002 PM 17237642 ER PT J AU Han, SH Koh, KK Quon, MJ Lee, Y Shin, EK AF Han, Seung Hwan Koh, Kwang Kon Quon, Michael J. Lee, Yonghee Shin, Eak Kyun TI The effects of simvastatin, losartan, and combined therapy on soluble CD40 ligand in hypercholesterolemic, hypertensive patients SO ATHEROSCLEROSIS LA English DT Article DE HMG-CoA reductase inhibitor; angiotensin II receptor blocker; CD40 ligand; inflammation ID ACUTE CORONARY SYNDROMES; POSTMENOPAUSAL WOMEN; ENDOTHELIAL-CELLS; RECEPTOR BLOCKER; CONTROLLED-TRIAL; STATIN THERAPY; RISK; INFLAMMATION; ACTIVATION; REDUCTION AB The proinflammatory mediator CD40 ligand plays an important role in atherogenesis. Biological mechanisms underlying statin and angiotensin 11 type I receptor blocker therapies differ. Therefore, we compared the effects of these therapies either alone or in combination on plasma soluble CD40 ligand (sCD40L). This was a randomized, double-blind, placebo-controlled cross-over trial with three treatment arms (each 2 months) and two washout periods (each 2 months). Forty-seven hypertensive, hypercholesterotemic patients were given simvastatin 20 mg and placebo, simvastatin 20 mg and losartan 100 mg, or losartan 100 mg and placebo daily during each 2 month treatment period. Simvastatin alone did not significantly reduce sCD40L levels relative to baseline measurements when the entire cohort was analyzed. However, simvastatin significantly reduced sCD40L levels from 5.10 +/- 0.34 to 3.07 +/- 0.43 ng/ml (P = 0.002) in a subgroup of 18 patients with high baseline sCD40L levels > 2.95 ng/ml. Combined therapy or losartan alone significantly decreased plasma sCD40L levels relative to baseline measurements by 14 +/- 7% (P = 0.001) and 13 +/- 10% (P = 0.001), respectively. These decreases were significantly greater than those observed with simvastatin alone (P = 0.023 by ANOVA). Significant inverse correlations between baseline sCD40L levels and percent changes in sCD40L levels were observed (r = -0.456, P = 0.001 after simvastatin alone; r = -0.476, P < 0.001 after combined therapy; r = -0.45 1, P = 0.002 after losartan alone). Losartan alone or combined therapy significantly reduced plasma sCD40L levels more than simvastatin alone in our subjects. Simvastatin, losartan and combined therapy significantly reduced sCD40L to the greatest extent in patients with high baseline sCD40L levels. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Gachon Med Sch, Gil Heart Ctr, Vasc Med & Atherosclerosis Unit, Inchon 405760, South Korea. NCCAM, Diabet Unit, Clin Invest Lab, NIH, Bethesda, MD USA. Ewha Womans Univ, Dept Stat, Seoul, South Korea. RP Koh, KK (reprint author), Gachon Med Sch, Gil Heart Ctr, Vasc Med & Atherosclerosis Unit, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@ghil.com RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 29 TC 29 Z9 32 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0021-9150 J9 ATHEROSCLEROSIS JI Atherosclerosis PD JAN PY 2007 VL 190 IS 1 BP 205 EP 211 DI 10.1016/j.atherosclerosis.2006.01.021 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 128PY UT WOS:000243671500032 PM 16500662 ER PT J AU Jirawuthiworavong, GV Levy-Clarke, GA Nussenblat, RB AF Jirawuthiworavong, Guy V. Levy-Clarke, Grace A. Nussenblat, Robert B. BE Shoenfeld, Y Gershwin, ME Meroni, PL TI RETINAL AUTOANTIBODIES SO AUTOANTIBODIES, 2ND EDITION LA English DT Article; Book Chapter ID RETINOPATHY; RECOVERIN; CANCER; IDENTIFICATION; ANTIBODIES AB Retinal autoantibodies, commonly referred to as antiretinal antibodies (ARA), have been implicated in the pathogenicity of a variety of immune-mediated visual disorders. In the paraneoplastic syndrome, cancer-associated retinopathy (CAR), ARA with their targeted retinal antigens have been identified. There are many other infectious, inflammatory as well as degenerative retinopathies associated with the presence of ARA. More than 15 ARA have been identified in CAR. For these autoantibodies, the autoantigens still remain unknown. Recoverin, a calcium-binding retinal protein involved in the reversal of the phototransduction cascade, is well established as the most common CAR autoantigen. The proposed mechanism of antibody-mediated degeneration involves molecular mimicry and loss of peripheral tolerance to residing retinal antigens. In vitro, ARA have been shown to cause apoptotic death of photoreceptors. Questions remain though, regarding the access and penetration of these antibodies into the retina. Furthermore, the titer of ARA does not always correlate with clinical disease status. There exists lack of standardization of antibody and antigen detection. Thus, results from different laboratories cannot exactly be compared. Sensitivity and specificity for the detection of pathogenic ARA is also lacking. Though there are many caveats, presence of ARA still serves as an adjunctive study for the clinician to confirm a diagnosis, which often is difficult to make. The study of ARA serves as an excellent model for the elucidation of pathological mechanisms underlying autoimmune retinopathy and its allied disorders. C1 [Jirawuthiworavong, Guy V.; Nussenblat, Robert B.] NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Jirawuthiworavong, GV (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr, Bethesda, MD 20892 USA. NR 10 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-046723-8 PY 2007 BP 653 EP 658 DI 10.1016/B978-044452763-9/50084-6 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA BCU46 UT WOS:000311481100083 ER PT J AU Annibali, V Di Giovanni, S Cannoni, S Giugni, E Bomprezzi, R Mattei, C Elkahloun, A Coccia, EM Alfo, M Orzi, F Ristori, G Salvetti, M AF Annibali, Viviana Di Giovanni, Simone Cannoni, Stefania Giugni, Elisabetta Bomprezzi, Roberto Mattei, Carlo Elkahloun, Abdel Coccia, Eliana Marina Alfo, Marco Orzi, Francesco Ristori, Giovanni Salvetti, Marco TI Gene expression profiles reveal homeostatic dynamics during interferon-beta therapy in multiple sclerosis SO AUTOIMMUNITY LA English DT Article DE multiple sclerosis; interferon-beta; cDNA microarrays; gene expression ID MOLECULES AB Understanding the mechanisms that sustain the effects of disease modifying drugs in multiple sclerosis (MS) may help refine current therapies and improve our knowledge of disease pathogenesis. By using cDNA microarrays, we investigated gene expression in the peripheral blood mononuclear cells (PBMC) of 7 MS patients, at baseline (T0) as well as after 1 (T1) and 3 months (T3) of interferon beta-1a (IFN-b-1a; Rebife 44 mg) therapy. Gene expression changes involved genes of both immunological and non-immunological significance. We validated IL-10 up-regulation, which is in accordance with previous reports, and other novel changes that underscore the capacity of IFN-b to impair antigen presentation and migration of inflammatory elements into the central nervous system (up-regulation of filamin B and down-regulation of IL-16 and rab7). Overall, gene expression changes became less pronounced after 3 months of therapy, suggesting a homeostatic response to IFN-b. This may be of use for the design of new treatment schedules. C1 Univ Roma La Sapienza, S Andrea Hosp, Dept Neurol, Rome, Italy. Univ Roma La Sapienza, S Andrea Hosp, Ctr Expt Neurol Therapy, Rome, Italy. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Ist Super Sanita, Dept Infect Parasit & Immune Mediated Dis, I-00161 Rome, Italy. Univ Roma La Sapienza, Dept Stat, Rome, Italy. RP Salvetti, M (reprint author), Osped S Andrea, Via Grottarossa 1035, I-00189 Rome, Italy. EM marco.salvetti@uniroma1.it RI Coccia, Eliana/B-4752-2013 OI Coccia, Eliana/0000-0002-1606-2949 NR 12 TC 16 Z9 16 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PY 2007 VL 40 IS 1 BP 16 EP 22 DI 10.1080/08916930601135241 PG 7 WC Immunology SC Immunology GA 145WZ UT WOS:000244897800003 PM 17364493 ER PT J AU Tarasenko, T Dean, JA Bolland, S AF Tarasenko, Tatyana Dean, Jonathan A. Bolland, Silvia TI Fc gamma RIIB as a modulator of autoimmune disease susceptibility SO AUTOIMMUNITY LA English DT Review DE SLE; susceptibility; Fc gamma receptors ( Fc gamma R); Fc gamma RIIB ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; INOSITOL PHOSPHATASE SHIP; ALTERS RECEPTOR EXPRESSION; COLLAGEN-INDUCED ARTHRITIS; B-CELL; DEFICIENT MICE; IN-VIVO; INHIBITORY RECEPTOR; PROMOTER HAPLOTYPE; ANTIINFLAMMATORY ACTIVITY AB Antibodies are secreted to recognize and in some cases directly neutralize pathogens. Another important means by which they are essential components of the immune system is through binding to Fc receptors. Effector responses triggered by antibody binding of Fc receptors affect a host of important cellular responses such as phagocytosis, inflammatory cytokine release, antigen presentation, and regulation of humoral responses. A crucial check on this antibody-mediated signal is through the inhibitory receptor, Fc gamma RIIB. In this review we discuss how dysregulation of FcgRIIB can result in a lowered threshold for autoimmunity in mice and humans. We close with a discussion of the potential for applying these findings to immunotherapy. C1 NIAID, Immunogenet Lab, Autoimmun & Funct Genom Sect, NIH, Rockville, MD 20852 USA. RP Bolland, S (reprint author), NIAID, Immunogenet Lab, Autoimmun & Funct Genom Sect, NIH, Rockville, MD 20852 USA. EM sbolland@niaid.nih.gov FU Intramural NIH HHS NR 113 TC 39 Z9 41 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0891-6934 J9 AUTOIMMUNITY JI Autoimmunity PY 2007 VL 40 IS 6 BP 409 EP 417 DI 10.1080/08916930701464665 PG 9 WC Immunology SC Immunology GA 205TH UT WOS:000249137000003 PM 17729034 ER PT J AU Tordjman, S Drapier, D Bonnot, O Graignic, R Fortes, S Cohen, D Millet, B Laurent, C Roubertoux, PL AF Tordjman, Sylvie Drapier, Dominique Bonnot, Olivier Graignic, Rozenn Fortes, Sylvia Cohen, David Millet, Bruno Laurent, Claudine Roubertoux, Pierre L. TI Animal models relevant to schizophrenia and autism: Validity and limitations SO BEHAVIOR GENETICS LA English DT Review DE psychiatry; autism; schizophrenia; animal models; neurobiological similarity; behavioral similarity; genetics; brain ID SENSORIMOTOR GATING ABNORMALITIES; ACOUSTIC STARTLE RESPONSE; HOXA1 A218G POLYMORPHISM; LATENT INHIBITION MODEL; PLASMA BETA-ENDORPHIN; LESCH-NYHAN SYNDROME; INFANTILE-AUTISM; SPECTRUM DISORDERS; ENDOGENOUS OPIOIDS; DOWN-SYNDROME AB Development of animal models is a crucial issue in biological psychiatry. Animal models provide the opportunity to decipher the relationships between the nervous system and behavior and they are an obligatory step for drug tests. Mouse models or rat models to a lesser extent could help to test for the implication of a gene using gene targeting or transfecting technologies. One of the main problem for the development of animal models is to define a marker of the psychiatric disorder. Several markers have been suggested for schizophrenia and autism, but for the moment no markers or etiopathogenic mechanisms have been identified for these disorders. We examined here animal models related to schizophrenia and autism and discussed their validity and limitations after first defining these two disorders and considering their similarities and differences. Animal models reviewed in this article test mainly behavioral dimensions or biological mechanisms related to autistic disorder or schizophrenia rather than providing specific categorical models of autism or schizophrenia. Furthermore, most of these studies focus on a behavioral dimension associated with an underlying biological mechanism, which does not correspond to the complexity of mental disorders. It could be useful to develop animal models relevant to schizophrenia or autism to test a behavioral profile associated with a biological profile. A multi-trait approach seems necessary to better understand multidimensional disorders such as schizophrenia and autism and their biological and clinical heterogeneity. Finally, animal models can help us to clarify complex mechanisms and to study relationships between biological and behavioral variables and their interactions with environmental factors. The main interest of animal models is to generate new pertinent hypotheses relevant to humans opening the path to innovative research. C1 Univ Rennes 1, Serv Hosp Univ Psychiat Enfant & Adolescent, F-35200 Rennes, France. Ctr Hosp Guillaume Regnier, Serv Hosp Univ Psychiat Adultes, F-35200 Rennes, France. Univ Paris 05, CNRS, Lab Psychol Percept, FRE 2929, F-75270 Paris, France. Univ Paris 06, AP HP, CNRS, Dept Child & Adolescent Psychiat,FRE 2987,GH Piti, Paris, France. NIMH, Lab Neurotoxicol, NIH, Bethesda, MD 20892 USA. Univ Mediterranee, Lab Plast & Physiopathol Motr, CNRS, UMR 6196, Marseille, France. RP Tordjman, S (reprint author), Univ Rennes 1, Serv Hosp Univ Psychiat Enfant & Adolescent, 154 Rue Chatillon, F-35200 Rennes, France. EM s.tordjman@ch-guillaumeregnier.fr NR 160 TC 52 Z9 54 U1 5 U2 24 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD JAN PY 2007 VL 37 IS 1 BP 61 EP 78 DI 10.1007/s10519-006-9120-5 PG 18 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 126ZK UT WOS:000243554100006 PM 17160702 ER PT J AU Carroll, JC Boyce-Rustay, JM Millstein, R Yang, R Wiedholz, LM Murphy, DL Holmes, A AF Carroll, Jenna C. Boyce-Rustay, Janel M. Millstein, Rachel Yang, Rebecca Wiedholz, Lisa M. Murphy, Dennis L. Holmes, Andrew TI Effects of mild early life stress on abnormal emotion-related behaviors in 5-HTT knockout mice SO BEHAVIOR GENETICS LA English DT Article DE 5-HT; serotonin transporter; anxiety; depression; gene; mouse ID SEROTONIN TRANSPORTER GENE; DORSAL RAPHE NUCLEUS; ANXIETY-LIKE BEHAVIOR; DEFICIENT MICE; MAJOR DEPRESSION; BRAIN; POLYMORPHISM; EVENTS; RAT; VULNERABILITY AB A low-expressing polymorphic variant of the serotonin transporter (5-HTT) gene has been associated with emotional disorders in humans and non-human primates following exposure to early life trauma. 5-HTT gene knockout (KO) mice exhibit increased anxiety- and depression-related behaviors, and provide a model to study interactions between 5-HTT gene variation and early life stress. The present study assessed the effects of postnatal footshock stress on the development of emotion-related behaviors in 5-HTT KO mice. Results showed that 5-HTT KO mice displayed a profile of suppressed exploratory behavior and increased anxiety-like behavior in the light/dark, elevated plus-maze and open field tests, as well as increased depression-related behavior in the forced swim test following repeated exposure to the test. Postnatal exposure to footshock stress did not affect emotion-related behaviors in non-mutant C57BL/6J mice or modify phenotypic abnormalities in 5-HTT KO. Data provide further evidence of emotional abnormalities following genetic disruption of the 5-HTT. C1 NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Holmes, A (reprint author), NIAAA, Sect Behav Sci & Genet, Lab Integrat Neurosci, NIH, Rockville, MD 20852 USA. EM holmesan@mail.nih.gov FU Intramural NIH HHS NR 44 TC 62 Z9 62 U1 3 U2 9 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0001-8244 J9 BEHAV GENET JI Behav. Genet. PD JAN PY 2007 VL 37 IS 1 BP 214 EP 222 DI 10.1007/s10519-006-9129-9 PG 9 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 126ZK UT WOS:000243554100013 PM 17177116 ER PT J AU Mozhui, K Hamre, KM Holmes, A Lu, L Williams, RW AF Mozhui, Khyobeni Hamre, Kristin M. Holmes, Andrew Lu, Lu Williams, Robert W. TI Genetic and structural analysis of the basolateral amygdala complex in BXD recombinant inbred mice SO BEHAVIOR GENETICS LA English DT Article DE linkage analysis; complex trait; bioinformatics; gene expression ID QUANTITATIVE-TRAIT LOCI; MEMORY CONSOLIDATION; CHONDROITIN SULFATE; NUCLEUS-ACCUMBENS; NATURAL VARIATION; COCAINE-SEEKING; NERVOUS-SYSTEM; MOUSE STRAINS; BRAIN; ETHANOL AB The amygdala integrates and coordinates emotional and autonomic responses. The genetics that underlie variation in amygdala structure may be coupled to variation in levels of aggression, fear, anxiety, and affiliated behaviors. We systematically quantified the volume and cell populations of the basolateral amygdala complex (BLAc) across 35 BXD recombinant inbred (RI) lines, the parental strains-C57BL/6J (B6) and DBA/2J (D2)-and F1 hybrids (n cases = 199, bilateral analysis). Neuron number and volume vary 1.7- to 2-fold among strains (e.g., neuron number ranged from 88,000 to 170,000). Glial and endothelial populations ranged more widely (5- to 8-fold), in part because of higher technical error. A quantitative trait locus (QTL) for the BLAc size is located on chromosome (Chr) 8 near the Large gene. This locus may also influence volume of other regions including hippocampus and cerebellum. Cell populations in the BLAc appear to be modulated more weakly by loci on Chrs 11 and 13. Candidate genes were selected on the basis of correlation with BLAc traits, chromosomal location, single nucleotide polymorphism (SNP) density, and expression patterns in the Allen Brain Atlas. Neurod2, a gene shown to be significant for the formation of the BLAc by knockout studies, is among the candidates genes. Other candidates include Large, and Thra. Responses to drugs of abuse and locomotor activity were the most notable behavioral correlates of the BLAc traits. C1 Univ Tennessee, Hlth Sci Ctr, Dept Anat & Neurobiol, Memphis, TN 38163 USA. NIAAA, Sect Behav Sci & Genet, Lab Integrat Sci, Rockville, MD 20852 USA. Nantong Univ, Key Lab Nerve Regenerat, Nantong, Jiangsu, Peoples R China. RP Williams, RW (reprint author), Univ Tennessee, Hlth Sci Ctr, Dept Anat & Neurobiol, 855 Monroe Ave, Memphis, TN 38163 USA. EM rwilliam@nb.utmem.edu OI Williams, Robert/0000-0001-8924-4447 FU NCI NIH HHS [U01CA105417]; NIAAA NIH HHS [U01AA13499, U24AA13513]; NIDA NIH HHS [P20-DA 21131]; NINR NIH HHS [U01NR 105417] NR 77 TC 22 Z9 22 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 JAN PY 2007 VL 37 IS 1 BP 223 EP 243 DI 10.1007/s10519-006-9122-3 PG 21 WC Behavioral Sciences; Genetics & Heredity; Psychology, Multidisciplinary SC Behavioral Sciences; Genetics & Heredity; Psychology GA 126ZK UT WOS:000243554100014 PM 17131200 ER PT J AU Blair, RJR AF Blair, R. J. R. TI Aggression, psychopathy and free will from a cognitive neuroscience perspective SO BEHAVIORAL SCIENCES & THE LAW LA English DT Article ID NEUROPSYCHOLOGICAL TEST FINDINGS; RESPONSE REVERSAL; PREFRONTAL CORTEX; IMPULSIVE AGGRESSION; ORBITOFRONTAL CORTEX; VIOLENT BEHAVIOR; AMYGDALA; INDIVIDUALS; PERSONALITY; MECHANISMS AB This article considers the notion of free will in the context of aggression and psychopathy research. The philosophical literature is very briefly considered to determine under what assumptions free will can be considered to exist. However, as the issue of free will is very difficult to address directly, the prime focus of this article is on issues raised in the philosophical debate, that may be empirically tractable and that are relevant to the understanding of psychopathy. Specifically, the following issues are considered: (1) The distinction between automatic and controlled processing; (2) Impairment related to automatic processing in individuals with psychopathy; and (3) Impairment related to controlled behavior in individuals with psychopathy. It is concluded that, while there is not a direct mapping of the automatic versus controlled processing dichotomy on to the reactive versus instrumental aggression dichotomy, some overlap can be considered. As such, it is possible to consider that certain episodes of reactive aggression might be considered to occur in the absence of free will. However, instrumental aggression, at least from a compatibilist perspective, must involve free will. Published in 2007 by John Wiley & Sons, Ltd. C1 NIMH, Mood & Anxiety Disorders Program, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Mood & Anxiety Disorders Program, Dept Hlth & Human Serv, NIH, 15K North Dr,Room 300A,MSC 2670, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov FU Intramural NIH HHS NR 64 TC 15 Z9 15 U1 8 U2 18 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0735-3936 J9 BEHAV SCI LAW JI Behav. Sci. Law PY 2007 VL 25 IS 2 BP 321 EP 331 DI 10.1002/bsl.750 PG 11 WC Psychology, Applied; Law SC Psychology; Government & Law GA 166LJ UT WOS:000246380000013 PM 17393398 ER PT J AU Teng, A Nair, M Wells, J Segre, JA Dai, X AF Teng, Andy Nair, Mahalakshmi Wells, Julie Segre, Julia A. Dai, Xing TI Strain-dependent perinatal lethality of Ovol1-deficient mice and identification of Ovol2 as a downstream target of Ovol1 in skin epidermis SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE Ovol1; Ovol2; perinatal lethality; skin barrier; cystic kidney; transcriptional repression ID DROSOPHILA-OVO; EGF RECEPTOR; GENE; DIFFERENTIATION; LACKING; SPERMATOGENESIS; TRANSCRIPTION; EXPRESSION; DEFECTS; HOMOLOG AB Ovoll encodes a zinc finger transcriptional repressor that is downstream of the LEF1/beta-catenin complex, nuclear effectors of canonical Wnt signaling. Previous gene knockout studies performed in a 129Sv x C57BL/6 mixed genetic background revealed that Ovoll-deficient mice survive to adulthood but display multiple tissue defects. In this study, we describe a C57BL/6 strain-specific reduction in perinatal survival of Ovoll mutant mice. The perinatal lethality is accompanied by kidney epithelial cysts of embryonic onset and delayed skin barrier acquisition. Genetic analysis suggests a partial functional compensation by Ovol2 for the loss of Ovol1. The expression of OvoI2 was up-regulated in Ovol1-deficient epidermis, and Ovoll represses the activity of OvoI2 promoter in a DNA binding-dependent manner. Collectively, these studies uncover novel functions of Ovoll in mouse development and identify OvoI2 as a downstream target of Ovoll. (c) 2006 Elsevier B.V. All rights reserved. C1 Univ Calif Irvine, Coll Med, Dept Biol Chem, Irvine, CA 92697 USA. Univ Calif Irvine, Ctr Dev Biol, Irvine, CA 92697 USA. NHGRI, NIH, Bethesda, MD 20892 USA. RP Dai, X (reprint author), Univ Calif Irvine, Coll Med, Dept Biol Chem, D250 Med Sci 1, Irvine, CA 92697 USA. EM xdai@uci.edu FU NIAMS NIH HHS [K02 AR051482, K02-AR51482, R01 AR047320, R01-AR47320] NR 27 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD JAN PY 2007 VL 1772 IS 1 BP 89 EP 95 DI 10.1016/j.bbadis.2006.08.012 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 127RT UT WOS:000243604700012 PM 17049212 ER PT J AU Bennasser, Y Yeung, ML Jeang, KT AF Bennasser, Yanzina Yeung, Man Lung Jeang, Kuan-Teh TI RNAi therapy for HIV infection - Principles and practicalities SO BIODRUGS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; SMALL INTERFERING RNAS; ANTIVIRAL IMMUNITY; MAMMALIAN-CELLS; PROTECTS MICE; HAIRPIN RNA; STRAND RNA; TAR RNA; SIRNA; INHIBITION AB Inside eukaryotic cells, small RNA duplexes, called small interfering RNAs (siRNAs), activate a conserved RNA interference (RNAi) pathway which leads to specific degradation of complementary target mRNAs through base-pairing recognition. As with other viruses, studies have shown that replication of the HIV-1 in cultured cells can be targeted and inhibited by synthetic siRNAs. The relative ease of siRNA design and the versatility of RNAi to target a broad spectrum of mRNAs have led to the promise that drug discovery in the RNAi pathway could be effective against pathogens. This review discusses the current experimental principles that guide the application of RNAi against HIV and describes challenges and limitations that need to be surmounted in order for siRNAs to become practical antiviral drugs. The practical use of RNAi therapy for HIV infection will depend on overcoming several challenges, including the ability to establish long-term expression of siRNA without off-target effects and the capacity to counteract mutant escape viruses. C1 NIAID, Mol Virol Sect, Lab Mol Microbiol, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), 9000 Rockville Pike,Bldg 4,Room 306, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS NR 74 TC 20 Z9 20 U1 1 U2 4 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PY 2007 VL 21 IS 1 BP 17 EP 22 DI 10.2165/00063030-200721010-00003 PG 6 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 137IL UT WOS:000244286200003 PM 17263586 ER PT J AU Deng, GM AF Deng, Guo-Min TI Tumor necrosis factor receptor pre-ligand assembly domain is an important therapeutic target in inflammatory arthritis SO BIODRUGS LA English DT Article ID COLLAGEN-INDUCED ARTHRITIS; RHEUMATOID-ARTHRITIS; STAPHYLOCOCCUS-AUREUS; FACTOR INHIBITORS; MICE; TNF; ALPHA; DESTRUCTION; OSTEOCLASTS; INFECTION AB Tumor necrosis factor (TNF)-alpha is an important proinflammatory cytokine and plays a crucial role in pathogenesis of inflammatory arthritis, such as rheumatoid and septic arthritis. TNF(x exerts its effect by binding to the extracellular domain of TNF receptor (TNFR) I and 2. The amino-terminal portion of the TNFR extracellular domain, known as cysteine rich domain I (CRD1), or the pre-ligand binding assembly domain (PLAD), plays an important role in the TNFR signaling pathway. TNFR1 PLAD and TNFR2 PLAD proteins block the actions of TNF alpha by interfering with assembly of the receptor complex required for TNF alpha binding. The TNFR1 PLAD protein have been shown to significantly inhibit inflammatory arthritis, such as arthritis induced by TNF alpha, bacterial DNA, lipopolysaccharide, and collagen. The TNFR1 PLAD protein inhibit nuclear factor (NF)-kappa B activation and osteoclastogenesis triggered by TNF alpha was able to inhibit expression of receptor activator of NF-kappa B (RANK), RANK ligand, matrix metalloproteinase and inducible nitric oxide synthase in collagen-induced arthritis. The TNFR1 PLAD protein could therefore be useful in treatment of inflammatory arthritis. C1 Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Div Rheumatol,Sch Med, Boston, MA 02115 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Deng, GM (reprint author), Harvard Univ, Inst Med, Beth Israel Deaconess Med Ctr, Div Rheumatol,Sch Med, 4 Blackfan Circle,HIM-238, Boston, MA 02115 USA. EM Gdeng@bidmc.harvard.edu NR 30 TC 3 Z9 4 U1 0 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PY 2007 VL 21 IS 1 BP 23 EP 29 DI 10.2165/00063030-200721010-00004 PG 7 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 137IL UT WOS:000244286200004 PM 17263587 ER PT J AU Elkashef, A Biswas, J Acri, JB Vocci, F AF Elkashef, Ahmed Biswas, Jamie Acri, Jane B. Vocci, Frank TI Biotechnology and the treatment of addictive disorders - New opportunities SO BIODRUGS LA English DT Article ID STRESS-INDUCED RELAPSE; CORTICOTROPIN-RELEASING-FACTOR; DOPAMINE D-3 RECEPTORS; ANTI-(+)-METHAMPHETAMINE MONOCLONAL-ANTIBODY; NICOTINE-SPECIFIC ANTIBODIES; ENVIRONMENTAL RISK-FACTORS; SUBSTANCE USE DISORDERS; LONG-TERM REDUCTIONS; DRUG-ADDICTION; FAMILIAL TRANSMISSION AB Addiction is a chronic relapsing illness with onset typically occurring in the early teenage years, followed by cycles of drug use and abstinence. The disease is mitigated by complex interactions between genes and environment. Viewed as such, the treatment of addiction could span the whole lifetime of the patient and, ideally, should be tailored to the illness cycle. The search for effective treatments has intensified recently due to our better understanding of the underlying neurobiologic mechanisms contributing to drug use and relapse. The three main types of treatment are behavioral, pharmacologic and, more recently, immunologic therapies. Vaccines and monoclonal antibodies are being developed mainly for stimulant use disorders and, nicotine addiction. In addition, new molecular targets identified by preclinical research have shown promise and are awaiting proof-of-concept studies in humans. The main focus of this review is on the development of immunotherapy for stimulants and nicotine addiction as a model. highlighting the current status of the science and potential emerging discoveries and development. C1 Natl Inst Drug Abuse, Clin Med Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. RP Elkashef, A (reprint author), Natl Inst Drug Abuse, Clin Med Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd,Room 4151, Bethesda, MD 20892 USA. EM ae8a@nih.gov NR 71 TC 9 Z9 10 U1 1 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1173-8804 J9 BIODRUGS JI Biodrugs PY 2007 VL 21 IS 4 BP 259 EP 267 DI 10.2165/00063030-200721040-00006 PG 9 WC Oncology; Immunology; Pharmacology & Pharmacy SC Oncology; Immunology; Pharmacology & Pharmacy GA 196WR UT WOS:000248514200006 PM 17628123 ER PT J AU Ottolenghi, C Uda, M Crisponi, L Omari, S Cao, A Forabosco, A Schlessinger, D AF Ottolenghi, Chris Uda, Manuela Crisponi, Laura Omari, Shakib Cao, Antonio Forabosco, Antonino Schlessinger, David TI Determination and stability of sex SO BIOESSAYS LA English DT Review ID MAMMALIAN Y-CHROMOSOME; ANTI-MULLERIAN HORMONE; GERM-CELLS; TRANSGENIC MICE; MOUSE GONADS; OVARIAN DEVELOPMENT; ESTROGEN-RECEPTORS; TESTIS DEVELOPMENT; INVERSUS SYNDROME; SOX9 EXPRESSION AB How is the embryonic bipotential gonad regulated to produce either an ovary or a testis? In males, transient early activation of the Y chromosome Sry gene makes both germ cells and soma male. However, in females, available evidence suggests that the process of ovary sex determination may take place independently in the germline and somatic lineages. In addition, in contrast to testis, in ovary somatic cells, female-to-male gonadal sex reversal can occur at times throughout ovary development and maturation. We suggest that a single gene pathway, likely hinging on the FoxI2 transcription factor, both initiates and maintains sex differentiation in somatic cells of the mammalian ovary. C1 NIA, Genet Lab, Baltimore, MD 21224 USA. CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy. Univ Modena & Reggio Emilia, Dipartimento Materno Infantile, Modena, Italy. RP Schlessinger, D (reprint author), NIA, Genet Lab, Baltimore, MD 21224 USA. EM schlessingerd@grc.nia.nih.gov FU Intramural NIH HHS; Telethon [GP0049Y01] NR 74 TC 38 Z9 40 U1 0 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0265-9247 J9 BIOESSAYS JI Bioessays PD JAN PY 2007 VL 29 IS 1 BP 15 EP 25 DI 10.1002/bies.20515 PG 11 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 123ZP UT WOS:000243336700004 PM 17187356 ER PT J AU Beck, J Ferrucci, L Sun, K Walston, J Fried, LP Varadhan, R Guralnik, JM Semba, RD AF Beck, Justine Ferrucci, Luigi Sun, Kai Walston, Jeremy Fried, Linda P. Varadhan, Ravi Guralnik, Jack M. Semba, Richard D. TI Low serum selenium concentrations are associated with poor grip strength among older women living in the community SO BIOFACTORS LA English DT Article DE aging; muscle; sarcopenia; selenium; strength; women ID HUMAN SKELETAL-MUSCLE; GROWTH-FACTOR-I; OXIDATIVE DAMAGE; SELENOPROTEIN-W; TOTAL MORTALITY; RAT MUSCLE; AGE; DISABILITY; SARCOPENIA; PROTEINS AB Aging is associated with a loss of muscle strength, and, in turn, loss of muscle strength has been associated with increased risk of frailty, disability and mortality. The factors that contribute to loss of muscle strength with aging have not been well characterized. Selenium is important in normal muscle function because of its role in selenoenzymes that protect muscle against oxidative damage. We hypothesized that low serum selenium concentrations were associated with poor grip strength. We examined the association between serum selenium and hand grip strength among 676 moderately to severely disabled community-dwelling women in the Women's Health and Aging Study I in Baltimore, Maryland. After adjusting for age, race, body mass index, Mini-Mental Status Examination score, current smoking, hypertension, congestive heart failure and depression, serum selenium was associated with grip strength (P = 0.04). This study supports the idea that selenium is important to muscle strength in older women. C1 Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. NIA, Epidemiol Demog & Biometry Branch, Baltimore, MD 21224 USA. RP Beck, J (reprint author), 600 N Wolfe St,Wilmer Woods Bldg Room 268, Baltimore, MD 21287 USA. EM jbeck19@jhmi.edu FU Intramural NIH HHS [Z99 AG999999]; NIA NIH HHS [R01 AG027012, R37 AG019905] NR 32 TC 20 Z9 20 U1 0 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0951-6433 J9 BIOFACTORS JI Biofactors PY 2007 VL 29 IS 1 BP 37 EP 44 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 194IG UT WOS:000248337500004 PM 17611292 ER PT J AU Wierzbicki, J AF Wierzbicki, Julie TI 4th parliamentary meeting on the subject of cancer SO BIOFUTUR LA French DT Editorial Material C1 NCI, Bethesda, MD 20892 USA. RP Wierzbicki, J (reprint author), NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0294-3506 J9 BIOFUTUR JI Biofutur PD JAN PY 2007 IS 273 BP 15 EP 15 PG 1 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 129ZB UT WOS:000243767500002 ER PT S AU Zaslavsky, L Bao, YM Tatusova, TA AF Zaslavsky, Leonid Bao, Yiming Tatusova, Tatiana A. BE Mandoiu, I Zelikovsky, A TI An adaptive resolution tree visualization of large influenza virus sequence datasets SO BIOINFORMATICS RESEARCH AND APPLICATIONS, PROCEEDINGS SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 3rd International Symposium on Bioinformatics Research and Applications CY MAY 07-10, 2007 CL Georgia State Univ, Atlanta, GA HO Georgia State Univ DE visualization; adaptive; sequence; tree; phylogenetic; virus; influenza; JavaScript; AJAX AB Rapid growth of the amount of influenza genome sequence data requires enhancing exploratory analysis tools. Results of the preliminary analysis should be represented in an easy-to-comprehend form and allow convenient manipulation of the data. We developed an adaptive approach to visualization of large sequence datasets on the web. A dataset is presented in an aggregated tree form with special representation of sub-scale details. The representation is calculated from the full phylogenetic tree and the amount of available screen space. Metadata, such as distribution over seasons or geographic locations, are aggregated/refined consistently with the tree. The user can interactively request further refinement or aggregation for different parts of the tree. The technique is implemented in Javascript on client site. It is a part of the new AJAX-based implementation of the NCBI Influenza Virus Resource. C1 [Zaslavsky, Leonid; Bao, Yiming; Tatusova, Tatiana A.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA. RP Zaslavsky, L (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, 8600 Rockville Pike, Bethesda, MD 20894 USA. EM zaslavsk@ncbi.nlm.nih.gov; bao@ncbi.nlm.nih.gov; tatiana@ncbi.nlm.nih.gov FU NIH; National Library of Medicine; NIAID FX This research was supported by the Intramural Research Program of the NIH, National Library of Medicine. The NCBI Influenza Virus Resource is developed and being continuously improved as a part of a collaborative effort, the Influenza Genome Sequencing Project led by NIAID ([19], [1] [2]). The authors are thankful to David J.Lipman, Yury Voronov, Boris Fedorov, Stacy Ciufo and Sergey Ponomarev for productive discussions. NR 19 TC 5 Z9 5 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-72030-0 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2007 VL 4463 BP 192 EP + PG 3 WC Biochemistry & Molecular Biology; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Computer Science GA BGE97 UT WOS:000246369100018 ER PT S AU Le, SY Chen, JH AF Le, Shu-Yun Chen, Jih-H. BE Hochreiter, S Wagner, R TI Statistical inference on distinct RNA stem-loops in genomic sequences SO BIOINFORMATICS RESEARCH AND DEVELOPMENT, PROCEEDINGS SE Lecture Notes in Computer Science LA English DT Proceedings Paper CT 1st International Conference on Bioinformatics Research and Development CY MAR 12-14, 2007 CL Berlin, GERMANY DE well-ordered RNA structure; dynamic programming; statistical inference; microRNA stem-loops ID SECONDARY STRUCTURE; NUCLEOTIDE-SEQUENCES; IDENTIFICATION; MICRORNAS; GENES; DEFINITION; PREDICTION; PATTERNS; PROGRAM AB Functional RNA elements in post-transcriptional regulation of gene expression are often correlated with distinct RNA stem-loop structures that are both thermodynamically stable and highly well-ordered. Recent Discoveries of microRNA (miRNA) and small regulatory RNAs indicate that there are a large class of small non-coding RNAs having the potential to form a distinct, well-ordered and/or stable stem-loop in numbers of genomes. The distinct RNA structure can be well evaluated by a quantitative measure, the energy difference (E-diff) between the optimal structure folded from the segment and its corresponding optimal restrained structure where all base pairings formed in the original optimal structure are forbidden. In this study, we present an efficient algorithm to compute E-diff of local segment by scanning a window along a genomic sequence. The complexity of computational time is O(L x n(2)), where L is the length of the genomic sequence and n is the size of the sliding window. Our results indicate that the known stem-loops folded by miRNA precursors have high normalized E-diff scores with highly statistical significance. The distinct well-ordered structures related to the known miRNA can be predicted in a genomic sequence by a robust statistical inference. Our computational method StemED can be used as a general approach for the discovery of distinct stem-loops in genomic sequences. C1 [Le, Shu-Yun] NCI, Ctr Canc Res, CCR Nanobiol Program, Bldg 469,Rm151, Frederick, MD 21702 USA. [Chen, Jih-H.] NCI, SAIC, FCRDC, Adv Biomed Comp Ctr, Frederick, MD 21702 USA. RP Le, SY (reprint author), NCI, Ctr Canc Res, CCR Nanobiol Program, Bldg 469,Rm151, Frederick, MD 21702 USA. FU Intramural Research Program of the NIH; National Cancer Institute; Center for Cancer Research FX This research was supported by the Intramural Research Program of the NIH,National Cancer Institute, Center for Cancer Research. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.a NR 23 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-71232-9 J9 LECT NOTES COMPUT SC PY 2007 VL 4414 BP 314 EP + PG 4 WC Biochemical Research Methods; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Computer Science GA BGE03 UT WOS:000246237400025 ER PT J AU Li, TK Volkow, ND Baler, RD Egli, M AF Li, Ting-Kai Volkow, Nora D. Baler, Ruben D. Egli, Mark TI The biological bases of nicotine and alcohol co-addiction SO BIOLOGICAL PSYCHIATRY LA English DT Editorial Material ID TRANSPORTER PROMOTER POLYMORPHISMS; SMOKING-CESSATION; ETHANOL WITHDRAWAL; RECEPTOR GENE; DEPENDENCE; ASSOCIATION; RAT; VULNERABILITY; 15-YEAR-OLDS; PRETREATMENT C1 NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Li, TK (reprint author), NIAAA, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 39 TC 26 Z9 27 U1 1 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 2007 VL 61 IS 1 BP 1 EP 3 DI 10.1016/j.biopsych.2006.11.004 PG 3 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 120AQ UT WOS:000243056200001 PM 17161671 ER PT J AU Ciccocioppo, R Economidou, D Rimondini, R Sommer, W Massi, M Heilig, M AF Ciccocioppo, Roberto Economidou, Daina Rimondini, Roberto Sommer, Wolfgang Massi, Maurizio Heilig, Markus TI Buprenorphine reduces alcohol drinking through activation of the nociceptin/orphanin FQ-NOP receptor system SO BIOLOGICAL PSYCHIATRY LA English DT Article DE buprenorphine; nociceptin/orphanin FQ; alcohol abuse; addiction ID TRIAL COMPARING BUPRENORPHINE; PREFERRING RATS; POSTOPERATIVE PAIN; DOUBLE-BLIND; PHARMACOLOGICAL CHARACTERIZATION; ORPHANIN FQ/NOCICEPTIN; EPIDURAL BUPRENORPHINE; METHADONE-MAINTENANCE; ANTAGONIST PROPERTIES; NUCLEUS-ACCUMBENS AB Background: Activation of the ATOP receptor by its endogenous ligand nociceptin/orphanin FQ reduces ethanol intake in genetically selected alcohol preferring Marchigian Sardinian alcohol preferring (msP) rats. Here we evaluated whether buprenorphine, a partial agonist at mu-opioid and NOP receptors, would reduce ethanol consumption in msP rats via activation of NOP receptors. Methods: Marchigian Sardinian alcohol preferring rats trained to drink 10% alcohol 2 hours/day were injected with buprenorphine (.03, .3, 3.0, or 6.0 mg/kg intraperitoneally [IP]) 90 min before access to ethanol. Results: Similar to prototypical mu-agonists, the two lowest doses of buprenorphine significantly increased ethanol consumption (p <.01); in contrast, the two highest doses reduced it (p <.05), Pretreatment with naltrexone (.25 mg/kg IP) prevented the increase of ethanol intake induced by .03 mg/kg of buprenorohine (p <.001) but did not affect inhibition of ethanol drinking induced by 3.0 mg/kg of buprenoiphine. Conversely, pretreatment with the selective NOP receptor antagonist UFP-101 (10.0 or 20.0 mu g/rat) abolished the suppression of ethanol drinking by 3.0 mg/kg of buprenorphine effects on ethanol drinking; low doses increase alcohol intake via stimulation I sic. Conclusions: Buprenorphine has dualistic effects as opioid receptors, whereas higher doses reduce it via activation of NOR receptors. We suggest that NOP agonistic properties of buprenorphine might be useful in the treatment of alcoholism. C1 Univ Camerino, Dept Expt Med & Publ Hlth, I-62032 Camerino, MC, Italy. Karolinska Inst, NEUROTEC, Div Psychiat, Stockholm, Sweden. NIAAA, Lab Clin & Translat Studies, NIH, Bethesda, MD USA. RP Ciccocioppo, R (reprint author), Univ Camerino, Dept Expt Med & Publ Hlth, Via Scalzino 3, I-62032 Camerino, MC, Italy. EM roberto.ciccocioppo@unicam.it RI Rimondini, Roberto/B-2500-2010; OI Rimondini, Roberto/0000-0003-4099-513X; Heilig, Markus/0000-0003-2706-2482; Sommer, Wolfgang/0000-0002-5903-6521 FU NIAAA NIH HHS [R01 AA014351, R01 AA014351-01A1, AA01435] NR 93 TC 42 Z9 42 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JAN 1 PY 2007 VL 61 IS 1 BP 4 EP 12 DI 10.1016/j.biopsych.2006.01.006 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 120AQ UT WOS:000243056200002 PM 16533497 ER PT J AU Funk, CK Zorrilla, EP Lee, MJ Rice, KC Koob, GF AF Funk, Cindy K. Zorrilla, Eric P. Lee, Mei-Jing Rice, Kenner C. Koob, George F. TI Corticotropin-releasing factor 1 antagonists selectively reduce ethanol self-administration in ethanol-dependent rats SO BIOLOGICAL PSYCHIATRY LA English DT Article DE alcohol; dependence; withdrawal; corticotropin-releasing factor; self-administration; rat ID CORTICOTROPIN-RELEASING-FACTOR; ANXIETY-LIKE BEHAVIOR; CRF1 RECEPTOR ANTAGONIST; ADENYLATE-CYCLASE ACTIVITY; IMPAIRED STRESS-RESPONSE; PITUITARY-ADRENAL AXIS; FAWN-HOODED RATS; CENTRAL NUCLEUS; ACOUSTIC STARTLE; HORMONE RECEPTOR-2 AB Background: Alcohol dependence is characterized by excessive alcohol consumption, loss of control over intake, and the presence of a withdrawal syndrome, which includes both motivational and physical symptoms. Similar to human alcoholics, ethanol-dependent animals display enhanced anxiety-like behaviors and enhanced ethanol self-administration during withdrawal, (effects hypothesized to result from a dysregulation of corticotropin-releasing factor (CRF) stress systems. Here, we used an animal model of ethanol dependence to test the effects of CRF1 receptor antagonists on excessive ethanol self-administration in dependent rats. Methods. Wistar rats, trained to orally self-administer ethanol, were exposed intermittently to ethanol vapors to induce ethanol dependence. Nondependent animals were. exposed to control air. Following a 2-hour period of withdrawal, dependent and nondependent animals were systemically administered antalarmin, MJL-1-109-2, or R121919 (CRF, antagonists) and ethanol self-administration was measured. Results: The nonpeptide, small molecule CRF1 antagonists selectively reduced excessive self-administration of ethanol in dependent animals during acute withdrawal. The antagonists bad no effect on ethanol self-administration in nondependent rats. Conclusions: These data demonstrate that CRF1 receptors play an important role in mediating excessive ethanol self-administration in dependent rats, with no effect in nondependent rats. CRF1 antagonists may be exciting new pharmacotherapeutic targets for the treatment of alcoholism in humans. C1 Scripps Res Inst, Mol & Integrat Neurosci, La Jolla, CA 92037 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Funk, CK (reprint author), Scripps Res Inst, Mol & Integrat Neurosci, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM creiter@scripps.edu RI koob, george/P-8791-2016 FU Intramural NIH HHS; NIAAA NIH HHS [AA015239, AA12602, F32 AA015239, R01 AA012602, R01 AA012602-08] NR 96 TC 164 Z9 166 U1 0 U2 2 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 JAN 1 PY 2007 VL 61 IS 1 BP 78 EP 86 DI 10.1016/j.biopsych.2006.03.063 PG 9 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 120AQ UT WOS:000243056200012 PM 16876134 ER PT J AU Oliansky, DM Rizzo, JD D Aplan, P Arceci, RJ Leone, L Ravindranath, Y Sanders, JE Smith, FO Wihnot, F McCarthy, PL Hahn, T AF Oliansky, Denise M. Rizzo, J. Douglas D Aplan, Peter Arceci, Robert J. Leone, Louis Ravindranath, Yaddanapudi Sanders, Jean E. Smith, Franklin O., III Wihnot, Fiona McCarthy, Philip L., Jr. Hahn, Theresa TI The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute myeloid leukemia in children: An evidence-based review SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Review DE acute myeloid leukemia; acute myelogenous leukemia; hematopoietic stem cell transplantation; therapy; pediatric ID BONE-MARROW-TRANSPLANTATION; ACUTE MYELOBLASTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; 1ST COMPLETE REMISSION; ACUTE PROMYELOCYTIC LEUKEMIA; PEDIATRIC-ONCOLOGY-GROUP; TOTAL-BODY IRRADIATION; ACUTE LYMPHOBLASTIC-LEUKEMIA; CORD BLOOD TRANSPLANTATION; HEMATOLOGY-AND-IMMUNOLOGY AB Clinical research examining the role of hematopoietic stem cell transplantation (SCT) in tire therapy of acute myeloid leukemia (AML) in children is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published literature and for grading the quality and strength of the evidence and the strength of the treatment recommendations. Treatment recommendations based on the evidence are presented in the table entitled "Summary of Treatment Recommendations Made by the Expert Panel for Pediatric Acute Myeloid Leukemia" and were reached unanimously by a panel of experts in AML. The identified priority areas of needed future research in pediatric AML include: What is the role of risk group stratification, including the role of cytogenetics, in selection of patients for allogeneic SCT, especially those in first CR? What is the appropriate timing and use of alter-native donor SCT, given that matched unrelated donor SCT appears to yield outcomes equivalent to matched related donor SCT? What is the role of reduced intensity SCT (including the use of fludarabine-based preparative regimens) and/or other immunomodulatory approaches to maximize the graft-versus-leukemic effect? and What is the role of biologically targeted agents (ie, tyrosine kinase inhibitors, farnesyl transferase inhibitors, Flt-3 inhibitors, etc) in the treatment of AML, including induction, consolidation, conditioning regimens, and after SCT? (C) 2007 American Society for blood and Marrow Transplantation. C1 Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. NCI, NIH, CCR, Genet Branch, Bethesda, MD 20892 USA. Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Childrens Oncol Grp, Arcadia, CA USA. Childrens Hosp Michigan, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Detroit, MI USA. Univ Washington, Fred Hutchinson Canc Res Ctr, Seattle, WA 98195 USA. Cincinnati Childrens Hosp & Med Ctr, Cincinnati, OH USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Blue Shield Calif, San Francisco, CA USA. RP Hahn, T (reprint author), Roswell Pk Canc Inst, Elm & Carlton St, Buffalo, NY 14263 USA. EM theresa.hahn@roswellpark.org NR 69 TC 49 Z9 50 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2007 VL 13 IS 1 BP 1 EP 25 DI 10.1016/j.bbmt.2006.10.024 PG 25 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 132RG UT WOS:000243959300001 PM 17222748 ER PT J AU Shlomchik, WD Lee, SJ Couriel, D Pavletic, SZ AF Shlomchik, Warren D. Lee, Stephanie J. Couriel, Daniel Pavletic, Steven Z. TI Transplantation's greatest challenges: Advances in chronic graft-versus-host disease SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE chronic graft-versus-host disease; immunology; response criteria; therapy ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; QUALITY-OF-LIFE; STEM-CELL TRANSPLANTATION; CLINICAL-TRIALS; RANDOMIZED-TRIAL; DONOR TRANSPLANTATION; AUTOIMMUNE-DISEASE; CHRONIC GVHD; BONE-MARROW AB Clinical research into chronic graft-versus-host disease (GVHD) lags behind that in other areas in the field. Interest in chronic GVHD has increased significantly in recent years for various reasons, including advances in biotechnology, a perceived increase in the incidence of chronic GVHD, and decreased regimen-related mortality, resulting in a new emphasis on quality of life and absence of disability as endpoints of major significance in transplantation survivors. In this overview, we address 3 key areas related to chronic GVHD that hold the highest promise for major advances in the near future: pathobiology, response criteria, and therapy. (c) 2007 American Society for Blood and Marrow Transplantation. C1 NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. Yale Univ, Sch Med, Dept Med Oncol, New Haven, CT 06520 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. Univ Texas, MD Anderson Canc Ctr, Dept Blood & Marrow Transplantat, Houston, TX 77030 USA. RP Pavletic, SZ (reprint author), NCI, Graft Versus Host & Autoimmun Unit, Expt Transplantat & Immunol Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM pavletis@mail.nih.gov FU Intramural NIH HHS NR 43 TC 41 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2007 VL 13 IS 1 SU 1 BP 2 EP 10 DI 10.1016/j.bbmt.2006.10.020 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133WE UT WOS:000244043800002 PM 17222762 ER PT J AU Gress, RE Komanduri, KV Einsele, H Cooper, LJN AF Gress, Ronald E. Komanduri, Krishna V. Einsele, Hermann Cooper, Laurence J. N. TI Lymphoid reconstruction and vaccines SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE hematopoietic stem cell transplantation; immune reconstitution; adoptive immunotherapy; vaccination; lymphodepletion ID STEM-CELL TRANSPLANTATION; ALLOGENEIC BONE-MARROW; VERSUS-HOST-DISEASE; CD8(+) T-CELLS; ADOPTIVE TRANSFER; DONOR LYMPHOCYTES; CANCER REGRESSION; THYMIC FUNCTION; PHASE-I; CYTOMEGALOVIRUS AB Allogeneic HSCT is the most reliable, robust, and effective cell-based biotherapy currently available to pediatric and adult patients with hematologic malignancies. The central role of donor-derived lymphocytes in mediating an effective antitumor effect, preventing and controlling opportunistic infections, and causing GVHD is well documented in animal experiments and human trials. The profound lymphopenia after conditioning regimens coupled with molecular tools to distinguish host versus donor cells provides investigators a window into immune recovery after allogeneic HSCT. Serial analyses of T cell subsets linking immunophenotype with function have revealed the kinetics of donor-derived T cell recovery after allografting and provided insights into ways the immune system can be manipulated to augment the graft-versus-tumor (GVT) effect without inducing GVHD. As this review demonstrates, investigators are not limited to being passive observers of this immune reconstitution; rather, we have an opportunity to shape the allografted T cells repertoire to selectively augment immune function. (c) 2007 American Society for Blood and Marrow Transplantation. C1 NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Div Pediat, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Houston, TX 77030 USA. Univ Wurzburg, Dept Internal Med 2, D-97070 Wurzburg, Germany. RP Cooper, LJN (reprint author), Univ Texas, MD Anderson Canc Ctr, Childrens Canc Hosp, Div Pediat,Unit 907, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM ljncooper@mdanderson.org RI Komanduri, Krishna/G-6012-2011; OI Komanduri, Krishna/0000-0003-3715-5236; Cooper, Laurence/0000-0003-1460-3905 FU Intramural NIH HHS [Z99 CA999999] NR 49 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2007 VL 13 IS 1 SU 1 BP 17 EP 22 DI 10.1016/j.bbmt.2006.10.012 PG 6 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133WE UT WOS:000244043800005 PM 17222765 ER PT J AU T Ueno, N Childs, RW AF T Ueno, Naoto Childs, Richard W. TI What's past is prologue: Lessons learned and the need for further development of allogeneic hematopoietic stem cell transplantation for renal cell carcinoma SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article ID IMMUNOTHERAPY; CANCER C1 Univ Texas, MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Unit 448, Houston, TX 77030 USA. NHLBI, Bethesda, MD 20892 USA. RP Childs, RW (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Stem Cell Transplantat & Cellular Therapy, Unit 448, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM childsr@nih.gov NR 8 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2007 VL 13 IS 1 BP 31 EP 33 DI 10.1016/j.bbmt.2006.09.011I PG 3 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 132RG UT WOS:000243959300003 ER PT J AU Sandmaier, BM Mackinnon, S Childs, RW AF Sandmaier, Brenda M. Mackinnon, Stephen Childs, Richard W. TI Reduced intensity conditioning for allogeneic hematopoietic cell transplantation: Current perspectives SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE reduced intensity; nonmyeloablative; allogeneic; hematopoietic cell transplantation ID VERSUS-HOST-DISEASE; METASTATIC BREAST-CANCER; TOTAL-BODY IRRADIATION; ADOPTIVE IMMUNOTHERAPY; SOLID TUMORS; HEMATOLOGIC MALIGNANCIES; MARROW-TRANSPLANTATION; PREPARATIVE REGIMEN; HODGKINS-LYMPHOMA; MYELOID-LEUKEMIA AB Allogeneic HCT after myeloablative conditioning is an effective therapy for patients with hematologic malignancies. In an attempt to extend this therapy to older patients or those with comorbidities, reduced intensity or truly nonmyeloablative regimens have been developed over the past decade. The principle underlying reduced intensity regimens is to provide some tumor kill with lessened regimen-related morbidity and mortality and then rely on graft-versus-tumor (GVT) effects to eradicate remaining malignant cells, whereas nonmyeloablative regimens rely primarily on GVT effects. In this article, 3 representative approaches are described, demonstrating the clinical application for hematopoietic and nonhematopoietic malignancies. Current challenges include controlling GVHD while allowing GVT to occur. In the future, clinical trials using reduced intensity and nonmyeloablative conditioning will be compared with myeloablative conditioning in selected malignancies to extend the application to standard-risk patients. (c) 2007 American Society for Blood and Marrow Transplantation. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Royal Free & UCL Sch Med, London, England. NHLBI, NIH, Bethesda, MD 20892 USA. RP Sandmaier, BM (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,D1-100,POB 19024, Seattle, WA 98109 USA. EM bsandmai@fhcrc.org RI Mackinnon, Stephen/C-5559-2008 FU Intramural NIH HHS; NCI NIH HHS [CA78902, CA18029, P01 CA018029, P01 CA078902]; NHLBI NIH HHS [HL36444, P01 HL036444] NR 58 TC 47 Z9 48 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2007 VL 13 IS 1 SU 1 BP 87 EP 97 DI 10.1016/j.bbmt.2006.10.015 PG 11 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133WE UT WOS:000244043800018 PM 17222778 ER PT J AU Barrett, J AF Barrett, John TI New technologies to visualize T cell function: A picture tells a thousand words SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article C1 NIH, Hematol Branch, Bethesda, MD 20892 USA. RP Barrett, J (reprint author), NIH, Hematol Branch, 9000 Rockville Pike,Bldg 10 CRC Room 3-5330, Bethesda, MD 20892 USA. EM barrettjj@mail.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JAN PY 2007 VL 13 IS 1 SU 1 BP 110 EP 110 DI 10.1016/j.bbmt.2006.11.007 PG 1 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 133WE UT WOS:000244043800022 ER PT J AU Archer, T AF Archer, Trevor TI None but ourselves can free our minds: Science in a majority world. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 21-25, 2007 CL San Antonio, TX SP Soc Study Reprod C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2007 SI SI BP 63 EP 63 PG 1 WC Reproductive Biology SC Reproductive Biology GA 189QB UT WOS:000248002500012 ER PT J AU Ko, M AF Ko, Minoru TI Systematic analysis of genes involved in the oocyte-to-embryo transition. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 21-25, 2007 CL San Antonio, TX SP Soc Study Reprod C1 NIA, NIH, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2007 SI SI BP 67 EP 67 PG 1 WC Reproductive Biology SC Reproductive Biology GA 189QB UT WOS:000248002500032 ER PT J AU Goldberg, E Odet, F Duan, C Willis, W Goulding, E Kung, A Eddy, M AF Goldberg, Erwin Odet, Fanny Duan, Chongwen Willis, William Goulding, Eugenia Kung, Aisha Eddy, Mitch TI Disruption of the sperm-specific LDHC gene is detreviental to sperm function and male fertility. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 21-25, 2007 CL San Antonio, TX SP Soc Study Reprod C1 Northwestern Univ, Evanston, IL USA. NIEHS, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2007 SI SI BP 72 EP 72 PG 1 WC Reproductive Biology SC Reproductive Biology GA 189QB UT WOS:000248002500051 ER PT J AU Falco, G Sharov, A Piao, Y Poosala, S Becker, K Zonderman, A Longo, D Schlessinger, D Ko, M AF Falco, Geppino Sharov, Alexei Piao, Yulan Poosala, Suresh Becker, Kevin Zonderman, Alan Longo, Dan Schlessinger, David Ko, Minoru TI Effects of aging and caloric restriction on the global gene expression profiles of testis and ovary. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 21-25, 2007 CL San Antonio, TX SP Soc Study Reprod C1 NIH, NIA, Baltimore, MD USA. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2007 SI SI BP 77 EP 77 PG 1 WC Reproductive Biology SC Reproductive Biology GA 189QB UT WOS:000248002500068 ER PT J AU Lee, SL Falco, G Stanghellini, I Bassey, UC Hamatani, T Ko, MSH AF Lee, Sung-Lim Falco, Geppino Stanghellini, Ilaria Bassey, Uwem C. Hamatani, Toshio Ko, Minoru S. H. TI Zscan4: A novel gene expressed exclusively in late 2-cell embryos. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 21-25, 2007 CL San Antonio, TX SP Soc Study Reprod C1 NIH, NIA, Baltimore, MD USA. Keio Univ, Sch Med, Tokyo, Japan. RI Ko, Minoru/B-7969-2009 OI Ko, Minoru/0000-0002-3530-3015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2007 SI SI BP 79 EP 79 PG 1 WC Reproductive Biology SC Reproductive Biology GA 189QB UT WOS:000248002500078 ER PT J AU Brown, P Mahato, D Zhou, T McCarrey, J Eddy, M AF Brown, Paula Mahato, Dipak Zhou, Tong McCarrey, John Eddy, Mitch TI Generation and analysis of ESTs from mouse spermatogenic cell and Sertoli cell cDNA libraries. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 21-25, 2007 CL San Antonio, TX SP Soc Study Reprod C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 EI 1529-7268 J9 BIOL REPROD JI Biol. Reprod. PY 2007 SI SI BP 91 EP 91 PG 1 WC Reproductive Biology SC Reproductive Biology GA 189QB UT WOS:000248002500123 ER PT J AU Choi, YS Ballow, D Zhao, YG Westphal, H Rajkovic, A AF Choi, Youngsok Ballow, Daniel Zhao, Yangu Westphal, Heiner Rajkovic, Aleksandar TI Lhx8 deficiency disrupts early folliculogenesis and oocyte-specific gene expression in the mouse ovary. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 21-25, 2007 CL San Antonio, TX SP Soc Study Reprod C1 Baylor Coll Med, Houston, TX 77030 USA. Natl Inst Child Hlth & Human Dev, Bethesda, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2007 SI SI BP 91 EP 91 PG 1 WC Reproductive Biology SC Reproductive Biology GA 189QB UT WOS:000248002500126 ER PT J AU Inselman, A Willis, W Goulding, E Eddy, M AF Inselman, Amy Willis, William Goulding, Eugenia Eddy, Mitch TI Determining the role of MPF in spermatogenesis: Generation of Cdc2a and Ccnb1 conditional knock out mice. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 21-25, 2007 CL San Antonio, TX SP Soc Study Reprod C1 Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2007 SI SI BP 115 EP 115 PG 1 WC Reproductive Biology SC Reproductive Biology GA 189QB UT WOS:000248002500218 ER PT J AU Jayes, F Couse, J Rodriguez, K Yates, M Hamilton, K Korach, K AF Jayes, Friederike Couse, John Rodriguez, Karina Yates, Mariana Hamilton, Katherine Korach, Kenneth TI Does the lack of a cyclical luteinizing hormone-surge contribute to the polycystic ovarian phenotype in estrogen receptor alpha-null mice? SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 21-25, 2007 CL San Antonio, TX SP Soc Study Reprod C1 Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2007 SI SI BP 120 EP 121 PG 2 WC Reproductive Biology SC Reproductive Biology GA 189QB UT WOS:000248002500239 ER PT J AU Hewitt, S Jameson, JL Korach, K AF Hewitt, Sylvia Jameson, J. Larry Korach, Kenneth TI Role of tethered er mechanisms in uterine responses. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 21-25, 2007 CL San Antonio, TX SP Soc Study Reprod C1 NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2007 SI SI BP 145 EP 145 PG 1 WC Reproductive Biology SC Reproductive Biology GA 189QB UT WOS:000248002500334 ER PT J AU Mori, C Shibata, H Nakamura, N Eddy, M AF Mori, Chisato Shibata, Haruna Nakamura, Noriko Eddy, Mitch TI Expression analysis of transcripts for germ cell-specific glycolytic enzymes (Hk1s, GAPDHS, PGK2, and LDHC) using laser capture microdissection. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 21-25, 2007 CL San Antonio, TX SP Soc Study Reprod C1 Chiba Univ, Chiba, Japan. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2007 SI SI BP 166 EP 167 PG 2 WC Reproductive Biology SC Reproductive Biology GA 189QB UT WOS:000248002500413 ER PT J AU Nakamura, N Mori, C Eddy, M AF Nakamura, Noriko Mori, Chisato Eddy, Mitch TI PFKMS binds to GSTM5 and tethers HK1S to the fibrous sheath in the mouse sperm flagellum. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 21-25, 2007 CL San Antonio, TX SP Soc Study Reprod C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Chiba Univ, Chiba, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2007 SI SI BP 167 EP 167 PG 1 WC Reproductive Biology SC Reproductive Biology GA 189QB UT WOS:000248002500416 ER PT J AU Zeng, W Honaramooz, A Fan, T Schmidtmann, A Baumann, C De la Fuente, R Muegge, K Dobrinski, I AF Zeng, Wenxian Honaramooz, Ali Fan, Tan Schmidtmann, Anja Baumann, Claudia De la Fuente, Rabindranath Muegge, Kathrin Dobrinski, Ina TI Testis tissue allografting reveals a phenotype of meiotic arrest in neonatally lethal lsh knock out mice. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 21-25, 2007 CL San Antonio, TX SP Soc Study Reprod C1 Univ Penn, Kennett Sq, PA USA. Natl Canc Inst, Frederick, MD USA. RI Dobrinski, Ina/A-1095-2007 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2007 SI SI BP 187 EP 187 PG 1 WC Reproductive Biology SC Reproductive Biology GA 189QB UT WOS:000248002500491 ER PT J AU Sitzmann, B Mattison, J Ingram, D Roth, G Ottinger, MA Urbanski, H AF Sitzmann, Brandon Mattison, Julie Ingram, Donald Roth, George Ottinger, Mary Ann Urbanski, Henryk TI Impact of moderate calorie restriction on pituitary gene expression in adult male rhesus macaques (Macaca mulatta). SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 21-25, 2007 CL San Antonio, TX SP Soc Study Reprod C1 Univ Maryland, College Pk, MD 20742 USA. Oregon Hlth & Sci Univ, Beaverton, OR USA. NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2007 SI SI BP 226 EP 226 PG 1 WC Reproductive Biology SC Reproductive Biology GA 189QB UT WOS:000248002500631 ER PT J AU Moore, LE Bergen, AW Haque, KA Qi, Y Castle, P Chanock, SJ Egan, K Newcomb, P Titus-Ernstoff, L Alguacil, J Rothman, N Garcia-Closas, M AF Moore, L. E. Bergen, A. W. Haque, K. A. Qi, Y. Castle, P. Chanock, S. J. Egan, K. Newcomb, P. Titus-Ernstoff, L. Alguacil, J. Rothman, N. Garcia-Closas, M. TI Whole genome amplification of buccal cytobrush DNA collected for molecular epidemiology studies SO BIOMARKERS LA English DT Article DE whole genome amplification; multiple displacement amplification; genetic susceptibility; molecular epidemiology; genotyping; TaqMan (R) assay ID MULTIPLE DISPLACEMENT AMPLIFICATION; PERFORMANCE AB When cytobrush buccal cell samples have been collected as a genomic DNA (gDNA) source for an epidemiological study, whole genome amplification (WGA) can be critical to maintain sufficient DNA for genotyping. We evaluated REPLI-g (TM) WGA using gDNA from two paired cytobrushes (cytobush 'A' kept in a cell lysis buffer, and 'B' dried and kept at room temperature for 3 days, and frozen until DNA extraction) in a pilot study (n = 21), and from 144 samples collected by mail in a breast cancer study. WGA success was assessed as the per cent completion/concordance of STR/SNP genotypes. Locus amplification bias was assessed using quantitative PCR of 23 human loci. The pilot study showed > 98% completion but low genotype concordance between cytobrush wgaDNA and paired blood gDNA (82% and 84% for cytobrushes A and B, respectively). Substantial amplification bias was observed with significantly lower human gDNA amplification from cytobrush B than A. Using cytobrush gDNA samples from the breast cancer study (n = 20), an independent laboratory demonstrated that increasing template gDNA to the REPLI-g reaction improved genotype performance for 49 SNPs; however, average completion and concordance remained below 90%. To reduce genotype misclassification when cytobrush wgaDNA is used, inclusion of paired gDNA/wgaDNA and/or duplicate wgaDNA samples is critical to monitor data quality. C1 NCI, Occupat & Environm Epidemiol Branch, DCEG, NIH, Rockville, MD 20852 USA. NCI, Core Genotyping Facil, NIH, Gaithersburg, MD USA. SAIC Frederick, Intramural Res Support Program, NCI FCRDC, Frederick, MD USA. NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD USA. Vanderbilt Univ, Nashville, TN USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Wisconsin, Madison, WI USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. RP Moore, LE (reprint author), NCI, Occupat & Environm Epidemiol Branch, DCEG, NIH, 6120 Execut Blvd,EPS 8118, Rockville, MD 20852 USA. EM moorele@mail.nih.gov RI Garcia-Closas, Montserrat /F-3871-2015; OI Garcia-Closas, Montserrat /0000-0003-1033-2650; Bergen, Andrew/0000-0002-1237-7644 FU Intramural NIH HHS NR 12 TC 5 Z9 5 U1 1 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1354-750X J9 BIOMARKERS JI Biomarkers PY 2007 VL 12 IS 3 BP 303 EP 312 DI 10.1080/13547500601162011 PG 10 WC Biotechnology & Applied Microbiology; Toxicology SC Biotechnology & Applied Microbiology; Toxicology GA 166HH UT WOS:000246369000006 PM 17453743 ER PT B AU Mejia, R Lynch, RM AF Mejia, Raymond Lynch, Ronald M. BE Mondaini, RP Dilao, R TI MATHEMATICAL PREDICTION OF HIGH ENERGY METABOLITE GRADIENTS IN MAMMALIAN CELLS SO BIOMAT 2006 LA English DT Proceedings Paper CT International Symposium on Mathematical and Computational Biology (BIOMAT 2006) CY NOV 27-30, 2006 CL Manaus, BRAZIL ID DIFFUSION AB Described is a mathematical model that evaluates the distribution of cellular adenosine nucleotides (ATP/ADP) to test the hypothesis that local changes in the concentrations of these molecules can modulate cell function without a significant change in global cytosolic concentrations. The model incorporates knowledge of cell structure to predict the spatial concentration profiles of ATP, ADP and inorganic phosphate. The steady state was perturbed by increasing the activity of membrane bound ion transporters including the Na-K ATPase on the cell periphery or the V-type H(+) ATPase which serves to acidify intracellular compartments including endosomes/lysosomes. Both of these transporters utilize ATP and produce ADP and Pi in the process. Both models are run over a range of cytosolic diffusivities, including local low diffusivity near the pump sites. Results suggest that local changes in the concentration of ADP (not ATP) during activation of ion transport, in particular at near membrane sites, may serve to modulate ion transport, and thereby cell behavior. C1 [Mejia, Raymond] NHLBI, NIH, Bethesda, MD 20892 USA. RP Mejia, R (reprint author), NHLBI, NIH, 10 Ctr Dr,Room 4A15, Bethesda, MD 20892 USA. EM ray@helix.nih.gov; rlynch@u.arizona.edu NR 5 TC 0 Z9 0 U1 0 U2 0 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA PO BOX 128 FARRER RD, SINGAPORE 9128, SINGAPORE BN 978-981-270-768-0 PY 2007 BP 221 EP 230 DI 10.1142/9789812708779_0014 PG 10 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA BIP52 UT WOS:000261596200014 ER PT J AU Nijdam, AJ Cheng, MMC Geho, DH Fedele, R Herrmann, P Killian, K Espina, V Petricoin, EF Liotta, LA Ferrari, M AF Nijdam, A. Jasper Cheng, Mark Ming- Cheng Geho, David H. Fedele, Roberta Herrmann, Paul Killian, Keith Espina, Virginia Petricoin, Emanuel F., III Liotta, Lance A. Ferrari, Mauro TI Physicochemically modified silicon as a substrate for protein microarrays SO BIOMATERIALS LA English DT Article DE protein adsorption; silicon; surface modification; surface treatment ID POLY(ETHYLENE GLYCOL) FILMS; POROUS SILICON; SEMICONDUCTOR NANOCRYSTALS; ENZYME IMMOBILIZATION; QUANTUM DOTS; HUMAN PLASMA; SURFACES; CANCER; MICRODEVICES; BIOMOLECULES AB Reverse phase protein microarrays (RPMA) enable high throughput screening of posttranslational modifications of important signaling proteins within diseased cells. One limitation of protein-based molecular profiling is the lack of a PCR-like intrinsic amplification system for proteins. Enhancement of protein microarray sensitivities is an important goal, especially because many molecular targets within patient tissues are of low abundance. The ideal array substrate will have a high protein-binding affinity and low intrinsic signal. To date, nitrocellulose-coated glass has provided an effective substrate for protein binding in the microarray format when using chromogenic detection systems. As fluorescent systems, such as quantum dots, are explored as potential reporter agents, the intrinsic fluorescent properties of nitrocellulose-coated glass slides limit the ability to image microarrays for extended periods of time where increases in net sensitivity can be attained. Silicon, with low intrinsic autofluorescence, is being explored as a potential microarray surface. Native silicon has low binding potential. Through titrated reactive ion etching (RIE), varying surface areas have been created on silicon in order to enhance protein binding. Further, via chemical modification, reactive groups have been added to the surfaces for comparison of relative protein binding. Using this combinatorial method of surface roughening and surface coating, 3-aminopropyltriethoxysilane (APTES) and mercaptopropyltrimethoxysilane (MPTMS) treatments were shown to transform native silicon into a protein-binding substrate comparable to nitrocellulose. (c) 2006 Elsevier Ltd. All rights reserved. C1 Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. Ohio State Univ, Ctr Comprehens Canc, Columbus, OH 43210 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat, Rockville, MD 20857 USA. Univ Texas, Hlth Sci Ctr, Houston, TX 77030 USA. RP Ferrari, M (reprint author), Ohio State Univ, Davis Heart & Lung Res Inst, Columbus, OH 43210 USA. EM Mauro.Ferrari@uth.tmc.edu OI Espina, Virginia/0000-0001-5080-5972 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400] NR 54 TC 46 Z9 47 U1 1 U2 15 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JAN PY 2007 VL 28 IS 3 BP 550 EP 558 DI 10.1016/j.biomaterials.2006.08.051 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 118SB UT WOS:000242960900020 PM 16987550 ER PT J AU Mauck, RL Byers, BA Yuan, X Tuan, RS AF Mauck, R. L. Byers, B. A. Yuan, X. Tuan, R. S. TI Regulation of cartilaginous ECM gene transcription by chondrocytes and MSCs in 3D culture in response to dynamic loading SO BIOMECHANICS AND MODELING IN MECHANOBIOLOGY LA English DT Article ID MESENCHYMAL STEM-CELLS; TISSUE ENGINEERED CARTILAGE; GROWTH-FACTOR-I; ARTICULAR-CARTILAGE; CHONDROGENIC DIFFERENTIATION; MECHANICAL COMPRESSION; BIOSYNTHETIC RESPONSE; STATIC COMPRESSION; AGAROSE CONSTRUCTS; SIGNALING PATHWAY AB This study explored the biologic response of chondrocytes and mesenchymal stem cells (MSCs) to a dynamic mechanical loading regime. We developed a time-efficient methodology for monitoring regional changes in extracellular matrix gene transcription using reporter promoter constructs. Specifically, transfected cells were homogenously distributed throughout agarose hydrogel constructs, and spatial and temporal gene expression and the ability to form functional ECM were analyzed in response to dynamic mechanical stimuli. Theoretical analyses were used to predict the physical signals generated within the gel in response to these loading regimes. Using a custom compression bioreactor system, changes in aggrecan and type 11 collagen promoter activity in transfected chondrocyte-laden cylindrical constructs were evaluated in response to a range of loading, frequencies and durations. In general, aggrecan promoter activity increased with increasing duration of loading, particularly in the outer annulus region. Interestingly, type 11 collagen promoter activity decreased in this annular region under identical loading conditions. In addition, we explored the role of mechanical compression in directing chondrogenic differentiation of MSCs by monitoring short-term aggrecan promoter activity. As an example of long-term utility, a specific loading protocol was applied to MSC-laden constructs for 5 days, and the resultant changes in glycosaminoglycan (GAG) production were evaluated over a 4-week period. This dynamic loading regime increased not only short-term aggrecan transcriptional activity but also GAG deposition in long-term culture. These results demonstrate the utility of a new reporter promoter system for optimizing loading protocols to improve the outcome of engineered chondrocyte- and MSC-laden cartilaginous constructs. C1 NIAMSD, US Dept HHS, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD 20892 USA. RP Tuan, RS (reprint author), NIAMSD, US Dept HHS, Cartilage Biol & Orthopaed Branch, NIH, 50 South Dr,MSC 8022,Bldg 80,Room 1503, Bethesda, MD 20892 USA. EM tuanr@mail.nih.gov FU NIAMS NIH HHS [Z01 AR41131] NR 60 TC 133 Z9 142 U1 2 U2 27 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1617-7959 J9 BIOMECH MODEL MECHAN JI Biomech. Model. Mechanobiol. PD JAN PY 2007 VL 6 IS 1-2 BP 113 EP 125 DI 10.1007/s10237-006-0042-1 PG 13 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 131MQ UT WOS:000243873500013 PM 16691412 ER PT J AU Siddiqui, MA Marquez, VE AF Siddiqui, Maqbool A. Marquez, Victor E. TI The triphosphate of beta-D-4 '-C-ethynyl-2 ',3 '-dideoxycytidine is the preferred enantiomer substrate for HIV reverse transcriptase SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE 4 '-C-ethynyldideoxynucleosides; enantioselective synthesis; HIV reverse transcriptase ID ASYMMETRIC-SYNTHESIS; STERIC HINDRANCE; 3TC RESISTANCE; NUCLEOSIDES AB The enantioselective synthesis of the beta-D (1) enantiomer of 4-C-ethynyl-2',3'-dideoxycytidine confirms an earlier stereochemical assignment that was strictly based on the ability of HIV reverse transcriptase and its M184V mutant to discriminate between the D- and L-configuration of nucleoside 5'-triphosphates. (c) 2006 Elsevier Ltd. All rights reserved. C1 NCI, Med Chem Lab, Canc Res Ctr, Frederick, MD 21702 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Canc Res Ctr, Frederick, MD 21702 USA. EM marquezv@dc37a.nci.nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 BC006173-20] NR 7 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 1 PY 2007 VL 15 IS 1 BP 283 EP 287 DI 10.1016/j.bmc.2006.09.061 PG 5 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 120LW UT WOS:000243087200026 PM 17046266 ER PT J AU Kaur, N Monga, V Lu, XP Gershengorn, MC Jain, R AF Kaur, Navneet Monga, Vikramdeep Lu, Xinping Gershengorn, Marvin C. Jain, Rahul TI Modifications of the pyroglutamic acid and histidine residues in thyrotropin-releasing hormone (TRH) yield analogs with selectivity for TRH receptor type 2 over type 1 SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article DE TRH; peptide synthesis; TRH-R1; TRH-R2; CNS activity; hormonal activity ID RECEPTOR-BINDING; CLONING; SUBTYPE; MODEL AB Thyrotropin -releasing hormone (TRH) analogs in which the N-l(tau) or the C-2 position of the imidazole ring of the histidine residue is substituted with various alkyl groups and the L-pyroglutamic acid (pGlu) is replaced with the L-pyro-2-aminoadipic acid (pAad) or (R)- and (S)-3-oxocyclopentane-1-carboxylic acid (Ocp) were synthesized and studied as agonists for TRH receptor subtype 1 (TRH-R1) and subtype 2 (TRH-R2). We observed that several analogs were selective agonists of TRH-R2 showing relatively less or no activation of TRH-R1. For example, the most selective agonist of the series 13, in which pGlu is replaced with the pAad and histidine residue is substituted at the N-1 position with an isopropyl group, was found to activate TRH-R2 with a potency (EC50 = 1.9 mu M) but did not activate TRH-R1 (potency > 100 mu M); that is, exhibited > 51-fold greater selectivity for TRH-R2 versus TRH-R1. Analog 8, in which pGlu is replaced with pAad and histidine is substituted at the N-1(tau) position with a methyl group, exhibited a binding affinity (K-i = 0.0032 mu M) to TRH-R1 that is similar to that of [N tau(1)-Me-His]-TRH and displayed potent activation of TRH-R1 and TRH-R2 (EC50 = 0.0049 and 0.0024 mu M, respectively). None of the analogs in which pGlu is replaced with the bioisosteric (R)- and (S)-(Ocp) and the imidazole ring is substituted at the N-1(tau) or C-2 position were found to bind or activate either TRH-R1 or TRH-R2 at the highest test dose of 100 mu M. (c) 2006 Elsevier Ltd. All rights reserved. C1 Natl Inst Pharmaceut Educ & Res, Dept Med Chem, Punjab 160062, India. NIDDK, Clin Endocrinol Branch, NIH, Bethesda, MD 20892 USA. RP Jain, R (reprint author), Natl Inst Pharmaceut Educ & Res, Dept Med Chem, Sector 67, Punjab 160062, India. EM rahuljain@niper.ac.in OI Kaur, Navneet/0000-0002-0012-6151 NR 34 TC 22 Z9 22 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JAN 1 PY 2007 VL 15 IS 1 BP 433 EP 443 DI 10.1016/j.bmc.2006.09.045 PG 11 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 120LW UT WOS:000243087200043 PM 17035026 ER PT J AU Kang, DW Ryu, H Lee, J Lang, KA Pavlyukovets, VA Pearce, LV Ikeda, T Lazar, J Blumberg, PM AF Kang, Dong Wook Ryu, HyungChul Lee, Jeewoo Lang, Krystle A. Pavlyukovets, Vladimir A. Pearce, Larry V. Ikeda, Tetsurou Lazar, Jozsef Blumberg, Peter M. TI Halogenation of 4-hydroxy-3-methoxybenzyl thiourea TRPV1 agonists showed enhanced antagonism to capsaicin SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE TRPV1 agonist; TRPV1 antagonist; halogenation; resiniferatoxin; capsaicinoid ID HIGH-AFFINITY ANTAGONISTS; VANILLOID RECEPTOR; POTENT; RESINIFERATOXIN; ANALOGS; ANALGESICS; MECHANISMS; CHANNELS; FAMILY AB Selected potent TRPV1 agonists (1-6) have been modified by 5- or 6-halogenation on the aromatic A-region to analyze their effects on potency and efficacy (agonism versus antagonism). The halogenation caused enhanced functional antagonism at TRPV1 compared to the corresponding prototype agonists. The analysis of SAR indicated that the antagonism was enhanced as the size of the halogen increased (I > Br > CI) and when the 6-position was halogenated. Compounds 23c and 31b were found to be potent full antagonists with K-i (as functional antagonist) = 23.1 and 30.3 nM in rTRPV1/CHO system, respectively. (c) 2006 Elsevier Ltd. All rights reserved. C1 Seoul Natl Univ, Res Inst Pharmaceut Sci, Coll Pharm, Seoul 151742, South Korea. NCI, Lab Cellular Carcinogenesis & Tumor Promot, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Lee, J (reprint author), Seoul Natl Univ, Res Inst Pharmaceut Sci, Coll Pharm, Seoul 151742, South Korea. EM jeewoo@snu.ac.kr FU Intramural NIH HHS NR 20 TC 8 Z9 8 U1 1 U2 5 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 JAN 1 PY 2007 VL 17 IS 1 BP 214 EP 219 DI 10.1016/j.bmcl.2006.09.059 PG 6 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 128BK UT WOS:000243630500042 PM 17035013 ER PT J AU Siddiqui, N Pandeya, SN Khan, SA Stables, J Rana, A Alam, M Arshad, MF Bhat, MA AF Siddiqui, Nadeem Pandeya, Surendra N. Khan, Suroor A. Stables, James Rana, Arpana Alam, Mahfuz Arshad, Md. Faiz Bhat, Mashooq A. TI Synthesis and anticonvulsant activity of sulfonamide derivatives-hydrophobic domain SO BIOORGANIC & MEDICINAL CHEMISTRY LETTERS LA English DT Article DE sulfonamide; benzothiazole; anticonvulsant AB A series of sulphonamide derivatives (1-11) were synthesized in good yield and evaluated for their possible anticonvulsant activity and neurotoxic study. The structures of the synthesized compounds were confirmed on the basis of their spectral data and elemental analysis. Majority of the compounds were active in MES and scPTZ tests. All the compounds were less toxic than the standard drug phenytoin. (c) 2006 Elsevier Ltd. All rights reserved. C1 Fac Pharm, Dept Pharmaceut Chem, New Delhi 110062, India. Dr KN Modi Inst Pharmaceut Educt & Res, Modinagar 201201, UP, India. NIH, Antiepilept Drug Dev Programme, Epilepsy Branch, Rockville, MD USA. RP Siddiqui, N (reprint author), Fac Pharm, Dept Pharmaceut Chem, Jamia Hamdard, New Delhi 110062, India. EM nadeems_03@yahoo.co.in NR 10 TC 75 Z9 77 U1 0 U2 6 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 JAN 1 PY 2007 VL 17 IS 1 BP 255 EP 259 DI 10.1016/j.bmcl.2006.09.053 PG 5 WC Chemistry, Medicinal; Chemistry, Organic SC Pharmacology & Pharmacy; Chemistry GA 128BK UT WOS:000243630500050 PM 17046248 ER PT J AU Bu, ZM Shi, Y Callaway, DJE Tycko, R AF Bu, Zimei Shi, Yuan Callaway, David J. E. Tycko, Robert TI Molecular alignment within beta-sheets in A beta(14-23) fibrils: Solid-state NMR experiments and theoretical predictions SO BIOPHYSICAL JOURNAL LA English DT Article ID NUCLEAR-MAGNETIC-RESONANCE; X-RAY-DIFFRACTION; AMYLOID FIBRILS; STRUCTURAL MODEL; HET-S; CONFORMATIONAL DISTRIBUTIONS; SUPRAMOLECULAR STRUCTURE; EXPERIMENTAL CONSTRAINTS; SENSITIVITY ENHANCEMENT; PEPTIDE FRAGMENT AB We report investigations of the molecular structure of amyloid fibrils formed by residues 14-23 of the beta-amyloid peptide associated with Alzheimer's disease (A beta(14-23)), using solid-state nuclear magnetic resonance (NMR) techniques in conjunction with electron microscopy and atomic force microscopy. The NMR measurements, which include two-dimensional proton-mediated C-13-C-13 exchange and two-dimensional relayed proton-mediated C-13-C-13 exchange spectra, show that A beta(14-23) fibrils contain antiparallel beta-sheets with a registry of backbone hydrogen bonds that aligns residue 17+k of each peptide molecule with residue 22-k of neighboring molecules in the same beta-sheet. We compare these results, as well as previously reported experimental results for fibrils formed by other beta-amyloid fragments, with theoretical predictions of molecular alignment based on databases of residue-specific alignments in antiparallel beta-sheets in known protein structures. While the theoretical predictions are not in exact agreement with the experimental results, they facilitate the design of experiments by suggesting a small number of plausible alignments that are readily distinguished by solid-state NMR. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. RP Callaway, DJE (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. EM david.callaway@fccc.edu; robertt@niddk.nih.gov NR 82 TC 35 Z9 35 U1 0 U2 4 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 VL 92 IS 2 BP 594 EP 602 DI 10.1529/biophysj.106.091017 PG 9 WC Biophysics SC Biophysics GA 121AU UT WOS:000243129800027 PM 17056725 ER PT J AU Jacobs, A Blumenthal, R AF Jacobs, Amy Blumenthal, Robert TI Targeting of nanofusion machines to cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc ID PROTEIN; FUSION C1 NIH, NCI, Frederick, MD USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 7A EP 7A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400028 ER PT J AU Greene, LE Steven, AC AF Greene, Lois E. Steven, Alasdair C. TI Probing the structures of coated vesicles by cryo-electron tomography SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIAMS, LSBR, Bethesda, MD 20892 USA. NIH, NHLBI, LCB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 10A EP 10A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400042 ER PT J AU Lasker, K Dror, O Nussinov, R Wolfson, HJ AF Lasker, Keren Dror, Oranit Nussinov, Ruth Wolfson, Haim J. TI EMatch: Discovery of high resolution structural homologues protein domains in intermediate resolution Cryo-EM maps SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Tel Aviv Univ, IL-69978 Tel Aviv, Israel. SAIC Frederick Inc, NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 10A EP 10A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400043 ER PT J AU Mears, JA Ray, P Ingerman, E Nunnari, J Hinshaw, JE AF Mears, Jason A. Ray, Pampa Ingerman, Elena Nunnari, Jodi Hinshaw, Jenny E. TI Structural analysis of dynamin family members offers insight into membrane fission SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIDDK, Bethesda, MD 20892 USA. Univ Calif Davis, Davis, CA 95616 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 10A EP 10A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400041 ER PT J AU Khursigara, CM Zhang, PJ Lefinan, J Hartnell, LM Subramaniam, S AF Khursigara, Cezar M. Zhang, Peijun Lefinan, Jonathan Hartnell, Lisa M. Subramaniam, Sriram TI Cryo-electron tomography of E.coli: structure and functional analysis of chemotaxis receptor assemblies SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 11A EP 11A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400046 ER PT J AU Vinogradova, TM Brochet, DX Sirenko, SG Lyashkov, AE Maltsev, VA Yang, DM Cheng, HP Lakatta, EG AF Vinogradova, Tatiana M. Brochet, Didier X. Sirenko, Syevda G. Lyashkov, Alexey E. Maltsev, Victor A. Yang, Dongmei Cheng, Heping Lakatta, Edward G. TI Sarcoplasmic reticulum (SR) Ca2+ refilling kinetics controls the period of local subsarcolemmal Ca2+ releases (LCR) and the spontaneous beating rate of sinoatrial node cells (SANC) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIA, Baltimore, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 31A EP 31A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400136 ER PT J AU Monterroso, B McPhie, P Minton, AP AF Monterroso, Begona McPhie, Peter Minton, Allen P. TI Effect of macromolecular crowding on the rate of refolding of carbonic anhydrase SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIDDK, NIH, Bethesda, MD USA. RI Monterroso, Begona/J-9748-2014 OI Monterroso, Begona/0000-0003-2538-084X NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 35A EP 35A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400157 ER PT J AU Gurnev, P Harries, D Parsegian, A Bezrukov, S AF Gurnev, Philip Harries, Daniel Parsegian, Adrian Bezrukov, Sergey TI Single-molecule probe of solute-specific water release upon association of adamantane with cyclodextrin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Inst Child Hlth & Human Dev, Bethesda, MD USA. Hebrew Univ Jerusalem, Fritz Haber Res Ctr, Dept Phys Chem, IL-91904 Jerusalem, Israel. RI Harries, Daniel/F-7016-2012 OI Harries, Daniel/0000-0002-3057-9485 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 36A EP 36A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400161 ER PT J AU Stanley, CB Krueger, S Parsegian, VA Rau, DC AF Stanley, Christopher B. Krueger, Susan Parsegian, V. Adrian Rau, Donald C. TI Structural changes in guanylate kinase studied by neutron scattering and osmotic stress SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIST, Ctr Neutron Res, Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. NICHD, Natl Inst Hlth, Lab Phys & Structural Biol, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 36A EP 36A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400160 ER PT J AU Bennett, MP Mitchell, DC AF Bennett, Michael P. Mitchell, Drake C. TI The effects of membrane composition on the activation energy of thermal denaturation of rhodopsin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 37A EP 37A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400165 ER PT J AU Damjanovic, A Fitch, CA Garcia, AE Garcia-Moreno E, B AF Damjanovic, Ana Fitch, Carolyn A. Garcia, Angel E. Garcia-Moreno E, Bertrand TI Role of flexibility and polarity as determinants of the hydration of internal cavities and pockets in proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Johns Hopkins Univ, Baltimore, MD USA. Natl Inst Hlth, Bethesda, MD USA. Rensselaer Polytech Inst, Troy, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 40A EP 41A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400183 ER PT J AU Cachau, RE Duque-Norena, MA Niimura, N Burt, SK AF Cachau, Raul E. Duque-Norena, Mario A. Niimura, Nobuo Burt, Stanley K. TI Towards an ultra-high resolution macromolecular structural database: analysis of proton acidities and peptide bond deformations by QM calculations, neutron scattering and X-ray crystallography studies. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NCI, SAIC Frederick, Adv Biomed Comp Ctr, Frederick, MD 21701 USA. Univ Andres Bello, Fac Ecol Recursos Nat, Santiago, Chile. Ibaraki Univ, Fac Engn, Grad Sch Engn Sci, Hitachi, Ibaraki 316, Japan. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 41A EP 41A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400184 ER PT J AU Kotova, S Smith, PD Lebowitz, J Narum, DL Jin, AJ AF Kotova, Svetlana Smith, Paul D. Lebowitz, Jack Narum, David L. Jin, Albert J. TI AFM structures of a potential malaria vaccine component: Escherichia coli derived Plasmodium falciparum merozoite surface protein 3 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA. NIH, NIAID, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 41A EP 41A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400187 ER PT J AU Li, YF Poole, S Rasulova, F Savarino, SJ Xia, D AF Li, Yong-Fu Poole, Steven Rasulova, Fatima Savarino, Stephen J. Xia, Di TI Crystal structure and receptor-binding site of the adhesin CfaE of enterotoxigenic Escherichia coli CFA/I fimbriae SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Inst Hlth, Bethesda, MD USA. Naval Med Res Ctr, Enter Dis dept, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 43A EP 43A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400195 ER PT J AU Parsegian, VA Podgornik, R Rau, D AF Parsegian, V. Adrian Podgornik, Rudi Rau, Donald TI DNA packing in vitro vs. in viro SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. RI Podgornik, Rudolf/C-6209-2008 OI Podgornik, Rudolf/0000-0002-3855-4637 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 46A EP 46A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400209 ER PT J AU Raviv, Y Blumenthal, R Viard, M AF Raviv, Yossef Blumenthal, Robert Viard, Mathias TI Inactivation of enveloped viruses with preservation of structural integrity by hydrophobic alkylating compounds. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NCI, CCR Nanbiol Program, BRP SAIC, Frederick, MD 21701 USA. NCI, CCR Nanobiol Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 50A EP 50A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400229 ER PT J AU Wang, F Stewart, KM Cruceanu, M Gorelick, RJ Rouzina, L Musier-Forsyth, K Williams, MC AF Wang, Fei Stewart, Kristen M. Cruceanu, Margareta Gorelick, Robert J. Rouzina, Loulia Musier-Forsyth, Karin Williams, Mark C. TI Nucleic acid chaperone activity of the HTLV-1 nucleocapsid protein SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Northeastern Univ, Dept Phys, Boston, MA 02115 USA. Univ Minnesota, Dept Chem, Minneapolis, MN 55455 USA. NCI, SAIC, AIDS Vaccine Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 53A EP 53A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400244 ER PT J AU Stephen, AG Rishi, V Hagan, NA Fabris, D Vinson, C Shoemaker, RH Fisher, RJ AF Stephen, Andrew G. Rishi, Vikas Hagan, Nathan A. Fabris, Daniele Vinson, Charles Shoemaker, Robert H. Fisher, Robert J. TI The position of fluorescein on oligonucleotide affects the apparent affinity of transcription factor binding SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NCI, Frederick, MD 21701 USA. NCI, Bethesda, MD 20892 USA. UMBC, Baltimore, MD USA. RI Fisher, Robert/B-1431-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 54A EP 54A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400248 ER PT J AU Schultz, ZD Crane, NJ Levin, IW AF Schultz, Zachary D. Crane, Nicole J. Levin, Ira W. TI Vibrational infrared spectroscopic studies of model biomembranes: Characterization of lipid raft formation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. NIDDK, Natl Inst Hlth, Phys Chem Lab, Bethesda, MD USA. RI Schultz, Zachary/L-5724-2013 OI Schultz, Zachary/0000-0003-1741-8801 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 60A EP 60A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400277 ER PT J AU Ravichandran, S Moaddel, R Bigi, F Collins, JR Yamaguchi, R Wainer, IW AF Ravichandran, Sirangan Moaddel, R. Bigi, F. Collins, Jack R. Yamaguchi, R. Wainer, Irving W. TI Pharmaeophore modeling of stereoselective inhibitor binding site of the human organic cation transporter, hOCT1 SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Adv Biomed Comp Ctr, Natl Canc Inst, Frederick, MD USA. Gerontol Res Ctr, Natl Inst Anim Hlth, NIA, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 62A EP 62A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400288 ER PT J AU Palma, F Rosenthal, J Holmgren, M AF Palma, Francisco Rosenthal, Joshua Holmgren, Miguel TI Functional role of RNA editing in the Na+/Ca2+ exchanger from the squid Loligo pealeii SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NINDS, NIH, Bethesda, MD 20892 USA. Univ Puerto Rico, Inst Neurobiol, Med Sci Campus, San Juan, PR 00901 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 64A EP 64A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400300 ER PT J AU Sun, JH Steenbergen, C Murphy, E AF Sun, Junhui Steenbergen, Charles Murphy, Elizabeth TI Preconditioning increases S-nitrosylation of L-type calcium channel and SERCA2a SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NHLBI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 64A EP 64A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400299 ER PT J AU Yeliseev, AA Lay, K Zoubak, L Gawrisch, K AF Yeliseev, Alexei A. Lay, Kenneth Zoubak, Lioudmila Gawrisch, Klaus TI Expression of recombinant peripheral cannabinoid receptor CB2 and its structural characterization in detergent micelles SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Rockville, MD USA. RI Yeliseev, Alexei/B-3143-2009 NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 72A EP 72A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400338 ER PT J AU Parsons, SP Vinogradova, TM Lyashkov, AE Spurgeon, HA Stem, MD Lakatta, EG Maltsev, VA AF Parsons, Sean P. Vinogradova, Tatiana M. Lyashkov, Alexey E. Spurgeon, Harold A. Stem, Michael D. Lakatta, Edward G. Maltsev, Victor A. TI Local Ca2+ waves rather than sparks boost the subplasmalemmal Ca2+ rise in late diastole of rabbit sinoatrial node cells: Characterization in two dimensions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIA, NIH, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. NR 0 TC 4 Z9 4 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 76A EP 76A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400357 ER PT J AU Maltsev, VA Brocht, DXP Parsons, SP Vinogradova, TM Sirenko, SG Cheng, HP Stern, MD Lakatta, EG AF Maltsev, Victor A. Brocht, Didier X. P. Parsons, Sean P. Vinogradova, Tatiana M. Sirenko, Syevda G. Cheng, Heping Stern, Michael D. Lakatta, Edward G. TI A numerical model of a Ca2+ clock within sinoatrial node cells: Interactive membrane and submembrane Ca2+ cycling provides a novel mechanism of normal cardiac pacemaker function SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIA, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 77A EP 77A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400358 ER PT J AU Santiago, DJ Curran, JW Lucero, SG Rios, E Bers, DM Lederer, WJ Stem, MD Shannon, TR AF Santiago, Demetrio J. Curran, Jerald W. Lucero, Sarah G. Rios, Eduardo Bers, Donald M. Lederer, W. J. Stem, Michael D. Shannon, Thomas R. TI Relationship between Ca sparks and SR Ca leak in mouse ventricular myocytes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Rush Univ, Chicago, IL 60612 USA. Loyola Univ, Chicago, IL 60611 USA. Univ Maryland, Inst Biotechnol, Baltimore, MD 21201 USA. Univ Maryland, Baltimore, MD 21201 USA. NIA, NIH, Baltimore, MD 21224 USA. RI Lederer, William/B-1285-2010; Bers, Donald/C-4507-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 77A EP 77A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400360 ER PT J AU Sirenko, SG Tarasova, Y Boheler, KR Stem, MD Lakatta, EG Maltsev, VA AF Sirenko, Syevda G. Tarasova, Yelena Boheler, Kenneth R. Stem, Michael D. Lakatta, Edward G. Maltsev, Victor A. TI Developmental regulation of spontaneous Ca2+ releases by protein kinase A in cardiomyocytes derived from mouse embryonic stem cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 78A EP 78A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400363 ER PT J AU Lizunov, VA Lisinski, I Ziminerberg, J Cushman, SW AF Lizunov, Vladimir A. Lisinski, Ivonne Ziminerberg, Joshua Cushman, Samuel W. TI Exo70 subunit of exocyst complex is not required for tethering and fusion of GLUT4 vesicles in rat adipose cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NICHD, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. NIH, NIDDK, Diabetes Branch, Bethesda, MD 20892 USA. RI Lizunov, Vladimir/B-5468-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 83A EP 83A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400387 ER PT J AU Ferguson, ML Prasad, K Boukari, H Sackett, DL Krueger, S Lafer, EM Nossal, R AF Ferguson, Matthew. L. Prasad, Kondury Boukari, Hacene Sackett, Dan L. Krueger, Susan Lafer, Eileen M. Nossal, Ralph TI Small angle neutron scattering studies of clathrin triskelia in solution show evidence of molecular flexibility SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NICHHD, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. Univ Maryland, Dept Phys, College Pk, MD 20742 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX USA. Ctr Neutron Res, Natl Inst Stand & Technol, Mat Sci & Engn Lab, Gaithersburg, MD 20899 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 84A EP 84A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400389 ER PT J AU Lizunov, VA Kirchhausen, T Frolov, V Zimmerberg, J AF Lizunov, Vladimir A. Kirchhausen, Tom Frolov, Vadim Zimmerberg, Joshua TI Membrane neck dynamics during normal and aborted endocytic events revealed by patch clamp admittance SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NICHD, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. Harvard Med Sch, CBRI, Dept Cell Biol, Boston, MA USA. RI Lizunov, Vladimir/B-5468-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 85A EP 85A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400393 ER PT J AU Melikov, K Leikina, E Gabrielian, A Lehrer, RI Chemomordik, LV AF Melikov, Kamran Leikina, Eugenia Gabrielian, Anna Lehrer, Robert I. Chemomordik, Leonid V. TI 0-defensin retrocyclin-2 promotes endocytosis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NICHD, Sect Membrane Biol, LCMD, Bethesda, MD USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA USA. RI Melikov, Kamran/A-6604-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 85A EP 85A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400394 ER PT J AU Rottlaender, D Reinijes, CP Witschas, K Matthes, J Soldatov, NM Herzig, S AF Rottlaender, Dennis Reinijes, Christian P. Witschas, Katja Matthes, Jan Soldatov, Nikolai M. Herzig, Stefan TI Functional modulation of human vascular alpha 1c-splice variants by beta-subunits SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Univ Cologne, Cologne, Germany. NIH, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 97A EP 97A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400446 ER PT J AU Kobrinsky, E Lee, JH Soldatov, NM AF Kobrinsky, E. Lee, J. H. Soldatov, N. M. TI Selective fluorophore-assisted light inactivation of voltage-gated calcium channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 100A EP 100A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400463 ER PT J AU Sul, B Twasa, KH AF Sul, Bora Twasa, Kuni H. TI Stochastic models for fast adaptation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIDCD, Biophys Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 119A EP 119A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400548 ER PT J AU Tiwari, S Zhang, YW Heller, J Abernethy, DR Soldatov, NM AF Tiwari, Swasti Zhang, Yuwei Heller, Jennifer Abernethy, Darrell R. Soldatov, Nikolai M. TI Remodeling of human Ca(v)1.2 calcium channels in atherosclerosis SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIA, Baltimore, MD 21224 USA. Johns Hopkins Bayview Med Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 129A EP 130A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400597 ER PT J AU Liu, X Shu, S Korn, ED AF Liu, Xiong Shu, Shi Korn, Edward D. TI Effects of Tyr-53 mutations on polymerization of Dictyostelium actin and cell phenotype SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 141A EP 141A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400649 ER PT J AU Liu, J McBride, MJ Subramaniam, S AF Liu, Jun McBride, Mark J. Subramaniam, Sriram TI Cryo tomographic analysis of Flavobacterium johnsoniae SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Milwaukee, WI 53201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 142A EP 142A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400654 ER PT J AU Colina, C Rosenthal, J DeGiorgis, JA Iruku, N Srikumar, D Holmgren, M AF Colina, Claudia Rosenthal, Joshua DeGiorgis, Joseph A. Iruku, Nikhila Srikumar, Deepa Holmgren, Miguel TI Structural basis of Na+/K+-ATPase adaptation to marine environments. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Univ Puerto Rico, Med Sci Campus, Inst Neurobiol, San Juan, PR 00936 USA. NIH, NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 144A EP 144A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400666 ER PT J AU Ma, J Xia, D AF Ma, Jichun Xia, Di TI Crystallization of the recombinant n-terminal domain of copper transport ATPase CopB from thermophilic bacteria Archaeoglobus Fulgidus SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 144A EP 144A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400663 ER PT J AU Albert, AD Edrington, T Bennett, M AF Albert, Arlene D. Edrington, Thomas Bennett, Michael TI The effect of opsin on the thermal stability of rhodopsin in bovine rod outer segment disk membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Univ Connecticut, Storrs, CT USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 147A EP 147A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400680 ER PT J AU Grossfield, A Pitman, MC Feller, SE Soubias, O Gawrisch, K AF Grossfield, Alan Pitman, Michael C. Feller, Scott E. Soubias, Olivier Gawrisch, Klaus TI The role of water in rhodopsin activation: Insights from two microsecond-scale molecular dynamics simulations SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 IBM TJ Watson Res, Yorktown Hts, NY 47933 USA. Wabash Coll, Dept Chem, Crawfordsville, IN USA. NIAAA, Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 147A EP 147A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400678 ER PT J AU Rosales, T Xu, JH Smirnov, AV Combs, C Davenport, L Knutson, JR AF Rosales, Tilman Xu, Jianhua Smirnov, Aleksandr V. Combs, Christian Davenport, Lesley Knutson, Jay R. TI Simultaneous imaging of NAD plus and NADH using CARS and 2-photon fluorescence microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NHLBI, NIH, LMB, Opt & Spect Sect, Bethesda, MD 20892 USA. NHLBI, NIH, Light Microscopy Core Facil, Bethesda, MD 20892 USA. CUNY Brooklyn Coll, Brooklyn, NY 11210 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 156A EP 156A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400725 ER PT J AU Cachau, RE Frius, MJ Topol, I Burt, SK Gonzalez-Nilo, FD Matties, M AF Cachau, Raul E. Frius, Martin J. Topol, Igor Burt, Stanley K. Gonzalez-Nilo, Fernando D. Matties, Mark TI New modeling strategies for the computational characterization of nanobioparticles SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Adv Biomed Comp Ctr, NCI, Frederick, MD 21701 USA. NCI, SAIC Frederick, Nanotechnol Characterizat Lab, Frederick, MD 21701 USA. Univ Talca, CBSM, Talca, Chile. Bowie State Univ, Dept Comp Sci, Bowie, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 162A EP 162A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400754 ER PT J AU Cachau, RE Sanjoh, A AF Cachau, Raul E. Sanjoh, Akira TI Protein crystal growth in a simulated microgravity environment SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Adv Biomed Comput Ctr, NCI, SAIC Frederick, Frederick, MD USA. Prot Wave Corp, Kyoto, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 163A EP 163A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400757 ER PT J AU Lee, DH Bianchi, K Walsh, JD Yu, P Wang, YX Draper, D AF Lee, Donghan Bianchi, Kristin Walsh, Joseph D. Yu, Ping Wang, Yun-Xing Draper, David TI Structural and thermodynamic studies of a ribosomal protein - RNA antibiotic complex SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NCI, Frederick, MD 21701 USA. Johns Hopkins Univ, Baltimore, MD USA. RI Lee, Donghan/B-6893-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 170A EP 170A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972400792 ER PT J AU Zheng, WJ Liao, JC Brooks, BR Doniach, S AF Zheng, Wenjun Liao, Jungchi Brooks, Bernard R. Doniach, Sebastian TI Towards the mechanism of dynamic couplings and translocation in Hepatitis C virus NS3 helicase using elastic network model SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. Stanford Univ, Stanford, CA 94305 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 177A EP 178A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401023 ER PT J AU Silver, J Ou, W AF Silver, Jonathan Ou, Wu TI Stoichiometry of membrane fusion mediated by a retroviral envelope protein and its neutralization by antibody SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 183A EP 183A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401045 ER PT J AU Niu, SL Doctrow, B Mitchell, DC AF Niu, Shui-Lin Doctrow, Brian Mitchell, Drake C. TI Rhodopsin-containing vesicles prepared by dialysis method vs dilution method: Differences in vesicle structure and rhodopsin function SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 187A EP 188A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401068 ER PT J AU Soubias, O Teague, W Gawrisch, K AF Soubias, Olivier Teague, Walter Gawrisch, Klaus TI Specificity in rhodopsin-lipid interactions probed by solid state NMR SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 187A EP 187A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401067 ER PT J AU Phillips, LR Swartz, KJ AF Phillips, L. Revell Swartz, Kenton J. TI Metal bridges constrain the position of the S4 helices during gating of KV channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NINDS, Natl Inst Gen Med Sci, MPBS, Bethesda, MD 20892 USA. NIH, NINDS, Mol Physiol & Biphys Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 189A EP 189A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401075 ER PT J AU Ma, XF Bao, JJ Adelstein, RS AF Ma, Xuefei Bao, Jianjun Adelstein, Robert S. TI Nonmuscle myosin II scaffolding properties but not motor activity are necessary to prevent hydrocephalus in the developing brain SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NHLBI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 191A EP 191A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401083 ER PT J AU Damjanovic, A Wu, XW Brooks, B Garcia-Moreno E, B AF Damjanovic, Ana Wu, Xiongwu Brooks, Bernard Garcia-Moreno E, Bertrand TI Backbone relaxation triggered by the ionization of internal groups in proteins: A Self-Guided Langevin Dynamics study SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Johns Hopkins Univ, Baltimore, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 193A EP 193A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401096 ER PT J AU Anishkin, A Shafrir, Y Durell, SR Guy, HR AF Anishkin, Andriy Shafrir, Yinon Durell, Stewart R. Guy, H. Robert TI Structural models of soluble and membrane Abeta oligomers SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Univ Maryland, Dept Biol, College Pk, MD 20742 USA. NIH, NCI, Cell Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 194A EP 194A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401100 ER PT J AU Buchete, NV Hummer, G AF Buchete, Nicolae-Viorel Hummer, Gerhard TI Exploring the structural stability and the mechanism of dissociation of Alzheimer's amyloid fibrils SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIDDKD, Chem Phys Lab, Bethesda, MD 20892 USA. RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 0 TC 1 Z9 1 U1 0 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 194A EP 194A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401098 ER PT J AU Tuncbag, N Gursoy, A Guney, E Nussinov, R Tsai, CJ Keskin, O AF Tuncbag, Nurcan Gursoy, Attila Guney, Emre Nussinov, Ruth Tsai, C. J. Keskin, Ozlem TI A new dataset of protein-protein interfaces SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Kochi Univ, Istanbul, Turkey. SAIC Frederick Inc, NCI, BRP, Frederick, MD USA. RI Tuncbag, Nurcan/D-3383-2011; Gursoy, Attila/E-9565-2015 OI Gursoy, Attila/0000-0002-2297-2113 NR 1 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 194A EP 194A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401101 ER PT J AU Mitchell, DC Niu, SL Bennett, M Hines, KG Greeley, LA Andersen, BM AF Mitchell, Drake C. Niu, Shui-Lin Bennett, Michael Hines, Kirk G. Greeley, Laura A. Andersen, Brian M. TI Effects of extremely long polyunsaturated acyl chains on receptor activation and membrane properties SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIAAA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 197A EP 197A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401114 ER PT J AU Chattopadhyay, R Iacob, R Tomer, KB Lentz, BR AF Chattopadhyay, Rima Iacob, Roxana Tomer, Kenneth B. Lentz, Barry R. TI Effect of C6PS-induced factor Xa dimerization on prothrombin proteolysis, FXa active site, substrate exosites, and FXa structure rima chattopadhyay SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC USA. NIEHS, Struct Biol Lab, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 BP 203A EP 203A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401141 ER PT J AU Ma, K Forbes, JG Gutierrez-Cruz, G Wang, K AF Ma, Kan Forbes, Jeffrey G. Gutierrez-Cruz, Gustavo Wang, Kuan TI Novel overlap and multi-orientation SH3 ligand motifs enhance signaling capacity of proline-rich domains of signaling proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIAMS, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 203A EP 204A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401144 ER PT J AU Cachau, RE Podjarny, AD Ruiz, F Ventura, ON Burt, SK AF Cachau, Raul E. Podjarny, Alberto D. Ruiz, Federico Ventura, Oscar N. Burt, Stanley K. TI Aldose reductase studied by comparative analysis of neutron scattering, X-ray ultra-high resolution and QM electron density maps and molecular dynamics SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Adv Biomed Computing Ctr, NCI, SAIC, Frederick, MD USA. UPR Biol Struct, IGBMC, Illkirch Graffenstaden, France. CNIO, Madrid, Spain. Univ Republica, Fac Chem, CCPG DETEMA, Montevideo, Uruguay. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 213A EP 213A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401192 ER PT J AU Ma, B Nussinov, R AF Ma, Buyong Nussinov, Ruth TI Why does nature want to avoid Isoleucine in protein-protein interactions: a hypothesis. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NCI, NIH, SAIC, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 220A EP 220A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401230 ER PT J AU Keskin, O Nussinov, R AF Keskin, Ozlem Nussinov, Ruth TI Protein-protein interactions: Similar binding sites; Different partners SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Koc Univ, Istanbul, Turkey. NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 222A EP 222A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401239 ER PT J AU Hastings, WA Jeong, JI Chirikjian, GS Shapiro, BA AF Hastings, Whitney A. Jeong, Jay I. Chirikjian, Gregory S. Shapiro, Bruce A. TI Enhanced elastic network model for tRNA folding SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Canc Inst, Frederick, MD USA. Johns Hopkins Univ, Baltimore, MD USA. Kookmin Univ, Seoul, South Korea. RI Chirikjian, Gregory/A-3314-2010 NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 227A EP 227A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401268 ER PT J AU Kasprzak, WK Linnstaedt, SD Casey, JL Shapiro, BA AF Kasprzak, Wojciech K. Linnstaedt, Sarah D. Casey, John L. Shapiro, Bruce A. TI Computational modeling of the HDV III secondary structure folding dynamics SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 SAIC Frederick, Frederick, MD USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. Natl Canc Inst, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 228A EP 228A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401269 ER PT J AU Ju, JH Maeng, JS Zemedkun, M Gelmann, EP Gruschus, JM AF Ju, Jeong Ho Maeng, Jin Soo Zemedkun, Micheas Gelmann, Edward P. Gruschus, James M. TI Detecting linear peptide motifs in the intrinsically unstructured regions of the transcription factor NKX3.1 homeoprotein by NMR SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Georgetown Univ, Washington, DC USA. Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 231A EP 231A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401288 ER PT J AU Sidorova, NY Muradymov, S Rau, DC AF Sidorova, Nina Y. Muradymov, Shakir Rau, Donald C. TI Differences in hydration coupled to specific and competitive BamHI-DNA binding SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NICHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 231A EP 232A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401290 ER PT J AU Pan, YP Nussinov, R AF Pan, Yongping Nussinov, Ruth TI Structural basis for specific p53 binding-induced DNA bending SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Canc Inst, SAIC, Frederick, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 233A EP 233A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401298 ER PT J AU Polozov, IV Gawrisch, K AF Polozov, Ivan V. Gawrisch, Klaus TI Membrane interactions of N-[8-(2-hydroxybenzoyl)amino]caprylate SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NICHD, NIH, Lab Cellular & Mol Biophys, Bethesda, MD USA. NIH, NIAAA, LMBB, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 239A EP 239A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401326 ER PT J AU Perry, M Rostovtseva, T Antonsson, B Lund, M Ogendal, L Klosgen, B AF Perry, Mark Rostovtseva, Tanya Antonsson, Bruno Lund, Marianne Ogendal, Lars Klosgen, Beate TI tBid and cardiolipin - Trying an insight to the interplay of cell apoptosis key players in a simple model system SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Univ Denmark So, Odense, Denmark. NICHD, LPSB, Bethesda, MD USA. Serono Pharmaceut Res Inst, Geneva, Switzerland. Royal Vet & Agr Univ, Copenhagen, Denmark. RI Ogendal, Lars/M-4644-2014 OI Ogendal, Lars/0000-0003-0609-3669 NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 240A EP 240A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401330 ER PT J AU Richard, JP Leikina, E Chernomordik, L AF Richard, Jean-Philippe Leikina, Evgenia Chernomordik, Leonid TI Cytoskeleton reorganization and syncytium formation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 244A EP 244A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401352 ER PT J AU Chen, AY Leikina, E Chernomordik, L AF Chen, Andrew Y. Leikina, Evgenia Chernomordik, Leonid TI Cell fusion mediated by baculovirus gp64: from local fusion to syncytium formation. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 245A EP 246A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401357 ER PT J AU Leikina, E Podbilewicz, B Sapir, AS Valansi, C Suissa, M Shemer, G Chernomordik, L AF Leikina, Evgenia Podbilewicz, Benjamin Sapir, Amir Sapir Valansi, Clari Suissa, Meital Shemer, Gidi Chernomordik, Leonid TI C. elegans EFF-1 mediates homotypic fusion of heterologous cells via hemifusion SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NICHD, Bethesda, MD USA. Technion Israel Inst Technol, Haifa, Israel. Technion Israel, Haifa, Israel. RI Podbilewicz, Benjamin/N-4825-2014; Sapir, Amir/C-5758-2015 OI Sapir, Amir/0000-0001-9888-1800 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 245A EP 245A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401354 ER PT J AU Puri, A Rawat, SS Zimmerman, C Johnson, BT Cho, E Lockett, SJ Blumenthal, R AF Puri, Ann Rawat, Satinder S. Zimmerman, Christina Johnson, Benitra T. Cho, Edward Lockett, Stephen J. Blumenthal, Robert TI Restricted lateral mobility of raft-associated CD4 results in inhibition of HIV-1 envelope glycoprotein mediated fusion SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NCI, Frederick, MD 21701 USA. RI Cho, Edward/B-3727-2012 OI Cho, Edward/0000-0002-0278-334X NR 2 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 246A EP 246A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401358 ER PT J AU Rafikova, ER Melikov, K Ramos, C Chernomordik, LV AF Rafikova, Elvira R. Melikov, Kamran Ramos, Corinne Chernomordik, Leonid V. TI Nuclear envelope assembly by fusion between nuclear membrane vesicles and protein-free liposomes. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, San Diego, CA 92103 USA. RI Melikov, Kamran/A-6604-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 247A EP 247A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401363 ER PT J AU Mazar, J Bezrukov, L Thomas, M Zimmerberg, J AF Mazar, Julia Bezrukov, Ludmila Thomas, Molly Zimmerberg, Joshua TI Adult stem cell - Lymphocyte interactions. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 253A EP 253A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401389 ER PT J AU Sauna, ZE Nandigama, K Anbudkar, SV AF Sauna, Zuben E. Nandigama, Krishnamachary Anbudkar, Suresh V. TI Catalytic cycle of ATP hydrolysis by P-glycoprotein (ABCB1): The E.S reaction intermediate with occluded ATP-gamma-S shows a high-affinity to low affinity switch at the transport substrate site SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 265A EP 265A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401445 ER PT J AU Bosmans, F Swartz, KJ AF Bosmans, Frank Swartz, Kenton J. TI Interaction of the gating-modifier toxin PaurTx3 with the voltageactivated sodium channel rNa(v)1.2a SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. RI Bosmans, Frank/A-9660-2013 OI Bosmans, Frank/0000-0002-6476-235X NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 269A EP 269A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401464 ER PT J AU Pillai, AD Solomon, T Pain, M Desai, SA AF Pillai, Ajay D. Solomon, Tsione Pain, Margaret Desai, Sanjay A. TI High affinity antagonists of the plasmodial surface anion channel inhibit nutrient acquisition by intraerythrocytic malaria parasites. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIAID, Lab Malaria & Vector Res, Rockville, MD USA. RI Desai, Sanjay/B-7110-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 272A EP 272A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401481 ER PT J AU Contreras, JE Srikumar, D Holmgren, M AF Contreras, Jorge E. Srikumar, Deepa Holmgren, Miguel TI The selectivity filter is the main gate in cyclic nucleotide gated (CNG) channels. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 282A EP 283A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401525 ER PT J AU Lukacs, V Thyagarajan, B Balla, A Vamai, P Balla, T Rohacs, T AF Lukacs, Viktor Thyagarajan, Baskaran Balla, Andras Vamai, Peter Balla, Tamas Rohacs, Tibor TI Dual regulation of TRPV1 by phosphatidylinositol 4,5-bisphosphate SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 290A EP 290A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401558 ER PT J AU Krepkiy, D Mihailescu, E Gawrisch, K Swartz, KJ AF Krepkiy, Dmitriy Mihailescu, Ella Gawrisch, Klaus Swartz, Kenton J. TI Influence of a potassium channel voltage sensor toxin on the structure of lipid membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NINDS, NIH, Mol Physiol & Biophys Sect, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA 92717 USA. NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. NIAAA, NIH, Lab Membrane Biochem & Biophys, NMR Sect, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 295A EP 295A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401578 ER PT J AU Milescu, M Swartz, KJ AF Milescu, Mirela Swartz, Kenton J. TI Influence of membrane alterations on the inhibition of K-v channels by voltage sensor toxins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NINDS, NIH, Porter Neurosci Res Ctr, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 295A EP 296A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401582 ER PT J AU Yu, LC Zaman, J Galperin, M Xu, S AF Yu, Leepo C. Zaman, Jessica Galperin, Mikail Xu, Sengen TI Structural effects of phosphorylation of myosin light chain in skeletal muscle. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 297A EP 297A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401588 ER PT J AU Sackett, DL AF Sackett, Dan L. TI Tubulin carboxy-terminal tail conformation is pH sensitive SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NICHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 309A EP 309A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972401646 ER PT J AU Combs, CA Smirnov, AV Knutson, JR Balaban, RS AF Combs, Christian A. Smirnov, Aleksandr V. Knutson, Jay R. Balaban, Robert S. TI Optimization of multi-photon excitation fluorescence microscopy emitted light detection SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 319A EP 319A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402041 ER PT J AU Chen, HM Puhl, HL Ikeda, SR AF Chen, Huanmian Puhl, Henry L., III Ikeda, Stephen R. TI Estimating protein-protein interaction affinity in living cells using quantitative FRET measurements SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIAAA, Lab Mol Physiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 322A EP 322A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402052 ER PT J AU Koushik, SV Chen, HM Thaler, C Puhl, HL Vogel, SS AF Koushik, Srinagesh V. Chen, Huanmian Thaler, Christopher Puhl, Henry L., III Vogel, Steven S. TI Genetically encoded FRET efficiency standards SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIAAA, Rockville, MD USA. RI Vogel, Steven/A-3585-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 322A EP 322A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402053 ER PT J AU Lin, DC Dimitriadis, EK Horkayne-Szakaly, I Basser, PJ Horkay, F AF Lin, David C. Dimitriadis, Emilios K. Horkayne-Szakaly, Iren Basser, Peter J. Horkay, Ferenc TI Swelling and biomechanical properties of tissue-engineering cartilage SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Inst Hlth, Bethesda, MD USA. RI Basser, Peter/H-5477-2011 NR 0 TC 0 Z9 0 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 334A EP 334A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402113 ER PT J AU Cohen, JA Podgomik, R Hansen, PL Parsegian, VA AF Cohen, Joel A. Podgomik, Rudi Hansen, Per Lyngs Parsegian, V. Adrian TI A universal one-parameter equation of state for osmotic pressures of neutral flexible polymers in good solvents SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NICHD, Phys Lab & Structural Biol, Bethesda, MD 20892 USA. Univ Pacific, San Francisco, CA USA. Univ Ljubljana, Ljubljana, Slovenia. Univ So Denmark, Odense, Denmark. NR 0 TC 0 Z9 0 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 335A EP 335A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402116 ER PT J AU Maltsev, AV Maltsev, VA Sirenko, SG Maltseva, LA Parsons, SP Lakatta, EG Stem, MD AF Maltsev, Anna V. Maltsev, Victor A. Sirenko, Syevda G. Maltseva, Larissa A. Parsons, Sean P. Lakatta, Edward G. Stem, Michael D. TI A simple stochastic mechanism of a roughly periodic Ca2+ clock within cardiac cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIA, Gerontol Res Ctr, NIH, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 344A EP 345A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402162 ER PT J AU Alcaraz, A Bezrukov, SM Aguilella, VM AF Alcaraz, Antonio Bezrukov, Sergey M. Aguilella, Vicente M. TI Divalent cations induce apparent inversion of OmpF cationic selectivity SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Univ Jaume 1, Castellon de La Plana, Spain. NIH, NICHD, Bethesda, MD 20892 USA. RI Aguilella, Vicente/B-7592-2008; Alcaraz, Antonio/F-8498-2016 OI Aguilella, Vicente/0000-0002-2420-2649; NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 345A EP 345A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402166 ER PT J AU Graves, AR Mindell, JA AF Graves, Austin R. Mindell, Joseph A. TI pH-dependent chloride transport in native lysosomal membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 347A EP 347A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402175 ER PT J AU Ryan, RM Mindell, JA AF Ryan, Renae M. Mindell, Joseph A. TI Is the chloride conductance of glutamate transporters evolutionarily conserved? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 347A EP 347A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402173 ER PT J AU Sinha, G Sabri, F Dimitriadis, E Iwasa, K AF Sinha, Ghanshyam Sabri, Firozeh Dimitriadis, Emilios Iwasa, Kuni TI Cytosolic surface of outer hair cells' plasma membrane: Search of membrane motor by atomic force microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIDCD, Bethesda, MD 20892 USA. NIH, ORS, DBEPS, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 348A EP 348A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402178 ER PT J AU Yadavalli, VK Forbes, JG Cruz, GG Wang, K AF Yadavalli, Vamsi K. Forbes, Jeffrey G. Cruz, Gustavo G. Wang, Kuan TI Nebulin elasticity and unfolding of transient alpha-helices: a stretched protein ruler pre-loads thin filaments of the skeletal muscle. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 349A EP 349A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402182 ER PT J AU Kannankeril, PJ Hlaing, T Coffa, S Akin, B Yang, T Zhang, W Pfeifer, K Jones, LR Knollmann, BC AF Kannankeril, Prince J. Hlaing, Thinn Coffa, Sergio Akin, Brandy Yang, Tao Zhang, Wei Pfeifer, Karl Jones, Larry R. Knollmann, Bjorn C. TI Modest reductions in cardiac calsequestrin render mice susceptible to ventricular arrhythmias SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Vanderbilt Univ, Sch Med, Nashville, TN 37212 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Indiana Univ, Sch Med, Krannert Inst Cardiol, Indianapolis, IN 46202 USA. NIH, NICHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 352A EP 352A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402196 ER PT J AU Kobrinsky, E Harry, JB Lao, QZ Ravindran, A Soldatov, NM AF Kobrinsky, Evgeny Harry, Jo Beth Lao, Qi Zong Ravindran, Arippa Soldatov, Nikolai M. TI beta 2-subunit facilitation of the Cav1.2 calcium channel current involves two independent determinants SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 353A EP 353A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402202 ER PT J AU Veatch, S Soubias, O Leung, S Keller, S Hancock, R Thewalt, J Gawrisch, K AF Veatch, Sarah Soubias, Olivier Leung, Sherry Keller, Sarah Hancock, Robert Thewalt, Jenifer Gawrisch, Klaus TI Complex phase behavior in 'simple' membranes: Phase diagram, critical behavior, and impurities in membranes of DOPC, DPPC, and cholesterol. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Cornell Univ, Ithaca, NY USA. Natl Inst Hlth, Rockville, MD USA. Simon Fraser Univ, Burnaby, BC V5A 1S6, Canada. Univ Washington, Seattle, WA 98195 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. NR 0 TC 1 Z9 1 U1 1 U2 9 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 356A EP 356A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402213 ER PT J AU Gruschus, JM Wu, XW Brooks, BR AF Gruschus, James M. Wu, Xiongwu Brooks, Bernard R. TI Protein-protein docking with the EMAP program of CHARMM: A map and grid based approach SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 368A EP 368A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402269 ER PT J AU Xu, JH Gleason, FK Toptygin, D Callis, PR Brand, L Knutson, JR AF Xu, Jianhua Gleason, Florence K. Toptygin, Dmitri Callis, Patrik R. Brand, Ludwig Knutson, Jay R. TI Femtosecond fluorescence dynamics of tryptophan in Anabaena and E-coli thioredoxins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Inst Hlth, Bethesda, MD USA. Univ Minnesota, Dept Plant Biol, St Paul, MN 55108 USA. Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. Montana State Univ, Dept Chem & Biochem, Bozeman, MT 59717 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 370A EP 370A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402280 ER PT J AU Abbondanzieri, EA Bokinsky, G Le Grice, SFJ Zhuang, XW AF Abbondanzieri, Elio A. Bokinsky, Gregory Le Grice, Stuart F. J. Zhuang, Xiaowei TI How does reverse transcriptase recognize nucleic acid substrates? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Harvard Univ, Cambridge, MA 02138 USA. Natl Canc Inst, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 372A EP 372A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402289 ER PT J AU Nahirney, PC Wang, K AF Nahirney, Patrick C. Wang, Kuan TI Biodiversity in Z bands of superfast muscles SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 372A EP 373A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402291 ER PT J AU Schroeder, J Luger-Hamer, M Kellman, P Ingalls, C Balaban, RS AF Schroeder, Jamie Luger-Hamer, Merav Kellman, Peter Ingalls, Christopher Balaban, Robert S. TI Quantitative analysis of function and structure of mouse skeletal muscle, in vivo, using multi-photon excitation microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. Georgia State Univ, Atlanta, GA 30303 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 373A EP 373A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402293 ER PT J AU Piszczek, G Fodor, E Peterkofsky, A Ginsburg, A AF Piszczek, Grzegorz Fodor, Elfrieda Peterkofsky, Alan Ginsburg, Ann TI Protein-protein interactions in a nitrogen signal pathway of E. coli SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NHLBI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 377A EP 377A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402313 ER PT J AU Rifkind, JM Ramasamy, S Nagababu, E AF Rifkind, Joseph M. Ramasamy, Somasundaram Nagababu, Enika TI Conformationally regulated uptake of nitrite by deoxyhemoglobin and release of the NO produced SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 383A EP 384A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402348 ER PT J AU Chiu, TK Li, M Davies, DR AF Chiu, Thang K. Li, Min Davies, David R. TI An induced-fit mechanism for substrate entry and enzyme catalysis in prolyl endopeptidase. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 385A EP 385A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402355 ER PT J AU Cachau, RE Krumpe, LRH Mori, T Ventura, ON Burt, SK AF Cachau, Raul E. Krumpe, Lauren R. H. Mori, Toshiyuki Ventura, Oscar N. Burt, Stanley K. TI Structural characterization of peptides from phage-display libraries SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Adv Biomed Comp Ctr, NCI, SAIC, Frederick, MD 21701 USA. NCI, SAIC, Mol Targets Dev Program, Frederick, MD USA. Takeda Pharmaceut Co Ltd, Osaka, Japan. Univ Republica, Fac Quim, CCPG DETEMA, Montevideo, Uruguay. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 388A EP 388A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402371 ER PT J AU Klauda, JB Brooks, BR AF Klauda, Jeffery B. Brooks, Bernard R. TI Structural changes in lactose permease and how sugar-type effects binding structure SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NHLBI, Bethesda, MD 20892 USA. RI Klauda, Jeffery/A-4345-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 393A EP 393A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402393 ER PT J AU Hoskins, JR Wickner, S AF Hoskins, Joel R. Wickner, Sue TI Interactions of E.coli ClpXP with RssB adapter protein and sigma(S) SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Natl Canc Inst, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 404A EP 405A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402450 ER PT J AU Camberg, JL Hoskins, J Wickner, S AF Camberg, Jodi L. Hoskins, Joel Wickner, Sue TI Degradation of the bacterial cell division protein FtsZ by ClpXP SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NCI, Mol Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 405A EP 405A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402451 ER PT J AU Yingling, YG Shapiro, BA AF Yingling, Yaroslava G. Shapiro, Bruce A. TI Theoretical investigation of formation and properties of RNA nanoparticles SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NCI, Frederick, MD 21701 USA. RI Yingling, Yaroslava/B-2901-2008 OI Yingling, Yaroslava/0000-0002-8557-9992 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 414A EP 414A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402500 ER PT J AU Tekle, E Wolfe, M Chock, PB AF Tekle, Ephrem Wolfe, Matt Chock, P. B. TI phagositic clearance of electric field induced 'apoptosis mimetic' cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NHLBI, NIH, LB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 421A EP 421A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402537 ER PT J AU Karpunin, DV Akimov, SA Zimmerberg, J Frolov, VA AF Karpunin, Dmitry V. Akimov, Sergei A. Zimmerberg, Joshua Frolov, Vadim A. TI Pore formation in lipid membranes containing lysolipids and cholesterol SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Shemyakin Ovchinnikov Inst Bioorgan Chem, Moscow, Russia. NICHD, NIH, Bethesda, MD USA. RAS, Inst Phys Chem & Electrochem, Moscow 117901, Russia. RI Akimov, Sergey/L-2001-2013; Akimov, Sergey/I-6432-2015 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 425A EP 425A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402557 ER PT J AU Shnyrova, A Ayllon, J Villar, E Zimmerberg, J Frolov, VA AF Shnyrova, Anna Ayllon, Juan Villar, Enrique Zimmerberg, Joshua Frolov, Vadim A. TI Reconstruction of membrane budding by viral matrix protein SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NHLBI, Bethesda, MD 20892 USA. Univ Salamanca, E-37008 Salamanca, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 427A EP 428A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402571 ER PT J AU Gawrisch, K Eldho, NV Mihailescu, E Kimura, T AF Gawrisch, Klaus Eldho, Nadukkudy V. Mihailescu, Ella Kimura, Tomohiro TI Structure, dynamics, and location of the endocannabinoid 2-AG in lipid bilayers - an NMR and neutron diffraction study SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIAAA, NIH, Bethesda, MD 92717 USA. Univ Calif Irvine, Dept Physiol & Biophys, Irvine, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 434A EP 434A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402602 ER PT J AU Rostovtseva, TK Hassanzadeh, E Sackett, DL Bezrukov, SM AF Rostovtseva, Tatiana K. Hassanzadeh, Elnaz Sackett, Dan L. Bezrukov, Sergey M. TI Tubulin regulates VDAC channel SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NICHD, NIH, LPSB, Bethesda, MD USA. NICHD, NIH, LIMB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 436A EP 436A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402610 ER PT J AU Li, MF Silberberg, SD Swartz, KJ AF Li, Mufeng Silberberg, Shai D. Swartz, Kenton J. TI Gated accessibility of MTS reagents to the pore of P2X receptor channels SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NINDS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 449A EP 449A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402668 ER PT J AU Kloda, JH Mitchell, DC AF Kloda, Jessica H. Mitchell, Drake C. TI Free fatty acids alter the function of inhibitory ligand gated ion channels. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIAAA, Sect Fluorescence Studies, LMBB, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 451A EP 451A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402677 ER PT J AU Plested, AJ Mayer, ML AF Plested, Andrew J. Mayer, Mark L. TI The anion binding site in kainate receptors SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NICHD, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 454A EP 455A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972402693 ER PT J AU Zahanich, H Tarasova, YS Boheler, KR Stern, MD Lakatta, EG Maltsev, VA AF Zahanich, Hor Tarasova, Yelena S. Boheler, Kenneth R. Stern, Michael D. Lakatta, Edward G. Maltsev, Victor A. TI Basal PKA-dependent protein phosphorylation contributes to generation of spontaneous action potentials in cardiomyocytes derived from mouse embryonic stem cells SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIA, NIH, Gerontol Res Ctr, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 461A EP 462A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403005 ER PT J AU Santos, MIB Swartz, K AF Santos, Maria Isabel Bahamonde Swartz, Kenton TI Compatibility of the paddle motif between Kv channels and voltage sensor proteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 467A EP 467A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403032 ER PT J AU Alabi, AA Swartz, KJ AF Alabi, AbdulRasheed A. Swartz, Kenton J. TI VSTx1 stabilizes a closed state in K(v)2.1-K(v)AP paddle chimeras SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NINDS, Porter Neurosci Res Ctr, Mol Phys & Biophys Sect, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 471A EP 471A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403049 ER PT J AU Amyot, F Small, A Boukari, H Plant, A McDaniel, D Gandjbakhche, A AF Amyot, Franck Small, Alex Boukari, Hacene Plant, Anne McDaniel, Denis Gandjbakhche, Amir TI Quantitative assay to study cell motility on collagen film SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NICHD, NIH, Bethesda, MD USA. NIST, Gaithersburg, MD 20899 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 484A EP 484A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403108 ER PT J AU Kim, KY Adelstein, RS AF Kim, Kye-Young Adelstein, Robert S. TI Defective cell-matrix attachment due to reduction of beta1-integrin expression in norimuscle myosin II null mouse embryonic fibroblasts SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 491A EP 491A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403141 ER PT J AU Forgacs, E Cartwright, S Kovacs, M Toth, J Conyers, B Tribby, M Webb, MR Corrie, JET Sellers, JR White, HD AF Forgacs, Eva Cartwright, Suzanne Kovacs, Mihaly Toth, Judit Conyers, Barbara Tribby, Marissa Webb, Martin R. Corrie, John E. T. Sellers, James R. White, Howard D. TI Mutational analysis of the myosinV active site SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Eastern Virginia Med Sch, Norfolk, VA 23501 USA. NIH, NHLBI, Bethesda, MD 20892 USA. Eotvos Lorand Univ, Budapest, Hungary. MRC, Natl Med Inst, London, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 493A EP 493A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403154 ER PT J AU Aronova, MA Kim, YC Sousa, AA Zhang, GF Leapman, RD AF Aronova, Maria A. Kim, Youngchan Sousa, Alioscka A. Zhang, Guofeng Leapman, Richard D. TI Quantitative three-dimensional elemental mapping of phosphorus using EFTEM tomography SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIBIB, Bethesda, MD USA. NIH, NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 509A EP 509A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403231 ER PT J AU Bartesaghi, A Sprechmann, P Randall, G Sapiro, G Subramaniam, S AF Bartesaghi, Alberto Sprechmann, Pablo Randall, Gregory Sapiro, Guillermo Subramaniam, Sriram TI A framework for classification and averaging of 3D tomographic volumes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. Univ Republica, Montevideo, Uruguay. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 509A EP 509A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403228 ER PT J AU Heymann, JAW Kim, S Shi, D Subramaniam, S AF Heymann, Jurgen A. W. Kim, Sang Shi, Dan Subramaniam, Sriram TI Three-dimensional visualization of cancer cells at 50 nm resolution using dual beam microscopy SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 509A EP 510A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403232 ER PT J AU Bennett, AE Liu, J Sougrat, R Subramaniam, S AF Bennett, Adam E. Liu, Jun Sougrat, Rachid Subramaniam, Sriram TI Electron tomographic analysis of HIV-1 envelope glycoproteins SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. Univ Cambridge, Dept Pharmacol, Cambridge CB2 1QJ, England. NR 2 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 510A EP 510A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403235 ER PT J AU Borgnia, MJ Subramaniam, S Milne, JLS AF Borgnia, Mario J. Subramaniam, Sriram Milne, Jacqueline L. S. TI 3D structure of a predatory bacterium SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NCI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 510A EP 510A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403233 ER PT J AU Lengyel, JS Wu, XW Stott, KM Schuck, P Perham, RN Subramaniam, S Milne, JLS AF Lengyel, Jeffrey S. Wu, Xiongwu Stott, Katherine M. Schuck, Peter Perham, Richard N. Subramaniam, Sriram Milne, Jacqueline L. S. TI Molecular architecture of the icosahedral pyruvate dehydrogenase complex SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. Univ Cambridge, Cambridge, England. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 510A EP 510A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403234 ER PT J AU Kotova, S Dimitriadis, EK Berzukov, L Zimmerberg, J Fera, A AF Kotova, Sveflana Dimitriadis, Emilios K. Berzukov, Ludmila Zimmerberg, Joshua Fera, Andrea TI Probing mechanical responses of influenza viral particles by imaging and nano-manipulation with an atomic force microscope. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIBIB, Bethesda, MD USA. NIH, LCBM, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 512A EP 513A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403246 ER PT J AU Lin, DC Dimitriadis, EK Horkay, F AF Lin, David C. Dimitriadis, Emilios K. Horkay, Ferenc TI Elastic modulus maps of soft, rubber-like gels and tissues from AFM nanoindentation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 514A EP 514A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403251 ER PT J AU Michelman-Ribeiro, A Sackett, D Horkay, F Nossal, R Boukari, H AF Michelman-Ribeiro, Ariel Sackett, Dan Horkay, Ferenc Nossal, Ralph Boukari, Hacene TI Comparison of fluorescence correlation spectroscopy measurements of probe diffusion in Poly(vinyl-alcohol) and flcoll70 solutions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 520A EP 520A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403280 ER PT J AU Forbes, JG Wang, K AF Forbes, Jeffrey G. Wang, Kuan TI Nanomechanics of intrinsically disordered muscle proteins: Computational approaches SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIAMSD, DHHS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 523A EP 524A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403297 ER PT J AU Best, RB Merchant, KA Louis, JM Gopich, IV Eaton, WA AF Best, Robert B. Merchant, Kusai A. Louis, John M. Gopich, Irina V. Eaton, William A. TI Structure and dynamics of unfolded proteins from single molecule FRET spectroscopy and molecular simulation SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. RI Best, Robert/H-7588-2016 OI Best, Robert/0000-0002-7893-3543 NR 0 TC 1 Z9 1 U1 1 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 534A EP 534A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972403349 ER PT J AU Asemu, G Fishbein, KW Canuto, HC Spencer, RGS Abernethy, DR Soldatov, NM AF Asemu, G. Fishbein, K. W. Canuto, H. C. Spencer, R. G. S. Abernethy, D. R. Soldatov, N. M. TI beta-Adrenegric stimulation of transgenic mouse overexpressing the exon-22 isoform of the human Cav1.2 alpha 1C channel enhanced development of cardiomyopathy as revealed by MRI imaging SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 542A EP 542A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404007 ER PT J AU Kimura, T Yeliseev, AA Rhodes, SD Gawrisch, K AF Kimura, Tomohiro Yeliseev, Alexei A. Rhodes, Steven D. Gawrisch, Klaus TI Reconstitution of a human peripheral cannabinoid receptor CB2 into phosphatidylcholine proteoliposomes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIAAA, NIH, Bethesda, MD USA. RI Yeliseev, Alexei/B-3143-2009 NR 0 TC 0 Z9 0 U1 1 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 556A EP 556A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404072 ER PT J AU Guy, HR Durell, SR AF Guy, H. Robert Durell, Stewart R. TI Structural models of lattice, fibril, and membrane-bound assemblies formed by the PrPSc prion protein SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NCI, NIH, Cell Biol Lab, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 559A EP 559A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404090 ER PT J AU Sen, A Baxa, U Simon, MN Wall, JS Sabate, R Saupe, SJ Steven, AC AF Sen, Anindito Baxa, Ulrich Simon, Martha N. Wall, Joseph S. Sabate, Raimon Saupe, Sven J. Steven, Alasdair C. TI Scanning transmission electron microscopy mass-per-length analysis and electron diffraction support the stacked beta-solenoid model of HET-s prion fibrils SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, NIAMS, Struct Biol Lab, Bethesda, MD 20892 USA. Brookhaven Natl Lab, Upton, NY 11973 USA. CNRS, Inst Biochim & Genet Cellulaire, Bordeaux, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 560A EP 560A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404091 ER PT J AU Jang, HB Nussinov, R AF Jang, Hyunbum Nussinov, Ruth TI Conformations and dynamics of the beta-sheet nanotube as an annular pore/channel in the lipid bilayer SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 SAIC, NCI, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 563A EP 563A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404109 ER PT J AU Zheng, J Tsai, CJ Nussinov, R AF Zheng, Jie Tsai, Chung-Jung Nussinov, Ruth TI Nanostructure design using protein building blocks SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Canc Inst, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 563A EP 563A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404110 ER PT J AU Tian, P AF Tian, Pu TI A molecular modelling study of autotransporter NaIP SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIDDK, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 565A EP 565A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404117 ER PT J AU Kamath, G Greene, S Guvench, O Pastor, R Brady, J MacKerell, AD AF Kamath, Ganesh Greene, Shannon Guvench, Olgun Pastor, Richard Brady, John MacKerell, Alexander D., Jr. TI CHARMM all-atom additive force field for carbohydrates SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Univ Baltimore, Baltimore, MD 21201 USA. NHLBI, NIH, Bethesda, MD 20892 USA. Cornell Univ, Ithaca, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 566A EP 566A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404124 ER PT J AU Yen, P Ventura, ON Burt, SK Cachau, RE AF Yen, Phillip Ventura, Oscar N. Burt, Stanley K. Cachau, Raul E. TI Fast pattern recognition of protein three dimensional features using a bit-pattern approach as a prescreen. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NCI, SAIC, Adv Biomed Comp Ctr, Frederick, MD 21701 USA. Univ Republica, Fac Quim, CCPG, DETEMA, Montevideo, Uruguay. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 567A EP 567A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404127 ER PT J AU Mekhedov, E Blank, PS Yin, SR Zimmerberg, J AF Mekhedov, Elena Blank, Paul S. Yin, Shu-Rong Zimmerberg, Joshua TI A novel method for analyzing cell surface protein density using intensity cumulative distribution functions SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NICHD, NIH, LCMB, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 571A EP 571A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404151 ER PT J AU Blank, PS Pata, V Zimmerberg, J AF Blank, Paul S. Pata, Veena Zimmerberg, Joshua TI Influenza hemagglutinin membrane localization and organization: a FRET distribution study. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 573A EP 573A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404159 ER PT J AU Bezrukov, L Blank, PS Polozov, IV Zimmerberg, J AF Bezrukov, Ludmila Blank, Paul S. Polozov, Ivan V. Zimmerberg, Josh TI Cyclodextrin differentially extracts cholesterol from cells and their membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NICHD, NIH, Cellular & Mol Biophys Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 574A EP 574A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404164 ER PT J AU Fera, A Farrington, JE Hess, ST Chen, XB Mekhedov, E Yin, SR Reese, T Zimmerberg, J AF Fera, Andrea Farrington, Jane E. Hess, Samuel T. Chen, Xiaobing Mekhedov, Elena Yin, Shu-Rong Reese, Thomas Zimmerberg, Joshua TI Probing the internal organization of the monomers in the influenza hemagglutinin. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NICHHD, NIH, Cellular & Mol Biophys Lab, Bethesda, MD 20892 USA. Univ Maine, Dept Phys & Astron, Orono, ME 04469 USA. NINDS, NIH, Neurobiol Lab, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 574A EP 574A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404163 ER PT J AU Shiu, B Boukari, H Banerjee, S Silver, J Youle, RJ Bezrukov, SM Rostovtseva, TK AF Shiu, Brian Boukari, Hacene Banerjee, Soojay Silver, Jonathan Youle, Richard J. Bezrukov, Sergey M. Rostovtseva, Tatiana K. TI Fluorescence based studies of endophilin B proteins and their interaction with lipid membranes SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NICHD, NIH, LPSB, Bethesda, MD USA. NICHD, NIH, LIMB, Bethesda, MD USA. NINDS, NIH, SNB, Bethesda, MD 20892 USA. NIAID, NIH, BVS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 575A EP 575A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404169 ER PT J AU Chen, YG Hummer, G AF Chen, Yng-Gwei Hummer, Gerhard TI Simulation of slow conformational dynamics of the calmodulin C-domain SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIDDK, NIH, Phys Chem Lab, Bethesda, MD USA. RI Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 595A EP 595A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404260 ER PT J AU Ostroumova, O Schagina, L Gurnev, P Takemoto, J Bezrukov, S AF Ostroumova, Olga Schagina, Ludmila Gurnev, Philip Takemoto, Jon Bezrukov, Sergey TI Probing pore geometry of the syringomycin E channel with polyethylene glycols SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Inst Cytol, St Petersburg, Russia. NICHD, NIH, Lab Phys & Stuctural Biol, Bethesda, MD USA. Utah State Univ, Logan, UT 84322 USA. RI Ostroumova, Olga/N-8636-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 613A EP 614A PG 2 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404346 ER PT J AU Nestorovich, EM Karginov, VA Bezrukov, SM AF Nestorovich, Ekaterina M. Karginov, Vladimir A. Bezrukov, Sergey M. TI Physical mechanisms of S-aureus alfa-Hemolysin and Bacillus anthracis lethal toxin inhibition by beta-cyclodextrin derivatives SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NICHD, Bethesda, MD USA. Innovat Biol Inc, Manassas, VA USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 614A EP 614A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404347 ER PT J AU Xie, L Gutierrez-Cruz, G Tsai, WL Wang, K AF Xie, Ling Gutierrez-Cruz, Gustavo Tsai, Wanxia L. Wang, Kuan TI beta Xin: Genes, splice variants and cellular distribution of a family of proteins implicated in the myofibrillogenesis of striated muscles. SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 622A EP 622A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404386 ER PT J AU Dahl, KN Scaffidi, P Islam, MF Yodh, AG Wilson, KL Misteli, T AF Dahl, Kris N. Scaffidi, Paola Islam, Mohammad F. Yodh, Arjun G. Wilson, Katherine L. Misteli, Tom TI Distinct structure, organization and mechanics of the nuclear lamina network in the premature aging disease Hutchinson-Gilford Progeria Syndrome SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Carnegie Mellon Univ, Pittsburgh, PA 15213 USA. NCI, NIH, Bethesda, MD USA. Univ Penn, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Baltimore, MD USA. RI Islam, Mohammad/B-7211-2011 OI Islam, Mohammad/0000-0001-9253-3709 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 631A EP 631A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404426 ER PT J AU Forgacs, E Cartwright, S Webb, M Sakamoto, T Selters, J White, H AF Forgacs, Eva Cartwright, Suzanne Webb, Martin Sakamoto, Takeshi Selters, Jim White, Howard TI The effect of IQ mutations upon the kinetics of ADP dissociation from ActomyosinV-HMM-ADP-Pi SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 Eastern Virginia Med Sch, Norfolk, VA 23501 USA. NIMR, London, England. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 637A EP 637A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404454 ER PT J AU Small, AR Neagu, A Amyot, F Sackett, D Chernomordik, V Gandjbakhche, A AF Small, Alexander R. Neagu, Adrian Amyot, Franck Sackett, Dan Chernomordik, Victor Gandjbakhche, Amir TI Which form of VEGF can guide endothelial cell migration? SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NICHHD, Bethesda, MD 20892 USA. Victor Babes Univ Med & Pharm, Timisoara, Romania. NR 0 TC 0 Z9 0 U1 1 U2 4 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 647A EP 647A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404504 ER PT J AU Milescu, LS Yildiz, A Selvin, PR Sachs, F AF Milescu, Lorin S. Yildiz, Ahmet Selvin, Paul R. Sachs, Frederick TI Maximum likelihood analysis of single molecule data SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 51st Annual Meeting of the Biophysical-Society CY MAR 03-07, 2007 CL Baltimore, MD SP Biophys Soc C1 NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Illinois, Urbana, IL 61801 USA. SUNY Buffalo, Buffalo, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2007 SU S BP 656A EP 656A PG 1 WC Biophysics SC Biophysics GA 132WA UT WOS:000243972404549 ER PT J AU Mochizuki, M Yamagata, N Philp, D Hozumi, K Watanabe, T Kikkawa, Y Kadoya, Y Kleinman, HK Nomizu, M AF Mochizuki, Mayumi Yamagata, Natsumi Philp, Deborah Hozumi, Kentaro Watanabe, Tadashi Kikkawa, Yamato Kadoya, Yuichi Kleinman, Hynda K. Nomizu, Motoyoshi TI Integrin-dependent cell behavior on ECM peptide-conjugated chitosan membranes SO BIOPOLYMERS LA English DT Article; Proceedings Paper CT 4th Peptide Engineering Meeting (PEM4) CY NOV 05-08, 2006 CL Yokohama, JAPAN DE extracellular matrix (ECM); cell adhesion; integrin; chitosan; peptide; laminin ID TERMINAL GLOBULAR DOMAIN; FIBRINOGEN-GAMMA-CHAIN; LAMININ ALPHA-1 CHAIN; NEURITE OUTGROWTH; SYNTHETIC PEPTIDES; BASEMENT-MEMBRANE; COLLAGEN ALPHA-1(IV)531-543; ADHESION SITES; BINDING-SITE; PC12 CELLS AB Extracellular matrix (ECM) plays an important role in tissue regeneration by promoting cell adhesion, migration, proliferation, and differentiation, ECM mimetics are of importance for tissue engineering because of their functions as scaffolds for cells. Previously, we developed Bioactive laminin-derived peptide-conjugated chistosan membranes and demonstrated their cell- and peptide-type specific functions. Here, we conjugated twelve integrin-binding peptides derived from ECM proteins onto chitosan membranes and examined biological activity. Seven peptide-chitosan membranes promoted human foreskin fibroblast attachment. Additionally, FIB1 (YAVTGRGDSPAS; from fibronectin), A99 (AGTFALRGDNPQG; from laminin alpha 1 chain), EF1zz (ATLQLQEGRLHFXFDLGKGR, X = Nle; from laminin alpha 1 chain), and 531 (GEFYFDLRLKGDKY; from collagen alpha 1 (IV) chain) conjugated chitosan membranes promoted integrin-dependent cell adhesion. Various integrins, including alpha v, beta 1, and beta 3, were involved in the cell adhecion to the peptide-chintosan membranes. Furthur, only the FIB1 and A99 chitosan membranes promoted neurite outgrowth with PC12 rat pheochromocytoma cells. These data demonstrate that peptide-chitosan membranes can regulate specific integrin-mediated cell responses and are useful constructs as ECM mimetics. (c) 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 122-130, 2007. C1 Tokyo Univ Pharm & Life Sci, Sch Pharm, Lab Clin Biochem, Hachioji, Tokyo 1920392, Japan. Hokkaido Univ, Grad Sch Environm Earth Sci, Sapporo, Hokkaido 0600810, Japan. NIDCR, NIH, Bethesda, MD 20892 USA. Kitasato Univ, Sch Med, Dept Anat, Sagamihara, Kanagawa 2288555, Japan. RP Nomizu, M (reprint author), Tokyo Univ Pharm & Life Sci, Sch Pharm, Lab Clin Biochem, Hachioji, Tokyo 1920392, Japan. EM nomizu@ps.toyaku.ac.jp RI Kikkawa, Yamato/D-1503-2010 NR 46 TC 28 Z9 28 U1 3 U2 8 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2007 VL 88 IS 2 BP 122 EP 130 DI 10.1002/bip.20684 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 151OC UT WOS:000245299000007 PM 17236208 ER PT J AU Lazar, KL Kurutz, JW Tycko, R AF Lazar, K. L. Kurutz, J. W. Tycko, R. TI Encapsulation and NMR on an aggregating peptide before fibrillogenesis SO BIOPOLYMERS LA English DT Meeting Abstract CT 20th American-Peptide-Society Symposium CY JUN 26-30, 2007 CL Montreal, CANADA SP Amer Peptide Soc C1 Univ Chicago, Dept Chem, Chicago, IL 60637 USA. Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA. NIDDK, NIH, Chem Phys Lab, Bethesda, MD 20892 USA. EM klazar@uchicago.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2007 VL 88 IS 4 SI SI BP 609 EP 609 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 181GT UT WOS:000247425900382 ER PT J AU Ghirlanda, G Fromme, R Fromme, P Katiliene, Z Bogani, F Giomarelli, B AF Ghirlanda, G. Fromme, R. Fromme, P. Katiliene, Z. Bogani, F. Giomarelli, B. TI A monovalent mutant of cyanovirin-N provides insight into the role of multiple interactions with gp120 for antiviral activity SO BIOPOLYMERS LA English DT Meeting Abstract CT 20th American-Peptide-Society Symposium CY JUN 26-30, 2007 CL Montreal, CANADA SP Amer Peptide Soc C1 Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. NCI, Ctr Canc Res, Frederick, MD 21702 USA. RI Fromme, Raimund/C-8885-2012 OI Fromme, Raimund/0000-0003-4835-1080 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PY 2007 VL 88 IS 4 SI SI BP 617 EP 617 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 181GT UT WOS:000247425900413 ER PT J AU Dobbin, KK Simon, RM AF Dobbin, Kevin K. Simon, Richard M. TI Sample size planning for developing classifiers using high-dimensional DNA microarray data SO BIOSTATISTICS LA English DT Article DE gene expression; microarrays; prediction; predictive inference; sample size ID PROGNOSTIC CLASSIFICATION; PREDICTION; CANCER AB Many gene expression studies attempt to develop a predictor of pre-defined diagnostic or prognostic classes. If the classes are similar biologically, then the number of genes that are differentially expressed between the classes is likely to be small compared to the total number of genes measured. This motivates a two-step process for predictor development, a subset of differentially expressed genes is selected for use in the predictor and then the predictor constructed from these. Both these steps will introduce variability into the resulting classifier, so both must be incorporated in sample size estimation. We introduce a methodology for sample size determination for prediction in the context of high-dimensional data that captures variability in both steps of predictor development. The methodology is based on a parametric probability model, but permits sample size computations to be carried out in a practical manner without extensive requirements for preliminary data. We find that many prediction problems do not require a large training set of arrays for classifier development. C1 NCI, Biometr Res Branch, Rockville, MD 20852 USA. RP Dobbin, KK (reprint author), NCI, Biometr Res Branch, 6130 Execut Blvd, Rockville, MD 20852 USA. EM dobbinke@mail.nih.gov NR 16 TC 69 Z9 72 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JAN PY 2007 VL 8 IS 1 BP 101 EP 117 DI 10.1093/biostatistics/kxj036 PG 17 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 115DQ UT WOS:000242715400007 PM 16613833 ER PT J AU Bratko, D Cellmer, T Prausnitz, JM Blanch, HW AF Bratko, Dusan Cellmer, Troy Prausnitz, John M. Blanch, Harvey W. TI Molecular simulation of protein aggregation SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE proteins; aggregation prevention; computer modeling ID SPONTANEOUS FIBRIL FORMATION; BETA-AMYLOID PEPTIDE; DYNAMICS SIMULATIONS; LATTICE-MODEL; POLYALANINE PEPTIDES; SEQUENCE; THERMODYNAMICS; COMPETITION; OLIGOMERS; BEHAVIOR AB Computer simulation offers unique possibities for investigating molecular-level phenomena difficult to probe experimentally. Drawing from a wealth of studies concerning protein folding, computational studies of protein aggregation are emerging. These studies have been successful in capturing aspects of aggregation known from experiment and are being used to refine experimental methods aimed at abating aggregation. Here we review molecular simulation studies of protein aggregation conducted in our laboratory. Specific attention is devoted to issues with implications for biotechnology. C1 Univ Calif Berkeley, Dept Chem Engn, Berkeley, CA 94720 USA. Virginia Commonwealth Univ, Dept Chem, Richmond, VA 23284 USA. NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Lawrence Berkeley Natl Lab, Div Chem Sci, Berkeley, CA 94720 USA. RP Blanch, HW (reprint author), Univ Calif Berkeley, Dept Chem Engn, Berkeley, CA 94720 USA. EM blanch@berkeley.edu NR 36 TC 18 Z9 18 U1 3 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JAN 1 PY 2007 VL 96 IS 1 BP 1 EP 8 DI 10.1002/bit.21232 PG 8 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 121SE UT WOS:000243176500001 PM 17136749 ER PT J AU Kawai, T Choi, U Cardwell, L DeRavin, SS Naumann, N Whiting-Theobald, NL Linton, GF Moon, J Murphy, PM Malech, HL AF Kawai, Toshinao Choi, Uimook Cardwell, Lanise DeRavin, Suk See Naumann, Nora Whiting-Theobald, Narda L. Linton, Gilda F. Moon, Jaehyun Murphy, Philip M. Malech, Harry L. TI WHIM syndrome myelokathexis reproduced in the NOD/SCID mouse xenotransplant model engrafted with healthy human stem cells transduced with C-terminus-truncated CXCR4 SO BLOOD LA English DT Article ID CHRONIC GRANULOMATOUS-DISEASE; HEMATOPOIETIC PROGENITOR CELLS; RECEPTOR BETA-CHAIN; G-CSF; MONOCLONAL-ANTIBODY; GENE-THERAPY; BONE-MARROW; IN-VIVO; MOBILIZATION; EXPRESSION AB WHIM (warts, hypogammaglobullnemia, recurrent bacterial infection, and myelokathexis) syndrome is a rare immunodeficiency caused in many cases by autosomal dominant C-terminal truncation mutations in the chemokine receptor CXCR4. A prominent and unexplained feature of WHIM is myelokathexis (hypercellularity with apoptosis of mature myeloid cells in bone marrow and neutropenia). We transduced healthy human CD34(+) peripheral blood-mobilized stem cells (PBSCs) with retrovirus vector encoding wild-type (wt) CXCR4 or WHIM-type mutated CXCR4 and studied these cells ex vivo in culture and after engraftment in a nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mouse xenograft model. Neither wt CXCR4 nor mutated CXCR4 transgene expression itself enhanced apoptosis of neutrophils arising in transduced PBSC cultures even with stimulation by a CXCR4 agonist, stromal cell-derived factor-1 (SDF-1 [CXCL12]). Excess wt CXCR4 expression by transduced human PBSCs enhanced marrow engraftment, but did not affect bone marrow (BM) apoptosis or the release of transduced leukocytes into PB. However, mutated CXCR4 transgene expression further enhanced BM engraftment, but was associated with a significant increase in apoptosis of transduced cells in BM and reduced release of transduced leukocytes into PB. We conclude that increased apoptosis of mature myeloid cells in WHIM is secondary to a failure of marrow release and progression to normal myeloid cell senescence, and not a direct effect of activation of mutated CXCR4. C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. Jikei Univ, Dept Genet Therapy, Sch Med, Inst DNA Med, Tokyo 201, Japan. Jikei Univ, Dept Pediat, Sch Med, Tokyo 201, Japan. RP Malech, HL (reprint author), NIAID, Host Def Lab, NIH, Bldg 10 CRC 5 W Labs,Rm 5-3750,10 Ctr Dr MSC 1456, Bethesda, MD 20892 USA. EM hmalech@nih.gov OI Malech, Harry/0000-0001-5874-5775 NR 35 TC 53 Z9 54 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 JAN 1 PY 2007 VL 109 IS 1 BP 78 EP 84 DI 10.1182/blood-2006-05-025296 PG 7 WC Hematology SC Hematology GA 121JM UT WOS:000243153900023 PM 16946301 ER PT J AU Mestre-Escorihuela, C Rubio-Moscardo, F Richter, JA Siebert, R Climent, J Fresquet, V Beltran, E Agirre, X Marugan, I Marin, M Rosenwald, A Sugimoto, KJ Wheat, LM Karran, EL Garcia, JF Sanchez, L Prosper, F Staudt, LM Pinkel, D Dyer, MJS Martinez-Climent, JA AF Mestre-Escorihuela, Cinta Rubio-Moscardo, Fanny Richter, Jose A. Siebert, Reiner Climent, Joan Fresquet, Vicente Beltran, Elena Agirre, Xabier Marugan, Isabel Marin, Miguel Rosenwald, Andreas Sugimoto, Kei-ji Wheat, Luise M. Karran, E. Loraine Garcia, Juan F. Sanchez, Lydia Prosper, Felipe Staudt, Louis M. Pinkel, Daniel Dyer, Martin J. S. Martinez-Climent, Jose A. TI Homozygous deletions localize novel tumor suppressor genes in B-cell lymphomas SO BLOOD LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; DNA COPY NUMBER; CHROMOSOMAL IMBALANCES; P53-INDUCED APOPTOSIS; CANDIDATE ONCOGENE; ANALYSIS REVEALS; TRANSGENIC MICE; CYCLIN D1; AMPLIFICATION; EXPRESSION AB Integrative genomic and gene-expression analyses have identified amplified oncogenes in B-cell non-Hodgkin lymphoma (B-NHL), but the capability of such technologies to localize tumor suppressor genes within homozygous deletions remains unexplored. Array-based comparative genomic hybridization (CGH) and gene-expression microarray analysis of 48 cell lines derived from patients with different B-NHLs delineated 20 homozygous deletions at 7 chromosome areas, all of which contained tumor suppressor gene targets. Further investigation revealed that only a fraction of primary biopsies presented inactivation of these genes by point mutation or intragenic deletion, but instead some of them were frequently silenced by epigenetic mechanisms. Notably, the pattern of genetic and epigenetic inactivation differed among B-NHL subtypes. Thus, the P53-inducible PIG7/LITAF was silenced by homozygous deletion in primary mediastinal B-cell lymphoma and by promoter hypermethylation in germinal center lymphoma, the proapoptotic BIM gene presented homozygous deletion in mantle cell lymphoma and promoter hypermethylation in Burkitt lymphoma, the proapoptotic BH3-only NOXA was mutated and preferentially silenced in diffuse large B-cell lymphoma, and INK4c/P18 was silenced by biallelic mutation in mantle-cell lymphoma. Our microarray strategy has identified novel candidate tumor suppressor genes inactivated by genetic and epigenetic mechanisms that substantially vary among the B-NHL subtypes. (c) 2007 by The American Society of Hematology C1 Univ Navarra, Div Oncol, Ctr Appl Med Res, CIMA, Pamplona 31008, Spain. Univ Kiel, Inst Human Genet, Hosp Schleswig Holstein, Kiel, Germany. Univ Valencia, Dept Hematol & Med Oncol, Hosp Clin, Valencia, Spain. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. Univ Leicester, MRC, Toxicol Unit, Leicester, Leics, England. Natl Ctr Oncol Res, Mol Pathol Program, CNIO, Madrid, Spain. NCI, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Canc Res Inst, San Francisco, CA 94143 USA. RP Martinez-Climent, JA (reprint author), Univ Navarra, Div Oncol, Ctr Appl Med Res, CIMA, Avda Pio 12,55, Pamplona 31008, Spain. EM jamcliment@unav.es RI Siebert, Reiner/A-8049-2010; Beltran, Elena/K-8785-2014; Rubio Moscardo, Francisca/L-6247-2014; Martinez-Climent, Jose/I-9199-2012; GARCIA, JUAN/L-2118-2016; Dyer, Martin/F-2691-2014 OI Rubio Moscardo, Francisca/0000-0002-3609-9992; Martinez-Climent, Jose/0000-0002-7938-3950; Sugimoto, Keiji/0000-0001-9835-5405; Prosper, Felipe/0000-0001-6115-8790; Dyer, Martin/0000-0002-5033-2236 FU Medical Research Council [MC_U132670597] NR 38 TC 143 Z9 151 U1 2 U2 13 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JAN 1 PY 2007 VL 109 IS 1 BP 271 EP 280 DI 10.1182/blood-2006-06-026500 PG 10 WC Hematology SC Hematology GA 121JM UT WOS:000243153900047 PM 16960149 ER PT J AU Nelson, RG Tuttle, KR AF Nelson, Robert G. Tuttle, Katherine R. CA NK Foundation TI The new KDOQI (TM) clinical practice guidelines and clinical practice recommendations for diabetes and CKD SO BLOOD PURIFICATION LA English DT Article; Proceedings Paper CT 9th International Conference on Dialysis CY JAN 24-26, 2007 CL Austin, TX SP Renal Res Inst DE chronic kidney disease; diabetes; guidelines, KDOQI AB Background/Aims: The National Kidney Foundation ( NKF) recently published new guidelines and clinical practice recommendations for the diagnosis and management of patients with diabetes and chronic kidney disease ( CKD). Methods: Guidelines were developed using an evidence-based approach. When sufficient evidence was lacking, recommendations were developed that reflect expert opinion. Results: Guidelines describe the process for screening and diagnosis of kidney disease in the setting of diabetes and the management of hyperglycemia, hypertension, dyslipidemia, and nutrition. Recommendations describe the management of albuminuria in the normotensive diabetic patient and the potential value of albuminuria as a marker of treatment efficacy; the impact of diabetes and CKD in special populations; the importance of behavioral self-management; and the value of intensive multifaceted intervention in these high risk patients. Conclusions: The new guidelines and recommendations update and extend the scope of the NKF's Kidney Disease Outcomes Quality Initiative ( KDOQI (TM)). Copyright (c) 2007 S. Karger AG, Basel. C1 NIDDKD, NIH, Phoenix Epidemiol & Clin Res Branch, Phoenix, AZ 85014 USA. Providence Med Res Ctr, Spokane, WA USA. RP Nelson, RG (reprint author), NIDDKD, NIH, Phoenix Epidemiol & Clin Res Branch, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rgnelson@mail.nih.gov RI Nelson, Robert/B-1470-2012 NR 10 TC 13 Z9 18 U1 0 U2 2 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0253-5068 J9 BLOOD PURIFICAT JI Blood Purif. PY 2007 VL 25 IS 1 BP 112 EP 114 DI 10.1159/000096407 PG 3 WC Hematology; Urology & Nephrology SC Hematology; Urology & Nephrology GA 117BP UT WOS:000242848000019 PM 17170547 ER PT J AU Kato, GJ Gladwin, MT Steinberg, MH AF Kato, Gregory J. Gladwin, Mark T. Steinberg, Martin H. TI Deconstructing sickle cell disease: Reappraisal of the role of hemolysis in the development of clinical subphenotypes SO BLOOD REVIEWS LA English DT Review DE sickle cell; pulmonary hypertension; priapism; ulcer; hemolysis; nitric oxide ID BETA-THALASSEMIA MAJOR; PRIAPISM FOLLOWING SPLENECTOMY; PYRUVATE-KINASE DEFICIENCY; TRANSCRANIAL DOPPLER ULTRASONOGRAPHY; NITRIC-OXIDE BIOAVAILABILITY; NF-KAPPA-B; PULMONARY-HYPERTENSION; ALPHA-THALASSEMIA; LEG ULCERS; HEREDITARY SPHEROCYTOSIS AB Hemotysis, long discounted as a critical measure of sickle cell disease severity when compared with sickle vaso-occlusion, may be the proximate cause of some disease complications. New mechanistic information about hemotysis and its effects on nitric oxide (NO) biology and further examination of the subpheno-types of disease requires a reappraisal and deconstruction of the clinical features of sickle cell disease. The biology underlying clinical phenotypes linked to hemotysis may increase our understanding of the pathogenesis of other chronic hemolytic diseases while providing new insights into treating sickle cell disease. The pathophysiological roles of dysregulated NO homeostasis and sickle reticulocyte adherence have linked hemolysis and hemolytic rate to sickle vasculopathy. Nitric oxide binds soluble guanylate cyclase which converts GTP to cGMP, relaxing vascular smooth muscle and causing vasoditatation. When plasma hemoglobin liberated from intravascutarly hemolyzed sickle erythrocytes consumes NO, the normal balance of vasoconstriction:vasodflation is skewed toward vasoconstriction. Pulmonary hypertension, priapism, leg ulceration and stroke, all subphenotypes of sickle cell disease, can be Linked to the intensity of hemotysis. Hemotysis plays less of a role in the vaso-occlusive-viscosity complications of disease like the acute painful episode, osteonecrosis of bone and the acute chest syndrome. Agents that decrease hemolysis or restore NO bioavailability or responsiveness may have potential to reduce the incidence and severity of the hemotytic subphenotypes of sickle cell disease. Some of these drugs are now being studied in clinical trials. (c) 2006 Elsevier Ltd. All rights reserved. C1 NHLBI, Vasc Med Branch, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. Boston Med Ctr, Ctr Excellence Sickle Cell Dis, Boston, MA 02118 USA. RP Kato, GJ (reprint author), NHLBI, Vasc Med Branch, 10 Ctr Dr,Bldg 10CRC 5-5140, Bethesda, MD 20892 USA. EM gkato@mail.nih.gov RI Kato, Gregory/I-7615-2014; OI Kato, Gregory/0000-0003-4465-3217; Steinberg, Martin/0000-0001-8800-8020 FU Intramural NIH HHS [Z99 HL999999, ZIA HL006014-02]; NHLBI NIH HHS [R01 HL68970, R01 HL70735, U554 HL 0708819] NR 124 TC 320 Z9 342 U1 1 U2 11 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0268-960X J9 BLOOD REV JI Blood Rev. PD JAN PY 2007 VL 21 IS 1 BP 37 EP 47 DI 10.1016/j.blre.2006.07.001 PG 11 WC Hematology SC Hematology GA 135RH UT WOS:000244170200003 PM 17084951 ER PT J AU Ruttenberg, A Clark, T Bug, W Samwald, M Bodenreider, O Chen, H Doherty, D Forsberg, K Gao, Y Kashyap, V Kinoshita, J Luciano, J Marshall, MS Ogbuji, C Rees, J Stephens, S Wong, GT Wu, E Zaccagnini, D Hongsermeier, T Neumann, E Herman, I Cheung, KH AF Ruttenberg, Alan Clark, Tim Bug, William Samwald, Matthias Bodenreider, Olivier Chen, Helen Doherty, Donald Forsberg, Kerstin Gao, Yong Kashyap, Vipul Kinoshita, June Luciano, Joanne Marshall, M. Scott Ogbuji, Chimezie Rees, Jonathan Stephens, Susie Wong, Gwendolyn T. Wu, Elizabeth Zaccagnini, Davide Hongsermeier, Tonya Neumann, Eric Herman, Ivan Cheung, Kei-Hoi TI Methodology - Advancing translational research with the Semantic Web SO BMC BIOINFORMATICS LA English DT Article ID LONG-TERM POTENTIATION; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE; NEUROTROPHIC FACTORS; DATABASE; NEURONS; BRAIN; INFORMATION; ONTOLOGY; MEMORY AB Background: A fundamental goal of the U. S. National Institute of Health (NIH) "Roadmap" is to strengthen Translational Research, defined as the movement of discoveries in basic research to application at the clinical level. A significant barrier to translational research is the lack of uniformly structured data across related biomedical domains. The Semantic Web is an extension of the current Web that enables navigation and meaningful use of digital resources by automatic processes. It is based on common formats that support aggregation and integration of data drawn from diverse sources. A variety of technologies have been built on this foundation that, together, support identifying, representing, and reasoning across a wide range of biomedical data. The Semantic Web Health Care and Life Sciences Interest Group (HCLSIG), set up within the framework of the World Wide Web Consortium, was launched to explore the application of these technologies in a variety of areas. Subgroups focus on making biomedical data available in RDF, working with biomedical ontologies, prototyping clinical decision support systems, working on drug safety and efficacy communication, and supporting disease researchers navigating and annotating the large amount of potentially relevant literature. Results: We present a scenario that shows the value of the information environment the Semantic Web can support for aiding neuroscience researchers. We then report on several projects by members of the HCLSIG, in the process illustrating the range of Semantic Web technologies that have applications in areas of biomedicine. Conclusion: Semantic Web technologies present both promise and challenges. Current tools and standards are already adequate to implement components of the bench-to-bedside vision. On the other hand, these technologies are young. Gaps in standards and implementations still exist and adoption is limited by typical problems with early technology, such as the need for a critical mass of practitioners and installed base, and growing pains as the technology is scaled up. Still, the potential of interoperable knowledge sources for biomedicine, at the scale of the World Wide Web, merits continued work. C1 Yale Univ, Sch Med, Ctr Med Informat, New Haven, CT 06520 USA. Yale Univ, Sch Med, W3C, New Haven, CT USA. Teranode Corp, Seattle, WA USA. Language & Comp, Reston, VA USA. Oracle, Burlington, MA USA. Sci Commons, Cambridge, MA USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Univ Amsterdam, Integrat Bioinformat Unit, Amsterdam, Netherlands. Harvard Univ, Sch Med, Boston, MA 02115 USA. Alzheimer Res Forum, Boston, MA USA. Partners HealthCare Syst, Wellesley, MA USA. Massachusetts Gen Hosp, MassGen Inst Neurodegenerat Dis, Charlestown, MA USA. AstraZeneca, Molndal, Sweden. Brainstage Res, Pittsburgh, PA USA. Agfa Healthcare, Waterloo, ON, Canada. Natl Lib Med, Bethesda, MD USA. Med Univ Vienna, Sect Med Expert & Knowledge Based Syst, Vienna, Austria. Drexel Univ, Coll Med, Dept Neurobiol & Anat, Lab Bioimaging & Anat Informat, Philadelphia, PA 19104 USA. Harvard Univ, Initiat Innovat Comp, Cambridge, MA 02138 USA. Millennium Pharmaceut Inc, Cambridge, MA USA. RP Cheung, KH (reprint author), Yale Univ, Sch Med, Ctr Med Informat, 333 Cedar St, New Haven, CT 06520 USA. EM alanruttenberg@gmail.com; tim_clark@harvard.edu; William.Bug@drexelmed.edu; samwald@gmx.at; olivier@nlm.nih.gov; helen.chen@agfa.com; donald.doherty@brainstage.com; kerstin.l.forsberg@astrazeneca.com; ygao@partners.org; vkashyap1@partners.org; junekino@alzforum.org; jluciano@cs.man.ac.uk; marshall@science.uva.nl; ogbujic@bio.ri.ccf.org; jar28@mumble.net; susie.stephens@gmail.com; wonglabow@verizon.net; ewu@alzforum.org; davide@landcglobal.com; thongsermeier@partners.org; eneumann@teranode.com; ivan@w3.org; kei.cheung@yale.edu OI Ruttenberg, Alan/0000-0002-1604-3078 FU Intramural NIH HHS [Z99 LM999999]; NCRR NIH HHS [RR043050-S2]; NIDCD NIH HHS [P01 DC004732, P01 DC04732]; NIMH NIH HHS [P20 MH062009, P20 MH62009] NR 85 TC 115 Z9 116 U1 0 U2 25 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2007 VL 8 SU 3 AR S2 DI 10.1186/1471-2105-8-S3-S2 PG 16 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 169OV UT WOS:000246602400002 PM 17493285 ER PT J AU Dumas, F Stanyon, R Sineo, L Stone, G Bigoni, F AF Dumas, Francesca Stanyon, Roscoe Sineo, Luca Stone, Gary Bigoni, Francesca TI Phylogenomics of species from four genera of New World monkeys by flow sorting and reciprocal chromosome painting SO BMC EVOLUTIONARY BIOLOGY LA English DT Article; Proceedings Paper CT 2nd Congress of Italian Evolutionary Biologists/1st Congress of the Italian-Society-for-Evolutionary-Biology CY SEP 04-07, 2006 CL Florence, ITALY SP Italian Soc Evolutionary Biol ID IN-SITU HYBRIDIZATION; PRIMATE PHYLOGENY; GENOMIC REARRANGEMENTS; ANCESTRAL KARYOTYPE; DIVERGENCE TIMES; PLATYRRHINE MONKEYS; MOLECULAR PHYLOGENY; MITOCHONDRIAL-DNA; ZOO-FISH; EVOLUTION AB Background: The taxonomic and phylogenetic relationships of New World monkeys (Platyrrhini) are difficult to distinguish on the basis of morphology and because diagnostic fossils are rare. Recently, molecular data have led to a radical revision of the traditional taxonomy and phylogeny of these primates. Here we examine new hypotheses of platyrrhine evolutionary relationships by reciprocal chromosome painting after chromosome flow sorting of species belonging to four genera of platyrrhines included in the Cebidae family: Callithrix argentata (silvered-marmoset), Cebuella pygmaea (pygmy marmoset), Callimico goeldii (Goeldi's marmoset) and Saimiri sciureus (squirrel monkey). This is the first report of reciprocal painting in marmosets. Results: The paints made from chromosome flow sorting of the four platyrrhine monkeys provided from 42 to 45 hybridization signals on human metaphases. The reciprocal painting of monkey probes on human chromosomes revealed that 21 breakpoints are common to all four studied species. There are only three additional breakpoints. A breakpoint on human chromosome 13 was found in Callithrix argentata, Cebuella pygmaea and Callimico goeldii, but not in Saimiri sciureus. There are two additional breakpoints on human chromosome 5: one is specific to squirrel monkeys, and the other to Goeldi's marmoset. Conclusion: The reciprocal painting results support the molecular genomic assemblage of Cebidae. We demonstrated that the five chromosome associations previously hypothesized to phylogenetically link tamarins and marmosets are homologous and represent derived chromosome rearrangements. Four of these derived homologous associations tightly nest Callimico goeldii with marmosets. One derived association 2/15 may place squirrel monkeys within the Cebidae assemblage. An apparently common breakpoint on chromosome 5q33 found in both Saimiri and Aotus nancymae could be evidence of a phylogenetic link between these species. Comparison with previous reports shows that many syntenic associations found in platyrrhines have the same breakpoints and are homologous, derived rearrangements showing that the New World monkeys are a closely related group of species. Our data support the hypothesis that the ancestral karyotype of the Platyrrhini has a diploid number of 2n = 54 and is almost identical to that found today in capuchin monkeys; congruent with a basal position of the Cebidae among platyrrhine families. C1 Univ Palermo, Dipartimento Biol Anim, Palermo, Italy. Dipartimento Biol Anim & Genet, Lab Antropol, I-50122 Florence, Italy. NCI, Frederick, MD 21701 USA. RP Sineo, L (reprint author), Univ Palermo, Dipartimento Biol Anim, Via Archirafi 18, Palermo, Italy. EM labhomo@unipa.it; roscoe.stanyon@unifi.it; llsineo@unipa.it; gstone@ncifcrf.gov; francesca.bigoni@unifi.it OI Stanyon, Roscoe/0000-0002-7229-1092 NR 76 TC 8 Z9 9 U1 1 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PY 2007 VL 7 SU 2 AR S11 DI 10.1186/1471-2148-7-S2-S11 PG 14 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 216PR UT WOS:000249891300011 PM 17767727 ER PT J AU Benjamin, EJ Dupuis, J Larson, MG Lunetta, KL Booth, SL Govindaraju, DR Kathiresan, S Keaney, JF Keyes, MJ Lin, JP Meigs, JB Robins, SJ Rong, J Schnabel, R Vita, JA Wang, TJ Wilson, PWF Wolf, PA Vasan, RS AF Benjamin, Emelia J. Dupuis, Josee Larson, Martin G. Lunetta, Kathryn L. Booth, Sarah L. Govindaraju, Diddahally R. Kathiresan, Sekar Keaney, John F., Jr. Keyes, Michelle J. Lin, Jing-Ping Meigs, James B. Robins, Sander J. Rong, Jian Schnabel, Renate Vita, Joseph A. Wang, Thomas J. Wilson, Peter W. F. Wolf, Philip A. Vasan, Ramachandran S. TI Genome-wide association with select biomarker traits in the Framingham Heart Study SO BMC MEDICAL GENETICS LA English DT Article ID C-REACTIVE PROTEIN; MONOCYTE CHEMOATTRACTANT PROTEIN-1; INTERCELLULAR-ADHESION MOLECULE-1; SINGLE NUCLEOTIDE POLYMORPHISM; ALKALINE-PHOSPHATASE ACTIVITY; GAMMA-GLUTAMYL-TRANSFERASE; NATRIURETIC PEPTIDE LEVELS; PLASMA CRP LEVELS; CARDIOVASCULAR-DISEASE; MYOCARDIAL-INFARCTION AB Background: Systemic biomarkers provide insights into disease pathogenesis, diagnosis, and risk stratification. Many systemic biomarker concentrations are heritable phenotypes. Genome-wide association studies ( GWAS) provide mechanisms to investigate the genetic contributions to biomarker variability unconstrained by current knowledge of physiological relations. Methods: We examined the association of Affymetrix 100K GeneChip single nucleotide polymorphisms ( SNPs) to 22 systemic biomarker concentrations in 4 biological domains: inflammation/oxidative stress; natriuretic peptides; liver function; and vitamins. Related members of the Framingham Offspring cohort ( n = 1012; mean age 59 +/- 10 years, 51% women) had both phenotype and genotype data ( minimum-maximum per phenotype n = 507-1008). We used Generalized Estimating Equations ( GEE), Family Based Association Tests ( FBAT) and variance components linkage to relate SNPs to multivariable-adjusted biomarker residuals. Autosomal SNPs ( n = 70,987) meeting the following criteria were studied: minor allele frequency >= 10%, call rate >= 80% and Hardy-Weinberg equilibrium p >= 0.001. Results: With GEE, 58 SNPs had p < 10(-6): the top SNPs were rs2494250 ( p = 1.00* 10(-14)) and rs4128725 ( p = 3.68* 10(-12)) for monocyte chemoattractant protein-1 ( MCP1), and rs2794520 ( p = 2.83* 10(-8)) and rs2808629 ( p = 3.19* 10(-8)) for C-reactive protein ( CRP) averaged from 3 examinations ( over about 20 years). With FBAT, 11 SNPs had p < 10(-6): the top SNPs were the same for MCP1 ( rs4128725, p = 3.28* 10(-8), and rs2494250, p = 3.55* 10(-8)), and also included B-type natriuretic peptide ( rs437021, p = 1.01* 10(-6)) and Vitamin K percent undercarboxylated osteocalcin ( rs2052028, p = 1.07* 10(-6)). The peak LOD ( logarithm of the odds) scores were for MCP1 ( 4.38, chromosome 1) and CRP ( 3.28, chromosome 1; previously described) concentrations; of note the 1.5 support interval included the MCP1 and CRP SNPs reported above ( GEE model). Previous candidate SNP associations with circulating CRP concentrations were replicated at p < 0.05; the SNPs rs2794520 and rs2808629 are in linkage disequilibrium with previously reported SNPs. GEE, FBAT and linkage results are posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Conclusion: The Framingham GWAS represents a resource to describe potentially novel genetic influences on systemic biomarker variability. The newly described associations will need to be replicated in other studies. C1 Framingham Haert Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Dept Math & Stat, Boston, MA USA. Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Broad Inst Massachusette Inst Technol, Cambridge, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Dept Med, Boston, MA 02115 USA. NHLBI, NIH, Off Biostat Res, Bethesda, MD 20892 USA. Emory Sch Med, Atlanta, GA USA. RP Benjamin, EJ (reprint author), Framingham Haert Study, NHLBI, Framingham, MA 01702 USA. EM emelia@bu.edu; dupuis@bu.edu; mlarson@bu.edu; klunetta@bu.edu; sarah.booth@tufts.edu; drgraju@bu.edu; SKATHIRESAN1@PARTNERS.ORG; jkeaney@bu.edu; mjkeyes@bu.edu; linj@nhlbi.nih.gov; jmeigs@partners.org; sjrobins@bu.edu; jrong@bu.edu; schnabel@bu.edu; jvita@bu.edu; tjwang@partners.org; pwwilso@emory.edu; pawolf@bu.edu; vasan@bu.edu RI Schnabel, Renate/F-6527-2014; OI Benjamin, Emelia/0000-0003-4076-2336; Vita, Joseph/0000-0001-5607-1797; Lunetta, Kathryn/0000-0002-9268-810X; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Dupuis, Josee/0000-0003-2871-3603 FU NCRR NIH HHS [M01-RR-01066, M01 RR001066, 1S10RR163736-01A1]; NHLBI NIH HHS [1K23 HL083102, 2 K24HL04334, HL064753, HL076784, HL71039, K23 HL083102, K24 HL004334, N01 HC025195, N01-HC25195, N01HC25195, R01 HL064753, R01 HL071039, R01 HL076784]; NIA NIH HHS [AG028321, AG14759, R01 AG014759, R01 AG028321] NR 74 TC 64 Z9 65 U1 0 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S11 DI 10.1186/1471-2350-8-S1-S11 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800011 PM 17903293 ER PT J AU Cupples, LA Arruda, HT Benjamin, EJ D'Agostino Sr, RB Demissie, S DeStefano, AL Dupuis, J Falls, KM Fox, CS Gottlieb, DJ Govindaraju, DR Guo, CY Heard-Costa, NL Hwang, SJ Kathiresan, S Kiel, DP Laramie, JM Larson, MG Levy, D Liu, CY Lunetta, KL Mailman, MD Manning, AK Meigs, JB Murabito, JM Newton-Cheh, C O'Connor, GT O'Donnell, CJ Pandey, M Seshadri, S Vasan, RS Wang, ZY Wilk, JB Wolf, PA Yang, Q Atwood, LD AF Cupples, L. Adrienne Arruda, Heather T. Benjamin, Emelia J. D'Agostino, Ralph B., Sr. Demissie, Serkalem DeStefano, Anita L. Dupuis, Josee Falls, Kathleen M. Fox, Caroline S. Gottlieb, Daniel J. Govindaraju, Diddahally R. Guo, Chao-Yu Heard-Costa, Nancy L. Hwang, Shih-Jen Kathiresan, Sekar Kiel, Douglas P. Laramie, Jason M. Larson, Martin G. Levy, Daniel Liu, Chun-Yu Lunetta, Kathryn L. Mailman, Matthew D. Manning, Alisa K. Meigs, James B. Murabito, Joanne M. Newton-Cheh, Christopher O'Connor, George T. O'Donnell, Christopher J. Pandey, Mona Seshadri, Sudha Vasan, Ramachandran S. Wang, Zhen Y. Wilk, Jemma B. Wolf, Philip A. Yang, Qiong Atwood, Larry D. TI The Framingham Heart Study 100K SNP genome-wide association study resource: overview of 17 phenotype working group reports SO BMC MEDICAL GENETICS LA English DT Article ID CORONARY-ARTERY-DISEASE; BODY-MASS INDEX; COMMUNITY-BASED SAMPLE; ALPHA GENE VARIATION; LINKAGE ANALYSIS; CARDIOVASCULAR-DISEASE; BLOOD-PRESSURE; RISK-FACTOR; UNIFIED APPROACH; CANDIDATE GENE AB Background: The Framingham Heart Study ( FHS), founded in 1948 to examine the epidemiology of cardiovascular disease, is among the most comprehensively characterized multi-generational studies in the world. Many collected phenotypes have substantial genetic contributors; yet most genetic determinants remain to be identified. Using single nucleotide polymorphisms ( SNPs) from a 100K genome-wide scan, we examine the associations of common polymorphisms with phenotypic variation in this community-based cohort and provide a full-disclosure, web-based resource of results for future replication studies. Methods: Adult participants ( n = 1345) of the largest 310 pedigrees in the FHS, many biologically related, were genotyped with the 100K Affymetrix GeneChip. These genotypes were used to assess their contribution to 987 phenotypes collected in FHS over 56 years of follow up, including: cardiovascular risk factors and biomarkers; subclinical and clinical cardiovascular disease; cancer and longevity traits; and traits in pulmonary, sleep, neurology, renal, and bone domains. We conducted genome-wide variance components linkage and population-based and family-based association tests. Results: The participants were white of European descent and from the FHS Original and Offspring Cohorts ( examination 1 Offspring mean age 32 +/- 9 years, 54% women). This overview summarizes the methods, selected findings and limitations of the results presented in the accompanying series of 17 manuscripts. The presented association results are based on 70,897 autosomal SNPs meeting the following criteria: minor allele frequency >= 10%, genotype call rate >= 80%, Hardy-Weinberg equilibrium p-value >= 0.001, and satisfying Mendelian consistency. Linkage analyses are based on 11,200 SNPs and short-tandem repeats. Results of phenotype-genotype linkages and associations for all autosomal SNPs are posted on the NCBI dbGaP website at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Conclusion: We have created a full-disclosure resource of results, posted on the dbGaP website, from a genome-wide association study in the FHS. Because we used three analytical approaches to examine the association and linkage of 987 phenotypes with thousands of SNPs, our results must be considered hypothesis-generating and need to be replicated. Results from the FHS 100K project with NCBI web posting provides a resource for investigators to identify high priority findings for replication. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Whitaker Cardiovasc Inst, Boston, MA 02215 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. NHLBI, Bethesda, MD 20892 USA. VA Boston Healthcare Syst, Boston, MA USA. Harvard Univ, Cambridge, MA 02138 USA. Broad Inst Massachusetts Inst Technol, Cambridge, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Cardiovasc Dis Prevent Ctr, Boston, MA 02114 USA. Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA. Inst Aging Res, Boston, MA USA. Boston Univ, Bioinformat Program, Boston, MA 02215 USA. Natl Ctr Biotechnol Informat, Bethesda, MD USA. Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. RP Cupples, LA (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. EM adrienne@bu.edu; harruda@bu.edu; emelia@bu.edu; ralph@bu.edu; demissie@bu.edu; adestef@bu.edu; dupuis@bu.edu; falls@morgan.harvard.edu; foxca@nhlbi.nih.gov; gottlieb@bu.edu; drgraju@bu.edu; chao-yu.guo@childrens.harvard.edu; nheard@bu.edu; hwangs2@nhlbi.nih.gov; skathiresan@partners.org; kiel@hrca.harvard.edu; laramiej@bu.edu; mlarson@bu.edu; levyd@nih.gov; liuchunyu2002@yahoo.com; klunetta@bu.edu; mm888r@nih.gov; amanning@bu.edu; jmeigs@PARTNERS.ORG; murabito@bu.edu; CNEWTONCHEH@PARTNERS.ORG; goconnor@lung.bumc.bu.edu; codonnell@nih.gov; mpandey@bu.edu; suseshad@bu.edu; vasan@bu.edu; wangzhe@mail.nih.gov; jwilk@bu.edu; pawolf@bu.edu; qyang@bu.edu; lda@bu.edu RI Yang, Qiong/G-5438-2014; OI Benjamin, Emelia/0000-0003-4076-2336; Heard-Costa, Nancy/0000-0001-9730-0306; Lunetta, Kathryn/0000-0002-9268-810X; Larson, Martin/0000-0002-9631-1254; Cupples, L. Adrienne/0000-0003-0273-7965; Murabito, Joanne/0000-0002-0192-7516; Seshadri, Sudha/0000-0001-6135-2622; O'Connor, George/0000-0002-6476-3926; Ramachandran, Vasan/0000-0001-7357-5970; Dupuis, Josee/0000-0003-2871-3603; Kiel, Douglas/0000-0001-8474-0310 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [HL54776, K24 HL 04334, K24 HL004334, N01-HC 25195, N01HC25195, R01 HL054776, R01 HL076784]; NIA NIH HHS [1R01 AG028321, 5R01-AG08122, 5R01-AG16495, R01 AG008122, R01 AG016495, R01 AG028321]; NINDS NIH HHS [R01 NS017950] NR 89 TC 105 Z9 107 U1 0 U2 9 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S1 DI 10.1186/1471-2350-8-S1-S1 PG 19 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800001 PM 17903291 ER PT J AU Fox, CS Heard-Costa, N Cupples, LA Dupuis, J Vasan, RS Atwood, LD AF Fox, Caroline S. Heard-Costa, Nancy Cupples, L. Adrienne Dupuis, Josee Vasan, Ramachandran S. Atwood, Larry D. TI Genome-wide association to body mass index and waist circumference: the Framingham Heart Study 100K project SO BMC MEDICAL GENETICS LA English DT Article ID LINKAGE ANALYSIS; US ADULTS; OBESITY; ADIPOSITY; GENE; MORTALITY; DISEASE; COHORT; FAMILY; SEX AB Background: Obesity is related to multiple cardiovascular disease ( CVD) risk factors as well as CVD and has a strong familial component. We tested for association between SNPs on the Affymetrix 100K SNP GeneChip and measures of adiposity in the Framingham Heart Study. Methods: A total of 1341 Framingham Heart Study participants in 310 families genotyped with the Affymetrix 100K SNP GeneChip had adiposity traits measured over 30 years of follow up. Body mass index ( BMI), waist circumference ( WC), weight change, height, and radiographic measures of adiposity ( subcutaneous adipose tissue, visceral adipose tissue, waist circumference, sagittal height) were measured at multiple examination cycles. Multivariable-adjusted residuals, adjusting for age, age-squared, sex, smoking, and menopausal status, were evaluated in association with the genotype data using additive Generalized Estimating Equations ( GEE) and Family Based Association Test ( FBAT) models. We prioritized mean BMI over offspring examinations ( 1-7) and cohort examinations ( 10, 16, 18, 20, 22, 24, 26) and mean WC over offspring examinations ( 4-7) for presentation. We evaluated associations with 70,987 SNPs on autosomes with minor allele frequencies of at least 0.10, Hardy-Weinberg equilibrium p >= 0.001, and call rates of at least 80%. Results: The top SNPs to be associated with mean BMI and mean WC by GEE were rs110683 ( p-value 1.22* 10(-7)) and rs4471028 ( p-values 1.96* 10(-7)). Please see http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007 for the complete set of results. We were able to validate SNPs in known genes that have been related to BMI or other adiposity traits, including the ESR1 Xba1 SNP, PPARG, and ADIPOQ. Conclusion: Adiposity traits are associated with SNPs on the Affymetrix 100K SNP GeneChip. Replication of these initial findings is necessary. These data will serve as a resource for replication as more genes become identified with BMI and WC. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. RP Fox, CS (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov; nheard@bu.edu; adrienne@bu.edu; dupuis@bu.edu; vasan@bu.edu; lda@bu.edu OI Heard-Costa, Nancy/0000-0001-9730-0306; Cupples, L. Adrienne/0000-0003-0273-7965; Ramachandran, Vasan/0000-0001-7357-5970; Dupuis, Josee/0000-0003-2871-3603 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [N01-HC-25195, N01HC25195]; NIDDK NIH HHS [R01 DK066241] NR 20 TC 75 Z9 75 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S18 DI 10.1186/1471-2350-8-S1-S18 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800018 PM 17903300 ER PT J AU Gottlieb, DJ O'Connor, GT Wilk, JB AF Gottlieb, Daniel J. O'Connor, George T. Wilk, Jemma B. TI Genome-wide association of sleep and circadian phenotypes SO BMC MEDICAL GENETICS LA English DT Article ID DAYTIME SLEEPINESS; PHASE SYNDROME; DIURNAL PREFERENCE; GENETIC INFLUENCES; NEUROPEPTIDE-S; HEART HEALTH; DURATION; MICE; POLYMORPHISM; MUTATION AB Background: Numerous studies suggest genetic influences on sleepiness and circadian rhythms. The Sleep Heart Health Study collected questionnaire data on sleep habits and sleepiness from 2848 Framingham Heart Study Offspring Cohort participants. More than 700 participants were genotyped using the Affymetrix 100K SNP GeneChip, providing a unique opportunity to assess genetic linkage and association of these traits. Methods: Sleepiness ( defined as the Epworth Sleepiness Scale score), usual bedtime and usual sleep duration were assessed by self-completion questionnaire. Standardized residual measures adjusted for age, sex and BMI were analyzed. Multipoint variance components linkage analysis was performed. Association of SNPs to sleep phenotypes was analyzed with both population-based and family-based association tests, with analysis limited to 70,987 autosomal SNPs with minor allele frequency >= 10%, call rate >= 80%, and no significant deviation from Hardy-Weinberg equilibrium ( p >= 0.001). Results: Heritability of sleepiness was 0.29, bedtime 0.22, and sleep duration 0.17. Both genotype and sleep phenotype data were available for 749 subjects. Linkage analysis revealed five linkage peaks of LOD > 2: four to usual bedtime, one to sleep duration. These peaks include several candidate sleep-related genes, including CSNK2A2, encoding a known component of the circadian molecular clock, and PROK2, encoding a putative transmitter of the behavioral circadian rhythm from the suprachiasmatic nucleus. Association tests identified an association of usual bedtime with a non-synonymous coding SNP in NPSR1 that has been shown to encode a gain of function mutation of the neuropeptide S receptor, whose endogenous ligand is a potent promoter of wakefulness. Each copy of the minor allele of this SNP was associated with a 15 minute later mean bedtime. The lowest p value was for association of sleepiness with a SNP located in an intron of PDE4D, which encodes a cAMP-specific phosphodiesterase widely expressed in human brain. Full association results are posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Conclusion: This analysis confirms prior reports of significant heritability of sleepiness, usual bedtime, and usual sleep duration. Several genetic loci with suggestive linkage to these traits are identified, including linkage peaks containing circadian clock-related genes. Association tests identify NPSR1 and PDE4D as possible mediators of bedtime and sleepiness. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. VA Boston Healthcare Syst, W Roxbury, MA 02130 USA. RP Gottlieb, DJ (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. EM gottlieb@bu.edu; goconnor@lung.bumc.bu.edu; jwilk@bu.edu OI O'Connor, George/0000-0002-6476-3926 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [N01HC25195, N01-HC 25195, U01 HL053941, U01 HL53941] NR 50 TC 106 Z9 107 U1 3 U2 16 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S9 DI 10.1186/1471-2350-8-S1-S9 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800009 PM 17903308 ER PT J AU Hwang, SJ Yang, Q Meigs, JB Pearce, EN Fox, CS AF Hwang, Shih-Jen Yang, Qiong Meigs, James B. Pearce, Elizabeth N. Fox, Caroline S. TI A genome-wide association for kidney function and endocrine-related traits in the NHLBI's Framingham Heart Study SO BMC MEDICAL GENETICS LA English DT Article ID GLOMERULAR-FILTRATION-RATE; STAGE RENAL-DISEASE; PERIPHERAL ARTERIAL-DISEASE; CYSTATIN-C; CARDIOVASCULAR OUTCOMES; SERUM CREATININE; RISK-FACTOR; ENVIRONMENTAL-INFLUENCES; ALBUMIN EXCRETION; BODY-COMPOSITION AB Background: Glomerular filtration rate ( GFR) and urinary albumin excretion ( UAE) are markers of kidney function that are known to be heritable. Many endocrine conditions have strong familial components. We tested for association between the Affymetrix GeneChip Human Mapping 100K single nucleotide polymorphism ( SNP) set and measures of kidney function and endocrine traits. Methods: Genotype information on the Affymetrix GeneChip Human Mapping 100K SNP set was available on 1345 participants. Serum creatinine and cystatin-C ( cysC; n = 981) were measured at the seventh examination cycle ( 1998-2001); GFR ( n = 1010) was estimated via the Modification of Diet in Renal Disease ( MDRD) equation; UAE was measured on spot urine samples during the sixth examination cycle ( 1995-1998) and was indexed to urinary creatinine ( n = 822). Thyroid stimulating hormone ( TSH) was measured at the third and fourth examination cycles ( 1981-1984; 1984-1987) and mean value of the measurements were used ( n = 810). Age-sex-adjusted and multivariable-adjusted residuals for these measurements were used in association with genotype data using generalized estimating equations ( GEE) and family-based association tests ( FBAT) models. We presented the results for association tests using additive allele model. We evaluated associations with 70,987 SNPs on autosomes with minor allele frequencies of at least 0.10, Hardy-Weinberg Equilibrium p-value >= 0.001, and call rates of at least 80%. Results: The top SNPs associated with these traits using the GEE method were rs2839235 with GFR ( p-value 1.6* 10(-05)), rs1158167 with cysC ( p-value 8.5* 10(-09)), rs1712790 with UAE ( p-value 1.9* 10(-06)), and rs6977660 with TSH ( p-value 3.7* 10(-06)), respectively. The top SNPs associated with these traits using the FBAT method were rs6434804 with GFR( p-value 2.4* 10(-5)), rs563754 with cysC ( p-value 4.7* 10(-5)), rs1243400 with UAE ( p-value 4.8* 10(-6)), and rs4128956 with TSH ( p-value 3.6* 10(-5)), respectively. Detailed association test results can be found at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Four SNPs in or near the CST3 gene were highly associated with cysC levels ( p- value 8.5* 10(-09) to 0.007). Conclusion: Kidney function traits and TSH are associated with SNPs on the Affymetrix GeneChip Human Mapping 100K SNP set. These data will serve as a valuable resource for replication as more SNPs associated with kidney function and endocrine traits are identified. C1 NHLBI, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol Diabetes & Hypertens, Boston, MA 02115 USA. RP Fox, CS (reprint author), NHLBI, Bldg 10, Bethesda, MD 20892 USA. EM hwangs2@nhlbi.nih.gov; qyang@bu.edu; jmeigs@partner.org; Elizabeth.pearce@bmc.org; foxca@nhlbi.nih.gov RI Yang, Qiong/G-5438-2014 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [N01-HC 25195, N01HC25195] NR 59 TC 43 Z9 46 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S10 DI 10.1186/1471-2350-8-S1-S10 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800010 PM 17903292 ER PT J AU Kathiresan, S Manning, AK Demissie, S D'Agostino, RB Surti, A Guiducci, C Gianniny, L Burtt, NP Melander, O Orho-Melander, M Arnett, DK Peloso, GM Ordovas, JM Cupples, LA AF Kathiresan, Sekar Manning, Alisa K. Demissie, Serkalem D'Agostino, Ralph B. Surti, Aarti Guiducci, Candace Gianniny, Lauren Burtt, Noeel P. Melander, Olle Orho-Melander, Marju Arnett, Donna K. Peloso, Gina M. Ordovas, Jose M. Cupples, L. Adrienne TI A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study SO BMC MEDICAL GENETICS LA English DT Article ID DENSITY-LIPOPROTEIN CHOLESTEROL; COMMON GENETIC VARIANT; PLASMA TRIGLYCERIDE; DISEASE; RISK; POLYMORPHISM; SUBCLASSES; METAANALYSIS; TRAITS; SEX AB Background: Blood lipid levels including low-density lipoprotein cholesterol ( LDL-C), high-density lipoprotein cholesterol ( HDL-C), and triglycerides ( TG) are highly heritable. Genome-wide association is a promising approach to map genetic loci related to these heritable phenotypes. Methods: In 1087 Framingham Heart Study Offspring cohort participants ( mean age 47 years, 52% women), we conducted genome-wide analyses ( Affymetrix 100K GeneChip) for fasting blood lipid traits. Total cholesterol, HDL-C, and TG were measured by standard enzymatic methods and LDL-C was calculated using the Friedewald formula. The long-term averages of up to seven measurements of LDL-C, HDL-C, and TG over a similar to 30 year span were the primary phenotypes. We used generalized estimating equations ( GEE), family-based association tests ( FBAT) and variance components linkage to investigate the relationships between SNPs ( on autosomes, with minor allele frequency >= 10%, genotypic call rate >= 80%, and Hardy-Weinberg equilibrium p >= 0.001) and multivariable-adjusted residuals. We pursued a three-stage replication strategy of the GEE association results with 287 SNPs ( P < 0.001 in Stage I) tested in Stage II ( n similar to 1450 individuals) and 40 SNPs ( P < 0.001 in joint analysis of Stages I and II) tested in Stage III ( n similar to 6650 individuals). Results: Long-term averages of LDL-C, HDL-C, and TG were highly heritable ( h(2) = 0.66, 0.69, 0.58, respectively; each P < 0.0001). Of 70,987 tests for each of the phenotypes, two SNPs had p < 10(-5) in GEE results for LDL-C, four for HDL-C, and one for TG. For each multivariable-adjusted phenotype, the number of SNPs with association p < 10(-4) ranged from 13 to 18 and with p < 10(-3), from 94 to 149. Some results confirmed previously reported associations with candidate genes including variation in the lipoprotein lipase gene ( LPL) and HDL-C and TG ( rs7007797; P = 0.0005 for HDL-C and 0.002 for TG). The full set of GEE, FBAT and linkage results are posted at the database of Genotype and Phenotype (dbGaP). After three stages of replication, there was no convincing statistical evidence for association ( i.e., combined P < 10(-5) across all three stages) between any of the tested SNPs and lipid phenotypes. Conclusion: Using a 100K genome-wide scan, we have generated a set of putative associations for common sequence variants and lipid phenotypes. Validation of selected hypotheses in additional samples did not identify any new loci underlying variability in blood lipids. Lack of replication may be due to inadequate statistical power to detect modest quantitative trait locus effects ( i.e., < 1% of trait variance explained) or reduced genomic coverage of the 100K array. GWAS in FHS using a denser genome-wide genotyping platform and a better-powered replication strategy may identify novel loci underlying blood lipids. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Harvard Univ, Cambridge, MA 02138 USA. MIT, Broad Inst, Cambridge, MA 02139 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Cardiovasc Dis Prevent Ctr,Cardiol Div, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Lund Univ, Malmo Univ Hosp, Dept Clin Sci, Malmo, Sweden. Univ Alabama, Dept Epidemiol, Birmingham, AL USA. Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr, Nutr & Genom Lab, Boston, MA 02111 USA. RP Kathiresan, S (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. EM skathiresan@partners.org; amanning@bu.du; demissie@bu.edu; Ralph@bu.edu; asurti@broad.mit.edu; candace@broad.mit.edu; gianniny@broad.mit.edu; burtt@broad.mit.edu; candace@broad.mit.edu; marju.orho@med.lu.se; arnett@ms.soph.uab.edu; gpeloso@bu.edu; jose.ordovas@tufts.edu; adrienne@bu.edu OI Cupples, L. Adrienne/0000-0003-0273-7965; Ordovas, Jose/0000-0002-7581-5680 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [K23 HL083102, N01-HC-25195, N01HC25195] NR 25 TC 149 Z9 150 U1 1 U2 7 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S17 DI 10.1186/1471-2350-8-S1-S17 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800017 PM 17903299 ER PT J AU Kiel, DP Demissie, S Dupuis, J Lunetta, KL Murabito, JM Karasik, D AF Kiel, Douglas P. Demissie, Serkalem Dupuis, Josee Lunetta, Kathryn L. Murabito, Joanne M. Karasik, David TI Genome-wide association with bone mass and geometry in the Framingham Heart Study SO BMC MEDICAL GENETICS LA English DT Article ID QUANTITATIVE TRAIT LOCI; CROSS-SECTIONAL GEOMETRY; PREDICTS HIP FRACTURE; MINERAL DENSITY; OSTEOPOROTIC FRACTURES; LINKAGE ANALYSIS; PROXIMAL FEMUR; STRUCTURAL GEOMETRY; REGULATORY REGION; FEMORAL-NECK AB Background: Osteoporosis is characterized by low bone mass and compromised bone structure, heritable traits that contribute to fracture risk. There have been no genome-wide association and linkage studies for these traits using high-density genotyping platforms. Methods: We used the Affymetrix 100K SNP GeneChip marker set in the Framingham Heart Study ( FHS) to examine genetic associations with ten primary quantitative traits: bone mineral density ( BMD), calcaneal ultrasound, and geometric indices of the hip. To test associations with multivariable-adjusted residual trait values, we used additive generalized estimating equation ( GEE) and family-based association tests ( FBAT) models within each sex as well as sexes combined. We evaluated 70,987 autosomal SNPs with genotypic call rates >= 80%, HWE p >= 0.001, and MAF >= 10% in up to 1141 phenotyped individuals ( 495 men and 646 women, mean age 62.5 yrs). Variance component linkage analysis was performed using 11,200 markers. Results: Heritability estimates for all bone phenotypes were 30-66%. LOD scores >= 3.0 were found on chromosomes 15 ( 1.5 LOD confidence interval: 51,336,679-58,934,236 bp) and 22 ( 35,890,398-48,603,847 bp) for femoral shaft section modulus. The ten primary phenotypes had 12 associations with 100K SNPs in GEE models at p < 0.000001 and 2 associations in FBAT models at p < 0.000001. The 25 most significant p-values for GEE and FBAT were all less than 3.5 x 10(-6) and 2.5 x 10(-5), respectively. Of the 40 top SNPs with the greatest numbers of significantly associated BMD traits ( including femoral neck, trochanter, and lumbar spine), one half to two-thirds were in or near genes that have not previously been studied for osteoporosis. Notably, pleiotropic associations between BMD and bone geometric traits were uncommon. Evidence for association ( FBAT or GEE p < 0.05) was observed for several SNPs in candidate genes for osteoporosis, such as rs1801133 in MTHFR; rs1884052 and rs3778099 in ESR1; rs4988300 in LRP5; rs2189480 in VDR; rs2075555 in COLIA1; rs10519297 and rs2008691 in CYP19, as well as SNPs in PPARG ( rs10510418 and rs2938392) and ANKH ( rs2454873 and rs379016). All GEE, FBAT and linkage results are provided as an open-access results resource at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Conclusion: The FHS 100K SNP project offers an unbiased genome-wide strategy to identify new candidate loci and to replicate previously suggested candidate genes for osteoporosis. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Hebrew SeniorLife Inst Aging Res, Boston, MA USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. RP Kiel, DP (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM kiel@hrca.harvard.edu; demissie@bu.edu; dupuis@bu.edu; klunetta@bu.edu; murabito@bu.edu; karasik@hrca.harvard.edu OI Lunetta, Kathryn/0000-0002-9268-810X; Murabito, Joanne/0000-0002-0192-7516; Dupuis, Josee/0000-0003-2871-3603; Kiel, Douglas/0000-0001-8474-0310; Karasik, David/0000-0002-8826-0530 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [N01-HC-25195, N01HC25195]; NIA NIH HHS [R01 AR/AG 41398]; NIAMS NIH HHS [R01 AR041398, R01 AR041398-15, R01 AR050066] NR 52 TC 135 Z9 140 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S14 DI 10.1186/1471-2350-8-S1-S14 PG 13 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800014 PM 17903296 ER PT J AU Larson, MG Atwood, LD Benjamin, EJ Cupples, LA D'Agostino, RB Fox, CS Govindaraju, DR Guo, CY Heard-Costa, NL Hwang, SJ Murabito, JM Newton-Cheh, C O'Donnell, CJ Seshadri, S Vasan, RS Wang, TJ Wolf, PA Levy, D AF Larson, Martin G. Atwood, Larry D. Benjamin, Emelia J. Cupples, L. Adrienne D'Agostino, Ralph B., Sr. Fox, Caroline S. Govindaraju, Diddahally R. Guo, Chao-Yu Heard-Costa, Nancy L. Hwang, Shih-Jen Murabito, Joanne M. Newton-Cheh, Christopher O'Donnell, Christopher J. Seshadri, Sudha Vasan, Ramachandran S. Wang, Thomas J. Wolf, Philip A. Levy, Daniel TI Framingham Heart Study 100K project: genome-wide associations for cardiovascular disease outcomes SO BMC MEDICAL GENETICS LA English DT Article ID RIGHT-VENTRICULAR CARDIOMYOPATHY; LIFETIME RISK; MYOCARDIAL-INFARCTION; ATRIAL-FIBRILLATION; CONFERS RISK; IDENTIFICATION; FAILURE; GENE; FAMILIES; STROKE AB Background: Cardiovascular disease ( CVD) and its most common manifestations - including coronary heart disease ( CHD), stroke, heart failure ( HF), and atrial fibrillation ( AF) - are major causes of morbidity and mortality. In many industrialized countries, cardiovascular disease ( CVD) claims more lives each year than any other disease. Heart disease and stroke are the first and third leading causes of death in the United States. Prior investigations have reported several single gene variants associated with CHD, stroke, HF, and AF. We report a community-based genome-wide association study of major CVD outcomes. Methods: In 1345 Framingham Heart Study participants from the largest 310 pedigrees ( 54% women, mean age 33 years at entry), we analyzed associations of 70,987 qualifying SNPs ( Affymetrix 100K GeneChip) to four major CVD outcomes: major atherosclerotic CVD ( n = 142; myocardial infarction, stroke, CHD death), major CHD ( n = 118; myocardial infarction, CHD death), AF ( n = 151), and HF ( n = 73). Participants free of the condition at entry were included in proportional hazards models. We analyzed model-based deviance residuals using generalized estimating equations to test associations between SNP genotypes and traits in additive genetic models restricted to autosomal SNPs with minor allele frequency >= 0.10, genotype call rate >= 0.80, and Hardy-Weinberg equilibrium p-value >= 0.001. Results: Six associations yielded p < 10(-5). The lowest p-values for each CVD trait were as follows: major CVD, rs499818, p = 6.6 x 10(-6); major CHD, rs2549513, p = 9.7 x 10(-6); AF, rs958546, p = 4.8 x 10(-6); HF: rs740363, p = 8.8 x 10(-6). Of note, we found associations of a 13 Kb region on chromosome 9p21 with major CVD ( p 1.7 - 1.9 x 10(-5)) and major CHD ( p 2.5 - 3.5 x 10(-4)) that confirm associations with CHD in two recently reported genome-wide association studies. Also, rs10501920 in CNTN5 was associated with AF ( p = 9.4 x 10(-6)) and HF ( p = 1.2 x 10(-4)). Complete results for these phenotypes can be found at the dbgap website http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Conclusion: No association attained genome-wide significance, but several intriguing findings emerged. Notably, we replicated associations of chromosome 9p21 with major CVD. Additional studies are needed to validate these results. Finding genetic variants associated with CVD may point to novel disease pathways and identify potential targeted preventive therapies. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Dept Math Stat, Boston, MA 02215 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Gen Internal Med Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02215 USA. Broad Inst Harvard, Cambridge, MA USA. MIT, Cambridge, MA 02139 USA. RP Larson, MG (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. EM mlarson@bu.edu; lda@bu.edu; emelia@bu.edu; adrienne@bu.edu; ralph@bu.edu; foxca@nhlbi.nih.gov; drgraju@bu.edu; Chao-Yu.Guo@childrens.harvard.edu; nheard@bu.edu; hwangs2@nhlbi.nih.gov; murabito@bu.edu; cnewtoncheh@partners.org; odonnellc@nhlbi.nih.gov; suseshad@bu.edu; vasan@bu.edu; tjwang@partners.org; pawolf@bu.edu; levyd@nhlbi.nih.gov OI Seshadri, Sudha/0000-0001-6135-2622; Larson, Martin/0000-0002-9631-1254; Heard-Costa, Nancy/0000-0001-9730-0306; Murabito, Joanne/0000-0002-0192-7516; Cupples, L. Adrienne/0000-0003-0273-7965; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [N01-HC 25195, N01HC25195]; NIA NIH HHS [R01 AG033193]; NINDS NIH HHS [R01 NS017950] NR 28 TC 107 Z9 111 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S5 DI 10.1186/1471-2350-8-S1-S5 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800005 PM 17903304 ER PT J AU Levy, D Larson, MG Benjamin, EJ Newton-Cheh, C Wang, TJ Hwang, SJ Vasan, RS Mitchell, GF AF Levy, Daniel Larson, Martin G. Benjamin, Emelia J. Newton-Cheh, Christopher Wang, Thomas J. Hwang, Shih-Jen Vasan, Ramachandran S. Mitchell, Gary F. TI Framingham Heart Study 100K Project: genome-wide associations for blood pressure and arterial stiffness SO BMC MEDICAL GENETICS LA English DT Article ID WAVE REFLECTION; LYSYL OXIDASE; HYPERTENSION; METAANALYSIS; FAMILIES; TISSUES; ADULTS; SCAN; AGE AB Background: About one quarter of adults are hypertensive and high blood pressure carries increased risk for heart disease, stroke, kidney disease and death. Increased arterial stiffness is a key factor in the pathogenesis of systolic hypertension and cardiovascular disease. Substantial heritability of blood-pressure ( BP) and arterial-stiffness suggests important genetic contributions. Methods: In Framingham Heart Study families, we analyzed genome-wide SNP ( Affymetrix 100K GeneChip) associations with systolic ( SBP) and diastolic ( DBP) BP at a single examination in 1971-1975 ( n = 1260), at a recent examination in 1998-2001 ( n = 1233), and long-term averaged SBP and DBP from 1971-2001 ( n = 1327, mean age 52 years, 54% women) and with arterial stiffness measured by arterial tonometry ( carotid-femoral and carotid-brachial pulse wave velocity, forward and reflected pressure wave amplitude, and mean arterial pressure; 1998-2001, n = 644). In primary analyses we used generalized estimating equations in models for an additive genetic effect to test associations between SNPs and phenotypes of interest using multivariable-adjusted residuals. A total of 70,987 autosomal SNPs with minor allele frequency >= 0.10, genotype call rate >= 0.80, and Hardy-Weinberg equilibrium p >= 0.001 were analyzed. We also tested for association of 69 SNPs in six renin-angiotensin-aldosterone pathway genes with BP and arterial stiffness phenotypes as part of a candidate gene search. Results: In the primary analyses, none of the associations attained genome-wide significance. For the six BP phenotypes, seven SNPs yielded p values < 10(-5). The lowest p-values for SBP and DBP respectively were rs10493340 ( p = 1.7 x 10(-6)) and rs1963982 ( p = 3.3 x 10(-6)). For the five tonometry phenotypes, five SNPs had p values < 10-5; lowest p-values were for reflected wave ( rs6063312, p = 2.1 x 10(-6)) and carotid-brachial pulse wave velocity ( rs770189, p = 2.5 x 10(-6)) in MEF2C, a regulator of cardiac morphogenesis. We found only weak association of SNPs in the renin-angiotensin-aldosterone pathway with BP or arterial stiffness. Conclusion: These results of genome-wide association testing for blood pressure and arterial stiffness phenotypes in an unselected community-based sample of adults may aid in the identification of the genetic basis of hypertension and arterial disease, help identify high risk individuals, and guide novel therapies for hypertension. Additional studies are needed to replicate any associations identified in these analyses. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Dept Math, Boston, MA 02215 USA. Boston Med Ctr, Div Cardiol, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Math, Boston, MA 02114 USA. Cardiovasc Engn Inc, Waltham, MA USA. RP Levy, D (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. EM Levyd@nih.gov; mlarson@bu.edu; emelia@bu.edu; cnewtoncheh@partners.org; tjwang@partners.org; hwangs2@nhlbi.nih.gov; vasan@bu.edu; garyfmitchell@mindspring.co OI Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [K24 HL004334, K24-HL04334, N01-HC 25195, N01HC25195, R01 HL060040, R01 HL070100, R01-HL60040, R01-HL70100] NR 23 TC 149 Z9 152 U1 0 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S3 DI 10.1186/1471-2350-8-S1-S3 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800003 PM 17903302 ER PT J AU Lunetta, KL D'Agostino, RB Karasik, D Benjamin, EJ Guo, CY Govindaraju, R Kiel, DP Kelly-Hayes, M Massaro, JM Pencina, MJ Seshadri, S Murabito, JM AF Lunetta, Kathryn L. D'Agostino, Ralph B., Sr. Karasik, David Benjamin, Emelia J. Guo, Chao-Yu Govindaraju, Raju Kiel, Douglas P. Kelly-Hayes, Margaret Massaro, Joseph M. Pencina, Michael J. Seshadri, Sudha Murabito, Joanne M. TI Genetic correlates of longevity and selected age-related phenotypes: a genome-wide association study in the Framingham Study SO BMC MEDICAL GENETICS LA English DT Article ID HUMAN LIFE-SPAN; KLOTHO GENE; POLYMORPHIC VARIANTS; NATURAL MENOPAUSE; SIRT3 GENE; MALE TWINS; INSULIN; HERITABILITY; SURVIVAL; FOXO3A AB Background: Family studies and heritability estimates provide evidence for a genetic contribution to variation in the human life span. Methods: We conducted a genome wide association study ( Affymetrix 100K SNP GeneChip) for longevity-related traits in a community-based sample. We report on 5 longevity and aging traits in up to 1345 Framingham Study participants from 330 families. Multivariable-adjusted residuals were computed using appropriate models ( Cox proportional hazards, logistic, or linear regression) and the residuals from these models were used to test for association with qualifying SNPs ( 70, 987 autosomal SNPs with genotypic call rate >= 80%, minor allele frequency >= 10%, Hardy-Weinberg test p >= 0.001). Results: In family-based association test ( FBAT) models, 8 SNPs in two regions approximately 500 kb apart on chromosome 1 ( physical positions 73,091,610 and 73, 527,652) were associated with age at death ( p-value < 10(-5)). The two sets of SNPs were in high linkage disequilibrium ( minimum r(2) = 0.58). The top 30 SNPs for generalized estimating equation ( GEE) tests of association with age at death included rs10507486 ( p = 0.0001) and rs4943794 ( p = 0.0002), SNPs intronic to FOXO1A, a gene implicated in lifespan extension in animal models. FBAT models identified 7 SNPs and GEE models identified 9 SNPs associated with both age at death and morbidity-free survival at age 65 including rs2374983 near PON1. In the analysis of selected candidate genes, SNP associations ( FBAT or GEE p-value < 0.01) were identified for age at death in or near the following genes: FOXO1A, GAPDH, KL, LEPR, PON1, PSEN1, SOD2, and WRN. Top ranked SNP associations in the GEE model for age at natural menopause included rs6910534 ( p = 0.00003) near FOXO3a and rs3751591 ( p = 0.00006) in CYP19A1. Results of all longevity phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Conclusion: Longevity and aging traits are associated with SNPs on the Affymetrix 100K GeneChip. None of the associations achieved genome-wide significance. These data generate hypotheses and serve as a resource for replication as more genes and biologic pathways are proposed as contributing to longevity and healthy aging. C1 Framingham Haert Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Cardiol, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Prevent Med, Boston, MA 02215 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Hebrew Senior Life Inst Aging Res, Boston, MA 02115 USA. Boston Univ, Dept Math, Stat & Consulat Unit, Boston, MA 02215 USA. RP Murabito, JM (reprint author), Framingham Haert Study, NHLBI, Framingham, MA 01702 USA. EM klunetta@bu.edu; ralph@bu.edu; karasik@hrca.harvard.edu; emelia@bu.edu; chaoyu@bu.edu; drgraju@bu.edu; kiel@hrca.harvard.edu; mkhayes@bu.edu; jmm@bu.edu; mpencina@bu.edu; suseshad@bu.edu; murabito@bu.edu OI Murabito, Joanne/0000-0002-0192-7516; Seshadri, Sudha/0000-0001-6135-2622; Lunetta, Kathryn/0000-0002-9268-810X; Massaro, Joseph/0000-0002-2682-4812; Benjamin, Emelia/0000-0003-4076-2336; Kiel, Douglas/0000-0001-8474-0310; Karasik, David/0000-0002-8826-0530 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [N01HC25195, N01-HC-25195]; NIA NIH HHS [AG028321, R01 AG028321, R01 AR/AG 41398]; NIAMS NIH HHS [R01 AR041398] NR 46 TC 103 Z9 106 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S13 DI 10.1186/1471-2350-8-S1-S13 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800013 PM 17903295 ER PT J AU Meigs, JB Manning, AK Fox, CS Florez, JC Liu, C Cupples, LA Dupuis, J AF Meigs, James B. Manning, Alisa K. Fox, Caroline S. Florez, Jose C. Liu, Chunyu Cupples, L. Adrienne Dupuis, Josee TI Genome-wide association with diabetes-related traits in the Framingham Heart Study SO BMC MEDICAL GENETICS LA English DT Article ID TRANSCRIPTION-FACTOR-7-LIKE-2 TCF7L2 GENE; BETA-CELL FUNCTION; INSULIN-RESISTANCE; GLUCOSE-TOLERANCE; TYPE-2; RISK; REPLICATION; MELLITUS; POLYMORPHISMS; POPULATION AB Background: Susceptibility to type 2 diabetes may be conferred by genetic variants having modest effects on risk. Genome-wide fixed marker arrays offer a novel approach to detect these variants. Methods: We used the Affymetrix 100K SNP array in 1,087 Framingham Offspring Study family members to examine genetic associations with three diabetes-related quantitative glucose traits ( fasting plasma glucose ( FPG), hemoglobin A1c, 28-yr time-averaged FPG ( tFPG)), three insulin traits ( fasting insulin, HOMA-insulin resistance, and 0-120 min insulin sensitivity index); and with risk for diabetes. We used additive generalized estimating equations ( GEE) and family-based association test ( FBAT) models to test associations of SNP genotypes with sex-age-age(2)-adjusted residual trait values, and Cox survival models to test incident diabetes. Results: We found 415 SNPs associated ( at p < 0.001) with at least one of the six quantitative traits in GEE, 242 in FBAT ( 18 overlapped with GEE for 639 non-overlapping SNPs), and 128 associated with incident diabetes ( 31 overlapped with the 639) giving 736 non-overlapping SNPs. Of these 736 SNPs, 439 were within 60 kb of a known gene. Additionally, 53 SNPs ( of which 42 had r(2) < 0.80 with each other) had p < 0.01 for incident diabetes AND ( all 3 glucose traits OR all 3 insulin traits, OR 2 glucose traits and 2 insulin traits); of these, 36 overlapped with the 736 other SNPs. Of 100K SNPs, one ( rs7100927) was in moderate LD ( r(2) = 0.50) with TCF7L2 ( rs7903146), and was associated with risk of diabetes ( Cox p-value 0.007, additive hazard ratio for diabetes = 1.56) and with tFPG ( GEE p-value 0.03). There were no common ( MAF > 1%) 100K SNPs in LD ( r2 > 0.05) with ABCC8 A1369S ( rs757110), KCNJ11 E23K ( rs5219), or SNPs in CAPN10 or HNFa. PPARG P12A ( rs1801282) was not significantly associated with diabetes or related traits. Conclusion: Framingham 100K SNP data is a resource for association tests of known and novel genes with diabetes and related traits posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Framingham 100K data replicate the TCF7L2 association with diabetes. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Brigham & Womens Hosp, Sch Med, Dept Biostat, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Ctr Human Genet Res, Boston, MA 02115 USA. Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA 02115 USA. MIT, Cambridge, MA 02139 USA. Broad Inst Harvard, Program Med & Populat Genet, Cambridge, MA 02139 USA. RP Meigs, JB (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM jmeigs@partners.org; amanning@bu.edu; foxca@nhlbi.nih.gov; jcflorez@partners.org; liuc@bu.edu; adrienne@bu.edu; dupuis@bu.edu OI Cupples, L. Adrienne/0000-0003-0273-7965; Dupuis, Josee/0000-0003-2871-3603 FU NCRR NIH HHS [M01 RR001066, M01-RR-01066]; NHLBI NIH HHS [N01HC25195, N01-HC-25195]; NIDDK NIH HHS [K23 DK065978, K23 DK65978-03] NR 40 TC 53 Z9 53 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S16 DI 10.1186/1471-2350-8-S1-S16 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800016 PM 17903298 ER PT J AU Murabito, JM Rosenberg, CL Finger, D Kreger, BE Levy, D Splansky, GL Antman, K Hwang, SJ AF Murabito, Joanne M. Rosenberg, Carol L. Finger, Daniel Kreger, Bernard E. Levy, Daniel Splansky, Greta Lee Antman, Karen Hwang, Shih-Jen TI A genome-wide association study of breast and prostate cancer in the NHLBI's Framingham Heart Study SO BMC MEDICAL GENETICS LA English DT Article ID COMPLEMENT FACTOR-H; MACULAR DEGENERATION; SUSCEPTIBILITY GENES; LINKAGE SCAN; RISK LOCUS; VARIANT; POLYMORPHISM; CONSORTIUM; EXPRESSION; MUTATIONS AB Background: Breast and prostate cancer are two commonly diagnosed cancers in the United States. Prior work suggests that cancer causing genes and cancer susceptibility genes can be identified. Methods: We conducted a genome-wide association study ( Affymetrix 100K SNP GeneChip) of cancer in the community-based Framingham Heart Study. We report on 2 cancer traits - prostate cancer and breast cancer in up to 1335 participants from 330 families ( 54% women, mean entry age 33 years). Multivariable-adjusted residuals, computed using Cox proportional hazards models, were tested for association with qualifying SNPs ( 70, 987 autosomal SNPs with genotypic call rate >= 80%, minor allele frequency >= 10%, Hardy-Weinberg test p >= 0.001) using generalized estimating equations ( GEE) models and family based association tests ( FBAT). Results: There were 58 women with breast cancer and 59 men with prostate cancer. No SNP associations attained genome-wide significance. The top SNP associations in GEE models for each trait were as follows: breast cancer, rs2075555, p = 8.0 x 10(-8) in COL1A1; and prostate cancer, rs9311171, p = 1.75 x 10(-6) in CTDSPL. In analysis of selected candidate cancer susceptibility genes, two MSR1 SNPs ( rs9325782, GEE p = 0.008 and rs2410373, FBAT p = 0.021) were associated with prostate cancer and three ERBB4 SNPs ( rs905883 GEE p = 0.0002, rs7564590 GEE p = 0.003, rs7558615 GEE p = 0.0078) were associated with breast cancer. The previously reported risk SNP for prostate cancer, rs1447295, was not included on the 100K chip. Results of cancer phenotype-genotype associations for all autosomal SNPs are web posted at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Conclusion: Although no association attained genome-wide significance, several interesting associations emerged for breast and prostate cancer. These findings can serve as a resource for replication in other populations to identify novel biologic pathways contributing to cancer susceptibility. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Sch Med, Dept Med, Hematol Oncol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Dept Med, Gen Internal Med Sect, Boston, MA 02215 USA. NHLBI, Bethesda, MD 20892 USA. RP Murabito, JM (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. EM murabito@bu.edu; crosenbe@bu.edu; Daniel.finger@bmc.org; Bernard.kreger@bmc.org; levyd@nhlbi.nih.gov; gretalee@bu.edu; kha4@bu.edu; hwangs2@nhlbi.nih.gov OI Antman, Karen/0000-0002-1093-8356; Murabito, Joanne/0000-0002-0192-7516 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [N01HC25195, N01-HC-25195] NR 39 TC 71 Z9 78 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S6 DI 10.1186/1471-2350-8-S1-S6 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800006 PM 17903305 ER PT J AU Newton-Cheh, C Guo, CY Wang, TJ O'Donnell, CJ Levy, D Larson, MG AF Newton-Cheh, Christopher Guo, Chao-Yu Wang, Thomas J. O'Donnell, Christopher J. Levy, Daniel Larson, Martin G. TI Genome-wide association study of electrocardiographic and heart rate variability traits: the Framingham Heart Study SO BMC MEDICAL GENETICS LA English DT Article ID QUANTITATIVE-TRAIT; LINKAGE ANALYSIS; SUDDEN-DEATH; RISK FACTOR; TWINS; POLYMORPHISM; MORTALITY AB Background: Heritable electrocardiographic ( ECG) and heart rate variability ( HRV) measures, reflecting pacemaking, conduction, repolarization and autonomic function in the heart have been associated with risks for cardiac arrhythmias. Whereas several rare monogenic conditions with extreme phenotypes have been noted, few common genetic factors contributing to interindividual variability in ECG and HRV measures have been identified. We report the results of a community-based genomewide association study of six ECG and HRV intermediate traits. Methods: Genotyping using Affymetrix 100K GeneChip was conducted on 1345 related Framingham Heart Study Original and Offspring cohort participants. We analyzed 1175 Original and Offspring participants with ECG data ( mean age 52 years, 52% women) and 548 Offspring participants with HRV data ( mean age 48 years, 51% women), in relation to 70,987 SNPs with minor allele frequency >= 0.10, call rate >= 80%, Hardy-Weinberg p-value >= 0.001. We used generalized estimating equations to test association of SNP alleles with multivariable-adjusted residuals for QT, RR, and PR intervals, the ratio of low frequency to high frequency power ( LF/HFP), total power ( TP) and the standard deviation of normal RR intervals ( SDNN). Results: Associations at p < 10(-3) were found for 117 ( QT), 105 ( RR), 111 ( PR), 102 ( LF/HF), 121 ( TP), and 102 ( SDNN) SNPs. Several common variants in NOS1AP ( 4 SNPs with p-values < 10(-3); lowest p-value, rs6683968, p = 1 x 10(-4)) were associated with adjusted QT residuals, consistent with our previously reported finding for NOS1AP in an unrelated sample of FHS Offspring and other cohorts. All results are publicly available at NCBI's dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Conclusion: In the community-based Framingham Heart Study none of the ECG and HRV results individually attained genomewide significance. However, the presence of bona fide QT-associated SNPs among the top 117 results for QT duration supports the importance of efforts to validate top results from the reported scans. Finding genetic variants associated with ECG and HRV quantitative traits may identify novel genes and pathways implicated in arrhythmogenesis and allow for improved recognition of individuals at high risk for arrhythmias in the general population. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Harvard Univ, Cambridge, MA 02138 USA. Broad Inst Massachusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. Harvard Univ, Dept Math & Stat, Boston, MA 02115 USA. NHLBI, Bethesda, MD 20892 USA. RP Newton-Cheh, C (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. EM cnewtoncheh@partners.org; chaoyu@bu.edu; tjwang@partners.org; odonnellc@nhlbi.nih.gov; levyd@nih.gov; mlarson@bu.edu OI Larson, Martin/0000-0002-9631-1254 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [N01HC25195, N01-HC25195] NR 16 TC 49 Z9 49 U1 0 U2 8 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S7 DI 10.1186/1471-2350-8-S1-S7 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800007 PM 17903306 ER PT J AU O'Donnell, CJ Cupples, LA D'Agostino, RB Fox, CS Hoffmann, U Hwang, SJ Ingellson, E Liu, C Murabito, JM Polak, JF Wolf, PA Demissie, S AF O'Donnell, Christopher J. Cupples, L. Adrienne D'Agostino, Ralph B. Fox, Caroline S. Hoffmann, Udo Hwang, Shih-Jen Ingellson, Erik Liu, Chunyu Murabito, Joanne M. Polak, Joseph F. Wolf, Philip A. Demissie, Serkalem TI Genome-wide association study for subclinical atherosclerosis in major arterial territories in the NHLBI's Framingham Heart Study SO BMC MEDICAL GENETICS LA English DT Article ID AORTIC CALCIFIC DEPOSITS; BEAM COMPUTED-TOMOGRAPHY; COMMON GENETIC VARIANT; ANKLE-BRACHIAL INDEX; MYOCARDIAL-INFARCTION; MEDIA THICKNESS; CONFERS RISK; HERITABILITY; DISEASE; STROKE AB Introduction: Subclinical atherosclerosis ( SCA) measures in multiple arterial beds are heritable phenotypes that are associated with increased incidence of cardiovascular disease. We conducted a genome-wide association study ( GWAS) for SCA measurements in the community-based Framingham Heart Study. Methods: Over 100,000 single nucleotide polymorphisms ( SNPs) were genotyped ( Human 100K GeneChip, Affymetrix) in 1345 subjects from 310 families. We calculated sex-specific age-adjusted and multivariable-adjusted residuals in subjects tested for quantitative SCA phenotypes, including ankle-brachial index, coronary artery calcification and abdominal aortic calcification using multi-detector computed tomography, and carotid intimal medial thickness ( IMT) using carotid ultrasonography. We evaluated associations of these phenotypes with 70,987 autosomal SNPs with minor allele frequency >= 0.10, call rate >= 80%, and Hardy-Weinberg p-value >= 0.001 in samples ranging from 673 to 984 subjects, using linear regression with generalized estimating equations ( GEE) methodology and family-based association testing ( FBAT). Variance components LOD scores were also calculated. Results: There was no association result meeting criteria for genome-wide significance, but our methods identified 11 SNPs with p < 10(-5) by GEE and five SNPs with p < 10(-5) by FBAT for multivariable-adjusted phenotypes. Among the associated variants were SNPs in or near genes that may be considered candidates for further study, such as rs1376877 ( GEE p < 0.000001, located in ABI2) for maximum internal carotid artery IMT and rs4814615 ( FBAT p = 0.000003, located in PCSK2) for maximum common carotid artery IMT. Modest significant associations were noted with various SCA phenotypes for variants in previously reported atherosclerosis candidate genes, including NOS3 and ESRI. Associations were also noted of a region on chromosome 9p21 with CAC phenotypes that confirm associations with coronary heart disease and CAC in two recently reported genome-wide association studies. In linkage analyses, several regions of genome-wide linkage were noted, confirming previously reported linkage of internal carotid artery IMT on chromosome 12. All GEE, FBAT and linkage results are provided as an open-access results resource at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Conclusion: The results from this GWAS generate hypotheses regarding several SNPs that may be associated with SCA phenotypes in multiple arterial beds. Given the number of tests conducted, subsequent independent replication in a staged approach is essential to identify genetic variants that may be implicated in atherosclerosis. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Boston Univ, Dept Math & Stat, Boston, MA 02215 USA. Massachusetts Gen Hosp, Dept Med, Div Cardiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Endocrinol Div, Boston, MA 02115 USA. Tufts Univ New England Med Ctr, Dept Radiol, Boston, MA 02115 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP O'Donnell, CJ (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. EM odonnellc@nhlbi.nih.gov; adrienne@bu.edu; ralph@bu.edu; foxca@nhlbi.nih.gov; uhoffman@partners.org; hwangs2@mail.nih.gov; erik.ingelsson@pubcare.uu.se; liuchunyu2002@yahoo.com; murabito@bu.edu; JPolak@tufts-nemc.org; pawolf@bu.edu; demissie@bu.edu OI Cupples, L. Adrienne/0000-0003-0273-7965; Murabito, Joanne/0000-0002-0192-7516 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [N01-HC-25195, N01HC25195] NR 36 TC 85 Z9 86 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S4 DI 10.1186/1471-2350-8-S1-S4 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800004 PM 17903303 ER PT J AU Seshadri, S DeStefano, AL Au, R Massaro, JM Beiser, AS Kelly-Hayes, M Kase, CS D'Agostino, RB DeCarli, C Atwood, LD Wolf, PA AF Seshadri, Sudha DeStefano, Anita L. Au, Rhoda Massaro, Joseph M. Beiser, Alexa S. Kelly-Hayes, Margaret Kase, Carlos S. D'Agostino, Ralph B., Sr. DeCarli, Charles Atwood, Larry D. Wolf, Philip A. TI Genetic correlates of brain aging on MRI and cognitive test measures: a genome-wide association and linkage analysis in the Framingham study SO BMC MEDICAL GENETICS LA English DT Article ID WHITE-MATTER HYPERINTENSITY; STROKE RISK PROFILE; ALZHEIMERS-DISEASE; ISCHEMIC-STROKE; BIPOLAR DISORDER; CONFERS RISK; SCHIZOPHRENIA; PERFORMANCE; EXPRESSION; DEMENTIA AB Background: Brain magnetic resonance imaging ( MRI) and cognitive tests can identify heritable endophenotypes associated with an increased risk of developing stroke, dementia and Alzheimer's disease ( AD). We conducted a genomewide association ( GWA) and linkage analysis exploring the genetic basis of these endophenotypes in a community-based sample. Methods: A total of 705 stroke- and dementia-free Framingham participants ( age 62 +9 yrs, 50% male) who underwent volumetric brain MRI and cognitive testing ( 1999-2002) were genotyped. We used linear models adjusting for first degree relationships via generalized estimating equations ( GEE) and family based association tests ( FBAT) in additive models to relate qualifying single nucleotide polymorphisms ( SNPs, 70,987 autosomal on Affymetrix 100K Human Gene Chip with minor allele frequency >= 0.10, genotypic call rate >= 0.80, and Hardy-Weinberg equilibrium p-value >= 0.001) to multivariable- adjusted residuals of 9 MRI measures including total cerebral brain ( TCBV), lobar, ventricular and white matter hyperintensity ( WMH) volumes, and 6 cognitive factors/tests assessing verbal and visuospatial memory, visual scanning and motor speed, reading, abstract reasoning and naming. We determined multipoint identity-by-descent utilizing 10,592 informative SNPs and 613 short tandem repeats and used variance component analyses to compute LOD scores. Results: The strongest gene-phenotype association in FBAT analyses was between SORL1 ( rs1131497; p = 3.2 x 10(-6)) and abstract reasoning, and in GEE analyses between CDH4 ( rs1970546; p = 3.7 x 10(-8)) and TCBV. SORL1 plays a role in amyloid precursor protein processing and has been associated with the risk of AD. Among the 50 strongest associations ( 25 each by GEE and FBAT) were other biologically interesting genes. Polymorphisms within 28 of 163 candidate genes for stroke, AD and memory impairment were associated with the endophenotypes studied at p < 0.001. We confirmed our previously reported linkage of WMH on chromosome 4 and describe linkage of reading performance to a marker on chromosome 18 ( GATA11A06), previously linked to dyslexia ( LOD scores = 2.2 and 5.1). Conclusion: Our results suggest that genes associated with clinical neurological disease also have detectable effects on subclinical phenotypes. These hypothesis generating data illustrate the use of an unbiased approach to discover novel pathways that may be involved in brain aging, and could be used to replicate observations made in other studies. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. Boston Univ, Dept Math, Stat & Consulting Unit, Boston, MA 02215 USA. Univ Calif Davis, Dept Neurol, Sacramento, CA 95817 USA. RP Seshadri, S (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. EM suseshad@bu.edu; adestef@bu.edu; rhodaau@bu.edu; jmm@bu.edu; alexab@bu.edu; mkhayes@bu.edu; cskase@bu.edu; ralph@bu.edu; cdecarli@bu.edu; lda@bu.edu; pawolf@bu.edu RI DeCarli, Charles/B-5541-2009; OI Seshadri, Sudha/0000-0001-6135-2622; Au, Rhoda/0000-0001-7742-4491; Massaro, Joseph/0000-0002-2682-4812; Beiser, Alexa/0000-0001-8551-7778 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [N01-HC-25195, N01HC25195]; NIA NIH HHS [5R01-AG08122, 5R01-AG16495, R01 AG008122, R01 AG016495]; NINDS NIH HHS [5R01-NS17950, R01 NS017950] NR 77 TC 113 Z9 113 U1 3 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S15 DI 10.1186/1471-2350-8-S1-S15 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800015 PM 17903297 ER PT J AU Vasan, RS Larson, MG Aragam, J Wang, TJ Mitchell, GF Kathiresan, S Newton-Cheh, C Vita, JA Keyes, MJ O'Donnell, CJ Levy, D Benjamin, EJ AF Vasan, Ramachandran S. Larson, Martin G. Aragam, Jayashri Wang, Thomas J. Mitchell, Gary F. Kathiresan, Sekar Newton-Cheh, Christopher Vita, Joseph A. Keyes, Michelle J. O'Donnell, Christopher J. Levy, Daniel Benjamin, Emelia J. TI Genome-wide association of echocardiographic dimensions, brachial artery endothelial function and treadmill exercise responses in the Framingham Heart Study SO BMC MEDICAL GENETICS LA English DT Article ID LEFT-VENTRICULAR MASS; FLOW-MEDIATED DILATION; BLOOD-PRESSURE; CARDIOVASCULAR HEALTH; GENETIC-VARIATION; I/D POLYMORPHISM; AMERICAN-INDIANS; HERITAGE FAMILY; ELDERLY COHORT; PROTEIN-KINASE AB Background: Echocardiographic left ventricular ( LV) measurements, exercise responses to standardized treadmill test ( ETT) and brachial artery ( BA) vascular function are heritable traits that are associated with cardiovascular disease risk. We conducted a genome-wide association study ( GWAS) in the community-based Framingham Heart Study. Methods: We estimated multivariable-adjusted residuals for quantitative echocardiography, ETT and BA function traits. Echocardiography residuals were averaged across 4 examinations and included LV mass, diastolic and systolic dimensions, wall thickness, fractional shortening, left atrial and aortic root size. ETT measures ( single exam) included systolic blood pressure and heart rate responses during exercise stage 2, and at 3 minutes post-exercise. BA measures ( single exam) included vessel diameter, flow-mediated dilation ( FMD), and baseline and hyperemic flow responses. Generalized estimating equations ( GEE), family-based association tests ( FBAT) and variance-components linkage were used to relate multivariable-adjusted trait residuals to 70,987 SNPs ( Human 100K GeneChip, Affymetrix) restricted to autosomal SNPs with minor allele frequency >= 0.10, genotype call rate >= 0.80, and Hardy-Weinberg equilibrium p >= 0.001. Results: We summarize results from 17 traits in up to 1238 related middle-aged to elderly men and women. Results of all association and linkage analyses are web-posted at http://ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. We confirmed modest-to-strong heritabilities ( estimates 0.30-0.52) for several Echo, ETT and BA function traits. Overall, p < 10(-5) in either GEE or FBAT models were observed for 21 SNPs ( nine for echocardiography, eleven for ETT and one for BA function). The top SNPs associated were ( GEE results): LV diastolic dimension, rs1379659 ( SLIT2, p = 1.17* 10(-7)); LV systolic dimension, rs10504543 ( KCNB2, p = 5.18* 10(-6)); LV mass, rs10498091 ( p = 5.68* 10(-6)); Left atrial size, rs1935881 ( FAM5C, p = 6.56* 10(-6)); exercise heart rate, rs6847149 ( NOLAI, p = 2.74* 10(-6)); exercise systolic blood pressure, rs2553268 ( WRN, p = 6.3* 10(-6)); BA baseline flow, rs3814219 ( OBFCI, 9.48* 10(-7)), and FMD, rs4148686 ( CFTR, p = 1.13* 10(-5)). Several SNPs are reasonable biological candidates, with some being related to multiple traits suggesting pleiotropy. The peak LOD score was for LV mass ( 4.38; chromosome 5); the 1.5 LOD support interval included NRG2. Conclusion: In hypothesis-generating GWAS of echocardiography, ETT and BA vascular function in a moderate-sized community-based sample, we identified several SNPs that are candidates for replication attempts and we provide a web-based GWAS resource for the research community. C1 Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Math & Stat, Boston, MA 02118 USA. Vat Adm Hosp, W Roxbury, MA USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. Cardiovasc Engn Inc, Waltham, MA USA. Harvard Univ, Cambridge, MA 02138 USA. Broad Inst Masschusetts Inst Technol, Program Med & Populat Genet, Cambridge, MA 02138 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Vasan, RS (reprint author), Framingham Heart Dis Epidemiol Study, NHLBI, Framingham, MA 01702 USA. EM vasan@bu.edu; mlarson@bu.edu; Jayashri.Aragam@va.gov; tjwang@partners.org; GaryFMitchell@mindspring.com; skathiresan1@partners.org; cnewtoncheh@partners.org; jvita@bu.edu; mjkeyes@bu.edu; codonnell@nih.gov; levyd@nih.gov; emelia@bu.edu OI Larson, Martin/0000-0002-9631-1254; Vita, Joseph/0000-0001-5607-1797; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [N01HC25195, 1R01 HL60040, HL080124, K23 HL074077, K23 HL080025, K23-HL-074077, K23-HL080025, K24 HL004334, K24-HL04334, N01-HC-25195, R01 HL060040, R01 HL070100, R01 HL080124, R01 HL70100]; NINDS NIH HHS [6R01-NS 17950, R01 NS017950] NR 69 TC 49 Z9 49 U1 1 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S2 DI 10.1186/1471-2350-8-S1-S2 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800002 PM 17903301 ER PT J AU Wilk, JB Walter, RE Laramie, JM Gottlieb, DJ O'Connor, GT AF Wilk, Jemma B. Walter, Robert E. Laramie, Jason M. Gottlieb, Daniel J. O'Connor, George T. TI Framingham Heart Study genome-wide association: results for pulmonary function measures SO BMC MEDICAL GENETICS LA English DT Article ID LUNG-FUNCTION; LINKAGE ANALYSIS; DISEASE; GENE; POLYMORPHISMS; POPULATION; BROWSER; DECLINE; COPD; UCSC AB Background: Pulmonary function measures obtained by spirometry are used to diagnose chronic obstructive pulmonary disease ( COPD) and are highly heritable. We conducted genome-wide association ( GWA) analyses ( Affymetrix 100 K SNP GeneChip) for measures of lung function in the Framingham Heart Study. Methods: Ten spirometry phenotypes including percent of predicted measures, mean spirometry measures over two examinations, and rates of change based on forced expiratory volume in one second ( FEV1), forced vital capacity ( FVC), forced expiratory flow from the 25(th) to 75(th) percentile ( FEF25-75), the FEV1/FVC ratio, and the FEF25-75/FVC ratio were examined. Percent predicted phenotypes were created using each participant's latest exam with spirometry. Predicted lung function was estimated using models defined in the set of healthy never-smokers, and standardized residuals of percent predicted measures were created adjusting for smoking status, pack-years, and body mass index ( BMI). All modeling was performed stratified by sex and cohort. Mean spirometry phenotypes were created using data from two examinations and adjusting for age, BMI, height, smoking and pack-years. Change in pulmonary function over time was studied using two to four examinations with spirometry to calculate slopes, which were then adjusted for age, height, smoking and pack-years. Results: Analyses were restricted to 70,987 autosomal SNPs with minor allele frequency >= 10%, genotype call rate >= 80%, and Hardy-Weinberg equilibrium p-value >= 0.001. A SNP in the interleukin 6 receptor ( IL6R) on chromosome 1 was among the best results for percent predicted FEF25-75. A non-synonymous coding SNP in glutathione S-transferase omega 2 ( GSTO2) on chromosome 10 had top-ranked results studying the mean FEV1 and FVC measurements from two examinations. SNPs nearby the SOD3 and vitamin D binding protein genes, candidate genes for COPD, exhibited association to percent predicted phenotypes. Conclusion: GSTO2 and IL6R are credible candidate genes for association to pulmonary function identified by GWA. These and other observed associations warrant replication studies. This resource of GWA results for pulmonary function measures is publicly available at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. C1 Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Med, Boston, MA 02118 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. Boston Univ, Program Bioinformat, Boston, MA 02215 USA. VA Boston Healthcare Syst, Boston, MA USA. RP Wilk, JB (reprint author), Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. EM jwilk@bu.edu; walterb@bu.edu; laramiej@bu.edu; dgottlieb@lung.bumc.bu.edu; goconnor@lung.bumc.bu.edu OI Walter, Robert/0000-0003-4931-5049; O'Connor, George/0000-0002-6476-3926 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [N01-HC25195, N01HC25195] NR 28 TC 58 Z9 62 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S8 DI 10.1186/1471-2350-8-S1-S8 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800008 PM 17903307 ER PT J AU Yang, Q Kathiresan, S Lin, JP Tofler, GH O'Donnell, CJ AF Yang, Qiong Kathiresan, Sekar Lin, Jing-Ping Tofler, Geoffrey H. O'Donnell, Christopher J. TI Genome-wide association and linkage analyses of hemostatic factors and hematological phenotypes in the Framingham Heart Study SO BMC MEDICAL GENETICS LA English DT Article ID TISSUE-PLASMINOGEN ACTIVATOR; COMMON GENETIC-VARIATION; MYOCARDIAL-INFARCTION; RISK-FACTOR; CARDIOVASCULAR-DISEASE; FIBRINOGEN; PLASMA; AGGREGATION; INHIBITOR-1; MARKERS AB Background: Increased circulating levels of hemostatic factors as well as anemia have been associated with increased risk of cardiovascular disease ( CVD). Known associations between hemostatic factors and sequence variants at genes encoding these factors explain only a small proportion of total phenotypic variation. We sought to confirm known putative loci and identify novel loci that may influence either trait in genome-wide association and linkage analyses using the Affymetrix GeneChip 100K single nucleotide polymorphism ( SNP) set. Methods: Plasma levels of circulating hemostatic factors ( fibrinogen, factor VII, plasminogen activator inhibitor-1, von Willebrand factor, tissue plasminogen activator, D-dimer) and hematological phenotypes ( platelet aggregation, viscosity, hemoglobin, red blood cell count, mean corpuscular volume, mean corpuscular hemoglobin concentration) were obtained in approximately 1000 Framingham Heart Study ( FHS) participants from 310 families. Population-based association analyses using the generalized estimating equations ( GEE), family-based association test ( FBAT), and multipoint variance components linkage analyses were performed on the multivariable adjusted residuals of hemostatic and hematological phenotypes. Results: In association analysis, the lowest GEE p-value for hemostatic factors was p = 4.5* 10(-16) for factor VII at SNP rs561241, a variant located near the F7 gene and in complete linkage disequilibrium ( LD) ( r(2) = 1) with the Arg353Gln F7 SNP previously shown to account for 9% of total phenotypic variance. The lowest GEE p-value for hematological phenotypes was 7* 10(-8) at SNP rs2412522 on chromosome 4 for mean corpuscular hemoglobin concentration. We presented top 25 most significant GEE results with p-values in the range of 10(-6) to 10(-5) for hemostatic or hematological phenotypes. In relating 100K SNPs to known candidate genes, we identified two SNPs ( rs1582055, rs4897475) in erythrocyte membrane protein band 4.1-like 2 ( EPB41L2) associated with hematological phenotypes ( GEE p < 10(-3)). In linkage analyses, the highest linkage LOD score for hemostatic factors was 3.3 for factor VII on chromosome 10 around 15 Mb, and for hematological phenotypes, LOD 3.4 for hemoglobin on chromosome 4 around 55 Mb. All GEE and FBAT association and variance components linkage results can be found at http://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?id=phs000007. Conclusion: Using genome-wide association methodology, we have successfully identified a SNP in complete LD with a sequence variant previously shown to be strongly associated with factor VII, providing proof of principle for this approach. Further study of additional strongly associated SNPs and linked regions may identify novel variants that influence the inter-individual variability in hemostatic factors and hematological phenotypes. C1 Framing Heart Study, NHLBI, Framingham, MA 01702 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02215 USA. MIT, Cambridge, MA 02139 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. NHLBI, NIH, Off Biostat Res, Bethesda, MD 20892 USA. Royal N Shore Hosp, Sydney, NSW, Australia. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02115 USA. RP O'Donnell, CJ (reprint author), Framing Heart Study, NHLBI, Framingham, MA 01702 USA. EM qyang@bu.edu; skathiresan1@partners.org; linj@nhlbi.nih.gov; gtofler@nsccahs.health.nsw.gov; odonnellc@nhlbi.nih.gov RI Yang, Qiong/G-5438-2014; OI Yang, Qiong/0000-0002-3658-1375 FU NCRR NIH HHS [1S10RR163736-01A1]; NHLBI NIH HHS [N01-HC-25195, N01HC25195] NR 34 TC 44 Z9 44 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PY 2007 VL 8 SU 1 AR S12 DI 10.1186/1471-2350-8-S1-S12 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 216PV UT WOS:000249891800012 PM 17903294 ER PT J AU Ramat, S Leigh, RJ Zee, DS Optican, LM AF Ramat, Stefano Leigh, R. John Zee, David S. Optican, Lance M. TI What clinical disorders tell us about the neural control of saccadic eye movements SO BRAIN LA English DT Review DE cerebellum; macrosaccadic oscillations; opsoclonus; saccadic palsy; superior colliculus ID MESENCEPHALIC RETICULAR-FORMATION; MONKEY SUPERIOR COLLICULUS; ALERT SQUIRREL-MONKEY; MEDIAL LONGITUDINAL FASCICULUS; ROSTRAL INTERSTITIAL NUCLEUS; PONTINE OMNIPAUSE NEURONS; EXCITATORY BURST NEURONS; VISUALLY GUIDED SACCADES; CAUDAL FASTIGIAL NUCLEUS; TAY-SACHS-DISEASE AB Saccades are rapid eye movements that redirect the fovea from one object to another. A great deal has been learned about the anatomy and physiology of saccades, making them an ideal system for studying the neural control of movement. Basic research on normal eye movements has greatly increased our understanding of saccadic performance, anatomy and physiology, and led to a large number of control system models. These models simulate normal saccades well, but are challenged by clinical disorders because they often do not incorporate the specific anatomical and physiological substrates needed to model clinically important abnormalities. Historically, studies of saccadic abnormalities in patients have played a critical role in understanding the neural control of saccades because they provide information that complements basic research and thus restricts hypotheses to those that are biologically plausible. This review presents four examples of clinical disorders (slow saccades, interrupted saccades, high-frequency saccadic oscillations and macrosaccadic oscillations) that have provided insights into the neurobiology of saccades, have driven the development of new models, and have suggested an explanation or treatment for these disorders. We raise general questions for both scientists and clinicians that will assist in their efforts to understand the neural control of movement, improve diagnostic criteria and develop new treatments. C1 NEI, Sensorimotor Res Lab, NIH, DHHS, Bethesda, MD 20892 USA. Univ Pavia, I-27100 Pavia, Italy. Case Western Reserve Univ, Cleveland, OH 44106 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. RP Optican, LM (reprint author), NEI, Sensorimotor Res Lab, NIH, DHHS, Bldg 49,Room 2A50, Bethesda, MD 20892 USA. EM LanceOptican@nih.gov RI Ramat, Stefano/E-6495-2011 OI Ramat, Stefano/0000-0001-5932-186X FU Intramural NIH HHS; NEI NIH HHS [EY01849, EY06717, EY08060] NR 137 TC 89 Z9 92 U1 2 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JAN PY 2007 VL 130 BP 10 EP 35 DI 10.1093/brain/awl309 PN 1 PG 26 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 120CP UT WOS:000243061500003 PM 17121745 ER PT J AU Ries, M Kim, HJ Zalewski, CK Mastroianni, MA Moore, DF Brady, RO Dambrosia, JM Schiffmann, R Brewer, CC AF Ries, M. Kim, H. J. Zalewski, C. K. Mastroianni, M. A. Moore, D. F. Brady, R. O. Dambrosia, J. M. Schiffmann, R. Brewer, C. C. TI Neuropathic and cerebrovascular correlates of hearing loss in Fabry disease SO BRAIN LA English DT Article DE Fabry disease; stroke; hearing impairment; peripheral neuropathy; X-linked disorder ID ENZYME-REPLACEMENT THERAPY; CLINICAL MANIFESTATIONS; ALPHA-GALACTOSIDASE; AGALSIDASE-ALPHA; MUTATIONS; PHENOTYPE; CHILDREN; IMPACT; COHORT AB Fabry disease, OMIM 301500, is a progressive multisystem storage disorder due to the deficiency of alpha-galactosidase A (GALA). Neurological and vascular manifestations of this disorder with regard to hearing loss have not been analysed quantitatively in large cohorts. We conducted a retrospective cross sectional analysis of hearing loss in 109 male and female patients with Fabry disease who were referred to and seen at the Clinical Center of the National Institutes of Health, Bethesda, MD, USA on natural history and enzyme replacement study protocols. There were 85 males aged 6-58 years (mean 31 years, SD 13) and 24 females aged 22-72 years (mean 42 years, SD 12). All patients underwent a comprehensive audiological evaluation. In addition, cerebral white matter lesions, peripheral neuropathy, and kidney function were quantitatively assessed. HL95, defined as a hearing threshold above the 95th percentile for age and gender matched normal controls, was present in 56% [95% CI (42.2-67.2)] of the males. Prevalence of HL95 was lower in the group of patients with residual GALA enzyme activity compared with those without detectable activity (33% versus 63%) HL95 was present in the low-, mid- and high-frequency ranges for all ages. Male patients with HL95 had a higher microvascular cerebral white matter lesion load [1.4, interquartile range (IQR) 0-30.1 +/- versus 0, IQR 0-0], more pronounced cold perception deficit [19.4 +/- 5.5 versus 13.5 +/- 5.5 of just noticeable difference (JND) units] and lower kidney function [creatinine: 1.6 +/- 1.2 versus 0.77 +/- 0.2 mg/dl; blood urea nitrogen (BUN): 20.1 +/- 14.1 versus 10.3 +/- 3.28 mg/dl] than those without HL95 (P < 0.001). Of the females, 38% had HL95. There was no significant association with cold perception deficit, creatinine or BUN in the females. Word recognition and acoustic reflexes analyses suggested a predominant cochlear involvement. We conclude that hearing loss involving all frequency regions significantly contributes to morbidity in patients with Fabry disease. Our quantitative analysis suggests a correlation of neuropathic and vascular damage with hearing loss in the males. Residual GALA activity appears to have a protective effect against hearing loss. C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Biostat Branch, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Otolaryngol Branch, Bethesda, MD USA. Univ Manitoba, Neurol Sect, Dept Internal Med, Winnipeg, MB R3T 2N2, Canada. RP Schiffmann, R (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, 9000 Rockville Pike,Room 3D03, Bethesda, MD 20892 USA. EM rs4e@nih.gov OI Ries, Markus/0000-0002-5054-5741 FU Intramural NIH HHS [Z01 NS002984-09] NR 33 TC 32 Z9 39 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 JAN PY 2007 VL 130 BP 143 EP 150 DI 10.1093/brain/awl310 PN 1 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 120CP UT WOS:000243061500013 PM 17105746 ER PT J AU Chanock, SJ Burdett, L Yeager, M Llaca, V Langerod, A Presswalla, S Kaaresen, R Strausberg, RL Gerhard, DS Kristensen, V Perou, CM Borresen-Dale, AL AF Chanock, Stephen J. Burdett, Laurie Yeager, Meredith Llaca, Victor Langerod, Anita Presswalla, Shafaq Kaaresen, Rolf Strausberg, Robert L. Gerhard, Daniela S. Kristensen, Vessela Perou, Charles M. Borresen-Dale, Anne-Lise TI Somatic sequence alterations in twenty-one genes selected by expression profile analysis of breast carcinomas SO BREAST CANCER RESEARCH LA English DT Article ID E-CADHERIN; PIK3CA GENE; TP53 GENE; COLORECTAL CANCERS; MICROARRAY DATA; HIGH-FREQUENCY; LUNG-CANCER; COPY NUMBER; MUTATIONS; GENOME AB Introduction Genomic alterations have been observed in breast carcinomas that affect the capacity of cells to regulate proliferation, signaling, and metastasis. Re-sequence studies have investigated candidate genes based on prior genetic observations ( changes in copy number or regions of genetic instability) or other laboratory observations and have defined critical somatic mutations in genes such as TP53 and PIK3CA. Methods We have extended the paradigm and analyzed 21 genes primarily identified by expression profiling studies, which are useful for breast cancer subtyping and prognosis. This study conducted a bidirectional re-sequence analysis of all exons and 5', 3', and evolutionarily conserved regions ( spanning more than 16 megabases) in 91 breast tumor samples. Results Eighty-seven unique somatic alterations were identified in 16 genes. Seventy-eight were single base pair alterations, of which 23 were missense mutations; 55 were distributed across conserved intronic regions or the 5' and 3' regions. There were nine insertion/deletions. Because there is no a priori way to predict whether any one of the identified synonymous and noncoding somatic alterations disrupt function, analysis unique to each gene will be required to establish whether it is a tumor suppressor gene or whether there is no effect. In five genes, no somatic alterations were observed. Conclusion The study confirms the value of re-sequence analysis in cancer gene discovery and underscores the importance of characterizing somatic alterations across genes that are related not only by function, or functional pathways, but also based upon expression patterns. C1 NCI, Canc Res Ctr, Pediat Oncol Branch, Sect Genom Variat,NIH, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, SAID Frederick, Intramural Res Support Program, Frederick, MD 21702 USA. Norwegian Radium Hosp, Rikshosp, Med Ctr, Inst Canc Res,Dept Genet, N-0310 Oslo, Norway. Univ Oslo, Ulleval Hosp, Dept Surg, N-0407 Oslo, Norway. J Craig Venter Inst, Rockville, MD 20850 USA. NCI, Off Canc Genom, Bethesda, MD 20892 USA. Univ Oslo, Fac Med, N-0316 Oslo, Norway. Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pathol, Chapel Hill, NC 27599 USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Lab Med, Chapel Hill, NC 27599 USA. RP Chanock, SJ (reprint author), NCI, Canc Res Ctr, Pediat Oncol Branch, Sect Genom Variat,NIH, Bethesda, MD 20892 USA. EM chanocks@mail.nih.gov OI Perou, Charles/0000-0001-9827-2247 FU Intramural NIH HHS; NCI NIH HHS [P50 CA058223, P50-CA58223-09A1, R01 CA101227, R01-CA-101227-01] NR 44 TC 20 Z9 29 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2007 VL 9 IS 1 AR R5 DI 10.1186/bcr1637 PG 9 WC Oncology SC Oncology GA 158RH UT WOS:000245810800011 PM 17224074 ER PT J AU Girard, GM Vanzulli, SI Cerliani, JP Bottino, MC Bolado, J Vela, J Becu-Villalobos, D Benavides, F Gutkind, S Patel, V Molinolo, A Lanari, C AF Girard, Guadalupe Montero Vanzulli, Silvia I. Cerliani, Juan Pablo Bottino, Maria Cecilia Bolado, Julieta Vela, Jorge Becu-Villalobos, Damasia Benavides, Fernando Gutkind, Silvio Patel, Vyomesh Molinolo, Alfredo Lanari, Claudia TI Association of estrogen receptor-alpha and progesterone receptor A expression with hormonal mammary carcinogenesis: role of the host microenvironment SO BREAST CANCER RESEARCH LA English DT Article ID MEDROXYPROGESTERONE ACETATE MPA; EPIDERMAL-GROWTH-FACTOR; BALB/C FEMALE MICE; BREAST-CANCER RISK; N-NITROSOUREA MNU; EPITHELIAL-CELLS; TUMOR SUSCEPTIBILITY; SIGNAL-TRANSDUCTION; MOUSE STRAINS; GLAND AB Introduction Medroxyprogesterone acetate (MPA) induces estrogen receptor (ER)-positive and progesterone receptor (PR)-positive ductal invasive mammary carcinomas in BALB/c mice. We sought to reproduce this MPA cancer model in C57BL/6 mice because of their widespread use in genetic engineering. Within this experimental setting, we studied the carcinogenic effects of MPA, the morphologic changes in mammary glands that are induced by MPA and progesterone, and the levels of ER and PR expression in MPA-treated and progesterone-treated mammary glands. Finally, we evaluated whether the differences found between BALB/c and C57BL/6 mouse strains were due to intrinsic differences in epithelial cells. Methods The carcinogenic effect of MPA was evaluated in C57BL/6 mice using protocols proven to be carcinogenic in BALB/c mice. In addition, BALB/c and C57BL/6 females were treated with progesterone or MPA for 1 or 2 months, and mammary glands were excised for histologic studies and for immunohistochemical and Western blot evaluation of ER and PR. Hormone levels were determined by radioimmunoassay. Isolated mammary epithelial cells were transplanted into cleared fat pads of 21-day-old female Swiss nu/nu mice or control congenic animals. Results MPA failed to induce mammary carcinomas or significant morphologic changes in the mammary glands of C57BL/6 mice. The expression of ER-alpha and PR isoform A in virgin mice was surprisingly much higher in BALB/c than in C57BL/6 mammary glands, and both receptors were downregulated in progestin-treated BALB/c mice ( P < 0.05). PR isoform B levels were low in virgin control mice and increased after progestin treatment in both strains. ER-beta expression followed a similar trend. No differences in hormone levels were found between strains. Surprisingly, the transplantation of the epithelial mammary gland cells of both strains into the cleared fat pads of Swiss (nu/nu) mice abolished the mammary gland morphologic differences and the ER and PR differences between strains. Conclusion C57BL/6 mammary glands are resistant to MPA-induced carcinogenesis and to hormone action. MPA and progesterone have different effects on mammary glands. Low ER-alpha and PR-A levels in untreated mammary glands may be associated with a low-risk breast cancer profile. Although we cannot at this time rule out the participation of other, untested factors, our findings implicate the stroma as playing a crucial role in the strain-specific differential hormone receptor expression and hormone responsiveness. C1 Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt, RA-1428 Buenos Aires, DF, Argentina. Acad Nacl Med Buenos Aires, Inst Invest Oncol, RA-1425 Buenos Aires, DF, Argentina. Univ Texas, MD Anderson Canc Ctr, Dept Carcinogenesis, Sci Pk Res Div, Smithville, TX 78957 USA. Natl Inst Dent & Craniofacial Res, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. RP Lanari, C (reprint author), Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt, 2490 V de Obligado, RA-1428 Buenos Aires, DF, Argentina. EM clanari@dna.uba.ar RI Gutkind, J. Silvio/A-1053-2009 NR 65 TC 7 Z9 7 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-542X EI 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2007 VL 9 IS 2 AR R22 DI 10.1186/bcr1660 PG 16 WC Oncology SC Oncology GA 186DY UT WOS:000247760500008 ER PT J AU Mack, DL Boulanger, CA Callahan, R Smith, GH AF Mack, David L. Boulanger, Corinne A. Callahan, Robert Smith, Gilbert H. TI Expression of truncated Int6/eIF3e in mammary alveolar epithelium leads to persistent hyperplasia and tumorigenesis SO BREAST CANCER RESEARCH LA English DT Article ID EUKARYOTIC TRANSLATION INITIATION-FACTOR-3; COP9 SIGNALOSOME; TRANSGENIC MICE; TUMOR VIRUS; CYCLIN-E; UBIQUITIN LIGASE; P48 EIF3E; GENE; SUBUNIT; INT-6 AB Introduction Int6 has been shown to be an interactive participant with the protein translation initiation complex eIF3, the COP9 signalosome and the regulatory lid of the 26S proteasome. Insertion of mouse mammary tumor virus into the Int6 locus creates a C-terminally truncated form of the protein. Expression of the truncated form of Int6 ( Int6sh) in stably transfected human and mouse mammary epithelial cell lines leads to cellular transformation. In addition, decreased expression of Int6/eIF3e is observed in approximately one third of all human breast carcinomas. Methods To validate that Int6sh has transforming activity in vivo, a transgenic mouse model was designed using the whey acidic protein ( Wap) promoter to target expression of truncated Int6 to differentiating alveolar epithelial cells in the mammary gland. Microarray analyses were performed on normal, premalignant and malignant WapInt6sh expressing tissues. Results Mammary tumors developed in 42% of WapInt6sh heterozygous parous females at an average age of 18 months. In WapInt6sh mice, the contralateral mammary glands from both tumorous and non-tumorous tissues contained widespread focal alveolar hyperplasia. Only 4% of WapInt6sh non-breeding females developed tumors by 2 years of age. The Wap promoter is active only during estrus in the mammary tissue of cycling nonpregnant mice. Microarray analyses of mammary tissues demonstrated that Int6sh expression in the alveolar tissue altered the mammary transcriptome in a specific manner that was detectable even in the first pregnancy. This Int6sh-specific transcriptome pattern subsequently persisted in both the Int6sh-expressing alveolar hyperplasia and mammary tumors. These observations are consistent with the conclusion that WapInt6sh-expressing alveolar cells survive involution following the cessation of lactation, and subsequently give rise to the mammary tumors that arise in aging multiparous females. Conclusion These observations provide direct in vivo evidence that mammary-specific expression of the Int6sh truncation leads to persistence of alveolar hyperplasia with the accompanying increased predisposition to mammary tumorigenesis. C1 NCI, NIH, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. RP Smith, GH (reprint author), NCI, NIH, Mammary Biol & Tumorigenesis Lab, Bethesda, MD 20892 USA. EM gs4d@nih.gov FU Intramural NIH HHS NR 31 TC 19 Z9 20 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2007 VL 9 IS 4 AR R42 DI 10.1186/bcr1742 PG 12 WC Oncology SC Oncology GA 230NL UT WOS:000250883100010 PM 17626637 ER PT J AU Stevenson, HS Fu, SW Pinzone, JJ Rheey, J Simmens, SJ Berg, PE AF Stevenson, Holly S. Fu, Sidney W. Pinzone, Joseph J. Rheey, Jinguen Simmens, Samuel J. Berg, Patricia E. TI BP1 transcriptionally activates bcl-2 and inhibits TNF alpha-induced cell death in MCF7 breast cancer cells SO BREAST CANCER RESEARCH LA English DT Article ID BETA-GLOBIN GENE; HOMEOBOX GENE; INDUCED APOPTOSIS; P53 EXPRESSION; PROTEIN; CLEAVAGE; INVASION; MANNER AB Introduction We have previously shown that the Beta Protein 1 (BP1) homeodomain protein is expressed in 81% of invasive ductal breast carcinomas, and that increased BP1 expression correlates with tumor progression. The purpose of our current investigation was to determine whether elevated levels of BP1 in breast cancer cells are associated with increased cell survival. Methods Effects on cell viability and apoptosis of MCF7 cells stably overexpressing BP1 were determined using MTT and Annexin V assays, and through examination of caspase activation. TNF alpha was used to induce apoptosis. The potential regulation of apoptosis-associated genes by BP1 was studied using real-time PCR and western blot analyses. Electrophoretic mobility shift assays, site-directed mutagenesis, and transient assays were performed to specifically characterize the interaction of BP1 with the promoter of the bcl-2 gene. Results Stable overexpression of BP1 led to inhibition of apoptosis in MCF7 breast cancer cells challenged with TNF alpha. Increased BP1 resulted in reduced processing and activation of caspase-7, caspase-8, and caspase-9, and inactivation of the caspase substrate Poly(ADP-Ribose) Polymerase (PARP). Increased levels of full-length PARP and a decrease in procaspase-8 were also associated with BP1 overexpression. The bcl-2 gene is a direct target of BP1 since: (i) BP1 protein bound to a consensus binding sequence upstream of the bcl-2 P1 promoter in vitro. (ii) MCF7 cells overexpressing BP1 showed increased levels of bcl-2 mRNA and protein. (iii) Transient assays indicated that increased bcl-2 promoter activity is due to direct binding and modulation by BP1 protein. BP1 expression also prevented TNF alpha-mediated downregulation of bcl-2 mRNA and protein. Conclusion These findings suggest mechanisms by which increased BP1 may impart a survival advantage to breast cancer cells, which could lead to increased resistance to therapeutic agents in patients. C1 [Stevenson, Holly S.] Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, Bethesda, MD 20892 USA. [Fu, Sidney W.; Rheey, Jinguen; Berg, Patricia E.] George Washington Univ, Med Ctr, Dept Biochem & Mol Biol, Washington, DC 20037 USA. [Pinzone, Joseph J.] Ohio State Univ, Dept Internal Med, Columbus, OH 43210 USA. [Pinzone, Joseph J.] Ohio State Univ, Med Ctr, Ctr Comprehens Canc, Columbus, OH 43210 USA. [Simmens, Samuel J.] George Washington Univ, Dept Epidemiol & Biostat, Washington, DC 20037 USA. RP Berg, PE (reprint author), Natl Inst Hlth, Natl Canc Inst, Ctr Canc Res, 37 Covent Dr, Bethesda, MD 20892 USA. EM bcmpeb@gwumc.edu FU NCI NIH HHS [CA101875, K08 CA101875, R03 CA102928, CA91149, CA102928, R21 CA091149] NR 32 TC 18 Z9 19 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2007 VL 9 IS 5 AR R60 DI 10.1186/bcr1766 PG 9 WC Oncology SC Oncology GA 264KI UT WOS:000253285800009 PM 17854498 ER PT J AU Trabert, B Malone, KE Daling, JR Doody, DR Bernstein, L Ursin, G Marchbanks, PA Strom, BL Humphrey, MC Ostrander, EA AF Trabert, Britton Malone, Kathleen E. Daling, Janet R. Doody, David R. Bernstein, Leslie Ursin, Giske Marchbanks, Polly A. Strom, Brian L. Humphrey, Mariela C. Ostrander, Elaine A. TI Vitamin D receptor polymorphisms and breast cancer risk in a large population-based case-control study of Caucasian and African-American women SO BREAST CANCER RESEARCH LA English DT Article ID BONE-MINERAL DENSITY; ANDROGEN DEPRIVATION THERAPY; PROSTATE-CANCER; GENE POLYMORPHISMS; UNITED-STATES; DAIRY-PRODUCTS; ASSOCIATION; CALCIUM; OSTEOPOROSIS; METAANALYSIS AB Introduction The involvement of vitamin D receptor (VDR), which is a key mediator in the vitamin D pathway, in breast cancer etiology has long been of interest. Methods We examined the association between polymorphisms in the 3' end of the VDR gene, specifically BsmI and Poly( A), and breast cancer risk within a large, population-based, case-control study of breast cancer. Cases (n = 1,631) were Caucasian and African-American women, aged 35 to 64 years, who were diagnosed with incident, invasive breast cancer between July 1994 and April 1998. Control individuals ( n = 1,435) were women without breast cancer ascertained through random digit dialing. Results Accounting for age, study site, and sampling weights, we observed a significantly increased risk for breast cancer among Caucasian, postmenopausal carriers of the bb genotype of BsmI ( odds ratio = 1.53, 95% confidence interval = 1.04 to 2.27). However, no associations with the bb genotype were observed in African-American women. Overall, there were no significant associations between the Poly( A) genotype and breast cancer risk in either racial group. Smoking status (ever/never) modified the association between both the BsmI and Poly( A) genotypes and breast cancer risk. The respective associations between these genotypes and breast cancer risk did not significantly vary by oral contraceptive use, hormone replacement therapy, or body mass index. Conclusion Our results provide additional support for an increased risk for breast cancer in postmenopausal Caucasian women with the BsmI bb genotype and shed light on possible differential effects by menopausal status and race. C1 [Humphrey, Mariela C.; Ostrander, Elaine A.] Fred Hutchinson Canc Res Ctr, Div Human Biol & Clin Res, Seattle, WA 98109 USA. [Trabert, Britton; Malone, Kathleen E.; Daling, Janet R.; Doody, David R.] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. [Trabert, Britton; Malone, Kathleen E.; Daling, Janet R.] Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98195 USA. [Bernstein, Leslie; Ursin, Giske] Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Prevent Med, Los Angeles, CA 90089 USA. [Ursin, Giske] Univ Oslo, Dept Nutr, N-0372 Oslo, Norway. [Marchbanks, Polly A.] Ctr Dis Control, Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. [Strom, Brian L.] Univ Penn, Ctr Clin Epidemiol & Biostat, Dept Biostat & Epidemiol, Philadelphia, PA 19104 USA. [Ostrander, Elaine A.] NIH, NHGRI, Canc Genet Branch, Bethesda, MD 20892 USA. RP Ostrander, EA (reprint author), Fred Hutchinson Canc Res Ctr, Div Human Biol & Clin Res, Seattle, WA 98109 USA. EM eostrand@mail.nih.gov RI Trabert, Britton/F-8051-2015; OI Ostrander, Elaine/0000-0001-6075-9738 FU Intramural NIH HHS; NCI NIH HHS [N01 CN065064, N01 PC067006, N01-CN-0532, N01-CN-65064, N01-CN-67010, N01-PC-67006]; NICHD NIH HHS [N01 HD 2-3166, N01 HD 3-3168, N01 HD 3-3174, N01 HD 3-3175, N01 HD 3-3176, Y01 HD007022] NR 37 TC 54 Z9 54 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1465-5411 J9 BREAST CANCER RES JI Breast Cancer Res. PY 2007 VL 9 IS 6 AR R84 DI 10.1186/bcr1833 PG 10 WC Oncology SC Oncology GA 264KJ UT WOS:000253285900021 PM 18067661 ER PT J AU Auer, RL Dighiero, G Goldin, LR Syndercombe-Court, D Jones, C McElwaine, S Newland, AC Fegan, CD Caporaso, N Cotter, FE AF Auer, Rebecca L. Dighiero, Guillaume Goldin, Lynn R. Syndercombe-Court, Denise Jones, Christopher McElwaine, Suzanne Newland, Adrian C. Fegan, Christopher D. Caporaso, Neil Cotter, Finbarr E. TI Trinucleotide repeat dynamic mutation identifying susceptibility in familial and sporadic chronic lymphocytic leukaemia SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE chronic lymphocytic leukaemia; familial chronic lymphocytic leukaemia; trinucleotide repeats; anticipation ID ANDROGEN RECEPTOR GENE; PROSTATE-CANCER RISK; CAG REPEAT; CELL-LINES; ANTICIPATION; EXPANSION; INSTABILITY; DISEASE; TUMORS; TRANSCRIPTION AB Chronic lymphocytic leukaemia (CLL) has a strong hereditary component, but an understanding of predisposition genes is poor. Anticipation with familial CLL has been reported, although the molecular mechanism is unknown. Expansion of trinucleotide repeat sequences underlies anticipation observed in neuro degenerative disease. A polymerase chain reaction-based assay was used to analyse the stability of ten CCG- and CAG-trinucleotide repeat tracts in 18 CLL families and 140 patients with the sporadic form of the disease. The study suggests that anticipation, if it occurs in CLL, is not linked to CCG- and CAG-repeat expansion, however, variation in repeat length at certain loci (FRA16A) may permit identification of susceptible family members. In addition, polymorphisms with prognostic significance were identified. These were high length (but not expanded) repeats at FRA11B (P = 0.01), ATXN1 (P = 0.032) and ATXN3 (P = 0.022), all associated with poor risk disease. C1 Barts & London Queen Mary Sch Med, Ctr Haematol, Inst Cell & Mol Sci, London E1 2AT, England. Inst Pasteur, Unite Immuno Hematol & Immunopathol, Paris, France. NCI, NIH, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Cardiff & Vale NHS Trust, Dept Haematol, Cardiff, Wales. RP Cotter, FE (reprint author), Barts & London Queen Mary Sch Med, Ctr Haematol, Inst Cell & Mol Sci, 4 Newark St, London E1 2AT, England. EM f.e.cotter@qmul.ac.uk NR 43 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2007 VL 136 IS 1 BP 73 EP 79 DI 10.1111/j.1365-2141.2006.06388.x PG 7 WC Hematology SC Hematology GA 134FT UT WOS:000244069600008 PM 17116127 ER PT J AU Davies, AJ Rosenwald, A Wright, G Lee, A Last, KW Weisenburger, DD Chan, WC Delabie, J Braziel, RM Campo, E Gascoyne, RD Jaffe, ES Muller-Hermelink, HK Ott, G Calaminici, M Norton, AJ Goff, LK Fitzgibbon, J Staudt, LM Lister, TA AF Davies, Andrew J. Rosenwald, Andreas Wright, George Lee, Abigail Last, Kim W. Weisenburger, Dennis D. Chan, Wing C. Delabie, Jan Braziel, Rita M. Campo, Elias Gascoyne, Randy D. Jaffe, Elaine S. Muller-Hermelink, H. Konrad Ott, German Calaminici, Maria Norton, Andrew J. Goff, Lindsey K. Fitzgibbon, Jude Staudt, Louis M. Lister, T. Andrew TI Transformation of follicular lymphoma to diffuse large B-cell lymphoma proceeds by distinct oncogenic mechanisms SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE follicular lymphoma; transformation; diffuse large B-cell lymphoma; expression profiling ID NON-HODGKINS-LYMPHOMA; POLYMERASE-CHAIN-REACTION; GENE-EXPRESSION; HISTOLOGICAL TRANSFORMATION; COPY NUMBER; SOMATIC MUTATION; BONE-MARROW; BCL-6 GENE; PROGRESSION; TRANSLOCATION AB This study was undertaken to further elucidate the biological mechanisms underlying the frequent event of transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL). The gene expression profiles of 20 paired lymph node biopsies, derived from the same patient pre- and post-transformation, were analysed using the Lymphochip cDNA microarray. TP53 mutation analysis was performed and copy number alterations at the c-REL and CDNK2A examined. Immunohistochemistry was performed on an independent panel of paired transformation paraffin-embedded samples. Transformed follicular lymphoma was predominantly of the germinal centre B-like phenotype both at the mRNA and protein level. Despite this homogeneity, transformation proceeded by at least two pathways. One mechanism was characterised by high proliferation, as assessed by the co-ordinately expressed genes of the proliferation signature. This group was associated with the presence of recurrent oncogenic abnormalities. In the remaining cases, proliferation was not increased and transformation proceeded by alternative routes as yet undetermined. Genes involved in cellular proliferation prevailed amongst those that were significantly increased upon transformation and T cell and follicular dendritic-associated genes predominated amongst those that decreased. t-FL is a germinal centre B (GCB)-like malignancy that evolves by two pathways, one that is similar in proliferation rate to the antecedent FL and the other that has a higher proliferation rate and is characterised by the presence of recognised oncogenic abnormalities. C1 St Bartholomews Hosp, Canc Res UK Med Oncol Unit, London C1A 7BE, England. Univ Wurzburg, Dept Pathol, D-8700 Wurzburg, Germany. Natl Canc Inst, Metab Branch, Ctr Canc Res, Bethesda, MD USA. Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68182 USA. Norwegian Radium Hosp, Dept Pathol, Oslo, Norway. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. Univ Barcelona, Hosp Clin Barcelona, Barcelona, Spain. British Columbia Canc Res Ctr, Dept Pathol, Vancouver, BC V5Z 1L3, Canada. Natl Canc Inst, Dept Pathol, Ctr Canc Res, Bethesda, MD USA. St Bartholomews Hosp, Dept Histopathol, London C1A 7BE, England. RP Davies, AJ (reprint author), St Bartholomews Hosp, Canc Res UK Med Oncol Unit, London C1A 7BE, England. EM andrew.davies@cancer.org.uk OI Delabie, Jan/0000-0001-5023-0689; Campo, elias/0000-0001-9850-9793 FU Intramural NIH HHS; NCI NIH HHS [U01 CA114778-01] NR 47 TC 73 Z9 74 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2007 VL 136 IS 2 BP 286 EP 293 DI 10.1111/j.1365-2141.2006.06439.x PG 8 WC Hematology SC Hematology GA 123LU UT WOS:000243298200012 PM 17278262 ER PT J AU Machado, RF Mack, AK Martyr, S Barnett, C MacArthur, P Sachdev, V Ernst, I Hunter, LA Coles, WA Nichols, JP Kato, GJ Gladwin, MT AF Machado, Roberto F. Mack, A. Kyle Martyr, Sabrina Barnett, Christopher MacArthur, Peter Sachdev, Vandana Ernst, Inez Hunter, Lori A. Coles, Wynona A. Nichols, James P. Kato, Gregory J. Gladwin, Mark T. TI Severity of pulmonary hypertension during vaso-occlusive pain crisis and exercise in patients with sickle cell disease SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE sickle cell disease; vaso-occlusive crisis; pulmonary hypertension; nitric oxide; haemolysis ID NITRIC-OXIDE BIOAVAILABILITY; PLASMA HEMOGLOBIN; ARGININE METABOLISM; RISK-FACTOR; DEATH; HEMOLYSIS; ANEMIA; DEHYDROGENASE; SPHEROCYTOSIS; ENDOTHELIN-1 AB Pulmonary hypertension is associated with sudden death and is a risk factor for mortality in adult patients with sickle cell disease. The high mortality despite only mild-to-moderate increases in pulmonary vascular resistance remains an unresolved paradox. Accordingly, little is known about the cardiovascular effects of stressors, such as vaso-occlusive pain crisis (VOC) and exercise, which may acutely increase pulmonary pressures and impair right heart function. We therefore evaluated pulmonary artery pressures by echocardiogram in 25 patients with sickle cell disease in steady-state and during VOC, and by right heart catheterisation with exercise in a second cohort of 21 patients to determine whether pulmonary hypertension worsens during acute cardiopulmonary stress. TRV increased during VOC (P < 0.001), and the increased pulmonary pressures during VOC were associated with decreases in haemoglobin levels (P < 0.001), and increases in lactate dehydrogenase (P < 0.001) and plasma haemoglobin levels (P = 0.03). During exercise stress performed during cardiac catheterisation, mean pulmonary artery pressures (P < 0.001) and pulmonary vascular resistance increased (P < 0.001) in all subjects. These data suggest that acute elevations in pulmonary pressures during VOC or exercise may contribute to morbidity and mortality in patients with sickle cell disease. C1 NHLBI, Vasc Med Branch, NIH, Bethesda, MD 20892 USA. NCI, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Nursing & Patient Care Serv, Bethesda, MD 20892 USA. RP Machado, RF (reprint author), NHLBI, Vasc Med Branch, NIH, 10 Ctr Dr,MSC 1476,Bldg 10CRC,Room 5-5140, Bethesda, MD 20892 USA. EM robertom@nhlbi.nih.gov RI Kato, Gregory/I-7615-2014 OI Kato, Gregory/0000-0003-4465-3217 FU Intramural NIH HHS [Z99 HL999999, ZIA HL006014-02] NR 42 TC 67 Z9 68 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JAN PY 2007 VL 136 IS 2 BP 319 EP 325 DI 10.1111/j.1365-2141.2006.06417.x PG 7 WC Hematology SC Hematology GA 123LU UT WOS:000243298200019 PM 17156401 ER PT J AU Young, L Koenigs, M AF Young, Liane Koenigs, Michael TI Investigating emotion in moral cognition: a review of evidence from functional neuroimaging and neuropsychology SO BRITISH MEDICAL BULLETIN LA English DT Review DE neuroscience; emotion; morality; ventromedial prefrontal cortex ID FRONTOTEMPORAL DEMENTIA; PREFRONTAL CORTEX; ACQUIRED SOCIOPATHY; JUDGMENT; DAMAGE; NETWORKS; FMRI AB Introduction: Human moral decision-making has long been a topic of philosophical debate, and, more recently, a topic for empirical investigation. Central to this investigation is the extent to which emotional processes underlie our decisions about moral right and wrong. Neuroscience offers a unique perspective on this question by addressing whether brain regions associated with emotional processing are involved in moral cognition. Method: We conduct a narrative review of neuroscientific studies focused on the role of emotion in morality. Specifically, we describe evidence implicating the ventromedial prefrontal cortex (VMPC), a brain region known to be important for emotional processing. Results: Functional imaging studies demonstrate VMPC activation during tasks probing moral cognition. Studies of clinical populations, including patients with VMPC damage, reveal an association between impairments in emotional processing and impairments in moral judgement and behaviour. Conclusions: Considered together, these studies indicate that not only are emotions engaged during moral cognition, but that emotions, particularly those mediated by VMPC, are in fact critical for human morality. C1 [Koenigs, Michael] NINDS, Cognit Neurosci Sect, NIH, Bethesda, MD 20892 USA. [Young, Liane] Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. RP Young, L (reprint author), Bldg 10 Room 7-S43,10 Ctr Dr MSC 1440, Bethesda, MD 20892 USA. EM lyoung@fas.harvard.edu; koenigsm@ninds.nih.gov OI Koenigs, Michael/0000-0002-5799-4881 FU Intramural NIH HHS NR 41 TC 65 Z9 69 U1 4 U2 27 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0007-1420 J9 BRIT MED BULL JI Br. Med. Bull. PY 2007 VL 84 BP 69 EP 79 DI 10.1093/bmb/ldm031 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 260YZ UT WOS:000253047600006 PM 18029385 ER PT J AU Baeck, GW Gornez, DK Oh, KS Kim, JH Choresca, CH Park, SC AF Baeck, G. W. Gornez, D. K. Oh, K. S. Kim, J. H. Choresca, C. H., Jr. Park, S. C. TI Detection of piscine nodaviruses from apparently healthy wild marine fish in Korea SO BULLETIN OF THE EUROPEAN ASSOCIATION OF FISH PATHOLOGISTS LA English DT Article ID NERVOUS NECROSIS VIRUS; SEA-BASS; ELISA; VNN AB Piscine nodaviruses are the causative agent of vital encephalopathy and retinopathy and wild marine fish. A total of 663 apparently healthy wild marine fish (70 species) were collected near aquaculture facilities in three different coastal areas (Donghae, Hwanghae and Namhae) of Korea. The brains of fish were examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and nested PCR to detect the coat protein gene of nodavirus. Fourteen samples collected in Donghae and 80 from Hwanghae were negative for nodavirus in both RT-PCR and nested PCR tests. Two and 48 of 569 samples collected in Namhae were positive for nodavirus in RTPCR and nested PCR, respectively. Samples from 21 species have been definitively found positive: Indian perch, white croakers, spearnose grenadier, moon dragonet, blue fin sea robin, robust tonguefish, black throat sea perch, moontail puffer, silver ponyfish, yellow goosefish, daggertooth pike conger, skate ray fish, red sea bream, marbled sole, five spots flounder, chub mackerel, silver whiting, grass puffer, Japanese jack mackerel, John dory and blotched eel pout. These results indicate that nodavirus occurs at a considerably level in populations of wild marine fish in the Southern part of Korea, suggesting an importance of these fish as carriers of virus. C1 Chonnam Natl Univ, Fac Marine Technol, Yeosu 550749, South Korea. Seoul Natl Univ, KRF Zoonot Dis Prior Res Inst, Seoul 151742, South Korea. NCI, Ctr Canc Res, Basic Res Labs, DNA Repair Sect, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Vet Med, Lab Aquat Anim Med, BK21 Program Vet Sci & Lab, Seoul 151742, South Korea. RP Park, SC (reprint author), Chonnam Natl Univ, Fac Marine Technol, Yeosu 550749, South Korea. EM parksec@snu.ac.kr RI Kim, Ji Hyung/B-7321-2011 OI Kim, Ji Hyung/0000-0002-7921-2625 NR 14 TC 8 Z9 8 U1 0 U2 4 PU EUR ASSOC FISH PATHOLOGISTS PI ABERDEEN PA C/O DR DAVID BRUNO, MARINE LABORATORY, PO BOX 101, VICTORIA RD, ABERDEEN AB11 9DB, SCOTLAND SN 0108-0288 J9 B EUR ASSOC FISH PAT JI Bull. Eur. Assoc. Fish Pathol. PY 2007 VL 27 IS 3 BP 116 EP 122 PG 7 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 209IX UT WOS:000249383300006 ER PT J AU Simeonov, K Polianova, M Jordanova, P Roussev, R AF Simeonov, Konstantin Polianova, Maria Jordanova, Plamena Roussev, R. TI Protein a-gold immunoelectron microscope analysis of the antigen activity of the structural components of bovine herpesvirus-4 (BHV-4) particles and surface antigen expression of cells infected with BHV-4 SO BULLETIN OF THE VETERINARY INSTITUTE IN PULAWY LA English DT Article DE bovine herpesvirus; prA-gold immuno-gold electron microscopy; surface antigen expression ID MONOCLONAL-ANTIBODIES; MEMBRANE IMMUNOFLUORESCENCE; GLYCOPROTEINS; TYPE-4; IDENTIFICATION; VIRUS AB Protein A-gold immuno-electron microscope (prA-g-IEM) study was performed to detect virus-induced cell surface antigens on bovine herpesvirus-4 (BHV-4) infected MDBK cells, using pre-embedding prA-g-IEM technique and polyclonal rabbit BHV-4 antiserum. The capability of serum antibodies to recognise epitopes of either capsid or virus envelope structural antigens, was preliminary determined with purified virus preparations using the same technique. Under EM observation, virtually all virions presented as nucleocapsids were intensively labelled, whilst only single gold particles were attached to the enveloped virions. This suggests that BHV-4 envelope do not appear as immunodominant viral structure. Surface immuno-labelling did not localise reactive BHV-4 antigens on membranes of infected MDBK cells, regardless of the stage of infection and mode of processing before immune reaction (fixed and unfixed cells). Those findings substantiate the low immunogenic potential of BHV-4, which could be one of the reasons for its prolonged persistence in infected animals. C1 Bulgarian Acad Sci, Inst Expt Pathol & Parasitol, BU-1113 Sofia, Bulgaria. NCI, Frederick Canc Res & Dev Ctr, Lab Leukocyte Biol, NIH, Frederick, MD 21702 USA. RP Simeonov, K (reprint author), Bulgarian Acad Sci, Inst Expt Pathol & Parasitol, BU-1113 Sofia, Bulgaria. EM kbsimeonov@yahoo.com NR 17 TC 1 Z9 1 U1 0 U2 1 PU NATL VETERINARY RESEARCH INST PI PULAWY PA C/O PUBICATIONS OFFICE, 24-100 PULAWY, POLAND SN 0042-4870 J9 B VET I PULAWY JI Bull. Vet. Inst. Pulawy PY 2007 VL 51 IS 2 BP 203 EP 206 PG 4 GA 186RD UT WOS:000247794900003 ER PT J AU Saslow, D Castle, PE Cox, JT Davey, DD Einstein, MH Ferris, DG Goldie, SJ Harper, DM Kinney, W Moscicki, AB Noller, KL Wheeler, CM Ades, T Andrews, KS Doroshenk, MK Kahn, KG Schmidt, C Shafey, O Smith, RA Partridge, EE AF Saslow, Debbie Castle, Philip E. Cox, J. Thomas Davey, Diane D. Einstein, Mark H. Ferris, Daron G. Goldie, Sue J. Harper, Diane M. Kinney, Walter Moscicki, Anna-Barbara Noller, Kenneth L. Wheeler, Cosette M. Ades, Terri Andrews, Kimberly S. Doroshenk, Mary K. Green Kahn, Kelly Schmidt, Christy Shafey, Omar Smith, Robert A. Partridge, Edward E. CA Gynecologic Canc Advisory Grp TI American Cancer Society guideline for human papillornavirus (HPV) vaccine use to prevent cervical cancer and its precursors SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Review ID HUMAN-PAPILLOMAVIRUS INFECTION; RECURRENT RESPIRATORY PAPILLOMATOSIS; SEXUALLY-TRANSMITTED-DISEASES; RANDOMIZED CONTROLLED-TRIAL; FEMALE UNIVERSITY-STUDENTS; SQUAMOUS-CELL CARCINOMA; VIRUS-LIKE PARTICLES; UNITED-STATES; YOUNG-WOMEN; NATURAL-HISTORY AB The American Cancer Society (ACS) has developed guidelines for the use of the prophylactic human papillomavirus (HPV) vaccine for the prevention of cervical intraepithelial neoplasia and cervical cancer. These recommendations are based on a formal review of the available evidence. They address the use of prophylactic HPV vaccines, including who should be vaccinated and at what age, as well as a summary of policy and implementation issues. Implications for screening are also discussed. C1 Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30329 USA. NCI, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD USA. Univ Calif Santa Barbara, Colposcopy & Gynecol Clin, Dept Hlth Serv, Santa Barbara, CA 93106 USA. Univ Kentucky, Med Ctr, Dept Pathol & Lab Med, Lexington, KY USA. Montefiore Med Ctr, Div Gynecol Oncol, Dept Obstet & Gynecol & Womens Hlth, Bronx, NY 10467 USA. Med Coll Georgia, Gynecol Canc Prevent Ctr, Augusta, GA 30912 USA. Med Coll Georgia, Dept Family Med, Augusta, GA 30912 USA. Med Coll Georgia, Dept Obstet & Gynecol, Augusta, GA 30912 USA. Harvard Univ, Sch Publ Hlth, Program Hlth Decis Sci, Dept Hlth Policy & Management, Boston, MA 02115 USA. Norris Cotton Canc Ctr, Dartmouth Med Sch, Gynecol Canc Prevent Res Grp, Hanover, NH USA. Permanente Med Grp Inc, Div Gynecol Oncol, Sacramento, CA USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Calif San Francisco, Div Adolescent Med, San Francisco, CA 94143 USA. Tufts Univ, New England Med Ctr, Boston, MA 02111 USA. Univ New Mexico, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. Univ New Mexico, Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. Amer Canc Soc, Hlth Promot Dept, Atlanta, GA 30329 USA. Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30329 USA. Amer Canc Soc, Canc Control Sci Dept, Washington, DC USA. Amer Canc Soc, Natl Govt Relat Dept, Washington, DC USA. Amer Canc Soc, Int Programs & Res, Int Affairs Dept, Atlanta, GA 30329 USA. Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. Univ Alabama, Div Gynecol Oncol, Birmingham, AL 35294 USA. Univ Arizona, Natl Ctr Excellence Womens Hlth, Tucson, AZ USA. Arizona Hispan Ctr Excellence, Tucson, AZ USA. RP Saslow, D (reprint author), Amer Canc Soc, Canc Control Sci Dept, Atlanta, GA 30329 USA. NR 167 TC 274 Z9 294 U1 7 U2 40 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD JAN-FEB PY 2007 VL 57 IS 1 BP 7 EP 28 PG 22 WC Oncology SC Oncology GA 133IZ UT WOS:000244007900006 PM 17237032 ER PT J AU Pickle, LW Hao, YP Jemal, A Zou, ZH Tiwari, RC Ward, E Hachey, M Howe, HL Feuer, EJ AF Pickle, Linda W. Hao, Yongping Jemal, Ahmedin Zou, Zhaohui Tiwari, Ram C. Ward, Elizabeth Hachey, Mark Howe, Holly L. Feuer, Eric J. TI A new method of estimating United States and state-level cancer incidence counts for the current calendar year SO CA-A CANCER JOURNAL FOR CLINICIANS LA English DT Article ID INCIDENCE RATES; US AB The American Cancer Society (ACS) has published the estimated number of new cancer cases and deaths in the current year for the United States that are commonly used by cancer control planners and the media. The methods used to produce these estimates have changed over the years as data (incidence) and statistical models improved. In this paper we present a new method that uses statistical models of cancer incidence that incorporate potential predictors of spatial and temporal variation of cancer occurrence and that account for delay in case reporting and then projects these estimated numbers of cases ahead 4 years using a piecewise linear (joinpoint) regression method. Based on evidence presented here that the new method produces more accurate estimates of the number of new cancer cases for years and areas for which data are available for comparison, the ACS has elected to use it to estimate the number of new cancer cases in Cancer Facts & Figures 2007 and in Cancer Statistics, 2007. C1 NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. Informat Management Serv Inc, Silver Spring, MD USA. Cent Canc Registries Inc, N Amer Assoc, Springfield, IL USA. RP Pickle, LW (reprint author), NCI, Stat Res & Applicat Branch, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NR 28 TC 59 Z9 62 U1 2 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0007-9235 J9 CA-CANCER J CLIN JI CA-Cancer J. Clin. PD JAN-FEB PY 2007 VL 57 IS 1 BP 30 EP 42 PG 13 WC Oncology SC Oncology GA 133IZ UT WOS:000244007900007 PM 17237034 ER PT J AU Chang, W Cabral, WA Barnes, AM Eyre, DR Weis, M Morello, R Lee, B Leikin, S Rosenbaum, K Tiffi, C Bulas, DI Kozma, C Smith, P Mulvihill, JJ Sundaram, UT Marini, JC AF Chang, W. Cabral, W. A. Barnes, A. M. Eyre, D. R. Weis, M. Morello, R. Lee, B. Leikin, S. Rosenbaum, K. Tiffi, C. Bulas, D. I. Kozma, C. Smith, P. Mulvihill, J. J. Sundaram, U. T. Marini, J. C. TI Deficiency of components of the collagen prolyl 3-hydroxylation complex causes a recessive bone dysplasia resembling lettial/severe osteogenesis imperfecta SO CALCIFIED TISSUE INTERNATIONAL LA English DT Meeting Abstract C1 NICHD, Bone Extracellular Matrix Branch, NIH, Bethesda, MD USA. Univ Washington, Orthoped Res Labs, Seattle, WA 98195 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. NICHD, Sect Phys Biochem, NIH, Bethesda, MD USA. Georgetown Univ Hosp, Childrens Natl Med Ctr, Dept Genet, Washington, DC 20007 USA. Georgetown Univ Hosp, Childrens Natl Med Ctr, Dept Diagnost Imaging & Radiol, Washington, DC 20007 USA. Georgetown Univ Hosp, Dept Pediat, Washington, DC 20007 USA. Shriners Hosp Crippled Children, Gait Anal Lab, Chicago, IL USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pediat, Oklahoma City, OK 73190 USA. Virginia Commonwealth Univ Med Coll Virginia, Richmond, VA 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 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PY 2007 VL 80 SU 1 BP S35 EP S36 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 170JP UT WOS:000246660000074 ER PT J AU Stone, SV McCrae, RR AF Stone, Stephanie V. McCrae, Robert R. BA Ayers, S Baum, A McManus, C Newman, S Wallston, K Weinman, J West, R BF Ayers, S Baum, A McManus, C Newman, S Wallston, K Weinman, J West, R TI Personality and health SO CAMBRIDGE HANDBOOK OF PSYCHOLOGY, HEALTH AND MEDICINE, 2ND EDITION LA English DT Article; Book Chapter ID 5-FACTOR MODEL; DEPRESSIVE SYMPTOMS; PLANNED BEHAVIOR; CONSCIENTIOUSNESS; PREDICTORS; HOSTILITY; ADHERENCE; TRIAL; RISK; CARE C1 [Stone, Stephanie V.] Johns Hopkins Univ, Baltimore, MD 21154 USA. [McCrae, Robert R.] NIA, NJH, DNHS, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Stone, SV (reprint author), Johns Hopkins Univ, 1119 Taylor Rd St, Baltimore, MD 21154 USA. NR 29 TC 4 Z9 4 U1 2 U2 3 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-52160-510-6 PY 2007 BP 151 EP 155 PG 5 WC Psychology, Multidisciplinary SC Psychology GA BYD80 UT WOS:000298164400033 ER PT J AU Lipkowitz, S Dennis, PA AF Lipkowitz, Stanley Dennis, Phillip A. TI PPAR gamma agonists follow an unknown TRAIL in lung cancer SO CANCER BIOLOGY & THERAPY LA English DT Editorial Material DE PPAR gamma; TRAIL; NSCLC; apoptosis; DR5; c-FLIP ID APOPTOSIS-INDUCING LIGAND; ACTIVATED RECEPTOR-GAMMA; SENSITIZES TUMOR-CELLS; IN-VIVO; TERMINAL DIFFERENTIATION; INHIBITORY PROTEIN; ANTITUMOR-ACTIVITY; DECOY RECEPTORS; TARGETING DEATH; BREAST-CANCER C1 NCI, Lab Cellular, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol & Med Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Dennis, PA (reprint author), 8901 Wisconsin Ave,Bldg 8,Rm 5101, Bethesda, MD 20889 USA. EM dennisp@mail.nih.gov NR 51 TC 5 Z9 5 U1 0 U2 0 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 JAN PY 2007 VL 6 IS 1 BP 107 EP 109 DI 10.4161/cbt.6.1.3751 PG 3 WC Oncology SC Oncology GA 158RJ UT WOS:000245811100030 PM 17224637 ER PT J AU Batchelor, TT Sorensen, AG di Tomaso, E Zhang, WT Duda, DG Cohen, KS Kozak, KR Cahill, DP Chen, PJ Zhu, MW Ancukiewicz, M Mrugala, MM Plotkin, S Drappatz, J Louis, DN Ivy, P Scadden, DT Benner, T Loeffler, JS Wen, PY Jain, RK AF Batchelor, Tracy T. Sorensen, A. Gregory di Tomaso, Emmanuelle Zhang, Wei-Ting Duda, Dan G. Cohen, Kenneth S. Kozak, Kevin R. Cahill, Daniel P. Chen, Poe-Jou Zhu, Mingwang Ancukiewicz, Marek Mrugala, Maciej M. Plotkin, Scott Drappatz, Jan Louis, David N. Ivy, Percy Scadden, David T. Benner, Thomas Loeffler, Jay S. Wen, Patrick Y. Jain, Rakesh K. TI AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients SO CANCER CELL LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RECURRENT MALIGNANT GLIOMA; RECTAL-CANCER PATIENTS; HIGH-GRADE GLIOMAS; BLOOD-VOLUME MAPS; PHASE-I TRIAL; ANTIANGIOGENIC THERAPY; PERMEABILITY FACTOR; PROGENITOR CELLS; CLINICAL-TRIALS AB Using MRI techniques, we show here that normalization of tumor vessels in recurrent glioblastoma patients by daily administration of AZD2171-an oral tyrosine kinase inhibitor of VEGF receptors-has rapid onset, is prolonged but reversible, and has the significant clinical benefit of alleviating edema. Reversal of normalization began by 28 days, though some features persisted for as long as four months. Basic FGF, SDF1 alpha, and viable circulating endothelial cells (CECs) increased when tumors escaped treatment, and circulating progenitor cells (CPCs) increased when tumors progressed after drug interruption. Our study provides insight into different mechanisms of action of this class of drugs in recurrent glioblastoma patients and suggests that the timing of combination therapy may be critical for optimizing activity against this tumor. C1 Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiat Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Radiol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA. Harvard Univ, Sch Med, Boston, MA 02114 USA. Massachusetts Gen Hosp, HST AA Martinos Ctr Biomed Imaging, Boston, MA 02114 USA. Harvard Univ, Sch Med, Div Hlth Sci & Technol, Boston, MA 02114 USA. MIT, Dept Nucl Sci & Engn, Cambridge, MA 02139 USA. Childrens Hosp, Dana Farber Canc Inst, Dept Adult Oncol, Boston, MA 02115 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. RP Batchelor, TT (reprint author), Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA. EM tbatchelor@partners.org; jain@steele.mgh.harvard.edu RI leng, xianwei/F-9073-2011; OI Cahill, Daniel/0000-0003-2552-6546 FU NCI NIH HHS [P01 CA080124, P01 CA080124-08, P01CA80124, R01 CA057683, R01 CA057683-15, R01 CA115767, R01 CA115767-03, R01CA115767, R01CA57683, R21 CA117079, R21 CA117079-02, R21CA117079]; NCRR NIH HHS [P41 RR014075, M01 RR001066, M01 RR001066-26, M01-RR-01066, P41 RR014075-10, P41-RR14075] NR 54 TC 1073 Z9 1105 U1 7 U2 59 PU CELL PRESS PI CAMBRIDGE PA 600 TECHNOLOGY SQUARE, 5TH FLOOR, CAMBRIDGE, MA 02139 USA SN 1535-6108 J9 CANCER CELL JI Cancer Cell PD JAN PY 2007 VL 11 IS 1 BP 83 EP 95 DI 10.1016/j.ccr.2006.11.021 PG 13 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 129AO UT WOS:000243701000009 PM 17222792 ER PT J AU Ullmannova, V Popescu, NC AF Ullmannova, Veronika Popescu, Nicholas C. TI Inhibition of cell proliferation, induction of apoptosis, reactivation of DLC1, and modulation of other gene expression by dietary flavone in breast cancer cell lines SO CANCER DETECTION AND PREVENTION LA English DT Article DE flavone; breast cancer; colon cancer; tumor suppressor genes; proto-oncogenes; DNA methylation; cell cycle; cell growth inhibition; apoptosis; deleted in liver cancer-1 gene (DLC-1 gene) ID SOY ISOFLAVONE GENISTEIN; TUMOR-SUPPRESSOR GENE; EPITHELIAL-CELLS; CARCINOMA-CELLS; IN-VIVO; HEPATOCELLULAR-CARCINOMA; ESTROGEN-RECEPTOR; MESSENGER-RNA; G(2)/M ARREST; GROWTH AB Background: Dietary flavone was previously shown to increase the expression of deleted in liver cancer-1 gene (DLC-1) in HT-29 colon carcinoma cell line [Herzog A, Kindermann B, Doring F, Daniel H, Wenzel U. Pleiotropic molecular effects of the pro-apoptotic dietary constituent flavone in human colon cancer cells identified by protein and mRNA expression profiling. Proteomics 2004;4:2455-64]. DLC-1 that encodes a Rho GTPase-activating protein, functions as a tumor suppressor gene and is frequently inactivated or down-regulated in several common cancers. Restoration of DLC-1 expression suppresses in vitro tumor cells proliferation and tumorigenicity in vivo. Methods: Here, the effect of flavone was examined in several DLC-1-deficient cell lines derived from different types human cancer using, assays for cell proliferation, gene expression and transfer. Results: We show that exposure to 150 mu M flavone increased DLC1 expression in breast but not in liver or prostate carcinoma cells or a nonmalignant breast epithelial cell line. Flavone restored the expression of DLC1 in the breast carcinoma cell lines MDA-MB-468, MDA-MB-361, and BT20 as well as in the colon carcinoma cell line HT-29 all of which are DLC-1-negative due to promoter hypermethylation. We further show that flavone inhibited cell proliferation, induced cell cycle arrest at G-M, increased p21(Waf1) gene expression, and caused apoptosis. Microarray analysis of these aggressive and metastatic breast carcinoma cells revealed 29 flavone-responsive genes, among which the DNA damage-inducible GADD genes were up-regulated and the proto-oncogene STMN1 and IGFBP3 were down-regulated. Conclusions: Flavone-mediated alterations of genes that regulate tumor cell proliferation, cell cycle, and apoptosis contribute to chemopreventive and antitumoral effects of flavone. Alone or in combination with demethylating agents, flavone may be an effective adjunct to chemotherapy in preventing breast cancer metastasis. (C) 2007 International Society for Preventive Oncology. Published by Elsevier Ltd. All fights reserved. C1 Natl Canc Inst, Lab Expt Carcinogenesis, Canc Res Ctr, Bethesda, MD 20892 USA. RP Popescu, NC (reprint author), Natl Canc Inst, Lab Expt Carcinogenesis, Canc Res Ctr, 37 Convent Dr,MSC 4264, Bethesda, MD 20892 USA. EM popescun@mail.nih.gov RI Benson, Veronika/D-9942-2014 OI Benson, Veronika/0000-0003-4770-9909 FU Intramural NIH HHS [Z99 CA999999] NR 52 TC 43 Z9 50 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2007 VL 31 IS 2 BP 110 EP 118 DI 10.1016/j.cdp.2007.02.005 PG 9 WC Oncology SC Oncology GA 177BK UT WOS:000247128400003 PM 17418982 ER PT J AU Breen, N Yabroff, KR Meissner, HI AF Breen, Nancy Yabroff, K. Robin Meissner, Helen I. TI What proportion of breast cancers are detected by mammography in the United States? SO CANCER DETECTION AND PREVENTION LA English DT Article DE breast cancer detection; mammography-detected breast cancer; breast cancer survivors; National Health Interview Survey; household interviews; age at diagnosis; race-ethnicity; education; income; insurance; smoking status; mortality; improved outcomes ID SCREENING PRACTICES; IMPROVEMENT; SURVIVAL; PROGRESS AB Background: None of the recent national studies has ascertained how women's breast cancer was detected in the United States. To rectify this gap, questions were added to the leading national health survey. Mammography was of special interest because it is widely used in the US and has evidence of a mortality benefit. Methods: We used the 2003 National Health Interview Survey (NHIS), to ascertain the self-reported modalities used to detect breast cancer in the non-institutionalized US population. The study included 345 women 40-84 years of age who, in 2003, reported a personal history of breast cancer. We examined the frequency of self-reported characteristics and tested for association with mammography-detected breast cancer using logistic regression. Results: Among the survivors in 2003, the percentage of breast cancers detected by mammography was much higher after 2001 (59%) than before 1993 (29%). Breast cancer survivors with less than high school education or less than US$ 20,000 household income were less likely to report detection by mammography. Conclusions: Women reported mammography-detected breast cancer at a slightly higher rate than published studies of mammography sensitivity and use would suggest. Lower rates of mammography-detected breast cancers among survivors with low income or low education raise the question whether mammography is underutilized as a diagnostic tool, especially for underserved women. (C) 2007 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved. C1 NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, Rockville, MD 20852 USA. NCI, Appl Canc Screening Res Branch, Behav Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20852 USA. RP Breen, N (reprint author), NCI, Hlth Serv & Econ Branch, Appl Res Program, Div Canc Control & Populat Sci, EPN 4005,6130 Execut Blvd,MSC 7344, Rockville, MD 20852 USA. EM Breenn@mail.nih.gov OI Yabroff, K. Robin/0000-0003-0644-5572 NR 21 TC 24 Z9 24 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2007 VL 31 IS 3 BP 220 EP 224 DI 10.1016/j.cdp.2007.04.006 PG 5 WC Oncology SC Oncology GA 210XO UT WOS:000249489100006 PM 17573202 ER PT J AU Wideroff, L Vaughan, TL Farin, FM Gammon, MD Risch, H Stanford, JL Chow, WH AF Wideroff, Louise Vaughan, Thomas L. Farin, Federico M. Gammon, Marilie D. Risch, Harvey Stanford, Janet L. Chow, Wong-Ho TI GST, NAT1, CYP1A1 polymorphisms and risk of esophageal and gastric adenocarcinomas SO CANCER DETECTION AND PREVENTION LA English DT Article DE polymorphism; genetic; cancer risk; gastrointestinal cancer; adenocarcinoma; esophageal; adenocarcinoma; gastric; epidemiology ID GENETIC POLYMORPHISMS; METABOLIZING-ENZYMES; BARRETTS-ESOPHAGUS; REGIONAL VARIATION; STOMACH-CANCER; TOBACCO; CARDIA; SUSCEPTIBILITY; ALCOHOL; EXPRESSION AB Background: Polymorphisms in glutathione-S-transferase (GST), N-acetyltransferase (NA7) 1, and CYP1A1 genes have been suggested as susceptibility factors for esophageal and gastric adenocarcinomas, but have not been consistently linked to elevated risks. In a population-based case-control study, we examined risks in relation to polymorphisms of the following genes: GSTP1; GSTM1; 6STT1; NAT1; and CYP1A1 Methods: Histologically confirmed incident cases, ages 30-79, were identified in three US locations. Population controls from the same catchment areas were frequency matched to expected age and sex distributions of esophageal and gastric cardia adenocarcinomas. DNA was extracted from buffy coat for PCR-based assays, with interpretable genotyping results obtained from 209 controls, 67 esophageal adenocarcinomas, 60 gastric cardia adenocarcinomas, and 56 noncardia gastric adenocarcinomas. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated among whites, adjusting for age, sex, and study center. Results: In all histologic subgroups, ORs were somewhat elevated for the GSTP1 Val/Val genotype (versus Ile/Ile), although 95% CIs included 1.00. The respective ORs for esophageal, cardia, and other gastric adenocarcinomas were 1.73 (0.75-4.02), 1.46 (0.57-3.73), and 1.22 (0.48-3.09). No consistent patterns of elevated risk were associated with the null GSTM1 or GSTT1 genotypes, one or two copies of NAT1*10 or *11 alleles, or CYP1A1 Val/Val or Ile/Val genotypes (versus Ile/Ile). Conclusions: Additional research in larger samples is needed to further assess polymorphisms and their interactions with epidemiologic risk factors, particularly for esophageal adenocarcinorna, which has been increasing markedly in incidence. Published by Elsevier Ltd on behalf of International Society of Preventive Oncology C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98104 USA. Univ Washington, Dept Environm & Occupat Hlth, Seattle, WA 98195 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06510 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Wideroff, L (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, EPN 4005,6130 Execut Blvd,MSC 7344, Bethesda, MD 20892 USA. EM Wideroff@nih.gov RI Hernandez, Jessica/G-6527-2011 FU Intramural NIH HHS [Z99 DA999999]; NCI NIH HHS [U01 CA057983, N01 CN005230, N01 CP040501, N01 CP040501-09, N01CP040501-009, U01 CA057923, U01 CA057923-03, U01 CA057949, U01 CA057949-03, U01 CA057983-03]; NIEHS NIH HHS [P30 ES007033, P30 ES007033-13, P30 ES010126, P30 ES010126-07] NR 25 TC 54 Z9 56 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2007 VL 31 IS 3 BP 233 EP 236 DI 10.1016/j.cdp.2007.03.004 PG 4 WC Oncology SC Oncology GA 210XO UT WOS:000249489100008 PM 17646057 ER PT J AU Hill, JW Evans, MK AF Hill, Jeff W. Evans, Michele K. TI A novel R229Q OGG1 polymorphism results in a thermolabile enzyme that sensitizes KG-1 leukemia cells to DNA damaging agents SO CANCER DETECTION AND PREVENTION LA English DT Article DE R229Q; OGG1; 8-oxoguanine; KG-1; leukemia; polymorphism ID HOGG1; 8-HYDROXYGUANINE; MUTATION; GLYCOSYLASE; 8-HYDROXYDEOXYGUANOSINE; ACCUMULATION; MITOCHONDRIA; 8-OXOGUANINE; EXCISION; CANCER AB Background: Mutations and polymorphisms of OGG1, the major mammalian 8-oxoguanine repair activity, are associated with increased risk for several cancers. Decreased 8-oxoguanine repair capacity due to variant forms of the OGG1 gene is a common feature of numerous cancer cell lines. One such cell line, human KG-I leukemia cells, has previously been demonstrated to be deficient in the excision of 8-oxoguanine from oxidatively damaged DNA. KG-I cells have a homozygous R229Q amino acid substitution in OGG1 that has been presumed to alter the function of OGG1 and result in elevated levels of genomic 8-oxoG and hypersensitivity to 8-hydroxydeoxyguanosine nucleoside and ionizing radiation observed in KG-I cells. Methods: We characterized the enzymatic activity of R229Q OGG1 and the effect of the enzyme on bell survival following treatment with DNA damaging agents. Results: R229Q OGG1 had activity similar to the wild-type enzyme, yet was easily heat inactivated at physiological temperature. R229Q OGGI expressed in human cells had significantly lower activity than wild-type OGG1 and was also highly thermolabile. Expression of R229Q OGG1 sensitized KG-I cells to killing by menadione and 8-hydroxydeoxyguanosine, but not ionizing radiation. Conclusions: These results suggest that decreased 8-oxoguanine repair in KG-1 is due to thermolability of R229Q OGG1 and that the enzyme variant increases cellular susceptibility to killing resulting from oxidative DNA damage. The R229Q OGGI variant is a validated polymorphism prevalent in world populations and not an isolated mutation in KG-I cells, thus the R229Q OGGI allele may be a novel marker for cancer susceptibility. (C) 2007 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved. C1 NIA, Cellular & Mol Biol Lab, NIH, Baltimore, MD 21224 USA. RP Evans, MK (reprint author), NIA, Cellular & Mol Biol Lab, NIH, 5600 Nathan Shock Dr,Mailbox 09, Baltimore, MD 21224 USA. EM evansmi@grc.nia.nih.gov FU Intramural NIH HHS [Z01 AG000517-04] NR 23 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2007 VL 31 IS 3 BP 237 EP 243 DI 10.1016/j.cdp.2007.05.001 PG 7 WC Oncology SC Oncology GA 210XO UT WOS:000249489100009 PM 17651912 ER PT J AU Louis, SN Wang, L Chow, L Rezmann, LA Imamura, K MacGregor, DP Casely, D Catt, KJ Frauman, AG Louis, WJ AF Louis, Simon N. Wang, Lin Chow, Laurie Rezmann, Linda A. Imamura, Keisaku MacGregor, Duncan P. Casely, David Catt, Kevin J. Frauman, Albert G. Louis, William J. TI Appearance of angiotensin II expression in non-basal epithelial cells is an early feature of malignant change in human prostate SO CANCER DETECTION AND PREVENTION LA English DT Article DE angiotensin II; prostate cancer; benign prostatic hyperplasia; prostatic intraepithelial neoplasia; immunohistochemistry ID ANTIPROLIFERATIVE ACTIVITY; RECEPTOR BLOCKER; CANCER CELLS; BASAL-CELLS; HYPERPLASIA; INHIBITORS; SYSTEM; RENIN; LINE AB Background: Despite increasing interest in the renin-angiotensin system in cancer, little is known about angiotensin II (Ang II) expression in human prostate tumors. Methods: Using immunohistochemistry, we examined Ang II expression in prostate cancer (Gleason grades 2-5), benign prostatic hyperplasia (BPH), and high-grade prostatic intraepithelial neoplasia (HGPIN). Results: Ang II was present in proliferating neoplastic cells in HGPIN, in malignant cells in all grades of prostate cancer examined, in basal but not luminal epithelial cells in BPH, and in the cytoplasm of LNCaP, DU145, and PO prostate cancer cells. Conclusions: The data establishes the presence of Ang II in pre-malignant and malignant prostate cells, suggests Ang II staining in non-basal epithelial cells is an early sign of malignant change, and supports suggestions that HGPIN and malignant prostate cells both arise from transformed basal cells. Using immunohistochemistry we examined Ang II expression in proliferative disorders of the prostate and concluded that Ang II staining in non-basal epithelial cells is evidence of early malignant change. (c) 2007 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved. C1 [Louis, Simon N.; Wang, Lin; Chow, Laurie; Rezmann, Linda A.; Imamura, Keisaku; Frauman, Albert G.; Louis, William J.] Univ Melbourne, Clin Pharmacol & Therapeut Unit, Dept Med, Heidelberg, Vic 3084, Australia. [MacGregor, Duncan P.] Dept Anat Pathol, Heidelberg, Vic 3084, Australia. [Catt, Kevin J.] NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Louis, SN (reprint author), Univ Melbourne, Clin Pharmacol & Therapeut Unit, Dept Med, Heidelberg, Vic 3084, Australia. EM simonnsl@unimelb.edu.au NR 26 TC 9 Z9 9 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2007 VL 31 IS 5 BP 391 EP 395 DI 10.1016/j.cdp.2007.08.002 PG 5 WC Oncology SC Oncology GA 249CH UT WOS:000252203900008 PM 18031950 ER PT J AU Xi, LF Koutsky, LA Hildesheim, A Galloway, DA Wheeler, CM Winer, RL Ho, J Kiviat, NB AF Xi, Long Fu Koutsky, Laura A. Hildesheim, Allan Galloway, Denise A. Wheeler, Cosette M. Winer, Rachel L. Ho, Jesse Kiviat, Nancy B. TI Risk for high-grade cervical Intraepithelial neoplasia associated with variants of human papillomavirus types 16 and 18 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HPV 16 E6; WORLDWIDE GENOMIC DIVERSITY; LONG CONTROL REGION; MOLECULAR VARIANTS; NATURAL VARIANTS; UTERINE CERVIX; CANCER; WOMEN; INFECTION; LESIONS AB Background: Although the variant lineages of human papillomavirus (HPV) types 16 and 18 are well established, their individual associations with high-grade cervical intra-epithelial neoplasia (CIN) have not been extensively evaluated. Methods: Study subjects were women participating in the Atypical Squamous Cells of Undetermined Significance/Low-Grade Squamous Intraepithelial Lesion Triage Study who were positive for HPV16 or HPV18 at enrollment. These women were followed every 6 months for 2 years. Viral isolates from enrollment samples were characterized by DNA sequencing and classified as variant lineages. Results: Over a 2-year study period, CIN3 was histologically diagnosed in 291 of the 779 HPV16-positive women and 47 of the 275 HPV18-positive women. Among women without CIN2-3 at enrollment, the risk of subsequent CIN3 was 2.7-fold greater for those with HPV16 African-2 [95% confidence interval (95% CI), 1.0-7.0] and 3.1-fold greater for those with HPV16 Asian American (95% Cl, 1.6-6.0), compared with European variants. Relative to infection with HPV18 African variants, the risk associating subsequent CIN3 was 3.8 (95% CI, 0.9-17.2) for infection with HPV18 European variants and 4.8 (95% CI, 1.0-23.6) for infection with HPV18 Asian American variants. Similar associations were observed when the 2-year prevalence of CIN3 was used as the end point. Further, for those with HPV16 European variants, the 2-year prevalence of CIN3 was higher in White women than in African American women (P = 0.01); this trend was reversed for those with HPV16 African-1 variants (P = 0.22). A similar pattern was present for infections with HPV18 European versus African variants. Conclusions: The lineages of HPV16 and HPV18 variants are associated with differing risks for high-grade CIN. C1 Univ Washington, Sch Med, Dept Pathol, Seattle, WA 98103 USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Epidemiol, Seattle, WA 98103 USA. Fred Hutchinson Canc Res Ctr, Washington, DC USA. NCI, Div Canc epidemiol & Genet, Bethesda, MD 20892 USA. Univ New Mexico, Sch Med, Dept Microbiol, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Dept Mol Genet, Albuquerque, NM 87131 USA. RP Xi, LF (reprint author), Univ Washington, Sch Med, Dept Pathol, 1914 N 34th St,Suite 300, Seattle, WA 98103 USA. EM longfu@u.washington.edu FU NCI NIH HHS [CA 84396] NR 51 TC 77 Z9 80 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 JAN PY 2007 VL 16 IS 1 BP 4 EP 10 DI 10.1158/1055-9965.EPI-06-0670 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 126XY UT WOS:000243550100002 PM 17220325 ER PT J AU Kreimer, AR Katki, HA Schiffman, M Wheeler, CM Castle, PE AF Kreimer, Aimee R. Katki, Hormuzd A. Schiffman, Mark Wheeler, Cosette M. Castle, Philip E. CA ASCUS-LSIL Triage Study Grp TI Viral determinants of human papillomavirus persistence following loop electrical excision procedure treatment for cervical Intraepithelial neoplasia grade 2 or 3 SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID OF-THE-LITERATURE; ELECTROSURGICAL EXCISION; RANDOMIZED-TRIAL; WOMEN; CARCINOGENICITY; PCR AB Background: Persistent infection with carcinogenic human papillomavirus (HPV) causes cervical precancer (cervical intraepithelial neoplasia grade 2+) which, in the United States, is commonly treated using the loop electrical excision procedure (LEEP). Data from Atypical Squamous Cells of Undetermined Significance - Low-Grade Squamous Intraepithelial Lesion Triage Study were used to evaluate HPV persistence and reappearance after LEEP. Methods: Cervical specimens, collected before LEEP and at 6-month study visits, were tested by L1-PCR for detection of >= 27 HPV types. HPV persistence, defined as the same HPV type being present before and 6 months after LEEP, was evaluated by: (a) genotype, (b) carcinogenicity, and (c) phylogenetic species. HPV infections that cleared post-LEEP (the complement of persistence) were followed for reappearance of the same type. Results: HPV infections (n = 1,130) were detected among 481 women who underwent LEEP. Overall, 20.4% [95% confidence interval (95% CI), 18.2-22.9%) of infections persisted. Assessment of heterogeneity within the three categorizations of HPV showed that phylogenetic species best fit the data. Persistence was significantly greater by HPV types in the alpha 3 species Fall are noncarcinogenic; 40.9% (95% Cl, 31.8-50.4%)] compared with HPV types in the alpha-9 (HPV16 and related types) and alpha 7 species (HPV18 and related types; 17.6% and 17.9%, respectively; P < 0.001 for both). HPV reappeared in 7.8% (95% Cl, 6.1-9.9%) of infections that cleared after LEEP. Infections in the alpha 3 species (22.6%) were the most likely to reappear compared with HPV types in the alpha 9 (7.5%) and alpha 7 (6.8%) species. Conclusions: Patterns of HPV persistence and reappearance following LEEP were better explained by phylogenetic rather than standard classifications. HPV types likely to persist after LEEP as well as those likely to repopulate the cervical/vaginal epithelium were those in the alpha 3 species, which are in effect not treated, but are not associated with cervical cancer and are unlikely to cause disease. C1 NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. Univ New Mexico, Sch Med, Hlth Sci Ctr, Dept Obstet & Gynecol, Albuquerque, NM 87131 USA. RP Kreimer, AR (reprint author), NCI, Div Canc Prevent, NIH, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM kreimera@mail.nih.gov RI Katki, Hormuzd/B-4003-2015; Kreimer, Aimee/H-1687-2015 FU NCI NIH HHS [CN-55156, CN-55105, CN-55153, CN-55154, CN-55155, CN-55157, CN-55158, CN-55159] NR 18 TC 20 Z9 20 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 JAN PY 2007 VL 16 IS 1 BP 11 EP 16 DI 10.1158/1055-9965.EPT-06-0710 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 126XY UT WOS:000243550100003 PM 17220326 ER PT J AU Purdue, MP Sakoda, LC Graubard, BI Welch, R Chanock, SJ Sesterhenn, IA Rubertone, MV Erickson, RL McGlynn, KA AF Purdue, Mark P. Sakoda, Lori C. Graubard, Barry I. Welch, Robert Chanock, Stephen J. Sesterhenn, Isabel A. Rubertone, Mark V. Erickson, R. Loren McGlynn, Katherine A. TI A case-control investigation of immune function gene polymorphisms and risk of testicular germ cell tumors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID TRANSFORMING GROWTH-FACTOR-BETA-1 GENE; SINGLE-NUCLEOTIDE POLYMORPHISMS; PROMOTER POLYMORPHISMS; RHEUMATOID-ARTHRITIS; MULTIPLE-SCLEROSIS; SEMINAL PLASMA; CANCER RISK; ASSOCIATION; TESTIS; REGION AB There is reason to suspect that testicular germ cell tumor (TGCT) development may be influenced by cytokines, secreted proteins that modulate tumor immune surveillance activity as well as a variety of processes in the testis. To address this hypothesis, we conducted a case-control analysis (508 cases, 608 controls) of 32 putatively functional single-nucleotide polymorphisms (SNP) in 16 immune function genes among non-Hispanic Caucasian participants in the U.S. Servicemen's Testicular Tumor Environmental and Endocrine Determinants Study. The TGFB1 Ex5-73C > T variant was positively associated with TGCT (CT/TT versus CC: odds ratio, 1.73; 95% confidence interval, 1.01-2.95; P-trend = 0.05); additionally, haplotypes of the assessed TGFB1 SNPs (-509C > T, 327C > T, Ex1-282C > G, and Ex5-73C > T) differed in frequency between cases and controls (all TGCT, P 0.07; seminoma, P 0.04; nonseminoma, P 0.11). We also observed excess frequencies among TGCT cases versus controls of LTA 252G (P-trend = 0.08) and of the TNF variants -1042C (P-trend = 0.06), -1036T (P-trend = 0.07), and -238G (P-trend = 0.09). Analyses of haplotypes for LTA-TNF SNPs (LTA -91C > A, LTA 252A > G, TNF -863C > A, TNF -857C > T, TNF -308G > A, and -238G > A) were similarly suggestive of an association with TGCT (P = 0.06) and nonseminoma (P = 0.04), but not seminoma (P = 0.21). Polymorphisms in other genes were found to be associated only with seminoma (IL2) or nonseminoma (IFNGR2 and IL10). However, none of the associations remained noteworthy after applying the false discovery rate method to control for multiple testing. In conclusion, our findings suggest that polymorphisms in TGFB1 and LTA/TNF, and possibly other immune function genes, may influence susceptibility to TGCT. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Depet Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, NIH, Dept Hlth & Human Serv, Gaithersburg, MD USA. Armed Forces Inst Pathol, Washington, DC 20306 USA. USA, Ctr Hlth Promot & Prevent Med, Washington, DC 20310 USA. Walter Reed Army Inst Res, Forest Glen, MD USA. RP Purdue, MP (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Depet Hlth & Human Serv, EPS-8009,6120 Execut Blvd, Bethesda, MD 20892 USA. EM purduem@mail.nih.gov RI Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 FU Intramural NIH HHS NR 48 TC 17 Z9 17 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JAN PY 2007 VL 16 IS 1 BP 77 EP 83 DI 10.1158/1055-9965.EPI-06-0573 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 126XY UT WOS:000243550100013 PM 17220333 ER PT J AU Zhang, FF Terry, MB Hou, LF Chen, JB Lissowska, J Yeager, M Zatonski, W Chanock, S Morabia, A Chow, WH AF Zhang, Fang Fang Terry, Mary Beth Hou, Lifang Chen, Jinbo Lissowska, Jolanta Yeager, Meredith Zatonski, Witold Chanock, Stephen Morabia, Alfredo Chow, Wong-Ho TI Genetic polymorphisms in folate metabolism and the risk of stomach cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID METHYLENETETRAHYDROFOLATE REDUCTASE POLYMORPHISM; MTHFR C677T POLYMORPHISM; GASTRIC-CANCER; COLORECTAL-CANCER; PLASMA HOMOCYSTEINE; METHIONINE SYNTHASE; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; HAPLOTYPE RECONSTRUCTION; MULTIETHNIC COHORT; CHINESE POPULATION AB Folate deficiency has been implicated in the etiology of stomach cancer through abnormal DNA methylation and disrupted DNA synthesis and repair. Enzyme-coding genes involved in folate metabolism are often polymorphic. In a population-based study of 305 cases and 427 controls in Warsaw, Poland, we evaluated the risk of stomach cancer in relation to polymorphisms in folate-metabolizing genes, including MTHFR (Ex5+79C > T and Ex8-62A > C), MTR (Ex26-20A > G), and MTRR (Ex2-64A > G, Ex5+123C > T, Ex15+572C > T, Ex15-405A > T, Ex9-85C > T, Ex15-526G > A, and Ex14+14C > T). Polymorphisms in the MTHFR gene were not associated with stomach cancer risk. No notable effect was found for polymorphisms in MTR or MTRR either, although MTR Ex26-20A > G and MTRR Ex5+123C>T polymorphisms were associated with a borderline increased risk of stomach cancer (MTR Ex26-20A > G, AG/GG versus AA: odds ratio, 1.35; 95% confidence interval, 0.96-1.90; MTRR Ex5+123C > T, CT/TT versus CC: odds ratio, 1.30; 95% confidence interval, 0.93-1.82). We did not find significant interactions between polymorphisms in MTHFR, MTR, and MTRR genes and dietary folate and alcohol consumption. Our study did not identify strong genetic determinants in the folate metabolism pathway for stomach cancer risk. C1 Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, New York, NY 10032 USA. NCI, Div Canc Epidemiol & Genet, Gaithersburg, MD USA. NCI, Core Genotyping Facil, Adv Technol Ctr, Gaithersburg, MD USA. Univ Penn, Sch Med, Dept Epidemiol & Biostat, Philadelphia, PA 19104 USA. M Sklosowska Curie Inst Oncol, Warsaw, Poland. Ctr Canc, Div Canc Epidemiol & Prevent, Warsaw, Poland. CUNY Queens Coll, Ctr Biol Nat Syst, Flushing, NY 11367 USA. RP Zhang, FF (reprint author), Columbia Univ, Dept Epidemiol, Mailman Sch Publ Hlth, 722 W 168th St, New York, NY 10032 USA. EM fz2004@columbia.edu OI Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS NR 53 TC 32 Z9 37 U1 0 U2 8 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 JAN PY 2007 VL 16 IS 1 BP 115 EP 121 DI 10.1158/1055-9965.EPI-06-0513 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 126XY UT WOS:000243550100019 PM 17220339 ER PT J AU Berndt, SI Chatterjee, N Huang, WY Chanock, SJ Welch, R Crawford, ED Hayes, RB AF Berndt, Sonja I. Chatterjee, Nilanjan Huang, Wen-Yi Chanock, Stephen J. Welch, Robert Crawford, E. David Hayes, Richard B. TI Variant in sex hormone-binding globulin gene and the risk of prostate cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID ADDITIONAL CARBOHYDRATE CHAIN; SHBG GENE; POSTMENOPAUSAL WOMEN; POLYMORPHISMS; ASSOCIATION; STEROIDS; REPEAT; PLASMA; GLYCOSYLATION; SEQUENCE AB Sex hormones have been implicated in prostate carcinogenesis and are thought to modulate cell proliferation and growth. To investigate the association between polymorphisms in hormone-related genes and prostate cancer risk, we conducted a two-stage, case-control study within the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Using DNA extracted from blood specimens, we initially genotyped 14 single nucleotide polymorphisms in genes involved in hormone regulation or metabolism (AKR1C3, CYP1A1, CYP1B1, CYP3A4, ESR1, GNRH1, HSD173B, HSD3B2, SHBG, and SRD5A2) in 488 prostate cancer cases and 617 matched controls. Heterozygotes at SHBG D356N were found to be associated with an increased risk of prostate cancer compared with the homozygous wild type, particularly among non-Hispanic whites (odds ratio, 1.54; 95% confidence interval, 1.13-2.09; P = 0.006). No significant associations were observed with the other polymorphisms. The SHBG D356N polymorphism, which has potential functional significance, was subsequently genotyped in additional 769 cases and 1,168 controls. Overall, SHBG D356N heterozygotes were found to have an increased risk of prostate cancer among whites (odds ratio, 1.34; 95% confidence interval, 1.10-1.63; P = 0.0007). This study suggests that genetic variation in SHBG may influence prostate cancer susceptibility. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ Colorado, Denver, CO 80202 USA. RP Berndt, SI (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, EPS 8012,MSC 7240,6120 Execut Blvd, Bethesda, MD 20892 USA. EM berndts@mail.nih.gov RI Perez , Claudio Alejandro/F-8310-2010; OI Perez , Claudio Alejandro/0000-0001-9688-184X; Hayes, Richard/0000-0002-0918-661X FU Intramural NIH HHS NR 37 TC 57 Z9 60 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 JAN PY 2007 VL 16 IS 1 BP 165 EP 168 DI 10.1158/1055-9965.EPI-06-0689 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 126XY UT WOS:000243550100027 PM 17220347 ER PT J AU Lonn, S Bhatti, P Alexander, BH Pineda, MA Doody, MM Struewing, JP Sigurdson, AJ AF Lonn, Stefan Bhatti, Parveen Alexander, Bruce H. Pineda, Marbin A. Doody, Michele M. Struewing, Jeffery P. Sigurdson, Alice J. TI Papillary thyroid cancer and polymorphic variants in TSHR- and RET-related genes: a nested case-control study within a cohort of US radiologic technologists SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID INCREASING INCIDENCE; POOLED ANALYSIS; GROWTH-FACTOR; CARCINOMA; PROTOONCOGENE; HAPLOTYPES; TRENDS; RISK AB Several variants in the TSHR and RET signaling pathways genes have been reported to be related to cancer risk. We hypothesized that polymorphic variants in these genes are associated with the risk of papillary thyroid cancer. A nested case-control study was conducted within the U.S. Radiologic Technologists cohort. Eligible validated papillary thyroid cancer cases (n = 167) and frequency-matched (by sex and birth year) controls (n = 491) donated blood for analysis. There were no statistically significant associations between papillary thyroid cancer and 10 selected polymorphic variants in analyses of men and women combined. A borderline significant increasing risk was found for RET G691S (P-trend = 0.05) and was especially pronounced among young women. For women under 38 years (the median age at diagnosis), the odds ratios were 2.1 (95% confidence interval, 1.2-3.7) for those heterozygous for the RET G691S polymorphism and 3.7 (95% confidence interval, 1.1-11.8) for those who were homozygous (P-trend = 0-001). Our data provide limited evidence that TSHR- and RET-related genes are related to papillary thyroid cancer risk. C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Lab Populat Genet, Bethesda, MD 20892 USA. Univ Minnesota, Sch Publ Hlth, Div Environm Hlth Sci, Minneapolis, MN USA. RP Lonn, S (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Room 7053,6120 Execut Blvd, Bethesda, MD 20892 USA. EM Lstefan@mail.nih.gov RI Struewing, Jeffery/I-7502-2013 OI Struewing, Jeffery/0000-0002-4848-3334 FU Intramural NIH HHS; NCI NIH HHS [N01-CP-15673, N01-CP-51016, N02-CP-81005, N02-CP-81121] NR 19 TC 22 Z9 23 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 JAN PY 2007 VL 16 IS 1 BP 174 EP 177 DI 10.1158/1055-9965.EPI-06-0665 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 126XY UT WOS:000243550100029 PM 17220349 ER PT J AU Pinapank, JF Alexander, HR Royal, RE Kammula, US Libutti, SK Hucyhes, MS Wood, B Kam, AW Ohl, S Emery, B Beresneva, T AF Pinapank, James F., Jr. Alexander, H. Richard, Jr. Royal, Richard E. Kammula, Udai S. Libutti, Steven K. Hucyhes, Marybeth S. Wood, Bradford Kam, Anthony W. Ohl, Susan Emery, Bryan Beresneva, Tatiana TI Regional treatment strategies for patients with hepatic metastases from melanoma SO CANCER INVESTIGATION LA English DT Meeting Abstract C1 NCI, Surg Branch, Surg Metab Sect, Bethesda, MD 20892 USA. Dept Surg, Div Surg Oncol, Baltimore, MD USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2007 VL 25 SU 1 BP 54 EP 54 PG 1 WC Oncology SC Oncology GA 217LW UT WOS:000249950400068 ER PT J AU Schrump, DS AF Schrump, David S. TI From the guest editor SO CANCER JOURNAL LA English DT Editorial Material C1 NCI, Thorac Oncol Sect, Surg Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Schrump, DS (reprint author), NCI, Thorac Oncol Sect, Surg Branch, Canc Res Ctr, Rm 4-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM david_schrump@nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2007 VL 13 IS 1 BP 2 EP 2 DI 10.1097/PPO.0b013e31803c514d PG 1 WC Oncology SC Oncology GA 150WV UT WOS:000245251200001 ER PT J AU Piekarz, RL Sackett, DL Bates, SE AF Piekarz, Richard L. Sackett, Dan L. Bates, Susan E. TI Histone deacetylase inhibitors and demethylating agents: Clinical development of histone deacetylase inhibitors for cancer therapy SO CANCER JOURNAL LA English DT Review DE epigenetics; histone deacetylase inhibitors; FK228; romidepsin; vormostat ID ACUTE MYELOID-LEUKEMIA; SUBEROYLANILIDE HYDROXAMIC ACID; TRANS-RETINOIC ACID; T-CELL LYMPHOMA; ACUTE PROMYELOCYTIC LEUKEMIA; PHASE-II TRIAL; REFRACTORY SOLID TUMORS; CEREBROSPINAL-FLUID PENETRATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; DNA TOPOISOMERASE-II AB The histone deacetytase inhibitors are a new class of agents that are currently in various stages of clinical development. Clinical trials have demonstrated activity, urging further investigation. At the same time, it has been discovered that these agents have their own challenges. In this review, we discuss clinical data gathered to date, combination therapies designed to increase efficacy, and toxicities attributed to this new class of agents. C1 NCI, Mol Therapeut Sect, Med Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. NICHHD, Lab Integrat & Med Biophys, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. RP Piekarz, RL (reprint author), 10 Ctr Dr MSC 1903,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM rpiekarz@nih.gov NR 125 TC 40 Z9 41 U1 1 U2 4 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2007 VL 13 IS 1 BP 30 EP 39 DI 10.1097/PPO.0b013e31803c73cc PG 10 WC Oncology SC Oncology GA 150WV UT WOS:000245251200006 PM 17464244 ER PT J AU Schrump, DS Hong, JA Nguyen, DM AF Schrump, David S. Hong, Julie A. Nguyen, Dao M. TI Utilization of chromatin remodeling agents for lung cancer therapy SO CANCER JOURNAL LA English DT Review DE epigenetics; lung cancer; 5-aza-2 '-deoxycytidine; depsipeptide FK228; flavopiridol; celecoxib ID HISTONE DEACETYLASE INHIBITORS; MESSENGER-RNA EXPRESSION; SUBEROYLANILIDE HYDROXAMIC ACID; CYTOLYTIC T-LYMPHOCYTES; GROWTH-FACTOR RECEPTOR; DNA METHYLATION; GENE-EXPRESSION; TUMOR-ANTIGENS; POOR-PROGNOSIS; METHYLTRANSFERASE ACTIVITY AB Lung cancer is a disease with enormous global medical and economic impact that remains refractory to conventional treatment modalities. Recent insights regarding mechanisms pertaining to epigenetic regulation of gene expression during malignant transformation, together with the identification of agents that modulate chromatin structure provide new opportunities for the treatment and prevention of this lethal disease. C1 NCI, Thorac Oncol Sect, Surg Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Schrump, DS (reprint author), NCI, Thorac Oncol Sect, Surg Branch, Canc Res Ctr, Rm 4-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM david_schrump@nih.gov NR 108 TC 6 Z9 6 U1 0 U2 1 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2007 VL 13 IS 1 BP 56 EP 64 DI 10.1097/PPO.0b013e31803c74cf PG 9 WC Oncology SC Oncology GA 150WV UT WOS:000245251200009 PM 17464247 ER PT J AU Bar-Sela, G Jacobs, KM Gius, D AF Bar-Sela, Gil Jacobs, Kristi Muldoon Gius, David TI Histone deacetylase inhibitor and demethylating agent chromatin compaction and the radiation response by cancer cells SO CANCER JOURNAL LA English DT Article DE histone deacetylases; radiation; epigenetic; methylation; chromatin ID SODIUM-BUTYRATE; TRANSCRIPTION; ENHANCEMENT; CODE; RADIOSENSITIVITY; ACETYLATION; METHYLATION; EPIGENETICS; EXPRESSION; BIOLOGY AB It now appears that epigenetics plays a central role in transformation, both in vitro and in vivo. The expression and regulation of DNA methylation and the subsequent chromatin structure are significantly altered in tumor cells, suggesting a direct role in the process of in vivo cellular transformation. If epigenetics and posttranslational modifications of histories play a role in transformation, then it seems logical that the genes regulating chromatin compaction may also be molecular targets and markers in profiling tumor cell resistance. Local remodeling of chromatin is a key step in the regulation of gene expression, and altering the expression of these genes might also favorably alter how tumor cells respond to anticancer agents. Several new agents that alter chromatin compaction, either methyltransferase or histone deacetylases inhibitors, are progressing through clinical trials and have shown promising preclinical interactions when combined with radiation. In this review, we discuss the potential for histone deacetylases inhibitors as radio-sensitizing agents. C1 NCI, Radiat Oncol Branch, Radiat Oncol Sci Program, NIH, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Gius, D (reprint author), NCI, Radiat Oncol Branch, Radiat Oncol Sci Program, NIH, 9000 Rockville Pikie, Bethesda, MD 20892 USA. EM giusd@mail.nih.gov NR 35 TC 16 Z9 16 U1 0 U2 1 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JAN-FEB PY 2007 VL 13 IS 1 BP 65 EP 69 DI 10.1097/PPO.0b013e31803c7565 PG 5 WC Oncology SC Oncology GA 150WV UT WOS:000245251200010 PM 17464248 ER PT J AU Whiteford, CC Bilke, S Greer, BT Chen, QR Braunschweig, TA Cenacchi, N Wei, JS Smith, MA Houghton, P Morton, C Reynolds, CP Lock, R Gorlick, R Khanna, C Thiele, CJ Takikita, M Catchpoole, D Hewitt, SM Khan, J AF Whiteford, Craig C. Bilke, Sven Greer, Braden T. Chen, Qingrong Braunschweig, Till A. Cenacchi, Nicola Wei, Jun S. Smith, Malcolm A. Houghton, Peter Morton, Christopher Reynolds, C. Patrick Lock, Richard Gorlick, Richard Khanna, Chand Thiele, Carol J. Takikita, Mikiko Catchpoole, Daniel Hewitt, Stephen M. Khan, Javed TI Credentialing preclinical pediatric xenograft models using gene expression and tissue microarray analysis SO CANCER RESEARCH LA English DT Article ID ARTIFICIAL NEURAL-NETWORKS; CANCER MODELS; IN-VITRO; CDNA; OSTEOSARCOMA; SENSITIVITY; METASTASIS; PREDICTION; PROFILES; TUMOR AB Human tumor xenografts have been used extensively for rapid screening of the efficacy of anticancer drugs for the past 35 years. The selection of appropriate xenograft models for drug testing has been largely empirical and has not incorporated a similarity to the tumor type of origin at the molecular level. This study is the first comprehensive analysis of the transcriptome of a large set of pediatric xenografts, which are currently used for preclinical drug testing. Suitable models representing the tumor type of origin were identified. It was found that the characteristic expression patterns of the primary tumors were maintained in the corresponding xenografts for the majority of samples. Because a prerequisite for developing rationally designed drugs is that the target is expressed at the protein level, we developed tissue arrays from these xenografts and corroborated that high mRNA levels yielded high protein levels for two tested genes. The web database and availability of tissue arrays will allow for the rapid confirmation of the expression of potential targets at both the mRNA and the protein level for molecularly targeted agents. The database will facilitate the identification of tumor markers predictive of response to tested agents as well as the discovery of new molecular targets. C1 NCI, Oncogenomics Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Comparat Oncol Program, NIH, Bethesda, MD 20892 USA. NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Childrens Hosp Los Angeles, Inst Pediat Clin Res, CHLA, USC,Dev Therapeut Program, Los Angeles, CA 90027 USA. Childrens Canc Inst Australia Med Res, Leukaemia Biol Program, Sydney, NSW, Australia. Childrens Hosp Montefiore, Hematol Oncol Sect, Bronx, NY USA. Childrens Hosp Westmead, Tumour Bank, Westmead, NSW, Australia. RP Khan, J (reprint author), NCI, Oncogenomics Sect, Pediat Oncol Branch, NIH, Room 134E,8717 Grovemont Circle, Bethesda, MD 20892 USA. EM khanjav@mail.nih.gov RI Houghton, Peter/E-3265-2011; Khan, Javed/P-9157-2014; Lock, Richard/G-4253-2013; OI Khan, Javed/0000-0002-5858-0488; Hewitt, Stephen/0000-0001-8283-1788; Reynolds, C. Patrick/0000-0002-2827-8536 FU Intramural NIH HHS NR 37 TC 67 Z9 68 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2007 VL 67 IS 1 BP 32 EP 40 DI 10.1158/0008-5472.CAN-06-0610 PG 9 WC Oncology SC Oncology GA 123TX UT WOS:000243320000007 PM 17210681 ER PT J AU Grade, M Hormann, P Becker, S Hummon, AB Wangsa, D Varma, S Simon, R Liersch, T Becker, H Difilippantonio, MJ Ghadimi, BM Ried, T AF Grade, Marian Hoermann, Patrick Becker, Sandra Hummon, Amanda B. Wangsa, Danny Varma, Sudhir Simon, Richard Liersch, Torsten Becker, Heinz Difilippantonio, Michael J. Ghadimi, B. Michael Ried, Thomas TI Gene expression profiling reveals a massive, aneuploidy-dependent transcriptional deregulation and distinct differences between lymph node-negative and lymph node-positive colon carcinomas SO CANCER RESEARCH LA English DT Article ID COLORECTAL-CANCER; OLIGONUCLEOTIDE ARRAYS; CELLULAR TRANSCRIPTOME; CDNA MICROARRAYS; DUKES-B; TUMORS; CELLS; CLASSIFICATION; PREDICTION; PATTERN AB To characterize patterns of global transcriptional deregulation in primary colon carcinomas, we did gene expression profiling of 73 tumors [Unio Internationale Contra Cancrum stage II (n = 33) and stage III (n = 40)] using oligonucleotide microarrays. For 30 of the tumors, expression profiles were compared with those from matched normal mucosa samples. We identified a set of 1,950 genes with highly significant deregulation between tumors and mucosa samples (P < 1e-7). A significant proportion of these genes mapped to chromosome 20 (P = 0.01). Seventeen genes had a > 5-fold average expression difference between normal colon mucosa and carcinomas, including up-regulation of MYC and of HMGA1, a putative oncogene. Furthermore, we identified 68 genes that were significantly differentially expressed between lymph node-negative and lymph node-positive tumors (P < 0.001), the functional annotation of which revealed a preponderance of genes that play a role in cellular immune response and surveillance. The microarray-derived gene expression levels of 20 deregulated genes were validated using quantitative real-time reverse transcription-PCR in > 40 tumor and normal mucosa samples with good concordance between the techniques. Finally, we established a relationship between specific genomic imbalances, which were mapped for 32 of the analyzed colon tumors by comparative genomic hybridization, and alterations of global transcriptional activity. Previously, we had conducted a similar analysis of primary rectal carcinomas. The systematic comparison of colon and rectal carcinomas revealed a significant overlap of genomic imbalances and transcriptional deregulation, including activation of the Wnt/beta-catenin signaling cascade, suggesting similar pathogenic pathways. C1 NCI, Genet Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. Univ Gottingen, Med Ctr, Dept Gen Surg, D-3400 Gottingen, Germany. RP Ried, T (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH, Room 1408,Bldg 50,50 S Dr, Bethesda, MD 20892 USA. EM mghadim@uni-goettingen.de RI Varma, Sudhir/N-8763-2014 OI Varma, Sudhir/0000-0002-4096-4782 FU Intramural NIH HHS [Z99 CA999999] NR 50 TC 74 Z9 75 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2007 VL 67 IS 1 BP 41 EP 56 DI 10.1158/0008-5472.CAN-06-1514 PG 16 WC Oncology SC Oncology GA 123TX UT WOS:000243320000008 PM 17210682 ER PT J AU Wang, M Vikis, HG Wang, Y Jia, DM Wang, DL Bierut, LJ Bailey-Wilson, JE Amos, CI Pinney, SM Petersen, GM de Andrade, M Yang, P Wiest, JS Fain, PR Schwartz, AG Gazdar, A Minna, J Gaba, C Rothschild, H Mandal, D Kupert, E Seminara, D Liu, Y Viswanathan, A Govindan, R Anderson, MW You, M AF Wang, Min Vikis, Haris G. Wang, Yian Jia, Dongmei Wang, Daolong Bierut, Laura J. Bailey-Wilson, Joan E. Amos, Christopher I. Pinney, Susan M. Petersen, Gloria M. de Andrade, Mariza Yang, Ping Wiest, Jonathan S. Fain, Pamela R. Schwartz, Ann G. Gazdar, Adi Minna, John Gaba, Colette Rothschild, Henry Mandal, Diptasri Kupert, Elena Seminara, Daniela Liu, Yan Viswanathan, Avinash Govindan, Ramaswamy Anderson, Marshall W. You, Ming TI Identification of a novel tumor suppressor gene p34 on human chromosome 6q25.1 SO CANCER RESEARCH LA English DT Article ID LUNG-CANCER; HETEROZYGOSITY; SUSCEPTIBILITY; ADENOCARCINOMA; IMBALANCES; CARCINOMA; PATTERNS; LOSSES; BREAST AB In this study, we observed loss of heterozygosity (LOH) in human chromosomal fragment 6q25.1 in sporadic lung cancer patients. LOH was observed in 65% of the 26 lung tumors examined and was narrowed down to a 2.2-Mb region. Single-nucleotide polymorphism (SNP) analysis of genes located within this region identified a candidate gene, termed p34. This gene, also designated as ZC3H12D, C6orf95, FLJ46041, or dJ281H8.1, carries an A/G nonsynonymous SNP at codon 106, which alters the amino acid from lysine to arginine. Nearly 73% of heterozygous lung cancer tissues with LOH and the A/G SNP also exhibited loss of the A allele. In vitro clonogenic and in vivo nude mouse studies showed that overexpression of the A allele exerts tumor suppressor function compared with the G allele. p34 is located within a recently mapped human lung cancer susceptibility locus, and association of the p34 A/G SNP was tested among these families. No significant association between the less frequent G allele and lung cancer susceptibility was found. Our results suggest that p34 may be a novel tumor suppressor gene involved in sporadic lung cancer but it seems not to be the candidate familial lung cancer susceptibility gene linked to chromosomal region 6q23-25. C1 Washington Univ, Sch Med, Dept Surg, St Louis, MO 63130 USA. Natl Human Genome Res Inst, Bethesda, MD USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Cincinnati, Cincinnati, OH 45221 USA. Mayo Clin, Coll Med, Rochester, MN USA. NCI, Rockville, MD USA. Univ Colorado, Denver, CO 80202 USA. Karmanos Canc Inst, Detroit, MI USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Med Univ Ohio, Toledo, OH USA. Louisiana State Univ, Hlth Sci Ctr, New Orleans, LA 70112 USA. RP You, M (reprint author), Washington Univ, Sch Med, Dept Surg, 660 Euclid Ave,Box 8109, St Louis, MO 63130 USA. EM youm@wustl.edu OI Bailey-Wilson, Joan/0000-0002-9153-2920 FU Intramural NIH HHS [ZIA BC010448-09]; NCI NIH HHS [R01 CA084354, P01 CA 89392, P01 CA089392, P50 CA 70907, P50 CA070907, R01 CA 099147, R01 CA 099187, R01 CA 80127, R01 CA 84354, R01 CA080127, R01 CA099147, R01 CA099187, U01 CA 76293, U01 CA076293]; NIEHS NIH HHS [P30 ES006096, R01 ES 012063, R01 ES 013340, R01 ES012063, R01 ES013340] NR 18 TC 20 Z9 24 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2007 VL 67 IS 1 BP 93 EP 99 DI 10.1158/0008-5472.CAN-06-2723 PG 7 WC Oncology SC Oncology GA 123TX UT WOS:000243320000013 PM 17210687 ER PT J AU Iwanaga, Y Chi, YH Miyazato, A Sheleg, S Haller, K Peloponese, JM Li, Y Ward, JM Benezra, R Jeang, KT AF Iwanaga, Yoichi Chi, Ya-Hui Miyazato, Akiko Sheleg, Sergey Haller, Kerstin Peloponese, Jean-Marie, Jr. Li, Yan Ward, Jerrold M. Benezra, Robert Jeang, Kuan-Teh TI Heterozygous deletion of mitotic arrest-deficient protein 1 (MAD1) increases the incidence of tumors in mice SO CANCER RESEARCH LA English DT Article ID SPINDLE ASSEMBLY CHECKPOINT; CHROMOSOME INSTABILITY; CANCER PREDISPOSITION; FREQUENT IMPAIRMENT; HUMAN LUNG; CELLS; GENE; ANEUPLOIDY; MUTATIONS; KINETOCHORE AB Mitotic arrest-deficient protein 1 (MAD1) is a component of the mitotic spindle assembly checkpoint. We have created a knockout mouse model to examine the physiologic consequence of reduced MAD1 function. Mad1(+/-) mice were successfully generated, but repeated paired mating of Mad1(+/-) with Mad1(+/-) mice failed to produce a single Mad1(-/-) animal, suggesting that the latter genotype is embryonic lethal. In aging studies conducted for > 18 months, Mad1(+/-) mice compared with control wild-type (wt) litter-mates showed a 2-fold higher incidence of constitutive tumors. Moreover, 42% of Mad1(+/-) (P < 0.03), but 0% of wt, mice developed neoplasia after treatment with vincristine, a microtubule depolymerization agent. Mad1(+/-) - mouse embryonic fibroblasts (MEF) were found to be more prone than wt cells to become aneuploid; Mad1(+/-), but not wt, MEFs produced fibrosarcomas when explanted into nude mice. Our results indicate an essential MAD1 function in mouse development and correlate Mad1 haploinsufficiency with increased constitutive tumors. C1 NIAID, Mol Microbiol Lab, Mol Virol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Infect Dis Pathogenesis Sect, Comparat Med Branch, Div Intramural Res,NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Canc Biol & Genet Program, New York, NY 10021 USA. RP Jeang, KT (reprint author), NIAID, Mol Microbiol Lab, Mol Virol Sect, NIH, Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Chi, Ya-Hui/B-1080-2010; Jeang, Kuan-Teh/A-2424-2008 FU Intramural NIH HHS NR 34 TC 100 Z9 101 U1 1 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2007 VL 67 IS 1 BP 160 EP 166 DI 10.1158/0008-5472.CAN-06-3326 PG 7 WC Oncology SC Oncology GA 123TX UT WOS:000243320000021 PM 17210695 ER PT J AU Belinsky, MG Guo, P Lee, K Zhou, F Kotova, E Grinberg, A Westphal, H Shchaveleva, I Klein-Szanto, A Gallo, JM Kruh, GD AF Belinsky, Martin G. Guo, Ping Lee, Kun Zhou, Feng Kotova, Elena Grinberg, Alex Westphal, Heiner Shchaveleva, Irina Klein-Szanto, Andres Gallo, James M. Kruh, Gary D. TI Multidrug resistance protein 4 protects bone marrow, thymus, spleen, and intestine from nucleotide analogue-induced damage SO CANCER RESEARCH LA English DT Article ID ORGANIC ANION TRANSPORTER; MRP4 CONFERS RESISTANCE; P-GLYCOPROTEIN; INCREASED SENSITIVITY; ANTICANCER DRUGS; ANTIVIRAL DRUGS; BRAIN; ADEFOVIR; 9-(2-PHOSPHONYLMETHOXYETHYL)ADENINE; PHARMACOKINETICS AB Nucleoside-based analogues are mainstays in the treatment of cancer, viral infections, and inflammatory diseases. Recent studies showing that the ATP-binding cassette transporter, multidrug resistance protein 4, is able to efflux nucleoside and nucleotide analogues from transfected cells suggests that the pump may affect the efficacy of this class of agents. However, the in vivo pharmacologic functions of the pump are largely unexplored. Here, using Mrp4(-/-) mice as a model system, and the nucleotide analogue, 9'-(2'-phosphonylmethoxyethyl)adenine (PMEA) as a probe, we investigate the ability of Mrp4 to function in vivo as an endogenous resistance factor. In the absence of alterations in plasma PMEA levels, Mrp4-null mice treated with PMEA exhibit increased lethality associated with marked toxicity in several tissues. Affected tissues include the bone marrow, spleen, thymus, and gastrointestinal tract. In addition, PMEA penetration into the brain is increased in Mrp4(-/-) mice. These findings indicate that Mrp4 is an endogenous resistance factor, and that the pump may be a component of the blood-brain barrier for nucleoside-based analogues. This is the first demonstration that an ATP-binding cassette transporter can affect in vivo tissue sensitivity towards this class of agents. C1 Fox Chase Canc Ctr, Div Med Sci, Philadelphia, PA 19111 USA. Fox Chase Canc Ctr, Dept Pathol, Philadelphia, PA 19111 USA. Temple Univ, Sch Pharm, Philadelphia, PA 19122 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Kruh, GD (reprint author), Fox Chase Canc Ctr, Div Med Sci, 333 Cottman Ave, Philadelphia, PA 19111 USA. EM gary.kruh@fccc.edu RI Klein-Szanto, Andres/E-6218-2010 FU NCI NIH HHS [CA 06927, CA 72937, CA 85577, CA 73728] NR 28 TC 54 Z9 55 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 1 PY 2007 VL 67 IS 1 BP 262 EP 268 DI 10.1158/0008-5472.CAN-06-2680 PG 7 WC Oncology SC Oncology GA 123TX UT WOS:000243320000033 PM 17210706 ER PT J AU Abnet, CC Fagundes, RB Strickland, PT Kamangar, F Roth, MJ Taylor, PR Dawsey, SM AF Abnet, Christian C. Fagundes, Renato B. Strickland, Paul T. Kamangar, Farin Roth, Mark J. Taylor, Philip R. Dawsey, Sanford M. TI The influence of genetic polymorphisms in Ahr, CYP1A1, CYP1A2, CYP1B1, GST M1, GST T1 and UGT1A1 on urine 1-hydroxypyrene glucuronide concentrations in healthy subjects from Rio Grande do Sul, Brazil SO CARCINOGENESIS LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; PAH EXPOSURE; CANCER; GSTM1; ASSOCIATION; METABOLITES; BIOMARKERS; PHENOTYPE; WORKERS; FOOD AB Polymorphisms in genes encoding polycyclic aromatic hydrocarbon (PAH) metabolizing enzymes may alter metabolism of these carcinogens and contribute to inter-individual difference in urine concentrations. We investigated the influence of genetic polymorphism on PAH metabolism in urine from 199 healthy subjects from Southern Brazil. We measured urine 1-hydroxypyrene glucuronide (1-OHPG) concentrations using immunoaffinity chromatography and synchronous fluorescence spectroscopy and genotyped subjects using standard methods. Genetic variants in CYP1B1 (rs1056827, rs1800440, rs10012) were strongly associated with urine 1-OHPG with P-values < 0.010. Variants in aryl hydrocarbon receptor (Ahr) (rs4986826), CYP1A1 (rs1799814) and CYP1A2 (rs2069514) were also, although less strongly, associated with changes in urine 1-OHPG concentrations. These variants had P-values of 0.074, 0.040 and 0.025, respectively. The median urine 1-OHPG concentrations (pmol/ml) in the homozygous wild-type and homozygous variants for CYP1B1 (rs10012) and the Ahr, CYP1A1 and CYP1A2 variants listed above were 2.16 and 0.10, 2.16 and 0.41, 2.03 and 0.46, 2.19 and 2.79, respectively. We found no effect of deletions in GST M1 or GST T1, or different alleles of UGT1A1*28. Adjusting for age, sex, place of residence, tobacco smoke exposure, mate drinking, cachaca and barbeque preparation had only a minor impact on the associations. A model containing just exposure variables had an r(2) of 0.21; a model with single genotypes for Ahr, CYP1A1, CYP1A2 and CYP1B1 had an r(2) of 0.10; and a model combining both exposure and genotype information had a total r(2) of 0.33. Our results suggest that CYP1B1 genotypes are strongly associated with urine 1-OHPG concentrations in this population. C1 NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Fed Santa Maria, Dept Clin Med, Ctr Ciencias Saude, BR-97119900 Santa Maria, RS, Brazil. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Abnet, CC (reprint author), NCI, Nutrit Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS-320,MSC 7232, Rockville, MD 20852 USA. EM abnetc@mail.nih.gov RI Abnet, Christian/C-4111-2015 OI Abnet, Christian/0000-0002-3008-7843 FU Intramural NIH HHS; NIEHS NIH HHS [P01-ES06052] NR 22 TC 19 Z9 21 U1 0 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2007 VL 28 IS 1 BP 112 EP 117 DI 10.1093/carcin/bg1131 PG 6 WC Oncology SC Oncology GA 120CV UT WOS:000243062100014 PM 16864595 ER PT J AU Hou, L El-Omar, EM Chen, J Grillo, P Rabkin, CS Baccarelli, A Yeager, M Chanock, SJ Zatonski, W Sobin, LH Lissowska, J Fraumeni, JF Chow, WH AF Hou, L. El-Omar, E. M. Chen, J. Grillo, P. Rabkin, C. S. Baccarelli, A. Yeager, M. Chanock, S. J. Zatonski, W. Sobin, L. H. Lissowska, J. Fraumeni, J. F., Jr. Chow, W. H. TI Polymorphisms in Th1-type cell-mediated response genes and risk of gastric cancer SO CARCINOGENESIS LA English DT Article ID TUMOR-NECROSIS-FACTOR; SINGLE NUCLEOTIDE POLYMORPHISMS; TNF-A GENES; HELICOBACTER-PYLORI; FACTOR-ALPHA; EPITHELIAL-CELLS; ACID-SECRETION; STOMACH-CANCER; T-CELLS; CARCINOMA AB Helicobacter pylori infection, the dominant risk factor for gastric cancers, has been shown to elicit T helper type 1 (Th1) polarized immunological responses. We conducted a population-based study of 305 gastric cancer cases and 427 age- and gender-matched controls in Warsaw, Poland, to evaluate the association with several variants in genes responsible for Th1-cell-mediated response. Genotyping was performed on genomic DNA by TaqMan(TM) assays to determine TNFA (-308 G > A, -417 G > A, -555 G > A, -1036 C > T, -1042 C > A, -1210 T > C), IL1A (-889 C > T), IFNGR2 (Ex7-128 T > C, Ex2-34 C > G and Ex2-16 A > G) and IL12A (IVS2-798 T > A, IVS2-701 C > A and Ex7+277 G > A) polymorphisms. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for sex, age, education and smoking status. Out of six single nucleotide polymorphisms (SNPs) tested in TNFA, gastric cancer risk was significantly associated with the TNFA (-308 G > A) polymorphism, with ORs of 1.4 (95% CI: 1.0-2.0) for the G/A and 2.5 (95% CI: 1.3-4.9) for the A/A genotype carriers, when compared with the more frequent genotype (G/G) (P-trend < 0.001). Among the three tested SNPs in the IFNGR2 gene, only the Ex7-128C > T polymorphism was associated with increased risk, with ORs of 1.5 (95% CI: 1.0-2.3) for T/C and 1.7 (95% CI: 1.1-2.7) for C/C carriers when compared with T/T carriers (P-trend = 0.01). Subjects carrying both IFNGR2 Ex7-128 C/C and TNFA -308 A/A genotypes had the highest risk (OR = 5.5, 95% CI: 1.5-19.4), although the interaction was not statistically significant. IL1A (-889 C > T) and the three examined IL12A variants were unrelated to gastric cancer risk. Our findings suggest that two Th1-related polymorphisms (TNFA -308 A > G and IFNGR2 Ex7-128 C > T) may increase the risk of gastric cancer. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Aberdeen, Inst Med Sci, Dept Med & Therapeut, Aberdeen AB25 2ZD, Scotland. IRCCS Osped Maggiore Policlin, Mol & Genet Epidemiol Ctr, Epidemiol Unit, Dept Occupat Clin & Prevent Med, I-20122 Milan, Italy. Univ Milan, Dept Occupat Med, EPOCA Res Ctr Clin Occupat & Environm Epidemiol, I-20122 Milan, Italy. NCI, Core Genotyping Facil, Ctr Adv Technol, Bethesda, MD 20892 USA. Ctr Canc, Div Canc Epidemiol & Prevent, PL-02781 Warsaw, Poland. M Sklodowska Curie Inst Oncol, PL-02781 Warsaw, Poland. Armed Forces Inst Pathol, Dept Hepat & Gastrointestinal Pathol, Washington, DC 20306 USA. RP Hou, L (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS 8123, Rockville, MD 20852 USA. EM lifangh2@mail.nih.gov RI Kim, Seongman/N-6910-2014; OI Lissowska, Jolanta/0000-0003-2695-5799 FU Intramural NIH HHS NR 44 TC 63 Z9 71 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2007 VL 28 IS 1 BP 118 EP 123 DI 10.1093/carcin/bg1130 PG 6 WC Oncology SC Oncology GA 120CV UT WOS:000243062100015 PM 16885196 ER PT J AU Alyaqoub, FS Tao, LH Kramer, PM Steele, VE Lubet, RA Gunning, WT Pereira, MA AF Alyaqoub, Fadel S. Tao, Lianhui Kramer, Paula M. Steele, Vernon E. Lubet, Ronald A. Gunning, William T. Pereira, Michael A. TI Prevention of mouse lung tumors and modulation of DNA methylation by combined treatment with budesonide and R115777 (Zarnestra(MT)) SO CARCINOGENESIS LA English DT Article ID FARNESYLTRANSFERASE INHIBITORS; A/J MICE; PULMONARY CARCINOGENESIS; AEROSOLIZED BUDESONIDE; CANCER; CHEMOPREVENTION; HYPOMETHYLATION; PROGRESSION; EXPRESSION; RECEPTOR AB Budesonide (an anti-inflammatory glucocorticoid), R115777 (a farnesyl transferase inhibitor, Zarnestra, Tipifarnib) or combinations of them were evaluated for prevention of lung tumors and for modulation of DNA methylation in tumors. Lung tumors were induced by vinyl carbamate in female strain A mice. One week later, mice received 60 or 100 mg/kg R115777 by oral gavage and 5 days/week, 0.8 or 1.6 mg/kg of budesonide in their diet, or their combined treatment until killed at 20, 28 and 36 weeks after administering the vinyl carbamate. Other mice were administered the drugs for 2 weeks before killing at Week 20. At Week 20, the rank order for prevention of lung tumors was the combined treatment > budesonide > R115777. At later killings, R115777 was no longer effective, whereas budesonide and the combinations continued to prevent tumors, albeit at a reduced efficacy. DNA hypomethylation in lung tumors was prevented by treatment with R115777, budesonide and the combinations. When administered starting at Week 18 to tumor-bearing mice, the drugs reversed DNA hypomethylation in the tumors. In summary, combined treatment with budesonide and R115777 produced the following results: (i)it was more efficacious in preventing lung tumors than the individual drugs; and (ii) it prevented and reversed DNA hypomethylation in lung tumors. These results support the combined use of budesonide and R115777 in prevention of lung tumors and suggest that reversal of DNA hypomethylation in lung tumors would be useful as a surrogate end-point biomarker for prevention. C1 Ohio State Univ, Coll Med & Publ Hlth, Dept Internal Med, Columbus, OH 43210 USA. Med Univ Ohio, Toledo, OH 43614 USA. NCI, Bethesda, MD 20892 USA. RP Pereira, MA (reprint author), Ohio State Univ, Coll Med & Publ Hlth, Dept Internal Med, 300 W 10th Ave,1148 CHRI, Columbus, OH 43210 USA. EM Pereira.25@osu.edu RI Gunning, William/E-4681-2010 FU NCI NIH HHS [R01-CA096129, N01-CN-15125]; PHS HHS [25126] NR 28 TC 7 Z9 7 U1 2 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2007 VL 28 IS 1 BP 124 EP 129 DI 10.1093/carcin/bgl136 PG 6 WC Oncology SC Oncology GA 120CV UT WOS:000243062100016 PM 16885199 ER PT J AU Zhang, X Mehta, RG Lantvit, DD Coschigano, KT Kopchick, JJ Green, JE Hedayat, S Christov, KT Ray, VH Unterman, TG Swanson, SM AF Zhang, Xiao Mehta, Rajendra G. Lantvit, Daniel D. Coschigano, Karen T. Kopchick, John J. Green, Jeffrey E. Hedayat, Samad Christov, Konstantin T. Ray, Vera H. Unterman, Terry G. Swanson, Steven M. TI Inhibition of estrogen-independent mammary carcinogenesis by disruption of growth hormone signaling SO CARCINOGENESIS LA English DT Article ID ANTIGEN TRANSGENIC MICE; HUMAN BREAST-CANCER; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; TUMOR PROGRESSION; BINDING PROTEIN; LARON-SYNDROME; FACTOR-I; RECEPTOR; GLAND AB Clinical trials and laboratory-based studies indicate that the growth hormone/insulin-like growth factor-I axis may affect the development of breast cancer. The purpose of the present investigation was to develop a genetic model of mammary cancer to test the hypothesis that downregulation of GH signaling can substantially retard mammary cancer progression. We crossed the Laron mouse, in which the gene for the GH receptor/binding protein has been disrupted, with the C3(1)/TAg mouse, which develops estrogen receptor alpha negative mammary cancers. All mice used in our experiments were heterozygous for the large T antigen (TAg) and either homozygous wild-type for GHR (Ghr(+/+)) or null for GHR (Ghr(-/-)). Compared with the TAg/Ghr(+/+) mice, the TAg/Ghr(-/-) mice showed delayed mammary cancer latency with significantly decreased multiplicity (9.8 +/- 1.4 versus 3.2 +/- 1.2) and volume (776.1 +/- 284.4 versus 50.5 +/- 8.9 mm(3)). Furthermore, the frequency of mammary hyperplasias was significantly reduced in the TAg/Ghr(-/-) mice (15.0 +/- 1.7 versus 6.8 +/- 1.7). To establish that these mammary cancers were estrogen-independent, 12-week-old TAg/Ghr(+/+) mice, which lack visible hyperplasia, were either ovariectomized (ovx) or sham operated (sham). Compared with the sham group, ovariectomy resulted in no difference in the frequency of mammary hyperplasia, mammary tumor latency, incidence, multiplicity or tumor size. Together, these data demonstrate that the disruption of GH signaling significantly retards TAg-driven mammary carcinogenesis, and suggest that disrupting GH signaling may be an effective strategy to inhibit the progression of estrogen-independent breast cancer. C1 Univ Illinois, Dept Med Chem & Pharmacognosy MC 781, Chicago, IL 60612 USA. Univ Illinois, Dept Surg Oncol, Chicago, IL 60612 USA. Univ Illinois, Dept Math Stat & Comp Sci, Chicago, IL 60612 USA. Univ Illinois, Dept Med, Chicago, IL 60612 USA. Dept Vet Affairs, Jesse Brown Med Ctr, Chicago, IL 60612 USA. IIT, Res Inst, Chicago, IL 60616 USA. Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA. Ohio Univ, Dept Biomed Sci, Athens, OH 45701 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD USA. Provident Hosp Cook Cty, Chicago, IL USA. RP Swanson, SM (reprint author), Univ Illinois, Dept Med Chem & Pharmacognosy MC 781, 833 S Wood St, Chicago, IL 60612 USA. EM swanson@uic.edu RI zhang, xiao/B-3947-2010 FU NIA NIH HHS [R01 AG 19899]; PHS HHS [R01 099904] NR 45 TC 29 Z9 31 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2007 VL 28 IS 1 BP 143 EP 150 DI 10.1093/carcin/bgl138 PG 8 WC Oncology SC Oncology GA 120CV UT WOS:000243062100019 PM 16916863 ER PT J AU Gitlin, JM Trivedi, DB Langenbach, R Loftin, CD AF Gitlin, Jonathan M. Trivedi, Darshini B. Langenbach, Robert Loftin, Charles D. TI Genetic deficiency of cyclooxygenase-2 attenuates abdominal aortic aneurysm formation in mice SO CARDIOVASCULAR RESEARCH LA English DT Article DE abdominal aortic aneurysm; cyclooxygenase-2; COX-2; inflammation; cyclooxygenase-2-deficient mice; cardiovascular disease ID PROSTAGLANDIN E-2 SYNTHESIS; SMOOTH-MUSCLE-CELLS; ANGIOTENSIN-II; INHIBITION; RECEPTOR; ATHEROSCLEROSIS; EXPRESSION; EXPANSION; CELECOXIB; KINASE AB Objective: Abdominal aortic aneurysms (AAAs) are characterized by chronic inflammation which contributes to the remodeling and eventual weakening of the vessel wall. Increased cyclooxygenase-2 (COX-2) expression is detected in human aneurysmal tissue and is suggested to contribute to the disease. The aim of the current study was to define the role of COX-2 expression in the development of AAAs, using a model of the disease. Methods: AAAs were induced in mice by chronic angiotensin II infusion, and were analyzed following 3, 7, 21 or 28 days of the infusion. AAA incidence and severity, together with the expression of inflammatory markers, were compared between abdominal aortas from COX-2-deficient mice and their wild-type littermate controls. Results: The AAA incidence in COX-2 wild-type mice was 54% (13/24), whereas AAAs were not detected in COX-2-deficient mice (0/23) following 28 days of angiotensin II infusion. The genetic deficiency of COX-2 also resulted in a 73% and 90% reduction in AAA incidence following 7 and 21 days of angiotensin II infusion, respectively. In COX-2 wild-type mice, COX-2 mRNA expression in the abdominal aorta was induced by angiotensin II beginning 3 days following initiation of the infusion, which continued throughout progression of the disease. Abundant COX-2 protein expression was detected in medial smooth muscle cells adjacent to the AAAs. The deficiency of COX-2 significantly attenuated mRNA expression in the abdominal aorta of the macrophage marker CD68, and the inflammatory cell recruitment chemokines, monocyte chemotactic protein-1 and macrophage inflammatory protein-1 alpha. Conclusions: Our findings suggest that increased COX-2 expression in smooth muscle cells of the abdominal aorta contributes to AAA formation in mice by enhancing inflammatory cell infiltration. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved. C1 Univ Kentucky, Dept Pharmaceut Sci, Coll Pharm, Lexington, KY 40536 USA. NIEHS, Lab Mol Carcinogenesis, NIH, Res Triangle Pk, NC 27709 USA. RP Loftin, CD (reprint author), Univ Kentucky, Dept Pharmaceut Sci, Coll Pharm, 725 Rose St,Rm 414, Lexington, KY 40536 USA. EM cdloft2@uky.edu RI Gitlin, Jonathan/H-4492-2011 NR 41 TC 45 Z9 46 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD JAN 1 PY 2007 VL 73 IS 1 BP 227 EP 236 DI 10.1016/j.cardiores.2006.10.015 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 131IZ UT WOS:000243863800028 PM 17137566 ER PT J AU O'Donnell, CJ AF O'Donnell, Christopher J. BA Gillard, J Graves, M Hatsukami, T Yuan, C BF Gillard, J Graves, M Hatsukami, T Yuan, C TI Epidemiology of carotid artery atherosclerosis SO CAROTID DISEASE: THE ROLE OF IMAGING IN DIAGNOSIS AND MANAGEMENT LA English DT Article; Book Chapter ID INTIMA-MEDIA THICKNESS; C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; WALL SHEAR-STRESS; RISK-ASSESSMENT STRATEGIES; POPULATION-BASED TWIN; NORTHERN-MANHATTAN; ISCHEMIC-STROKE; ENVIRONMENTAL CONTRIBUTIONS; CARDIOVASCULAR-DISEASE C1 [O'Donnell, Christopher J.] NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. [O'Donnell, Christopher J.] Harvard Univ, Massachusetts Gen Hosp, Sch Med, Dept Med, Boston, MA USA. RP O'Donnell, CJ (reprint author), NHLBI, Framingham Heart Study, Bldg 10, Bethesda, MD 20892 USA. NR 91 TC 1 Z9 1 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-52186-226-4 PY 2007 BP 22 EP 34 D2 10.2277/ 0521862264 PG 13 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA BXT44 UT WOS:000297021200003 ER PT J AU Zalla, T AF Zalla, Tiziana BA Marraffa, M DeCaro, M Ferretti, F BF Marraffa, M DeCaro, M Ferretti, F TI THE COGNITIVE ROLE OF PHENOMENAL CONSCIOUSNESS SO CARTOGRAPHIES OF THE MIND: PHILOSOPHY AND PSYCHOLOGY IN INTERSECTION SE Studies in Brain and Mind LA English DT Article; Book Chapter C1 [Zalla, Tiziana] French Ctr Natl Rech Sci CNRS, Paris, France. [Zalla, Tiziana] NIH, Bethesda, MD 20892 USA. [Zalla, Tiziana] Inst Cognit Sci, Lyon, France. RP Zalla, T (reprint author), Inst Jean Nicod, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS BN 978-1-4020-5444-0 J9 STUD BRAIN MIND PY 2007 VL 4 BP 189 EP 199 D2 10.1007/1-4020-5444-0 PG 11 WC Philosophy; Psychology, Multidisciplinary SC Philosophy; Psychology GA BKZ96 UT WOS:000269717100015 ER PT J AU Khatami, M AF Khatami, Mahin TI Standardizing cancer biomarkers criteria: data elements as a foundation for a database. Inflammatory mediator/M-CSF as model marker SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE cancer biomarkers; data elements; standardizing biomarkers criteria; database; inflammatory mediators; macrophage colony-stimulating factor; early detection; chemoprevention; therapy; oncology ID COLONY-STIMULATING FACTOR; SURROGATE END-POINTS; OF-THE-LITERATURE; CELL LUNG-CANCER; COLORECTAL-CANCER; PROSTATE-CANCER; CIRCULATING LEVELS; OVARIAN-CANCER; SERUM-LEVELS; EXPRESSION AB The purpose of this position article was to design a set of criteria (data elements) for a wide range of cancer biomarkers (CBs) in an attempt to standardize biomarkers features through a common language as a foundation for a database. Data elements are described as a set of generic criteria, which should characterize nearly all biomarkers introduced in the literature. Data elements were extracted from the review of prominent features that biomarkers represent within various categories. The extracted characteristics of biomarkers produced a short list of shared and unique generic features such as biological nature and history; stage/phase of study; sensitivity and specificity; modes of action; risk assessment; validation status; technology, and recommendation status for diversified biomarkers. To tailor data elements on specific markers, a cytokine, such as macrophage-colony stimulating factor (M-CSF), which has been proposed as a 'potentially suitable biomarker' for diagnosis of ovarian, lung, breast, pancreatic, and colorectal cancers, was selected as a Model biomarker. Small scale clinical studies suggested the superior usefulness of M-CSF compared with traditional markers for cancer detection. A key criterion for selecting Model marker and tailoring data elements for detection of cancer was the comparison of data on its specificity and sensitivity with traditional markers. The design of data elements for standardizing CBs criteria is considered a Research Tool and a foundation for developing a comprehensive CBs database useful for oncology researchers for a wide range of biomarkers. Validation, integration and proper packaging, data visualization and recommendation of suitability of CBs, by a panel of experts, for technology development are important challenging next steps toward developing a reliable database, which would allow professionals to effectively retrieve and study integrated information on potentially useful markers; identify important knowledge gaps and limitations of data; and assess state of technologies and commercialization of markers at a point of need. Appropriate use of integrated information on biomarkers in clinical practices would eventually account for more costeffective characteristics of an individual's state of health. C1 NCI, Technol Program Dev, Off Technol & Ind Relat, Off Director,DHHS,NIH, Bethesda, MD 20892 USA. RP Khatami, M (reprint author), NCI, Technol Program Dev, Off Technol & Ind Relat, Off Director,DHHS,NIH, Bethesda, MD 20892 USA. EM Khatamim@mail.nih.gov NR 51 TC 12 Z9 12 U1 0 U2 5 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2007 VL 47 IS 2 BP 187 EP 198 DI 10.1007/s12013-007-0003-z PG 12 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 181PE UT WOS:000247447800003 PM 17652771 ER PT J AU Sinha, N Li, YL Lipschultz, CA Smith-Gill, SJ AF Sinha, Neethi Li, Yili Lipschultz, Claudia A. Smith-Gill, Sandra J. TI Understanding antibody-antigen associations by molecular dynamics simulations: Detection of important intra- and inter-molecular salt bridges SO CELL BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE antibody-antigen associations; molecular dynamics simulation; salt-bridges; hydrogen-bonds; flexibility; antibody binding site ID PROTEIN-PROTEIN INTERACTIONS; EGG-WHITE LYSOZYME; BINDING INTERACTIONS; ELECTROSTATIC STRENGTHS; MONOCLONAL-ANTIBODIES; CRYSTAL-STRUCTURE; CROSS-REACTIVITY; FREE-ENERGIES; LIGHT-CHAINS; COMPLEX AB 1 NSec molecular dynamics (MD) simulation of anti-hen egg white antibody, HyHEL63 (HH63), complexed with HEL reveals important molecular interactions, not revealed in its X-ray crystal structure. These molecular interactions were predicted to be critical for the complex formation, based on structure-function studies of this complex and 3-other anti-HEL antibodies, HH8, HH10 and HH26, HEL complexes. All four antibodies belong to the same structural family, referred to here as HH10 family. Ala scanning results show that they recognize 'coincident epitopes'. 1 NSec explicit, with periodic boundary condition, MD simulation of HH63-HEL reveals the presence of functionally important salt-bridges. Around 200 ps in vacuo and an additional 20 ps explicit simulation agree with the observations from 1 Nsec simulation. Intra-molecular salt-bridges predicted to play significant roles in the complex formation, were revealed during MD simulation. A very stabilizing salt-bridge network, and another intra-molecular salt-bridge, at the binding site of HEL, revealed during the MD simulation, is proposed to predipose binding site geometry for specific binding. All the revealed salt-bridges are present in one or more of the other three complexes and/or involve "hot-spot" epitop6 and para-tope residues. Most of these charged epitope residues make large contribution to the binding free energy. The "hot spot" epitope residue Lys97(Y), which signiticantly contributes to the free energy of binding in all the complexes, forms an intermolecular salt-bridge in several MD conformers. Our earlier computations have shown that this inter-molecular salt-bridge plays a signiticant role in determining specificity and flexibility of binding in the HH8-HEL and HH26-HEL complexes. Using a robust criterion of salt-bridge detection, this intermolecular salt-bridge was detected in the native structures of the HH8-HEL and HH26-HEL complexes, but was not revealed in the crystal structure of HH63-HEL complex. The electrostatic strength of this revealed salt-bridge was very strong. During 1 Nsec MD simulation this salt-bridge networks with another inter-molecular salt-bridge to form an inter-molecular salt-bridge triad. Participation of Lys97(Y) in the formation of inter-molecular triad further validates the functional importance of Lys97(Y) in HH63-HEL associations. These results demonstrate that many important structural details of bio-molecular interactions can be better understood when studied in a dynamic environment, and that MD simulations can complement and expand information obtained from static X-ray structure. This study also highlights "hot-spot" molecular interactions in HyHEL63-HEL complex. C1 NIH, Natl Canc Inst, Frederick Canc Res & Dev Ctr, Div Basic Sci,Struct Biophys Lab, Frederick, MD 21702 USA. RP Sinha, N (reprint author), Johns Hopkins Univ, 106 Mudd Hall,3400 N Charles St, Baltimore, MD 21218 USA. EM nsinha@jhu.edu NR 63 TC 5 Z9 5 U1 1 U2 16 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 1085-9195 J9 CELL BIOCHEM BIOPHYS JI Cell Biochem. Biophys. PY 2007 VL 47 IS 3 BP 361 EP 375 DI 10.1007/s12013-007-0031-8 PG 15 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 182JU UT WOS:000247501700004 PM 17652781 ER PT S AU Putney, JW AF Putney, James W., Jr. BE Wakelam, MJO TI Inositol lipids and TRPC channel activation SO CELL BIOLOGY OF INOSITOL LIPIDS AND PHOSPHATES SE BIOCHEMICAL SOCIETY SYMPOSIUM LA English DT Article; Proceedings Paper CT 74th Biochemical-Society Symposium CY MAR 29-31, 2006 CL Univ Birmingham, Med Sch, Birmingham, ENGLAND SP Biochem Soc HO Univ Birmingham, Med Sch ID CAPACITATIVE CA2+ ENTRY; CA2+-PERMEABLE CATION CHANNEL; SMOOTH-MUSCLE-CELLS; PROTEIN-KINASE-C; CALCIUM-STORE DEPLETION; SALIVARY-GLAND CELLS; PORTAL-VEIN MYOCYTES; TRANSIENT RECEPTOR; FUNCTIONAL EXPRESSION; SIGNALING MECHANISM AB The original hypothesis put forth by Bob Michell in his seminal 1975 review held that inositol lipid breakdown was involved in the activation of plasma in embrane calcium channels or 'gates'. Subsequently, it was demonstrated that while the interposition of inositol lipid breakdown upstream of calcium signalling was correct, it was predominantly the release of Ca2+ that was activated, through the formation of Ins(1,4,5)P-3. Ca2+ entry across the plasma membrane involved a secondary mechanism signalled in an unknown manner by depletion of intracellular Ca2+ stores. In recent years, however, additional non-store-operated mechanisms for Ca2+ entry have emerged. In many instances, these pathways involve homologues of the Drosophila trp (transient receptor potential) gene. In mammalian systems there are seven members of the TRP superfamily, designated TRPC1-TRPC7, which appear to be reasonably close structural and functional homologues of Drosophila TRP. Although these channels can sometimes function as store-operated channels, in the majority of instances they function as channels more directly linked to phospholipase C activity. Three members of this family, TRPC3, 6 and 7, are activated by the phosphoinositide breakdown product, diacylglycerol. Two others, TRPC4 and 5, are also activated as a consequence of phospholipase C activity, although the precise substrate or product molecules involved are still unclear. Thus the TRPCs represent a family of ion channels that are directly activated by inositol lipid breakdown, confirming Bob Michell's original prediction 30 years ago. C1 Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Putney, JW (reprint author), Natl Inst Environm Hlth Sci, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. EM putney@niehs.nih.gov NR 82 TC 9 Z9 9 U1 0 U2 1 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON W1N 3AJ, ENGLAND SN 0067-8694 BN 978-1-85578-166-5 J9 BIOCHEM SOC SYMP PY 2007 VL 74 BP 37 EP 45 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BFV61 UT WOS:000244887500004 ER PT S AU Shears, SB AF Shears, Stephen B. BE Wakelam, MJO TI Understanding the biological significance of diphosphoinositol polyphosphates ('inositol phosphates') SO CELL BIOLOGY OF INOSITOL LIPIDS AND PHOSPHATES SE BIOCHEMICAL SOCIETY SYMPOSIUM LA English DT Article; Proceedings Paper CT 74th Biochemical-Society Symposium CY MAR 29-31, 2006 CL Univ Birmingham, Med Sch, Birmingham, ENGLAND SP Biochem Soc HO Univ Birmingham, Med Sch ID OVARIAN-CARCINOMA CELLS; SACCHAROMYCES-CEREVISIAE; HEXAKISPHOSPHATE KINASE-2; MYOINOSITOL HEXAKISPHOSPHATE; TELOMERE LENGTH; PROTEIN; TETRAKISPHOSPHATE; PYROPHOSPHATES; DICTYOSTELIUM; PHOSPHOHYDROLASE AB Among the many derivatives of the inositol-based signalling family are a subgroup that possess diphosphates. In this review, some recent research into the actions of these specialized polyphosphates is analysed, and key goals for future studies are identified, which, it is hoped, will result in the wider cell-signalling community giving considerably greater attention to this intriguing but relatively neglected class of Mositol polyphosphates. C1 Natl Inst Environm Hlth Sci, Inositide Signaling Grp, NIH, DHHS, Res Triangle Pk, NC 27709 USA. RP Shears, SB (reprint author), Natl Inst Environm Hlth Sci, Inositide Signaling Grp, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov NR 65 TC 12 Z9 12 U1 0 U2 0 PU PORTLAND PRESS LTD PI LONDON PA 59 PORTLAND PL, LONDON W1N 3AJ, ENGLAND SN 0067-8694 BN 978-1-85578-166-5 J9 BIOCHEM SOC SYMP PY 2007 VL 74 BP 211 EP 221 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA BFV61 UT WOS:000244887500018 ER PT J AU Belov, GA Ehrenfeld, E AF Belov, George A. Ehrenfeld, Ellie TI Involvement of cellular membrane traffic proteins in poliovirus replication SO CELL CYCLE LA English DT Article DE membrane traffic; Arf GTPases; GEF; poliovirus; RNA replication ID NUCLEOTIDE EXCHANGE FACTOR; BREFELDIN-A; ENDOPLASMIC-RETICULUM; 3CD PROTEINASE; RNA-SYNTHESIS; FACTOR GBF1; 3A PROTEIN; INHIBITION; INFECTION; VESICLES AB Expression of viral genes results in the modulation of cellular metabolism to support virus replication. Poliovirus infection of HeLa cells induces a dramatic rearrangement of intracellular membrane structures: virtually all cellular organelles except mitochondria are converted into virus replication vesicles. Although this phenomenon is known for almost half a century, very few mechanistic details explaining this transformation are understood. Recently we found that small GTPases, Arf, key components of the secretory pathway, translocate to sites of poliovirus RNA replication in infected cells, and that two poliovirus proteins, 3A and 3CD, can independently induce such translocation in vitro. Our most recent work shows the recruitment to viral replication complexes of activators of Arf, specific guanine nucleotide exchange factors ( GEFs). Diversion of these GEFs from their normal activities in the secretory pathway provides a plausible explanation for the inhibition of protein secretion in poliovirus-infected cells as well as for the sensitivity of poliovirus infection to brefeldin A, a drug known to inhibit the secretory pathway. Identification of these cellular components defines a new class of host factors involved in virus replication complex formation and allows us to propose a hypothesis for remodeling of endoplasmic reticulum membranes into poliovirus replication complexes. C1 NIAID, NIH, Bethesda, MD 20892 USA. RP Ehrenfeld, E (reprint author), NIAID, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM eehrenfeld@niaid.nih.gov RI Belov, George/B-4625-2008 OI Belov, George/0000-0002-0892-1731 NR 35 TC 44 Z9 44 U1 0 U2 3 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JAN 1 PY 2007 VL 6 IS 1 BP 36 EP 38 DI 10.4161/cc.6.1.3683 PG 3 WC Cell Biology SC Cell Biology GA 149AF UT WOS:000245117800008 PM 17245115 ER PT J AU Sharan, SK Kuznetsov, SG AF Sharan, Shyam K. Kuznetsov, Sergey G. TI Resolving RAD51C function in late stages of homologous recombination SO CELL DIVISION LA English DT Article AB DNA double strand breaks are efficiently repaired by homologous recombination. One of the last steps of this process is resolution of Holliday junctions that are formed at the sites of genetic exchange between homologous DNA. Although various resolvases with Holliday junctions processing activity have been identified in bacteriophages, bacteria and archaebacteria, eukaryotic resolvases have been elusive. Recent biochemical evidence has revealed that RAD51C and XRCC3, members of the RAD51-like protein family, are involved in Holliday junction resolution in mammalian cells. However, purified recombinant RAD51C and XRCC3 proteins have not shown any Holliday junction resolution activity. In addition, these proteins did not reveal the presence of a nuclease domain, which raises doubts about their ability to function as a resolvase. Furthermore, oocytes from infertile Rad51C mutant mice exhibit precocious separation of sister chromatids at metaphase II, a phenotype that reflects a defect in sister chromatid cohesion, not a lack of Holliday junction resolution. Here we discuss a model to explain how a Holliday junction resolution defect can lead to sister chromatid separation in mouse oocytes. We also describe other recent in vitro and in vivo evidence supporting a late role for RAD51C in homologous recombination in mammalian cells, which is likely to be resolution of the Holliday junction. C1 [Sharan, Shyam K.; Kuznetsov, Sergey G.] NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. RP Sharan, SK (reprint author), NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. EM ssharan@ncifcrf.gov; skuznetsov@ncifcrf.gov OI Kuznetsov, Sergey/0000-0002-5662-9700 NR 63 TC 17 Z9 18 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1747-1028 J9 CELL DIV JI Cell Div. PY 2007 VL 2 AR 15 DI 10.1186/1747-1028-2-15 PG 9 WC Cell Biology SC Cell Biology GA V14GV UT WOS:000207723800015 PM 17547768 ER PT B AU Coecke, S Balls, M Bowe, G Davis, J Gstraunthaler, G Hartung, T Hay, R Price, A Merten, OW Stokes, W Schechtman, L Stacey, G AF Coecke, Sandra Balls, Michael Bowe, Gerard Davis, John Gstraunthaler, Gerhard Hartung, Thomas Hay, Robert Price, Anna Merten, Otto-Wilhelm Stokes, William Schechtman, Leonard Stacey, Glyn BE Smith, R TI Guidance on good cell culture practice SO CELL TECHNOLOGY FOR CELL PRODUCTS LA English DT Proceedings Paper CT 19th Meeting of the European-Society-for-Animal-Cell-Technology (ESACT) CY JUN 05-08, 2005 CL Harrogate, ENGLAND SP European Soc Anim Cell Technol DE cell culture; best practice AB The history of cell culture teaches us that there is a need to attend to certain fundamental aspects of best practice when preparing cells for routine use. As cell culture techniques and applications become more complex it becomes increasingly necessary to be aware of the impact of poorly controlled or suboptimal cell culture procedures. The Good Cell Culture Practice guidance has been prepared to promote an awareness of a broad range of important issues in cell culture in workers coming to use cells for their work for the first time and to remind others of the fundamental aspects of good practice in cell and tissue culture. C1 [Coecke, Sandra; Bowe, Gerard; Price, Anna] European Commiss, Inst Hlth & Consumer Protect, ECVAM, I-21020 Ispra, Italy. [Balls, Michael] FRAME, Nottingham, England. [Davis, John] Bio Products Lab, Dept Res & Dev, Hereford, England. [Gstraunthaler, Gerhard] Innsbruck Med Univ, Dept Phys, Innsbruck 6010, Austria. [Hay, Robert] ATCC, Manassas, VA USA. [Merten, Otto-Wilhelm] Genethon, F-91000 Evry, France. [Stokes, William] Natl Toxicol Program Interagency Ctr, Evaluat Alternative Toxicol Methods, Environ Toxicol Program, Natl Inst Environ Hlth Sci, Res Triangle Pk, NC 27709 USA. [Schechtman, Leonard] Natl Ctr Toxicol Res & Drug Adm, Rockville 20857, MD USA. [Stacey, Glyn] Natl Inst Biol Standards & Control, Div Cell Biol & UK Stem Cell Bank, Potters Bar, Herts, England. RP Coecke, S (reprint author), European Commiss, Inst Hlth & Consumer Protect, ECVAM, I-21020 Ispra, Italy. EM John.Davis@bpl.co.uk; omerten@genethon.fr; gstacey@nibsc.ac.uk NR 2 TC 0 Z9 1 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4020-5475-4 PY 2007 BP 313 EP + DI 10.1007/978-1-4020-5476-1_49 PG 2 WC Biotechnology & Applied Microbiology; Cell Biology SC Biotechnology & Applied Microbiology; Cell Biology GA BGB45 UT WOS:000245916900049 ER PT J AU Amable, R Lee, CT Hayashi, T Shen, J Sanchez, JF Chen, J Spivak, CE Lupica, CR Freed, WJ AF Amable, R. Lee, C. -T. Hayashi, T. Shen, J. Sanchez, J. F. Chen, J. Spivak, C. E. Lupica, C. R. Freed, W. J. TI FGF8 promotes glutannatergic and GABAergic neuronal differentiation of human neocortical neural progenitor cells SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 14th Annual Meeting of the American-Society-for-Neural-Therapy-and Repair CY 2007 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 NIH, Natl Inst Drug Abuse, Intramural Res Program, Cellular Neurobiol Res Branch, Baltimore, MD USA. SciCell Res Labs, San Diego, CA USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2007 VL 16 IS 3 BP 313 EP 313 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 163NR UT WOS:000246167200013 ER PT J AU Kleitman, N AF Kleitman, N. TI Translational neuroscience SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 14th Annual Meeting of the American-Society-for-Neural-Therapy-and Repair CY 2007 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 NIH, Natl Inst Neurol Disorders & Stroke, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2007 VL 16 IS 3 BP 330 EP 330 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 163NR UT WOS:000246167200060 ER PT J AU Vazin, T Chen, J Lee, CT Amable, R Freed, WJ AF Vazin, T. Chen, J. Lee, C. -T. Amable, R. Freed, W. J. TI Assessment of stromal-derived inducing activity in generation of dopaminergic neurons from human embryonic stem cells SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 14th Annual Meeting of the American-Society-for-Neural-Therapy-and Repair CY 2007 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 NIH, Natl Inst Drug Abuse, Dept Hlth & Human Serv, Cell Neurobiol Res Branch,Dev & Plastic Sect, Baltimore, MD USA. Royal Inst Technol, AlbaNova Univ Ctr, Dept Biotechnol, Stockholm, Sweden. NR 0 TC 3 Z9 3 U1 0 U2 1 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2007 VL 16 IS 3 BP 349 EP 349 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 163NR UT WOS:000246167200114 ER PT J AU Walczak, P Magnus, T Gilad, AA Kedziorek, DA McMahon, MT Kerr, DA Bulte, JWM AF Walczak, P. Magnus, T. Gilad, A. A. Kedziorek, D. A. McMahon, M. T. Kerr, D. A. Bulte, J. W. M. TI Monitoring cell-based therapy of demyelination with bioluminescence and MRI SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 14th Annual Meeting of the American-Society-for-Neural-Therapy-and Repair CY 2007 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Inst Cell Engn, Baltimore, MD 21205 USA. NIA, NIH, Neurosci Lab, Gerontol Res Ctr,Stem Cell Biol Unit, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurol, Baltimore, MD 21205 USA. RI Bulte, Jeff/A-3240-2008; Walczak, Piotr/B-8707-2008; Kedziorek, Dorota/B-8742-2008; KERR, Douglas /B-9270-2008 OI Bulte, Jeff/0000-0003-1202-1610; NR 0 TC 3 Z9 3 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2007 VL 16 IS 3 BP 349 EP 350 PG 2 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 163NR UT WOS:000246167200115 ER PT J AU Wang, Y Harvey, BK Powers, K Shen, H Hoffer, B AF Wang, Y. Harvey, B. K. Powers, K. Shen, H. Hoffer, B. TI Astaxanthin reduces ischemic brain injury induced by transient middle cerebral artery ligation in rats SO CELL TRANSPLANTATION LA English DT Meeting Abstract CT 14th Annual Meeting of the American-Society-for-Neural-Therapy-and Repair CY 2007 CL Clearwater, FL SP Amer Soc Neural Therapy & Repair C1 Natl Inst Drug Abuse, Baltimore, MD USA. RI Harvey, Brandon/A-5559-2010 NR 0 TC 4 Z9 4 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2007 VL 16 IS 3 BP 350 EP 350 PG 1 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 163NR UT WOS:000246167200116 ER PT J AU Harvey, BK Chen, GJ Schoen, CJ Lee, CT Howard, DB Dillon-Carter, O Coggiano, M Freed, WJ Wang, Y Hoffer, BJ Sanchez, JF AF Harvey, B. K. Chen, G. J. Schoen, C. J. Lee, C. T. Howard, D. B. Dillon-Carter, O. Coggiano, M. Freed, W. J. Wang, Y. Hoffer, B. J. Sanchez, J. F. TI An immortalized rat ventral mesencephalic cell line, RTC4, is protective in a rodent model of stroke SO CELL TRANSPLANTATION LA English DT Article DE platelet-derived growth factor (PDGF); stroke; ischemia; transplantation; ventral mesencephaton ID MIDDLE CEREBRAL-ARTERY; LARGE T-ANTIGEN; SV40 LARGE T; ADENOASSOCIATED VIRUS VECTORS; REDUCES INFARCT SIZE; GROWTH-FACTOR; NEUROTROPHIC FACTOR; IN-VIVO; ISCHEMIA; EXPRESSION AB One therapeutic approach to stroke is the transplantation of cells capable of trophic support, reinnervation, and/or regeneration. Previously, we have described the use of novel truncated isoforms of SV40 large T antigen to generate unique cell lines from several primary rodent tissue types. Here we describe the generation of two cell lines, RTC3 and RTC4, derived from primary mesencephalic tissue using a fragment of mutant T antigen, T155c (cDNA) expressed from the RSV promoter. Both lines expressed the glial markers vimentin and S100 beta, but not the neuronal markers NeuN, MAP2, or beta-III-tubulin. A screen for secreted trophic factors revealed substantially elevated levels of platelet-derived growth factor (PDGF) in RTC4, but not RTC3 cells. When transplanted into rat cortex, RTC4 cells survived for at least 22 days and expressed PDGF. Because PDGF has been reported to reduce ischemic injury, we examined the protective functions of RTC4 cells in an animal model of stroke. RTC4 or RTC3 cells, or vehicle, were injected into rat cortex 15-20 min prior to a 60-min middle cerebral artery ligation. Forty-eight hours later, animals were sacrificed and the stroke volume was assessed by triphenyl-tetrazolium chloride (TTC) staining. Compared to vehicle or RTC3 cells, transplanted RTC4 cells significantly reduced stroke volume. Overall, we generated a cell line with glial properties that produces PDGF and reduces ischemic injury in a rat model of stroke. C1 NIDA, Intramural Res Program, Mol Neuropsychiat Res Branch, NIH, Baltimore, MD 21224 USA. NIDA, Cellular Neurobiol Res Branch, NIH, Baltimore, MD USA. RP Freed, WJ (reprint author), NIDA, Intramural Res Program, Mol Neuropsychiat Res Branch, NIH, 333 Cassell Dr,Triad Bldg,Room 3501, Baltimore, MD 21224 USA. EM wfreed@mail.nih.gov RI Harvey, Brandon/A-5559-2010 FU Intramural NIH HHS [Z01 DA000410-10, Z01 DA000429-09, Z99 DA999999] NR 32 TC 6 Z9 6 U1 0 U2 0 PU COGNIZANT COMMUNICATION CORP PI ELMSFORD PA 3 HARTSDALE ROAD, ELMSFORD, NY 10523-3701 USA SN 0963-6897 J9 CELL TRANSPLANT JI Cell Transplant. PY 2007 VL 16 IS 5 BP 483 EP 491 PG 9 WC Cell & Tissue Engineering; Medicine, Research & Experimental; Transplantation SC Cell Biology; Research & Experimental Medicine; Transplantation GA 194UX UT WOS:000248370400004 PM 17708338 ER PT J AU Hart, PS Hart, TC AF Hart, P. Suzanne Hart, Thomas C. TI Disorders of human dentin SO CELLS TISSUES ORGANS LA English DT Article DE dentin; dentin dysplasia; dentinogenesis imperfecta; DSPP; small integrin-binding ligand N-linked glycoprotein ID IMPERFECTA TYPE-II; FAMILIAL TUMORAL CALCINOSIS; DENTINOGENESIS IMPERFECTA; OSTEOGENESIS IMPERFECTA; SIBLING PROTEINS; DOMINANT FORM; HEARING-LOSS; MUTATION; DSPP; SIALOPHOSPHOPROTEIN AB Dentin, the most abundant tissue in teeth, is produced by odontoblasts, which differentiate from mesenchymal cells of the dental papilla. Dentinogenesis is a highly controlled process that results in the conversion of unmineralized predentin to mineralized dentin. By weight, 70% of the dentin matrix is mineralized, while the organic phase accounts for 20% and water constitutes the remaining 10%. Type I collagen is the primary component (> 85%) of the organic portion of dentin. The non-collagenous part of the organic matrix is composed of various proteins, with dentin phosphoprotein predominating, accounting for about 50% of the non-collagenous part. Dentin defects are broadly classified into two major types: dentinogenesis imperfectas (DIs, types I-III) and dentin dysplasias (DDs, types I and II). To date, mutations in DSPP have been found to underlie the dentin disorders DI types II and III and DD type II. With the elucidation of the underlying genetic mechanisms has come the realization that the clinical characteristics associated with DSPP mutations appear to represent a continuum of phenotypes. Thus, these disorders should likely be called DSPP-associated dentin defects, with DD type II representing the mild end of the phenotypic spectrum and DI type III representing the severe end. Copyright (c) 2007 S. Karger AG, Basel. C1 NHGRI, NIH, Off Clin Director, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, NIH, Sect Dent & Craniofacial Genet, Bethesda, MD 20892 USA. RP Hart, PS (reprint author), NHGRI, NIH, Off Clin Director, Natl Inst Dent & Craniofacial Res, Bldg 10 CRC Room 3-2551,10 Ctr Dr, Bethesda, MD 20892 USA. EM shart@mail.nih.gov FU Intramural NIH HHS [Z99 HG999999] NR 44 TC 49 Z9 54 U1 0 U2 8 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-6405 J9 CELLS TISSUES ORGANS JI Cells Tissues Organs PY 2007 VL 186 IS 1 BP 70 EP 77 DI 10.1159/000102682 PG 8 WC Anatomy & Morphology; Cell Biology; Developmental Biology SC Anatomy & Morphology; Cell Biology; Developmental Biology GA 187CT UT WOS:000247825600006 PM 17627120 ER PT J AU Ochillo, RF Denaro, FJ Robinson, TJ Mcnairy, SA Mcclure, SA AF Ochillo, R. F. Denaro, F. J. Robinson, T. J. Mcnairy, S. A. Mcclure, S. A. TI Research Centers on Minority Institutions (RCMI): II SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article DE minority institutions; RCMI programs AB The goal of the Research Centers in Minority Institutions (RCMI) is to develop biomedical and behavioral research at institutions with 50% minority enrollment ( African Americans, Hispanics, Native Hawaiians, Pacific Islanders, Native Americans and Alaska Natives) who have been underrepresented in the biomedical sciences. The program has made available resources vital to scientific development and progress. While these resources have included, equipment, personnel supplies, Core laboratories etc, important effective approaches to research also have been emerging. C1 Morgan State Univ, Dept Biol, Baltimore, MD 21251 USA. Morgan State Univ, Off Provost, Baltimore, MD 21251 USA. NIH, Div Res Infrastruct, Natl Ctr Res Resources, Bethesda, MD 20892 USA. RP Ochillo, RF (reprint author), Morgan State Univ, Dept Biol, 1700 E Cold Spring Lane, Baltimore, MD 21251 USA. EM Denaro@umbi.umd.edu FU NCRR NIH HHS [RR017581]; NINDS NIH HHS [NS31875]; PHS HHS [MS-29494] NR 1 TC 0 Z9 0 U1 0 U2 2 PU C M B ASSOC PI POITIERS PA 40 AVENUE RECTEUR PINEAU, BAT MECANIQUE, 86022 POITIERS, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PY 2007 VL 53 IS 4 BP 3 EP 7 DI 10.1170/T801 PG 5 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 197JH UT WOS:000248550400002 PM 17531154 ER PT J AU Davis, JH Desoto, JA Fryar, EB Southerland, WM Bowen, D AF Davis, J. H. Desoto, J. A. Fryar, E. B. Southerland, W. M. Bowen, D. TI Sequential combination chemotherapy in human breast cancer: A basis for increased antineoplastic activity and bone marrow protection SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT 10th RCMI International Symposium on Health Disparities CY DEC 13-16, 2006 CL San Juan, PR SP Univ Puerto Rico Med Sci Campus DE tamoxifen; priming dose of 5-fluorouracil; methotrexate ID HIGH-DOSE CHEMOTHERAPY; STEM-CELL TRANSPLANTATION; RESISTANCE; METHOTREXATE; ANTIMETABOLITES; SALVAGE; PATHWAY; AGENTS; TUMOR AB These studies were designed to develop procedures that would capitalize on the growth inhibitory effects of tamoxifen (Tam) and methotrexate (MTX) in breast cancer, while protecting bone marrow with a priming dose of 5-fluorouracil (5-FU). High-dose MTX ( 10 mu M) cytotoxicity is maintained in MCF-7 breast cancer cells but reduced in human bone marrow by a priming and nontoxic dose of 5-FU ( 10 mu M). MTX cytotoxicity is decreased in MCF-7 breast cancer cells when the selective estrogen receptor modulator ( SERM) Tam ( 10 mu M) is administered 24 hours prior to 5-FU ( 10 mu M) followed two hours later by MTX ( early Tam) resulting in a growth rate of 57.42 +/- 4.38% of the control rate. However, when breast cancer cells are exposed to Tam 24 hours after 5-FU + MTX ( late Tam), the interaction between MTX and Tam is not antagonistic, the percentage of the control is 29.47 +/- 4.54%. Bone marrow exposure to these drug combinations exhibits a protective effect to the MTX cytotoxicity, with the early Tam combination yielding 59.45 +/- 16.38% of the control for MTX alone. These studies suggest that a) Tam in combination with a priming dose of 5-FU protects bone marrow from MTX cytotoxicity, b) the interactions between Tam and MTX are sequence-dependent, c) Tam decreases the effect of MTX when Tam administration precedes MTX. C1 Hampton Univ, Sch Pharm, Hampton, VA 23668 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Univ N Carolina Chapel Hill, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. Howard Univ, Coll Med, Dept Biochem, Washington, DC 20059 USA. Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA. Hampton Univ, Sch Pharm, Hampton, VA 23668 USA. RP Davis, JH (reprint author), Hampton Univ, Sch Pharm, 213 Kittrell Hall, Hampton, VA 23668 USA. EM jillian.davis@hamptonu.edu FU NCRR NIH HHS [5G12RR03048] NR 19 TC 1 Z9 1 U1 0 U2 3 PU C M B ASSOC PI POITIERS PA 40 AVENUE RECTEUR PINEAU, BAT MECANIQUE, 86022 POITIERS, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PY 2007 VL 53 IS 3 BP 18 EP 26 DI 10.1170/T792 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 197IZ UT WOS:000248549500004 PM 17531145 ER PT S AU Zhang, PJ Weis, RM Peters, PJ Subramaniam, S AF Zhang, Peijun Weis, Robert M. Peters, Peter J. Subramaniam, Sriram BE McIntosh, JR TI Electron tomography of bacterial chemotaxis receptor assemblies SO CELLULAR ELECTRON MICROSCOPY SE Methods in Cell Biology LA English DT Review; Book Chapter ID ESCHERICHIA-COLI; CELLS; TSR; CHEMORECEPTORS; VISUALIZATION; SUPERFAMILY; MICROSCOPY AB Bacteria sense many of the changes in their local chemical environment by the binding of ligands to a family of chemotaxis receptors, which in turn trigger the activation of a signaling pathway that ultimately regulates the rotation of the flagellar motor. We are using three-dimensional electron microscopy to describe the spatial architectures of chemotaxis receptor assemblies in bacterial cells. Here, we review our recent studies aimed at understanding the organization of the bacterial serine receptor Tsr in intact cells using electron tomography at room and cryogenic temperatures, coupled with imaging of thin vitreous sections obtained from rapidly frozen bacterial cells. We show that starting from tomograms of whole bacteria, the subvolumes corresponding to individual receptor units can be extracted and averaged to determine the three-dimensional structures of receptor assemblies in the physiologically relevant context of an intact cell. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Massachusetts, Dept Chem, Amherst, MA 01003 USA. Netherlands Canc Inst, Div Tumor Biol, Amsterdam, Netherlands. RP Zhang, PJ (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. NR 18 TC 7 Z9 7 U1 0 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-370647-8 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2007 VL 79 BP 373 EP 384 DI 10.1016/S0091-679X(06)79014-8 PG 12 WC Cell Biology SC Cell Biology GA BFV68 UT WOS:000244890300018 PM 17327165 ER PT S AU Leapman, RD Aronova, MA AF Leapman, Richard D. Aronova, Maria A. BE McIntosh, JR TI Localizing specific elements bound to macromolecules by EFTEM SO CELLULAR ELECTRON MICROSCOPY SE Methods in Cell Biology LA English DT Review; Book Chapter ID TRANSMISSION ELECTRON-MICROSCOPY; ENERGY-LOSS SPECTROSCOPY; CRYOELECTRON TOMOGRAPHY; BIOLOGICAL STRUCTURES; CORRELATIVE LIGHT; IMAGING FILTER; VISUALIZATION; MICROANALYSIS; RESOLUTION; SECTIONS AB This chapter contains a description of the basic principles of energy filters and their application for mapping elements in sectioned cells. Quantitative elemental distributions are obtained by subtracting a scaled image acquired at an energy loss just below a core-edge from an image acquired just above the edge. The net signal is then normalized by the zero-loss intensity and divided by the ionization cross section to give the number of atoms per unit area. An expression is also derived for the statistical errors in the measured number of atoms for a particular set of imaging conditions, accelerating voltage, and probe current. Energy filtered imaging of phosphorus, which serves as an intrinsic label for nucleic acid, reveals the distribution of DNA in the cell nucleus. However, it is shown that determining the phosphorus distributions in specimens of variable thickness requires a correction for plural inelastic scattering. An important application of electron spectroscopic imaging is its ability to image specific metal atoms bound to macromolecules. As an example, iron maps are acquired from sections containing the iron storage protein, ferritin. Finally, by acquiring electron spectroscopic images in tilt series and employing established methods of electron tomography, it is possible to reconstruct the distributions of specific elements in three dimensions. C1 Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Leapman, RD (reprint author), Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. FU Intramural NIH HHS NR 46 TC 6 Z9 7 U1 0 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0091-679X BN 978-0-12-370647-8 J9 METHOD CELL BIOL JI Methods Cell Biol. PY 2007 VL 79 BP 593 EP 613 DI 10.1016/S0091-679X(06)79024-0 PG 21 WC Cell Biology SC Cell Biology GA BFV68 UT WOS:000244890300029 PM 17327176 ER PT J AU Lustig, A Weeraratna, AT Wood, WW Teichberg, D Bertak, D Carter, A Poosala, S Firman, J Becker, KG Zonderman, AB Longo, DL Taub, DD AF Lustig, Ana Weeraratna, Ashani T. Wood, William W., III Teichberg, Diane Bertak, Dorothy Carter, Arnell Poosala, Suresh Firman, Jeffrey Becker, Kevin G. Zonderman, Alan B. Longo, Dan L. Taub, Dennis D. TI Transcriptome analysis of age-, gender- and diet-associated changes in murine thymus SO CELLULAR IMMUNOLOGY LA English DT Article DE thymus; involution; aging; microarray; AGEMAP; thymocytes; caloric restriction ID SITE-MEDIATED TRANSLATION; T-CELL REGENERATION; CALORIC RESTRICTION; GLUCOCORTICOID-RECEPTOR; GENE-EXPRESSION; THYMOCYTE DEVELOPMENT; MOLECULAR-MECHANISMS; CYTOKINE PRODUCTION; PROTEIN-SYNTHESIS; OXIDATIVE STRESS AB The loss of thymic function with age may be due to diminished numbers of T-cell progenitors and the loss of critical mediators within the thymic microenvironment. To assess the molecular changes associated with this loss, we examined transcriptomes of progressively aging mouse thymi, of different sexes and on caloric-restricted (CR) vs. ad libitum (AL) diets. Genes involved in various biological and molecular processes including transcriptional regulators, stress response, inflammation and immune function significantly changed during thymic aging. These differences depended on variables such as sex and diet. Interestingly, many changes associated with thymic aging are either muted or almost completely reversed in mice on caloric-restricted diets. These studies provide valuable insight into the molecular mechanisms associated with thymic aging and emphasize the need to account for biological variables such as sex and diet when elucidating the genomic correlates that influence the molecular pathways responsible for thymic involution. Published by Elsevier Inc. C1 NIA, Intramural Res Program, Immunol Lab, NIH, Baltimore, MD 21224 USA. NIA, Intramural Res Program, Res Resources Branch, NIH, Baltimore, MD 21224 USA. RP Taub, DD (reprint author), NIA, Intramural Res Program, Immunol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM taubd@grc.nia.nih.gov OI Becker, Kevin/0000-0002-6794-6656; Zonderman, Alan B/0000-0002-6523-4778 FU Intramural NIH HHS [Z01 AG000766-07] NR 83 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JAN PY 2007 VL 245 IS 1 BP 42 EP 61 DI 10.1016/j.cellimm.2007.03.008 PG 20 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 176WN UT WOS:000247115700006 PM 17499630 ER PT J AU Xiao, Q Li, L Xie, YB Tan, N Wang, CQ Xu, JY Xia, KY Gardner, K Li, QQ AF Xiao, Qiang Li, Lei Xie, Yubo Tan, Ning Wang, Changqing Xu, Junyi Xia, Keyi Gardner, Kevin Li, Qingdi Q. TI Transcription factor E2F-1 is upregulated in human gastric cancer tissues and its overexpression suppresses gastric tumor cell proliferation SO CELLULAR ONCOLOGY LA English DT Article DE E2F-1; mutation; gastric cancer; human tissues; MKN-45 cells; cell cycle; cell proliferation; cell growth; cell survival ID NF-KAPPA-B; S-PHASE; CARCINOMA-CELLS; E2F-1-INDUCED APOPTOSIS; PROGNOSTIC-SIGNIFICANCE; DEREGULATED EXPRESSION; ADVERSE PROGNOSIS; RB/E2F PATHWAY; CYCLIN D1; C-MYC AB The E2F family members play a critical role in cell cycle regulation and other biological processes in the cell. To better understand the involvement of E2F-1 in the development and progression of gastric tumors, we investigated the mutation and expression of E2F-1 in human gastric cancer tissues and the effect of E2F-1 overexpression on the proliferation of gastric carcinoma cells. In this study, 80 pairs of gastric cancer specimens and paratumor tissues from different patients and 40 stomach mucosa specimens from healthy individuals were examined. PCR-SSCP analysis demonstrated that mutations were not detected in an), of the gastric cancer and normal tissue specimens. In addition, the results of an immunohistochemistry assay revealed higher expression rates of E2F-1 (P < 0.01) in gastric cancer tissues (72.5%) than in paratumor tissues (30.0%) of the same individuals and stomach mucosa from healthy individuals (22.5%). However, no correlation was observed between the E2F-1 levels and patients' clinical features, such as sex, age, histological types, lymph node metastasis, and clinical stages (P > 0.05). Finally, the influence of E2F-1 overexpression on the growth of human gastric carcinoma MKN-45 cells in vitro was assessed by measuring colony formation, cell survival, and cell cycle progression. Our data clearly showed that cell growth and proliferation were significantly inhibited in MKN-45 tumor cells transfected with the expression vector encoding E2F-1 in comparison with nontransfected cells or cells transfected with empty vector. These findings suggest that E2F-1, a stable and conservative gene during the oncogenesis and progression of stomach cancers, may potentially serve as a biomarker for clinical diagnosis of gastric carcinomas and as a target for the development of novel therapeutic interventions to treat this disease. C1 NIH, NCI, Lab Receptor Biol & Gene Express, Bethesda, MD 20892 USA. Guangxi Med Univ, First Hosp, Dept Surg, Nanning 530021, Peoples R China. Guangxi Med Univ, First Hosp, Dept Anesthesiol, Nanning, Peoples R China. RP Li, QQ (reprint author), NIH, NCI, Lab Receptor Biol & Gene Express, Bldg 41,Room D305, Bethesda, MD 20892 USA. EM liquenti@mail.nih.gov NR 65 TC 13 Z9 26 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 2211-3428 J9 CELL ONCOL JI Cell. Oncol. PY 2007 VL 29 IS 4 BP 335 EP 349 PG 15 WC Oncology; Cell Biology; Pathology SC Oncology; Cell Biology; Pathology GA 206SU UT WOS:000249204000007 PM 17641417 ER PT J AU Zmuda-Trzebiatowska, E Manganiello, V Degerman, E AF Zmuda-Trzebiatowska, Emilia Manganiello, Vincent Degerman, Eva TI Novel mechanisms of the regulation of Protein kinase B in adipocytes; implications for Protein kinase A, Epac, Phosphodiesterases 3 and 4 SO CELLULAR SIGNALLING LA English DT Article DE insulin; PI3K; phosphodiesterase inhibitor; cAMP; adipocyte; lipogenesis; ACC ID CYCLIC-NUCLEOTIDE PHOSPHODIESTERASE; INSULIN-INDUCED PHOSPHORYLATION; FAT-CELLS; ADENOSINE MONOPHOSPHATE; ADIPOSE-TISSUE; RAT ADIPOCYTES; GLUCOSE-UPTAKE; CROSS-TALK; CAMP; ACTIVATION AB Crosstalk between insulin and cAMP signalling pathways has a great impact on adipocyte metabolism. Whilst Protein kinase B (PKB) is a pivotal mediator of insulin action, in some cells regulation of PKB by cAMP has also been demonstrated. Here we provide evidence that, in a phosphatidyl inositol 3-kinase dependent manner, beta 3-adrenergic stimulation (using CL316243) in adipocytes induces PKB phosphorylation in the absence of insulin and also potentiates insulin-induced phosphorylation of PKB. Interestingly, insulin- and CL316243-induced PKB phosphorylation was found to be inhibited by pools of cAMP controlled by PDE3B and PDE4 (mainly in the context of insulin), whereas a cAMP pool controlling protein kinase A appeared to mediate stimulation of PKB phosphorylation (mainly in the context of CL316243). Furthermore, an Epac (exchange protein directly activated by cAMP) agonist (8-pCPT-2'-O-Me-cAMP) mimicked the effect of the PDE inhibitors, giving evidence that Epac has an inhibitory effect on PKB phosphorylation in adipocytes. Further, we put the results obtained at the level of PKB in the context of possible downstream signalling components in the regulation of adipocyte metabolism. Thus, we found that overexpression of PKB induced lipogenesis in a PDE3B-dependent manner. Furthermore, overexpression or inhibition of PDE3B was associated with reduced or increased phosphorylation of the key lipogenic enzyme acetyl-CoA carboxylase (ACC), respectively. These PDE3B-dependent effects on ACC correlated with changes in lipogenesis. The Epac agonist, 8-pCPT-2'-O-Me-cAMP, mimicked the effect of PDE3B inhibition on ACC phosphorylation and lipogenesis. (c) 2006 Elsevier Inc. All rights reserved. C1 Biomed Ctr, Dept Expt Med Sci, S-22184 Lund, Sweden. NHLB, Pulm Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Zmuda-Trzebiatowska, E (reprint author), Biomed Ctr, Dept Expt Med Sci, C11, S-22184 Lund, Sweden. EM emilia.zmuda-trzebiatowska@med.lu.se NR 39 TC 24 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0898-6568 J9 CELL SIGNAL JI Cell. Signal. PD JAN PY 2007 VL 19 IS 1 BP 81 EP 86 DI 10.1016/j.cellsig.2006.05.024 PG 6 WC Cell Biology SC Cell Biology GA 128AS UT WOS:000243628600009 PM 16839743 ER PT J AU Ledberg, A Bressler, SL Ding, MZ Coppola, R Nakamura, R AF Ledberg, Anders Bressler, Steven L. Ding, Mingzhou Coppola, Richard Nakamura, Richard TI Large-scale visuomotor integration in the cerebral cortex SO CEREBRAL CORTEX LA English DT Review DE event-related potentials; local field potentials; prefrontal cortex; timing; visual pathways ID PRIMATE PREFRONTAL CORTEX; FRONTAL EYE FIELD; VISUAL RESPONSE LATENCIES; SUPERIOR TEMPORAL SULCUS; PARABELT AUDITORY-CORTEX; REACTION-TIME; EVOKED-POTENTIALS; MACAQUE MONKEYS; AWAKE MACAQUE; FLASH VEP AB Efficient visuomotor behavior depends on integrated processing by the visual and motor systems of the cerebral cortex. Yet, many previous cortical neurophysiology studies have examined the visual and motor modalities in isolation, largely ignoring questions of large-scale cross-modal integration. To address this issue, we analyzed event-related local field potentials simultaneously recorded from multiple visual, motor, and executive cortical sites in monkeys performing a visuomotor pattern discrimination task. The timing and cortical location of four aspects of event-related activities were examined: stimulus-evoked activation onset, stimulus-specific processing, stimulus category-specific processing, and response-specific processing. Activations appeared earliest in striate cortex and rapidly thereafter in other visual areas. Stimulus-specific processing began early in most visual cortical areas, some at activation onset. Early onset latencies were also observed in motor, premotor, and prefrontal areas, some as early as in striate cortex, but these early-activating frontal sites did not show early stimulus-specific processing. Response-specific processing began around 150 ms poststimulus in widespread cortical areas, suggesting that perceptual decision formation and response selection arose through concurrent processes of visual, motor, and executive areas. The occurrence of stimulus-specific and stimulus category-specific differences after the onset of response-specific processing suggests that sensory and motor stages of visuomotor processing overlapped in time. C1 Florida Atlantic Univ, Ctr Complex Syst & Brain Sci, Boca Raton, FL 33431 USA. Univ Florida, Dept Biomed Engn, Gainesville, FL 32611 USA. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. Univ Pompeu Fabra, Dept Tecnol, Barcelona 08003, Spain. RP Bressler, SL (reprint author), Florida Atlantic Univ, Ctr Complex Syst & Brain Sci, 777 Glades Rd, Boca Raton, FL 33431 USA. EM bressler@fau.edu OI Ledberg, Anders/0000-0003-3827-8721 FU NIMH NIH HHS [MH42900, MH64204, MH070498] NR 111 TC 44 Z9 44 U1 2 U2 9 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2007 VL 17 IS 1 BP 44 EP 62 DI 10.1093/cercor/bhj123 PG 19 WC Neurosciences SC Neurosciences & Neurology GA 117TP UT WOS:000242896500006 PM 16452643 ER PT J AU Stam, CJ Jones, BF Nolte, G Breakspear, M Scheltens, P AF Stam, C. J. Jones, B. F. Nolte, G. Breakspear, M. Scheltens, Ph. TI Small-world networks and functional connectivity in Alzheimer's disease SO CEREBRAL CORTEX LA English DT Article DE Alzheimer's disease; complexity; EEG; small-world network; synchronization ID MILD COGNITIVE IMPAIRMENT; NEURAL COMPLEXITY MEASURE; GENERALIZED SYNCHRONIZATION; EEG SYNCHRONIZATION; CEREBRAL-CORTEX; BRAIN NETWORKS; LIKELIHOOD; TASK; ORGANIZATION; INFORMATION AB We investigated whether functional brain networks are abnormally organized in Alzheimer's disease (AD). To this end, graph theoretical analysis was applied to matrices of functional connectivity of beta band-filtered electroencephalography (EEG) channels, in 15 Alzheimer patients and 13 control subjects. Correlations between all pairwise combinations of EEG channels were determined with the synchronization likelihood. The resulting synchronization matrices were converted to graphs by applying a threshold, and cluster coefficients and path lengths were computed as a function of threshold or as a function of degree K. For a wide range of thresholds, the characteristic path length L was significantly longer in the Alzheimer patients, whereas the cluster coefficient C showed no significant changes. This pattern was still present when L and C were computed as a function of K. A longer path length with a relatively preserved cluster coefficient suggests a loss of complexity and a less optimal organization. The present study provides further support for the presence of "small-world" features in functional brain networks and demonstrates that AD is characterized by a loss of small-world network characteristics. Graph theoretical analysis may be a useful approach to study the complexity of patterns of interrelations between EEG channels. C1 Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Alzheimer Ctr, NL-1007 MB Amsterdam, Netherlands. Vrije Univ Amsterdam, Med Ctr, Dept Clin Neurophysiol, NL-1007 MB Amsterdam, Netherlands. NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Fraunhofer First, D-12489 Berlin, Germany. Westmead Hosp, Brain Dynam Ctr, Westmead, NSW 2145, Australia. Univ Sydney, Sch Phys, Sydney, NSW 2006, Australia. RP Jones, BF (reprint author), Vrije Univ Amsterdam, Med Ctr, Dept Neurol, Alzheimer Ctr, POB 7057, NL-1007 MB Amsterdam, Netherlands. EM b.jones@vumc.nl RI Breakspear, Michael/M-5859-2014 NR 45 TC 301 Z9 308 U1 12 U2 66 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2007 VL 17 IS 1 BP 92 EP 99 DI 10.1093/cercor/bhj127 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 117TP UT WOS:000242896500010 ER PT J AU Saksida, LM Bussey, TJ Buckmaster, CA Murray, EA AF Saksida, Lisa M. Bussey, Timothy J. Buckmaster, Cindy A. Murray, Elisabeth A. TI Impairment and facilitation of transverse patterning after lesions of the perirhinal cortex and hippocampus, respectively SO CEREBRAL CORTEX LA English DT Article DE configural learning; discrimination learning; inferotemporal cortex; object recognition; rhesus monkey; ventral visual stream ID CONFIGURAL ASSOCIATION THEORY; VISUAL RECOGNITION MEMORY; RHESUS-MONKEYS; TEMPORAL-LOBE; NEUROTOXIC LESIONS; FORNIX TRANSECTION; POSTRHINAL CORTEX; LOCATION MEMORY; OBJECT; DAMAGE AB We have recently suggested that certain effects of perirhinal cortex removals in monkeys can be attributed to the lesion compromising complex configural representations of visual stimuli. On this view, monkeys with perirhinal cortex lesions will be impaired on acquisition of discrimination problems that possess high "feature ambiguity," that is, those in which many of the same features belong to both rewarded and unrewarded stimuli. A subclass of feature-ambiguous problems includes "configural" discrimination problems in which all features are ambiguous. In the present study, we tested control monkeys and monkeys with bilateral lesions of perirhinal cortex on a configural discrimination problem, the transverse-patterning task (i.e., A+ vs. B-, B+ vs. C-, C+ vs. A-), using complex 2-dimensional visual stimuli. In addition, we investigated the effects of lesions to another structure that has been implicated in configural learning, the hippocampus. Monkeys with perirhinal cortex lesions were impaired, whereas monkeys with selective hippocampal lesions were facilitated, on acquisition of the transverse-patterning task. These data do not provide support for mass action theories of medial temporal lobe function, which cannot account for the opposing effects of the 2 lesions. These results are, however, compatible with a view that perirhinal cortex, and not the hippocampus, contains complex configural representations of visual stimuli critical to the solution of the transverse-patterning task. C1 Univ Cambridge, Dept Expt Psychol, Cambridge CB2 3EB, England. NIMH, Neuropsychol Lab, Bethesda, MD 20892 USA. RP Saksida, LM (reprint author), Univ Cambridge, Dept Expt Psychol, Downing St, Cambridge CB2 3EB, England. EM lms42@cam.ac.uk RI Saksida, Lisa/M-2753-2016; Bussey, Timothy/M-2758-2016; OI Saksida, Lisa/0000-0002-8416-8171; Bussey, Timothy/0000-0001-7518-4041; Murray, Elisabeth/0000-0003-1450-1642 FU Intramural NIH HHS; Medical Research Council [G0001354] NR 49 TC 46 Z9 47 U1 0 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1047-3211 J9 CEREB CORTEX JI Cereb. Cortex PD JAN PY 2007 VL 17 IS 1 BP 108 EP 115 DI 10.1093/cercor/bhj128 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 117TP UT WOS:000242896500012 PM 16452641 ER PT J AU Masson, MJ Peterson, RA Chung, CJ Graf, ML Carpenter, LD Ambroso, JL Krull, DL Sciarrotta, J Pohl, LR AF Masson, Mary Jane Peterson, Richard A. Chung, Christine J. Graf, Mary L. Carpenter, Leah D. Ambroso, Jeffrey L. Krull, David L. Sciarrotta, Janeice Pohl, Lance R. TI Lymphocyte loss and immunosuppression following acetaminophen-induced hepatotoxicity in mice as a potential mechanism of tolerance SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ACUTE LIVER-FAILURE; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; KUPFFER CELLS; T-CELLS; TOLEROGENIC ROLE; HEPATIC-INJURY; UNITED-STATES; IFN-GAMMA; PARACETAMOL; GLUCOCORTICOIDS AB Current evidence suggests that drug-induced liver disease can be caused by an allergic response (drug-induced allergic hepatitis, DIAH) induced by hepatic drug-protein adducts. The relatively low incidence of these reactions has led us to hypothesize that tolerogenic mechanisms prevent DIAH from occurring in most people. Here, we present evidence for the existence of one of these regulatory pathways. Following a hepatotoxic dose of acetaminophen in C57B1/6 mice, lymphocyte loss that appeared to be due at least in part to apoptosis was noted in the spleen, thymus, and draining lymph nodes of the liver. There was no observable lymphocyte loss in the absence of hepatotoxicity. Acetaminophen-induced liver injury (AILI) also led to a functional suppression of the immune system as determined by the inhibition of a delayed-type hypersensitivity response to dinitrochlorobenzene. Further studies with adrenalectomized mice suggested a role for corticosterone in the depletion of lymphocytes following APAP-induced liver injury. In conclusion, these findings suggest that lymphocyte loss and immunosuppression following AILI may prevent subsequent occurrences of allergic hepatitis and possibly other forms of APAP-induced allergies induced by hepatic drug-protein adducts. Similar regulatory pathways may inhibit other hepatotoxic drugs from causing allergic reactions. C1 NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. GlaxoSmithKline Inc, Safety Assessment, Res Triangle Pk, NC USA. RP Masson, MJ (reprint author), NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH,Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. EM massonm@nhlbi.nih.gov FU Intramural NIH HHS NR 49 TC 14 Z9 15 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2007 VL 20 IS 1 BP 20 EP 26 DI 10.1021/tx060190c PG 7 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 126AC UT WOS:000243483600005 PM 17226923 ER PT J AU Pitt, MA Johnson, DW AF Pitt, Melanie A. Johnson, Darren W. TI Main group supramolecular chemistry SO CHEMICAL SOCIETY REVIEWS LA English DT Review ID STRUCTURAL-CHARACTERIZATION; PI INTERACTIONS; COMPLEXES; MERCURY(II); MACROCYCLES; DESIGN; SUPERMOLECULES; FUNCTIONALITY; ARSENIC(III); PERSPECTIVES AB Metal directed self-assembly has yielded a wide array of two- and three-dimensional structures with fascinating new chemical properties. These structures have typically been prepared utilizing transition metals as directing units, owing to the well-defined coordination preferences these metals exhibit. An area of growing research interest involves the preparation of structures containing main group elements as directing units. This tutorial review surveys the wide range of structure types available through this approach, specifically covering unique structure types accessible from the unusual coordination geometries often exhibited by the elements in Groups 12-17 of the periodic table. This review should be of interest to supramolecular and main group chemists, and researchers in the fields of crystal engineering, host-guest chemistry, and molecular recognition. C1 Univ Oregon, Dept Chem, Inst Mat Sci, Eugene, OR 97403 USA. Oregon Nanosci & Microtechnol Inst, Eugene, OR USA. Indiana Univ, Indianapolis, IN 46204 USA. Univ Oregon, Dept Chem, Eugene, OR 97403 USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Univ Oregon, NIH, Scripps Res Inst, Eugene, OR 97403 USA. RP Johnson, DW (reprint author), Univ Oregon, Dept Chem, Inst Mat Sci, Eugene, OR 97403 USA. EM dwj@uoregon.edu NR 50 TC 105 Z9 106 U1 4 U2 34 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0306-0012 J9 CHEM SOC REV JI Chem. Soc. Rev. PY 2007 VL 36 IS 9 BP 1441 EP 1453 DI 10.1039/b610405n PG 13 WC Chemistry, Multidisciplinary SC Chemistry GA 194OL UT WOS:000248353600005 PM 17660877 ER PT J AU Huestis, MA AF Huestis, Marilyn A. TI Human cannabinoid pharmacokinetics SO CHEMISTRY & BIODIVERSITY LA English DT Review ID CHROMATOGRAPHY-MASS-SPECTROMETRY; METABOLITE 11-NOR-DELTA(9)-TETRAHYDROCANNABINOL-9-CARBOXYLIC ACID; URINARY-EXCRETION PROFILES; SOLID-PHASE EXTRACTION; ORAL FLUID COLLECTION; SINGLE-DOSE KINETICS; DRUG-TESTING DEVICES; GAS-CHROMATOGRAPHY; GC-MS; THC-COOH C1 Natl Inst Drug Abuse, NIH, Intramural Res Program, Baltimore, MD 21146 USA. RP Huestis, MA (reprint author), Natl Inst Drug Abuse, NIH, Intramural Res Program, 500 Nathan Shock Dr, Baltimore, MD 21146 USA. EM mhuestis@intra.nida.nih.gov FU Intramural NIH HHS [Z01 DA000412-10, Z01 DA000413-10, Z01 DA000415-10] NR 189 TC 94 Z9 96 U1 8 U2 33 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1612-1872 J9 CHEM BIODIVERS JI Chem. Biodivers. PY 2007 VL 4 IS 8 BP 1770 EP 1804 DI 10.1002/cbdv.200790152 PG 35 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 208KI UT WOS:000249317800010 PM 17712819 ER PT J AU Mulkidjanian, AY Galperin, MY AF Mulkidjanian, Armen Y. Galperin, Michael Y. TI Physico-chemical and evolutionary constraints for the formation and selection of first biopolymers: Towards the consensus paradigm of the abiogenic origin of life SO CHEMISTRY & BIODIVERSITY LA English DT Review ID RNA WORLD; PREBIOTIC CHEMISTRY; UV-RADIATION; PRIMITIVE EARTH; METABOLISM; EMERGENCE; CATALYSIS; MONTMORILLONITE; ULTRAVIOLET; FORMAMIDE AB During the last two decades, the common school of thought has split into two, so that the problem of the origin of life is tackled in the framework of either the 'replication first' paradigm or the 'metabolism first' scenario. The first paradigm suggests that the life started from the spontaneous emergence of the first, supposedly RNA-based 'replicators' and considers in much detail their further evolution in the so-called 'RNA world'. The alternative hypothesis of 'metabolism first' derives the life from increasingly complex autocatalytic chemical cycles. In this work, we emphasize the role of selection during the prebiological stages of evolution and focus on the constraints that are imposed by physical, chemical, and biological laws. We try to demonstrate that the 'replication first' and 'metabolism first' hypotheses complement, rather than contradict, each other. We suggest that life on Earth has started from a 'metabolism-driven replication'; the suggested scenario might serve as a consensus scheme in the framework of which the molecular details of origin of life can be further elaborated. The key feature of the scenario is the participation of the UV irradiation both as driving and selecting forces during the earlier stages of evolution. C1 Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. Moscow MV Lomonosov State Univ, AN Belozersky Inst Physiochem Biol, Moscow 119992, Russia. Natl Lib Med, Natl Inst Hlth, Natl Ctr Biotechnol Informat, Bethesda, MD 20894 USA. RP Mulkidjanian, AY (reprint author), Univ Osnabruck, Sch Phys, D-49069 Osnabruck, Germany. EM amulkid@uos.de; galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013; Mulkidjanian, Armen/J-8086-2013 OI Galperin, Michael/0000-0002-2265-5572; Mulkidjanian, Armen/0000-0001-5844-3064 FU Intramural NIH HHS NR 66 TC 13 Z9 14 U1 1 U2 10 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1612-1872 J9 CHEM BIODIVERS JI Chem. Biodivers. PY 2007 VL 4 IS 9 BP 2003 EP 2015 DI 10.1002/cbdv.200790167 PG 13 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 216FI UT WOS:000249863500005 PM 17886857 ER PT J AU Earnshaw, W Nakano, M Cardinale, S Noskov, V Larionov, V Masumoto, H AF Earnshaw, William Nakano, Megumi Cardinale, Stefano Noskov, Vladimir Larionov, Vladimir Masumoto, Hiroshi TI Production of a human artificial chromosome with a conditional centromere SO CHROMOSOME RESEARCH LA English DT Meeting Abstract CT 16th International Chromosome Conference (ICC 16) CY AUG 25-29, 2007 CL Amsterdam, NETHERLANDS C1 Univ Edinburgh, Wellcome Trust Ctr Cell Biol, Edinburgh, Midlothian, Scotland. NCI, NIH, Bethesda, MD 20892 USA. Nagoya Univ, Div Biol Sci, Nagoya, Aichi, Japan. RI Cardinale, Stefano/F-4024-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0967-3849 J9 CHROMOSOME RES JI Chromosome Res. PY 2007 VL 15 SU 2 BP 59 EP 60 PG 2 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 204BP UT WOS:000249018100146 ER PT J AU Motzkus, D Lourni, S Cadenas, C Vinson, C Forssmann, WG Maronde, E AF Motzkus, Dirk Lourni, Sabine Cadenas, Christina Vinson, Charles Forssmann, Wolf-Georg Maronde, Erik TI Activation of human period-1 by PKA or clock/BMAL1 is conferred by separate signal transduction pathways SO CHRONOBIOLOGY INTERNATIONAL LA English DT Article DE circadian rhythm; chronobiology; human period-1; signaling pathway; peripheral clock ID MAMMALIAN CIRCADIAN CLOCK; HUMAN PER1 GENE; PROTEIN-KINASE; BINDING PROTEIN; DNA-BINDING; CYCLIC-AMP; IN-VIVO; CAMP; TRANSCRIPTION; EXPRESSION AB Circadian clocks are self-sustained biochemical oscillators that autonomously generate a near-24 h cycle in the absence of external signals. The process of synchronization to the environment involves the transcriptional activation of several genes. Photic input signals from the retina are transduced via the retinohypothalamic tract to the central pacemaker located in the suprachiasmatic nuclei (SCN) of the hypothalamus. It is known that cells of peripheral organs possess similar molecular organizations, but the signal transductional pathways lack direct light entrainment. It has been assumed that the adaptation of peripheral organs to the SCN phase is achieved by the alternate usage of promoter elements. This question has been addressed by characterizing the signal transductional pathways regulating human Period-1 gene expression in human hepatoma cells (HuH-7). Plasmids coding for key modulators of circadian rhythm, hCLOCK, hBMAL1, and hCRY2 were used to analyze the activation of a human period-1 promoter luciferase (hPER1-luc) construct. Beside classical CLOCK/BMAL1 activation, hPER1-luc was also inducible by the overexpression of the catalytic subunit of PKA (C alpha). The cotransfection of dominant negative constructs to c-FOS, CREB, PKA, and C/EBP were used to characterize both regulatory pathways. It was found that hCLOCK/hBMAL1-mediated hPER1 activation was influenced by AP1, but not significantly by other regulators. Conversely, PKA-induced activation of hPER1 was reduced by the inhibition of CREB and the CCAAT-box binding protein C/EBP, but not by AP1. The present findings imply that CLOCK/BMAL1-mediated activation of hPER1 by AP1 and E-Box elements isdistinct from peripheral transcriptional modulation via cAMP-induced CREB and C/EBP. C1 Univ Frankfurt, Inst Anat 3, D-60590 Frankfurt, Germany. IPF Phamaceut GmbH, Hannover, Germany. Max Planck Inst Expt Endocrinol, Hannover, Germany. Natl Canc Inst, NIH, Lab Metab, Bethesda, MD USA. RP Maronde, E (reprint author), Univ Frankfurt, Inst Anat 3, Theodor Stern Kai 7, D-60590 Frankfurt, Germany. EM e.maronde@em.uni-frankfurt.de OI Maronde, Erik/0000-0002-5574-6323 NR 42 TC 12 Z9 12 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0742-0528 J9 CHRONOBIOL INT JI Chronobiol. Int. PY 2007 VL 24 IS 5 BP 783 EP 792 DI 10.1080/07420520701672481 PG 10 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 226JC UT WOS:000250584300001 PM 17994337 ER PT J AU Csako, G AF Csako, Gyorgy TI Analysis of the most highly cited articles from the 50-year history of CCA SO CLINICA CHIMICA ACTA LA English DT Review DE citation analysis; current contents; geographic distribution; impact factor; journalology; science citation index ID CITATION INDEXES; IMPACT; SCIENCE AB Background: The 50th anniversary of CCA in 2006 prompted analysis of the most highly cited articles from the Journal's history. Methods: Lists of most highly cited CCA articles were obtained from Current Contents (1974, 1991) and CCA (2006); all based on the ISI/Thomson Scientific database. PubMed search identified country of origin. Results: Distribution of the most highly cited CCA articles was skewed towards those with high total citations. From the beginning, these articles originated from a diverse group of countries. This diversity increased with time to include countries from 4 continents. The most highly cited articles emerged at least 8-16 years following their publication. During the first 35 years of the Journal, there was a significant positive correlation between the total number of citations and the publication date of cited articles. Initially, virtually all most highly cited articles were methods papers, whereas during the past 25 years less than half of them reported methods; clinical research papers and reviews making up the rest. Conclusions: Results of this analysis may help in editorial policy-making and marketing of the Journal and in assessing the impact of individual countries on the field, and may guide authors' decision in submitting articles to the Journal. (c) 2006 Elsevier B.V. All rights reserved. C1 NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. RP Csako, G (reprint author), NIH, Ctr Clin, Dept Lab Med, Bldg 10,Rm 2C-407, Bethesda, MD 20892 USA. EM gcsako@nih.gov FU Intramural NIH HHS NR 15 TC 4 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD JAN PY 2007 VL 375 IS 1-2 BP 43 EP 48 DI 10.1016/j.cca.2006.07.020 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 112IQ UT WOS:000242519600005 PM 16962570 ER PT J AU Brent, L Cohen, IR Doherty, PC Feldmann, M Matzinger, P Holgate, ST Lachmann, P Mitchison, NA Nossal, G Rose, NR Zinkernagel, R AF Brent, L. Cohen, I. R. Doherty, P. C. Feldmann, M. Matzinger, P. Holgate, S. T. Lachmann, P. Mitchison, N. A. Nossal, G. Rose, N. R. Zinkernagel, R. CA Ghost Lab TI Crystal-ball gazing - the future of immunological research viewed from the cutting edge SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Review ID ATOPIC-DERMATITIS; BARRIER FUNCTION; ASTHMA; FILAGGRIN; GENE; PREDISPOSE; RHINOVIRUS; INFECTION; CHILDREN; CELLS C1 Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel. Univ Melbourne, Dept Microbiol & Immunol, Melbourne, Vic, Australia. Univ London Imperial Coll Sci Technol & Med, Kennedy Inst, Div Rheumatol, London, England. NIAID, LCMI, NIH, Bethesda, MD 20892 USA. Univ Southampton, Sch Med, Southampton, Hants, England. Univ Cambridge, Cambridge, England. UCL, Inst Ophthalmol, London, England. Univ Melbourne, Dept Pathol, Melbourne, Vic, Australia. Johns Hopkins Ctr Autoimmune Dis Res, Johns Hopkins Sch Med, Baltimore, MD USA. Univ Zurich Hosp, Inst Expt Immunol, CH-8091 Zurich, Switzerland. RP Brent, L (reprint author), 30 Hugo Rd, London N19 5EU, England. EM irun.cohen@weizmann.ac.il; peter.doherty@stjude.org; m.feldmann@imperial.ac.uk; sth@soton.ac.uk; pjl1000@cam.ac.uk; n.mitchison@ucl.ac.uk; gnossal@bigpond.net.au; nrrose@jhsph.edu; rolf.zinkernagel@usz.ch RI Cohen, Irun/B-3542-2009; Doherty, Peter Charles/C-4185-2013 OI Doherty, Peter Charles/0000-0002-5028-3489 FU Medical Research Council [G0800766] NR 22 TC 8 Z9 8 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JAN PY 2007 VL 147 IS 1 BP 1 EP 10 DI 10.1111/j.1365-2249.2006.03234.x PG 10 WC Immunology SC Immunology GA 122KT UT WOS:000243226600001 PM 17177957 ER PT J AU Lee, MT Hooper, LC Kump, L Hayashi, K Nussenblatt, R Hooks, JJ Detrick, B AF Lee, M. T. Hooper, L. C. Kump, L. Hayashi, K. Nussenblatt, R. Hooks, J. J. Detrick, B. TI Interferon-beta and adhesion molecules (E-selectin and s-intracellular adhesion motecule-1) are detected in sera from patients with retinal vasculitis and are induced in retinal vascular endothelial cells by Toll-like receptor 3 signalling SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE Behcet's disease; E-selectin; idiopathic uveitis; IFN-beta; retinal vasculitis; sICAM-1 ID PIGMENT EPITHELIAL-CELLS; HUMAN RECOMBINANT INTERFERON-ALPHA-2A; REMITTING MULTIPLE-SCLEROSIS; DOUBLE-STRANDED-RNA; OF-THE-LITERATURE; BEHCETS-DISEASE; INNATE IMMUNITY; RECOGNITION; ACTIVATION; EXPRESSION AB Retinal vasculitis is a major component of ocular inflammation that plays a role in retinal tissue damage in patients with idiopathic uveitis and Behcet's disease. Here we show that type 1 interferons (IFN alpha/beta) were not detected in sera from normal individuals but were identified in up to 46% of the sera from retinal vasculitis patients. The predominant form of IFN observed was IFN-beta, which was detected in 39% of Behcet's disease patients and 47% of idiopathic uveitis patients. Seven patients whose sera contained IFN-beta were monitored prospectively. IFN-beta was shown to be present for 6-12 months in all seven of the sera samples tested. Furthermore, the adhesion molecule profile identified in this study was strikingly different when Behcet's and uveitis patient sera were compared to sera from normal controls. Sera from Behcet's disease patients contained significantly elevated levels of the soluble adhesion molecules, sE-selectin and s-intracellular adhesion molecule-1 (sICAM-1), whereas sera from patients with idiopathic uveitis contained significantly increased sE-selectin. In vitro studies evaluating the cell source of these cytokines revealed that polyriboinosinic polyribocytidylic acid (poly I:C) activated retinal vascular endothelial cells produce sE-selectin, sICAM-1 and IFN-beta. Production of these molecules was inhibited by pretreatment with anti-Toll-like receptor 3 (TLR-3) antibody. In conclusion, IFN-beta, sE-selectin and sICAM-1 are elevated in patients with retinal vasculitis and are induced in retinal vascular endothelial cells in vitro by activating the innate immune system through TLR-3. Further analysis of innate immune signalling may prove to be a novel target for future studies on pathogenic mechanisms and therapeutic approaches in retinal vasculitis. C1 Johns Hopkins Univ, SOM, Dept Pathol, Sch Med, Baltimore, MD 21287 USA. NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Detrick, B (reprint author), Johns Hopkins Univ, SOM, Dept Pathol, Sch Med, Meyer B125A,600 N Wolfe St, Baltimore, MD 21287 USA. EM bdetrick@jhmi.edu FU Intramural NIH HHS NR 34 TC 21 Z9 22 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD JAN PY 2007 VL 147 IS 1 BP 71 EP 80 DI 10.1111/j.1365-2249.2006.03253.x PG 10 WC Immunology SC Immunology GA 122KT UT WOS:000243226600009 PM 17177965 ER PT J AU Suh, KS Crutchley, JM Koochek, A Ryscavage, A Bhat, K Tanaka, T Oshima, A Fitzgerald, P Yuspa, SH AF Suh, Kwang S. Crutchley, John M. Koochek, Arash Ryscavage, Andrew Bhat, Kiran Tanaka, Takemi Oshima, Akira Fitzgerald, Peter Yuspa, Stuart H. TI Reciprocal modifications of CLIC4 in tumor epithelium and stroma mark malignant progression of multiple human cancers SO CLINICAL CANCER RESEARCH LA English DT Article ID CHLORIDE CHANNEL PROTEIN; ALTERED SUBCELLULAR-LOCALIZATION; HUMAN BREAST-CANCER; NUCLEAR-LOCALIZATION; ION CHANNEL; PROTEOMIC ANALYSIS; COLORECTAL-CANCER; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; BETA-CATENIN AB Purpose: CLIC4, a member of a family of intracellular chloride channels, is regulated by p53, c-Myc, and tumor necrosis factor-alpha. Regulation by factors involved in cancer pathogenesis, together with the previously shown proapoptotic activity of CLIC4, suggests that the protein may have a tumor suppressor function. To address this possibility, we characterized the expression profile, subcellular localization, and gene integrity of CLIC4 in human cancers and determined the functional consequences of CLIC4 expression in tumor epithelium and stromal cells. Experimental Design: CLIC4 expression profiles were analyzed by genomics, proteomics, bioinformatics, and tissue microarrays. CLIC4 expression, as a consequence of crosstalk between stroma and epithelium, was tested in vitro by coculture of breast epithelial tumor cells and normal fibroblasts, and the functional consequences of CLIC4 expression was tested in vivo in xenografts of human breast tumor cell lines reconstituted with CLIC4 or mixed with fibroblasts that overexpress CLIC4 transgenically. Results: In cDNA arrays of matched human normal and tumor tissues, CLIC4 expression was reduced in renal, ovarian, and breast cancers. However, CLIC4 protein levels were variable in tumor lysate arrays. Transcript sequences of CLIC4 from the human expressed sequence tag database and manual sequencing of cDNA from 60 human cancer cell lines (NCI60) failed to reveal deletion or mutations in the CLIC4 gene. On matched tissue arrays, CLIC4 was predominantly nuclear in normal human epithelial tissues but not cancers. With advancing malignant progression, CLIC4 staining became undetectable in tumor cells, but expression increased in stromal cells coincident with up-regulation of alpha-smooth muscle actin, suggesting that CLIC4 is up-regulated in myofibroblasts. Coculture of cancer cells and fibroblasts induced the expression of both CLIC4 and a-smooth muscle actin in fibroblasts adjacent to tumor nests. Introduction of CLIC4 or nuclear targeted CLIC4 via adenovirus into human breast cancer xenografts inhibited tumor growth, whereas overexpression of CLIC4 in stromal cells of xenografts enhanced tumor growth. Conclusion: Loss of CLIC4 in tumor cells and gain in tumor stroma is common to many human cancers and marks malignant progression. Up-regulation of CLIC4 in tumor stroma is coincident with myofibroblast conversion, generally a poor prognostic indicator. Reactivation and restoration of CLIC4 in tumor cells or the converse in tumor stromal cells could provide a novel approach to inhibit tumor growth. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Lab Cell Regulat & Carcinogenesis, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Genome Anal Unit, Ctr Canc Res, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, Ctr Canc Res, Bldg 37, Bethesda, MD 20892 USA. EM yuspas@mail.nih.gov FU Intramural NIH HHS NR 52 TC 42 Z9 45 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2007 VL 13 IS 1 BP 121 EP 131 DI 10.1158/1078-0432.CCR-06-1562 PG 11 WC Oncology SC Oncology GA 123UF UT WOS:000243320800016 PM 17200346 ER PT J AU Crawford, NP Qain, XL Ziogas, A Boersma, B Lukes, L Walker, R Anton-Culver, H Ambs, S Lowy, D Hunter, K AF Crawford, Nigel P. Qain, Xiaolan Ziogas, Argyrios Boersma, Brenda Lukes, Luanne Walker, Renard Anton-Culver, Hoda Ambs, Stefan Lowy, Doug Hunter, Kent TI Identification and characterization of Anakin, a novel metastasis efficiency modifying gene, through genometic analysis SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA 92697 USA. NCI, NIH, Human Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RI Boersma, Brenda/A-9270-2009 OI Boersma, Brenda/0000-0002-8992-2735 NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2007 VL 24 IS 4 BP 225 EP 225 PG 1 WC Oncology SC Oncology GA 199HQ UT WOS:000248687200025 ER PT J AU Hunter, KW Crawford, N Lukes, L Walker, R AF Hunter, Kent W. Crawford, Nigel Lukes, Luanne Walker, Renard TI The intersection of gene expression and constitutional susceptibility to metastasis SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 NCI, Lab Populat Genet, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2007 VL 24 IS 4 BP 229 EP 230 PG 2 WC Oncology SC Oncology GA 199HQ UT WOS:000248687200033 ER PT J AU Kubo, H AF Kubo, Hajime TI Lymphangiogenesis and cancer SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 NIH, NCI, Lab Populat Genet, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2007 VL 24 IS 4 BP 229 EP 229 PG 1 WC Oncology SC Oncology GA 199HQ UT WOS:000248687200032 ER PT J AU Raz, A AF Raz, Avraham TI On the role of galectin-3 in tumor metastasis from the bench to the clinic and back SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract ID ANTITUMOR IMMUNITY; ANTIGENS C1 NIA, NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 EI 1573-7276 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2007 VL 24 IS 4 BP 239 EP 239 PG 1 WC Oncology SC Oncology GA 199HQ UT WOS:000248687200052 ER PT J AU Steeg, PS Lee, JH Elkahloun, A Boissan, M Dumont, S Maga, JK Christensen, JG Arnaud-Dabernat, S Palmieri, D Daniel, JY Lacombe, ML Meltzer, PS Horak, CE AF Steeg, Patricia S. Lee, Jong Heun Elkahloun, Abdel Boissan, Mathieu Dumont, Sylvie Maga, Jara K. Christensen, James G. Arnaud-Dabernat, Sandrine Palmieri, Diane Daniel, Jean-Yves Lacombe, Marie-Lise Meltzer, Paul S. Horak, Christine E. TI Nm23-H1 suppresses tumor cell motility through the downregutation of the LPA receptor EDG2 and the hepatocyte growth factor receptor MET SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. INSERM, F-75654 Paris 13, France. Univ Victor Segalen, Bordeaux, France. RI Palmieri, Diane/B-4258-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2007 VL 24 IS 4 BP 244 EP 245 PG 2 WC Oncology SC Oncology GA 199HQ UT WOS:000248687200062 ER PT J AU Green, JE Costes, SV Cho, EH Kamaraju, AK Hoenorhoff, M Lockett, S Kleinman, H Chambers, AF Barkan, D AF Green, Jeffrey E. Costes, Sylvain V. Cho, Edward H. Kamaraju, Anil K. Hoenorhoff, Mark Lockett, Stephen Kleinman, Hynda Chambers, Ann F. Barkan, Dalit TI Extracellular matrix: a gatekeeper in the transition from dormancy to metastasis SO CLINICAL & EXPERIMENTAL METASTASIS LA English DT Meeting Abstract C1 NCI, Lab Cell Regulat & Carcinogenesis, NIH, Bethesda, MD USA. Lawrence Berkeley Natl Lab, Canc Biol Dept, Berkeley, CA USA. NCI, SAIC, Image Anal Lab, Frederick, MD 21701 USA. Natl Inst Dental & Craniofacial Res, Craniofacial Dev Biol & Regenerat BRanch, NIH, Bethesda, MD USA. London Reg Canc Program, London, ON, Canada. RI Costes, Sylvain/D-2522-2013; Chambers, Ann/L-6285-2015; Cho, Edward/B-3727-2012 OI Costes, Sylvain/0000-0002-8542-2389; Chambers, Ann/0000-0002-9509-5123; Cho, Edward/0000-0002-0278-334X NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0262-0898 J9 CLIN EXP METASTAS JI Clin. Exp. Metastasis PY 2007 VL 24 IS 4 BP 264 EP 265 PG 2 WC Oncology SC Oncology GA 199HQ UT WOS:000248687200102 ER PT J AU Adriani, M Aoki, J Horai, R Kon, A Thornton, AM Kirby, M Anderson, SM Siegel, RM Schwartzberg, PL Condotti, F AF Adriani, Marsilio Aoki, Joseph Horai, Reiko Kon, Akihiro Thornton, Angela M. Kirby, Martha Anderson, Stacie M. Siegel, Richard M. Schwartzberg, Pamela L. Condotti, Fabio TI Impaired in vitro regulatory T cell function associated with wiskott-aldrich syndrome SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 NHGRI, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NIAMS, NIH, Bethesda, MD USA. RI Adriani, Marsilio/F-2553-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S14 EP S14 DI 10.1016/j.clim.2007.03.210 PG 1 WC Immunology SC Immunology GA 177EU UT WOS:000247137200033 ER PT J AU Brodsky, NN Brown, MR Holland, SM Uzel, G AF Brodsky, Nina N. Brown, Margaret R. Holland, Steven M. Uzel, Gulbu TI Peripheral blood flow cytometric evaluation of a large cohort of hyper immunoglobulin E syndrome patients SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 NIH, NIAID, LCID, Bethesda, MD 20892 USA. NIH, CC, DLM, Bethesda, MD 20892 USA. NIH, NIAID, LCID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S67 EP S68 DI 10.1016/j.clim.2007.03.370 PG 2 WC Immunology SC Immunology GA 177EU UT WOS:000247137200176 ER PT J AU Dissanayake, S Rosenthal, D Hewitt, K Wade, M Yang, S Leotlela, P Taub, D Riker, A Nickoloff, B Weeraratna, A AF Dissanayake, Samudra Rosenthal, Devin Hewitt, Kyle Wade, Michael Yang, Sherry Leotlela, Poloko Taub, Dennis Riker, Adam Nickoloff, Brian Weeraratna, Ashani TI Wnt5a regulates melanoma antigen recognized by T cells 1 (MART-1), a predominant antigen in melanoma cells SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 Natl Inst Aging, NIH, Baltimore, MD USA. Natl Inst Aging, NIH, Immunol Lab, Baltimore, MD USA. Univ S Alabama, Mitchell Canc Inst, N Mobile, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S113 EP S114 DI 10.1016/j.clim.2007.03.502 PG 2 WC Immunology SC Immunology GA 177EU UT WOS:000247137200296 ER PT J AU Jaimes, M Darden, J D'Souza, P Maecker, H AF Jaimes, Maria Darden, Janice D'Souza, Patricia Maecker, Holden TI Standardization and quality assurance of cytokine flow cytometry assays SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 BD Biosci, San Jose, CA USA. NIAID, DAIDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S58 EP S58 DI 10.1016/j.clim.2007.03.345 PG 1 WC Immunology SC Immunology GA 177EU UT WOS:000247137200151 ER PT J AU Jain, A Nelson, D Kovacs, J Liu, S Fleisher, T Fanslow, W Ochs, H Strober, W AF Jain, Ashish Nelson, David Kovacs, Jospeh Liu, Shuying Fleisher, Thomas Fanslow, William Ochs, Hans Strober, Warren TI Immune reconstitution in x-linked hyper-IgM syndrome with recombinant CD40 ligand SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 NIH, NIAID, Lab Host Def, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Clin Ctr, Bethesda, MD USA. NIAID, Bethesda, MD 20892 USA. Amgen Seattle, Seattle, WA USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S129 EP S129 DI 10.1016/j.clim.2007.03.006 PG 1 WC Immunology SC Immunology GA 177EU UT WOS:000247137200335 ER PT J AU Jesus, A Oliveira, J Aksentijevich, I Silva, C Duarte, AJS AF Jesus, Adriana Oliveira, Joao Aksentijevich, Ivona Silva, Clovis Duarte, Alberto J. S. TI Cryopyrin-associated periodic syndromes (CAPS): Report of two Brazilian cases, including a rare non-exon 3 CIAS1 mutation SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 Univ Sao Paulo, Dept Pediat, Sao Paulo, Brazil. Univ Sao Paulo, Mol Immunol & Genet Sect, Lab Med Invest, Sao Paulo, Brazil. NIAMS, NIH, GGB, Bethesda, MD USA. Dept Pediat, Head Pediat Rheuamatol Unit, Sao Paulo, Brazil. Univ Sao Paulo, Lab Med Invest, Sao Paulo, Brazil. RI Duarte, Alberto/D-4382-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S90 EP S90 DI 10.1016/j.clim.2007.03.438 PG 1 WC Immunology SC Immunology GA 177EU UT WOS:000247137200235 ER PT J AU Li, ZQ Mahesh, S Liu, BY Clarke, G Lim, WK Nussenblatt, R AF Li, Zhuqing Mahesh, Sankaranarayana Liu, Baoying Clarke, Grace Lim, Wee Kiak Nussenblatt, Robert TI Gene expression profiling of non-infectious uveitis patients using pathway specific cDNA microarray analysis SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S167 EP S167 DI 10.1016/j.clim.2007.03.118 PG 1 WC Immunology SC Immunology GA 177EU UT WOS:000247137200439 ER PT J AU Linington, C Mathey, E Derfuss, T Rasband, M Storch, M Hohlfeld, R Meinl, E AF Linington, Christopher Mathey, Emily Derfuss, Tobias Rasband, Matthew Storch, Maria Hohlfeld, Reinhard Meinl, Edgar TI Neu rofascin-specific autoantibodies mediate axonal injury in inflammatory demyelinating diseases of the central nervous system SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 NIH, NIAID, Lab Host Def, Bethesda, MD 20892 USA. NCI, Bethesda, MD 20892 USA. Clin Ctr, Bethesda, MD USA. NIAID, Bethesda, MD 20892 USA. Amgen Seattle, Seattle, WA USA. Univ Washington, Dept Pediat, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S129 EP S130 DI 10.1016/j.clim.2007.03.007 PG 2 WC Immunology SC Immunology GA 177EU UT WOS:000247137200336 ER PT J AU Luger, D Cua, D Chen, Z Iwokura, Y Bowman, E Chan, CC Caspi, R AF Luger, Dror Cua, Daniel Chen, Zoe Iwokura, Yoichiro Bowman, Edward Chan, Chi-Chao Caspi, Rachel TI IL-23 and IL-17 in pathogenesis of experimental ocular autoimmunity: Requirement for IL-23 may extend beyond its role in sustaining the IL-17 effector response SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Schering Plough Biopharma, DNAX, Palo Alto, CA USA. Schering Plough Biopharma, Palo Alto, CA USA. Univ Tokyo, Tokyo, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S61 EP S61 DI 10.1016/j.clim.2007.03.353 PG 1 WC Immunology SC Immunology GA 177EU UT WOS:000247137200159 ER PT J AU Manzanet, RR Hartt-Meyers, J Slavik, J Dardalhon, V Kassam, N Greenfield, EA Sobel, RA Strom, TB Hafter, DA Kuchroo, VK AF Manzanet, Roselynn Rodriguez Hartt-Meyers, Jennifer Slavik, Jacqueline Dardalhon, Valerie Kassam, Nasim Greenfield, Edward A. Sobel, Raymond A. Strom, Terry B. Hafter, David A. Kuchroo, Vijay K. TI Tim-4 expressed on antigen-presenting cells induces T cell expansion and survival SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 Brigham & Womens Hosp, Boston, MA 02115 USA. NIH, NIAID, LIR, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Biomed Res Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA. Stanford Univ, Sch Med, Dept Pathol, Stanford, CA 94305 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S124 EP S125 DI 10.1016/j.clim.2007.03.533 PG 2 WC Immunology SC Immunology GA 177EU UT WOS:000247137200325 ER PT J AU Oliveira, JB Jesus, A Aksentijevich, I Silva, C Duarte, AJS AF Oliveira, Joao B. Jesus, AdriGna Aksentijevich, Ivona Silva, Clovis Duarte, Alberto J. S. TI TNF receptor-associated periodic fever syndrome (TRAPS) caused by a novel C30F mutation associated with the common R92Q low-penetrance mutation in TNFRSF1A SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 Univ Sao Paulo, Mol Immunol & Genet Sect, Lab Med Invest, Sao Paulo, Brazil. Univ Sao Paulo, Dept Pediat, Sao Paulo, Brazil. NIAMS, NIH, GGB, Bethesda, MD USA. Univ Sao Paulo, Dept Pediat, Head Pediat Rheumatol Unit, Sao Paulo, Brazil. Univ Sao Paulo, Lab Med Invest, Sao Paulo, Brazil. RI Duarte, Alberto/D-4382-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S90 EP S90 DI 10.1016/j.clim.2007.03.437 PG 1 WC Immunology SC Immunology GA 177EU UT WOS:000247137200234 ER PT J AU Pantanelli, S Li, ZQ Fariss, R Cunningham, M Liu, BY Mahesh, S Nussenblatt, R AF Pantanelli, Seth Li, Zhuqing Fariss, Rober Cunningham, Matthew Liu, Baoying Mahesh, Sankara Nussenblatt, Robert TI Autofluorescence can be used to differentiate between normal, activated, or malignant lymphocyte populations SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 NEI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S168 EP S168 DI 10.1016/j.clim.2007.03.120 PG 1 WC Immunology SC Immunology GA 177EU UT WOS:000247137200441 ER PT J AU Pietra, G Vacca, P Moretta, L Prefumo, F Mingari, MC AF Pietra, Gabriella Vacca, Paola Moretta, Lorenzo Prefumo, Federico Mingari, Maria Cristina TI Analysis of natural killer cells isolated from human decidua: Evidence that 2B4 (CD244) functions as an inhibitory receptor and blocks NK cell function SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 Univ Genoa, DIMES, I-16126 Genoa, Italy. Gaslini Inst, Genoa, Italy. Natl Canc Inst, Genoa, Italy. RI pietra, gabriella/J-7204-2016 OI pietra, gabriella/0000-0002-7080-531X NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S187 EP S187 DI 10.1016/j.clim.2007.03.555 PG 1 WC Immunology SC Immunology GA 177EU UT WOS:000247137200492 ER PT J AU Rachitskaya, AV Hansen, AM Agarwal, RK Luger, D Silver, PB Chan, CC Caspi, RR AF Rachitskaya, Aleksandra V. Hansen, Anna M. Agarwal, Rajeev K. Luger, Dror Silver, Phyllis B. Chan, Chi-Chao Caspi, Rachel R. TI Endogenous IL-6 is required for inducing and sustaining an antigen-specific IL-17 memory response in experimental autoimmune uveitis (EAU), but not for innate IL-17 production SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. HHMI NIH Res Scholars Program, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S62 EP S62 DI 10.1016/j.clim.2007.03.356 PG 1 WC Immunology SC Immunology GA 177EU UT WOS:000247137200162 ER PT J AU Raqheb, J Snyder, J Shen, J Hu, P Azmi, H Chen, Q AF Raqheb, Jack Snyder, James Shen, Jijia Hu, Paul Azmi, Hooman Chen, Qian TI A novel cell contact-dependent requirement for human CD40 ligand expression SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S58 EP S58 DI 10.1016/j.clim.2007.03.346 PG 1 WC Immunology SC Immunology GA 177EU UT WOS:000247137200152 ER PT J AU Sampaio, E Elloumi, H Zelazny, A Shea, Y Ding, L Holland, S AF Sampaio, Elizabeth Elloumi, Houda Zelazny, Adrian Shea, Yvonne Ding, Li Holland, Steven TI Differential cytokine response induced by M. Avium and M. Abscessus in human macrophages is mediated through p38 MapKinase signalling pathway and partially dependent on TLR2 activation SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S36 EP S36 DI 10.1016/j.clim.2007.03.279 PG 1 WC Immunology SC Immunology GA 177EU UT WOS:000247137200091 ER PT J AU Sawalha, AH Kaufman, K Kelly, J Aberle, T Adler, A Kilpatrick, J Wakeland, E Li, QZ Wandstrat, A James, J Merrill, J Lipsky, P Harley, JB AF Sawalha, Amr H. Kaufman, Kenneth Kelly, Jennifer Aberle, Teresa Adler, Adam Kilpatrick, Jeff Wakeland, Edward Li, Quan-Zhen Wandstrat, Amy James, Judith Merrill, Joan Lipsky, Peter Harley, John B. TI Genetic association of IL-21 polymorphisms with systemic lupus erythematosus SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, VA Med Ctr,Dept Med, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Univ Texas, SW Med Ctr, Ctr Immunol, Dallas, TX 75216 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Oklahoma Med Res Fdn, Clin Pharmacol, Oklahoma City, OK 73104 USA. NIAMS, Bethesda, MD USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma Med Res Fdn, Oklahoma City, OK USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S134 EP S135 DI 10.1016/j.clim.2007.03.021 PG 2 WC Immunology SC Immunology GA 177EU UT WOS:000247137200349 ER PT J AU Shearer, W Pahwa, S Read, J Wijoyawardana, S Chen, J Easley, K Palumbo, P Abrams, E AF Shearer, William Pahwa, Savita Read, Jennifer Wijoyawardana, Sameera Chen, Jing Easley, Kirk Palumbo, Paul Abrams, Elaine TI CD4/CD8 T cell ratio predicts HIV infection in infants: The NHLBI P2C2HIV study SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 Texas Childrens Hosp, Baylor Coll Med, Houston, TX 77030 USA. Univ Miami, Miller Sch Med, Miami, FL 33152 USA. NICHHD, Bethesda, MD 20892 USA. Emory Univ, Rollins Sch Med, Atlanta, GA 30322 USA. Dartmouth Coll Sch Med, Hanover, NH USA. Columbia Univ, New York, NY USA. Emory Univ, Sch Med, Atlanta, GA USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S46 EP S46 DI 10.1016/j.clim.2007.03.307 PG 1 WC Immunology SC Immunology GA 177EU UT WOS:000247137200119 ER PT J AU Sheng, SJ Fu, Q Chapman, J Van Eyk, J Feitelson, J AF Sheng, Shijun Fu, Qin Chapman, Jeff Van Eyk, Jennifer Feitelson, Jerald TI Industrial science: Biomarker discovery from plasma: Maximizing proteomic breath and depth using protein partitioning and fractionation followed by shotgun mass spectrometry SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 Johns Hopkins Univ, NHLBI, Proteom Ctr, Baltimore, MD USA. Biomarker Discovery & Automat Business Ctr, Fullerton, CA USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S185 EP S185 DI 10.1016/j.clim.2007.03.173 PG 1 WC Immunology SC Immunology GA 177EU UT WOS:000247137200487 ER PT J AU Temmerman, S Ma, C Jain, A AF Temmerman, Stephan Ma, Chi Jain, Ashish TI Impaired dendritic cell function in ectodermal dysplasia with immune deficiency is linked to defective NEMO ulbiquitination SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 7th Annual Meeting of the Federation-of-Clinical-Immunology-Societies CY JUN 07-11, 2007 CL San Diego, CA SP Federat Clin Immunol Soc C1 NIAID, NIH, LHD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2007 VL 123 SU S BP S13 EP S14 DI 10.1016/j.clim.2007.03.208 PG 2 WC Immunology SC Immunology GA 177EU UT WOS:000247137200031 ER PT J AU Walsh, TJ Raad, I Patterson, TF Chandrasekar, P Donowitz, GR Graybill, R Greene, RE Hachem, R Hadley, S Herbrecht, R Langston, A Louie, A Ribaud, P Segal, BH Stevens, DA van Burik, JAH White, CS Corcoran, G Gogate, J Krishna, G Pedicone, L Hardalo, C Perfect, JR AF Walsh, Thomas J. Raad, Issam Patterson, Thomas F. Chandrasekar, Pranatharthi Donowitz, Gerald R. Graybill, Richard Greene, Reginald E. Hachem, Ray Hadley, Susan Herbrecht, Raoul Langston, Amelia Louie, Arnold Ribaud, Patricia Segal, Brahm H. Stevens, David A. van Burik, Jo-Anne H. White, Charles S. Corcoran, Gavin Gogate, Jagadish Krishna, Gopal Pedicone, Lisa Hardalo, Catherine Perfect, John R. TI Treatment of invasive aspergillosis with posaconazole in patients who are refractory to or intolerant of conventional therapy: An externally controlled trial SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IN-VITRO ACTIVITIES; AMPHOTERICIN-B; PULMONARY ASPERGILLOSIS; FUNGAL-INFECTIONS; MURINE MODEL; EFFICACY; SAFETY; ITRACONAZOLE; VORICONAZOLE; SCH-56592 AB Background. Invasive aspergillosis is an important cause of morbidity and mortality in immunocompromised patients. Current treatments provide limited benefit. Posaconazole is an extended-spectrum triazole with in vitro and in vivo activity against Aspergillus species. Methods. We investigated the efficacy and safety of posaconazole oral suspension (800 mg/day in divided doses) as monotherapy in an open-label, multicenter study in patients with invasive aspergillosis and other mycoses who were refractory to or intolerant of conventional antifungal therapy. Data from external control cases were collected retrospectively to provide a comparative reference group. Results. Cases of aspergillosis deemed evaluable by a blinded data review committee included 107 posaconazole recipients and 86 control subjects (modified intent-to-treat population). The populations were similar and balanced with regard to prespecified demographic and disease variables. The overall success rate (i.e., the data review committee-assessed global response at the end of treatment) was 42% for posaconazole recipients and 26% for control subjects (odds ratio, 4.06; 95% confidence interval, 1.50-11.04;). The differences in response Pp. 006 between the modified intent-to-treat treatment groups were preserved across additional, prespecified subsets, including infection site (pulmonary or disseminated), hematological malignancy, hematopoietic stem cell transplantation, baseline neutropenia, and reason for enrollment(patient was refractory to or intolerant of previous antifungal therapy). An exposure-response relationship was suggested by pharmacokinetic analyses. Conclusions. Although the study predates extensive use of echinocandins and voriconazole, these findings demonstrate that posaconazole is an alternative to salvage therapy for patients with invasive aspergillosis who are refractory to or intolerant of previous antifungal therapy. C1 NCI, Immunocompromised Host Sect, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78285 USA. Wayne State Univ, Detroit, MI USA. Univ Virginia, Charlottesville, VA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Emory Univ Hosp, Atlanta, GA 30322 USA. Albany Med Ctr, Albany, NY USA. Roswell Pk Mem Canc Ctr, Buffalo, NY USA. Santa Clara Valley Med Ctr, San Jose, CA 95128 USA. Univ Minnesota, Sch Med, Minneapolis, MN USA. Schering Plough Res Inst, Kenilworth, NJ USA. Duke Univ, Durham, NC USA. Hop Hautepierre, Strasbourg, France. Hosp St Louis, Paris, France. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, CRC 1-5750,10 Ctr Dr, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov RI Herbrecht, Raoul/D-3471-2013; Young, Jo-Anne/G-2617-2013; OI Young, Jo-Anne/0000-0003-4182-341X; Herbrecht, Raoul/0000-0002-9381-4876 NR 23 TC 400 Z9 423 U1 0 U2 9 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 JAN 1 PY 2007 VL 44 IS 1 BP 2 EP 12 DI 10.1086/508774 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 111UC UT WOS:000242479500001 PM 17143808 ER PT J AU Dharnidharka, VR Agodoa, LY Abbott, KC AF Dharnidharka, Vikas R. Agodoa, Lawrence Y. Abbott, Kevin C. TI Effects of urinary tract infection on outcomes after renal transplantation in children SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the American-Society-of-Nephrology CY OCT 27-NOV 01, 2004 CL St Louis, MO SP Amer Soc Nephrol ID KIDNEY-TRANSPLANTATION; UNITED-STATES; RECIPIENTS; COMPLICATIONS; HOSPITALIZATIONS; PROPHYLAXIS; PREVALENCE; REJECTION; DISEASE; RISK AB Urinary tract infection (UTI) is the most common infection after kidney transplantation. A previous analysis showed that late (>6 mo after transplantation) UTI is associated with earlier graft loss in adults. It was hypothesized that children who are younger than 18 yr would be at higher risk to develop UTI and develop graft loss after both early and late UTI. The US Renal Data System database was analyzed from 1996 to 2000 for Medicare claims (composite of inpatient and outpatient) for UTI up to 36 mo after transplantation. SPSS software and Cox regression models were used to determine association of UTI and age after adjustment for covariates. Early UTI was defined as occurring <6 mo after transplantation, and late UTI was defined as occurring >= 6 mo after transplantation. The risk for graft loss after early UTI was elevated in all children (adjusted hazard ratio [AHR] 5.47; 95% confidence interval [CI] 1.93 to 15.4; P<0.001) but not after late UTI (AHR 2.09; 95% CI 0.56 to 7.80; P=0.27). Risk for posttransplantation death was not increased significantly after either early UTI (AHR 1.23; 95% CI 0.37 to 4.08) or late UTI (relative risk 2.22; 95% CI 0.90 to 5.44). Boys aged 2 to 5 (versus age 13 to <18 years) were at significantly higher risk for UTI. In girls, only those in the youngest age category (0 to 1) had higher risk for UTI. Children are at greater risk for graft loss after early but not necessarily late UTI. UTI was not an independent predictor of death in this population. C1 Univ Florida, Hlth Sci Ctr, Div Pediat Nephrol, Coll Med, Gainesville, FL 32610 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Walter Reed Army Med Ctr, Serv Nephrol, Washington, DC 20307 USA. RP Dharnidharka, VR (reprint author), Univ Florida, Hlth Sci Ctr, Div Pediat Nephrol, Coll Med, POB 100296,1600 SW Archer Rd, Gainesville, FL 32610 USA. EM vikasmd@ufl.edu OI Abbott, Kevin/0000-0003-2111-7112 FU NIDDK NIH HHS [1R21DK069535] NR 25 TC 16 Z9 18 U1 0 U2 0 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2007 VL 2 IS 1 BP 100 EP 106 DI 10.2215/CJN.01820506 PG 7 WC Urology & Nephrology SC Urology & Nephrology GA 123VP UT WOS:000243324500018 PM 17699393 ER PT J AU Torres, VE King, BF Chapman, AB Brummer, ME Bae, KT Glockner, JF Arya, K Risk, D Felmlee, JP Grantham, JJ Guay-Woodford, LM Bennett, WM Klahr, S Meyers, CM Zhang, XL Thompson, PA Miller, JP AF Torres, Vicente E. King, Bernard F. Chapman, Arlene B. Brummer, Marijn E. Bae, Kyongtae T. Glockner, James F. Arya, Kraisthith Risk, Dana Felmlee, Joel P. Grantham, Jared J. Guay-Woodford, Lisa M. Bennett, William M. Klahr, Saulo Meyers, Catherine M. Zhang, Xiaoling Thompson, Paul A. Miller, J. Philip CA CRISP TI Magnetic resonance measurements of renal blood flow and disease progression in autosomal dominant polycystic kidney disease SO CLINICAL JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID SMOOTH-MUSCLE-CELLS; ENDOTHELIAL DYSFUNCTION; VASCULAR EXPRESSION; VOLUME PROGRESSION; CONVERTING ENZYME; ALBUMIN OVERLOAD; TUBULE CELLS; HYPERTENSION; PROLIFERATION; INHIBITION AB Whether changes in renal blood flow (RBF) are associated with and possibly contribute to cystic disease progression in autosomal dominant polycystic kidney disease (ADPKD) has not been ascertained. The Consortium for Radiologic Imaging Studies of Polycystic Kidney Disease (CRISP) was created to develop imaging techniques and analyses to evaluate progression. A total of 131 participants with early ADPKD had measurements of RBF and total kidney (TKV) and cyst (TCV) volumes by magnetic resonance and of GFR by iothalamate clearance at baseline and 1, 2, and 3 yr. The effects of age, gender, body mass index, hypertension status, mean arterial pressure (MAP), TKV, TCV, RBF, renal vascular resistance (RVR), GFR, serum uric acid, HDL and LDL cholesterol, 24-h urine volume, sodium (UNaE) and albumin (UAE) excretions, and estimated protein intake were examined at baseline on TKV, TCV, and GFR slopes. TKV and TCV increased, RBF decreased, and GFR remained stable. TKV, TCV, RVR, serum uric acid, UAE, UNaE, age, body mass index, MAP, and estimated protein intake were positively and RBF and GFR negatively correlated with TKV and TCV slopes. TKV, RBF, UNaE, and UAE were independent predictors of TKV and TCV slopes (structural disease progression). TKV, TCV, RVR, and MAP were negatively and RBF positively correlated with GFR slopes. Regression to the mean confounded the analysis of GFR slopes. TKV and RBF were independent predictors of GFR decline (functional disease progression). In ADPKD, RBF reduction (1) parallels TKV increase, (2) precedes GFR decline, and (3) predicts structural and functional disease progression. C1 Mayo Clin, Div Nephrol & Hypertens, Coll Med, Rochester, MN 55901 USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Univ Alabama, Birmingham, AL USA. NW Renal Clin, Portland, OR USA. NIDDKD, NIH, Div Kidney Urol & Hematol Dis, Bethesda, MD 20892 USA. Washington Univ, St Louis, MO USA. RP Torres, VE (reprint author), Mayo Clin, Div Nephrol & Hypertens, Coll Med, Rochester, MN 55901 USA. EM torres.vicente@mayo.edu FU NCRR NIH HHS [M01-RR00039, M01-RR00585]; NIDDK NIH HHS [DK56943, DK56956, DK56957, DK56961] NR 38 TC 75 Z9 78 U1 0 U2 1 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1555-905X J9 CLIN J AM SOC NEPHRO JI Clin. J. Am. Soc. Nephrol. PD JAN PY 2007 VL 2 IS 1 BP 112 EP 120 DI 10.2215/CJN.00910306 PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 123VP UT WOS:000243324500020 PM 17699395 ER PT J AU de Jong, FA Scott-Horton, TJ Kroetz, DL McLeod, HL Friberg, LE Mathijssen, RH Verweij, J Marsh, S Sparreboom, A AF de Jong, F. A. Scott-Horton, T. J. Kroetz, D. L. McLeod, H. L. Friberg, L. E. Mathijssen, R. H. Verweij, J. Marsh, S. Sparreboom, A. TI Irinotecan-induced diarrhea: Functional significance of the polymorphic ABCC2 transporter protein SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article; Proceedings Paper CT 107th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 08-11, 2006 CL Baltimore, MD SP Amer Soc Clin Pharmacol & Therapeut ID SINGLE NUCLEOTIDE POLYMORPHISMS; CRIGLER-NAJJAR SYNDROME; HYDROCHLORIDE CPT-11; ACTIVE METABOLITE; BILIARY-EXCRETION; GILBERTS-SYNDROME; CLINICAL PHARMACOKINETICS; INTESTINAL MICROFLORA; BETA-GLUCURONIDASE; COLORECTAL-CANCER AB Interindividual pharmacokinetic variability of the anticancer agent irinotecan is high. Life-threatening diarrhea is observed in up to 25% of patients receiving irinotecan and has been related with irinotecan pharmacokinetics and UGT1A1 genotype status. Here, we explore the association of ABCC2 (MRP2) polymorphisms and haplotypes with irinotecan disposition and diarrhea. A cohort of 167 Caucasian cancer patients who were previously assessed for irinotecan pharmacokinetics (90-min infusion given every 21 days), toxicity, and UGT1A1*28 genotype were genotyped for polymorphisms in ABCC2 using Pyrosequencing. Fifteen ABCC2 haplotypes were identified in the studied patients. The haplotype ABCC2*2 was associated with lower irinotecan clearance (28.3 versus 31.6 l/h; P = 0.020). In patients who did not carry a UGT1A1*28 allele, a significant reduction of severe diarrhea was noted in patients with the ABCC2*2 haplotype (10 versus 44%; odds ratio, 0.15; 95% confidence interval, 0.04-0.61; P = 0.005). This effect was not observed in patients with at least one UGT1A1*28 allele (32 versus 20%; odds ratio, 1.87; 95% confidence interval, 0.49-7.05; P = 0.354). This study suggests that the presence of the ABCC2*2 haplotype is associated with less irinotecan-related diarrhea, maybe as a consequence of reduced hepatobiliary secretion of irinotecan. As the association was seen in patients not genetically predisposed at risk for diarrhea due to UGT1A1*28, confirmatory studies of the relationships of ABCC2 genotypes and irinotecan disposition and toxicity are warranted. C1 Erasmus Univ, Med Ctr, Dr Daniel Den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Univ Calif San Francisco, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA. Uppsala Univ, Dept Pharmaceut Biosci, Div Pharmacokinet & Drug Therapy, Uppsala, Sweden. NCI, Bethesda, MD 20892 USA. RP Sparreboom, A (reprint author), Erasmus Univ, Med Ctr, Dr Daniel Den Hoed Canc Ctr, Dept Med Oncol, Rotterdam, Netherlands. EM alex.sparreboom@stjude.org RI Sparreboom, Alex/B-3247-2008; de Jong, Floris/F-5486-2011 FU NIGMS NIH HHS [U01 GM63340, GM61390] NR 61 TC 108 Z9 113 U1 0 U2 8 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2007 VL 81 IS 1 BP 42 EP 49 DI 10.1038/sj.clpt.6100019 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 117LI UT WOS:000242874200016 PM 17185998 ER PT J AU Smith, NF Marsh, S Scott-Horton, TJ Hamada, A Mielke, S Mross, K Figg, WD Verweij, J McLeod, HL Sparreboom, A AF Smith, N. F. Marsh, S. Scott-Horton, T. J. Hamada, A. Mielke, S. Mross, K. Figg, W. D. Verweij, J. McLeod, H. L. Sparreboom, A. TI Variants in the SLCO1B3 gene: Interethnic distribution and association with paclitaxel pharmacokinetics SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ANION TRANSPORTING POLYPEPTIDE; SINGLE-NUCLEOTIDE POLYMORPHISMS; BODY-SURFACE AREA; OATP-C SLC21A6; UNBOUND PACLITAXEL; SUBSTRATE-SPECIFICITY; ENCODING OATP1B1; HUMAN PLASMA; HUMAN LIVER; PRAVASTATIN AB To explore retrospectively the relationships between paclitaxel pharmacokinetics and three known, non-synonymous single-nucleotide polymorphisms (SNPs) in SLCO1B3, the gene encoding organic anion transporting polypeptide (OATP) 1B3. Accumulation of [H-3]paclitaxel was studied in Xenopus laevis oocytes injected with cRNA of Oatp1b2, OATP1A2, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, and INITCP. The 334T > G (Ser112Ala), 699G > A (Met233lle), and 1564G > T (Gly522Cys) loci of SLCO1B3 were screened in 475 individuals from five ethnic groups and 90 European Caucasian cancer patients treated with paclitaxel. Only OATP1B3 was capable of transporting paclitaxel to a significant extent (P = 0.003). The 334T > G and 699G > A SNPs were less common in the Africa n-American and Ghanaian populations (P < 0.000001). Paclitaxel pharmacokinetics were riot associated with the studied SNPs or haplotypes (P > 0.3). The studied SNPs in SLCO1B3 appear to play a limited role in the disposition of paclitaxel, although their clinical significance in other ethnic populations remains to be investigated. C1 NCI, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. Washington Univ, Dept Med, Sch Med, St Louis, MO 63130 USA. Univ Freiburg, Ctr Med, Dept Hematol & Oncol, D-7800 Freiburg, Germany. Univ Freiburg, Tumor Biol Ctr, D-7800 Freiburg, Germany. Dr Daniel Den Hoed Canc Ctr, Erasmus MC, Dept Med Oncol, NL-3008 AE Rotterdam, Netherlands. RP Sparreboom, A (reprint author), NCI, Ctr Canc Res, Med Oncol Branch, Bethesda, MD 20892 USA. EM alex.sparreboom@stjude.org RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 FU Intramural NIH HHS; NIGMS NIH HHS [U01 GM63340] NR 48 TC 93 Z9 95 U1 0 U2 4 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2007 VL 81 IS 1 BP 76 EP 82 DI 10.1038/sj.clpt.6100011 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 117LI UT WOS:000242874200020 PM 17186002 ER PT J AU Zerhouni, EA AF Zerhouni, E. A. TI Translational research: Moving discovery to practice SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB In the first week of October, I announced the launch of a national consortium that will transform how clinical and translational research is conducted, ultimately enabling researchers to provide new treatments more efficiently and quickly to patients. This new consortium, funded through Clinical and Translational Science Awards (CTSAs), begins with 12 academic health centers (AHCs) located throughout the nation. An additional 52 AHCs are receiving planning grants to help them prepare to apply for a CTSA. C1 NIH, Bethesda, MD 20892 USA. RP Zerhouni, EA (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM MarshalL@od.nih.gov NR 1 TC 93 Z9 95 U1 0 U2 9 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2007 VL 81 IS 1 BP 126 EP 128 DI 10.1038/sj.clpt.6100029 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 117LI UT WOS:000242874200029 PM 17186011 ER PT J AU Fall-Dickson, JM Ramsay, ES Castro, K Woltz, P Sportes, C AF Fall-Dickson, Jane M. Ramsay, Edward S. Castro, Kathleen Woltz, Patricia Sportes, Claude TI Oral mucositis-related oropharyngeal pain and correlative tumor necrosis factor-alpha expression in adult oncology patients undergoing hematopoietic stem cell transplantation SO CLINICAL THERAPEUTICS LA English DT Article DE oral mucositis; oropharyngeal pain; hematopoietic stem cell transplantation ID BONE-MARROW-TRANSPLANTATION; CANCER; OUTCOMES; CONSEQUENCES; CHEMOTHERAPY; PATHOBIOLOGY; PREVENTION; INJURY AB Background: Oral mucositis is the most common sequela of conditioning chemotherapy (CT) for hematopoietic stem cell transplantation (HSCT) and is the principal cause of most of the associated pain. Tumor necrosis factor-alpha (TNF-alpha) is a key pathogenic component of oral mucositis. Objectives: The primary purpose of this study was to describe oral mucositis-related oropharyngeal pain in the setting of HSCT. A secondary purpose was to assess the effectiveness of molecular biology methods for measuring TNF-a concentrations in plasma, saliva, and buccal epithelia[ cells in patients with oral mucositis undergoing HSCT. Methods: This descriptive, correlative study recruited subjects aged >= 18 years who were scheduled to receive HSCT with CT. Subjects assessed their pain at baseline and 9 (lays (+/-24 hours) after CT using a pain visual analog scale (VAS) from 0 = no pain to 10 worst possible pain, as well as word descriptors of sensory and affective pain. The extent and severity of oral mucositis were evaluated using the Oral Mucositis Assessment Scale. Saliva and blood samples and buccal brush biopsies were obtained at the same time points. Salivary and plasma TNF-alpha concentrations were measured using an enzyme-linked immunosorbent assay. Quantitative real-time polymerase chain reaction testing was used to measure buccal TNF-a gene expression. To determine the optimal method of RNA isolation, samples were extracted using 3 different methods: TRIzol, RNeasy, and RLT/TRIzol. Results: Twenty-five adult men and women (mean age, 46 years; age range, 32-68 years; 64% white) underwent HSCT with CT. Significant differences from baseline to day 9 were observed in the severity of oral mucositis (P < 0.001), the overall intensity of oral pain (P < 0.05), the overall intensity of oral pain with swallowing (P < 0.01.), the sensory dimension of oral pain with swallowing (P < 0.05), and the sensory and affective dimension of oral pain with swallowing (P < 0.05). The severity of oral mucositis was significantly associated with the overall intensity of oral pain (P < 0.05). Although mean scores for oral pain were low, 8 subjects had clinically unacceptable pain VAS scores (>3) while receiving opioids. Fourteen subjects had measurable increases in buccal TNF-alpha RNA expression at day 9 (P = 0.027 vs baseline), as measured using the TRIzol method, which was found to be the best method for measuring this variable. TNF-alpha RNA content in buccal samples was significantly associated with the worst intensity of oral pain with swallowing (partial R-2 = 0.19; P < 0.05). Conclusions: Despite the use of opioids, oropharyngeal pain remained a treatment challenge in approximately one third of these subjects after CT with HSCT. The sensitive assay used to measure TNF-alpha. gene expression in buccal cells may be useful in investigating molecular events in oral mucositis-related pain, as well as in evaluating the therapeutic response to investigational agents. C1 [Fall-Dickson, Jane M.; Woltz, Patricia] Natl Inst Nursing Res, Mucosal Injury Unit, NIH, Bethesda, MD 20892 USA. [Ramsay, Edward S.] Ntal Inst Nursing Res, Lab Symptom Management, NIH, Bethesda, MD USA. [Castro, Kathleen] NIH, Ctr Clin, Nursing & Patient Care Serv, Res & Practice Dev Serv, Bethesda, MD 20892 USA. [Sportes, Claude] NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Fall-Dickson, JM (reprint author), Natl Inst Nursing Res, Mucosal Injury Unit, NIH, 10 Clin Res Ctr,Room 2NE-1339,10 Ctr Dr, Bethesda, MD 20892 USA. EM dicksonj@mall.nih.gov NR 27 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 2007 VL 29 SI 2 BP 2547 EP 2561 DI 10.1016/j.clinthera.2007.12.004 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 249EZ UT WOS:000252211600006 PM 18164921 ER PT J AU Villacorta, V Kegeles, S Galea, J Konda, KA Cuba, JP Palacios, CFC Coates, TJ AF Villacorta, Victoria Kegeles, Susan Galea, Jerome Konda, Kelika A. Pajuelo Cuba, Jose Caceres Palacios, Carlos F. Coates, Thomas J. CA NIMH Collaborative TI Innovative approaches to cohort retention in a community-based HIV/STI prevention trial for socially marginalized Peruvian young adults SO CLINICAL TRIALS LA English DT Article ID FOLLOW-UP; INTERVENTION; PARTICIPANTS; POPULATIONS; ATTRITION; TRACKING AB Background The conduct of longitudinal clinical trials must involve effective strategies to retain study participants in order to ensure internal validity, adequate statistical power and generalizability of results. Purpose In a large trial in Peru, we implemented various retention strategies to maintain high participation rates over time. Methods Novel participant retention strategies were used to follow highly marginalized populations for two years because traditional locator information, such as telephone numbers and official identification (eg, passport, driver's license, the local equivalent of a social security number) were often unreliable or unavailable. These strategies included detailed preliminary ethnographic research to identify the behaviours of key target groups, approaches to develop strong informal bonds between project staff and participants outside of study settings, and methods to enhance positive participant attitudes towards the study. Results The overall study retention rate after two years was 84%, even though only 26% of the study populations supplied complete locator information (telephone, address and the names of two friends). Limitations The retention strategies used were labour intensive and iterative, which could prove difficult to replicate. Conclusions The two-year retention rate in this study was sufficient to maintain required sample sizes. The methods used to maintain contact with the populations were labour intensive, low tech and adequate for these populations and could be used to retain study participants in other marginalized, urban, low-income areas. C1 Univ Peruana Cayetano Heredia, Lima 18, Peru. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Los Angeles, CA USA. NIMH, Multisite Int Grp, Bethesda, MD 20892 USA. RP Villacorta, V (reprint author), Univ Peruana Cayetano Heredia, Av Armendariz 445, Lima 18, Peru. EM 06688@upch.edu.pe FU NIMH NIH HHS [U10 MH61536, U10 MH061536, U10 MH061536-08, U10 MH061536-07] NR 17 TC 12 Z9 12 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2007 VL 4 IS 1 BP 32 EP 41 DI 10.1177/1740774506075869 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 150EZ UT WOS:000245199700004 PM 17327244 ER PT J AU Simon, R AF Simon, Richard TI New challenges for 21st century clinical trials SO CLINICAL TRIALS LA English DT Article ID BREAST-CANCER; CLASSIFIERS; CHEMOTHERAPY; THERAPEUTICS; TRASTUZUMAB; EFFICIENCY C1 NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Simon, R (reprint author), NCI, Biometr Res Branch, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM rsimon@nih.gov NR 19 TC 11 Z9 12 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2007 VL 4 IS 2 BP 167 EP 169 DI 10.1177/1740774507076800 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 175PX UT WOS:000247026600007 PM 17456517 ER PT J AU Anderson, GL Kooperberg, C Geller, N Rossouw, JE Pettinger, M Prentice, RL AF Anderson, Garnet L. Kooperberg, Charles Geller, Nancy Rossouw, Jacques E. Pettinger, Mary Prentice, Ross L. TI Monitoring and reporting of the Women's Health Initiative randomized hormone therapy trials SO CLINICAL TRIALS LA English DT Article ID CORONARY-HEART-DISEASE; ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; PREVENTION; INTERVENTION AB Background The Women's Health Initiative (WHI) randomized trial of estrogen plus progestin (E+P) was terminated early based on an assessment of harms exceeding benefits for disease prevention. The results contravened prevailing wisdom and a large body of literature regarding benefits of menopausal hormone therapy. The results and their interpretation have been the subject of considerable debate. Purpose/methods To describe the process of developing a trial monitoring plan, the key interim and final data, and to explain the choice of statistical methods used in trial monitoring and reporting. Results A formalized monitoring plan was developed using statistical methods that acknowledged protocol-defined design and analysis plans, input of monitoring board members especially regarding the role of various study outcomes, and multiple comparisons. Major early departures from design assumptions concerning treatment effects indicated a need for additional flexibility in safety monitoring. When the trials were stopped early, questions arose as to how closely the statistical methods in published reports should correspond to those defined by protocol or used in monitoring. Methods were selected to provide a simple and transparent summary of the primary results, with a cautious interpretation promoted by acknowledgement of multiple testing. Conclusions Developing a formal trial monitoring plan with a view towards influencing clinical practice is useful for creating consensus among DSMB members regarding the evidence that would justify stopping a trial and the framework to be used to address statistical complexities. Departures from design assumptions typically occur. These reinforce the role of the DSMB in exercising their judgment, and the judicious adaptation of these statistical guidelines in monitoring and reporting trials. In communicating the results in such circumstances, priority should be given to presenting as fair, accurate and transparent a view of the data and findings as current methods and technology allow. C1 Fred Hutchinson Canc Res Ctr, WHI Clin Coordinating Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. NHLBI, Bethesda, MD 20892 USA. RP Anderson, GL (reprint author), Fred Hutchinson Canc Res Ctr, WHI Clin Coordinating Ctr, Div Publ Hlth Sci, 1100 Fairview Ave N,M3-A410,POB 19024, Seattle, WA 98109 USA. EM garnet@whi.org FU NCI NIH HHS [CA53996] NR 28 TC 14 Z9 14 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2007 VL 4 IS 3 BP 207 EP 217 DI 10.1177/1740774507079252 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 210XP UT WOS:000249489200002 PM 17715246 ER PT J AU Wittes, J Barrett-Connor, E Braunwald, E Chesney, M Cohen, HJ DeMets, D Dunn, L Dwyer, J Heaney, RP Vogel, V Walters, L Yusuf, S AF Wittes, Janet Barrett-Connor, Elizabeth Braunwald, Eugene Chesney, Margaret Cohen, Harvey Jay DeMets, David Dunn, Leo Dwyer, Johanna Heaney, Robert P. Vogel, Victor Walters, Leroy Yusuf, Salim TI Monitoring the randomized trials of the Women's Health Initiative the experience of the data and safety monitoring board SO CLINICAL TRIALS LA English DT Article ID DIETARY MODIFICATION TRIAL; ESTROGEN PLUS PROGESTIN; POSTMENOPAUSAL WOMEN; CARDIOVASCULAR-DISEASE; ORAL-CONTRACEPTIVES; CLINICAL-TRIAL; RISK; PREVENTION; THERAPY; PATTERN AB Data Safety Monitoring Committees (DSMB) for large, long-term randomized trials of agents in common use face challenging problems especially when the emerging data indicate unanticipated effects. The DSMB for the Women's Health Initiative Clinical Trials, on observing early indication of a surprising adverse cardiovascular effect of post-menopausal hormones, spent several years deliberating what recommendations it should make. This paper describes the dilemmas faced by the DSMB and the considerations it made over the course of its existence. The paper concludes with some recommendations for other DSMBs. C1 Stat Collaborat Inc, Washington, DC 20036 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Natl Ctr Complementary & Alternat Med, Bethesda, MD USA. Duke Univ, Sch Med, Durham, NC USA. Univ Wisconsin, Madison, WI USA. Virginia Commonwealth Univ, Richmond, VA USA. NIH, Bethesda, MD 20892 USA. Creighton Univ, Omaha, NE 68178 USA. Univ Pittsburgh, Pittsburgh, PA USA. Georgetown Univ, Washington, DC USA. McMaster Univ, Hamilton, ON, Canada. RP Wittes, J (reprint author), Stat Collaborat Inc, 1625 Massachusetts Ave NW,Suite 600, Washington, DC 20036 USA. EM Janet@statcollab.com OI Dwyer, Johanna/0000-0002-0783-1769 NR 22 TC 23 Z9 23 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 EI 1740-7753 J9 CLIN TRIALS JI Clin. Trials PY 2007 VL 4 IS 3 BP 218 EP 234 DI 10.1191/1740774507079439 PG 17 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 210XP UT WOS:000249489200003 PM 17715247 ER PT J AU Tilburt, J Ford, JG Howerton, MW Gary, TL Lai, GY Bolen, S Baffi, C Wilson, RF Tanpitukpongse, TP Powe, NR Bass, EB Sugarman, J AF Tilburt, Jon Ford, Jean G. Howerton, Mollie W. Gary, Tiffany L. Lai, Gabriel Y. Bolen, Shari Baffi, Charles Wilson, Renee F. Tanpitukpongse, Teerath Peter Powe, Neil R. Bass, Eric B. Sugarman, Jeremy TI Applying justice in clinical trials for diverse populations SO CLINICAL TRIALS LA English DT Article ID DISPARITIES AB Background Considerable attention has focused on increasing clinical trial participation for members of "underrepresented groups'". However, doing so involves clarifying how to meet the demands of justice, or fairness, which provides the ethical mandate to enhance broad trial representation. Purpose To examine the ethical principle of justice as it applies to recruiting diverse populations to clinical trials representation. Methods In this paper, we analyse the conceptual and practical challenges in applying the principle of justice to clinical trials representation. Results Different facets of justice include demands for both fair outcomes and fair processes. Including both of these facets in clinical trials policy should not only promote access to trials, but also help to provide a framework to improve fairness in representation in clinical trials. Efforts to evaluate recruitment of representation should include outcome and process measures. Limitations The suggestions offered based on this conceptual analysis need to be tested empirically. Conclusions Those involved in the design, conduct and oversight of clinical trials should consider all of the facets of justice when assessing representation in clinical trials and attempt to balance fair access to trials with a fair process that may require protection from being unduly pressured to participate. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Div Gen Internal Med, Baltimore, MD USA. Johns Hopkins Univ, Berman Inst Bioeth, Baltimore, MD USA. Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. Johns Hopkins Univ, Evidence Based Practice Ctr, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Welch Ctr Prevent Epidemiol & Clin Res, Baltimore, MD USA. NCI, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. Johns Hopkins Univ, Urban Hlth Inst, Baltimore, MD USA. RP Tilburt, J (reprint author), NIH, Dept Clin Bioeth, Bldg 10,Room 1C 141, Bethesda, MD 20892 USA. EM tilburtj@cc.nih.gov NR 20 TC 5 Z9 5 U1 0 U2 2 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2007 VL 4 IS 3 BP 264 EP 269 DI 10.1177/1740774507079440 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 210XP UT WOS:000249489200009 PM 17715253 ER PT J AU Fay, MP Huang, CY Twum-Danso, NAY AF Fay, Michael P. Huang, Chiung-Yu Twum-Danso, Nona A. Y. TI Monitoring rare serious adverse events from a new treatment and testing for a difference from historical controls SO CLINICAL TRIALS LA English DT Article ID CLINICAL-TRIALS; LOA-LOA; SAMPLE-SIZE; IVERMECTIN TREATMENT; ONCHOCERCIASIS; EFFICACY; POWER; EQUIVALENCE; INFECTION; SAFETY AB Background We detail the design of a study to monitor the safety of including albendazole to an existing treatment regimen to eliminate lymphatic filariasis. We wish to show that this new regimen does not increase the rate of a rare serious adverse event (SAE) compared to the old regimen. Controlled but small clinical trials have not detected any increase in the SAE using albendazole, and it is known to have added benefits; therefore, it is unethical to randomize patients to the old regimen. Purpose A sample size for the new regimen is needed to test that the new rate of SAE is noninferior to the historic rate. If the new regimen does have an inferior rate of SAE then we wish to stop the study early. This setup is different from traditional early stopping for efficacy and futility. In that traditional case, the two stopping decisions are relative to the same null hypothesis of equality, while in our setup, we have two different null hypotheses: the noninferiority null and the equality null. When testing the former, we need not stop early if the new regimen appears better because no subjects are receiving the old regimen anymore anyway. When testing the equality of SAE rates, however, we want to stop early if the new regimen has a significantly higher rate of SAE. Methods We create a design that uses an exact difference in proportions test for testing noninferiority, but calculates maximal sample size based on conditional power which treats the historical rates as true rates. The design allows for early stopping if the new treatment appears inferior with respect to SAE rate but makes no corrections for multiple testing. We explore the properties of this naive design without assuming the historical rates are known. Results For our example, we show that our naive design strategy bounds the type I error of the noninferiority hypothesis in all cases and bounds it for the equality hypothesis at 0.05, as long as the true SAE rate is < 0.00015. The same design has unconditional power for the noninferiority hypothesis greater than the nominal 80% as long as the true SAE rate for both regimens are <0.00025. Limitations The type I and power results above hold only for our historical sample size of 17 877. We expect similar type I and power properties to hold with studies with SAE rates similar or less (i.e., < 0.00015) and historical sample sizes similar or smaller. Conclusions Our design for comparing very rare historical SAE rates to SAE rates of a new treatment has large power to conclude noninferiority of the new treatment SAE rate when both rates are equal, but allows early stopping if the new SAE rates are worse. C1 [Fay, Michael P.; Huang, Chiung-Yu] NIAID, Biostat Res Branch, Bethesda, MD 20892 USA. [Twum-Danso, Nona A. Y.] Task Force Child Survival & Dev, Decatur, GA 30030 USA. RP Fay, MP (reprint author), 6700B Rockledge Dr, Bethesda, MD 20892 USA. EM mfay@niaid.nih.gov OI Fay, Michael P./0000-0002-8643-9625 NR 29 TC 3 Z9 3 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2007 VL 4 IS 6 BP 598 EP 610 DI 10.1177/1740774507084978 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 253MH UT WOS:000252521800002 PM 18042569 ER PT J AU Murray, KF Rodrigue, JR Gonzalez-Peralta, RP Shepherd, J Barton, BA Robuck, PR Schwarz, KB AF Murray, Karen F. Rodrigue, James R. Gonzalez-Peralta, Regino P. Shepherd, John Barton, Bruce A. Robuck, Patricia R. Schwarz, Kathleen B. CA PEDS-C Clinical Res Network TI Design of the PEDS-C trial: pegylated interferon +/- ribavirin for children with chronic hepatitis C viral infection SO CLINICAL TRIALS LA English DT Article ID QUALITY-OF-LIFE; X-RAY ABSORPTIOMETRY; PLUS RIBAVIRIN; PEGINTERFERON ALPHA-2A; NUTRITIONAL-STATUS; INITIAL TREATMENT; RANDOMIZED-TRIAL; CLINICAL-TRIALS; VIRUS-INFECTION; THERAPY AB Background PEDS-C is the first multicenter placebo-controlled trial for the treatment of chronic hepatitis C (HCV) in childhood that has ever been conducted in the United States (USA). Establishment of the research team, protocol, administrative infrastructure, and ancillary contributors for the pediatric trial took years of planning. Purpose To study the safety and efficacy of pegylated-interferon alpha (PEG-2a) plus ribavirin (RV) with PEG-2a monotherapy in children aged 5 years through 18years. To assess the health-related quality of life and growth and body composition in children with chronic hepatitis C infection, before, during, and after treatment. Methods Eleven centers of pediatric hepatobiliary clinical research were united in a National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) funded grant with financial support from the Food and Drug Administration (FDA) and a corporate sponsor to conduct the treatment trial. Limitations The most important initial limitation in the design of this complex study was securing the financial support and infrastructural organization, a process that took several years. Challenges faced by the study group included identifying the optimal study design given the limited study population, and determining what ancillary studies could be incorporated into the treatment trial. Conclusions In this article the process taken to design the study and administrative infrastructure, the lessons learned, and the controversial issues deliberated during the planning process are discussed. The evolution of the study and the considerations taken in the development of the protocol are valuable tools which can be applied to pediatric clinical trials in general. C1 [Murray, Karen F.] Univ Washington, Childrens Hosp & Reg Med Ctr, Dept Pediat, Div Gastroenterol & Nutr, Seattle, WA 98105 USA. [Rodrigue, James R.] Beth Israel Deaconess Med Ctr, Transplant Ctr, Boston, MA 02215 USA. [Gonzalez-Peralta, Regino P.] Univ Florida, Dept Pediat, Sect Hepatol & Liver Transplantat, Gainesville, FL USA. [Shepherd, John] Univ Calif San Francisco, Dept Radiol, San Francisco, CA 94143 USA. [Barton, Bruce A.] Maryland Med Res Inst, Baltimore, MD USA. [Robuck, Patricia R.] NIDDKD, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. [Schwarz, Kathleen B.] Johns Hopkins Univ, Sch Med, Div Pediat Gastroenterol & Nutr, Baltimore, MD USA. RP Murray, KF (reprint author), Univ Washington, Childrens Hosp & Reg Med Ctr, Dept Pediat, Div Gastroenterol & Nutr, 4800 Sand Point Way,NE POB 5371,Mail Stop A5950, Seattle, WA 98105 USA. EM Karen.murray@seattlechildrens.org OI Barton, Bruce/0000-0001-7878-8895 FU NCRR NIH HHS [5-M01-RR-000240, 5-M01-RR-020359-01, M01 RR000037, M01 RR000069, M01 RR000082, M01 RR000240, M01 RR000645, M01 RR000750, M01 RR001271, M01 RR002172, M01 RR008084, M01 RR020359, M01-RR-00037, M01-RR-00069, M01-RR-00082, M01-RR-00645, M01-RR-00750, M01-RR-01271, M01-RR-02172, M01-RR-08084]; NIDDK NIH HHS [U01 DK067767-02, 1U01DK067767-01, U01 DK067767, U01 DK067767-01, U01 DK067767-03, U01-DK-067767-02] NR 53 TC 20 Z9 21 U1 0 U2 4 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2007 VL 4 IS 6 BP 661 EP 673 DI 10.1177/1740774507085445 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 253MH UT WOS:000252521800008 PM 18042575 ER PT J AU Apud, JA Weinberger, DR AF Apud, Jose A. Weinberger, Daniel R. TI Treatment of cognitive deficits associated with schizophrenia - Potential role of catechol-O-methyltransferase inhibitors SO CNS DRUGS LA English DT Review ID MEDIAL PREFRONTAL CORTEX; CEREBRAL-BLOOD-FLOW; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; MESOCORTICAL DOPAMINE NEURONS; SELECTIVE COMT INHIBITORS; VAL(108/158) MET GENOTYPE; WORKING-MEMORY DEFICITS; IBOTENIC ACID LESIONS; CARD SORTING TEST; PARKINSONS-DISEASE AB In the last two decades, understanding of the dynamics of dopamine function in the prefrontal cortex and its role in prefrontal cortex physiology has opened up new avenues for therapeutic interventions in conditions in which prefrontal cortex function is compromised. Neuropsychological and imaging studies of prefrontal information processing have confirmed specific cognitive and neurophysiological abnormalities in individuals with schizophrenia. Because such findings are also observed in the healthy siblings of patients with schizophrenia, they may represent intermediate phenotypes related to schizophrenia susceptibility genes. Catechol-O-methyltransferase (COMT) represents an important candidate as a susceptibility gene for cognitive dysfunction in schizophrenia because of the unique role this enzyme plays in regulating prefrontal dopaminergic function. A functional COMT polymorphism (Val158Met) predicts performance in tasks of prefrontal executive function and the neurophysiological response measured with electroencephalography and functional magnetic resonance imaging in tasks assessing working memory. In fact, individuals with the Val/Val genotype, which encodes for the high-activity enzyme resulting in lower dopamine concentrations in the prefrontal cortex, perform less well and are less efficient physiologically than Met/Met individuals. These findings raise the possibility of new pharmacological interventions for the treatment of prefrontal cortex dysfunction and of predicting outcome based on COMT genotype. One strategy consists of the use of CNS-penetrant COMT inhibitors such as tolcapone. A second strategy is to increase extracellular dopamine concentrations in the frontal cortex by blocking the noradrenaline (norepinephrine) reuptake system, a secondary mechanism responsible for the disposal of dopamine from synaptic clefts in the prefrontal cortex. A third possibility involves the use of modafinil, a drug with an unclear mechanism of action but with positive effects on working memory in rodents. The potential of these drugs to improve executive cognitive function by selectively increasing dopamine load in the frontal cortex but not in subcortical territories, and the possibility that response to them may be modified by a COMT polymorphism, provides a novel genotype-based targeted pharmacological approach without abuse potential for the treatment of cognitive disorder in schizophrenia and in other conditions involving prefrontal cortex dysfunction. C1 NIMH, NIH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, Bethesda, MD 20892 USA. RP Apud, JA (reprint author), NIMH, NIH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, 10 Ctr Dr,CRC 7-3342, Bethesda, MD 20892 USA. EM apudj@mail.nih.gov NR 192 TC 49 Z9 49 U1 1 U2 8 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 1172-7047 J9 CNS DRUGS JI CNS Drugs PY 2007 VL 21 IS 7 BP 535 EP 557 DI 10.2165/00023210-200721070-00002 PG 23 WC Clinical Neurology; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 197BT UT WOS:000248529000002 PM 17579498 ER PT S AU Conforti, PF Yingling, YG Garrison, BJ AF Conforti, P. F. Yingling, Y. G. Garrison, B. J. BE Hess, WP Herman, PR Bauerle, D Koinuma, H TI Computational studies of ultraviolet ablation of poly(methyl methacrylate) SO COLA'05: 8TH INTERNATIONAL CONFERENCE ON LASER ABLATION SE Journal of Physics Conference Series LA English DT Proceedings Paper CT 8th International Conference on Laser Ablation CY SEP 11-16, 2005 CL Banff, CANADA ID LASER-ABLATION; MODEL; DEGRADATION; INCUBATION; POLYMERS AB The results from our recent molecular dynamics and electronic calculations studies of the interaction of ultraviolet light with poly(methyl methacrylate) are discussed. Molecular dynamics simulations in the photochemical and photothermal. regimes demonstrate the delayed onset of ablation due to the slow pressure relaxation in the polymeric material. Electronic structure calculations show the possible wavelength-dependent pathways of exothermic and endothermic release of gaseous and small molecules which could induce the ablation process. The results from our studies are the centerpiece for the current development of the mesoscale model of the light irradiation of polymeric material. C1 [Conforti, P. F.; Garrison, B. J.] Penn State Univ, Dept Chem, University Pk, PA 16802 USA. [Yingling, Y. G.] NIH, NCI, Ctr Canc Res Nanobiol Program, Frederick, MD 21702 USA. RP Conforti, PF (reprint author), Penn State Univ, Dept Chem, University Pk, PA 16802 USA. EM pfc112@psu.edu RI Yingling, Yaroslava/B-2901-2008; Garrison, Barbara/P-1807-2014 OI Yingling, Yaroslava/0000-0002-8557-9992; Garrison, Barbara/0000-0002-7053-5284 FU National Science Foundation; US Air Force Office of Scientific Research FX The authors acknowledge funding from the National Science Foundation through the Information Technology and Research program and the US Air Force Office of Scientific Research through the MultiUniversity Research Initiative. Computer support was provided by the Academic Services and Emerging Technologies at Penn State University. NR 26 TC 2 Z9 2 U1 0 U2 0 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1742-6588 J9 J PHYS CONF SER PY 2007 VL 59 BP 322 EP + DI 10.1088/1742-6596/59/1/068 PG 2 WC Optics SC Optics GA BGP13 UT WOS:000249266200068 ER PT J AU Schisterman, EF Perkins, N AF Schisterman, Enrique F. Perkins, Neil TI Confidence intervals for the Youden index and corresponding optimal cut-point SO COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION LA English DT Article DE confidence intervals; optimal cut-point; ROC curve; sensitivity and specificity; Youden index ID MEASUREMENT ERROR; CURVE; AREA AB A global measure of biomarker effectiveness is the Youden index, the maximum difference between sensitivity, the probability of correctly classifying diseased individuals, and 1-specificity, the probability of incorrectly classifying healthy individuals. The cut-point leading to the index is the optimal cut-point when equal weight is given to sensitivity and specificity. Using the delta method, we present approaches for estimating confidence intervals for the Youden index and corresponding optimal cut-point for normally distributed biomarkers and also those following gamma distributions. We also provide confidence intervals using various bootstrapping methods. A comparison of interval width and coverage probability is conducted through simulation over a variety of parametric situations. Confidence intervals via delta method are shown to have both closer to nominal coverage and shorter interval widths than confidence intervals from the bootstrapping methods. C1 NICHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. American Univ, Dept Math & Stat, Washington, DC 20016 USA. RP Schisterman, EF (reprint author), NICHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, 6100 Execut Blvd,7B03, Rockville, MD 20852 USA. EM schistee@mail.nih.gov OI Perkins, Neil/0000-0002-6802-4733; Schisterman, Enrique/0000-0003-3757-641X NR 15 TC 31 Z9 31 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-0918 J9 COMMUN STAT-SIMUL C JI Commun. Stat.-Simul. Comput. PY 2007 VL 36 IS 3 BP 549 EP 563 DI 10.1080/03610910701212181 PG 15 WC Statistics & Probability SC Mathematics GA 176NK UT WOS:000247091800008 ER PT J AU Rotimi, C Leppert, M Matsuda, I Zeng, C Zhang, H Adebamowo, C Ajayi, I Aniagwu, T Dixon, M Fukushima, Y Macer, D Marshall, P Nkwodimmah, C Peiffer, A Royal, C Suda, E Zhao, H Wang, VO McEwen, J AF Rotimi, Charles Leppert, Mark Matsuda, Ichiro Zeng, Changqing Zhang, Houcan Adebamowo, Clement Ajayi, Ike Aniagwu, Toyin Dixon, Missy Fukushima, Yoshimitsu Macer, Darryl Marshall, Patricia Nkwodimmah, Chibuzor Peiffer, Andy Royal, Charmaine Suda, Eiko Zhao, Hui Wang, Vivian Ota McEwen, Jean CA Internatl HapMap Consortium TI Community engagement and informed consent in the international HapMap project SO COMMUNITY GENETICS LA English DT Article DE community engagement; community consultation; public consultation; informed consent; international HapMap project; genetic variation research AB The International HapMap Consortium has developed the HapMap, a resource that describes the common patterns of human genetic variation (haplotypes). Processes of community/public consultation and individual informed consent were implemented in each locality where samples were collected to understand and attempt to address both individual and group concerns. Perceptions about the research varied but we detected no critical opposition to the research. Incorporating community input and responding to concerns raised was challenging. However, the experience suggests that approaching genetic variation research in a spirit of openness can help investigators better appreciate the views of the communities whose samples they seek to study and help communities become more engaged in the science. Copyright (c) 2007 S. Karger AG, Basel. C1 NHGRI, US NIH, Bethesda, MD 20892 USA. Univ Utah, Dept Human Genet, Salt Lake City, UT USA. Howard Univ, Natl Human Genome Ctr, Washington, DC USA. Case Western Reserve Univ, Sch Med, Dept Bioeth, Cleveland, OH USA. Shinshu Univ, Sch Med, Dept Med Genet, Matsumoto, Nagano, Japan. Univ Tsukuba, Eubios Eth Inst, Tsukuba, Ibaraki 305, Japan. Chinese Acad Sci, Beijing Genom Inst, Beijing, Peoples R China. Beijing Normal Univ, Beijing 100875, Peoples R China. Univ Ibadan, Coll Med, Ibadan, Nigeria. UNESCO, Bangkok, Thailand. RP McEwen, J (reprint author), NHGRI, US NIH, 5635 Fishers Lane,Suite 4076, Bethesda, MD 20892 USA. EM mcewenj@mail.nih.gov OI Adebamowo, Clement/0000-0002-6571-2880 FU Wellcome Trust NR 20 TC 33 Z9 34 U1 0 U2 5 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1422-2795 J9 COMMUNITY GENET JI Community Genet. PY 2007 VL 10 IS 3 BP 186 EP 198 DI 10.1159/000101761 PG 13 WC Genetics & Heredity; Public, Environmental & Occupational Health SC Genetics & Heredity; Public, Environmental & Occupational Health GA 181GM UT WOS:000247425200009 PM 17575464 ER PT J AU Field, D Garrity, G Gray, T Selengut, J Sterk, P Thomson, N Tatusova, T Cochrane, G Glockner, FO Kottmann, R Lister, AL Tateno, Y Vaughan, R AF Field, Dawn Garrity, George Gray, Tanya Selengut, Jeremy Sterk, Peter Thomson, Nick Tatusova, Tatiana Cochrane, Guy Gloeckner, Frank Oliver Kottmann, Renzo Lister, Allyson L. Tateno, Yoshio Vaughan, Robert TI eGenomics: Cataloguing our complete genome collection III SO COMPARATIVE AND FUNCTIONAL GENOMICS LA English DT Editorial Material AB This meeting report summarizes the proceedings of the "eGenomics: Cataloguing our Complete Genome Collection III" workshop held September 11 - 13, 2006, at the National Institute for Environmental eScience (NIEeS), Cambridge, United Kingdom. This 3rd workshop of the Genomic Standards Consortium was divided into two parts. The first half of the three-day workshop was dedicated to reviewing the genomic diversity of our current and future genome andmetagenome collection, and exploring linkages to a series of existing projects through formal presentations. The second half was dedicated to strategic discussions. Outcomes of the workshop include a revised "Minimum Information about a Genome Sequence" (MIGS) specification (v1.1), consensus on a variety of features to be added to the Genome Catalogue (GCat), agreement by several researchers to adopt MIGS for imminent genome publications, and an agreement by the EBI and NCBI to input their genome collections into GCat for the purpose of quantifying the amount of optional data already available (e. g., for geographic location coordinates) and working towards a single, global list of all public genomes and metagenomes. Copyright (c) 2007 Dawn Field et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. C1 Oxford Ctr Ecol & Hydrol, Mol Evolut & Bioinformat Sect, Oxford OX1 3SR, England. Michigan State Univ, Dept Microbiol & Mol Genet, E Lansing, MI 48824 USA. Inst Genom Res, Rockville, MD 20850 USA. European Mol Biol Lab, European Bioinformat Inst, Cambridge CB10 1SD, England. Wellcome Trust Sanger Inst, Pathogen Sequencing Unit, Cambridge CB10 1SA, England. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Max Planck Inst Marine Microbiol, Microbial Genom Grp, D-28359 Bremen, Germany. Int Univ Bremen, D-28359 Bremen, Germany. Univ Newcastle Upon Tyne, CISBAN, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Univ Newcastle Upon Tyne, Sch Comp Sci, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Natl Inst Genet, Res Org Informat & Syst, Ctr Informat Biol, Shizuoka 4418540, Japan. Natl Inst Genet, Res Org Informat & Syst, DNA Data Bank Japan, Shizuoka 4418540, Japan. RP Field, D (reprint author), Oxford Ctr Ecol & Hydrol, Mol Evolut & Bioinformat Sect, Mansfield Rd, Oxford OX1 3SR, England. RI Field, Dawn/C-1653-2010; Garrity, George/F-7551-2013; Smith, Barry/A-9525-2011; OI Garrity, George/0000-0002-4465-7034; Smith, Barry/0000-0003-1384-116X; Gray, Tanya/0000-0003-1561-7364; Lister, Allyson/0000-0002-7702-4495; Sterk, Peter/0000-0003-1668-7778 NR 16 TC 2 Z9 2 U1 0 U2 0 PU HINDAWI PUBLISHING CORPORATION PI NEW YORK PA 410 PARK AVENUE, 15TH FLOOR, #287 PMB, NEW YORK, NY 10022 USA SN 1531-6912 J9 COMP FUNCT GENOM JI Compar. Funct. Genom. PY 2007 BP 1 EP 7 DI 10.1155/2007/47304 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 183ST UT WOS:000247593200001 ER PT S AU Zheng, J Rogozin, IB Koonin, EV Przytycka, TM AF Zheng, Jie Rogozin, Igor B. Koonin, Eugene V. Przytycka, Teresa M. BE Tesler, G Durand, D TI A rigorous analysis of the pattern of intron conservation supports the Coelomata clade of animals SO COMPARATIVE GENOMICS, PROCEEDINGS SE Lecture Notes in Bioinformatics LA English DT Proceedings Paper CT 5th RECOMB International Workshop on Comparative Genomics CY SEP 16-18, 2007 CL San Diego, CA ID PHYLOGENETIC ANALYSIS; MODEL ORGANISMS; GENOME TREES; EVOLUTION; ECDYSOZOA; SEQUENCES; RECONSTRUCTION; ARTHROPODS; NEMATODES; GAIN AB Many intron positions are conserved in varying subsets of eukaryotic genomes and, consequently, comprise a potentially informative class of phylogenetic characters. Roy and Gilbert developed a method of phylogenetic reconstruction using the patterns of intron presence-absence in eukaryotic genes and, applying this method to the analysis of animal phylogeny, obtained support for an Ecdysozoa clade ((11). The critical assumption in the method was the independence of the rates of intron loss in different branches of the phylogenetic. Here, this assumption is refuted by showing that the branch-specific intron loss rates are strongly correlated. We show that different tree topologies are obtained, in each case with a significant statistical support, when different subsets of intron positions are analyzed. The analysis of the conserved intron positions supports the Coelomata topology, i.e., a clade comprised of arthropods and chordates, whereas the analysis of more variable intron positions favors the Ecdysozoa topology, i.e., a clade of arthropods and nematodes. We show, however, that the support for Ecdysozoa is fully explained by parallel loss of introns in nematodes and arthropods, a factor that does not contribute to the analysis of the conserved introns. The developed procedure for the identification and analysis of conserved introns and other characters with minimal or no homoplasy is expected to be useful for resolving many hard phylogenetic problems. C1 [Zheng, Jie; Rogozin, Igor B.; Koonin, Eugene V.; Przytycka, Teresa M.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20894 USA. EM zhengj@ncbi.nlm.nih.gov; rogozin@ncbi.nlm.nih.gov; koonin@ncbi.nlm.nih.gov; przytyck@ncbi.nlm.nih.gov RI Zheng, Jie/C-1356-2011 OI Zheng, Jie/0000-0001-6774-9786 FU Intramural Research Program of the NIH; National Library of Medicine FX This research was supported by the Intramural Research Program of the NIH, National Library of Medicine. The authors would like to thank Yuri I. Wolf for valuable discussions. NR 60 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0302-9743 BN 978-3-540-74959-2 J9 LECT N BIOINFORMAT JI Lect. Notes Bioinforma. PY 2007 VL 4751 BP 177 EP + PG 4 WC Computer Science, Information Systems; Genetics & Heredity SC Computer Science; Genetics & Heredity GA BGQ43 UT WOS:000249740900014 ER PT S AU Tilburt, J AF Tilburt, Jon BE Snyder, L TI Whose Evidence, Which Methods? Ethical Challenges in Complementary and Alternative Medicine Research SO COMPLEMENTARY AND ALTERNATIVE MEDICINE: ETHICS, THE PATIENT, AND THE PHYSICIAN SE Biomedical Ethics Reviews LA English DT Article; Book Chapter ID INTEGRATIVE MEDICINE; CLINICAL-RESEARCH; DECISION-MAKING; UNITED-STATES; HEALTH-CARE; PLACEBO; TRIALS; PERSPECTIVE; VARIETIES; PLURALISM C1 [Tilburt, Jon] Johns Hopkins, Johns Hopkins Complementary & Alternat Med Ctr, Baltimore, MD 21218 USA. [Tilburt, Jon] NIH, Dept Clin Bioeth, Bethesda, MD USA. RP Tilburt, J (reprint author), Johns Hopkins, Johns Hopkins Complementary & Alternat Med Ctr, Baltimore, MD 21218 USA. NR 46 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 0742-1796 BN 978-1-59745-381-3 J9 BIOMED ETHICS REV PY 2007 BP 201 EP 230 DI 10.1007/978-1-59745-381-3_7 D2 10.1007/978-1-59745-381-3 PG 30 WC Integrative & Complementary Medicine; Medical Ethics SC Integrative & Complementary Medicine; Medical Ethics GA BLY58 UT WOS:000271450100008 ER PT B AU Hallett, M Bai, O AF Hallett, Mark Bai, Ou BE Wu, LJ Ito, K Tobimatsu, S Nishida, T Fukuyama, H TI Predicting motor intention SO COMPLEX MEDICAL ENGINEERING LA English DT Proceedings Paper CT 1st International Conference on Complex Medical Engineering (CME2005) CY 2005 CL Takamatsu, JAPAN DE voluntary movement; EEG; Bereitschaftspotential; event-related desynchronization; intention ID VOLUNTARY; POTENTIALS; MOVEMENT; INITIATION; ACTS; EEG; HZ AB People have the perception that prior to making a voluntary movement, there is an intention to move. This subjective impression has been measured objectively using Libet's clock and is on average about 300 ms prior to EMG onset. The EEG shows activity prior to movement, and by the voltage measurement, there is a rising negativity called the Bereitschaftspotential beginning about 1.5 s prior to EMG onset. This indicates that the brain mechanisms for generating a voluntary movement begin prior to the subjective intention, that is, unconsciously. If it were possible to detect relevant EEG signals with single events in real time, then it would be possible to identify that movement is being prepared prior to the subjective experience. Work in our laboratory has been making progress in accomplishing this aim. Such a signal could also be used to drive a brain-computer interface. C1 [Hallett, Mark; Bai, Ou] NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 10 TC 2 Z9 2 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-4-431-30961-1 PY 2007 BP 439 EP + DI 10.1007/978-4-431-30962-8_38 PG 3 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Robotics; Rehabilitation SC Computer Science; Engineering; Robotics; Rehabilitation GA BFU94 UT WOS:000244738800038 ER PT B AU Nishida, S Nakamura, M Ikeda, A Nagamine, T Shibasaki, H AF Nishida, Shigeto Nakamura, Masatoshi Ikeda, Akio Nagamine, Takashi Shibasaki, Hiroshi BE Wu, LJ Ito, K Tobimatsu, S Nishida, T Fukuyama, H TI Time series of awake background EEG generated by a model reflecting the EEG report SO COMPLEX MEDICAL ENGINEERING LA English DT Proceedings Paper CT 1st International Conference on Complex Medical Engineering (CME2005) CY 2005 CL Takamatsu, JAPAN DE awake background EEG; model construction; EEG report; EEG interpretation ID AUTOMATIC INTEGRATIVE INTERPRETATION; SYSTEM AB Awake background electroencephalogram (EEG) is interpreted by electroencephalographer (EEGer), and the results of EEG interpretation are described in EEG reports. Desired EEG reports should include enough information so that the time series of the raw EEG can be imagined from them. Then, it is important to know how much information about the characteristics of EEG is included in the report. In this study, a method for constructing an EEG model, which reflects the EEG report is proposed. First, EEG parameters for EEG interpretation items are determined based on EEGer's report, then the model parameters are calculated from the determined EEG parameters. The proposed models were constructed from the EEG reports of 7 subjects. The time series of the constructed models were visually evaluated by the EEGer, and satisfactory results were obtained. The information included in the EEG report can be represented through the time series of the model constructed by the proposed method. The proposed method can be utilized for the training of EEG report making. C1 [Nishida, Shigeto] Fukuoka Inst Technol, Dept Comp & Commun Engn, Fukuoka, Japan. [Nakamura, Masatoshi] Saga Univ, Dept Adv Syst Control Engn, Saga, Japan. [Ikeda, Akio] Kyoto Univ, Grad Sch Med, Dept Neurol, Kyoto, Japan. [Nagamine, Takashi] Kyoto Univ, Grad Sch Med, Human Brain Res Ctr, Kyoto, Japan. [Shibasaki, Hiroshi] Natl Inst Hlth, Natl Inst Neurol Disorders & Stroke, Washington, DC USA. RP Nishida, S (reprint author), Fukuoka Inst Technol, Dept Comp & Commun Engn, Fukuoka, Japan. NR 6 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-4-431-30961-1 PY 2007 BP 489 EP + DI 10.1007/978-4-431-30962-8_43 PG 2 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Robotics; Rehabilitation SC Computer Science; Engineering; Robotics; Rehabilitation GA BFU94 UT WOS:000244738800043 ER PT S AU Rybak, IA Abdala, APL Markin, SN Paton, JFR Smith, JC AF Rybak, Ilya A. Abdala, Ana P. L. Markin, Sergey N. Paton, Julian F. R. Smith, Jeffrey C. BE Cisek, P Drew, T Kalaska, JF TI Spatial organization and state-dependent mechanisms for respiratory rhythm and pattern generation SO COMPUTATIONAL NEUROSCIENCE: THEORETICAL INSIGHTS INTO BRAIN FUNCTION SE Progress in Brain Research LA English DT Review; Book Chapter DE respiratory CPG; brainstem; medulla; pons; pre-Botzinger complex; computational modeling; respiratory rhythm generation ID PRE-BOTZINGER COMPLEX; MODELING NEURAL MECHANISMS; BRAIN-STEM; PACEMAKER NEURONS; PERSISTENT SODIUM; IN-VITRO; RAT; CURRENTS; NETWORK; GENESIS AB The brainstem respiratory network can operate in multiple functional states engaging different state-dependent neural mechanisms. These mechanisms were studied in the in situ perfused rat brain-stem-spinal cord preparation using sequential brainstem transections and administration of riluzole, a pharmacological blocker of persistent sodium current (I(NaP)). Dramatic transformations in the rhythmogenic mechanisms and respiratory motor pattern were observed after removal of the pons and subsequent medullary transactions down to the rostral end of pre-Botzinger complex (pre-BotC). A computational model of the brainstem respiratory network was developed to reproduce and explain these experimental findings. The model incorporates several interacting neuronal compartments, including the ventral respiratory group (VRG), pre-BotC, Botzinger complex (BotC), and pons. Simulations mimicking the removal of circuit components following transections closely reproduce the respiratory motor output patterns recorded from the intact and sequentially reduced brainstem preparations. The model suggests that both the operating rhythmogenic mechanism (i.e., network-based or pacemaker-driven) and the respiratory pattern generated (e.g., three-phase, two-phase, or one-phase) depend on the state of the pre-BotC (expression of I(NaP)-dependent intrinsic rhythmogenic mechanisms) and the BotC (providing expiratory inhibition in the network). At the same time, tonic drives from pons and multiple medullary chemoreceptive sites appear to control the state of these compartments and hence the operating rhythmogenic mechanism and motor pattern. Our results suggest that the brainstem respiratory network has a spatial (rostral-to-caudal) organization extending from the rostral pons to the VRG, in which each functional compartment is controlled by more rostral compartments. The model predicts a continuum of respiratory network states relying on different contributions of intrinsic cellular properties versus synaptic interactions for the generation and control of the respiratory rhythm and pattern. C1 [Rybak, Ilya A.; Markin, Sergey N.] Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA. [Abdala, Ana P. L.; Paton, Julian F. R.] Univ Bristol, Sch Med Sci, Dept Physiol, Bristol BS8 1TD, Avon, England. [Smith, Jeffrey C.] NINDS, Cellular & Syst Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Rybak, IA (reprint author), Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA. EM rybak@drexel.edu RI Abdala, Ana Paula/G-9104-2014; OI Abdala, Ana Paula/0000-0001-6051-2591; Paton, Julian/0000-0001-7410-2913 FU Intramural NIH HHS; NINDS NIH HHS [R01 NS048844, R01 NS048844-01A2, R01 NS048844-02, R01 NS057815, R01 NS057815-01, R01 NS057815-02] NR 46 TC 80 Z9 82 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0079-6123 BN 978-0-444-52823-0 J9 PROG BRAIN RES JI Prog. Brain Res. PY 2007 VL 165 BP 201 EP 220 DI 10.1016/S0079-6123(06)65013-9 PG 20 WC Mathematical & Computational Biology; Neurosciences SC Mathematical & Computational Biology; Neurosciences & Neurology GA BQC07 UT WOS:000280608900014 PM 17925248 ER EF