FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Trimble, EL Christian, MC AF Trimble, EL Christian, MC TI Cancer treatment and the older patient SO CLINICAL CANCER RESEARCH LA English DT Editorial Material ID CLINICAL-TRIALS; ADJUVANT CHEMOTHERAPY; OVARIAN-CANCER; UNITED-STATES; COLON-CANCER; AGE; PATTERNS; PARTICIPATION; PERSPECTIVES; EXPERIENCE C1 NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, NIH, Bethesda, MD 20892 USA. RP Trimble, EL (reprint author), NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, NIH, Room 741,MSC 7436,6130 Execut Blvd, Bethesda, MD 20892 USA. EM trimblet@ctep.nci.nih.gov NR 25 TC 6 Z9 9 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2006 VL 12 IS 7 BP 1956 EP 1957 DI 10.1158/1078-0432.CCR-06-0364 PN 1 PG 2 WC Oncology SC Oncology GA 034BI UT WOS:000236899000004 PM 16609002 ER PT J AU Gray, R Manola, J Saxman, S Wright, J Dutcher, J Atkins, M Carducci, M See, W Sweeney, C Liu, G Stein, M Dreicer, R Wilding, G DiPaola, RS AF Gray, R Manola, J Saxman, S Wright, J Dutcher, J Atkins, M Carducci, M See, W Sweeney, C Liu, G Stein, M Dreicer, R Wilding, G DiPaola, RS TI Phase II clinical trial design: Methods in translational research from the Genitourinary Committee at the Eastern Cooperative Oncology Group SO CLINICAL CANCER RESEARCH LA English DT Article ID RANDOMIZED DISCONTINUATION DESIGN; CANCER; CETUXIMAB; AGENTS; NECK; HEAD AB Given the increase in novel agents and difficulty with planning and completing many phase III studies, various phase II trial design options should be considered to more effectively guide phase III trial plans. The need for novel phase II trial designs has increased, given the number of novel molecular targeted therapies now available for testing, an abundance of cytostatic agents, and limited resources to conduct phase III studies for all interesting agents or combinations. This review will focus on options for phase II trial designs. We review randomized phase II designs with placebo control, randomized selection designs, and randomized discontinuation designs. As agents become available for testing in the clinic, the strengths and weaknesses of different phase II trial designs should be considered to optimize a trial development plan that guides phase III trial decisions more effectively. C1 Univ Med & Dent New Jersey, Canc Inst New Jersey, New Brunswick, NJ 08901 USA. Harvard Univ, Sch Publ Hlth, Eastern Cooperat Oncol Grp, Boston, MA 02115 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Our Lady Mercy, Bronx, NY USA. Johns Hopkins Univ, Baltimore, MD USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Indiana Univ, Bloomington, IN USA. Univ Wisconsin, Ctr Comprehens Canc, Madison, WI USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. RP DiPaola, RS (reprint author), Univ Med & Dent New Jersey, Canc Inst New Jersey, 195 Little Albany St, New Brunswick, NJ 08901 USA. EM dipaolrs@umdnj.edu NR 13 TC 18 Z9 18 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2006 VL 12 IS 7 BP 1966 EP 1969 DI 10.1158/1078-0432.CCR-05-1136 PN 1 PG 4 WC Oncology SC Oncology GA 034BI UT WOS:000236899000007 PM 16609005 ER PT J AU Sabichi, AL Lee, JJ Taylor, RJ Thompson, IM Miles, BJ Tangen, CM Minasian, LM Pisters, LL Caton, JR Basler, JW Lerner, SP Menter, DG Marshall, JR Crawford, ED Lippman, SM AF Sabichi, AL Lee, JJ Taylor, RJ Thompson, IM Miles, BJ Tangen, CM Minasian, LM Pisters, LL Caton, JR Basler, JW Lerner, SP Menter, DG Marshall, JR Crawford, ED Lippman, SM TI Selenium accumulation in prostate tissue during a randomized, controlled short-term trial of l-selenomethionine: a Southwest Oncology Group study SO CLINICAL CANCER RESEARCH LA English DT Article ID CANCER PREVENTION; THIOREDOXIN REDUCTASE; PROSPECTIVE COHORT; SUBSEQUENT RISK; CELL-CYCLE; SUPPLEMENTATION; CARCINOMA; LEVEL; CHEMOPREVENTION; SELENOPROTEINS AB Purpose: Epidemiologic and clinical data suggest that selenium could prevent prostate cancer, but it has not been shown that supplemental selenium leads to an increased concentration of selenium in prostate tissue compared with adjacent tissue Experimental Design. We conducted a randomized, controlled, short-term trial of I-selenomethionine (SeMet) versus observation in men with organ-confined prostate cancer The primary endpoint was the measurement of selenium concentration in prostate tissue and seminal vesicle (SV). We assessed baseline selenium levels in serum and in toenail specimens (reflecting long-term intake) and post-intervention selenium levels in serum, and in prostate and SV tissues using hydride generation atomic fluorescence spectroscopy. Results: Sixty-six eligible patients were randomly assigned to the SeMet (n = 34) or observation (n = 32) arm; both arms had similar baseline patient characteristics Baseline serum selenium was similar in the two groups (P = 0.64). Baseline toenail selenium levels were slightly higher in the SeMet group than in the control group (P = 0.07). After the intervention, the mean serum selenium level increased 15% in the SeMet arm and was higher than in the observation arm (P = 0.001). The selenium concentration in prostate tissue was 22% higher in the SeMet arm (n = 26) than in the observation arm (n = 25; 1.80 versus 147 ppm; P = 0.003, Wilcoxon rank sum test) and remained significantly higher after adjusting for chronic selenium intake (P = 0.021, ANCOVA). SV selenium concentration was similar in both groups (P = 0.384) and was lower than in prostate tissue. Conclusions: The present study is the first to show that selenium taken as oral supplementation accumulates preferentially in the human prostate gland as opposed to the SV. These findings support the hypothesis that oral selenium supplementation may contribute to the cancer preventive effects of selenium. C1 Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77230 USA. Baylor Coll Med, Houston, TX 77030 USA. Texas A&M Univ, College Stn, TX USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX USA. Wilford Hall USAF Med Ctr, Brooke Army Med Ctr, San Antonio, TX 78236 USA. SW Oncol Grp, Ctr Stat, Seattle, WA USA. Natl Canc Inst Hlth, Bethesda, MD USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Sabichi, AL (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, 1515 Holcombe Blvd,POB 301439,Unit 1360, Houston, TX 77230 USA. EM asabichi@mdanderson.org FU NCI NIH HHS [CA42777, CA105409, CA22433, CA37429, CA76447]; NIEHS NIH HHS [5 P30 ES07784] NR 41 TC 29 Z9 30 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR 1 PY 2006 VL 12 IS 7 BP 2178 EP 2184 DI 10.1158/1078-0432.CCR-05-0937 PN 1 PG 7 WC Oncology SC Oncology GA 034BI UT WOS:000236899000034 PM 16609032 ER PT J AU McCann, E Fryer, AE Craigie, R Baillie, C Ba'ath, ME Selby, A Blesecker, LG AF McCann, Emma Fryer, Alan E. Craigie, Ross Baillie, Colin Ba'ath, Muhammed E. Selby, Andrew Blesecker, Leslie G. TI Genitourinary malformations as a feature of the Pallister-Hall syndrome SO CLINICAL DYSMORPHOLOGY LA English DT Article DE GL13; hydrometrocolpos; hypothalamic hamartoma; McKusick-Kaufman; Pallister-Hall ID KAUFMAN SYNDROME; SONIC HEDGEHOG; HYDROMETROCOLPOS; HYPOPITUITARISM; MUTATIONS; ANOMALIES; DISEASE AB Pallister-Hall and McKusick-Kaufman syndromes are developmental disorders with well defined phenotypes, distinct loci and different patterns of inheritance. The clinical features can overlap and may cause diagnostic difficulty, particularly if complex genitourinary malformations are present. A case is presented with features of both syndromes but in which a GL13 mutation has been identified. A literature review of similar cases is presented and it is proposed that these cases probably represent the Pallister-Hall syndrome. A detailed abdominal and perineal examination should be considered in all female patients with the Pallister-Hall syndrome, looking for associated genitourinary anomalies. Conversely, all girls with features suggestive of McKusick-Kaufman syndrome require neuroimaging to look for features of the Pallister-Hall syndrome. The correct diagnosis is important so that the patient and the family may receive appropriate management. It also allows provision for an accurate recurrence risk. C1 [McCann, Emma; Fryer, Alan E.] Royal Liverpool Childrens Hosp, Dept Clin Genet, Liverpool L12 2AP, Merseyside, England. [Craigie, Ross; Baillie, Colin; Ba'ath, Muhammed E.] Royal Liverpool Childrens Hosp, Dept Paediat Surg, Liverpool L12 2AP, Merseyside, England. [Selby, Andrew] Royal Liverpool Childrens Hosp, Dept Paediat Intens Care, Liverpool L12 2AP, Merseyside, England. [Blesecker, Leslie G.] Natl Inst Hlth, NHGRI, Bethesda, MD USA. RP McCann, E (reprint author), Royal Liverpool Childrens Hosp, Dept Clin Genet, Liverpool L12 2AP, Merseyside, England. EM emma.mccann@rlc.nhs.uk NR 19 TC 5 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0962-8827 J9 CLIN DYSMORPHOL JI Clin. Dysmorphol. PD APR PY 2006 VL 15 IS 2 BP 75 EP 79 DI 10.1097/01.mcd.0000184972.76657.e1 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 248LL UT WOS:000252154700005 PM 16531732 ER PT J AU Holleran, WM Ziegler, SG Goker-Alpan, O Eblan, MJ Elias, PM Schiffmann, R Sidransky, E AF Holleran, WM Ziegler, SG Goker-Alpan, O Eblan, MJ Elias, PM Schiffmann, R Sidransky, E TI Skin abnormalities as an early predictor of neurologic outcome in Gaucher disease SO CLINICAL GENETICS LA English DT Letter ID PHENOTYPE; THERAPY; TYPE-1 C1 NHGRI, Sect Mol Neurogenet, Med Genet Branch, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Med, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Univ Calif San Francisco, Sch Pharm, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NHGRI, Sect Mol Neurogenet, Med Genet Branch, Bldg 35,Room 1A213,35 Convent Dr,MSC 3708, Bethesda, MD 20892 USA. EM sidranse@mail.nih.gov FU Intramural NIH HHS; NIAMS NIH HHS [P01-AR39448] NR 13 TC 12 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD APR PY 2006 VL 69 IS 4 BP 355 EP 357 DI 10.1111/j.1399-0004.2006.00589.x PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 027DI UT WOS:000236393500009 PM 16630170 ER PT J AU Brown-Elliott, BA Brown, JM Conville, PS Wallace, RJ AF Brown-Elliott, BA Brown, JM Conville, PS Wallace, RJ TI Clinical and laboratory features of the Nocardia spp. based on current molecular taxonomy SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID 16S RIBOSOMAL-RNA; RESTRICTION-ENDONUCLEASE ANALYSIS; SEQUENCE-BASED IDENTIFICATION; CHRONIC GRANULOMATOUS-DISEASE; RENAL-TRANSPLANT RECIPIENTS; FIELD GEL-ELECTROPHORESIS; SP-NOV.; RAPID IDENTIFICATION; GENUS NOCARDIA; CEREBRAL NOCARDIOSIS AB The recent explosion of newly described species of Nocardia results from the impact in the last decade of newer molecular technology, including PCR restriction enzyme analysis and 16S rRNA sequencing. These molecular techniques have revolutionized the identification of the nocardiae by providing rapid and accurate identification of recognized nocardiae and, at the same time, revealing new species and a number of yet-to-be-described species. There are currently more than 30 species of nocardiae of human clinical significance, with the majority of isolates being N. nova complex, N. abscessus, N. transvalensis complex, N. farcinica, N. asteroides type VI (N. cyriacigeorgica), and N. brasiliensis. These species cause a wide varies, of diseases and have variable drug susceptibilities. Accurate identification often requires referral to a reference laboratory with molecular capabilities, as many newer species are genetically distinct front established species yet have few or no distinguishing phenotypic characteristics. Correct identification is important in deciding the clinical relevance of a species and in the clinical management and treatment of patients with nocardial disease. This review characterizes the currently known pathogenic species of Nocardia, including clinical disease, drug susceptibility; and methods of identification. C1 Univ Texas Hlth Ctr, Dept Microbiol, Tyler, TX 75708 USA. Ctr Dis Control & Prevent, Div Bacterial & Mycot Dis, Atlanta, GA USA. NIH, Dept Lab Med, Bethesda, MD 20892 USA. RP Wallace, RJ (reprint author), Univ Texas Hlth Ctr, Dept Microbiol, 11937 US Highway 271, Tyler, TX 75708 USA. EM richard.wallace@uthct.edu NR 232 TC 314 Z9 332 U1 2 U2 35 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD APR PY 2006 VL 19 IS 2 BP 259 EP + DI 10.1128/CMR.19.2.259-282.2006 PG 25 WC Microbiology SC Microbiology GA 037YQ UT WOS:000237184400001 PM 16614249 ER PT J AU Valls-Sole, J Hallett, M AF Valls-Sole, J Hallett, M TI On technical features of neurophysiological equipment and their reliability SO CLINICAL NEUROPHYSIOLOGY LA English DT Editorial Material ID STIMULATION C1 Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi I Sunyer, IDIBAPS,Dept Neurol,EMG Unit, Barcelona, Catalunya, Spain. NINDS, NIH, Bethesda, MD 20892 USA. RP Valls-Sole, J (reprint author), Univ Barcelona, Hosp Clin Barcelona, Inst Invest Biomed August Pi I Sunyer, IDIBAPS,Dept Neurol,EMG Unit, Villarroel,170, Barcelona, Catalunya, Spain. EM jvalls@clinic.ub.es NR 5 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD APR PY 2006 VL 117 IS 4 BP 714 EP 715 DI 10.1016/j.clinph.2005.12.024 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 030VS UT WOS:000236663800003 PM 16497554 ER PT J AU Gandiga, PC Hummel, FC Cohen, LG AF Gandiga, PC Hummel, FC Cohen, LG TI Transcranial DC stimulation (OCS): A tool for double-blind sham-controlled clinical studies in brain stimulation SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE DC stimulation; stroke; double-blinding; sham stimulation; neurorehabilitation ID HUMAN MOTOR CORTEX; NONINVASIVE CORTICAL STIMULATION; MAGNETIC STIMULATION; CHRONIC STROKE; EXCITABILITY; SAFETY; POLARIZATION; MODULATION; HUMANS; TRIALS AB Objective: Brain polarization in the form of transcranial direct current stimulation (tDCS), which influences motor function and learning processes, has been proposed as an adjuvant strategy to enhance training effects in Neurorehabilitation. Proper testing in Neurorehabilitation requires double-blind sham-controlled study designs. Here, we evaluated the effects of tDCS and sham stimulation (SHAM) on healthy subjects and stroke patients' self-report measures of attention, fatigue, duration of elicited sensations and discomfort. Methods: tDCS or SHAM was in all cases applied over the motor cortex. Attention, fatigue, and discomfort were self rated by study participants using visual analog scales. Duration of perceived sensations and the ability to distinguish tDCS from Sham sessions were determined. Investigators questioning the patients were blind to the intervention type. Results: tDCS and SHAM elicited comparably minimal discomfort and duration of sensations in the absence of differences in attention or fatigue, and could not be distinguished from SHAM by study participants nor investigators. Conclusions: Successful blinding of subjects and investigators and ease of application simultaneously with training protocols supports the feasibility of using tDCS in double-blind, sham-controlled randomized trials in clinical Neurorehabilitation. Significance: tDCS could evolve into a useful tool, in addition to TMS, to modulate cortical activity in Neurorehabilitation. (c) 2006 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All fights reserved. C1 Univ Tubingen, Dept Neurol, Cort Physiol Res Grp, D-72076 Tubingen, Germany. Univ Tubingen, Hertie Inst Clin Brain Res, D-72076 Tubingen, Germany. NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20892 USA. RP Hummel, FC (reprint author), Univ Tubingen, Dept Neurol, Cort Physiol Res Grp, Hoppe Seyler Str 3, D-72076 Tubingen, Germany. EM friedhelm.hummel@uni-tuebingen.de NR 35 TC 587 Z9 603 U1 6 U2 61 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD APR PY 2006 VL 117 IS 4 BP 845 EP 850 DI 10.1016/j.clinph.2005.12.003 PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 030VS UT WOS:000236663800017 PM 16427357 ER PT J AU Wang, XM Wu, TX Lee, YS Dionne, RA AF Wang, XM Wu, TX Lee, YS Dionne, RA TI Rofecoxib regulates the expression of genes related to the matrix metalloproteinase pathway in humans: Implication for the adverse effects of cyclooxygenase-2 inhibitors SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; VASOACTIVE-INTESTINAL-PEPTIDE; ATHEROSCLEROTIC PLAQUE; RHEUMATOID-ARTHRITIS; VITRONECTIN RECEPTOR; HUMAN MACROPHAGES; EPITHELIAL-CELLS; E-PROSTAGLANDINS; DOWN-REGULATION; TNF-ALPHA AB Background: Cyclooxygenase-2 (COX-2) and COX-2-derived Prostaglandins contribute to acute inflammation and pain, as well as resolution of inflammation; inhibition of COX-2 results in persistence of inflammation. Because matrix metalloproteinases (MMPs) play an essential role in inflammatory tissue injury and their activity is regulated by COX-2-derived prostaglandin E-2, we evaluated whether COX-2 inhibition is associated with AMP overexpression during acute inflammation. Methods: A total of 102 oral mucosal biopsy specimens were taken from 51 healthy volunteers who required extraction of impacted third molars. Subjects randomly received either rofecoxib (50 mg daily), ibuprofen (400 mg 4 times per day), or placebo 90 minutes before surgery and up to 48 hours after surgery. Total ribonucleic acid extracted from each biopsy specimen was used to analyze changes in gene expression related to the MMP pathway after tissue injury and drug treatments by use of microarray and quantitative real-time polymerase chain reaction in this clinical model of acute inflammation. Results: Following tissue injury, rofecoxib increased the expression of genes associated with degradation of the extracellular matrix, including MMP-1 (64.7 +/- 6.5, P =.010), MMP-3 (41.7 +/- 4.8, P =.007), PLAT (encoding tissue plasminogen activator) (10.9 +/- 4.6, P =.032), and IL8 (encoding interleukin 8) (8.3 +/- 6.7, P =.020), and decreased the expression of TIMP3 (encoding tissue inhibitor of metalloproteinase 3) (6.2 +/- 2.8, P =.027). Ibuprofen produced similar effects on the expression of MMP-1 (23.4 +/- 5.0, P =.016) and MMP-3 (26.3 +/- 4.2, P =.003). In contrast, the expression of these genes was not statistically changed after tissue injury in the placebo group. The microarray data were in concordance with the changes in gene expression confirmed by quantitative real-time polymerase chain reaction. Conclusion: These findings provide evidence at the transcriptional level that inhibition of COX-2, in the presence of acute inflammation, induces changes in gene expression related to the MAIP pathway. These changes may contribute to the adverse effects attributed to COX-2 inhibition by interfering with resolution of inflammation. C1 CRC, NIH, NINR, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Pain & Neurosurg Mechanisms Branch & Biostat Core, Bethesda, MD USA. RP Dionne, RA (reprint author), CRC, NIH, NINR, Bldg 10,Room 2-1339, Bethesda, MD 20892 USA. EM dionner@mail.nih.gov NR 42 TC 21 Z9 22 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD APR PY 2006 VL 79 IS 4 BP 303 EP 315 DI 10.1016/j.clpt.2005.12.306 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 032CU UT WOS:000236752300002 PM 16580899 ER PT J AU Rio, DE Rawlings, RR Woltz, LA Salloum, JB Hommer, DW AF Rio, DE Rawlings, RR Woltz, LA Salloum, JB Hommer, DW TI Single subject image analysis using the complex general linear model - An application to functional magnetic resonance imaging with multiple inputs SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE functional MRI; image processing; time series analysis; Fourier analysis; statistics ID TEMPORAL AUTOCORRELATION; STATISTICAL-ANALYSIS; DOMESTIC VIOLENCE; SELECT GROUP; FMRI; DATA/ AB A linear time invariant model is applied to functional fMRI blood flow data. Based on traditional time series analysis, this model assumes that the fMRI stochastic output sequence can be determined by a constant plus a linear filter (hemodynamic response function) of several fixed deterministic inputs and an error term assumed stationary with zero mean. The input function consists of multiple exponential distributed (time delay between images) visual stimuli consisting of negative and erotic images. No a priori assumptions are made about the hemodynamic response function that, in essence, is calculated at each spatial position from the data. The sampling rate for the experiment is 400 ms in order to allow for filtering out higher frequencies associated with the cardiac rate. Since the statistical analysis is carried out in the Fourier domain, temporal correlation problems associated with inference in the time domain are avoided. This formal model easily lends itself to further development based on previously developed statistical techniques. Published by Elsevier Ireland Ltd. C1 NIAAA, Sect Brain Electrophysiol & Imaging, Clin Studies Lab, NIH, Bethesda, MD 20892 USA. Synergy Res Inc, Monrovia, MD 21770 USA. RP Rio, DE (reprint author), NIAAA, Sect Brain Electrophysiol & Imaging, Clin Studies Lab, NIH, Bldg 10,CRC,Rm 2-2332,10 Ctr Dr,MSC 1540, Bethesda, MD 20892 USA. EM drio@nih.gov NR 22 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD APR PY 2006 VL 82 IS 1 BP 10 EP 19 DI 10.1016/j.cmpb.2005.12.003 PG 10 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 036BT UT WOS:000237046600002 PM 16530880 ER PT J AU Maxwell, SK Nuckols, JR Ward, MH AF Maxwell, SK Nuckols, JR Ward, MH TI A method for mapping corn using the US Geological Survey 1992 National Land Cover Dataset SO COMPUTERS AND ELECTRONICS IN AGRICULTURE LA English DT Article DE National Land Cover Dataset (NLCD); Landsat; crop mapping; corn; Platte River Valley; Nebraska ID IDENTIFICATION; NITRATE; RISK AB Long-term exposure to elevated nitrate levels in community drinking water supplies has been associated with an elevated risk of several cancers including non-Hodgkin's lymphoma, colon cancer, and bladder cancer. To estimate human exposure to nitrate, specific crop type information is needed as fertilizer application rates vary widely by crop type. Corn requires the highest application of nitrogen fertilizer of crops grown in the Midwest US. We developed a method to refine the US Geological Survey National Land Cover Dataset (NLCD) (including map and original Landsat images) to distinguish corn from other crops. Overall average agreement between the resulting corn and other row crops class and ground reference data was 0.79 kappa coefficient with individual Landsat images ranging from 0.46 to 0.93 kappa. The highest accuracies occurred in Regions where corn was the single dominant crop (greater than 80.0%) and the crop vegetation conditions at the time of image acquisition were optimum for separation of corn from all other crops. Factors that resulted in lower accuracies included the accuracy of the NLCD map, accuracy of corn areal estimates, crop mixture, crop condition at the time of Landsat overpass, and Landsat scene anomalies. (c) 2006 Elsevier B.V. All rights reserved. C1 US Geol Survey, Natl Ctr Earth Resources Observat & Sci, Sci Applicat Int Corp, Sioux Falls, SD 57198 USA. Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80521 USA. NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, NIH,US Dept HHS, Bethesda, MD 20892 USA. RP Maxwell, SK (reprint author), US Geol Survey, Natl Ctr Earth Resources Observat & Sci, Sci Applicat Int Corp, Sioux Falls, SD 57198 USA. EM maxwell@usgs.gov NR 12 TC 3 Z9 5 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0168-1699 J9 COMPUT ELECTRON AGR JI Comput. Electron. Agric. PD APR PY 2006 VL 51 IS 1-2 BP 54 EP 65 DI 10.1016/j.compag.2005.11.003 PG 12 WC Agriculture, Multidisciplinary; Computer Science, Interdisciplinary Applications SC Agriculture; Computer Science GA 023MQ UT WOS:000236131200004 ER PT J AU Brandt, CA Argraves, S Money, R Ananth, G Trocky, NM Nadkarni, PM AF Brandt, CA Argraves, S Money, R Ananth, G Trocky, NM Nadkarni, PM TI Informatics tools to improve clinical research study implementation SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE informatics; clinical trials; database management system; study coordination ID QUALITY-ASSURANCE; DATA MANAGEMENT; DATA-ENTRY; TRIAL; SYSTEM AB Background: There are numerous potential sources of problems when performing complex clinical research trials. These issues are compounded when studies are multi-site and multiple personnel from different sites are responsible for varying actions from case report form design to primary data collection and data entry. Methods: We describe an approach that emphasizes the use of a variety of informatics tools that can facilitate study coordination, training, data checks and early identification and correction of faulty procedures and data problems. The paper focuses on informatics tools that can help in case report form design, procedures and training and data management. Conclusion: Informatics tools can be used to facilitate study coordination and implementation of clinical research trials. (c) 2005 Elsevier Inc. All rights reserved. C1 Yale Univ, Sch Med, Ctr Med Informat, New Haven, CT 06520 USA. Yale Univ, Sch Med, Dept Psychiat, Treatment Res Ctr CMHC, New Haven, CT 06520 USA. NCI, Harris Corp, NIH, Falls Church, VA USA. RP Brandt, CA (reprint author), Yale Univ, Sch Med, Ctr Med Informat, POB 208009, New Haven, CT 06520 USA. EM cynthia.brandt@yale.edu FU NCI NIH HHS [U01 CA78266]; NCRR NIH HHS [K23 RR16042, K23 RR016042, M01 RR06022]; NIEHS NIH HHS [U01 ES10867]; NLM NIH HHS [R01 LM06843] NR 29 TC 18 Z9 18 U1 0 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD APR PY 2006 VL 27 IS 2 BP 112 EP 122 DI 10.1016/j.cct.2005.11.013 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 032PK UT WOS:000236786500002 PM 16388990 ER PT J AU Magone, MT Maric, I Hwang, DG AF Magone, MT Maric, I Hwang, DG TI Peripheral interstitial keratitis - A novel monifestotion of oculor mastocytosis SO CORNEA LA English DT Article DE mastocytosis; urticaria pigmentosa; interstitial keratitis; mast cell AB Purpose: To report a case of peripheral interstitial keratitis in a patient with mastocytosis. Methods: Clinical case description and immunohistologic examination of biopsied ocular tissue. Results: A 22-year-old woman with biopsy-proven urticaria pigmentosa, a subset of mastocytosis, presented with an active peripheral interstitial keratitis with vascularization associated with foreign body sensation and itching. Biomicroscopy of the cornea showed deep corneal inflammatory infiltrates and midstromal vascularization adjacent to a region of superior bulbar conjunctiva, which was mildly chemotic and inflamed. Topical mast cell stabilizers and a short course of topical steroids produced dramatic resolution of the lesion. Biopsy of the erythematous conjunctiva adjacent to the area of corneal inflammation shoved the presence of mast cells. Conclusion: This is the first case of corneal inflammatory infiltration in a patient with mastocytosis. Therapy for this condition consists of a combination of topical mast cell stabilizers, topical steroids, and systemic antihistaminic therapy. C1 Univ Calif San Francisco, Dept Ophthalmol, Cornea Serv, San Francisco, CA 94143 USA. Dept Vet Affairs Med Ctr, Dept Ophthalmol, Washington, DC USA. NIH, Dept Lab Med, Hematol Sect, Bethesda, MD 20892 USA. RP Hwang, DG (reprint author), Univ Calif San Francisco, Dept Ophthalmol, Cornea Serv, San Francisco, CA 94143 USA. EM dghwang@itsa.ucsf.edu NR 10 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0277-3740 J9 CORNEA JI Cornea PD APR PY 2006 VL 25 IS 3 BP 364 EP 367 DI 10.1097/01.ico.0000176604.95000.f3 PG 4 WC Ophthalmology SC Ophthalmology GA 032EO UT WOS:000236756900023 PM 16633043 ER PT J AU Truog, RD Brock, DW Cook, DJ Danis, M Luce, JM Rubenfeld, GD Levy, MM AF Truog, RD Brock, DW Cook, DJ Danis, M Luce, JM Rubenfeld, GD Levy, MM CA VERICC TI Rationing in the intensive care unit SO CRITICAL CARE MEDICINE LA English DT Article DE critical care; health care rationing; ethics; intensive care units; severity of illness index; triage ID COST-EFFECTIVENESS ANALYSIS; HEALTH-CARE; RESOURCE-ALLOCATION; TRIAGE; ADMISSION; DECISIONS; LIFE; INEVITABILITY; EPIDEMIOLOGY; CONTAINMENT AB Background: Critical care services represent a large and growing proportion of health care expenditures. Limiting the magnitude of these costs while maintaining a just allocation of these services will require rationing. We define rationing as "the allocation of healthcare resources in the face of limited availability, which necessarily means that beneficial interventions are withheld from some individuals." Although some have maintained that rationing of health care is unethical, we argue that rationing is not only unavoidable but essential to ensuring the ethical distribution of medical goods and services. Principal Findings: Intensivists have little to guide them in the rationing of critical care services. We have developed a taxonomy of the rationing choices faced by intensivists as a framework for ethical analysis. This taxonomy divides rationing decisions into three categories. First are those rationing decisions that may be justified by external constraints (such as not prescribing a potentially beneficial medication because it is not available on the hospital formulary). Second are those that may be justified by reference to clinical guidelines (as, for example, not prescribing a potentially beneficial medication because a valid guideline recommends treatment with a less expensive alternative). Third are those that are justified by individual clinical judgment (such as choosing which of two patients should be admitted into the last ICU bed, in the absence of any evidence-based guidance). Judgments made on the basis of clinical judgment deserve particular scrutiny, since they may mask unethical prejudices or bias. Conclusions: Although this taxonomy does not by itself determine which decisions are ethical, it does clarify the type of evidence that is appropriate to supporting the decision that is made. Additional work is needed to elucidate how both empirical evidence and ethical analysis can further inform the rationing decisions that arise in the taxonomy described here. C1 Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. McMaster Univ, Med Ctr, Hamilton, ON, Canada. NIH, Dept Clin Bioeth, Bioeth Consultat Serv, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Washington, Seattle, WA 98195 USA. Brown Med Sch, Providence, RI USA. Rhode Isl Hosp, Med Intens Care Unit, Providence, RI USA. RP Truog, RD (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. RI Embrett, Mark/H-4466-2014 OI Embrett, Mark/0000-0002-3969-0219 NR 50 TC 91 Z9 93 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2006 VL 34 IS 4 BP 958 EP 963 DI 10.1097/01.CCM.0000206116.10417.D9 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 025YH UT WOS:000236303000004 PM 16484912 ER PT J AU Baumann, JG AF Baumann, JG TI Intracellular restriction factors in mammalian cells - An ancient defense system finds a modern foe SO CURRENT HIV RESEARCH LA English DT Review DE retroviruses; restriction; APOBEC; Trim5; Fv-1; vif; lentiviruses; HIV ID HUMAN-IMMUNODEFICIENCY-VIRUS; MURINE LEUKEMIA-VIRUS; INDUCED CYTIDINE DEAMINASE; HEPATITIS-B-VIRUS; SINGLE-STRANDED-DNA; TYPE-1 VIF PROTEIN; RNA-EDITING ENZYME; BLOOD MONONUCLEAR-CELLS; COILED-COIL PROTEIN; CROSS-SPECIES TRANSMISSION AB Cross-species transmission of retroviruses poses a threat to mammalian species. Zoonoses have given rise to devastating diseases because the host organism is not prepared to resist a new pathogen. Mammals have developed several layers of defense against viruses, including an intracellular antiretroviral defense, a part of innate immunity. Retroviral restrictions had been studied for decades using murine leukemia virus in mice, however it has become clear that primates too have intrinsic mechanisms to ward off infections by retroviruses. Several of these antiretroviral restriction mechanisms have recently been identified, with two particularly well described factors being members of the tripartite motif (Trim) and APOBEC families. Both systems provide a strong barrier against lentiviral infections. The viruses have developed Countermeasures that allow them to replicate despite the host factors. This review discusses our current knowledge of this ancient battle between mammalian hosts and their retroviral opponents. C1 NCI, HIV Drug Resistance Program, Frederick, MD 21702 USA. RP Baumann, JG (reprint author), NCI, HIV Drug Resistance Program, POB B,Bldg 535, Frederick, MD 21702 USA. EM jbaumann@ncifcrf.gov NR 407 TC 24 Z9 24 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-162X J9 CURR HIV RES JI Curr. HIV Res. PD APR PY 2006 VL 4 IS 2 BP 141 EP 168 DI 10.2174/157016206776055093 PG 28 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 033KE UT WOS:000236845100003 PM 16611054 ER PT J AU Kang, SH Cho, KK Bok, JD Kim, SC Cho, JS Lee, PCW Kang, SK Lee, HG Woo, JH Lee, HJ Lee, SC Choi, YJ AF Kang, SH Cho, KK Bok, JD Kim, SC Cho, JS Lee, PCW Kang, SK Lee, HG Woo, JH Lee, HJ Lee, SC Choi, YJ TI Cloning, sequencing and characterization of a novel phosphatase gene, phoI, from soil bacterium Enterobacter sp. 4 SO CURRENT MICROBIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; ACID-PHOSPHATASE; ASPERGILLUS-NIGER; MICROBIAL PHYTASE; PHOSPHORUS AVAILABILITY; HAEMOPHILUS-INFLUENZAE; SOYBEAN-MEAL; PURIFICATION; BROILERS; FICUUM AB A gene, phoI, coding for a phosphatase from Enterobacter sp. 4 was cloned in Escherichia coli and sequenced. Analysis of the sequence revealed one open reading frame (ORF) that encodes a 269-amino acid protein with a calculated molecular mass of 29 kDa. PhoI belongs to family B acid phosphatase and exhibits 49.4% identity and 62.4% homology to the hel gene from Heamophilus influenzae, which encoded an outer membrane protein (P4). The optimum pH and temperature for phosphatase activity were pH 5.5 and 40 degrees C, respectively. Its specific activity on rho-nitrophenyl phosphatate was 70 U/mg at pH 5.5 and 40 degrees C. Enzyme activity was inhibited by Al3+, EDTA, and DTT, but fivefold activated by Cu2+ ion (350 U/mg). PhoI showed a strong synergistic effect when used with a purified E. coli phytase, AppA, to estimate combination effects. C1 Seoul Natl Univ, Sch Agr Biotechnol, Seoul 151921, South Korea. Chinju Natl Univ, Dept Int Livestock Ind, Chinju 660758, Kyongnam, South Korea. Choong Ang Biotech Co Ltd, R&D Ctr, Ansan, Kyunggi Do, South Korea. NIMH, Sect Biophys Chem, Mol Biol Lab, Bethesda, MD 20892 USA. RP Choi, YJ (reprint author), Seoul Natl Univ, Sch Agr Biotechnol, Seoul 151921, South Korea. EM cyjcow@snu.ac.kr RI Choi, Yunjaie /B-4697-2014 NR 32 TC 4 Z9 6 U1 2 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD APR PY 2006 VL 52 IS 4 BP 243 EP 248 DI 10.1007/s00284-005-4467-z PG 6 WC Microbiology SC Microbiology GA 026QK UT WOS:000236357000001 PM 16550460 ER PT J AU Scripture, CD Figg, WD Sparreboom, A AF Scripture, CD Figg, WD Sparreboom, A TI Peripheral neuropathy induced by paclitaxel: Recent insights and future perspectives SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Taxol; cremophor; ABI-007; peripheral neuropathy ID NERVE GROWTH-FACTOR; HIGH-DOSE PACLITAXEL; METASTATIC BREAST-CANCER; TAXOL-INDUCED NEUROPATHY; OVARIAN-CANCER; PHASE-I; EXPERIMENTAL CISPLATIN; INDUCED NEUROTOXICITY; SENSORY NEUROPATHY; GANGLION EXPLANTS AB Paclitaxel is an antineoplastic agent derived from the bark of the western ycw, Taxus brevifolia, with a broad spectrum of activity. Because paclitaxel promotes microtubule assembly, neurotoxicity is one of its side effects. Clinical use of paclitaxel has led to peripheral neuropathy and this has been demonstrated to be dependent upon the dose administered, the duration of the infusion, and the schedule of administration. Vehicles in the drug formulation, for example Cremophor in Taxol (R), have been investigated for their potential to induce peripheral neuropathy. A variety of neuroprotective agents have been tested in animal and clinical studies to prevent paclitaxel neurotoxicity. Recently, novel paclitaxel formulations have been developed to minimize toxicities. This review focuses on recent advances in the etiology of paclitaxel-mediated peripheral neurotoxicity, and discusses current and ongoing strategies for amelioration of this side effect. C1 NCI, Clin Pharmacol Res Core, Bethesda, MD USA. RP Scripture, CD (reprint author), NCI, Med Oncol Clin Res Unit, 9000 Rockville Pike,Bldg 10,Rm 5A01,MSC1910, Bethesda, MD 20892 USA. EM wdfigg@helix.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 69 TC 73 Z9 75 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD APR PY 2006 VL 4 IS 2 BP 165 EP 172 DI 10.2174/157015906776359568 PG 8 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 040LN UT WOS:000237380200006 PM 18615126 ER PT J AU El-Mansi, M Cozzone, AJ Shiloach, J Eikmanns, BJ AF El-Mansi, M Cozzone, AJ Shiloach, J Eikmanns, BJ TI Control of carbon flux through enzymes of central and intermediary metabolism during growth of Escherichia coli on acetate SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID ISOCITRATE DEHYDROGENASE; CORYNEBACTERIUM-GLUTAMICUM; ACETYL PHOSPHATE; COENZYME-A; PROTEIN-PHOSPHORYLATION; HALOARCULA-MARISMORTUI; ENTERIC BACTERIA; AEROBIC GROWTH; AND/OR GLUCOSE; GLOBAL SIGNAL AB During aerobic growth of Escherichia coli on acetate, the component parts of the 'acetate switch' are turned-on as a consequence of direct competition, on the one hand, between phosphotransacetylase (PTA) and alpha-ketoglutarate dehydrogenase (alpha-KGDH) for their common co-factor free-CoA (HS-CoA) and, on the other hand, between isocitrate lyase (ICL) and isocitrate dehydrogenase (ICDH) for their common substrate isocitrate. Flux analysis revealed that competitions at both junctions in central metabolism are resolved in a precise way, so that the fraction of HS-CoA flux processed through PTA for biosynthesis relative to that processed through alpha-KGDH for energy generation, matches that observed for isocitrate flux through ICL relative to ICDH at the junction of isocitrate. Whereas the mechanism involved in the partition of carbon flux at the level of HS-CoA in central metabolism remains to be unravelled, the competition at the junction of isocitrate is resolved by the reversible phosphorylation/inactivation of ICDH and the operation of the glyoxylate bypass, the expression of which is subject to regulation at the transcriptional and translational levels as well as being dependent on growth rate. C1 Napier Univ, Fac Hlth & Life Sci, Sch Life Sci, Edinburgh EH10 5DT, Midlothian, Scotland. Univ Lyon 1, CNRS, Inst Biol & Chem Prot, F-69622 Villeurbanne, France. NIDDK, Biotechnol Unit, NIH, Bethesda, MD 20892 USA. Univ Ulm, Dept Microbiol & Biotechnol, D-89069 Ulm, Germany. RP El-Mansi, M (reprint author), Napier Univ, Fac Hlth & Life Sci, Sch Life Sci, Edinburgh EH10 5DT, Midlothian, Scotland. EM m.el-mansi@napier.ac.uk NR 41 TC 36 Z9 36 U1 2 U2 23 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD APR PY 2006 VL 9 IS 2 BP 173 EP 179 DI 10.1016/j.mib.2006.02.002 PG 7 WC Microbiology SC Microbiology GA 037ZC UT WOS:000237185900009 PM 16530464 ER PT J AU Warfield, KL Panchal, RG Aman, MJ Bavari, S AF Warfield, KL Panchal, RG Aman, MJ Bavari, S TI Antisense treatments for biothreat agents SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Review DE antisense; biothreat; oligonucleotide; phosphorodiamidate morpholino; phosphorothioate; small interfering RNA ID HUMAN-IMMUNODEFICIENCY-VIRUS; PHOSPHOROTHIOATE OLIGONUCLEOTIDES INHIBIT; CHOLESTERYL-CONJUGATED OLIGONUCLEOTIDES; PHOSPHORODIAMIDATE MORPHOLINO OLIGOMER; CHRONICALLY INFECTED-CELLS; PEPTIDE NUCLEIC-ACIDS; ANTI-HIV ACTIVITY; DNA-RNA DUPLEXES; GENE-EXPRESSION; MESSENGER-RNA AB Antisense oligomers (ASOs) represent a promising technology to treat viral and bacterial infections, and have already been shown to be successful against a variety of pathogens in cell culture studies and nonhuman primate models of infection. For these reasons, antisense technologies are being pursued as treatments against biothreat agents such as Ebola virus, dengue virus and Bacillus anthracis. Several generations of modified oligonucleotides have been developed to maximize nuclease resistance, target affinity, potency, cell entry, and other pharmacokinetic properties. First-generation ASOs contain phosphorothioate modifications to increase stability through nuclease resistance. Further chemical modifications in second-generation ASOs include 2'-O-methyl and 2'-O-methoxyethyl oligos, which increase nuclease resistance and oligo: RNA binding affinities. Third-generation ASOs contain a variety of chemical modifications that enhance stability, affinity and bioavailability. A fourth class of oligonucleotide-based compounds consists of small interfering RNAs, which have recently become widely used for gene knockdown in vitro and in vivo. This review focuses on the third-generation phosphorodiamidate morpholino oligomers, which are nonionic and contain a morpholine ring instead of a ribose, as well as phosphorodiamidate linkages in place of phosphorothioates. Multiple antisense oligomer-based therapeutics are being developed for use against biothreat agents, and antisense drugs will likely become a critical member of our arsenal in the defense against highly pathogenic, emerging or genetically engineered pathogens. C1 USA, Med Res Inst Infect Dis, Ft Detrick, Frederick, MD 21702 USA. NCI, Target Struct Based Drug Discovery Grp, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Bavari, S (reprint author), USA, Med Res Inst Infect Dis, Ft Detrick, Frederick, MD 21702 USA. EM sina.bavari@amedd.army.mil FU NCI NIH HHS [N01-CO-12400] NR 128 TC 24 Z9 25 U1 0 U2 5 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD APR PY 2006 VL 8 IS 2 BP 93 EP 103 PG 11 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 025RT UT WOS:000236285300002 PM 16610760 ER PT J AU Pacher, P Szabo, C AF Pacher, P Szabo, C TI Role of peroxynitrite in the pathogenesis of cardiovascular complications of diabetes SO CURRENT OPINION IN PHARMACOLOGY LA English DT Review ID POLY(ADP-RIBOSE) POLYMERASE ACTIVATION; NITRIC-OXIDE SYNTHASE; OXIDATIVE-NITROSATIVE STRESS; PROTEIN-KINASE-C; ENDOTHELIAL DYSFUNCTION; HIGH GLUCOSE; DECOMPOSITION CATALYST; TYROSINE NITRATION; ANGIOTENSIN-II; HEART-FAILURE AB Hyperglycemic episodes, which complicate even well-controlled cases of diabetes, lead to increased polyol pathway flux, activation of protein kinase C and accelerated nonenzymatic formation of advanced glycation end products. Many of these pathways become activated in response to the production of superoxide anion. Superoxide can interact with nitric oxide, forming the potent cytotoxin peroxynitrite. Peroxynitrite attacks various biomolecules in the vascular endothelium, vascular smooth muscle and myocardium, eventually leading to cardiovascular dysfunction via multiple mechanisms. This review focuses on emerging evidence suggesting that peroxynitrite plays a key role in the pathogenesis of the cardiovascular complications of diabetes, which underlie the development and progression of diabetic retinopathy, neuropathy and nephropathy. C1 NIAAA, NIH, Lab Physiol Studies, Rockville, MD 20852 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Surg, Newark, NJ 07103 USA. RP Pacher, P (reprint author), NIAAA, NIH, Lab Physiol Studies, 5625 Fishers Lane MSC 9413, Rockville, MD 20852 USA. EM pacher@mail.nih.gov RI Pacher, Pal/B-6378-2008 OI Pacher, Pal/0000-0001-7036-8108 FU Intramural NIH HHS [Z01 AA000375-02] NR 52 TC 97 Z9 104 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1471-4892 J9 CURR OPIN PHARMACOL JI Curr. Opin. Pharmacol. PD APR PY 2006 VL 6 IS 2 BP 136 EP 141 DI 10.1016/j.coph.2006.01.001 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 028NC UT WOS:000236493600004 PM 16483848 ER PT J AU Singh, SR Oh, SW Liu, W Chen, X Zheng, ZY Hou, SX AF Singh, SR Oh, SW Liu, W Chen, X Zheng, ZY Hou, SX TI Rap-GEF/Rap signaling restricts the formation of supernumerary spermathecae in Drosophila melanogaster SO DEVELOPMENT GROWTH & DIFFERENTIATION LA English DT Article DE cell adhesion; Rap signaling; sperm storage; supernumerary spermathecae ID DIRECT BINDING; CELL-ADHESION; PATHWAY; GTPASE; KINASE; ZO-1; ACTIVATION; CANOE; GENE; AF-6 AB Sperm storage in the female is a key factor for reproductive success in a variety of organisms, including Drosophila melanogaster. The spermathecae (SP) are the Drosophila organs for long-term storage. While wild-type female flies have two SP, occasionally, three or four SP have been observed in mutant flies. However, the molecular mechanism of SP formation is unknown. Here we show that loss of function of a Drosophila Rap-GEF (GEF26) result in an occurrence of the supernumerary SP; females have three SP (varies from 11 to 62% in different allele combinations) instead of the normal two SP. In addition, the Gef26 mutant flies also have ectopic wing veins and extra mechanosensory organs. The supernumerary SP phenotype of the Gef26 mutation can be enhanced by the Drosophila Rap mutations and rescued by overexpressing the cell adhesion molecule DE-cadherin. These data suggest that the Rap-GEF/Rap signaling controls the formation of supernumerary spermathecae through modulating cell adhesion in Drosophila. C1 NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. RP Singh, SR (reprint author), NCI, Mouse Canc Genet Program, NIH, Frederick, MD 21702 USA. EM sshreeram@ncifcrf.gov RI Singh, Shree Ram/B-7614-2008 OI Singh, Shree Ram/0000-0001-6545-583X FU Intramural NIH HHS [Z99 CA999999] NR 23 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0012-1592 J9 DEV GROWTH DIFFER JI Dev. Growth Diff. PD APR PY 2006 VL 48 IS 3 BP 169 EP 175 DI 10.1111/j.1440-169x.2006.00854.x PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 025CJ UT WOS:000236242600003 PM 16573734 ER PT J AU Khosla, M Kriebel, P Parent, CA Spiegelman, GB Weeks, G AF Khosla, M Kriebel, P Parent, CA Spiegelman, GB Weeks, G TI A secondary disruption of the dmpA gene encoding a large membrane protein allows aggregation defective Dictyostelium rasC(-) cells to form multicellular structures SO DEVELOPMENTAL BIOLOGY LA English DT Article DE Dictyostelium; Ras; aggregation; membrane protein; gene disruption; cAMP; MS 53 ID ADENYLYL-CYCLASE; CHEMOTAXIS; DISCOIDEUM; LOCALIZATION; RAS; ACTIVATION; EXPRESSION; AKT/PKB; GROWTH; CAMP AB The disruption of the gene encoding the Dictyosteliuni Ras subfamily protein, RasC, results in a strain that does not aggregate and has defects in both cAMP signal relay and cAMP chemotaxis. Disruption of a second gene in the rasC(-) strain by Restriction Enzyme Mediated Integration produced cells that were capable of forming multicellular structures in plaques on bacterial lawns. The disrupted gene (dmpA) encoded a novel membrane protein that was designated Dmp1. Although the rasC(-)/dmpA(-) cells progressed through early development, they did not form aggregation streams on a plastic Surface under submerged starvation conditions. Phosphorylation of PKB in response to cAMP, which is significantly reduced in rasC(-) cells, remained low in the rasC(-)/dmpA(-) cells. However, in spite of this low PKB phosphorylation, the rasC(-)/dmPA(-) cells underwent efficient chemotaxis to cAMP in a spatial gradient. Cyclic AMP accumulation, which was greatly reduced in the rasC(-) cells, was restored in the rasC(-)/dmpA(-) strain, but cAMP relay in these cells was not apparent. These data indicate that although the rasC(-)/dmpA(-) cells were capable of associating to form multicellular structures, normal aggregative cell signaling was clearly not restored. Disruption of the dmpA gene in a wild-type background resulted in cells that exhibited a slight defect in aggregation and a more Substantial defect in late development. These results indicate that, in addition to the role played by Dmp1 in aggregation, it is also involved in late development. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ British Columbia, Dept Microbiol & Immunol, Vancouver, BC V6T 1Z3, Canada. NCI, Cellular & Mol Biol Lab, Bethesda, MD 20892 USA. RP Weeks, G (reprint author), 2350 Hlth Sci Mall, Vancouver, BC V6T 1Z3, Canada. EM gerwee@interchange.ubc.ca NR 29 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 1 PY 2006 VL 292 IS 1 BP 68 EP 78 DI 10.1016/j.ydbio.2005.12.051 PG 11 WC Developmental Biology SC Developmental Biology GA 031TN UT WOS:000236727100007 PM 16490188 ER PT J AU Wilting, J Aref, Y Huang, R Tomarev, SI Schweigerer, L Christ, B Valasek, P Papoutsi, M AF Wilting, J Aref, Y Huang, R Tomarev, SI Schweigerer, L Christ, B Valasek, P Papoutsi, M TI Dual origin of avian lymphatics SO DEVELOPMENTAL BIOLOGY LA English DT Article DE lymphangiogenesis; Prox1; Tie2; low density lipoprotein; lymphatic endothelial cell; lymphangioblast; lymph sac; lymph heart; quail-chick chimera ID CHORIOALLANTOIC MEMBRANE; SYSTEM; LYMPHANGIOGENESIS; PROX1; VASCULOGENESIS; ENDOTHELIUM; INDUCTION; INJECTION; VESSELS; EMBRYOS AB The earliest signs of the lymphatic vascular system are the lymph sacs, which develop adjacent to specific embryonic veins. It has been suggested that sprouts from the lymph sacs form the complete lymphatic vascular system. We have studied the origin of the jugular lymph sacs (JLS), the dermal lymphatics and the lymph hearts of avian embryos. In day 6.5 embryos, the JLS is an endothelial-lined sinusoidal structure. The lymphatic endothelial cells (LECs) stain (in the quail) positive for QH1 antibody and soybean agglutinin. As early as day 4, the anlagen of the JLS can be recognized by their Prox1 expression. Prox1 is found in the jugular section of the cardinal veins, and in scattered cells located in the dermatomes along the cranio-caudal axis and in the splanchnopleura. In the quail, such cells are positive for Prox1 and QH1 . In tjugular region, the veins co-express the angiopoietin receptor Tie2. Quail-chick-chimera studies show that the peripheral parts of the JLS form by integration of cells from the paraxial mesoderm. Intra-venous application of Dil-conjugated acetylated low-density lipoprotein into day 4 embryos suggests a venous origin of the deep parts of the JLS. Superficial lymphatics are directly derived from the dermatomes, as shown by dermatome grafting. The lymph hearts in the lumbo-sacral region develop from a plexus of Prox I-positive lymphatic capillaries. Both LECs and muscle cells of the lymph hearts are of somitic origin. In sum, avian lymphatics are of dual origin. The deep parts of the lymph sacs are derived from adjacent veins, the superficial parts of the JLS and the dermal lymphatics from local lymphangioblasts. (c) 2006 Elsevier Inc. All rights reserved. C1 Univ Gottingen, Childrens Hosp, D-37075 Gottingen, Germany. Univ Freiburg, Anat Inst 2, D-79104 Freiburg, Germany. NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. Univ London Royal Vet Coll, London NW1 0TU, England. RP Wilting, J (reprint author), Univ Gottingen, Childrens Hosp, Robert Koch Str 40, D-37075 Gottingen, Germany. EM joerg.wilting@med.uni-goettingen.de RI Valasek, Petr/R-4567-2016 OI Valasek, Petr/0000-0001-9224-4560 NR 37 TC 64 Z9 66 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD APR 1 PY 2006 VL 292 IS 1 BP 165 EP 173 DI 10.1016/j.ydbio.2005.12.043 PG 9 WC Developmental Biology SC Developmental Biology GA 031TN UT WOS:000236727100015 PM 16457798 ER PT J AU Chitnis, A AF Chitnis, A TI Why is Delta endocytosis required for effective activation of Notch? SO DEVELOPMENTAL DYNAMICS LA English DT Review DE Delta; endocytosis; recycling; Notch signaling; mind bomb; neuralized ID PROTEIN-COUPLED RECEPTORS; UBIQUITIN LIGASE; MIND BOMB; DROSOPHILA DEVELOPMENT; BINDING-PROTEINS; BETA-ARRESTIN; GROWTH-FACTOR; LIPID RAFTS; E-CADHERIN; CELL FATE AB A number of recent studies have shown that endocytosis of Notch ligands is required for activation of Notch. There are at least two broad models that account for how Delta endocytosis in one cell might contribute to activation of Notch in the neighboring cell. The first class of models is related to the possibility that Delta endocytosis facilitates S2 cleavage and removal of the Notch extracellular domain, a critical step in Notch activation. A second class of models is related to the possibility that Delta ubiquitylation and endocytosis facilitates interactions between Delta and Notch. In the second set of models, Delta undergoes endocytosis and its subsequent trafficking back to the surface, following modifications or some change in the context in which it is presented, makes Delta a more effective ligand. Though it is still not clear how either or both mechanisms contribute, recent evidence points to the importance of both endocytosis and recycling in Delta signaling. C1 NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Chitnis, A (reprint author), Bldg 3B 315,Room 3B 315,6 Ctr Dr, Bethesda, MD 20892 USA. EM chitnisa@mail.nih.gov FU Intramural NIH HHS [ZIA HD001012-12] NR 77 TC 60 Z9 62 U1 1 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1058-8388 J9 DEV DYNAM JI Dev. Dyn. PD APR PY 2006 VL 235 IS 4 BP 886 EP 894 DI 10.1002/dvdy.20683 PG 9 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 027VT UT WOS:000236444600004 PM 16425217 ER PT J AU Jaffe, BD Evans, TA Howell, S Westergaard, GC Snoy, PJ Higley, JD AF Jaffe, BD Evans, TA Howell, S Westergaard, GC Snoy, PJ Higley, JD TI Left versus right nipple preference in free-ranging infant rhesus macaques (Macaca mulatta) SO DEVELOPMENTAL PSYCHOBIOLOGY LA English DT Article DE nipple preference; nursing; laterality; infancy; development; macaque; Macaca mulatta ID JAPANESE MACAQUES; NONHUMAN-PRIMATES; LATERALITY; MONKEYS; HANDEDNESS; BEHAVIOR; MOTHER; FIELD; HAND AB The examination of nonhuman primate (NHP) lateralized behaviors may provide insight into the evolution of hemispheric specialization. This study examined nipple preference in 64 infant macaques in order to consider the ontogeny of lateralized behavior We used a focal animal sampling method to record nipple contact during 15, 30-min observation sessions collected across each infant's first year of lift. Using a lateralized behavior index (LBI) we calculated individual and population preferences (LBI = (R-L)I(R + L); "R" = mean right nipple contact, "L" = mean left nipple contact). Strength of preference was calculated as the absolute value of this score. Infants exhibited no population preference for a particular nipple, but showed a significant strength of preference that developed after 48 hr Interestingly, successive siblings preferred the nipple not used by the previous infant. These findings suggest that nipple preference is guided by external stimuli, and that nipple preference during infancy may not be a behavioral representation of hemispheric specialization. (c) 2006 Wiley Periodicals, Inc. C1 Alpha Genesis Inc, Yemassee, SC 29945 USA. US FDA, Div Vet Serv, Poolesville, MD USA. NIAAA, NIH, Poolesville, MD USA. RP Howell, S (reprint author), Alpha Genesis Inc, 95 Castle Hall Rd,POB 557, Yemassee, SC 29945 USA. EM suehowell@alphagenesisinc.com FU NIAAA NIH HHS [N01AA02018]; PHS HHS [223-01-1101] NR 25 TC 7 Z9 9 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0012-1630 J9 DEV PSYCHOBIOL JI Dev. Psychobiol. PD APR PY 2006 VL 48 IS 3 BP 266 EP 272 DI 10.1002/dev.20128 PG 7 WC Developmental Biology; Psychology SC Developmental Biology; Psychology GA 031UN UT WOS:000236729800007 PM 16568413 ER PT J AU Wolford, JK Yeatts, KA Eagle, ARR Nelson, RG Knowler, WC Hanson, RL AF Wolford, JK Yeatts, KA Eagle, ARR Nelson, RG Knowler, WC Hanson, RL TI Variants in the gene encoding aldose reductase (AKR1B1) and diabetic nephropathy in American Indians SO DIABETIC MEDICINE LA English DT Article DE aldose reductase; candidate gene; diabetic nephropathy; microvascular complications ID STAGE RENAL-DISEASE; PIMA-INDIANS; MICROVASCULAR COMPLICATIONS; LINKAGE DISEQUILIBRIUM; PROMOTER REGION; PAIR ANALYSIS; MELLITUS; POLYMORPHISM; SUSCEPTIBILITY; ASSOCIATION AB Aims The aldose reductase gene (AKR1B1) is a strong candidate for diabetic nephropathy, and the T allele at rs759853 and the Z-2 allele at an [AC](n) microsatellite are associated with diabetic kidney disease in some populations. As AKR1B1 is located on 7q35, where we have previously reported linkage to diabetic nephropathy in Pima Indians, this study examined the association of AKR1B1 variants with diabetic nephropathy in this population. Methods AKR1B1 variants were identified by sequencing and genotyped using allelic discrimination and pyrosequencing. Genotype distributions were compared between 107 cases with diabetic end-stage renal disease and 108 control subjects with diabetes for ! 10 years and no evidence of nephropathy, and between 141 individuals with nephropathy and 416 individuals without heavy proteinuria in a family study of 257 sibships. Results We identified 11 AKR1B1 single nucleotide polymorphisms (SNPs) and the [AC](n) microsatellite polymorphism. Three SNPs were rare and two were in 100% genotypic concordance; thus, eight polymorphisms were genotyped. No variant was associated with diabetic kidney disease in the case-control or family-based study. For example, the T allele at rs759853 had ail allele frequency of 0.165 in cases and 0.171 in control subjects (OR = 0.96, 95% CI, 0.57-1.59, P = 0.86); in the family study its frequency was 0.140 and 0.169 in affected and unaffected individuals, respectively (OR = 0.90, 95% CI, 0.53-1.54 P = 0.71). Corresponding values for the Z-2 allele at the [AC](n) microsatellite were OR = 1.09 (95% CI 0.72-1.66, P = 0.67) and OR = 1.25 (95% CI 0.81-1.95, P = 0.31) in the case-control and family studies, respectively. Conclusions Common AKR1B1 polymorphisms are unlikely to be major determinants of diabetic nephropathy in this population. C1 NIDDKD, Translat Genom Res Inst, Diabet Res Unit, NIH, Phoenix, AZ 85004 USA. NIDDKD, Diabet Epidemiol & Clin Res Sect, NIH, Phoenix, AZ 85004 USA. RP Wolford, JK (reprint author), NIDDKD, Translat Genom Res Inst, Diabet Res Unit, NIH, 445 N 5th St, Phoenix, AZ 85004 USA. EM jwolford@tgen.org RI Nelson, Robert/B-1470-2012; Hanson, Robert/O-3238-2015 OI Hanson, Robert/0000-0002-4252-7068 FU Intramural NIH HHS NR 36 TC 15 Z9 15 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0742-3071 J9 DIABETIC MED JI Diabetic Med. PD APR PY 2006 VL 23 IS 4 BP 367 EP 376 DI 10.1111/j.1464-5491.2006.01834.x PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 035SX UT WOS:000237023100005 PM 16620264 ER PT J AU Kuhn, JF Hoerth, P Hoehn, ST Preckel, T Tomer, KB AF Kuhn, JF Hoerth, P Hoehn, ST Preckel, T Tomer, KB TI Proteomics study of anthrax lethal toxin-treated murine macrophages SO ELECTROPHORESIS LA English DT Article DE anthrax; anthrax lethal toxin; Off-Gel (TM) electrophoresis; quantitative proteomics; O-18 labeling ID TANDEM MASS-SPECTROMETRY; QUANTITATIVE-ANALYSIS; PROTECTIVE ANTIGEN; INDUCED APOPTOSIS; CRYSTAL-STRUCTURE; CELL-DEATH; PROTEIN; IDENTIFICATION; ACTIVATION; RECEPTOR AB The anthrax lethal toxin (LeTx) is composed of two proteins, protective antigen and lethal factor, which bind and enter the cell through a host receptor termed the anthrax toxin receptor (ATR). In the cell, LeTx targets p38, part of the MAP kinase signaling pathway. The toxin appears to initiate an apoptotic pathway in infected cells, indicating additional downstream targets of the toxin. We have applied a proteomics approach to investigate these downstream targets and the affected processes. In this study we have used an improved strategy for fractionation based on protein pl, off-gel electrophoresis, employed in conjunction with relative quantitation using the mass labeling approach. In our survey, 67 proteins were observed and quantified from the cytosol of RAW 264.7 cells with respect to control versus toxin-treated cells. Many of these proteins are involved in the oxidative stress response, as well as apoptosis, and thus likely to be relevant to the effects of anthrax in infected cells. Our results indicate that the tumor necrosis factor-alpha-mediated pathway is compromised in intoxicated cells. The knowledge of such changes and the pathways leading to the changes should be of great value in understanding and combating this disease. C1 NIEHS, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Agilent Technol Inc, Waldbronn, Germany. RP Kuhn, JF (reprint author), NIEHS, NIH, DHHS, 111 TW Alexander Dr,MD F0-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM kuhn1@niehs.nih.gov RI Tomer, Kenneth/E-8018-2013 FU Intramural NIH HHS NR 67 TC 15 Z9 15 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD APR PY 2006 VL 27 IS 8 SI SI BP 1584 EP 1597 DI 10.1002/elps.200500747 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 042CM UT WOS:000237504800018 PM 16609935 ER PT J AU Viboud, C Tam, T Fleming, D Miller, MA Simonsen, L AF Viboud, C Tam, T Fleming, D Miller, MA Simonsen, L TI 1951 influenza epidemic, England and Wales, Canada, and the United States SO EMERGING INFECTIOUS DISEASES LA English DT Article ID 1918 PANDEMIC INFLUENZA; EXCESS MORTALITY; AGE DISTRIBUTION; IMPACT AB Influenza poses a continuing public health threat in epidemic and pandemic seasons. The 1951 influenza epidemic (A/H1N1) caused an unusually high death toll in England; in particular, weekly deaths in Liverpool even surpassed those of the 1918 pandemic. We further quantified the death rate of the 1951 epidemic in 3 countries. In England and Canada, we found that excess death rates from pneumonia and influenza and all causes were substantially higher for the 1951 epidemic than for the 1957 and 1968 pandemics (by >= 50%). The age-specific pattern of deaths in 1951 was consistent with that of other interpandemic seasons; no age shift to younger age groups, reminiscent of pandemics, occurred in the death rate. In contrast to England and Canada, the 1951 epidemic was not particularly severe in the United States. Why this epidemic was so severe in some areas but not others remains unknown and highlights major gaps in our understanding of interpandemic influenza. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Publ Hlth Agcy Canada, Ottawa, ON, Canada. Royal Coll Gen Practitioners, Birmingham, W Midlands, England. RP Viboud, C (reprint author), NIH, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA. EM viboudc@mail.nih.gov OI Simonsen, Lone/0000-0003-1535-8526 NR 37 TC 27 Z9 30 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD APR PY 2006 VL 12 IS 4 BP 661 EP 668 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 028BJ UT WOS:000236460200018 PM 16704816 ER PT J AU Palacios, G Briese, T Kapoor, V Jabado, O Liu, ZQ Venter, M Zhai, JH Renwick, N Grolla, A Geisbert, TW Drosten, C Towner, J Ju, JY Paweska, J Nichol, ST Swanepoel, R Feldmann, H Jahrling, PB Lipkin, WI AF Palacios, G Briese, T Kapoor, V Jabado, O Liu, ZQ Venter, M Zhai, JH Renwick, N Grolla, A Geisbert, TW Drosten, C Towner, J Ju, JY Paweska, J Nichol, ST Swanepoel, R Feldmann, H Jahrling, PB Lipkin, WI TI MassTag polymerase chain reaction for differential diagnosis of viral hemorrhagic fevers SO EMERGING INFECTIOUS DISEASES LA English DT Article ID VACCINES; RIBAVIRIN; THERAPY AB Viral hemorrhagic fevers are associated with high rates of illness and death. Although therapeutic options are limited, early differential diagnosis has implications for containment and may aid in clinical management. We describe a diagnostic system for rapid, multiplex polymerase chain reaction identification of 10 different causes of viral hemorrhagic fevers. C1 Columbia Univ, Greene Infect Dis Lab, Mailman Sch Publ Hlth, New York, NY 10032 USA. Univ Pretoria, ZA-0002 Pretoria, South Africa. Natl Hlth Lab Serv, Pretoria, South Africa. Publ Hlth Agcy Canada, Winnipeg, MB, Canada. USA, Med Res Inst Infect Dis, Frederick, MD USA. Bernhard Nocht Inst Trop Med, Hamburg, Germany. Ctr Dis Control & Prevent, Atlanta, GA USA. Natl Inst Communicable Dis, Johannesburg, South Africa. Univ Manitoba, Winnipeg, MB, Canada. NIAID, Integrated Res Facil, Frederick, MD USA. RP Briese, T (reprint author), Columbia Univ, Greene Infect Dis Lab, Mailman Sch Publ Hlth, 722 W 168th St,Rm 1801, New York, NY 10032 USA. EM thomas.briese@columbia.edu RI Jabado, Omar/B-3406-2008; Venter, Marietjie/H-3032-2011; Palacios, Gustavo/I-7773-2015; Venter, Marietjie/P-9604-2016 OI Palacios, Gustavo/0000-0001-5062-1938; Venter, Marietjie/0000-0003-2696-824X FU NIAID NIH HHS [AI056118, AI51292, AI55466, R01 AI051292, R21 AI055466, R21 AI056118, U54 AI057158, U54AI57158] NR 15 TC 40 Z9 46 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD APR PY 2006 VL 12 IS 4 BP 692 EP 695 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 028BJ UT WOS:000236460200027 PM 16704825 ER PT J AU Jaeschke, H Neumann, S Kleinau, G Mueller, S Claus, M Krause, G Paschke, R AF Jaeschke, H Neumann, S Kleinau, G Mueller, S Claus, M Krause, G Paschke, R TI An aromatic environment in the vicinity of serine 281 is a structural requirement for thyrotropin receptor function SO ENDOCRINOLOGY LA English DT Article ID LUTEINIZING-HORMONE RECEPTOR; LUTROPIN CHORIOGONADOTROPIN RECEPTOR; THYROID-STIMULATING HORMONE; TSH RECEPTOR; CONSTITUTIVE ACTIVITY; EXTRACELLULAR DOMAIN; TRANSMEMBRANE DOMAIN; SIGNAL GENERATION; HINGE REGION; ACTIVATION AB The majority of constitutively activating human TSH receptor ( hTSHR) mutations are located in the transmembrane helices as well as in the extracellular (ECLs) and intracellular loops. S-281 is one of two positions in the ectodomain in which activating hTSHR mutations have been identified in vivo (S281T, I, and N). To investigate the functional properties of this key residue in more detail, S281 was replaced by each of the other 19 amino acids. Many substitutions led to constitutive receptor activation, suggesting that S281 plays a pivotal role in maintaining the receptor in its inactive state. Strikingly, all substitutions with aromatic residues (S281W, F, Y, and H) show expression similar to that of wild-type hTSHR and are tolerated at this position because they maintain basal activity or express only slight constitutive activity. Three-dimensional modeling of the hTSHR suggested that S-281 and surrounding residues are in close proximity to ECL1. To investigate the possible importance of an aromatic environment between the ectodomain in the vicinity of S-281 and ECL1, aromatic residues Y-279, Y-476, H-478, Y-481, Y-482, and H-484 were replaced by alanine. Functional characterization showed impaired cell surface expression and signaling for Y(279)A and Y(481)A, in contrast to the other alanine mutants. However, substitutions of Y279 and Y481 with other aromatic residues exhibited surface expression and signaling comparable to wild-type hTSHR. Our results suggest that Y-279 in the extracellular domain and probably Y-481 in the ECL1 also are involved in an aromatic environment around S-281 in the hTSHR, which is important for functional receptor conformation and intramolecular receptor signaling. C1 Univ Leipzig, Dept Med 3, D-04103 Leipzig, Germany. NIDDK, NIH, Bethesda, MD 20892 USA. Leibniz Inst Mol Pharmacol, D-13125 Berlin, Germany. RP Paschke, R (reprint author), Univ Leipzig, Dept Med 3, Ph Rosenthal Str 27, D-04103 Leipzig, Germany. EM ralf.paschke@medizin.uni-leipzig.de OI Claus, Maren/0000-0001-8732-0645 NR 48 TC 28 Z9 28 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD APR PY 2006 VL 147 IS 4 BP 1753 EP 1760 DI 10.1210/en.2005-1138 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 022HA UT WOS:000236045000021 PM 16410307 ER PT J AU Lee, WJ Baccarelli, A Tretiakova, M Gorbanev, S Lomtev, A Klimkina, I Tchibissov, V Averkina, O Dosemeci, M AF Lee, WJ Baccarelli, A Tretiakova, M Gorbanev, S Lomtev, A Klimkina, I Tchibissov, V Averkina, O Dosemeci, M TI Pesticide exposure and lung cancer mortality in Leningrad province in Russia SO ENVIRONMENT INTERNATIONAL LA English DT Article DE lung neoplasms; occupation; pesticide exposure; Russia ID AGRICULTURAL HEALTH; PHENOXY HERBICIDES; COHORT; APPLICATORS; WORKERS; RISK; DIOXINS; FLORIDA; ACID AB This study was carried out to examine the association between pesticide exposure and lung cancer mortality, We conducted an autopsy based case-control study in Leningrad Province in Russia. A total of 540 lung cancer cases and 582 controls were identified among subjects who had died in the hospitals of the Leningrad province between 1993 and 1998. Using work history records, we assessed exposure to pesticide at the level of industry and job title. Unconditional logistic regression was used to calculate adjusted odds ratio for pesticide exposure and lung cancer mortality. There was no association between ever exposure to pesticide and lung cancer mortality overall (odds ratio=1.06, 95% confidence interval=0.82-1.36) and in both men (odds ratio=1.11, 95% confidence interval =0.84-1.46) and women (odds ratio=0.74, 95% confidence interval=0.37-1.46). We observed no statistically significant odds ratio by duration of pesticide exposure, intensity of pesticide exposure, and cumulative pesticide exposures with lung cancer mortality in both smokers and nonsmokers. Odds ratio also did not differ when the analysis was restricted to individuals who had exposure data with high confidence scores. Our findings suggest no associations between pesticide exposures and mortality of lung cancer in the population of the Leningrad province in Russia that deserves further evaluation. (c) 2005 Elsevier Ltd. All rights reserved. C1 Korea Univ, Coll Med, Dept Prevent Med, Seoul 136705, South Korea. Natl Canc Inst, Div Canc Epidemiol & Genet, Rockville, MD USA. Univ Milan, Dept Environm & Occupat Hlth, Milan, Italy. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. Reg Ctr Hyg & Sanitat, St Petersburg, Russia. Leningrad Oblast Pathol Bur, St Petersburg, Russia. RP Lee, WJ (reprint author), Korea Univ, Coll Med, Dept Prevent Med, 126-1,5-KA,Anam Dong, Seoul 136705, South Korea. EM leewj@korea.ac.kr OI Baccarelli, Andrea/0000-0002-3436-0640 NR 26 TC 3 Z9 3 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0160-4120 J9 ENVIRON INT JI Environ. Int. PD APR PY 2006 VL 32 IS 3 BP 412 EP 416 DI 10.1016/j.envint.2005.10.001 PG 5 WC Environmental Sciences SC Environmental Sciences & Ecology GA 027IP UT WOS:000236409200015 PM 16280162 ER PT J AU Cohn, RD Arbes, SJ Jaramillo, R Reid, LH Zeldin, DC AF Cohn, RD Arbes, SJ Jaramillo, R Reid, LH Zeldin, DC TI National prevalence and exposure risk for cockroach allergen in US households SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE allergens; asthma; Bla g 1; cockroach allergen ID INNER-CITY CHILDREN; SKIN-TEST RESPONSES; ENVIRONMENTAL INTERVENTION; INDOOR ALLERGENS; LOW-INCOME; DUST-MITE; ASTHMA; HOMES; QUESTIONNAIRE; SENSITIZATION AB We characterized the prevalence of cockroach allergen exposure in a nationally representative sample of U.S. homes and assessed risk factors for elevated concentrations. DESIGN: We used data from the National Survey of Lead and Allergens in Housing, a population-based cross-sectional survey. PARTICIPANTS: Participants were residents of 831 U.S. homes in the survey. EVALUATIONS/MEASUREMENTS: We analyzed allergen, questionnaire, and observational data of 831 U.S. homes. RESULTS: Cockroach allergen (Bla g 1) concentrations exceed 2.0 U/g, a level associated with allergic sensitization, in 11% of U.S. living room floors and 13% of kitchen floors. Concentrations exceed 8.0 U/g, a level associated with asthma morbidity, in 3% of living room floors and 10% of kitchen floors. Elevated concentrations were observed in high-rise apartments, urban settings, pre-1940 constructions, and households with incomes < $20,000. Odds of having concentrations > 8.0 U/g were greatest when roach problems were reported or observed and increased with the number of cockroaches observed and with indications of recent cockroach activity. CONCLUSIONS: Household cockroach allergen exposure is characterized in a nationally representative context. The allergen is prevalent in many settings, at levels that may contribute to allergic sensitization and asthma morbidity. RELEVANCE TO CLINICAL OR PROFESSIONAL PRACTICE: Likelihood of exposure can be assessed by consideration of demographic and household determinants. C1 NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Constella Grp LLC, Durham, NC USA. RP Zeldin, DC (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, 11 Alexander Dr,Mail Drop D2-02, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov FU Intramural NIH HHS NR 27 TC 50 Z9 52 U1 1 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2006 VL 114 IS 4 BP 522 EP 526 DI 10.1289/ehp.8561 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 030QX UT WOS:000236650500034 PM 16581539 ER PT J AU Peddada, SD Kissling, GE AF Peddada, SD Kissling, GE TI A survival-adjusted quantal-response test for analysis of tumor incidence rates in animal carcinogenicity studies SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cancer bioassay; Cochran-Armitage trend test; multiple pairwise comparisons; National Toxicology Program; order-restricted inference; poly-3 trend test ID ORDER RESTRICTIONS AB In rodent cancer bioassays, groups of animals are exposed to different doses of a chemical of interest and followed for tumor occurrence. The resulting tumor rates are commonly analyzed using a survival-adjusted Cochran-Armitage (CA) trend test. The CA trend test has reasonable power when the tumor-response curve is linear in dose, but it may be underpowered for a nonlinear response. An alternative survival-adjusted test procedure based on isotonic regression methodology has previously been proposed. Although this alternative procedure performs well when the tumor response is nonlinear in dose, it has less power than the CA trend test when the response is linear in dose. Here, we introduce a new survival-adjusted test procedure that makes use of both the CA trend test and the isotonic regression-based trend test. Using a broad range of experimental conditions typical of National Toxicology Program (NTP) bioassays, we conducted extensive computer simulations to compare the false-positive error rate and power of the proposed procedure with the survival-adjusted CA trend test. The new procedure competes well with the survival-adjusted CA trend test when observed tumor rates are linear in dose and performs substantially better when observed tumor rates are nonlinear in dose. Further, the proposed trend test almost always has a smaller false-positive rate than does the survival-adjusted CA trend test. We also developed an order-restricted inference-based procedure for performing multiple pairwise comparisons between each of the dose groups and the control group. The trend test and the multiple pairwise comparisons test are demonstrated using an example from a study conducted by the NTP. C1 NIEHS, Biostat Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Peddada, SD (reprint author), NIEHS, Biostat Branch, NIH, Dept Hlth & Human Serv, MD A3-03, Res Triangle Pk, NC 27709 USA. EM peddada@niehs.nih.gov RI Peddada, Shyamal/D-1278-2012 FU Intramural NIH HHS NR 10 TC 7 Z9 7 U1 3 U2 9 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2006 VL 114 IS 4 BP 537 EP 541 DI 10.1289/ehp.8590 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 030QX UT WOS:000236650500037 PM 16581542 ER PT J AU Zhou, T Chou, JW Simpson, DA Zhou, YC Mullen, TE Medeiros, M Bushel, PR Paules, RS Yang, XB Hurban, P Lobenhofer, EK Kaufmann, WK AF Zhou, T Chou, JW Simpson, DA Zhou, YC Mullen, TE Medeiros, M Bushel, PR Paules, RS Yang, XB Hurban, P Lobenhofer, EK Kaufmann, WK TI Profiles of global gene expression in ionizing-radiation-damaged human diploid fibroblasts reveal synchronization behind the G(1) checkpoint in a G(0)-like state of quiescence SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE cell cycle checkpoints; DNA damage; gene expression; human fibroblasts; ionizing radiation; microarray ID DNA-DAMAGE; CELL-CYCLE; GAMMA-IRRADIATION; P53; ARREST; GROWTH; PATHWAY; KINASE; RADIOSENSITIVITY; INACTIVATION AB Cell cycle arrest and stereotypic transcriptional responses to DNA damage induced by ionizing radiation (IR) were quantified in telomerase-expressing human diploid fibroblasts. Analysis of cytotoxicity demonstrated that 1.5 Gy IR inactivated colony formation by 40-45% in three fibroblast lines; this dose was used in all subsequent analyses. Fibroblasts exhibited > 90% arrest of progression from G(2) to M at 2 hr post-IR and a similarly severe arrest of progression from G(1) to S at 6 and 12 hr post-IR. Normal rates of DNA synthesis and mitosis 6 and 12 hr post-IR caused the S and M compartments to empty by > 70% at 24 hr. Global gene expression was analyzed in IR-treated cells. A microarray analysis algorithm, EPIG, identified nine IR-responsive patterns of gene expression that were common to the three fibroblast lines, including a dominant p53-dependent G(1) checkpoint response. Many p53 target genes, such as CDKN1A, GADD45, BTG2, and PLK3, were significantly up-regulated at 2 hr post-IR. Many genes whose expression is regulated by E2F family transcription factors, including CDK2, CCNE1, CDC6, CDC2, MCM2, were significantly down-regulated at 24 hr post-IR. Numerous genes that participate in DNA metabolism were also markedly repressed in arrested fibroblasts apparently as a result of cell synchronization behind the G(1) checkpoint. However, cluster and principal component analyses of gene expression revealed a profile 24 hr post-IR with similarity to that of G(0) growth quiescence. The results reveal a highly stereotypic pattern of response to IR in human diploid fibroblasts that reflects primarily synchronization behind the G, checkpoint but with prominent induction of additional markers of GO quiescence such as GAS1. C1 Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Ctr Environm Hlth & Susceptibil, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Icoria Inc, Paradigm Array Labs, Res Triangle Pk, NC USA. RP Kaufmann, WK (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, CB 7295,Room 31-325, Chapel Hill, NC 27599 USA. EM wkarlk@med.unc.edu FU NIEHS NIH HHS [P30 ES010126, ES 10126, U19 ES011391, ES 11391, N01ES25497, N01 ES 25497] NR 43 TC 40 Z9 43 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2006 VL 114 IS 4 BP 553 EP 559 DI 10.1289/ehp.8026 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 030QX UT WOS:000236650500040 PM 16581545 ER PT J AU Chen, AM Rhoads, GG Cai, B Salganik, M Rogan, WJ AF Chen, AM Rhoads, GG Cai, B Salganik, M Rogan, WJ TI The effect of chelation on blood pressure in lead-exposed children: A randomized study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE blood pressure; chelation; child; lead; succimer ID YOUNG-CHILDREN; BONE LEAD; HYPERTENSION; LEVEL; RATS; ASSOCIATION; THERAPY; CALCIUM; WORKERS; RENIN AB Studies in children suggest a weak association between blood lead concentration and blood pressure. To understand this better, we tested the strength of the association in children with elevated blood lead concentrations and whether succimer chelation changed blood pressure as it did blood lead. In a randomized clinical trial of 780 children with blood lead concentrations of 20-44 mu g/dL at 12-33 months of age, we compared the systolic and diastolic blood pressure in the succimer-treated group and placebo group for up to 5 years of follow-up. We also analyzed the relation of blood lead to blood pressure. Children in the succimer group had lower blood lead concentrations for 9-10 months during and after treatment, but their blood pressure did not differ from those in the placebo group during this period. During 1-5 years of follow-up, children in the succimer group had systolic blood pressure 1.09 (95% confidence interval, 0.27-1.90) mmHg higher than did untreated children in a model with repeated measurements, but the difference in diastolic blood pressure was not statistically significant. No association between blood lead and blood pressure was found. Overall, there is no association between blood lead and blood pressure in these children with moderately high lead exposure, nor does chelation with succimer change blood pressure. C1 NIEHS, Epidemiol Branch, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. Univ Med & Dent New Jersey, Environm & Occupat Hlth Sci Inst, Piscataway, NJ 08854 USA. US Dept HHS, Biostat Branch, NIEHS, NIH, Res Triangle Pk, NC USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. RP Rogan, WJ (reprint author), NIEHS, Epidemiol Branch, NIH, US Dept HHS, MD A3-05,POB 12233, Res Triangle Pk, NC 27709 USA. EM rogan@nichs.nih.gov RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 NR 39 TC 7 Z9 8 U1 2 U2 5 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2006 VL 114 IS 4 BP 579 EP 583 DI 10.1289/ehp.8634 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 030QX UT WOS:000236650500044 PM 16581549 ER PT J AU Selgrade, MK Lemanske, RF Gilmour, MI Neas, LM Ward, MDW Henneberger, PK Weissman, DN Hoppin, JA Dietert, RR Sly, PD Geller, AM Enright, PL Backus, GS Bromberg, PA Germolec, DR Yeatts, KB AF Selgrade, MK Lemanske, RF Gilmour, MI Neas, LM Ward, MDW Henneberger, PK Weissman, DN Hoppin, JA Dietert, RR Sly, PD Geller, AM Enright, PL Backus, GS Bromberg, PA Germolec, DR Yeatts, KB TI Induction of asthma and the environment: What we know and need to know SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air pollution; allergy; asthma economic impact; asthma induction; asthma prevalence; biologics; indoor environment; occupational exposure; public health; susceptibility ID DETERGENT INDUSTRY; RISK-FACTORS; SENSITIZATION; PREVENTION; EXPOSURE; APPRENTICES; EDUCATION; ALLERGY; IMPACT AB The prevalence of asthma has increased dramatically over the last 25 years in the United States and in other nations as a result of ill-defined changes in living conditions in modern society. On 18 and 19 October 2004 the U.S. Environmental Protection Agency and the National Institute of Environmental Health Sciences sponsored the workshop "Environmental Influences on the Induction and Incidence of Asthma" to review current scientific evidence with respect to factors that may contribute to the induction of asthma. Participants addressed two broad questions: a) What does the science suggest that regulatory and public health agencies could do now to reduce the incidence of asthma? and b) What research is needed to improve our understanding of die factors that contribute to the induction of asthma and our ability to manage this problem? In this article (one of four articles resulting from the workshop), we briefly characterize asthma and its public health and economic impacts, and intervention strategies that have been successfully used to prevent induction of asthma in the workplace. We conclude with the findings of seven working groups that focus on ambient air, indoor pollutants (biologics), occupational exposures, early life stages, older adults, intrinsic susceptibility, and lifestyle. These groups found strong scientific support for public health efforts to limit in utero and postnatal exposure to cigarette smoke. However, with respect to other potential types of interventions, participants noted many scientific questions, which are summarized in this article. Research to address these questions could have a significant public health and economic impact that would be well worth the investment. C1 US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Univ Wisconsin, Div Pediat Allergy Immunol & Rheumatol, Madison, WI 53706 USA. NIOSH, Morgantown, WV 26505 USA. NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Ithaca, NY 14853 USA. Univ Western Australia, Ctr Child Hlth Res, Perth, WA 6009, Australia. Univ N Carolina, Sch Med, Ctr Environm Med Asthma & Lung Biol, Chapel Hill, NC USA. RP Selgrade, MK (reprint author), US EPA, Natl Hlth & Environm Effects Res Lab, MD B143-01, Res Triangle Pk, NC 27711 USA. EM selgrade.maryjane@epa.gov RI Sly, Peter/F-1486-2010; Neas, Lucas/J-9378-2012; Osborne, Nicholas/N-4915-2015 OI Sly, Peter/0000-0001-6305-2201; Osborne, Nicholas/0000-0002-6700-2284 FU Intramural NIH HHS NR 36 TC 55 Z9 59 U1 0 U2 6 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2006 VL 114 IS 4 BP 615 EP 619 DI 10.1289/ehp.8376 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 030QX UT WOS:000236650500050 PM 16581555 ER PT J AU Zeldin, DC Eggleston, P Chapman, M Piedimonte, G Renz, H Peden, D AF Zeldin, DC Eggleston, P Chapman, M Piedimonte, G Renz, H Peden, D TI How exposures to biologics influence the induction and incidence of asthma SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE asthma; allergy; allergens; endotoxin; respiratory virus; immunoglobulins; tolerance; leukotrienes; neurotrophins ID RESPIRATORY SYNCYTIAL VIRUS; NERVE GROWTH-FACTOR; DUST-MITE ALLERGEN; MODIFIED TH2 RESPONSE; SUBSTANCE-P RECEPTOR; EARLY-LIFE; COCKROACH ALLERGEN; CRYSTAL-STRUCTURE; NEUROGENIC INFLAMMATION; AIRWAY INFLAMMATION AB A number of environmental factors can affect the development and severity of allergy and asthma; however, it can be argued that the most significant inhaled agents that modulate the development of these conditions are biologics. Sensitization to environmental allergens is an important risk factor for the development of asthma. Innate immune responses are often mediated by receptors on mononuclear cells whose primary ligands arise from microorganisms. Many pathogens, especially viruses, target epithelial cells and affect the host immune response to those pathogens. The acquired immune response to an allergen is influenced by the nature of the innate immune system. Products of innate immune responses to microbes promote T(H)1-acquired responses. In the absence of T(H)1 responses, T(H)2 responses can dominate. Central to T(H)1/T(H)2 balance is the composition of contaminants that derive from microbes. In this review we examine the biology of the response to allergens, viruses, and bacterial products in the context of the development of allergy and asthma. C1 NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Johns Hopkins Univ, Dept Pediat, Baltimore, MD 21218 USA. Univ Virginia, Dept Med, Charlottesville, VA USA. W Virginia Univ, Dept Pediat, Morgantown, WV 26506 USA. Univ Marburg, Dept Clin Chem, D-35032 Marburg, Germany. Univ N Carolina, Dept Pediat, Chapel Hill, NC USA. RP Zeldin, DC (reprint author), NIEHS, Div Intramural Res, NIH, Dept Hlth & Human Serv, 11 TW Alexander Dr,Bldg 101,Rm D236, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov FU NHLBI NIH HHS [R01 HL061007, R01 HL 61007]; NIEHS NIH HHS [R44 ES011920, R01 ES 012706, R44 ES 011920, P01 ES 09606, P01 ES009606, R01 ES012706] NR 93 TC 44 Z9 46 U1 0 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2006 VL 114 IS 4 BP 620 EP 626 DI 10.1289/ehp.8379 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 030QX UT WOS:000236650500051 PM 16581556 ER PT J AU Gilmour, M Jaakkola, MS London, SJ Nel, AE Rogers, CA AF Gilmour, M Jaakkola, MS London, SJ Nel, AE Rogers, CA TI How exposure to environmental tobacco smoke, outdoor air pollutants, and increased pollen burdens influences the incidence of asthma SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE air pollution; asthma; cigarette smoke; climate change; diesel exhaust; environment; inflammation; mechanisms; ozone; particulate matter; pollen ID EXHAUST PARTICLE CHEMICALS; LOWER RESPIRATORY ILLNESS; DIESEL EXHAUST; PARENTAL SMOKING; OXIDATIVE STRESS; ATMOSPHERIC CO2; ELEVATED CO2; CARBON-DIOXIDE; CLIMATE-CHANGE; HEALTH AB Asthma is a multifactorial airway disease that arises from a relatively common genetic background interphased with exposures to allergens and airborne irritants. The rapid rise in asthma over the past three decades in Western societies has been attributed to numerous diverse factors, including increased awareness of the disease, altered lifestyle and activity patterns, and ill-defined changes in environmental exposures. It is well accepted that persons with asthma are more sensitive than persons without asthma to air pollutants such as cigarette smoke, traffic emissions, and photochemical smog components. It has also been demonstrated that exposure to a mix of allergens and irritants can at times promote the development phase (induction) of the disease. Experimental evidence suggests that complex organic molecules from diesel exhaust may act as allergic adjuvants through the production of oxidative stress in airway cells. It also seems that climate change is increasing the abundance of aeroallergens Such as pollen, which may result in greater incidence or severity of allergic diseases. In this review we illustrate how environmental tobacco smoke, outdoor air pollution, and climate change may act as environmental risk factors for the development of asthma and provide mechanistic explanations for how some of these effects can occur. C1 US EPA, Res Triangle Pk, NC 27711 USA. Univ Birmingham, Inst Occupat & Environm Med, Birmingham, AL USA. NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Univ Calif Los Angeles, Dept Med, Los Angeles, CA 90024 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Gilmour, M (reprint author), US EPA, Res Triangle Pk, NC 27711 USA. EM gilmour.ian@epa.gov RI Rogers, Christine/A-2189-2008; Nel, Andre/J-2808-2012; Osborne, Nicholas/N-4915-2015; OI Rogers, Christine/0000-0003-0887-9606; Osborne, Nicholas/0000-0002-6700-2284; London, Stephanie/0000-0003-4911-5290 NR 77 TC 175 Z9 177 U1 4 U2 41 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2006 VL 114 IS 4 BP 627 EP 633 DI 10.1289/ehp.8380 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 030QX UT WOS:000236650500052 PM 16581557 ER PT J AU Schwartz, DA Martin, WJ AF Schwartz, DA Martin, WJ TI Translating translational biomedicine for environmental health SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Res Triangle Pk, NC 27709 USA. RP Schwartz, DA (reprint author), NIEHS, Res Triangle Pk, NC 27709 USA. EM david.schwartz@niehs.nih.gov; wjmartin@niehs.nih.gov NR 0 TC 0 Z9 0 U1 1 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 2006 VL 114 IS 4 BP A206 EP A206 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 030QX UT WOS:000236650500002 PM 16581522 ER PT J AU Galperin, MY AF Galperin, MY TI The minimal genome keeps growing SO ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI K-12; ANAEROBIC BACTERIUM; GENE-SET; SYNTROPHUS-ACIDITROPHICUS; MYXOCOCCUS-XANTHUS; SEQUENCE; CELL; MICROORGANISMS; FUMIGATUS; BENZOATE C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 30 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD APR PY 2006 VL 8 IS 4 BP 569 EP 573 DI 10.1111/j.1462-2920.2060.01021.x PG 5 WC Microbiology SC Microbiology GA 020EU UT WOS:000235892000001 PM 16584469 ER PT J AU Domanski, M AF Domanski, M TI Prognosis in atrial fibrillation SO EUROPEAN HEART JOURNAL LA English DT Editorial Material ID STROKE PREVENTION; WARFARIN; RISK; RHYTHM C1 NHLBI, Clin Trials Grp, Bethesda, MD 20892 USA. RP Domanski, M (reprint author), NHLBI, Clin Trials Grp, Bldg 10, Bethesda, MD 20892 USA. EM domanskm@nih.gov NR 11 TC 3 Z9 3 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0195-668X J9 EUR HEART J JI Eur. Heart J. PD APR PY 2006 VL 27 IS 8 BP 895 EP 896 DI 10.1093/eurheartj/ehi756 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 027SK UT WOS:000236435500003 PM 16449247 ER PT J AU Malila, N Virtanen, MJ Virtamo, J Albanes, D Pukkala, E AF Malila, N Virtanen, MJ Virtamo, J Albanes, D Pukkala, E TI Cancer incidence in a cohort of Finnish male smokers SO EUROPEAN JOURNAL OF CANCER PREVENTION LA English DT Article DE standardized incidence ratio; cancer; smoking ID CIGARETTE-SMOKING; COLORECTAL-CANCER; PROSTATE-CANCER; PHYSICIANS HEALTH; BETA-CAROTENE; UNITED-STATES; RISK; TOBACCO; REGISTRY; FINLAND AB A total of 29133 male smokers, aged 50-69 years, were recruited into the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study in 1984-1988. The nationwide Finnish Cancer Registry (FCR) recorded 5944 incident cases of cancer in this cohort through the end of 1999. Compared with the FCR data of the entire Finnish male population of same age the standardized incidence ratio (SIR) of total cancer in the ATBC cohort was 1.55 [95% confidence interval (CI) 1.51-1.59]. There was a significant excess of established smoking-related malignancies, such as lung cancer (SIR 2.45, 95% Cl 2.35-2.56), and cancers of the tongue, mouth, pharynx, larynx, oesophagus, pancreas, stomach, liver, urinary bladder and kidney. In addition to these sites, cancers of the prostate and colon were slightly more common in the ATBC cohort than in the total Finnish male population (SIR 1.10, 95% Cl 1.04-1.18 and SIR 1.14, 95% Cl 1.00-1.30, respectively). In conclusion, the risk of many cancers was significantly higher in the ATBC Study cohort compared with the total Finnish male population of same age. In addition to the well known smoking-related cancers, cigarette smoking may increase slightly the risk of colon and prostate cancer, too. C1 Finnish Canc Registry, Inst Stat & Epidemiol Canc Res, FIN-00170 Helsinki, Finland. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. NCI, Bethesda, MD USA. RP Malila, N (reprint author), Finnish Canc Registry, Inst Stat & Epidemiol Canc Res, Liisankatu 21B, FIN-00170 Helsinki, Finland. EM nea.malila@cancer.fi RI Albanes, Demetrius/B-9749-2015 NR 18 TC 7 Z9 7 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-8278 J9 EUR J CANCER PREV JI Eur. J. Cancer Prev. PD APR PY 2006 VL 15 IS 2 BP 103 EP 107 DI 10.1097/01.cej.0000197448.49239.60 PG 5 WC Oncology SC Oncology GA 033QO UT WOS:000236864100001 PM 16523006 ER PT J AU Mahabir, S Baer, DJ Giffen, C Subar, A Campbell, W Hartman, TJ Clevidence, B Albanes, D Taylor, PR AF Mahabir, S Baer, DJ Giffen, C Subar, A Campbell, W Hartman, TJ Clevidence, B Albanes, D Taylor, PR TI Calorie intake misreporting by diet record and food frequency questionnaire compared to doubly labeled water among postmenopausal women SO EUROPEAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE energy intake misreporting; doubly labeled water; postmenopausal women ID REPORTED ENERGY-INTAKE; MIDDLE-AGED WOMEN; ROOM CALORIMETRY; URINARY NITROGEN; INTAKE-BALANCE; RISK-FACTORS; EXPENDITURE; VALIDATION; CANCER; MENOPAUSE AB Objective: We assessed the extent of energy misreporting from the use of a self-administered 7-day diet record (7-DDR) and a widely used food frequency questionnaire (FFQ) compared to total energy expenditure from doubly labeled water (DLW) in a group of postmenopausal women. Design: At baseline, 65 healthy postmenopausal women were instructed to fill out the National Cancer Institute's (NCI) FFQ and a 7-DDR. Average total energy expenditure using the DLW method was also performed at baseline. Results: On average, the women underestimated total energy intake compared to total energy expenditure assessed from DLW by 37% on the 7-DDR and 42% on the FFQ. Conclusions: These findings suggest that the interpretation of findings from the 7-DDR- and FFQ-based energy-disease association studies in postmenopausal women needs further evaluation. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Agr Res Serv, Human Nutr Res Ctr, USDA, Beltsville, MD USA. Informat Management Serv Inc, Silver Spring, MD USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Penn State Univ, Dept Nutr, University Pk, PA 16802 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Mahabir, S (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM smahabir@mdanderson.org RI Mahabir, Somdat/A-9788-2008; Albanes, Demetrius/B-9749-2015 FU Intramural NIH HHS NR 21 TC 30 Z9 30 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0954-3007 J9 EUR J CLIN NUTR JI Eur. J. Clin. Nutr. PD APR PY 2006 VL 60 IS 4 BP 561 EP 565 DI 10.1038/sj.ejcn.1602359 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 029AL UT WOS:000236530100016 PM 16391574 ER PT J AU Walcheck, B Herrera, AH Hill, CS Mattila, PE Whitney, AR DeLeo, FR AF Walcheck, B Herrera, AH Hill, CS Mattila, PE Whitney, AR DeLeo, FR TI ADAM17 activity during human neutrophil activation and apoptosis SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE apoptosis; human; inflammation; neutrophil ID TUMOR-NECROSIS-FACTOR; ALPHA-CONVERTING-ENZYME; HUMAN POLYMORPHONUCLEAR LEUKOCYTES; ADHESION MOLECULE EXPRESSION; SOLUBLE L-SELECTIN; DOWN-REGULATION; PROTEIN-KINASE; IN-VITRO; MONOCLONAL-ANTIBODY; RECEPTOR AB Substrates of the metalloprotease ADAM17 (also known as TNF-alpha converting enzyme or TACE) undergo ectodomain shedding and include various inflammatory modulators. Though polymorphonuclear leukocytes contribute significantly to inflammation, direct analyses of ADAM17 on human neutrophils are very limited. In addition, the current understanding of the processes regulating ADAM17 activity primarily relate to its rapid activation. Therefore, to extend insights into the mechanisms of ADAM17 activity, we examined its surface expression and the shedding of its substrates during extended periods of neutrophil activation and apoptosis. Contrary to studies with immortalized hematopoietic cell lines, we report that surface expression of ADAM17 is maintained by human neutrophils activated with formyl peptides or by FcR/complement receptor-mediated phagocytosis. Interestingly, bacterial phagocytosis resulted in a significant increase in ADAM17 expression several hours after pathogen engulfment. We provide novel evidence that ADAM17 surface expression is also maintained during spontaneous and anti-Fas-induced neutrophil apoptosis. The well-validated ADAM17 substrates L-selectin and proTNF-alpha were shed efficiently by neutrophils under each of the conditions tested. Our data thus indicate prolonged ADAM17 expression during neutrophil effector functions. The implications of this may be a role by ADAM17 in both the induction and down-regulation of neutrophil activity. C1 Univ Minnesota, Dept Vet & Biomed Sci, St Paul, MN 55108 USA. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. RP Walcheck, B (reprint author), Univ Minnesota, Dept Vet & Biomed Sci, 295 AS-VM Bldg,1988 Fitch Ave, St Paul, MN 55108 USA. EM walch003@umn.edu OI DeLeo, Frank/0000-0003-3150-2516 FU NHLBI NIH HHS [HL61613] NR 63 TC 37 Z9 37 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD APR PY 2006 VL 36 IS 4 BP 968 EP 976 DI 10.1002/eji.200535257 PG 9 WC Immunology SC Immunology GA 035DH UT WOS:000236979900019 PM 16541467 ER PT J AU Nomura, M Andersson, S Korach, KS Gustafsson, JA Pfaff, DW Ogawa, S AF Nomura, M Andersson, S Korach, KS Gustafsson, JA Pfaff, DW Ogawa, S TI Estrogen receptor-beta gene disruption potentiates estrogen-inducible aggression but not sexual behaviour in male mice SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE androgen receptor; knockout mouse; estrogen receptor alpha; sex difference; testosterone ID CENTRAL-NERVOUS-SYSTEM; ER-BETA; ALPHA GENE; PARAVENTRICULAR NUCLEUS; OXYTOCIN GENE; FEMALE MICE; RAT-BRAIN; VASOPRESSIN; EXPRESSION; NEURONS AB Aggressive behaviour of gonadally intact male mice is increased by estrogen receptor (ER)-beta gene disruption, whereas sexual behaviour remains unchanged. The elevated aggression levels following ER-beta gene disruption is pronounced during repeated aggression tests in young animals and the first aggression test in adults. In the present study, the roles of ER-beta activation in the regulation of aggressive and sexual behaviour were investigated in gonadectomized ER-beta knockout (beta ERKO) and wild-type (WT) male mice treated with various doses of estrogen. Overall, estradiol benzoate (EB) treatment induced higher levels of aggression in beta ERKO mice than in WT mice. In WT mice, the levels of aggression induced by EB were highest in the lowest-dose (2.5 mu g/day) group and gradually decreased in higher-dosage groups. On the other hand, equally high levels of aggressive behaviour were induced by all three doses of EB in beta ERKO mice. A marked genotype difference in dose responses is inferred, such that the ER-alpha-mediated facilitatory action of estrogen is more pronounced at lower and physiological doses and the ER-beta-mediated inhibitory action is only unveiled at higher doses of estrogen. In contrast to aggression, the levels of sexual behaviour induced by EB were not different between beta ERKO and WT at either dose of EB (2.5 and 12.5 mu g/day) examined. These findings support the notion that ER-beta activation may exert an attenuating action on male aggression induced by estrogen through ER-alpha-mediated brain mechanisms, whereas its effect on male sexual behaviour is relatively small. C1 Rockefeller Univ, Neurobiol & Behav Lab, New York, NY 10021 USA. Karolinska Inst, Dept Med Nutr, S-14186 Huddinge, Sweden. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Ogawa, S (reprint author), Rockefeller Univ, Neurobiol & Behav Lab, 1230 York Ave, New York, NY 10021 USA. EM ogawa@mail.rockefeller.edu OI Korach, Kenneth/0000-0002-7765-418X FU NIMH NIH HHS [MH 62147] NR 46 TC 36 Z9 39 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD APR PY 2006 VL 23 IS 7 BP 1860 EP 1868 DI 10.1111/j.1460-9568.2006.04703.x PG 9 WC Neurosciences SC Neurosciences & Neurology GA 028AK UT WOS:000236457500020 PM 16623843 ER PT J AU Vitorino, R Guedes, SDM Ferreira, R Lobo, MJC Duarte, J Ferrer-Correia, AJ Tomer, KB Domingues, PM Amado, FML AF Vitorino, R Guedes, SDM Ferreira, R Lobo, MJC Duarte, J Ferrer-Correia, AJ Tomer, KB Domingues, PM Amado, FML TI Two-dimensional electrophoresis study of in vitro pellicle formation and dental caries susceptibility SO EUROPEAN JOURNAL OF ORAL SCIENCES LA English DT Article DE dental caries; enamel pellicle; hydroxyapatite; two-dimensional electrophoresis; whole saliva ID PROLINE-RICH PROTEINS; WHOLE SALIVA; ENAMEL PELLICLE; HYDROXYAPATITE; IDENTIFICATION; COMPONENTS; PROTEOMICS; CYSTATINS; VIVO AB In the present study, a proteomic approach was applied to evaluate the influence of salivary protein composition on in vitro dental pellicle formation and its possible correlation with dental caries. Whole saliva, collected from caries-free and caries-susceptible subjects, was analyzed by two-dimensional electrophoresis, and protein spots were identified by mass spectrometry. Data analysis of salivary protein composition showed a statistically significant correlation between the quantity of acidic proline-rich proteins (PRPs), lipocalin, cystatin SN and cystatin S, and samples from the caries-free group of subjects [decayed, missing or filled teeth (DMFT) = 0]. Samples from subjects with a high DMFT index appear to be correlated with high levels of amylase, immunoglobulin A, and lactoferrin. In vitro pellicle-composition experiments showed the same correlations found for whole saliva. As cystatins are known physiological inhibitors of cathepsins, the higher quantities of lipocalin, and cystatins S and SN found in the samples from the caries-free subjects suggest that inhibition of proteolytic events on other salivary proteins may indirectly provide tooth protection. The correlation between higher levels of the phosphorylated acidic PRPs 1/2 with samples from the caries-free group also suggests a protective role for these proteins. C1 Univ Aveiro, Dept Chem, P-3810193 Aveiro, Portugal. Sch Dent Med, High Sch Hlth N, Gandra, Portugal. NIEHS, Struct Biol Lab, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Univ Porto, Fac Sports, CIAFEL, P-4100 Oporto, Portugal. RP Univ Aveiro, Dept Chem, P-3810193 Aveiro, Portugal. EM famado@dq.ua.pt RI Ferreira, Rita/C-4020-2014; Tomer, Kenneth/E-8018-2013; Domingues, Pedro/E-5202-2010; Amado, Francisco/M-5337-2015; Duarte, Jose/F-1443-2013; PTMS, RNEM/C-1589-2014; Vitorino, Rui/G-7356-2014 OI Ferreira, Rita/0000-0002-6872-4051; Domingues, Pedro/0000-0002-8060-7675; Guedes, Sofia de Morais/0000-0001-9556-3639; Amado, Francisco/0000-0001-8256-1749; Duarte, Jose/0000-0003-4756-5917; Vitorino, Rui/0000-0003-3636-5805 FU Intramural NIH HHS NR 25 TC 44 Z9 48 U1 0 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0909-8836 EI 1600-0722 J9 EUR J ORAL SCI JI Eur. J. Oral Sci. PD APR PY 2006 VL 114 IS 2 BP 147 EP 153 DI 10.1111/j.1600-0722.2006.00328.x PG 7 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 026GJ UT WOS:000236327100009 PM 16630307 ER PT J AU Ambudkar, SV Kim, IW Sauna, ZE AF Ambudkar, SV Kim, IW Sauna, ZE TI The power of the pump: Mechanisms of action of P-glycoprotein (ABCB1) SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Review DE ATP-binding cassette; ATP hydrolysis; catalytic cycle; drug transport; multidrug resistance; P-glycoprotein ID MULTIDRUG-RESISTANCE PROTEIN; NUCLEOTIDE-BINDING SITES; STIMULATED ATPASE ACTIVITY; CATALYTIC CYCLE; TRANSPORTER SUPERFAMILY; CASSETTE TRANSPORTERS; MUTATIONAL ANALYSIS; GLUTAMATE RESIDUES; ESCHERICHIA-COLI; STRUCTURAL BASIS AB Members of the superfamily of ATP-binding cassette (ABC) transporters mediate the movement of a variety of substrates including simple ions, complex lipids and xenobiotics. At least 18 ABC transport proteins are associated with disease conditions. P-glycoprotein (Pgp, ABCB1) is the archetypical mammalian ABC transport protein and its mechanism of action has received considerable attention. There is strong biochemical evidence that Pgp moves molecular cargo against a concentration gradient using the energy of ATP hydrolysis. However, the molecular details of how the energy of ATP hydrolysis is coupled to transport remain in dispute and it has not been possible to reconcile the data from various laboratories into a single model. The functional unit of Pgp consists of two nucleotide binding domains (NBDs) and two trans-membrane domains which are involved in the transport of drug substrates. Considerable progress has been made in recent years in characterizing these functionally and spatially distinct domains of Pgp. In addition, our understanding of the domains has been augmented by the resolution of structures of several non-mammalian ABC proteins. This review considers: (i) the role of specific conserved amino acids in ATP hydrolysis mediated by Pgp; (ii) emerging insights into the dimensions of the drug binding pocket and the interactions between Pgp and the transport substrates and (iii) our current understanding of the mechanisms of coupling between energy derived from ATP binding and/or hydrolysis and efflux of drug substrates. (c) 2005 Elsevier B.V. All rights reserved. C1 NCI, Cell Biol Lab, Canc Res Ctr, NIH,DHHS, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, NIH,DHHS, Bldg 37, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov NR 83 TC 130 Z9 139 U1 2 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD APR PY 2006 VL 27 IS 5 BP 392 EP 400 DI 10.1016/j.ejps.2005.10.010 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 029KQ UT WOS:000236561600002 PM 16352426 ER PT J AU Chaix, B Navaie-Waliser, M Viboud, C Parizot, I Chauvin, P AF Chaix, B Navaie-Waliser, M Viboud, C Parizot, I Chauvin, P TI Lower utilization of primary, specialty and preventive care services by individuals residing with persons in poor health SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Article DE family caregivers; family health; health service use ID FAMILY CAREGIVERS; MULTILEVEL ANALYSIS; SPOUSAL CAREGIVERS; STRESS PROCESS; DEMENTIA; BURDEN; SUPPORT; DISEASE; CHILD; HUSBANDS AB Background: Since household time and financial resources for health care are primarily spent for those household members with the most urgent health needs, individuals residing with persons in poor health may be at risk of underusing health-care services. We examined whether these individuals had a lower use of primary, specialty and preventive care than those who did not reside with persons in poor health. Methods: Data collected in 2000 from a representative sample of 8210 French individuals aged 18 years and older from 3810 households were analysed with logistic regression models adjusted for health, demographic and socioeconomic variables. Results: We found that individuals residing with one other survey respondent had a higher risk of not using primary care, specialty care and preventive care in the 12 months preceding the study when the health status of the other survey respondent was poorer ( fair or alternatively poor versus good). Furthermore, individuals residing with two other survey respondents had a higher risk of not using primary care, specialty care and preventive care in the 12 months preceding the study when they resided with a higher number of respondents in fair or poor health ( one or alternatively two versus zero). Conclusion: The lower use of health services by individuals residing with persons in poor health may signal a need for health practitioners to broaden the scope of care beyond their patients, and for policy makers to consider the long-term impact of this situation on the health-care system. C1 INSERM, Fac Med St Antoine, U707, Natl Inst Hlth & Med Res,Res Unit Epidemiol & Inf, F-75571 Paris 12, France. Visiting Nurse Serv New York, Ctr Home Care Policy & Res, New York, NY USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. RP Chaix, B (reprint author), INSERM, Fac Med St Antoine, U707, Natl Inst Hlth & Med Res,Res Unit Epidemiol & Inf, 27 Rue Chaligny, F-75571 Paris 12, France. EM chaix@u707.jussieu.fr RI Chauvin, Pierre/G-2034-2010; Chaix, Basile/B-8625-2014; Chauvin, Pierre/G-1095-2015 OI Chauvin, Pierre/0000-0002-9183-6406; Chauvin, Pierre/0000-0002-9183-6406 NR 41 TC 2 Z9 2 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1101-1262 J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD APR PY 2006 VL 16 IS 2 BP 209 EP 216 DI 10.1093/eurpub/cki094 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 027SG UT WOS:000236435100021 PM 16569906 ER PT J AU Hammond, D Fong, GT Mcdonald, PW Brown, KS Cameron, R AF Hammond, D Fong, GT Mcdonald, PW Brown, KS Cameron, R TI Showing leads to doing: graphic cigarette warning labels are an effective public health policy SO EUROPEAN JOURNAL OF PUBLIC HEALTH LA English DT Letter ID SMOKING; SMOKERS; IMPACT C1 Univ Waterloo, Dept Hlth Sci, Waterloo, ON N2L 3G1, Canada. NCI, Ctr Behav Res & Program Evaluat, Canadian Canc Soc, Waterloo, ON N2L 3G1, Canada. Ontario Tobacco Res Unit, Toronto, ON, Canada. Univ Waterloo, Dept Stat & Actuarial Sci, Waterloo, ON N2L 3G1, Canada. RP Hammond, D (reprint author), Univ Waterloo, Dept Hlth Sci, 200 Univ Ave W, Waterloo, ON N2L 3G1, Canada. EM dhammond@uwaterloo.ca RI Fong, Geoffrey/H-2810-2014 OI Fong, Geoffrey/0000-0001-9098-6472 NR 15 TC 16 Z9 17 U1 3 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1101-1262 J9 EUR J PUBLIC HEALTH JI Eur. J. Public Health PD APR PY 2006 VL 16 IS 2 BP 223 EP 224 DI 10.1093/eurpub/ckl037 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 027SG UT WOS:000236435100023 PM 16569907 ER PT J AU Besseau, L Benyassi, A Moller, M Coon, SL Weller, JL Boeuf, G Klein, DC Falcon, J AF Besseau, L Benyassi, A Moller, M Coon, SL Weller, JL Boeuf, G Klein, DC Falcon, J TI Melatonin pathway: breaking the 'high-at-night' rule in trout retina SO EXPERIMENTAL EYE RESEARCH LA English DT Article DE arylalkylamine N-acetyltransferase; hydroxyindole-O-methyltransferase; melatonin; circadian clock; pineal; retina; fish ID ARYLALKYLAMINE N-ACETYLTRANSFERASE; HYDROXYINDOLE-O-METHYLTRANSFERASE; IN-SITU HYBRIDIZATION; MESSENGER-RNA; PINEAL ORGAN; PROTEASOMAL PROTEOLYSIS; IMMUNOCYTOCHEMICAL LOCALIZATION; CIRCADIAN REGULATION; SYNTHESIS ENZYMES; EPITHELIAL-CELLS AB Pineal melatonin synthesis increases at night in all vertebrates, due to an increase in the activity of arylalkylamine N-acetyltransferase (AANAT). Melatonin is also synthesized in the retina of some vertebrates and it is generally assumed that patterns of pineal and retinal AANAT activity and melatonin production are similar, i.e. they exhibit a high-at-night pattern. However, the situation in fish is atypical because in some cases retinal melatonin increases during the day, not the night. Consistent with this, we now report that light increases the activity and abundance of the AANAT expressed in trout retina, AANAT I, at a time when the activity and abundance of pineal AANAT, AANAT2, decreases. Likewise, exposure to darkness causes retinal AANAT protein and activity to decrease coincident with increases in the pineal gland. Rhythmic changes in retinal AANAT protein and activity are 180 degrees out of phase with those of retinal AANAT1 mRNA; all appear to be driven by environmental lighting, not by a circadian oscillator. The atypical high-during-the-day pattern of retinal AANAT I activity may reflect an evolutionary adaptation that optimizes an autocrine/paracrine signaling role of melatonin in photoadaptation and phototransduction; alternatively, it might reflect an adaptation that broadens and enhances aromatic amine detoxification in the retina. Published by Elsevier Ltd. C1 Univ Paris 06, Lab Arago, F-66651 Banyuls sur Mer, France. CNRS, UMR 7628, F-66651 Banyuls sur Mer, France. Fac Sci Tanger, Physiol Anim Lab, Tanger, Morocco. Univ Copenhagen, Panum Inst, Inst Med Anat, DK-2200 Copenhagen, Denmark. NICHHD, Sect Neuroendocrinol, Dev Neurobiol Lab, NIH, Bethesda, MD 20892 USA. RP Falcon, J (reprint author), Univ Paris 06, Lab Arago, BP44, F-66651 Banyuls sur Mer, France. EM falcon@obs-banyuls.fr RI FALCON, Jack/I-5302-2013; Besseau, Laurence/O-9942-2015 OI FALCON, Jack/0000-0002-7572-6581; Besseau, Laurence/0000-0002-9617-8190 NR 44 TC 48 Z9 49 U1 1 U2 3 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD APR PY 2006 VL 82 IS 4 BP 620 EP 627 DI 10.1016/j.exer.2005.08.025 PG 8 WC Ophthalmology SC Ophthalmology GA 028TI UT WOS:000236511300009 PM 16289161 ER PT J AU Amable, RJ Lee, CT Sanchez, JF Hayashi, T Wang, E Shen, J Becker, KG Freed, WJ AF Amable, RJ Lee, CT Sanchez, JF Hayashi, T Wang, E Shen, J Becker, KG Freed, WJ TI Gene expression profiling of cocaine-induced alterations in human fetal CNS SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 13th Annual Conference of the American-Society-for-Neural-Therapy-and-Repair CY APR 11-MAY 14, 2006 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 NIDA NIH DHHS, Cellular Neurobiol Res Branch, Baltimore, MD USA. NIA, NIH DHHS, Baltimore, MD USA. ScienCell Res Labs, San Diego, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD APR PY 2006 VL 198 IS 2 BP 559 EP 559 DI 10.1016/j.expneurol.2006.02.019 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 033RJ UT WOS:000236866400032 ER PT J AU Sanchez, JF Schoen, CJ Shen, L Lee, CT Chen, J Harvey, BK Howard, D Wang, Y Shen, J Freed, WJ AF Sanchez, JF Schoen, CJ Shen, L Lee, CT Chen, J Harvey, BK Howard, D Wang, Y Shen, J Freed, WJ TI A novel telomerase-T antigen fusion gene capable of immortalizing human type-1 astrocytes SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 13th Annual Conference of the American-Society-for-Neural-Therapy-and-Repair CY APR 11-MAY 14, 2006 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 NIDA NIH DHHS, Cellular Neurobiol Res Branch, Baltimore, MD USA. Sciencell Res Labs, San Diego, CA USA. RI Harvey, Brandon/A-5559-2010 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD APR PY 2006 VL 198 IS 2 BP 587 EP 587 DI 10.1016/j.expneurol.2006.02.087 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 033RJ UT WOS:000236866400101 ER PT J AU Schoen, CJ Sanchez, JF Harvey, BK Dillon-Carter, O Chen, GJ Wang, Y Freed, WJ Hoffer, BJ AF Schoen, CJ Sanchez, JF Harvey, BK Dillon-Carter, O Chen, GJ Wang, Y Freed, WJ Hoffer, BJ TI Transplantation of a ventral mesencephalon-derived cell line, RTC4, reduces ischemic brain damage in rats SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 13th Annual Conference of the American-Society-for-Neural-Therapy-and-Repair CY APR 11-MAY 14, 2006 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 NIDA NIH DHHS, Cellular Neurobiol Res Branch, Baltimore, MD USA. RI Harvey, Brandon/A-5559-2010 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD APR PY 2006 VL 198 IS 2 BP 587 EP 588 DI 10.1016/j.expneurol.2006.02.089 PG 2 WC Neurosciences SC Neurosciences & Neurology GA 033RJ UT WOS:000236866400103 ER PT J AU Vazin, T Shen, L Sanchez, JF Lee, CT Schoen, CJ Spivak, C Shen, J Freed, WJ AF Vazin, T Shen, L Sanchez, JF Lee, CT Schoen, CJ Spivak, C Shen, J Freed, WJ TI Derivation of 5-HT neurons from human neural progenitor cells SO EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 13th Annual Conference of the American-Society-for-Neural-Therapy-and-Repair CY APR 11-MAY 14, 2006 CL Clearwater Beach, FL SP Amer Soc Neural Therapy & Repair C1 NIDA NIH DHHS, Cellular Neurobiol Res Branch, Baltimore, MD USA. Sciencell Res Labs, San Diego, CA 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 0014-4886 J9 EXP NEUROL JI Exp. Neurol. PD APR PY 2006 VL 198 IS 2 BP 591 EP 591 DI 10.1016/j.expneurol.2006.02.097 PG 1 WC Neurosciences SC Neurosciences & Neurology GA 033RJ UT WOS:000236866400112 ER PT J AU Chung, EJ Lee, MJ Lee, S Trepel, JB AF Chung, Eun Joo Lee, Min-Jung Lee, Sunmin Trepel, Jane B. TI Assays for pharmacodynamic analysis of histone deacetylase inhibitors SO EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY LA English DT Review DE acetylation; anticancer drugs; epigenetic therapy; histone deacetylase inhibitors; pharmacodynamic assays; transcription ID SUBEROYLANILIDE HYDROXAMIC ACID; ACUTE MYELOID-LEUKEMIA; HEAT-SHOCK-PROTEIN; TRANSCRIPTIONAL COACTIVATOR P300; DEPSIPEPTIDE-MEDIATED APOPTOSIS; CHRONIC MYELOGENOUS LEUKEMIA; ACUTE PROMYELOCYTIC LEUKEMIA; DISSEMINATED TUMOR-CELLS; REFRACTORY SOLID TUMORS; BREAST-CANCER CELLS AB Histone deacetylase inhibitors (HDACls) are a promising new class of targeted anticancer drugs. The pharmacodynamic (PD) assessment of whether a drug has hit its target is critically important to the successful development of any molecular targeted therapy. In the case of HDACls there are many issues to be considered in PD development and implementation. Although originally it was thought that measurement of core histone hyperacetylation in peripheral blood mononuclear cells might suffice as a PD marker, as the field is evolving it is becoming evident that other measures may be essential, and are likely to be tumour context specific. This paper provides an overview of the assays that have been performed thus far in HDACl clinical trials, with an analysis of relative strengths and weaknesses, and a delineation of the complexity of HDACl PD analysis. Consideration is given to where new approaches are needed and potential approaches for future monotherapy and combination therapy trials are suggested. C1 NCI, Ctr Canc Res, NIH, Med Oncol Branch, Bethesda, MD 20892 USA. RP Trepel, JB (reprint author), NCI, Ctr Canc Res, NIH, Med Oncol Branch, Bldg 10,Room 12N230,10 Ctr Dr, Bethesda, MD 20892 USA. EM trepel@helix.nih.gov NR 207 TC 13 Z9 13 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1742-5255 J9 EXPERT OPIN DRUG MET JI Expert Opin. Drug Metab. Toxicol. PD APR PY 2006 VL 2 IS 2 BP 213 EP 230 DI 10.1517/17425255.2.2.213 PG 18 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 167VD UT WOS:000246479700003 PM 16866608 ER PT J AU Madan, RA Gulley, JL Arlen, PM AF Madan, Ravi A. Gulley, James L. Arlen, Philip M. TI PSA-based vaccines for the treatment of prostate cancer SO EXPERT REVIEW OF VACCINES LA English DT Review DE agonist epitopes; costimulatory molecule; dendritic cell; enzyme-linked immunosorbent spot assay; peptide; pox vector; prostate-specific antigen; recombinant vaccine; vaccine ID PHASE-I TRIAL; DENDRITIC CELLS; ANTITUMOR IMMUNITY; T-CELLS; CTL RESPONSES; LYMPHOCYTES-T; DNA VACCINES; ANTIGEN; VIRUS; IMMUNOTHERAPY AB Prostate cancer is the second leading cause of cancer-related death among men in the USA. Vaccine strategies represent a novel therapeutic approach. One potential target for a prostate cancer vaccine is prostate-specific antigen, owing to its restricted expression in prostate cancer and normal prostatic epithelial cells. A number of prostate-specific antigen-specific epitopes have been identified that can activate cytotoxic T lymphocytes and, in turn, result in the killing of tumor targets by the peptide-specific cytotoxic T lymphocytes. Strategies employed in clinical trials consist of dendritic cell vaccines, recombinant protein and recombinant DNA vaccines, as well as viral vector delivery of vaccines. New approaches incorporating a combination of a vaccine with traditional treatments for prostate cancer are also being investigated. C1 NCI, Clin Res Grp, Tumor Immunol & Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Clin Immunotherapy Grp, Tumor Immunol & Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Madan, RA (reprint author), NCI, Clin Res Grp, Tumor Immunol & Biol Lab, Ctr Canc Res,NIH, 10 Ctr Dr,Room 8B09, Bethesda, MD 20892 USA. EM madanr@mail.nih.gov; gj50i@nih.gov; pa52s@nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 65 TC 14 Z9 14 U1 0 U2 2 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD APR PY 2006 VL 5 IS 2 BP 199 EP 209 DI 10.1586/14760584.5.2.199 PG 11 WC Immunology SC Immunology GA 089ZX UT WOS:000240921500008 PM 16608420 ER PT J AU Mager, DE Wan, RQ Brown, M Cheng, AW Wareski, P Abernethy, DR Mattson, MP AF Mager, Donald E. Wan, Ruiqian Brown, Martin Cheng, Aiwu Wareski, Przemyslaw Abernethy, Darrell R. Mattson, Mark P. TI Caloric restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats SO FASEB JOURNAL LA English DT Article; Proceedings Paper CT 34th Annual Meeting of the Society-for-Neuroscience CY OCT 23-27, 2004 CL San Diego, CA SP Soc Neurosci DE blood pressure; heart rate; autonomic nervous system; nutrition ID SYMPATHETIC NERVOUS-SYSTEM; DIETARY RESTRICTION; NEUROTROPHIC FACTOR; ENERGY-METABOLISM; PANIC DISORDER; MICE; PAROXETINE; AGE; RESISTANCE; DISEASE AB Dietary restriction (DR) has been shown to increase life span, delay or prevent age-associated diseases, and improve functional and metabolic cardiovascular risk factors in rodents and other species. To investigate the effects of DR on beat-to-beat heart rate and diastolic blood pressure variability (HRV and DPV) in male Sprague-Dawley rats, we implanted telemetric transmitters and animals were maintained on either intermittent fasting (every other day feeding) or calorie-restricted (40% caloric reduction) diets. Using power spectral analysis, we evaluated the temporal profiles of the low- and high-frequency oscillatory components in heart rate and diastolic blood pressure signals to assess cardiac autonomic activity. Body weight, heart rate, and systolic and diastolic blood pressure were all found to decrease in response to DR. Both methods of DR produced decreases in the low-frequency component of DPV spectra, a marker for sympathetic tone, and the high-frequency component of HRV spectra, a marker for parasympathetic activity, was increased. These parameters required at least 1 month to become maximal, but returned toward baseline values rapidly once rats resumed ad libitum diets. These results suggest an additional cardiovascular benefit of DR that merits further studies of this potential effect in humans.-Mager, D. E., Wan, R., Brown, M., Cheng, A., Wareski, P., Abernethy, D. R., Mattson, M. P. Caloric restriction and intermittent fasting alter spectral measures of heart rate and blood pressure variability in rats. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Clin Invest Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS NR 30 TC 88 Z9 90 U1 2 U2 13 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2006 VL 20 IS 6 BP 631 EP 637 DI 10.1093/fj.05-5263com PG 7 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 078UW UT WOS:000240130900009 PM 16581971 ER PT J AU King, RB Davis, J AF King, RB Davis, J TI Introduction: health disparities in infertility SO FERTILITY AND STERILITY LA English DT Editorial Material AB A scientific workshop. entitled "Health Disparities in Infertility," was held on March 10-11, 2005 at the National Institutes of Health in Bethesda, Maryland. Several evolving directions in infertility research that deserve increased emphasis were presented during the workshop; joint work between clinician scientists and social scientists in this area will lead to improved strategies for the prevention and treatment of infertility in different racial, ethnic, and socioeconomic status Populations. C1 NICHHD, Demog & Behav Sci Branch, Bethesda, MD 20892 USA. NICHHD, Reprod Sci Branch, Populat Res Ctr, Bethesda, MD 20892 USA. US Dept HHS, NIH, Bethesda, MD USA. RP King, RB (reprint author), NICHHD, Demog & Behav Sci Branch, 6100 Execut Blvd,Room 8B07, Bethesda, MD 20892 USA. EM rozking@mail.nih.gov NR 0 TC 6 Z9 6 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD APR PY 2006 VL 85 IS 4 BP 842 EP 843 DI 10.1016/j.fertnstert.2006.01.007 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 032IU UT WOS:000236768900008 ER PT J AU Feinberg, EC Larsen, FW Catherino, WH Zhang, J Armstrong, AY AF Feinberg, EC Larsen, FW Catherino, WH Zhang, J Armstrong, AY TI Comparison of assisted reproductive technology utilization and outcomes between Caucasian and African American patients in an equal-access-to-care setting SO FERTILITY AND STERILITY LA English DT Article; Proceedings Paper CT Workshop on Health Disparities in Infertility CY MAR 10-11, 2005 CL Bethesda, MD SP NICHD, Off Behav & Social Sci Res, Off Res Womens Hlth, US Dept HHS, Agcy Healthcare Res & Qual DE racial disparity; leiomyoma; ART outcomes ID IN-VITRO FERTILIZATION; RACIAL DISPARITY; UTERINE LEIOMYOMATA; INFANT-MORTALITY; WOMEN; HYPERTENSION; SUBSEROSAL; ATTITUDES; FIBROIDS; BELIEFS AB Objective: Racial disparity in assisted reproductive technology (ART) outcomes has been reported but remains controversial. Reasons for the disparity are unclear, and access to care has been suggested as a causative factor. In this study, we sought to examine minority utilization of ART in the Department of Defense (DoD) compared with minority utilization in the U.S. ART population. Outcomes from ART were compared between Caucasian (Cau) and African American (AA) patients, and etiologies of dispirity were examined. Design: Retrospective cohort Study. Setting: University-based ART program. Patient(S): A total of 1,457 patients undergoing first-cycle fresh, nondonor ART. Intervention(s): None. Main Outcome Measure(s): Clinical pregnancy rate, live birth rate, implantation rate, spontaneous abortion rate. Result(s): Within the DoD population, AA women had a fourfold increase in utilization of ART services relative to the U.S. ART population. In this equal-access-to-care setting, AA women experienced a clinically significant decrease in live birth rate that did not reach statistical significance (29.6% vs. 35.8%, risk ratio [RR] 0.83. 95% confidence interval [CI] 0.67-1.02) and a statistically significant increase in spontaneous abortions compared with Cau women (25% vs. 15.9%, RR 1.57, 95% CI 1.05-2.36). This might be explained, in part, by a higher prevalence of uterine leiomyomas in AA women (30.8% AA vs. 10.7% Cau, RR 2.85, 95% CI 2.06-3.95). For both AA and Cau women, the presence of fibroids at baseline ultrasound was associated with reductions in clinical pregnancy rates (35% with leiomyomas vs. 43.2% without leiomyomas, RR 0.74, 95% CI 0.51-0.98), live birth rates (26.2% vs. 36.0%. RR 0.63, 95% CI 0.44-0.90), and implantation rates (25.6% vs. 31.1% RR 0.82, 95% CI 0.69-0.98). Conclusion(s): Utilization of ART services among AA women increased when access to care was improved. A clinically significant reduction in live birth rate and statistically significant increase in spontaneous abortion rate was observed in AA women compared with Cau women. Leiomyomas were three times more prevalent in AA women and reduced ART success. regardless of race. The persistence of racial differences in an equal-accessto-care environment might be explained, in part, by the increased prevalence of leiomyomas in AA women. C1 NICHHD, NIH, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Walter Reed Army Med Ctr, NIH, Combined Fed Fellowship Reprod Endocrinol & Infer, Bethesda, MD USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NICHD, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Assisted Reprod Technol Program, Washington, DC 20307 USA. RP Armstrong, AY (reprint author), NICHHD, NIH, Reprod Biol & Med Branch, 10 Ctr Dr MSC 1109,Bldg 10,CRC,1-3140, Bethesda, MD 20892 USA. EM armstroa@mail.nih.gov FU Intramural NIH HHS NR 29 TC 69 Z9 71 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD APR PY 2006 VL 85 IS 4 BP 888 EP 894 DI 10.1016/j.fertnstert.2005.10.028 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 032IU UT WOS:000236768900016 PM 16580370 ER PT J AU Zhao, YF Wang, LM Chaiswing, L Yen, HC Oberley, TD Lien, YC Lin, SM Mattson, MP St Clair, D AF Zhao, YF Wang, LM Chaiswing, L Yen, HC Oberley, TD Lien, YC Lin, SM Mattson, MP St Clair, D TI Tamoxifen protects against acute tumor necrosis factor alpha-induced cardiac injury via improving mitochondrial functions SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE tamoxifen; tumor necrosis factor; cardiac injury; superoxide removal; mitochondria ID CHRONIC HEART-FAILURE; BREAST-CANCER; ADJUVANT TAMOXIFEN; TNF-ALPHA; SUPEROXIDE-DISMUTASE; TRANSGENIC MICE; RESPIRATION; RECEPTORS; MORTALITY; MECHANISM AB Tamoxifen is the most commonly used antiestrogen for the treatment of breast cancer. Several clinical trials demonstrate that tamoxifen reduces the risk of heart disease and osteoporosis. However, the mechanism by which tamoxifen causes cardioprotection is unclear. Because increased levels of tumor necrosis factor alpha (TNF alpha) in tissue and/or plasma have been observed in virtually all forms of cardiac injury, we investigated whether tamoxifen prevents cardiac injury in a murine model of acute TNFa challenge. Five- to six-week-old female mice were injected (ip) with tamoxifen at 0.25 mg/kg daily for 3 or 7 days before receiving an injection of TNF alpha. Ultrastructural examination of cardiac tissues revealed remarkable protection against TNF alpha-induced mitochondrial damage in tamoxifen pretreated mice. Tamoxifen treatment significantly improved the mitochondrial respiratory function and enhanced superoxide-scavenging activity of mitochondria. These findings reveal a novel mitochondria-mediated mechanism by which tamoxifen exerts its cardiac protection effect against acute TNF alpha-induced heart injury. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA. Univ Wisconsin, Dept Pathol, Madison, WI 53705 USA. Univ Wisconsin, VA Hosp, Madison, WI 53705 USA. Mahidol Univ, Fac Med Technol, Bangkok 10700, Thailand. NIA, Lab Neurosci, Baltimore, MD 21224 USA. RP St Clair, D (reprint author), Univ Kentucky, Grad Ctr Toxicol, Lexington, KY 40536 USA. EM DSTCLOO@POP.UKY.EDU RI Mattson, Mark/F-6038-2012 FU NCI NIH HHS [CA80152, CA94853] NR 30 TC 15 Z9 17 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD APR 1 PY 2006 VL 40 IS 7 BP 1234 EP 1241 DI 10.1016/j.freeradbiomed.2005.11.009 PG 8 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 028KJ UT WOS:000236485800016 PM 16545692 ER PT J AU de Leusse, A Dupuy, E Huizing, M Danel, C Meyer, G Jian, R Marteau, P AF de Leusse, A Dupuy, E Huizing, M Danel, C Meyer, G Jian, R Marteau, P TI Ileal Crohn"s disease in a woman with Hermansky-Pudlak syndrome SO GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE LA English DT Article ID PULMONARY-FIBROSIS; GRANULOMATOUS COLITIS; BETA-3A SUBUNIT; SYNDROME TYPE-5; MUTATIONS; GENE; ALBINISM; FORM; DEFICIENCY; ADAPTER AB Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder characterized by oculocutaneous albinism and platelet dysfunction. A subset of patients also show ceroid deposition, which can result in pulmonary fibrosis or granulomatous colitis. Whether this colitis may be considered Crohn's disease is under debate. We report a case of a patient with HPS associated with inflammatory bowel disease which affected the distal small bowel but not the colon. Ileitis was severe, and recurred rapidly after surgery. Search for mutations' in HPS1, ADTB3A, HPS3, HPS4 and for CARD15 were negative. Symptoms and ileal ulcerations which recurred after surgery were successfully treated with azathioprine and infliximab. C1 Hop Lariboisiere, Dept Medicochirurg & Pathol Digest, Serv Angiohematol Clin, F-75010 Paris, France. Hop Europeen Georges Pompidou, Serv Gastroenterol, Paris, France. NHGRI, NIH, Bethesda, MD 20892 USA. Hop Europeen Georges Pompidou, Serv Anat Pathol, Paris, France. Hop Europeen Georges Pompidou, Serv Pneumol, Paris, France. RP Marteau, P (reprint author), Hop Lariboisiere, Dept Medicochirurg & Pathol Digest, Serv Angiohematol Clin, 2 Rue Ambroise Pare, F-75010 Paris, France. EM philippe.marteau@lrb.aphp.fr NR 29 TC 5 Z9 5 U1 0 U2 0 PU MASSON EDITEUR PI MOULINEAUX CEDEX 9 PA 21 STREET CAMILLE DESMOULINS, ISSY, 92789 MOULINEAUX CEDEX 9, FRANCE SN 0399-8320 J9 GASTROEN CLIN BIOL JI Gastroenterol. Clin. Biol. PD APR PY 2006 VL 30 IS 4 BP 621 EP 624 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 043SD UT WOS:000237621000018 PM 16733390 ER PT J AU Calvisi, DF Ladu, S Gorden, A Farina, M Conner, EA Lee, JS Factor, VM Thorgeirsson, SS AF Calvisi, DF Ladu, S Gorden, A Farina, M Conner, EA Lee, JS Factor, VM Thorgeirsson, SS TI Ubiquitous activation of Ras and Jak/Stat pathways in human HCC SO GASTROENTEROLOGY LA English DT Article ID HUMAN HEPATOCELLULAR CARCINOMAS; RASSF1A PROMOTER METHYLATION; TUMOR-SUPPRESSOR GENE; GROWTH-FACTOR ALPHA; PROTEIN-KINASE; K-RAS; EPIGENETIC INACTIVATION; LIVER CARCINOGENESIS; LUNG-CANCER; CELL-GROWTH AB Background & Aims: Although the natural history and pathologic characteristics of human hepatocellular carcinoma (HCC) are well documented, the molecular pathogenesis of HCC remains poorly understood. Here, we define the role for Ras and Janus kinase (Jak)/signal transducer and activator of transcription (Stat) pathways in human HCC. Methods: Promoter and genomic status of Ras and Jak/Stat inhibitors were assessed in 80 HCCs by methylation-specific polymerase chain reaction and microsatellite analysis. Activation of Ras and Jak/Stat signaling pathways was determined by DNA sequencing, Western blot, and immunoprecipitation analysis. Suppression of Ras and Jak/Stat pathways in HCC cell lines was evaluated by viability and apoptosis assays. Results: Activation of Ras and Jak/Stat pathways was enhanced in all HCCs when compared with nonneoplastic surrounding and normal livers coincidently with the suppression of at least 1 Ras (RASSF1A and/or NORE1A) and 2 Jak/Stat inhibitors (cytokine-inducible SH2-protein [CIS]; suppressor of cytokine signaling (SOCS]1, 2, 3; and SH2-containing phosphatases (SHP1]). HCC associated with cirrhosis showed significantly higher frequency of RASSF1A, CIS, and SOCS1 promoter methylation than HCC without cirrhosis (P <.002, P <.02, and P <.02, respectively). Furthermore, aberrant methylation of NORE1A and SOCS3 promoters was observed only in a subclass of HCC with poor survival, suggesting that inactivation of these 2 genes might be involved in HCC progression. Combined treatment of HCC cell lines with Ras and Jak/Stat inhibitors as well as with the demethylating agent zebularine induced a strong apoptotic response. Conclusions: These data demonstrate the ubiquitous activation of Ras and Jak/Stat pathways in HCC and suggest the potential use of Ras and Jak/Stat inhibitors and demethylating agents as therapeutic modality for human liver cancer. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bldg 37,Room 4146A,37 Convent Dr MSC 4262, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov FU Intramural NIH HHS NR 57 TC 356 Z9 373 U1 8 U2 44 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2006 VL 130 IS 4 BP 1117 EP 1128 DI 10.1053/j.gastro.2006.01.006 PG 12 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 031ZG UT WOS:000236743100017 PM 16618406 ER PT J AU Wallace, MB Sullivan, D Rustgi, AK AF Wallace, MB Sullivan, D Rustgi, AK CA AITGN Symposium Faculty TI Advanced imaging and technology in gastrointestinal neoplasia: Summary of the AGA-NCI Symposium October 4-5, 2004 SO GASTROENTEROLOGY LA English DT Review ID ABERRANT CRYPT FOCI; COMPUTED TOMOGRAPHIC COLONOGRAPHY; SPECIALIZED INTESTINAL METAPLASIA; LIGHT-SCATTERING SPECTROSCOPY; LASER-INDUCED FLUORESCENCE; BLUE-DIRECTED BIOPSIES; BARRETTS-ESOPHAGUS; VIRTUAL COLONOSCOPY; CT COLONOGRAPHY; METHYLENE-BLUE AB Imaging and other advanced technologies for detection of gastrointestinal cancers are undergoing a major revolution on several fronts. This is facilitated by convergence of key technologies including advanced endoscopic-detection systems, more specific contrast agents, rapid and high-resolution cross-sectional imaging, and miniaturization of construction systems for making all imaging equipment smaller and less invasive. This convergence is occurring along traditional translational research pathways (clinical medicine-molecular biology) as well as nontraditional lines (clinical medicine-optical physics/engineering and molecular biology-optical physics/engineering). These new efforts are producing a wide array of technologies aimed at improving detection, classification, and monitoring of gastrointestinal neoplasia, especially for colorectal and esophageal cancer because of easier accessibility. A critical goal is to detect lesions at their premalignant stages, thereby permitting meaningful intervention. Inspired by these advances, the American Gastroenterological Association and the National Cancer Institute sponsored a symposium held in Bethesda, MD, from October 4-5, 2004, bringing together leading investigators with diverse backgrounds in imaging technology. The aims of this symposium were to summarize the state of the art and priorities for research in the coming decade in the field of imaging and advanced technology for gastrointestinal neoplasia. In this overview, we summarize the salient results of that symposium. The initial sections discuss the major technologies in each area of endoluminal imaging and molecular imaging followed by applications to specific diseases such as Barrett's esophagus and colon neoplasia. Each section focuses on the current state of the art then lists major priorities for research in the field. C1 Mayo Clin, AGA Sect Imaging & Adv Technol, Jacksonville, FL 32224 USA. NCI, Canc Imaging Program, Bethesda, MD 20892 USA. Univ Penn, Dept Gastroenterol, Philadelphia, PA 19104 USA. RP Wallace, MB (reprint author), Mayo Clin, AGA Sect Imaging & Adv Technol, 4500 San Pablo Rd, Jacksonville, FL 32224 USA. EM wallace.michael@mayo.edu FU NIDCR NIH HHS [P01 DE012467] NR 67 TC 10 Z9 10 U1 0 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2006 VL 130 IS 4 BP 1333 EP 1342 DI 10.1053/j.gastro.2006.01.009 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 031ZG UT WOS:000236743100036 PM 16618424 ER PT J AU Katano, H Kok, MR Cotrim, AP Yamano, S Schmidt, M Afione, S Baum, BJ Chiorini, JA AF Katano, H Kok, MR Cotrim, AP Yamano, S Schmidt, M Afione, S Baum, BJ Chiorini, JA TI Enhanced transduction of mouse salivary glands with AAV5-based vectors SO GENE THERAPY LA English DT Article DE salivary glands; mice; AAV; adeno-associated virus; serotype ID ADENOASSOCIATED VIRUS TYPE-2; MEDIATED GENE-TRANSFER; GROWTH-FACTOR RECEPTOR; ADENOVIRAL VECTOR; SJOGRENS-SYNDROME; AIRWAY EPITHELIA; SIALIC-ACID; INFECTION; CORECEPTOR; AAV5 AB We previously demonstrated that recombinant adeno-associated virus vectors based on serotype 2 (rAAV2) can direct transgene expression in salivary gland cells in vitro and in vivo. However, it is not known how other rAAV serotypes perform when infused into salivary glands. The capsids of serotypes 4 and 5 are distinct from rAAV2 and from each other, suggesting that they may direct binding and entry into different cell types. In the present study, we investigated the tropisms, transduction efficiencies, and antibody response to AAV vectors based on AAV serotypes 2, 4, and 5. Administration of rAAV2 beta-galactosidase (beta gal), rAAV4 beta gal, or rAAV5 beta gal to murine submandibular salivary glands by retrograde ductal instillation resulted in efficient transduction of salivary epithelial cells, with AAV4 and AAV5 producing 2.3 and 7.3 times more beta gal activity compared with AAV2. Improved transduction with AAV5 was confirmed by QPCR of DNA extracted from glands and immunohistochemical staining for transgene expression. Like AAV2, AAV5 primarily transduced striated and intercalated ductal cells. AAV4 transduction was evident in striated, intercalated, and excretory ductal cells, as well as in convoluted granular tubules. In keeping with the encapsulated nature of the salivary gland, the majority of persistent viral genomes were found in the gland and not in other tissues. Neutralizing antibodies (NABs) found in the serum of virus-infused animals were serotype specific and there was no cross-reactivity between serotypes. No NABs were detected in saliva but sialic acid conjugates present in saliva could neutralize AAV4 at low dilutions. Together our data suggest that because of differences in receptor binding and transduction pathways, other serotypes may have improved utility as gene transfer vectors in the salivary gland and these differences could be exploited in gene therapy applications. C1 Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Chiorini, JA (reprint author), Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, US Dept Hlth & Human Serv, NIH 10,1N113,10 Ctr Dr,MSC1190, Bethesda, MD 20892 USA. EM jchiorini@dir.nidcr.nih.gov OI Yamano, Seiichi/0000-0003-2056-4359 NR 41 TC 26 Z9 26 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0969-7128 J9 GENE THER JI Gene Ther. PD APR PY 2006 VL 13 IS 7 BP 594 EP 601 DI 10.1038/sj.gt.3302691 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 024NP UT WOS:000236202500004 PM 16341060 ER PT J AU Siesser, WB Zhao, J Miller, LR Cheng, SY McDonald, MP AF Siesser, WB Zhao, J Miller, LR Cheng, SY McDonald, MP TI Transgenic mice expressing a human mutant beta 1 thyroid receptor are hyperactive, impulsive, and inattentive SO GENES BRAIN AND BEHAVIOR LA English DT Review DE ADHD; attention; behavior; dopamine; hyperactivity; impulsivity; mouse; receptor; thyroid; transgenic ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DORSAL NORADRENERGIC BUNDLE; HORMONE RECEPTOR; DOPAMINE TRANSPORTER; ANIMAL-MODEL; BEHAVIORAL VIGILANCE; RAT-BRAIN; MATERNAL HYPOTHYROXINEMIA; PROGRESSIVE RATIO; CHILD-DEVELOPMENT AB Attention deficit hyperactivity disorder (ADHD) is the most commonly diagnosed childhood psychiatric disorder. We have found that a transgenic mouse bearing a human mutant thyroid receptor (TR beta 1) expresses all of the defining symptoms of ADHD-inattention, hyperactivity, and impulsivity-as well as a 'paradoxical' response to methylphenidate (MPH). As with ADHD, the behavioral phenotypes expressed by the TR beta transgenic mice are dynamic and sensitive to changes in environmental conditions, stress, and reinforcement. TR beta transgenic mice are euthyroid except for a brief period during postnatal development, but the behavioral phenotypes, elevated dopamine turnover, and paradoxical response to MPH persist into adulthood. Thus, like the vast majority of children with ADHD, the TR beta transgenic mice exhibit the symptoms of ADHD in the complete absence of thyroid abnormalities. This suggests that even transient perturbations in developmental thyroid homeostasis can have long-lasting behavioral and cognitive consequences, including producing the full spectrum of symptoms of ADHD. C1 Vanderbilt Univ, Program Neurosci, Nashville, TN 37232 USA. Vanderbilt Univ, Dept Pharmacol, Nashville, TN 37232 USA. Vanderbilt Univ, John F Kennedy Ctr Res Human Dev, Nashville, TN 37232 USA. NCI, Gene Regulat Sect, Mol Biol Lab, Bethesda, MD 20892 USA. RP McDonald, MP (reprint author), Vanderbilt Univ, Program Neurosci, 851 Light Hall, Nashville, TN 37232 USA. EM mike.mcdonald@vanderbilt.edu OI McDonald, Michael P./0000-0002-9642-964X FU NICHD NIH HHS [5P30HD015052-23]; NINDS NIH HHS [1R21NS043581-01A1] NR 107 TC 39 Z9 40 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1601-1848 J9 GENES BRAIN BEHAV JI Genes Brain Behav. PD APR PY 2006 VL 5 IS 3 BP 282 EP 297 DI 10.1111/j.1601-183X.2005.00161.x PG 16 WC Behavioral Sciences; Neurosciences SC Behavioral Sciences; Neurosciences & Neurology GA 028BQ UT WOS:000236460900007 PM 16594981 ER PT J AU Bougdour, A Wickner, S Gottesman, S AF Bougdour, A Wickner, S Gottesman, S TI Modulating RssB activity: IraP, a novel regulator of as stability in Escherichia coli SO GENES & DEVELOPMENT LA English DT Article DE RpoS; sigma(38); YaiB; regulated proteolysis; starvation ID ATP-DEPENDENT PROTEASES; SIGMA-FACTOR SIGMA(S); BACILLUS-SUBTILIS; STATIONARY-PHASE; RNA-POLYMERASE; RECOGNITION FACTOR; COMPETENCE DEVELOPMENT; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; CARBON STARVATION AB The sigma(S) subunit of Escherichia coli RNA polymerase regulates the expression of stationary phase and stress response genes. sigma(S) is highly unstable in exponentially growing cells, whereas its stability increases dramatically upon starvation or under certain stress conditions. The degradation of sigma(S) is controlled by the phosphorylatable adaptor protein RssB and the C1pXP protease. RssB specifically directs sigma(S) to C1pXP. An unanswered question is how RssB-mediated degradation of sigma(S) is blocked by conditions such as glucose or phosphate starvation. We report here the identification and characterization of a new regulator of sigma(S) stability, IraP (inhibitor of RssB activity during phosphate starvation), that stabilizes sigma(S) both in vivo and in vitro. Deletion of iraP interferes with sigma(S) stabilization during phosphate starvation, but not during carbon starvation, and has a partial effect in stationary phase and nitrogen starvation. IraP interferes with RssB-dependent degradation of sigma(S) through a direct protein-protein interaction with RssB. A point mutant of IraP was isolated and found to be defective both for inhibition of sigma(S) degradation and interaction with RssB. Our results reveal a novel mechanism of regulation of sigma(S) stability through the regulation of RssB activity and identify IraP as a member of a new class of regulators, the anti-adaptor proteins. C1 NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Gottesman, S (reprint author), NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM susang@helix.nih.gov RI Bougdour, Alexandre/K-3795-2014 OI Bougdour, Alexandre/0000-0002-5895-0020 FU Intramural NIH HHS NR 64 TC 85 Z9 89 U1 0 U2 10 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0890-9369 J9 GENE DEV JI Genes Dev. PD APR 1 PY 2006 VL 20 IS 7 BP 884 EP 897 DI 10.1101/gad.1400306 PG 14 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 030LM UT WOS:000236636100013 PM 16600914 ER PT J AU Fukuda, T Scott, G Komatsu, Y Araya, R Kawano, M Ray, MK Yamada, M Mishina, YJ AF Fukuda, T Scott, G Komatsu, Y Araya, R Kawano, M Ray, MK Yamada, M Mishina, YJ TI Generation of a mouse with conditionally activated signaling through the BMP receptor, ALK2 SO GENESIS LA English DT Article DE Cre-IoxP system; Smad; transgenic mouse; constitutively active; bone morphogenetic protein ID NEURAL CREST CELLS; TGF-BETA RECEPTOR; GENE; MICE; EXPRESSION; PROTEIN; RECOMBINASE; EMBRYO; DEFECTS; SYSTEM AB BMP signaling plays pleiotropic roles in various tissues. Transgenic mouse lines that overexpress BMP signaling in a tissue-specific manner would be beneficial; however, production of each tissue-specific transgenic mouse line is labor-intensive. Here, using a Cre-loxP system, we generated a conditionally overexpressing mouse line for BMP signaling through the type I receptor ALK2 (alternatively known as AVCRI, ActRI, or ActRIA). By mating this line with Cre-expression mouse lines, Cre-mediated recombination removes an intervening floxed lacZ expression cassette and thereby permits the expression of a constitutively active form of Alk2 (caAlk2) driven by a ubiquitous promoter, CAG. Tissue specificity of Cre recombination was monitored by a bicistronically expressed EGFP following Alk2 cDNA. Increased BMP signaling was confirmed by ectopic phosphorylation of SMAD1/5/8 in the areas where Cre recombination had occurred. The conditional overexpression system described here provides versatility in investigating gene functions in a tissue-specific manner without having to generate independent tissue-specific transgenic lines. C1 NIEHS, LRDT, Mol Dev Biol Grp, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Carcinogenesis Lab, Hormones & Canc Grp, Res Triangle Pk, NC 27709 USA. RIKEN Brain Sci Inst, Yamada Res Unit, Saitama, Japan. RIKEN Brain Sci Inst, Lab Cell Culture Dev, Saitama, Japan. RP Mishina, YJ (reprint author), NIEHS, LRDT, Mol Dev Biol Grp, 111 Alexander Dr,RTP, Res Triangle Pk, NC 27709 USA. EM mishina@niehs.nih.gov FU Intramural NIH HHS NR 30 TC 46 Z9 46 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1526-954X J9 GENESIS JI Genesis PD APR PY 2006 VL 44 IS 4 BP 159 EP 167 DI 10.1002/dvg.20201 PG 9 WC Developmental Biology; Genetics & Heredity SC Developmental Biology; Genetics & Heredity GA 046NU UT WOS:000237819100001 PM 16604518 ER PT J AU Malagon, F Kireeva, ML Shafer, BK Lubkowska, L Kashlev, M Strathern, JN AF Malagon, F Kireeva, ML Shafer, BK Lubkowska, L Kashlev, M Strathern, JN TI Mutations in the Saccharomyces cerevisiae RPB1 gene conferring hypersensitivity to 6-azauracil SO GENETICS LA English DT Article ID RNA-POLYMERASE-II; ELONGATION-FACTOR TFIIS; TRANSCRIPTION ELONGATION; LARGEST SUBUNIT; STRUCTURAL BASIS; ANGSTROM RESOLUTION; CONSERVED RESIDUES; IN-VITRO; YEAST; COMPLEX AB RNA polymerase II (RNAPII) in eukaryotic cells drives transcription of most messenger RNAs. RNAPII core enzyme is composed of 12 polypeptides where Rpb1 is the largest subunit. To further understand the mechanisms of RNAPII transcription, we isolated and characterized novel point mutants of RPB1 that are sensitive to the nucleotide-depleting drug 6-azauracil (6AU), In this work we reisolated the rpo21-24/rpb1-E1230K allele, which reduces the interaction of RNAPII-TFIIS, and identified five new point mutations in RPB1 that cause hypersensitivity to 6AU. The novel mutants affect highly conserved residues of Rpb1 and have differential genetic and biochemical effects. Three of the mutations affect the "lid" and "rudder," two small loops suggested by structural studies to play a central role in the separation of the RNA-DNA hybrids. Most interestingly, two mutations affecting the catalytic center (rpb1-N488D) and the homology box G (rpb1-E1103G) have strong opposite effects on the intrinsic in vitro polymerization rate of RNAPII. Moreover, the synthetic interactions of these mutants with soh1, spt4, and dst1 suggest differential in vivo effects. C1 NCI, Gene Regulat & Chromosome Biol Lab, NIH, Ft Detrick, MD 21702 USA. RP Strathern, JN (reprint author), Bldg 539,Room 151,POB B, Ft Detrick, MD 21702 USA. EM strather@ncifcrf.gov RI Malagon, Francisco/A-7059-2013 FU Intramural NIH HHS NR 47 TC 53 Z9 53 U1 0 U2 3 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 2006 VL 172 IS 4 BP 2201 EP 2209 DI 10.1534/genetics.105.052415 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 038ML UT WOS:000237225800016 PM 16510790 ER PT J AU James, CA Hadley, DW Holtzman, NA Winkelstein, JA AF James, CA Hadley, DW Holtzman, NA Winkelstein, JA TI How does the mode of inheritance of a genetic condition influence families? A study of guilt, blame, stigma, and understanding of inheritance and reproductive risks in families with X-linked and autosomal recessive diseases SO GENETICS IN MEDICINE LA English DT Article DE genetic counseling; chronic granulomatous disease; stigma; guilt; knowledge ID CHRONIC GRANULOMATOUS-DISEASE; DUCHENNE MUSCULAR-DYSTROPHY; CYSTIC-FIBROSIS; CARRIER STATUS; ATAXIA-TELANGIECTASIA; PRENATAL-DIAGNOSIS; OBLIGATE CARRIERS; ATTITUDES; EXPERIENCES; HEMOPHILIA AB Purpose: While the mode of inheritance of a genetic condition has long been considered to have not only medical, but also psychosocial consequences for families, this supposition has never been tested. Methods: We surveyed 112 members of 51 families (59% response) with chronic granulomatous disease to determine the influence of mode of inheritance on parents', siblings', and patients' (1) knowledge of inheritance and reproductive risk; (2) concern about risk to future family-members; (3) feelings of guilt and blame; and (4) feelings of stigmatization. Ninety-six members of 51 families (49% response) with Duchenne/Becker muscular dystrophy and spinal muscular atrophy types II/III were also studied. Results: X-linked families had better understanding of inheritance (P < 0.001) and reproductive risks (P < 0.01). X-linked mothers worried more about risks to future generations; other autosomal-recessive family members were as worried. X-linked mothers were more likely to feel guilty (P < 0.01) and blame themselves (P < 0.001). X-linked fathers blamed their child's mother (P < 0.05) and X-linked mothers felt more blamed by the father (P < 0.01). X-linked family-members were more likely to consider being a carrier stigmatizing (P < 0.05). Conclusion: When providing genetic counseling, attention should be given to guilt and blame in X-linked families and understanding reproductive risks in autosomal recessive families. Genet Med 2006: 8(4):234-242. C1 Johns Hopkins Univ Hosp, Sch Med, Dept Med, Baltimore, MD 21287 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21218 USA. NHGRI, Social & Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP James, CA (reprint author), Johns Hopkins Univ Hosp, Sch Med, Dept Med, 600 N Wolfe St, Baltimore, MD 21287 USA. FU Intramural NIH HHS NR 45 TC 37 Z9 37 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1098-3600 J9 GENET MED JI Genet. Med. PD APR PY 2006 VL 8 IS 4 BP 234 EP 242 DI 10.1097/01.gim.0000215177.28010.6e PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 036AZ UT WOS:000237044500005 PM 16617244 ER PT J AU Stroncek, D AF Stroncek, D TI Primary chronic cold agglutinin disease: warming up to therapy SO HAEMATOLOGICA-THE HEMATOLOGY JOURNAL LA English DT Editorial Material C1 NIH, Dept Transfus Med, Ctr Clin, Bethesda, MD 20892 USA. RP Stroncek, D (reprint author), NIH, Dept Transfus Med, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM dstroncek@cc.nih.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU FERRATA STORTI FOUNDATION PI PAVIA PA STRADA NUOVA 134, 27100 PAVIA, ITALY SN 0390-6078 J9 HAEMATOL-HEMATOL J JI Haematol-Hematol. J. PD APR PY 2006 VL 91 IS 4 BP 434 EP 434 PG 1 WC Hematology SC Hematology GA 031BP UT WOS:000236679400002 ER PT J AU Bryan, A Robbins, RN Ruiz, MS O'Neill, D AF Bryan, A Robbins, RN Ruiz, MS O'Neill, D TI Effectiveness of an HIV prevention intervention in prison among African Americans, Hispanics, and Caucasians SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE HIV prevention; HIV intervention; prison; inmates; treatment efficacy; evaluation ID BEHAVIORAL SKILLS MODEL; RISK BEHAVIOR; CONDOM USE; INCARCERATED WOMEN; AIDS EDUCATION; DRUG-USERS; INMATES; ADOLESCENTS; REDUCTION; ATTITUDES AB Prisons and prison inmates present important targets for HIV/AIDS prevent ion interventions. Inmates often have histories of high-risk behavior that place them in danger of contracting HIV/AIDS, and rates of HIV/AIDS tend to be much higher in this population. The goal of this study was to assess the effectiveness of a prison-based HIV/AIDS intervention to change attitudes toward HIV prevention, norms supporting HIV prevention, perceived behavioral control (i.e., self-efficacy) for HIV prevention behaviors, and intentions to engage in HIV prevention behaviors postrelease. The intervention also had the goal of encouraging inmates to become HIV/AIDS peer educators. The intervention appeared most successful at influencing beliefs and behaviors related to peer education and somewhat successful at influencing beliefs and intentions related to condom use. Analyses also showed some significant differences in effectiveness by race/ethnicity. Results are discussed from the perspectives of both research and practice with regard to prison-based HIV prevention efforts. C1 Univ Colorado, Dept Psychol, Boulder, CO 80309 USA. Fordham Univ, Dept Psychol, Bronx, NY 10458 USA. NIAID, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Community Partners Act, Hartford, CT USA. RP Bryan, A (reprint author), Univ Colorado, Dept Psychol, Campus Box 345, Boulder, CO 80309 USA. EM abryan@psych.colorado.edu NR 42 TC 36 Z9 36 U1 8 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD APR PY 2006 VL 33 IS 2 BP 154 EP 177 DI 10.1177/1090198105277336 PG 24 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 036XR UT WOS:000237111100003 PM 16531511 ER PT J AU Minenko, VF Ulanovsky, AV Drozdovitch, VV Shemiakina, EV Gavrilin, YI Khrouch, VT Shinkarev, SM Voilleque, PG Bouville, A Anspaugh, LR Luckyanov, N AF Minenko, VF Ulanovsky, AV Drozdovitch, VV Shemiakina, EV Gavrilin, YI Khrouch, VT Shinkarev, SM Voilleque, PG Bouville, A Anspaugh, LR Luckyanov, N TI Individual thyroid dose estimates for a case-control study of Chernobyl-related thyroid cancer among children of Belarus - Part II. Contributions from long-lived radionuclides and external radiation SO HEALTH PHYSICS LA English DT Article DE Chernobyl; thyroid; exposure; population; children ID ACCIDENT; PRODUCTS; CS-137 AB Significant quantities of long-lived radionuclides were released to the environment during the Chernobyl nuclear power plant accident in 1986. These radionuclides contributed to radiation doses due to ingestion of contaminated foods and external exposure from the ground deposition that resulted. The contributions of these exposure pathways to thyroid doses received by subjects of an epidemiologic study of children from Belarus are evaluated and presented. The analysis shows that ingestion of the long-lived radionuclides, primarily radiocesium, typically contributed a small percentage of the total thyroid dose received by the study subjects. The median and mean fractional contributions were 0.76 and 0.95%, respectively. The contribution of external exposure to the thyroid dose was generally larger and more variable, with median and mean contributions of 1.2 and 1.8% of the total thyroid doses, respectively. For regions close to the reactor site, where radionuclide deposition was highest, the contributions of radiocesium ingestion and external exposure were generally lower than those of the short-lived radioiodine isotopes (I-132 and I-133) and their precursors (Te-132). In other areas, the contributions of these two pathways were comparable to those of the short-lived radioiodines. For all subjects, intakes of I-131 were the primary source of dose to the thyroid. C1 MJP Risk Assessment Inc, Denver, CO 80220 USA. Minist Hlth, Belarusian Acad Post Grad Educ, Minsk 220714, Byelarus. GSF, Natl Res Ctr Environm & Hlth, Inst Radiat Protect, D-85764 Neuherberg, Germany. Joint Inst Power & Nucl Res, SOSNY Branch, Inst Power Engn Problems, Minsk 220109, Byelarus. Int Agcy Res Canc, F-69008 Lyon, France. Minist Publ Hlth Russia, State Res Ctr, Inst Biophys, Moscow 123182, Russia. NCI, Div Canc Epidemiol & Genet, NIH, DHHS, Rockville, MD 20852 USA. Univ Utah, Dept Radiol, Div Radiobiol, Salt Lake City, UT 84112 USA. RP Voilleque, PG (reprint author), MJP Risk Assessment Inc, POB 200937, Denver, CO 80220 USA. EM pgv@mindspring.com RI Shinkarev, Sergey /B-3254-2017 NR 23 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD APR PY 2006 VL 90 IS 4 BP 312 EP 327 DI 10.1097/01.HP.0000183761.30158.c1 PG 16 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 024JY UT WOS:000236192500002 PM 16538137 ER PT J AU Gonzalez, FJ AF Gonzalez, FJ TI Role of beta-catenin in the adult liver SO HEPATOLOGY LA English DT Editorial Material ID PATHWAY; MOUSE; EXPRESSION; GENE; TRANSCRIPTION; CYP1A2; GROWTH; MICE C1 NCI, Lab Metabol, NIH, Bethesda, MD 20892 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metabol, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU NCI NIH HHS [Z01 BC005562-18] NR 23 TC 6 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2006 VL 43 IS 4 BP 650 EP 653 DI 10.1002/hep.21154 PG 4 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 027RU UT WOS:000236433900002 PM 16557535 ER PT J AU Perumalswami, P Kleiner, DE Lutchman, G Heller, T Borg, B Park, Y Liang, TJ Hoofnagle, JH Ghany, MG AF Perumalswami, P Kleiner, DE Lutchman, G Heller, T Borg, B Park, Y Liang, TJ Hoofnagle, JH Ghany, MG TI Steatosis and progression of fibrosis in untreated patients with chronic hepatitis C infection SO HEPATOLOGY LA English DT Article ID VIRUS GENOTYPE-3; LIVER-DISEASE; DIAGNOSIS; EVOLUTION; FEATURES AB Hepatic steatosis is common in patients with chronic hepatitis C (CHC) and is reported to be a risk factor for progression of fibrosis. The aims of this study were to evaluate the interactions between hepatic steatosis and fibrosis in a well-defined cohort of patients with CHC. The computerized pathology database at the National Institutes of Health Clinical Center was searched for patients with CHC who had undergone liver biopsy between 1980 and 2003. Biopsies were scored for necroinflammation using a modified histology activity index, fibrosis using the Ishak system, and steatosis as either none (< 5% of cells), mild (5%-25%), or moderate-to-severe (> 25%). Four hundred ninety-four patients were identified. The mean age was 44 +/- 9.8 years; 60% were male, 80% Caucasian, and 65% were infected with genotype 1. Steatosis was mild in 31% and moderate to severe in 9% of patients. In univariate analysis, steatosis was associated with increased age, body weight, body mass index (BMI), alanine aminotransferase (ALT) levels, histological necroinflammatory activity, and fibrosis. However, in multivariate analysis, steatosis was associated only with increased age, BMI, and ALT levels and not with fibrosis. One hundred thirty-six patients had 2 liver biopsies separated by 0.5 to 17 years. Worsening of fibrosis occurred in 40% of patients and correlated independently with increasing age, periportal necroinflammation, and ALT elevations but not with steatosis. In conclusion, in this cohort of patients with CHC, steatosis was associated with older age, higher BMI, and higher serum ALT levels but not with the presence of or subsequent progression of fibrosis. C1 NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Washington, DC USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Ghany, MG (reprint author), NIDDK, Liver Dis Branch, NIH, Bldg 10,Room 9B-16,10 Ctr Dr,MSC 1800, Bethesda, MD 20892 USA. EM marcg@intra.niddk.nih.gov OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 31 TC 52 Z9 53 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2006 VL 43 IS 4 BP 780 EP 787 DI 10.1002/hep.21078 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 027RU UT WOS:000236433900018 PM 16557550 ER PT J AU Purohit, V Brenner, DA AF Purohit, V Brenner, DA TI Mechanisms of alcohol-induced hepatic fibrosis: A summary of the Ron Thurman Symposium SO HEPATOLOGY LA English DT Article ID TRANSFORMING-GROWTH-FACTOR; STELLATE CELL ACTIVATION; RAT-LIVER FIBROSIS; C VIRUS CORE; HEPATOCYTE APOPTOSIS; OXIDATIVE STRESS; TISSUE INHIBITOR; CYTOKINE EXPRESSION; COLLAGEN PRODUCTION; DISEASE AB This report is a summary of Ron Thurman Symposium on the Mechanisms of Alcohol-Induced Hepatic Fibrosis which was organized by The National Institutes of Health in Santa Barbara, California, June 25, 2005. The Symposium and this report highlight the unique aspects by which drinking alcoholic beverages may result in hepatic fibrosis. Acetaldehyde, the first metabolite of ethanol, can upregulate transcription of collagen I directly as well as indirectly by upregulating the synthesis of transforming growth factor-beta 1 (TGF-beta 1). Reactive oxygen species (ROS) generated in hepatocytes by alcohol metabolism can activate collagen production in hepatic stellate cells (HSCs) in a paracrine manner. Alcohol-induced hepatocyte apoptotic bodies can be phagocytosed by HSCs and Kupffer cells and result in increased expression of TGF-beta 1 and subsequent HSC activation. Kupffer cells may contribute to the activation of HSCs by releasing ROS and TGF-beta 1. Innate immunity may suppress hepatic fibrosis by killing activated HSCs and blocking TGF-beta 1 signaling. In patients infected with hepatitis C virus (HCV), alcohol may promote hepatic fibrosis by suppressing innate immunity. HCV core and non-structural proteins contribute to HCV-induced hepatic fibrosis. Alcohol and HCV together may promote hepatic fibrosis through increased oxidative stress and upregulation of fibrogenic cytokines. The inactive aldehyde dehydrogenase (ALDH2) and the super-active alcohol dehydrogenase (ADH2) alleles may promote hepatic fibrosis through increased accumulation of acetaldehyde in the liver. Hepatic fibrosis can be reversed by inducing selective apoptosis or necrosis of activated HSCs, or by reverse trans-differentiation of activated HSCs into the quiescent phenotype. C1 NIAAA, Div Met & Hlth Effects, Bethesda, MD USA. Columbia Univ, Coll Phys & Surg, Med Ctr, Dept Med, New York, NY USA. RP Purohit, V (reprint author), 5635 Fishers Lane,Room 2035,MSC 9304, Bethesda, MD 20892 USA. EM upurohit@mail.nih.gov NR 57 TC 82 Z9 82 U1 2 U2 11 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2006 VL 43 IS 4 BP 872 EP 878 DI 10.1002/hep.21107 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 027RU UT WOS:000236433900027 PM 16502397 ER PT J AU Piatigorsky, J AF Piatigorsky, J TI Evolutionary genetics - Seeing the light: the role of inherited developmental cascades in the origins of vertebrate lenses and their crystallins SO HEREDITY LA English DT Editorial Material ID BETA-GAMMA-CRYSTALLIN; EYE LENS; EXPRESSION; STABILITY; PROTEINS C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Piatigorsky, J (reprint author), NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM joramp@nei.nih.gov NR 16 TC 6 Z9 7 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0018-067X J9 HEREDITY JI Heredity PD APR PY 2006 VL 96 IS 4 BP 275 EP 277 DI 10.1038/sj.hdy.6800793 PG 3 WC Ecology; Evolutionary Biology; Genetics & Heredity SC Environmental Sciences & Ecology; Evolutionary Biology; Genetics & Heredity GA 027CG UT WOS:000236390700001 PM 16508666 ER PT J AU Zhang, W Chaloner, K Tillmann, HL Williams, CF Stapleton, JT AF Zhang, W Chaloner, K Tillmann, HL Williams, CF Stapleton, JT TI Effect of early and late GB virus C viraemia on survival of HIV-infected individuals: a meta-analysis SO HIV MEDICINE LA English DT Article DE Bayesian meta-analysis; GB virus C; hepatitis G virus; HIV; survival ID HEPATITIS-G VIRUS; C/HEPATITIS-G VIRUS; DISEASE PROGRESSION; AMSTERDAM COHORT; COINFECTION; ASSOCIATION; MORTALITY; INHIBITION; HEMOPHILIA; MEN AB Objectives To conduct a meta-analysis to synthesize the evidence regarding the effect of co-infection with GB virus C (GBV-C) on survival of HIV-infected individuals, and to estimate the effect. Methods A Bayesian meta-analysis was conducted to synthesize evidence from eligible studies. Prospective survival studies of HIV-1-infected individuals, with outcome defined as time from baseline to all-cause death, were included and classified by whether GBV-C status was determined in early or late HIV disease. The primary measure was the hazard ratio (HR) of death for HIV-infected individuals with GBV-C infection versus those without GBV-C infection. Results Eleven studies from eight publications met the inclusion criteria. For studies with GBV-C status measured 2 years or less after HIV seroconversion (912 subjects), the combined HR was 0.88 [95% credible interval (CI) 0.30, 1.50]. For studies with GBV-C status measured more than 2 years after HIV seroconversion (1294 subjects), the combined HR was 0.41 (95% CI 0.23, 0.69). Conclusions No conclusive evidence was found of an association between survival and GBV-C infection early in HIV disease. However, when GBV-C infection was present later in HIV disease, a significant reduction in the hazard for mortality was observed for those with co-infection. Potential explanations for this difference include a non-proportional benefit of GBV-C over time, possibly related to clearance of GBV-C infection early in HIV disease. The timing of GBV-C infection appears to account for the contradictory results of studies on the effect of GBV-C coinfection on survival of HIV-infected people. C1 Univ Iowa, Dept Biostat, Coll Publ Hlth, Iowa City, IA 52242 USA. Univ Iowa, Dept Stat & Actuarial Sci, Iowa City, IA 52242 USA. Univ Iowa, Dept Internal Med, Iowa City, IA 52242 USA. Iowa City VA Med Ctr, Med Serv, Iowa City, IA USA. Univ Leipzig, Med Hosp & Hlth Ctr 2, D-7010 Leipzig, Germany. NIAID, Epidemiol Branch, Div AIDS, Bethesda, MD 20892 USA. RP Chaloner, K (reprint author), Univ Iowa, Dept Biostat C22N GH, Iowa City, IA 52242 USA. EM kathryn-chaloner@uiowa.edu RI Chaloner, Kathryn/B-5090-2013 FU NCRR NIH HHS [M01-RR00071, M01-RR00079, 5-M01-RR-00052, MO1-RR00083]; NIAID NIH HHS [U01-AI-35039, U01-AI-37613, U01-AI42590, U01-AI-35042, U01-AI-37984, U01-AI34993, U01-AI31834, AI 058740, U01-AI-35040, U01-AI-35043, U01-AI35004]; NICHD NIH HHS [U01-HD32632]; PHS HHS [R01 058740, U01-34994] NR 39 TC 61 Z9 61 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1464-2662 J9 HIV MED JI HIV Med. PD APR PY 2006 VL 7 IS 3 BP 173 EP 180 DI 10.1111/j.1468-1293.2006.00366.x PG 8 WC Infectious Diseases SC Infectious Diseases GA 015HB UT WOS:000235541400006 PM 16494631 ER PT J AU Wang, JH Voutetakis, A Mineshiba, F Illei, GG Dang, HW Yeh, CK Baum, BJ AF Wang, JH Voutetakis, A Mineshiba, F Illei, GG Dang, HW Yeh, CK Baum, BJ TI Effect of serotype 5 adenoviral and serotype 2 adeno-associated viral vector-mediated gene transfer to salivary glands on the composition of saliva SO HUMAN GENE THERAPY LA English DT Article ID IMMUNE-RESPONSES; PAROTID-GLANDS; VIRUS VECTORS; IN-VIVO; FLUID SECRETION; ORAL CAVITY; THERAPY; THERAPEUTICS; EXPRESSION; INDUCTION AB Key to the development of a useful clinical therapy is the minimization of side effects. Routine safety testing, however, does not provide information about the physiological status of many potentially useful gene transfer target sites. In this study, we evaluated the longitudinal effects of intrasalivary duct delivery of recombinant serotype 5 adenoviral (rAd5; 10(9)-10(10) particles/gland in rats) and recombinant serotype 2 adeno-associated viral (rAAV2; 10(8)-10(9) particles/gland in mice) vectors on salivary composition. Both vectors led to modest, transient alterations in several salivary components that thereafter returned to normal. The changes suggested two initial specific consequences of rAd5 and rAAV2 vector administration: ( 1) a modest breach of the mucosal barrier in the targeted glands, indicated by elevations in salivary albumin, total protein, and Na+ levels, and ( 2) an innate host response, indicated by transient elevations in either salivary lactoferrin and IgA levels ( rAd5) or mucin ( rAAV2). These studies are consistent with the notion that administration of modest doses of rAd5 and rAAV2 vectors to salivary glands for a therapeutic purpose can be accomplished without severe or permanent injury to the target tissue, or compromise to its essential exocrine physiological function. C1 NIDCR, GTTB, NIH, DHHS, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Community Dent, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Dent Diagnost Sci, San Antonio, TX 78229 USA. Audie L Murphys VA Hosp, Ctr Geriatr Res Educ & Clin, San Antonio, TX 78229 USA. RP Baum, BJ (reprint author), NIDCR, GTTB, NIH, DHHS, Bldg 10,Room 1N113, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov FU Intramural NIH HHS; NIDCR NIH HHS [R21-DE-15381] NR 46 TC 11 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD APR PY 2006 VL 17 IS 4 BP 455 EP 463 DI 10.1089/hum.2006.17.455 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 033QV UT WOS:000236864800008 PM 16610933 ER PT J AU Zhu, SG Hsu, AP Vacek, MM Zheng, L Schaffer, AA Dale, JK Davis, J Fischer, RE Straus, SE Boruchov, D Saulsbury, FT Lenardo, MJ Puck, JM AF Zhu, SG Hsu, AP Vacek, MM Zheng, L Schaffer, AA Dale, JK Davis, J Fischer, RE Straus, SE Boruchov, D Saulsbury, FT Lenardo, MJ Puck, JM TI Genetic alterations in caspase-10 may be causative or protective in autoimmune lymphoproliferative syndrome SO HUMAN GENETICS LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; DEFECTIVE LYMPHOCYTE; FAS LIGAND; MUTATIONS; APOPTOSIS; DISORDER; DISEASE; ASSOCIATION; FAMILIES; PATIENT AB Autoimmune lymphoproliferative syndrome (ALPS) is characterized by lymphadenopathy, elevated numbers of T cells with alpha beta-T cell receptors but neither CD4 nor CD8 co-receptors, and impaired lymphocyte apoptosis in vitro. Defects in the Fas receptor are the most common cause of ALPS (ALPS Ia), but in rare cases other apoptosis proteins have been implicated, including caspase-10 (ALPS II). We investigated the role of variants of caspase-10 in ALPS. Of 32 unrelated probands with ALPS who did not have Fas defects, two were heterozygous for the caspase-10 missense mutation 1406L. Like the previously reported ALPS II-associated mutation L285F, I406L impaired apoptosis when transfected alone and dominantly inhibited apoptosis mediated by wild type caspase-10 in a co-transfection assay. Other variants in caspase-10, V410I and Y446C, were found in 3.4 and 1.6% of chromosomes in Caucasians, and in 0.5 and < 0.5% of African Americans, respectively. In contrast to L285F and 1406L, these variants had no dominant negative effect in co-transfection assays into the H9 lymphocytic cell line. We found healthy individuals homozygous for V410I, challenging the earlier suggestion that homozygosity for V4101 alone causes ALPS. Moreover, an association analysis suggested protection from severe disease by caspase-10 V4101 in 63 families with ALPS la due to dominant Fas mutations (P < 0.05). Thus, different genetic variations in caspase-10 can produce contrasting phenotypic effects. C1 NHGRI, Genet & Mol Biol Branch, NIH, DHHS, Bethesda, MD 20892 USA. NIAID, Mol Dev Sect, NIH, DHHS, Bethesda, MD 20892 USA. NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH,DHHS, Bethesda, MD 20892 USA. NIH, Computat Biol Branch, Natl Ctr Biotechnol Informat, Natl Lib Med,DHHS, Bethesda, MD 20892 USA. Brookdale Univ Hosp, Med Ctr, Div Pediat Hematol & Oncol, Dept Pediat, Brooklyn, NY USA. Univ Virginia Hlth Syst, Dept Pediat, Charlottesville, VA USA. RP Puck, JM (reprint author), GMBB, Bldg 49,Room 4A14,49 Convent Dr, Bethesda, MD 20892 USA. EM jpuck@mail.nih.gov RI Schaffer, Alejandro/F-2902-2012 FU Intramural NIH HHS NR 29 TC 24 Z9 27 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-6717 J9 HUM GENET JI Hum. Genet. PD APR PY 2006 VL 119 IS 3 BP 284 EP 294 DI 10.1007/s00439-006-0138-9 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 036GH UT WOS:000237059100006 PM 16446975 ER PT J AU Marchetti, F Pearson, FS Bishop, JB Wyrobek, AJ AF Marchetti, F Pearson, FS Bishop, JB Wyrobek, AJ TI Etoposide induces chromosomal abnormalities in mouse spermatocytes and stem cell spermatogonia SO HUMAN REPRODUCTION LA English DT Article DE aneuploidy; chemotherapy; FISH; male germ cells; structural aberrations ID DNA TOPOISOMERASE-II; IN-SITU HYBRIDIZATION; TESTICULAR CANCER; MULTICOLOR FISH; HUMAN SPERM; INHIBITOR ETOPOSIDE; CLEAVABLE COMPLEX; ANTICANCER DRUGS; HEALTHY-MEN; ANEUPLOIDY AB BACKGROUND: Etoposide (ET) is a chemotherapeutic agent widely used in the treatment of leukaemia, lymphomas and many solid tumours such as testicular and ovarian cancers, all of which are common in patients of reproductive age. The purpose of the study was to characterize the long-term effects of ET on male germ cells using sperm fluorescence in situ hybridization (FISH) analyses. METHODS: Chromosomal aberrations (partial duplications and deletions) and whole chromosomal aneuploidies were detected in sperm of mice treated with a clinical dose of ET. Semen samples were collected at 25 and 49 days after dosing to investigate the effects of ET on meiotic pachytene cells and spermatogonial stem-cells, respectively. RESULTS: ET treatment resulted in major increases in the frequencies of sperm-carrying chromosomal aberrations in both meiotic pachytene (27- to 578-fold) and spermatogonial stem-cells (8- to 16-fold), but aneuploid sperm were induced only after treatment of meiotic cells (27-fold) with no persistent effects in stem cells. CONCLUSION: These results show that ET may have long-lasting effects on the frequencies of sperm with structural aberrations. This has important implications for cancer patients undergoing chemotherapy with ET because they may remain at higher risk for abnormal reproductive outcomes long after the end of chemotherapy. C1 Lawrence Livermore Natl Lab, Biosci Directorate, Livermore, CA 94550 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Marchetti, F (reprint author), Lawrence Livermore Natl Lab, Biosci Directorate, Livermore, CA 94550 USA. EM marchetti2@llnl.gov OI Marchetti, Francesco/0000-0002-9435-4867 FU NIEHS NIH HHS [Y01-ES-8016-5] NR 55 TC 14 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD APR PY 2006 VL 21 IS 4 BP 888 EP 895 DI 10.1093/humrep/dei416 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 025GN UT WOS:000236253500008 PM 16311288 ER PT J AU Rabinovich, A Krajewski, S Krajewska, M Shabaik, A Hewitt, SM Belongie, S Reed, JC Price, JH AF Rabinovich, A Krajewski, S Krajewska, M Shabaik, A Hewitt, SM Belongie, S Reed, JC Price, JH TI Framework for parsing, visualizing and scoring tissue microarray images SO IEEE TRANSACTIONS ON INFORMATION TECHNOLOGY IN BIOMEDICINE LA English DT Article DE automated tissue microarray (TMA) scoring; densitometry/fluorometry; image acquisition; texture segmentation; tissue microarrays (TMAs) ID PROTEIN EXPRESSION; BREAST-CANCER; PERFORMANCE; MICROSCOPY; CELLS; BCL-2 AB Increasingly automated techniques for arraying, immunostaining, and imaging tissue sections led us to design software for convenient management, display, and scoring. Demand for molecular marker data derived in situ from tissue has driven histology informatics automation to the point where one can envision the computer, rather than the microscope, as the primary viewing platform for histopathological scoring and diagnoses. Tissue microarrays (TMAs), with hundreds or even thousands of patients' tissue sections on each slide, were the first step in this wave of automation. Via TMAs, increasingly rapid identification of the molecular patterns of cancer that define distinct clinical outcome groups among patients has become possible. TMAs have moved the bottleneck of acquiring molecular pattern information away from sampling and processing the tissues to the tasks of scoring and results analyses. The need to read large numbers of new slides, primarily for research purposes, is driving continuing advances in commercially available automated microscopy instruments that already do or soon will automatically image hundreds of slides per day. We reviewed strategies for acquiring, collating, and storing histological images with the goal of streamlining subsequent data analyses. As a result of this work, we report an implementation of software for automated preprocessing, organization, storage, and display of high resolution composite TMA images. C1 Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USA. Burnham Inst, La Jolla, CA 92037 USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. Natl Canc Inst, Tissue Array Res Program, Pathol Lab, NIH, Bethesda, MD 20894 USA. Burnham Inst Med Res, La Jolla, CA 92037 USA. Univ Calif San Diego, Whitaker Inst Biomed Engn, Dept Bioengn, La Jolla, CA 92093 USA. Vala Sci, La Jolla, CA 92037 USA. RP Rabinovich, A (reprint author), Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USA. EM amrabino@ucsd.edu; stan@burnham.org; maryla@burnham.org; ashabaik@ucsd.edu; hewitts@mail.nih.gov; sjb@cs.ucsd.edu; jreed@burnham.org; jhprice10@yahoo.com OI Hewitt, Stephen/0000-0001-8283-1788; Shabaik, Ahmed/0000-0003-1987-3453 FU NICHD NIH HHS [HD37782] NR 34 TC 11 Z9 11 U1 0 U2 5 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 1089-7771 J9 IEEE T INF TECHNOL B JI IEEE T. Inf. Technol. Biomed. PD APR PY 2006 VL 10 IS 2 BP 209 EP 219 DI 10.1109/TITB.2005.855544 PG 11 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Mathematical & Computational Biology; Medical Informatics GA 030ZR UT WOS:000236674400001 PM 16617609 ER PT J AU Qiang, R Wu, DG Chen, J Wang, SM Wilton, D Kainz, W AF Qiang, R Wu, DG Chen, J Wang, SM Wilton, D Kainz, W TI An efficient two-dimensional FDTD method for bio-electromagnetic applications SO IEEE TRANSACTIONS ON MAGNETICS LA English DT Article; Proceedings Paper CT 15th Biennial Conference on Computation of Electromagnetic Fields CY JUN 26-30, 2005 CL Shenyang, PEOPLES R CHINA DE algebraic multi-grid method; bio-electromagnetics; FDTD method; unconditionally stable algorithm ID ALGORITHM; MODEL AB We propose an efficient algorithm for the simulation of densely sampled biological objects. This technique is based on an algebraic multi-grid (AMG) accelerated Crank-Nicholson (CN) finite-difference time-domain (FDTD) method. Using this scheme, simulation time step sizes are no longer limited by the Courant-Friedrich-Levy (CFL) number. A practical guideline on how to choose appropriate time-step sizes for accurate bioelectromagnetic applications is also presented. Numerical examples are used to demonstrate the effectiveness of this technique. C1 Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. NIH, Bethesda, MD 20892 USA. US FDA, CDRH, Rockville, MD 20852 USA. RP Qiang, R (reprint author), Univ Houston, Dept Elect & Comp Engn, Houston, TX 77204 USA. EM jchen18@uh.edu NR 17 TC 4 Z9 4 U1 1 U2 4 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9464 J9 IEEE T MAGN JI IEEE Trans. Magn. PD APR PY 2006 VL 42 IS 4 BP 1391 EP 1394 DI 10.1109/TMAG.2006.871947 PG 4 WC Engineering, Electrical & Electronic; Physics, Applied SC Engineering; Physics GA 030ZZ UT WOS:000236675200223 ER PT J AU Shaffer, AL Staudt, LM AF Shaffer, AL Staudt, LM TI Genomics & proteomics: reduce, rebuild, reveal SO IMMUNOLOGICAL REVIEWS LA English DT Editorial Material C1 NCI, Metab Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, Canc Res Ctr, NIH, Bldg 10,Rm 4N114, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov NR 14 TC 1 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD APR PY 2006 VL 210 BP 5 EP 7 DI 10.1111/j.0105-2896.2006.00376.x PG 3 WC Immunology SC Immunology GA 026GO UT WOS:000236327600001 ER PT J AU Shaffer, AL Wright, G Yang, LM Powell, J Ngo, V Lamy, L Lam, LT Davis, RE Staudt, LM AF Shaffer, AL Wright, G Yang, LM Powell, J Ngo, V Lamy, L Lam, LT Davis, RE Staudt, LM TI A library of gene expression signatures to illuminate normal and pathological lymphoid biology SO IMMUNOLOGICAL REVIEWS LA English DT Review ID B-CELL LYMPHOMA; UNFOLDED PROTEIN RESPONSE; GERMINAL-CENTER FORMATION; CHRONIC LYMPHOCYTIC-LEUKEMIA; DEREGULATED BCL6 EXPRESSION; TRANSCRIPTION FACTOR XBP-1; SECRETING PLASMA-CELLS; ENDOPLASMIC-RETICULUM; RNA-INTERFERENCE; HODGKIN-LYMPHOMA AB Genomics has provided a lever to pry open lymphoid cells and examine their regulatory biology. The large body of available gene expression data has also allowed us to define the of coordinately expressed genes, termed gene expression signatures, which characterize the states of cellular physiology that reflect cellular differentiation, activation of signaling pathways, and the action of transcription factors. Gene expression signatures that reflect the action of individual transcription factors can be defined by perturbing transcription factor function using RNA interference (RNAi), small-molecule inhibition, and dominant-negative approaches. We have used this methodology to define gene expression signatures of various transcription factors controlling B-cell differentiation and activation, including BCL-6, B lymphocyte-induced maturation protein-1 (Blimp-1), X-box binding protein-1 (XBP1), nuclear factor-kappa B (NF-kappa B), and c-myc. We have also curated a wide variety of gene expression signatures from the literature and assembled these into a signature database. Statistical methods can define whether any signature in this database is differentially expressed in independent biological samples, an approach we have used to gain mechanistic insights into the origin and clinical behavior of B-cell lymphomas. We also discuss the use of genomic-scale RNAi libraries to identify genes and pathways that may serve as therapeutic targets in B-cell malignancies. C1 NCI, Metab Branch, CCR, NIH, Bethesda, MD 20892 USA. Natl Canc Inst, Biometr Res Branch, DCTD, Bethesda, MD USA. NIH, Bioinformat & Mol Anal Sect, Computat Biosci & Engn Lab, CIT, Bethesda, MD 20892 USA. RP Staudt, LM (reprint author), NCI, Metab Branch, CCR, NIH, Bldg 10,Rm4 N114,, Bethesda, MD 20892 USA. EM lstaudt@mail.nih.gov FU Intramural NIH HHS NR 143 TC 100 Z9 100 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD APR PY 2006 VL 210 BP 67 EP 85 DI 10.1111/j.0105-2896.2006.00373.x PG 19 WC Immunology SC Immunology GA 026GO UT WOS:000236327600006 PM 16623765 ER PT J AU Benoist, C Germain, RN Mathis, D AF Benoist, C Germain, RN Mathis, D TI A Plaidoyer for 'systems immunology' SO IMMUNOLOGICAL REVIEWS LA English DT Editorial Material AB A complete understanding of the immune system will ultimately require an integrated perspective on how genetic and epigenetic entities work together to produce the range of physiologic and pathologic behaviors characteristic of immune function. The immune network encompasses all of the connections and regulatory associations between individual cells and the sum of interactions between gene products within a cell. With 30 000+ protein-coding genes in a mammalian genome, further compounded by microRNAs and yet unrecognized layers of genetic controls, connecting the dots of this network is a monumental task. Over the past few years, high-throughput techniques have allowed a genome-scale view on cell states and cell- or system-level responses to perturbations. Here, we observe that after an early burst of enthusiasm, there has developed a distinct resistance to placing a high value on global genomic or proteomic analyses. Such reluctance has affected both the practice and the publication of immunological science, resulting in a substantial impediment to the advances in our understanding that such large-scale studies could potentially provide. We propose that distinct standards are needed for validation, evaluation, and visualization of global analyses, such that in-depth descriptions of cellular responses may complement the gene/factor-centric approaches currently in favor. C1 Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Dept Med,Sect Immunol & Immunog, Boston, MA 02215 USA. NIAID, Lymphocyte Biol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Benoist, C (reprint author), Harvard Univ, Brigham & Womens Hosp, Sch Med, Joslin Diabet Ctr,Dept Med,Sect Immunol & Immunog, 1 Joslin Pl, Boston, MA 02215 USA. EM cbdm@joslin.harvard.edu FU Intramural NIH HHS NR 0 TC 35 Z9 38 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD APR PY 2006 VL 210 BP 229 EP 234 DI 10.1111/j.0105-2896.2006.00374.x PG 6 WC Immunology SC Immunology GA 026GO UT WOS:000236327600015 PM 16623774 ER PT J AU Cortez, KJ Lyman, CA Kottilil, S Kim, HS Roilides, E Yang, J Fullmer, B Lempicki, R Walsh, TJ AF Cortez, KJ Lyman, CA Kottilil, S Kim, HS Roilides, E Yang, J Fullmer, B Lempicki, R Walsh, TJ TI Functional genomics of innate host defense molecules in normal human monocytes in response to Aspergillus fumigatus SO INFECTION AND IMMUNITY LA English DT Article ID TOLL-LIKE RECEPTORS; NF-KAPPA-B; CANDIDA-ALBICANS; GENE-EXPRESSION; ANTIFUNGAL ACTIVITY; MONONUCLEAR PHAGOCYTES; SIGNAL-TRANSDUCTION; BASEMENT-MEMBRANE; PROTEIN; CELLS AB Aspergillus fumigatus induces the release of innate immune-related molecules from phagocytic cells early in the course of infection. Little is known, however, about the complex expression profiles of the multiple genes involved in this response. We therefore investigated the kinetics of early gene expression in human monocytes (HMCs) infected with conidia of A. fumigatus using DNA microarray analysis. Total RNA from HMCs at 0, 2, 4, and 6 h was extracted, linearly amplified, hybridized onto Affymetrix HG133 Plus 2.0 gene chips, and analyzed with an Affymetrix scanner. Changes in gene expression were calculated as a ratio of those expressed by infected versus control HMCs. Aspergillus fumigatus induced differential regulation of expression in 1,827 genes (P < 0.05). Genes encoding cytokines and chemokines involved in host defense against A. fumigatus, including interleukin-1 beta (IL-1 beta), IL-8, CXCL2, CCL4, CCL3, and CCL20, as well as the opsonin long pentraxin 3, were up-regulated during the first 2 to 6 h, coinciding with an increase in phagocytosis. Simultaneously, genes encoding CD14, ficolin1, and MARCO were down-regulated, and genes encoding IL-10 and matrix metalloproteinase I were up-regulated. Up-regulation of the genes encoding heat shock proteins 40 and 110 and connexins 26 and 30 may point to novel molecules whose role in the pathogenesis of aspergillosis has not been previously reported. Verification of the transcriptional profiling was obtained for selected genes by reverse transcription-PCR and enzyme immunoassay. Thus, A. fumigatus conidia induced a coordinated expression of genes important in host defense and immunomodulation. C1 NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD USA. Aristotle Univ Thessaloniki, Dept Pediat 3, GR-54006 Thessaloniki, Greece. SAIC Frederick Inc, Clin Serv Program, Frederick, MD USA. RP Walsh, TJ (reprint author), NCI, Pediat Oncol Branch, Immunocompromised Host Sect, NIH, 10 Ctr Dr,CRC Rm 1-5250, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov RI Lempicki, Richard/E-1844-2012 OI Lempicki, Richard/0000-0002-7059-409X FU Intramural NIH HHS NR 49 TC 52 Z9 56 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2006 VL 74 IS 4 BP 2353 EP 2365 DI 10.1128/IAI.74.4.2353-2365.2006 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 028HF UT WOS:000236477000038 PM 16552065 ER PT J AU Krzan, M Schwartz, JP AF Krzan, M Schwartz, JP TI Histamine transport in neonatal and adult astrocytes SO INFLAMMATION RESEARCH LA English DT Article; Proceedings Paper CT 34th Meeting of the European-Histamine-Research-Society CY MAY 11-14, 2005 CL Univ Ljubljana, Bled, SLOVENIA HO Univ Ljubljana ID NERVOUS-SYSTEM GLIA; CATION TRANSPORTER; CELLS; RELEASE; EXISTS C1 NINDS, Neurotroph Factors Sect, NIH, Bethesda, MD USA. RP Krzan, M (reprint author), Fac Med, Dept Pharmacol & Expt Toxicol, Ljubljana 1000, Slovenia. EM mojca.limpel@mf.uni-lj.si NR 8 TC 5 Z9 5 U1 0 U2 0 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD APR PY 2006 VL 55 SU 1 BP S36 EP S37 DI 10.1007/s00011-005-0031-3 PG 2 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 046ZZ UT WOS:000237850900018 PM 16547817 ER PT J AU Chieppa, M Huang, A Rescigno, M Germain, RN AF Chieppa, M Huang, A Rescigno, M Germain, RN TI Intravital 2-photon microscopy of dendritic cell extension sampling pathogen bacteria into the small bowell lumen SO INFLAMMATORY BOWEL DISEASES LA English DT Meeting Abstract CT 4th International Meeting on Inflammatory Bower Diseases CY APR 09-12, 2006 CL Capri, ITALY SP European Crohns & Colitis Org, European Federat Crohns & Ulcerat Colitis Assoc, Crohns & Colitis Fdn Amer, Italian Assoc Chron Inflammatory Bowel Dis C1 NIH, Lymphocyte Biol Sect, Immunol Lab, Bethesda, MD 20892 USA. European Inst Oncol, Milan, Italy. RI Rescigno, Maria/J-9704-2012 OI Rescigno, Maria/0000-0002-6464-509X NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1078-0998 J9 INFLAMM BOWEL DIS JI Inflamm. Bowel Dis. PD APR PY 2006 VL 12 SU 2 BP S20 EP S20 DI 10.1097/00054725-200604002-00042 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 030KN UT WOS:000236633500040 ER PT J AU Tsirogianni, AK Moutsopoulos, NM Moutsopoulos, HM AF Tsirogianni, AK Moutsopoulos, NM Moutsopoulos, HM TI Wound heating: Immunological aspects SO INJURY-INTERNATIONAL JOURNAL OF THE CARE OF THE INJURED LA English DT Article; Proceedings Paper CT 2nd European Clinical Symposium on Bone and Tissue Regeneration CY NOV 25-27, 2005 CL Univ Athens, Dept Trauma & Orthopaed Sch Med, Athens, GREECE SP Stryker HO Univ Athens, Dept Trauma & Orthopaed Sch Med DE wound heating; inflammation; macrophage; adhesion molecules; cytokines; chemokines ID T-CELLS; LYMPHOCYTE RECIRCULATION; ADAPTIVE IMMUNITY; INNATE IMMUNITY; GROWTH-FACTOR; RECEPTOR; REPAIR; TOLL; MACROPHAGE; CHEMOKINES AB Wound heating is a complex biological process, comprised of a series of a sequential events aiming to repair injured tissue. The role of the immune system in this process is not only to recognise and combat the newly presented antigens at the site of injury, but also to participate in the debridement of the damaged area and to contribute to the process of heating. In this review, we discuss the molecules and cells of the immune system that participate in tissue repair. We describe the mechanisms of immune recognition during initial insult and the innate and adaptive immune responses to injury. Finally, we address the role of the immune system in regeneration and repair. (C) 2006 Elsevier Ltd. All rights reserved. C1 Univ Athens, Sch Med, Dept Pathophysiol, GR-11527 Athens, Greece. Natl Inst Dent Craniofacial Res, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Moutsopoulos, HM (reprint author), Univ Athens, Sch Med, Dept Pathophysiol, 75 M Asias St, GR-11527 Athens, Greece. EM hmoutsop@med.uoa.gr NR 35 TC 56 Z9 58 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0020-1383 J9 INJURY JI Injury-Int. J. Care Inj. PD APR PY 2006 VL 37 SU 1 BP S5 EP S12 DI 10.1016/j.injury.2006.02.035 PG 8 WC Critical Care Medicine; Emergency Medicine; Orthopedics; Surgery SC General & Internal Medicine; Emergency Medicine; Orthopedics; Surgery GA 048TZ UT WOS:000237970700003 PM 16616753 ER PT J AU Cheng, TL Wright, JL Pearson-Fields, AS Brenner, RA AF Cheng, TL Wright, JL Pearson-Fields, AS Brenner, RA CA DC Child Adolescent Injury Res Net TI The spectrum of intoxication and poisonings among adolescents: surveillance in an urban population SO INJURY PREVENTION LA English DT Article ID SELF-INFLICTED INJURY; AT-RISK ADOLESCENTS; EMERGENCY-DEPARTMENT; SUICIDE ATTEMPTERS; ALCOHOL; INTERVENTION; MORTALITY AB Aim: Among adolescents, poisoning is a leading cause of injury mortality in the United States. This study describes the epidemiology of poisonings, intoxication, and maladaptive effects of drugs among adolescents age 10-19 years in a large city. Methods: An injury surveillance system used records at seven hospitals, medical examiner records, and vital records over a two year period. Results: Of 633 cases (618 injuries/100 000/year), 6% were unintentional, 36% self-inflicted, 41% alcohol intoxication, and 15% maladaptive effects of drugs. Alcohol was involved in 45% of cases, 23% illegal drugs, 23% nonprescription drugs, 19% prescription drugs; 19% involved more than one substance. Hospitalization was required in 20%; 8% transferred to another hospital; one died from intoxication. The authors found high rates of self-inflicted poisoning, intoxication, and maladaptive effects of drugs among this urban population. Conclusion: The study highlights the need to broadly define poisonings among adolescents and the challenge of assessing intent in some cases. C1 Johns Hopkins Univ, Sch Med, Div Gen Pediat & Adolescent Med, Baltimore, MD 21287 USA. Bloomberg Sch Publ Hlth, Baltimore, MD USA. Childrens Res Inst, Washington, DC USA. George Washington Univ, Sch Med, Washington, DC 20052 USA. George Washington Univ, Sch Publ Hlth, Washington, DC 20052 USA. Childrens Natl Med Ctr, Dept Emergency Med, Washington, DC 20010 USA. Mautner Project, Washington, DC USA. NICHHD, Bethesda, MD 20892 USA. RP Cheng, TL (reprint author), Johns Hopkins Univ, Sch Med, Div Gen Pediat & Adolescent Med, 600 N Wolfe St,Pk 392, Baltimore, MD 21287 USA. FU NIMHD NIH HHS [P20 MD000165, P20 MD00165]; PHS HHS [R49/CCR311657-01] NR 23 TC 8 Z9 9 U1 1 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1353-8047 J9 INJURY PREV JI Inj. Prev. PD APR PY 2006 VL 12 IS 2 BP 129 EP 132 DI 10.1136/ip.2005.010710 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 029AH UT WOS:000236529600016 PM 16595430 ER PT J AU Noriega, FG Ribeiro, JMC Koener, JF Valenzuela, JG Hernandez-Martinez, S Pham, VM Feyereisen, R AF Noriega, FG Ribeiro, JMC Koener, JF Valenzuela, JG Hernandez-Martinez, S Pham, VM Feyereisen, R TI Comparative genomics of insect juvenile hormone biosynthesis SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article DE juvenile hormone (JH); corpora allata (CA) ID COCKROACH CORPORA-ALLATA; DROSOPHILA TAKEOUT GENE; DIPLOPTERA-PUNCTATA; BINDING-PROTEIN; MANDUCA-SEXTA; BOMBYX-MORI; METHYL FARNESOATE; ANOPHELES-GAMBIAE; SALIVARY-GLAND; AEDES-AEGYPTI AB The biosynthesis of insect juvenile hormone (JH) and its neuroendocrine control are attractive targets for chemical control of insect pests and vectors of disease. To facilitate the molecular study of JH biosynthesis, we analyzed ESTs from the glands producing JH, the corpora allata (CA) in the cockroach Diploptera punctata, an insect long used as a physiological model species and compared them with ESTs from the CA of the mosquitoes Aedes aegypti and Anopheles albimanus. The predicted genes were analyzed according to their probable functions with the Gene Ontology classification, and compared to Drosophila and Anopheles gambiae genes. A large number of reciprocal matches in the cDNA libraries of cockroach and mosquito CA were found. These matches defined known and suspected enzymes of the JH biosynthetic pathway, but also several proteins associated with signal transduction that might play a role in the modulation of JH synthesis by neuropeptides. The identification in both cockroach and mosquito CA of homologs of the small ligand binding proteins from insects, Takeout/JH binding protein and retinol-binding protein highlights a hitherto unsuspected complexity of metabolite trafficking, perhaps JH precursor trafficking, in these endocrine glands. Furthermore, many reciprocal matches for genes of unknown function may provide a fertile ground for an in-depth study of allatal-specific cell physiology. (c) 2006 Elsevier Ltd. All rights reserved. C1 Florida Int Univ, Dept Biol Sci, Miami, FL 33199 USA. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. Univ Arizona, Dept Entomol, Tucson, AZ 85721 USA. INSP, Ctr Invest Sobre Enfermedades Infecc, Cuernavaca 62100, Morelos, Mexico. INRA, F-06903 Sophia Antipolis, France. Univ Nice, Ctr INRA Sophia Antipolis, F-06903 Sophia Antipolis, France. RP Noriega, FG (reprint author), Florida Int Univ, Dept Biol Sci, 11200 SW 8th St, Miami, FL 33199 USA. EM noriegaf@fiu.edu RI Feyereisen, Rene/I-3140-2012; OI Feyereisen, Rene/0000-0002-9560-571X; Ribeiro, Jose/0000-0002-9107-0818 FU NIAID NIH HHS [R01 AI045545-08, AI 45545, R01 AI045545]; NIDDK NIH HHS [DK 34549] NR 45 TC 41 Z9 45 U1 5 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0965-1748 J9 INSECT BIOCHEM MOLEC JI Insect Biochem. Mol. Biol. PD APR PY 2006 VL 36 IS 4 BP 366 EP 374 DI 10.1016/j.ibmb.2006.01.013 PG 9 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 032DV UT WOS:000236755000015 PM 16551550 ER PT J AU Bandyopadhyay, PK Clark, K Stevenson, BJ Rivier, JE Olivera, BM Golic, KG Rong, YS AF Bandyopadhyay, PK Clark, K Stevenson, BJ Rivier, JE Olivera, BM Golic, KG Rong, YS TI Biochemical characterization of Drosophila gamma-glutamyl carboxylase and its role in fly development SO INSECT MOLECULAR BIOLOGY LA English DT Article DE vitamin K; Drosophila; gamma-glutamyl carboxylase; recombination; fly development ID K-DEPENDENT CARBOXYLASE; MATRIX GLA PROTEIN; VITAMIN-K; CARBOXYGLUTAMIC ACID; EPOXIDE REDUCTASE; CONANTOKIN-G; ACTIVE-SITE; FACTOR-IX; HOMOLOGOUS RECOMBINATION; COAGULATION-FACTORS AB To investigate structure-function relationships in gamma-glutamyl carboxylases, the enzyme from Drosophila melanogaster was characterized. Four cysteine residues were shown to be important determinants for enzymatic activity. Native Drosophila substrates have not yet been identified, but propeptides of human prothrombin and factor IX are recognized by the Drosophila enzyme. The presence of the propeptide region increased apparent affinity by similar to 200-fold, and mutation of a hydrophobic residue of factor IX propeptide (F-16A) decreased carboxylation by 90%, as in the human enzyme. Substrate recognition appears to be highly conserved between the human and Drosophila gamma-glutamyl carboxylases. Inactivation of Drosophila gamma-glutamyl carboxylase by non-sense mutations or insertional mutagenesis by P-element insertion have no apparent effects on growth and fertility under laboratory conditions. C1 Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. Salk Inst Biol Studies, La Jolla, CA 92037 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Bandyopadhyay, PK (reprint author), Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA. EM bandyop@biology.utah.edu RI rong, yikang/G-6179-2011 FU NIGMS NIH HHS [GM-48677] NR 60 TC 8 Z9 8 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0962-1075 J9 INSECT MOL BIOL JI Insect Mol. Biol. PD APR PY 2006 VL 15 IS 2 BP 147 EP 156 DI 10.1111/j.1365-2583.2006.00619.x PG 10 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 028BK UT WOS:000236460300005 PM 16640725 ER PT J AU Dalakas, MC AF Dalakas, MC TI The role of high-dose immune globulin intravenous in the treatment of dermatomyositis SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article ID INCLUSION-BODY MYOSITIS; AUTOIMMUNE NEUROMUSCULAR DISEASES; INFLAMMATORY MYOPATHIES; CONTROLLED TRIAL; GAMMA-GLOBULIN; IMMUNOGLOBULIN; POLYMYOSITIS; MUSCLE AB Dermatomyositis (DM) is a complement-mediated microangiopathy affecting skin and muscle resulting in skin abnormalities, including subcutenous calcifications, muscle weakness and disability. The disease generally responds to steroids or immunosuppressive drugs, but a number of patients are resistant or partially responsive to these therapies, prompting us to examine the efficacy of Mg. A double-blind placebo-controlled study demonstrated that fVlg is very effective in improving both the muscle strength and the skin rash. The clinical benefit, which was impressive in patients with early disease, was associated with improvement in the muscle cytoarchitecture. Quantitative histological studies in repeated muscle biopsies showed a statistically significant increase in the size of muscle fibers and the number of capillaries with normalization of the capillary diameter. Resolution of the aberrant immunopathological parameters, including interception of complement activation products and downregulation of T cells, ICAM-I, VCAM, TGF-beta and MHC-I molecules, was also noted. Further, a number of immunoregulatory and structural genes were modified in the patients' muscle biopsies after therapy. The study concluded that fVlg is an effective second-line therapy for patients with DM incompletely responding to steroids. (c) 2005 Elsevier B.V. All rights reserved. C1 NINDS, Neuromuscl Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscl Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov NR 19 TC 25 Z9 26 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD APR PY 2006 VL 6 IS 4 BP 550 EP 556 DI 10.1016/j.intimp.2005.11.016 PG 7 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 023WF UT WOS:000236156200007 PM 16504918 ER PT J AU Lusa, L Cappelletti, V Gariboldi, M Ferrario, C De Cecco, L Reid, JF Toffanin, S Gallus, G McShane, LM Daidone, MG Pierotti, MA AF Lusa, L. Cappelletti, V. Gariboldi, M. Ferrario, C. De Cecco, L. Reid, J. F. Toffanin, S. Gallus, G. McShane, L. M. Daidone, M. G. Pierotti, M. A. TI Questioning the utility of pooling samples in microarray experiments with cell lines SO INTERNATIONAL JOURNAL OF BIOLOGICAL MARKERS LA English DT Article DE sample pooling; DNA microarrays; Affymetrix GeneChips; breast cancer; MCF-7 cell line; toremifene ID GENE-EXPRESSION; DESIGN; VARIANCE AB We describe a microarray experiment using the MCF-7 breast cancer cell line in two different experimental conditions for which the same number of independent pools as the number of individual samples was hybridized on Affymetrix GeneChips. Unexpectedly, when using individual samples, the number of probe sets found to be differentially expressed between treated and untreated cells was about three times greater than that found using pools. These findings indicate that pooling samples in microarray experiments where the biological variability is expected to be small might not be helpful and could even decrease one's ability to identify differentially expressed genes. C1 Fdn Ist FIRC Oncol Mol, IFOM, Mol Genet Canc Grp, I-20139 Milan, Italy. Ist Nazl Studio & Cura Tumori, Dept Expt Oncol, I-20133 Milan, Italy. Univ Milan, Inst Med Stat & Biometry, Milan, Italy. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Lusa, L (reprint author), Fdn Ist FIRC Oncol Mol, IFOM, Mol Genet Canc Grp, Via Adamello 16, I-20139 Milan, Italy. EM lara.lusa@ifom-ieo-campus.it RI Reid, James/G-2496-2010; Lusa, Lara/C-6692-2015; Cappelletti, Vera/B-9310-2017; De Cecco, Loris/K-7036-2016; gariboldi, manuela/K-4744-2016; Daidone, Maria Grazia/E-9232-2017; OI Lusa, Lara/0000-0002-8981-2421; Cappelletti, Vera/0000-0002-9709-0676; De Cecco, Loris/0000-0002-7066-473X; gariboldi, manuela/0000-0001-8406-165X; Daidone, Maria Grazia/0000-0002-4786-1321; Reid, James/0000-0001-6997-2850; Pierotti, Marco Alessandro/0000-0002-7431-8332 NR 21 TC 7 Z9 7 U1 1 U2 2 PU WICHTIG EDITORE PI MILAN PA 72/74 VIA FRIULI, 20135 MILAN, ITALY SN 0393-6155 J9 INT J BIOL MARKER JI Int. J. Biol. Markers PD APR-JUN PY 2006 VL 21 IS 2 BP 67 EP 73 PG 7 WC Biotechnology & Applied Microbiology; Oncology SC Biotechnology & Applied Microbiology; Oncology GA 064FP UT WOS:000239074900001 PM 16847808 ER PT J AU Goodman, JE Mechanic, LE Luke, BT Ambs, S Chanock, S Harris, CC AF Goodman, JE Mechanic, LE Luke, BT Ambs, S Chanock, S Harris, CC TI Exploring SNP-SNP interactions and colon cancer risk using polymorphism interaction analysis SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE polymorphism interaction analysis; single nucleotide polymorphism; colon cancer ID MULTIFACTOR-DIMENSIONALITY REDUCTION; DETECTING GENE-GENE; COLORECTAL-CANCER; BREAST-CANCER; GENOTYPES; SUSCEPTIBILITY; P53; GSTM1; GSTT1; ADENOCARCINOMA AB Several single nucleotide polymorphisms (SNPs) in genes derived from distinct pathways are associated with colon cancer risk; however, few studies have examined SNP-SNP interactions concurrently. We explored the association between colon cancer and 94 SNPs, using a novel approach, polymorphism interaction analysis (PIA). We developed PIA to examine all possible SNP combinations, based on the 94 SNPs studied in 216 male colon cancer cases and 255 male controls, employing 2 separate functions that cross-validate and minimize false-positive results in the evaluation of SNP combinations to predict colon cancer risk. PIA identified previously described null polymorphisms in glutathione-S-transferase T1 (GSTT1) as the best predictor of colon cancer among the studied SNPs, and also identified novel polymorphisms in the inflammation and hormone metabolism path ways that singly or jointly predict cancer risk. PIA identified SNPs that may interact with the GSTT1 polymorphism, including coding polymorphisms in TP53 (Arg72Pro in p53) and CASP8 (Asp302His in caspase 8), which may modify the association between this polymorphism and colon cancer. This was confirmed by logistic regression, as the GSTT1 null polymorphism in combination with either the TP53 or the CASP8 polymorphism significantly alter colon cancer risk (P-interaction < 0.02 for both). GSTT1 prevents DNA damage by detoxifying mutagenic compounds, while the p53 protein facilitates repair of DNA damage and induces apoptosis, and caspase 8 is activated in p53-mediated apoptosis. Our results suggest that PIA is a valid method for suggesting SNP-SNP interactions that may be validated in future studies, using more traditional statistical methods on different datasets. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res Facil, NIH, Frederick, MD 21701 USA. NCI, Pediat Oncol Branch, Ctr Adv Technol, Gaithersburg, MD USA. RP Harris, CC (reprint author), NCI, Human Carcinogenesis Lab, NIH, 37 Convent Dr,Rm 3068,MSC 4255, Bethesda, MD 20892 USA. EM Curtis_Harris@nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 BC010033-10] NR 18 TC 51 Z9 56 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 1 PY 2006 VL 118 IS 7 BP 1790 EP 1797 DI 10.1002/ijc.21523 PG 8 WC Oncology SC Oncology GA 024RV UT WOS:000236214700026 PM 16217767 ER PT J AU Glezen, WP Simonsen, L AF Glezen, WP Simonsen, L TI Commentary: Benefits of influenza vaccine in US elderly - new studies raise questions SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID RESPIRATORY SYNCYTIAL VIRUS; UNITED-STATES; INFECTIONS; MORTALITY; ADULTS; IMPACT C1 Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Baylor Coll Med, Dept Pediat, Houston, TX 77030 USA. NIAID, Off Global Res, NIH, Bethesda, MD 20892 USA. RP Glezen, WP (reprint author), Baylor Coll Med, Dept Mol Virol & Microbiol, 1 Baylor Plaza,MS BCM-280, Houston, TX 77030 USA. EM wglezen@bcm.edu OI Simonsen, Lone/0000-0003-1535-8526 NR 11 TC 20 Z9 21 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 2006 VL 35 IS 2 BP 352 EP 353 DI 10.1093/ije/dyi293 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 033AI UT WOS:000236817900030 PM 16368723 ER PT J AU Freedman, DM Sigurdson, AJ Doody, MM Love-Schnur, S Linet, MS AF Freedman, DM Sigurdson, AJ Doody, MM Love-Schnur, S Linet, MS TI Comparison between cancers identified by state cancer registry, self-report, and death certificate in a prospective cohort study of US radiologic technologists SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Letter ID HEALTH; VALIDATION; VALIDITY C1 NCI, Div Epidemiol & Genet, NIH, DHHS, Bethesda, MD 20892 USA. Yale Univ, New Haven, CT 06520 USA. RP Freedman, DM (reprint author), NCI, Div Canc Epidemiol & Genet, Radiat Epidemiol Branch, Execut Plaza S,Room 7036,6120 Execut Blvd, Bethesda, MD 20892 USA. EM mf101e@nih.gov FU Intramural NIH HHS NR 9 TC 11 Z9 11 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD APR PY 2006 VL 35 IS 2 BP 495 EP 497 DI 10.1093/ije/dyi286 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 033AI UT WOS:000236817900057 PM 16330477 ER PT J AU Al-Rahawan, MM Giri, N Alter, BP AF Al-Rahawan, MM Giri, N Alter, BP TI Intensive immunosuppression therapy for aplastic anemia associated with dyskeratosis congenita SO INTERNATIONAL JOURNAL OF HEMATOLOGY LA English DT Article C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. George Washington Univ, Med Ctr, Childrens Natl Med Ctr, Ctr Canc & Blood Disorders, Washington, DC 20052 USA. RP Alter, BP (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,Execut Plaza S,Room 7020, Rockville, MD 20852 USA. EM alterb@mail.nih.gov FU Intramural NIH HHS NR 10 TC 15 Z9 16 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 0925-5710 J9 INT J HEMATOL JI Int. J. Hematol. PD APR PY 2006 VL 83 IS 3 BP 275 EP 276 DI 10.1532/IJH97.NA0511 PG 2 WC Hematology SC Hematology GA 039UU UT WOS:000237333700022 PM 16720563 ER PT J AU Kong, KF Vuong, C Otto, M AF Kong, KF Vuong, C Otto, M TI Staphylococcus quorum sensing in biofilm formation and infection SO INTERNATIONAL JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Review DE agr; luxS; Staphylococcus; quorum sensing; biofilm; infection ID ACCESSORY GENE REGULATOR; PHENOL-SOLUBLE MODULINS; VIRULENCE FACTORS; AUREUS VIRULENCE; DIMINISHED VIRULENCE; IN-VITRO; AGR; EXPRESSION; EPIDERMIDIS; PHEROMONE AB Cell population density-dependent regulation,of gene expression is an important determinant of bacterial pathogenesis. Staphylococci have two quorum-sensing (QS) systems. The accessory gene regulator (agr) is genus specific and uses a post-translationally modified peptide as an autoinducing signal. In the pathogens Staphylococcus aureus and Staphylococcus epidermidis, agr controls the expression of a series of toxins and virulence factors and the interaction with the innate immune system. However, the role or agr during infection is controversial. A possible second QS system of staphylococci, luxS, is found in a variety of Gram-positive and Gram-negative bacteria. Importantly, unlike many QS systems described in Gram-negative bacteria, agr and luxS of staphylococci reduce rather than induce biofilm formation and virulence during biofilm-associated infection. agr enhances biofilm detachment by up-regulation of the expression of detergent-like peptides, whereas luxS reduces cell-to-cell adhesion by down-regulating expression of biofilm exopolysaccharide. Significant QS activity in staphylococci is observed for actively growing cells at a high cell density, such as during the initial stages of an infection and under optimal environmental conditions. In contrast, the metabolically quiescent biofilm mode of growth appears to be characterized by an overall low activity of the staphylococcal QS systems. It remains to be shown whether QS control in staphylococci represents a promising target for the development of novel antibacterial agents. Published by Elsevier GmbH. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. Florida Int Univ, Dept Biol Sci, Miami, FL 33199 USA. RP Otto, M (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59840 USA. EM MOtto@niaid.nih.gov OI Otto, Michael/0000-0002-2222-4115 FU PHS HHS [UFEC020639] NR 45 TC 155 Z9 179 U1 4 U2 50 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 1438-4221 J9 INT J MED MICROBIOL JI Int. J. Med. Microbiol. PD APR PY 2006 VL 296 IS 2-3 BP 133 EP 139 DI 10.1016/j.ijmm.2006.01.042 PG 7 WC Microbiology; Virology SC Microbiology; Virology GA 033BF UT WOS:000236820500010 PM 16487744 ER PT J AU Vadakkumpadan, F Tong, YX Sun, YL AF Vadakkumpadan, F Tong, YX Sun, YL TI Statistical analysis of morphological differences between brains SO INTERNATIONAL JOURNAL OF NEUROSCIENCE LA English DT Article DE computational neuroscience; cortical surfaces; morphological study; principal coordinate analysis ID VOXEL-BASED MORPHOMETRY; AUTOMATIC SEGMENTATION; CORTICAL SURFACE; GRAY-MATTER; VISUALIZATION AB Recent study in neuroscience has observed evidence that the anatomic structures in human brains might have certain connection with the functioning. This triggers the interest in morphological study of cortical surfaces and in comparison of different ethnic groups. This article compares the MRI brain datasets of 10 Chinese and 10 Caucasians. A statistical analysis was applied to the white matter volumes in these datasets and evaluate the dissimilarities between the two groups using various intuitive measures. This analysis has revealed systematic morphological differences between the two ethnic groups. C1 Purdue Univ, Dept Comp Sci, W Lafayette, IN 47907 USA. Nalt Inst Mental Hlth, Clin Brain Disorder Branch, Bethesda, MD USA. RP Sun, YL (reprint author), Purdue Univ, Dept Comp Sci, 250 Univ St, W Lafayette, IN 47907 USA. EM sun@cs.purdue.edu RI Tong, Yunxia/C-1276-2010 NR 25 TC 6 Z9 6 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0020-7454 J9 INT J NEUROSCI JI Int. J. Neurosci. PD APR PY 2006 VL 116 IS 4 BP 407 EP 418 DI 10.1080/00207450500505662 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 024EZ UT WOS:000236179600003 PM 16574579 ER PT J AU Bonilla, C Panguluri, RK Taliaferro-Smith, L Argyropoulos, G Chen, G Adeyemo, AA Amoah, A Owusu, S Acheampong, J Agyenim-Boateng, K Eghan, BA Oli, J Okafor, G Abbiyesuku, F Johnson, T Rufus, T Fasanmade, O Chen, Y Collins, FS Dunston, GM Rotimi, C Kittles, RA AF Bonilla, C Panguluri, RK Taliaferro-Smith, L Argyropoulos, G Chen, G Adeyemo, AA Amoah, A Owusu, S Acheampong, J Agyenim-Boateng, K Eghan, BA Oli, J Okafor, G Abbiyesuku, F Johnson, T Rufus, T Fasanmade, O Chen, Y Collins, FS Dunston, GM Rotimi, C Kittles, RA TI Agouti-related protein promoter variant associated with leanness and decreased risk for diabetes in West Africans SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE AGRP; diabetes; West Africans ID MELANOCORTIN-4 RECEPTOR GENE; BODY-MASS INDEX; BIOELECTRICAL-IMPEDANCE; PREDICTION EQUATIONS; SUSCEPTIBILITY GENES; OBESITY PHENOTYPES; ENERGY HOMEOSTASIS; LEPTIN; PROOPIOMELANOCORTIN; POLYMORPHISM AB Objective: The role of the central melanocortin system in the development of obesity has been extensively studied. Single-nucleotide polymorphisms (SNPs) within several candidate genes have been associated with food intake and obesity-related phenotypes; however, few of these associations have been replicated. SNPs in the agouti-related protein (AGRP) gene coding (Ala67Thr, 199G/A) and promoter (-38C/T) have been reported to be associated with body mass index (BMI), fat mass (FM) and percent body fat, in populations of European and African descent. In this study, we evaluated the association between the functional AGRP -38C/T promoter SNP and weight-related traits, namely BMI, FM and fat-free mass (FFM), as well as diabetes status. Design: An association study of the AGRP -38C/T SNP and indices of obesity and diabetes status. Subjects: A well-characterized population of 538 West Africans from Ghana and Nigeria recruited in the AADM (Africa America Diabetes Mellitus) study (mean age 52 years, 41.3% males, 71% diabetic). Measurements: Genotyping of the AGRP -38C/T SNP, BMI, FM, FFM and fasting plasma glucose. Results: Women carrying two copies of the variant T allele had significantly lower BMI (OR 0.47; 95% CI, 0.25-0.87). Also, men with at least one copy of the variant T allele were over two times less likely to be diabetic than other men (OR 0.44; 95% CI, 0.22-0.89). Conclusion: Our results replicate previous findings and implicate the AGRP -38C/T SNP in the regulation of body weight in West Africans. C1 Howard Univ, Natl Ctr Human Genome, Washington, DC 20059 USA. Pennington Biomed Res Ctr, Baton Rouge, LA USA. Univ Ibadan, Coll Med, Ibadan, Nigeria. Univ Ghana, Dept Med, Sch Med, Accra, Ghana. Univ Sci & Technol, Dept Med, Kumsai, Ghana. Univ Nigeria, Teaching Hosp, Dept Med, Enugu, Nigeria. Univ Lagos, Coll Med, Endocrine & Metab Unit, Lagos, Nigeria. NHGRI, NIH, Bethesda, MD 20892 USA. RP Kittles, RA (reprint author), Ohio State Univ, Ctr Comprehens Canc, 494A Tzagournis Med Res Facil,420 W 12th Ave, Columbus, OH 43210 USA. EM kittles-1@medctr.osu.edu OI Bonilla, Carolina/0000-0002-9972-6383; Adeyemo, Adebowale/0000-0002-3105-3231 NR 41 TC 21 Z9 22 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD APR PY 2006 VL 30 IS 4 BP 715 EP 721 DI 10.1038/sj.ijo.0803047 PG 7 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 026LH UT WOS:000236339900021 PM 16130030 ER PT J AU Osei-Hyiaman, D Harvey-White, J Batkai, S Kunos, G AF Osei-Hyiaman, D Harvey-White, J Batkai, S Kunos, G TI The role of the endocannabinoid system in the control of energy homeostasis SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article; Proceedings Paper CT 6th Annual International Symposium on Endocannabinoid System an Its Role in Energy Homeostasis ad Abdominal Obesity Management CY NOV 20, 2004 CL Quebec City, CANADA DE enclocannabinoids; CB1; leptin; diet-induced obesity; hepatic fatty acid synthesis ID ACTIVATED PROTEIN-KINASE; CANNABINOID RECEPTOR ANTAGONIST; DIET-INDUCED OBESITY; FATTY-ACID SYNTHASE; FOOD-INTAKE; CB1 RECEPTORS; 2-ARACHIDONOYL GLYCEROL; SELECTIVE ANTAGONIST; ADIPOSE-TISSUE; EXPRESSION AB The endocannabinoid system has recently emerged as an important regulator of energy homeostasis, involved in the control of both appetite and peripheral fat metabolism. We briefly review current understanding of the possible sites of action and cellular mechanisms involved in the central appetitive and peripheral metabolic effects of endocannabinoids. Studies in our laboratory, using leptin-deficient obese rodents and CB1 cannabinoid receptor (CBI)-deficient mice, have indicated that endocannabinoids acting via CB1 are involved in the hunger-induced increase in food intake and are negatively regulated by leptin in brain areas involved in appetite control, including the hypothalamus, limbic forebrain and amygdala. CB1 (-/-) mice are lean and are resistant to diet-induced obesity (DIO) despite similar energy intake to wild-type mice with DIO, suggesting that CB1 regulation of body weight involves additional peripheral targets. Such targets appear to include both adipose tissue and the liver. CBI expressed in adipocytes has been implicated in the control of adiponectin secretion and lipoprotein lipase activity. Recent findings indicate that both endocannabinoids and CB1 are present in the liver and are upregulated in DIO. CB1 stimulation increases de novo hepatic lipogenesis through activation of the fatty acid biosynthetic pathway. Components of this pathway are also expressed in the hypothalamus where they have been implicated in the regulation of appetite. The fatty acid biosynthetic pathway may thus represent a common molecular target for the central appetitive and peripheral metabolic effects of endocannabinoids. C1 NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Kunos, G (reprint author), NIAAA, Lab Physiol Studies, NIH, 5625 Fishers Lane,MSC-9413, Bethesda, MD 20892 USA. EM gkunos@mail.nih.gov RI Batkai, Sandor/G-3889-2010; Batkai, Sandor/H-7983-2014 NR 57 TC 54 Z9 54 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0307-0565 J9 INT J OBESITY JI Int. J. Obes. PD APR PY 2006 VL 30 SU 1 BP S33 EP S38 DI 10.1038/sj.ijo.0803276 PG 6 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 031MU UT WOS:000236709500008 PM 16570103 ER PT J AU Sharp, GB Mizuno, T Fukuhara, T Tokuoka, S AF Sharp, GB Mizuno, T Fukuhara, T Tokuoka, S TI Lack of association between acute exposure to ionizing radiation and liver cirrhosis SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article DE A-bomb liver irradiation; hepatitis B and C virus; liver cirrhosis ID ATOMIC-BOMB SURVIVORS; NONCANCER DISEASE INCIDENCE; B SURFACE-ANTIGEN; HEPATITIS-B; THOROTRAST PATIENTS; CANCER INCIDENCE; VIRUS-INFECTION; MORTALITY; PREVALENCE; ANTIBODY AB Purpose: Although previous studies have shown significantly increased risks of liver cirrhosis and chronic liver disease for acute radiation exposure among survivors of the atomic bombings of Hiroshima and Nagasaki, Japan, these studies have not taken into account hepatitis B virus (HBV) infections. Because HBV is associated with both A-bomb radiation and liver cirrhosis, our goal was to investigate the relationship of acute ionizing radiation to liver cirrhosis adjusting for HBV, co-occurring primary liver cancer (PLC), and other potential confounders. Materials and methods: Using a cross-sectional design and pathology review of a cohort of Japanese atomic-bomb survivors, we found that 213 of 335 (63.6%) subjects with PLC and 55 of 776 (7.1%) subjects without PLC had cirrhosis. Results: We found no association between acute exposure to A-bomb radiation and liver cirrhosis. The adjusted odds ratio of cirrhosis per Sv liver irradiation was 0.59 (95% confidence interval: 0.27-1.27). Cirrhosis risks for the highest tertile of radiation exposure (mean exposure 0.7 Sv) were also not elevated (0.8, 0.26-2.12 and 0.2, 0.03-0.98 among subjects with and without PLC. Conclusions: Acute exposure to liver irradiation does not increase risks of liver cirrhosis, regardless of PLC status. C1 Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima, Japan. Natl Acad Sci, Washington, DC 20418 USA. Radiat Effects Res Fdn, Dept Radiobiol & Mol Epidemiol, Hiroshima, Japan. Hiroshima Prefectural Hosp, Dept Pathol, Hiroshima, Japan. RP Sharp, GB (reprint author), NIAID, Div AIDS, Basic Sci Program, Epidemiol Branch,NIH, 6700-B Rockledge Dr,Rm 4103, Bethesda, MD 20892 USA. EM gsharp@niaid.nih.gov FU PHS HHS [NCI-4893-8-001] NR 35 TC 1 Z9 1 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD APR PY 2006 VL 82 IS 4 BP 231 EP 240 DI 10.1080/09553000600649224 PG 10 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 041QL UT WOS:000237470700002 PM 16690591 ER PT J AU Chen, YY Trotti, A Coleman, CN Machtay, M Mirimanoff, RO Hay, J O'Brien, PC El-Gueddari, B Salvajoli, JV Jeremic, B AF Chen, YY Trotti, A Coleman, CN Machtay, M Mirimanoff, RO Hay, J O'Brien, PC El-Gueddari, B Salvajoli, JV Jeremic, B TI Adverse event reporting and developments in radiation biology after normal tissue injury: International atomic energy agency consultation SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT Technical Meeting of the International-Atomic-Energy-Agency CY OCT 02, 2004 CL Atlanta, GA SP Int Atom Energy Agcy DE IAEA; radiotherapy; late effects; biomarkers; common toxicity criteria ID COMPREHENSIVE GRADING SYSTEM; GENE-EXPRESSION CHANGES; IONIZING-RADIATION; INDUCED FIBROSIS; ONCOLOGY-GROUP; TOXICITY CRITERIA; PULMONARY INJURY; CANCER INCIDENCE; BOMB SURVIVORS; NECK-CANCER AB Purpose: Recent research has enhanced our understanding of radiation injury at the molecular-cellular and Tissue levels; significant strides have occurred in standardization of adverse event reporting in clinical trials. In response, the International Atomic Energy Agency, through its Division of Human Health and its section for Applied Radiation Biology and Radiotherapy, organized a consultation meeting in Atlanta (October 2, 2004) to discuss developments in radiobiology, normal tissue reactions, and adverse event reporting. Methods and Materials: Representatives from cooperative groups of African Radiation Oncology Group, Curriculo Radioterapeutica Ibero Latino Americana, European Organization for Research and Treatment of Cancer, National Cancer Institute of Canada Clinical Trials Group, Radiation Therapy Oncology Group, and Trans-Tasman Radiation Oncology Group held the meeting discussion. Results: Representatives of major radiotherapy groups/organizations and prominent leaders in radiotherapy discussed current understanding of normal tissue radiobiologic effects, the design and implementation of future clinical and translational projects for normal tissue injury, and the standardization of adverse-event reporting worldwide. Conclusions: The consensus was to adopt NCI comprehensive adverse event reporting terminology and grading system (CTCAE v3.0) as the new standard for all cooperative group trials. Future plans included the implementation of coordinated research projects focusing on normal tissue biomarkers and data collection methods. (c) 2006 Elsevier Inc. C1 Univ Rochester, Sch Med & Dent, James P Wilmot Canc Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Div Radiat Oncol, Tampa, FL 33682 USA. NCI, Radiat Oncol Sci Program, Bethesda, MD 20892 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Radiat Therapy Oncol Grp, Lausanne, Switzerland. CHU Vaudois, CH-1011 Lausanne, Switzerland. European Org Res Treatment Canc, Brussels, Belgium. British Columbia Canc Agcy, Vancouver, BC V5Z 4E6, Canada. Natl Canc Inst Canada, Clin Trials Grp, Toronto, ON, Canada. Newcastle Mater Hosp, Dept Radiat Oncol, Newcastle, NSW, Australia. Trans Tasman Radiat Oncol Grp, Newcastle, NSW, Australia. African Radiat Oncol Grp, Cape Town, South Africa. Natl Inst Oncol, Rabat, Morocco. Hosp Canc AC, Sao Paulo, Brazil. Curriculo Radioterapeut Ibero Latino Amer, Lima, Peru. IAEA, Appl Radiat Biol & Radiotherapy Sect, A-1400 Vienna, Austria. RP Chen, YY (reprint author), Univ Rochester, Sch Med & Dent, James P Wilmot Canc Ctr, Dept Radiat Oncol, 601 Elmwood Ave,Box 647, Rochester, NY 14642 USA. EM Yuhchyau_chen@urmc.rochester.edu NR 75 TC 13 Z9 14 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 EI 1879-355X J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD APR 1 PY 2006 VL 64 IS 5 BP 1442 EP 1451 DI 10.1016/j.ijrobp.2005.10.014 PG 10 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 028HG UT WOS:000236477200021 PM 16414207 ER PT J AU Hemila, H Kaprio, J Albanes, D Virtamo, J AF Hemila, H Kaprio, J Albanes, D Virtamo, J TI Physical activity and the risk of pneumonia in male smokers administered vitamin E and beta-carotene SO INTERNATIONAL JOURNAL OF SPORTS MEDICINE LA English DT Article DE antioxidants; exercise; oxidative stress; randomized controlled trials; smoking ID OXIDATIVE STRESS; IMMUNE FUNCTION; EXERCISE; INFECTION; SUPPLEMENTATION; ANTIOXIDANTS; MICE AB It has been proposed that moderate exercise may enhance the immune system. We evaluated whether physical activity at work or at leisure is associated with the risk of pneumonia, and whether the antioxidants vitamin E and beta-carotene affect pneumonia risk in physically active people. A cohort of 16 804 male smokers aged 50 - 69 years and working at study entry was drawn from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study, which examined the effect of vitamin E, 50 mg/day, and beta-carotene, 20 mg/day, on lung and other cancers. Physical activity at work, and the type of leisure-time exercise, were recorded at study entry. We retrieved the first occurrence of hospital-treated pneumonia during a 3-year follow-up from the National Hospital Discharge Register (133 cases). Physical activity at work and at leisure had no association with the risk of pneumonia. In participants with physically loading jobs, neither vitamin E nor beta-carotene affected the risk of pneumonia. In participants carrying out moderate or heavy exercise at leisure, beta-carotene had no effect, but vitamin E reduced the risk of pneumonia by 50% (95% CI: 16-70%). Previously, exercise has been shown to affect diverse laboratory measures of the immune system which are, however, only surrogate markers for the resistance to infections. The lack of association between physical activity and the risk of pneumonia observed in our study emphasizes the problem of drawing conclusions from surrogate end points. The finding that vitamin E reduced the risk of pneumonia in persons carrying out leisure-time exercise warrants further study. C1 Univ Helsinki, Dept Publ Hlth, Helsinki, Finland. Univ Helsinki, Dept Mental Hlth & Alcohol Res, Natl Publ Hlth Inst, Helsinki, Finland. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Hemila, H (reprint author), Univ Helsinki, Dept Publ Hlth, POB 41, Helsinki, Finland. EM harri.hemila@helsinki.fr RI Kaprio, Jaakko/A-1820-2008; Albanes, Demetrius/B-9749-2015; OI Hemila, Harri/0000-0002-4710-307X; Kaprio, Jaakko/0000-0002-3716-2455 FU NCI NIH HHS [CN-45 035, N01-CN-45 165] NR 30 TC 24 Z9 24 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0172-4622 J9 INT J SPORTS MED JI Int. J. Sports Med. PD APR PY 2006 VL 27 IS 4 BP 336 EP 341 DI 10.1055/s-2005-865670 PG 6 WC Sport Sciences SC Sport Sciences GA 030IO UT WOS:000236628200013 PM 16572378 ER PT J AU Begnami, MD Rushing, EJ Evangelista, R Santi, M Quezado, M AF Begnami, MD Rushing, EJ Evangelista, R Santi, M Quezado, M TI Evaluation of RB gene and cyclin-dependent kinase inhibitors p21 and p27 in pleomorphic xantoastrocytoma SO INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE pleomorphic xantoastrocytoma; p21; pRb; p27; cell cycle; immunohistochemistry ID RETINOBLASTOMA GENE; XANTHOASTROCYTOMA; EXPRESSION; P53; ASTROCYTOMAS; REGULATORS; PRODUCT; GLIOMAS; BLADDER; CANCER AB Pleomorphic xantoastrocytoma (PXA) is a rare, circumscribed astrocytic tumor that usually occurs in the superficial cerebral hemispheres in children and young adults. Most patients have a favorable prognosis, but recurrence and malignant transformation have been reported. In diffuse gliomas, approximately one third demonstrate mutations of the RB gene. Low expression level and high activity of p27 are known to constitute an independent prognostic factor in patients with malignant gliomas, while p21 expressions have variable labeling ranges. The molecular and genetic basis for tumorigenesis and progression of PXA are still largely unknown. In this study, 13 PXAs were examined immunohistochemically for pRb, p21, and p27 expression. Nine PXAs expressed homogeneous pRb positivity in the most nuclei of the tumor cells. Four cases showed an abnormal pRb staining pattern. All PXAs were positive for nuclear expression of p21. Diffuse nuclear positivity of p27 was seen in 10 cases, focal in 2, and in 1 case was not present. The cases with focal and negative p27 nuclear expression had few pRb-positive nuclei. The majority of PXAs appear to have preserved pRb, p2l, and p27 functions. Additional studies are necessary to investigate whether cases with altered pRb and p27 expressions are associated with increased risk of recurrence or malignant transformation. C1 NCI, Pathol Lab, Surg Pathol Sect, NIH, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Neuropathol & Ophthalm Pathol, Washington, DC 20306 USA. Biopse Labs, Fortaleza, Ceara, Brazil. Childrens Hosp, Natl Med Ctr, Dept Pathol, Washington, DC 20010 USA. RP Quezado, M (reprint author), NCI, Pathol Lab, Surg Pathol Sect, NIH, Bldg 10,Room 2N214,10 Ctr Dr, Bethesda, MD 20892 USA. RI Begnami, Maria/D-9663-2012 OI Begnami, Maria/0000-0003-0848-7813 NR 25 TC 1 Z9 2 U1 0 U2 0 PU WESTMINSTER PUBL INC PI GLEN HEAD PA 708 GLEN COVE AVE, GLEN HEAD, NY 11545 USA SN 1066-8969 J9 INT J SURG PATHOL JI Int. J. Surg. Pathol. PD APR PY 2006 VL 14 IS 2 BP 113 EP 118 DI 10.1177/106689690601400202 PG 6 WC Pathology; Surgery SC Pathology; Surgery GA 044WC UT WOS:000237702800002 PM 16703171 ER PT J AU Hibbeln, JR Ferguson, TA Blasbalg, TL AF Hibbeln, JR Ferguson, TA Blasbalg, TL TI Omega-3 fatty acid deficiencies in neurodevelopment, aggression and autonomic dysregulation: Opportunities for intervention SO INTERNATIONAL REVIEW OF PSYCHIATRY LA English DT Review ID HEART-RATE-VARIABILITY; POLYUNSATURATED FATTY-ACIDS; FLUID 5-HYDROXYINDOLEACETIC ACID; PLACEBO-CONTROLLED TRIAL; DISRUPTIVE BEHAVIOR DISORDERS; AGE-RELATED-CHANGES; RAT FRONTAL-CORTEX; CEREBROSPINAL-FLUID; DOUBLE-BLIND; DOCOSAHEXAENOIC ACID AB Mechanisms by which aggressive and depressive disorders may be exacerbated by nutritional deficiencies in omega-3 fatty acids are considered. Early developmental deficiencies in docosahexaenoic acid ( DHA) and eicosapentaenoic acid ( EPA) may lower serotonin levels at critical periods of neurodevelopment and may result in a cascade of suboptimal development of neurotransmitter systems limiting regulation of the limbic system by the frontal cortex. Residual developmental deficits may be manifest as dysregulation of sympathetic responses to stress including decreased heart rate variability and hypertension, which in turn have been linked to behavioral dysregulation. Little direct data are available to disentangle residual neurodevelopmental effects from reversible adult pathologies. Ensuring optimal intakes of omega-3 fatty acids during early development and adulthood shows considerable promise in preventing aggression and hostility. C1 NIAAA, Bethesda, MD 20892 USA. RP Hibbeln, JR (reprint author), NIAAA, 31 Ctr Dr 31-1B58, Bethesda, MD 20892 USA. EM jhibbeln@niaaa.nih.gov NR 120 TC 70 Z9 77 U1 4 U2 11 PU ROUTLEDGE JOURNALS, TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXFORDSHIRE, ENGLAND SN 0954-0261 J9 INT REV PSYCHIATR JI Int. Rev. Psych. PD APR PY 2006 VL 18 IS 2 BP 107 EP 118 DI 10.1080/09540260600582967 PG 12 WC Psychiatry SC Psychiatry GA 050HF UT WOS:000238077400004 PM 16777665 ER PT J AU Liu, BY Li, ZQ Mahesh, SP Kurup, SK Giam, CZ Nussenblatt, RB AF Liu, BY Li, ZQ Mahesh, SP Kurup, SK Giam, CZ Nussenblatt, RB TI HTLV-1 infection of human retinal pigment epithelial cells and inhibition of viral infection by an antibody to ICAM-1 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; LEUKEMIA-VIRUS; T-CELLS; CYTOKINE PRODUCTION; CLINICAL ENTITY; LYMPHOCYTES-T; TYPE-1; MYELOPATHY; UVEITIS AB PURPOSE. To examine whether human T-cell leukemia virus type 1 (HTLV-1) could infect a human retinal pigment epithelial (RPE) cell Line, ARPE-19, in vitro and to investigate its regulation. METHODS. A coculture system with ARPE-19 and irradiated cells of an HTLV-1-producing T-cell line, MT2 was used to determine the permissivity of RPE to HTLV-I infection in vitro. The susceptibility to HTLV-1 was assessed by detection of viral DNA using the polymerase chain reaction (PCR), viral mRNA transcripts with reverse transcription PCR (RT-PCR) and viral antigen 1)), immunofluorescence staining. An HTLV-1 Tax-activated HTLV-LTR-luciferase reporter assay was developed to measure viral infection quantitatively. The ICAM-1 expression on cocultured ARPE-19 cells was detected by flow cytometry and an ICAM-1-neutralizing antibody was used to test ICAM-1's role in the HTLV-1 infection of ARPE-19 cells. The regulation of HTLV-1 infection was investigated by Culturing ARPE-19 cells with proinflammatory cytokines. RESULTS. HTLV-1 infected ARPE-19 cells in vitro. The infection correlated with elevated expression of intercellular adhesion molecule (ICAM)-1 oil the surface of ARPE-19 cells. ICAM-1-neutralizing antibody dramatically inhibited viral infection. Furthermore, proinflammatory cytokines dramatically suppressed HTLV-1 viral infection. CONCLUSIONS. The tropism of HTLV-1 to retinal pigment epithelium could provide an explanation for the pathogenesis of HTLV-1-related ophthalmic diseases. A better Understanding of specific roles of proinflammatory cytokines in the development of ophthalmic diseases may be beneficial for treatment. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM drbob@nei.nih.gov FU Intramural NIH HHS NR 37 TC 6 Z9 6 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2006 VL 47 IS 4 BP 1510 EP 1515 DI 10.1167/iovs.05-1277 PG 6 WC Ophthalmology SC Ophthalmology GA 029KI UT WOS:000236560800033 PM 16565386 ER PT J AU Elliot, S Catanuto, P Stetler-Stevenson, W Cousins, SW AF Elliot, S Catanuto, P Stetler-Stevenson, W Cousins, SW TI Retinal pigment epithelium protection from oxidant-mediated loss of MMP-2 activation requires both MMP-14 and TIMP-2 SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID TYPE-1 MATRIX-METALLOPROTEINASE; TISSUE INHIBITOR; CELL-SURFACE; MACULAR DEGENERATION; ESTROGEN-RECEPTORS; FUNDUS DYSTROPHY; BRUCHS MEMBRANE; MESANGIAL CELLS; EXPRESSION; PROGELATINASE AB PURPOSE. Eyes with age-related macular degeneration (AMD) demonstrate accumulation of specific deposits and extracellular matrix (ECM) molecules under the retinal pigment epithelium (RPE). Metalloproteinases (MMP) are crucial regulators of basement membrane and ECM turnover. Accordingly, loss of RPE MMP activity most likely leads to excessive accumulation of Collagen and other ECM, a potential mechanism for formation of deposits. A prior Study showed that MMP-2 activity, but not pro-MMP-2 protein, decreases after RPE oxidative injury, indicating that oxidant injure, disrupts the enzymatic cleavage of pro-MMP-2. Activation of MMP-2 requires the formation of a tri-molecular complex of pro-MMP-2, MMP-14, and tissue inhibitor of metalloproteinases (TIMP)-2. Therefore, a study was conducted to investigate the impact of oxidant injury on the interaction between these three molecules. METHODS. Human GFP-RPE cells were oxidant injured by transient exposure to H,02 and myeloperoxidase, and the time course of recovery determined. Supernatants and cell lysates were collected for analysis of MMP-2, MMP-14, and TIMP-2 activity, mRNA and protein expression. In some studies, overexpression with either MMP-14 or TIMP-2 was performed to revert the cells to a preinjury phenotype. RESULTS. Transient injury resulted in a decrease of both MMP-14 and TIMP-2 activity and protein. Overexpression of each single molecule failed to prevent the injury-induced decrease of MMP-2 activity. In contrast, overexpression of MMP-14 together with the addition of exogenous TIMP-2 prevented the reduction of MMP-2 activation. CONCLUSIONS. Loss of MMP-2 activity after oxidant injury is caused by the downregulation of MMP-14 and TIMP-2. Overexpression of either MMP-14 or TIMP-2 alone before oxidant injury is not enough to prevent loss of MMP-2 activity. All three components of the tri-molecular complex must be present to preserve normal MMP-2 activity after oxidant injury. C1 Univ Miami, Miller Sch Med, Dept Med, Vasc Biol Inst, Miami, FL 33136 USA. NCI, Lab Cell & Canc Biol, NIH, Bethesda, MD 20892 USA. Duke Univ, Ctr Eye, Duke Ctr Macular Degenerat, Durham, NC USA. RP Elliot, S (reprint author), Univ Miami, Miller Sch Med, Dept Med, Vasc Biol Inst, 1600 NW 10th Ave,RSMB 1043,R104, Miami, FL 33136 USA. EM selliot@med.miami.edu RI Stetler-Stevenson, William/H-6956-2012 OI Stetler-Stevenson, William/0000-0002-5500-5808 FU NEI NIH HHS [R01 EY014477, R01 EY14477-02] NR 39 TC 9 Z9 10 U1 0 U2 1 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD APR PY 2006 VL 47 IS 4 BP 1696 EP 1702 DI 10.1167/iovs.05-1258 PG 7 WC Ophthalmology SC Ophthalmology GA 029KI UT WOS:000236560800058 PM 16565411 ER PT J AU Biggar, RJ Taha, TE Hoover, DR Yellin, F Kumwenda, N Broadhead, R AF Biggar, RJ Taha, TE Hoover, DR Yellin, F Kumwenda, N Broadhead, R TI Higher in utero and perinatal HIV infection risk in girls than boys SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE vertical transmission; gender; infants; female; male; retrovirus; HLA ID IMMUNODEFICIENCY-VIRUS TYPE-1; VERSUS-HOST-DISEASE; ALLOANTIGEN RECOGNITION; AFRICAN INFANTS; TRANSMISSION; TRIAL; TRANSPLANTATION; CONCORDANCE; ZIDOVUDINE; CHILDREN AB Objective: This Study analyzed mother-to-child HIV transmission rates by sex and exposure time for babies born to HIV-infected, untreated African women. Methods: Data were analyzed from 2 independent studies done in Malawi during the 1990s. Infections were established by polymerase chain reaction oil blood samples. Odds ratios (ORs) for transmission were examined by period at risk: in utero (infected in umbilical cord blood), perinatal (infected in 1st postnatal blood :4 weeks), and postnatal (later postnatal infection). Results: Among 1394 singleton births, girls were more likely to become infected than boys. For in utero transmission, the OR was 1.4 (95% CI: 0.9 to 2.2). For transmission during early life (umbilical cord blood not available) the OR was 2.7 (95% CI: 1.5 to 4.9). However, transmission risks in the perinatal and postnatal infection periods did not differ in boys and girls. Among 303 tested twin-birth pairs, girls were at higher risk than boys for in utero (OR: 2.6; 95% CI: 1.2 to 5.8) and perinatal (OR: 1.9; 95% CI: 1.0 to 3.7) infection. Recognized mother-to-child transmission risk factors did not explain the higher risk of infection in girls. Conclusions: Girls were at higher risk of early (in utero and perinatal) HIV infection than boys. It is proposed that minor histocompatibility reactions between maternal lymphocytes and infant Y chromosome-derived antigens reduce the risk of HIV transmission in boys. C1 NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,Div Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. Rutgers State Univ, Dept Stat, Piscataway, NJ USA. Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, Piscataway, NJ USA. Comp Sci Corp, Rockville, MD USA. Univ Malawi, Coll Med, Blantyre, Malawi. RP Biggar, RJ (reprint author), 6120 Execut Blvd,Room 8014, Rockville, MD 20852 USA. EM biggarb@mail.nih.gov FU Intramural NIH HHS NR 21 TC 9 Z9 10 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD APR 1 PY 2006 VL 41 IS 4 BP 509 EP 513 DI 10.1097/01.qai.0000191283.85578.46 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 031YN UT WOS:000236741200016 PM 16652061 ER PT J AU Tang, J Gokhale, PA Brooks, SE Blain, D Brooks, BP AF Tang, J Gokhale, PA Brooks, SE Blain, D Brooks, BP TI Increased corneal thickness in patients with ocular coloboma SO JOURNAL OF AAPOS LA English DT Article AB Uveal coloboma is a developmental abnormality of the eye caused by failure of the optic fissure to close during the fifth week of gestation.(1-3) To characterize the anatomy of colobomatous eyes, we have measured central corneal thickness (CCT) in consecutive patients that were able to cooperate with testing. Increased CCT may artifactually elevate intraoperative pressure (IOP) on Goldmann applanation tonometry. C1 NIH, Ophthalm Genet & Visual Funct Branch, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Med Coll Georgia, Dept Ophthalmol, Augusta, GA 30912 USA. Eye Consultants Augusta, Augusta, GA USA. NHGRI, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Brooks, BP (reprint author), NIH, Ophthalm Genet & Visual Funct Branch, Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. EM brooksb@mail.nih.gov NR 5 TC 6 Z9 6 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 1091-8531 J9 J AAPOS JI J. AAPOS PD APR PY 2006 VL 10 IS 2 BP 175 EP 177 DI 10.1016/j.jaapos.2005.12.003 PG 3 WC Ophthalmology; Pediatrics SC Ophthalmology; Pediatrics GA 042ZL UT WOS:000237569000017 PM 16678756 ER PT J AU Patel, KV Peek, MK Wong, R Markides, KS AF Patel, KV Peek, MK Wong, R Markides, KS TI Comorbidity and disability in elderly Mexican and Mexican American adults - Findings from Mexico and the southwestern United States SO JOURNAL OF AGING AND HEALTH LA English DT Article DE comorbidity; aging; chronic disease; disability ID FUNCTIONAL LIMITATIONS; MEDICAL CONDITIONS; HEALTH CONDITIONS; LATIN-AMERICA; IMPACT; POPULATION; MORTALITY AB This article aims to compare the effects of morbid and comorbid medical conditions on disability in elderly Mexican and Mexican American adults. Data from the 2001 Mexican Health and Aging Study (N= 4,872) and 1993 to 1994 Hispanic Established Population for Epidemiologic Studies of the Elderly (N= 3,050) were analyzed. Prevalence of medical conditions and disability in activities of daily living were calculated and logistic models were used to test associations. Prevalence of disability in older Mexicans was 16.3% while it was slightly lower in Mexican Americans (13.1%). Prevalence of arthritis, cancer, diabetes, heart attack, and stroke were substantially higher in Mexican Americans than in older adults living in Mexico. Diabetes, stroke, and heart attack were cornorbid conditions that raised the likelihood of disability in both populations among subjects with other medical conditions. Despite differences in prevalence, the associations of morbidity and comorbidity with disability had similar magnitudes in both populations. C1 NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. Univ Texas, Med Branch, Galveston, TX 77550 USA. Univ Maryland, College Pk, MD 20742 USA. RP Patel, KV (reprint author), NIA, Lab Epidemiol Demog & Biometry, 7201 Wisconsin Ave,Suite 3C309, Bethesda, MD 20892 USA. EM patelku@mail.nih.gov FU NIA NIH HHS [F31 AG021872, R01 AG018016, R01 AG025533, R01 AG10939] NR 22 TC 25 Z9 25 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0898-2643 J9 J AGING HEALTH JI J. Aging Health PD APR PY 2006 VL 18 IS 2 BP 315 EP 329 DI 10.1177/0898264305285653 PG 15 WC Gerontology; Health Policy & Services SC Geriatrics & Gerontology; Health Care Sciences & Services GA 025AA UT WOS:000236236500009 PM 16614346 ER PT J AU Atienza, AA Oliveira, B Fogg, BJ King, AC AF Atienza, Audie A. Oliveira, Brian Fogg, B. J. King, Abby C. TI Using Electronic Diaries to Examine Physical Activity and Other Health Behaviors of Adults Age 50+ SO JOURNAL OF AGING AND PHYSICAL ACTIVITY LA English DT Article DE computer; assessment; real-time; eHealth AB This pilot investigation used portable electronic diaries to assess the physical activity and other health behaviors of 20 adults age 50+ (mean age = 61 years). Study aims were to examine whether computerized cognitive-behavioral strategies could increase adherence to the assessments, the acceptability of electronic diaries to assess everyday health, and the relationship between computerized physical activity assessments with a standardized physical activity measure. Although approximately two thirds of participants had never used an electronic diary, results indicated that a large majority (83%) reported enjoying the use of the electronic diaries, and most (72%) reported enjoying answering all of the health questions. The cognitive-behavioral strategies employed did not enhance assessment adherence, but electronic-diary-based activity levels corresponded more strongly with the poststudy standardized activity measure than the baseline standardized measure, providing evidence of temporal convergence. Findings suggest that the use of portable electronic technology in physical activity assessment of middle-aged and older adults deserves further study. C1 [Atienza, Audie A.] NCI, Hlth Promot Res Branch, Bethesda, MD 20982 USA. [Oliveira, Brian; King, Abby C.] Stanford Univ, Stanford Prevent Res Ctr, Stanford, CA 94305 USA. [Fogg, B. J.] Stanford Univ, Ctr Study Language & Informat, Stanford, CA 94309 USA. RP Atienza, AA (reprint author), NCI, Hlth Promot Res Branch, Bethesda, MD 20982 USA. FU NHLBI NIH HHS [5T32-HL07034]; NIA NIH HHS [AG-12358] NR 32 TC 15 Z9 15 U1 2 U2 5 PU HUMAN KINETICS PUBL INC PI CHAMPAIGN PA 1607 N MARKET ST, PO BOX 5076, CHAMPAIGN, IL 61820-2200 USA SN 1063-8652 J9 J AGING PHYS ACTIV JI J. Aging Phys. Act. PD APR PY 2006 VL 14 IS 2 BP 192 EP 202 PG 11 WC Geriatrics & Gerontology; Gerontology; Sport Sciences SC Geriatrics & Gerontology; Sport Sciences GA V85TD UT WOS:000205795700006 PM 19462549 ER PT J AU Puck, JM Malech, HL AF Puck, JM Malech, HL TI Gene therapy for immune disorders: Good news tempered by bad news SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT 61st Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 18-22, 2005 CL San Antonio, TX SP Amer Acad Allergy Asthma & Immunol DE gene therapy; retrovirus; severe combined immunodeficiency; insertional mutagenesis; leukemia; IL2RG; adenosine deaminase ID SEVERE COMBINED IMMUNODEFICIENCY; STEM-CELL TRANSPLANTATION; HUMAN GENOME; BONE-MARROW; INTEGRATION; TRANSCRIPTION; RETROVIRUS; SURVIVAL AB After a dozen years of human gene therapy trials characterized by minimal gene correction and disappointing clinical impact, the field of gene therapy received some good news in 2000. Infants with X-linked severe combined immunodeficiency who received retroviral gene addition to cells from their bone marrow developed impressive immune reconstitution. During the following 2 years, additional patients were treated and the news was even better-babies receiving gene therapy had sustained T-cell production and in several cases developed better cell function than most patients treated with standard bone marrow transplants. Unfortunately, bad news followed. Three of the patients experienced leukemic T-cell expansions, found to be associated with retroviral insertions into genomic DNA. Where does the field stand today? C1 NHGRI, NIH, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. NIAID, Host Def Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Puck, JM (reprint author), NHGRI, NIH, Genet & Mol Biol Branch, NIH Bldg 49,Rm 4A14, Bethesda, MD 20892 USA. EM jpuck@mail.nih.gov OI Malech, Harry/0000-0001-5874-5775 NR 31 TC 9 Z9 11 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2006 VL 117 IS 4 BP 865 EP 869 DI 10.1016/j.jaci.2006.01.041 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 033QB UT WOS:000236862800022 PM 16630946 ER PT J AU Notarangelo, L Casanova, JL Conley, ME Chapel, H Fischer, A Puck, J Roifman, C Seger, R Geha, RS AF Notarangelo, L Casanova, JL Conley, ME Chapel, H Fischer, A Puck, J Roifman, C Seger, R Geha, RS CA Int Union Immunological Soc Primar TI Primary immunodeficiency diseases: An update from the International Union of Immunological Societies Primary Immunodeficiency Diseases Classification Committee Meeting in Budapest, 2005 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE primary immunodeficiency diseases; T cells; B cells; phagocytes; complement; immune dysregulation syndromes; innate immunity AB Although relatively rare, primary immunodeficiency diseases (PIDs) provide an excellent window into the functioning of the immune system. In the late 1960s, observations on these diseases, with their associated infections and genetics, bisected the immune system into humoral immunity and cell-mediated immunity. These diseases also represent a challenge in their diagnosis and treatment. Beginning in 1970, a unified nomenclature for the then-known PIDs was created by a committee convoked by the World Health Organization. Since then, and later under the aegis of the International Union of Immunological Societies, an international committee of experts has met every 2 to 3 years to update the classification of PIDs. During the past 15 years, the molecular basis of more than 120 PIDs has been elucidated. This update results from the latest meeting of this committee in Budapest, Hungary, in June 2005, which followed 21/2 days of scientific discussions. As a result of this work, new entities have been included, and the nomenclature of some PIDs (specifically of the various forms of class-switch recombination defects, previously known as hyper-IgM syndromes) has been changed. C1 Univ Brescia, Spedali Civili, Dept Pediat, I-25121 Brescia, Italy. Hop Necker Enfants Malad, Paris, France. Univ Tennessee, Memphis, TN USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Univ Oxford, Nuffield Dept Med, Oxford OX1 2JD, England. NIH, Bethesda, MD 20892 USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Univ Kinderklin, Zurich, Switzerland. Childrens Hosp, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. RP Geha, RS (reprint author), Div Immunol, 300 Longwood Ave, Boston, MA 02115 USA. EM raif.geha@childrens.harvard.edu RI Notarangelo, Luigi/F-9718-2016 OI Notarangelo, Luigi/0000-0002-8335-0262 FU NIAID NIH HHS [AI-35714] NR 4 TC 136 Z9 147 U1 0 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2006 VL 117 IS 4 BP 883 EP 896 DI 10.1016/j.jaci.2005.12.1347 PG 14 WC Allergy; Immunology SC Allergy; Immunology GA 033QB UT WOS:000236862800025 PM 16680902 ER PT J AU Antas, PRZ Ding, L Hackman, J Reeves-Hammock, L Shintani, AK Schiffer, J Holland, SM Sterling, TR AF Antas, PRZ Ding, L Hackman, J Reeves-Hammock, L Shintani, AK Schiffer, J Holland, SM Sterling, TR TI Decreased CD4(+) lymphocytes and innate immune responses in adults with previous extrapulmonary tuberculosis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE Mycobacterium tuberculosis; extrapulmonary tuberculosis; cytokines; innate immunity; CD4(+) lymphocytes ID TUMOR-NECROSIS-FACTOR; HUMAN-IMMUNODEFICIENCY-VIRUS; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; INTERFERON-GAMMA; FACTOR-ALPHA; CELL COUNTS; IFN-GAMMA; INFECTION; SUSCEPTIBILITY AB Background: CD4(+) lymphocytes control Mycobacterium tuberculosis infection through cytokine-mediated macrophage activation. Extrapulmonary tuberculosis is presumably a marker of immunodeficiency, but cytokine responses have not been well studied in such patients. Objective: Assess immune defects in persons with previous extrapulmonary tuberculosis. Methods: In vitro cytokine responses of PBMCs from HIV-seronegative adults with previous extrapulmonary tuberculosis (n = 10) were compared with responses from persons with previous pulmonary tuberculosis (n = 24) and latent M tuberculosis infection (n = 30) in a case-control study. Results: Patients and controls did not differ according to age, sex, race, or monocytes. The median time between tuberculosis diagnosis and study entry was 72 and 122 weeks in extrapulmonary and pulmonary patients, respectively (P = .2). Median CD4+ counts were 660, 814, and 974 lymphocytes/mm(3) in extrapulmonary, pulmonary, and latently infected patients, respectively (P = .03). At 48 hours, median unstimulated cytokine levels were uniformly lower in extrapulmonary patients than both sets of controls. These differences persisted after controlling for CD4(+) count by linear regression analysis. Despite lower unstimulated levels, median TNF-alpha response was higher in patients with extrapulmonary and pulmonary tuberculosis than latently infected persons after stimulation with PHA 1% (P = .006) and PHA + IL-12 (1 ng/mL; P = .02); IL-10 remained low in patients with extrapulmonary tuberculosis after the same stimuli (P = .04 and .06, respectively). There was no primary immunodeficiency in the IL-12/23-1FN-gamma axis. Conclusion: HIV-seronegative adults with previous extrapulmonary tuberculosis had lower CD4+ lymphocytes and unstimulated cytokine production. This suggests a subtle abnormality in innate immune function. Clinical implications: These characteristics could identify persons at risk for severe tuberculosis manifestations. C1 Vanderbilt Univ, Med Ctr, Div Infect Dis, Nashville, TN 37232 USA. Vanderbilt Univ, Med Ctr, Dept Biostat, Nashville, TN 37232 USA. NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. Baltimore City Hlth Dept Eastern Chest Clin, Baltimore, MD USA. Nashville Metropolitan Hlth Dept TB Clin, Nashville, TN USA. RP Sterling, TR (reprint author), Vanderbilt Univ, Med Ctr, Div Infect Dis, A2209 Med Ctr N,1161 21st Ave S, Nashville, TN 37232 USA. EM timothy.sterling@vanderbilt.edu FU NCRR NIH HHS [M01-RR00052]; NIAID NIH HHS [K23-AI01654] NR 42 TC 18 Z9 19 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2006 VL 117 IS 4 BP 916 EP 923 DI 10.1016/j.jaci.2006.01.042 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 033QB UT WOS:000236862800029 PM 16630952 ER PT J AU Mitre, E Nutman, TB AF Mitre, E Nutman, TB TI IgE memory: Persistence of antigen-specific IgE responses years after treatment of human filarial infections SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE IgE; immunologic memory; histamine; IL-4; helminth; basophil; humoral immunity; filaria; parasite ID FOLLICULAR DENDRITIC CELLS; TROPICAL PULMONARY EOSINOPHILIA; IMMUNOGLOBULIN-E; PLASMA-CELLS; B-CELLS; BANCROFTIAN FILARIASIS; TRICHINELLA-SPIRALIS; PERIPHERAL-BLOOD; IMMUNIZED MICE; MAST-CELLS AB Background: The human immune response to helminth infections is characterized by elevated serum levels of antigen-specific IgE. Although it is well established that IgG Immoral immunity can persist for years, as yet there have been no longitudinal studies of antigen-specific IgE responses to helminth infection in the absence of re-exposure to pathogen. Objective: We sought to determine the presence of filaria-specific IgE responses years after treatment of human filarial infections in patients no longer living in a region endemic for filariasis. Methods: Filaria-specific IgE levels were measured in 34 filaria-infected patients before and I I to 178 (median = 33) months after anthelmintic therapy. Frequencies of filaria-specific IgE-producing cells and measures of filaria-specific IgE-mediated histamine and IL-4 release from basophils were measured in subsets of these patients. Results: At follow-up, all patients were asymptomatic without evidence of active infection, and none had travelled to filaria-endemic regions since initial evaluation. Although frequencies of Brugia malayi antigen (BmAg)-specitic IgE-producing cells and serum levels of BmAg-specific IgE decreased significantly over time, both remained detectable in the majority of patients years after initial treatment. Six of 10 patients' basophils released histamine in response to BmAg after treatment (vs 7 of 10 before treatment). Basophils also continued to release IL-4 after stimulation with BmAg years after treatment. Conclusion: These results demonstrate that filaria-specific IgE production and filaria-specific IgE-mediated basophil release of histamine and IL-4 persist for years after treatment of human filarial infections. Clinical implications: These findings suggest that (1) absolute allergen avoidance may not result in the loss of allergy, and (2) parasite-specific IgE-inducing vaccines, if effective, could potentially induce longstanding protection. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Mitre, E (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Room B4104, Bethesda, MD 20814 USA. EM emitre@usuhs.mil FU Intramural NIH HHS NR 49 TC 29 Z9 29 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2006 VL 117 IS 4 BP 939 EP 945 DI 10.1016/j.jaci.2005.12.1341 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 033QB UT WOS:000236862800033 PM 16630955 ER PT J AU Orange, JS Hossny, EM Weiler, CR Ballow, M Berger, M Bonilla, FA Buckley, R Chinen, J El-Gamal, Y Mazer, BD Nelson, RP Patel, DD Secord, E Sorensen, RU Wasserman, RL Cunningham-Rundles, CC AF Orange, JS Hossny, EM Weiler, CR Ballow, M Berger, M Bonilla, FA Buckley, R Chinen, J El-Gamal, Y Mazer, BD Nelson, RP Patel, DD Secord, E Sorensen, RU Wasserman, RL Cunningham-Rundles, CC TI Use of intravenous immunoglobulin in human disease: A review of evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE immunoglobulin; IGIV; intravenous immunoglobulin; transfusion; adverse events; primary immunodeficiency()% immunomodulation; autoimmunity ID BONE-MARROW-TRANSPLANTATION; GUILLAIN-BARRE-SYNDROME; COMMON VARIABLE IMMUNODEFICIENCY; X-LINKED AGAMMAGLOBULINEMIA; IMMUNE GLOBULIN THERAPY; MULTIFOCAL MOTOR NEUROPATHY; HIGH-DOSE IMMUNOGLOBULIN; WISKOTT-ALDRICH-SYNDROME; IDIOPATHIC THROMBOCYTOPENIC PURPURA; OBSESSIVE-COMPULSIVE DISORDER AB Human immunoglobulin prepared for intravenous administration (IGIV) has a number of important uses in the treatment of disease. Some of these are in diseases for which acceptable treatment alternatives do not exist. In this review we have evaluated the evidence underlying a wide variety of IGIV uses and make specific recommendations on the basis of these data. Given the potential risks and inherent scarcity of IGIV, careful consideration of the indications for and administration of IGIV is warranted. C1 Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Ain Shams Univ, Dept Pediat, Pediat Allergy & Immunol Unit, Childrens Hosp, Cairo, Egypt. Mayo Clin, Coll Med, Dept Med, Div Allergy, Rochester, MN USA. SUNY Buffalo, Dept Pediat, Sch Med & Biomed Sci, Womens & Childrens Hosp Buffalo, Buffalo, NY 14260 USA. Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pediat, Cleveland, OH 44106 USA. Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Dept Pathol, Cleveland, OH 44106 USA. Harvard Univ, Sch Med, Dept Pediat, Childrens Hosp Boston, Boston, MA 02115 USA. Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Immunol, Durham, NC USA. NHGRI, NIH, Bethesda, MD 20892 USA. ESPAI, Cairo, Egypt. McGill Univ, Montreal Childrens Hosp, Montreal, PQ H3H 1P3, Canada. McGill Univ, Dept Pediat, Montreal, PQ H3A 2T5, Canada. Indiana Univ, Sch Med, Dept Med, Div Hematol Oncol,Hematol Malignancy Program Immu, Indianapolis, IN 46204 USA. Thursyon Arthritis Res Ctr, Dept Med, Chapel Hill, NC USA. Thursyon Arthritis Res Ctr, Dept Microbiol & Immunol, Chapel Hill, NC USA. Div Rheumatol Allergy & Immunol, Chapel Hill, NC USA. Wayne State Univ, Dept Pediat, Childrens Hosp Michigan, Detroit, MI 48202 USA. Louisiana State Univ, Ctr Hlth Sci, Dept Pediat, New Orleans, LA USA. Univ Texas, SW Med Ctr, Dept Pediat, Dallas, TX USA. Mt Sinai Sch Med, Dept Med & Clin Immunol, New York, NY USA. RP Orange, JS (reprint author), Univ Penn, Childrens Hosp Philadelphia, Dept Pediat, 3615 Civ Ctr Blvd,ARC 1216F, Philadelphia, PA 19104 USA. EM Orange@mail.med.upenn.edu RI Orange, Jordan/D-5239-2009; OI orange, jordan/0000-0001-7117-7725 NR 356 TC 298 Z9 307 U1 7 U2 23 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD APR PY 2006 VL 117 IS 4 SU S BP S525 EP S553 DI 10.1016/j.jaci.2006.01.015 PG 29 WC Allergy; Immunology SC Allergy; Immunology GA 034FF UT WOS:000236913700001 PM 16580469 ER PT J AU Troiano, RP AF Troiano, RP TI Translating accelerometer counts into energy expenditure: advancing the quest SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Editorial Material C1 NCI, Appl Res Program, Risk Factor Monitoring & Methods Branch, NIH, Bethesda, MD 20892 USA. RP Troiano, RP (reprint author), NCI, Appl Res Program, Risk Factor Monitoring & Methods Branch, NIH, Bethesda, MD 20892 USA. EM troianor@mail.nih.gov OI Troiano, Richard/0000-0002-6807-989X NR 8 TC 28 Z9 28 U1 0 U2 5 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 8750-7587 J9 J APPL PHYSIOL JI J. Appl. Physiol. PD APR PY 2006 VL 100 IS 4 BP 1107 EP 1108 DI 10.1152/japplphysiol.01577.2005 PG 2 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 033NF UT WOS:000236854500006 PM 16540708 ER PT J AU Beare, PA Samuel, JE Howe, D Virtaneva, K Porcella, SF Heinzen, RA AF Beare, PA Samuel, JE Howe, D Virtaneva, K Porcella, SF Heinzen, RA TI Genetic diversity of the Q fever agent, Coxiella burnetii, assessed by micro array-based whole-genome comparisons SO JOURNAL OF BACTERIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; CHLAMYDIA-TRACHOMATIS; PHASE-II; INTRACELLULAR PARASITES; RICKETTSIA-PROWAZEKII; SEQUENCE-ANALYSIS; ACUTE DISEASE; PLASMID; LIPOPOLYSACCHARIDE; DNA AB Coxiella burnetii, a gram-negative obligate intracellular bacterium, causes human Q fever and is considered a potential agent of bioterrorism. Distinct genomic groups of C. burnetti are revealed by restriction fragment-length polymorphisms (RFLP). Here we comprehensively define the genetic diversity of C burnetii by hybridizing the genomes of 20 RFLP-grouped and four ungrouped isolates from disparate sources to a high-density custom Affymetrix GeneChip containing all open reading frames (ORFs) of the Nine Mile phase I (NMI) reference isolate. We confirmed the relatedness of RFLP-grouped isolates and showed that two ungrouped isolates represent distinct genomic groups. Isolates contained up to 20 genomic polymorphisms consisting of 1 to 18 ORFs each. These were mostly complete ORE deletions, although partial deletions, point mutations, and insertions were also identified. A total of 139 chromosomal and plasmid ORFs were polymorphic among all C. burnetii isolates, representing ca. 7% of the NMI coding capacity. Approximately 67% of all deleted ORFs were hypothetical, while 9% were annotated in NMI as nonfunctional (e.g., frameshifted). The remaining deleted ORFs were associated with diverse cellular functions. The only deletions associated with isogenic NMI variants of attenuated virulence were previously described large deletions containing genes involved in lipopolysaccharide (LPS) biosynthesis, suggesting that these polymorphisms alone are responsible for the lower virulence of these variants. Interestingly, a variant of the Australia QD isolate producing truncated LPS had no detectable deletions, indicating LPS truncation can occur via small genetic changes. Our results provide new insight into the genetic diversity and virulence potential of Coxiella species. C1 NIAID, Intracellular Parasites Lab, Rocky Mt Labs, Coxiella Pathogenesis Sect, Hamilton, MT 59840 USA. NIAID, Persistent Viral Dis Lab, Rocky Mt Labs, Hamilton, MT 59840 USA. NIAID, Genom Core Facil, Rocky Mt Labs, Hamilton, MT 59840 USA. Texas A&M Univ Syst, Hlth Sci Ctr, Dept Med Microbiol & Immunol, College Stn, TX 77843 USA. RP Heinzen, RA (reprint author), NIAID, Intracellular Parasites Lab, Rocky Mt Labs, Coxiella Pathogenesis Sect, 903 S 4th St, Hamilton, MT 59840 USA. EM rheinzen@niaid.nih.gov FU Intramural NIH HHS NR 84 TC 68 Z9 70 U1 0 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2006 VL 188 IS 7 BP 2309 EP 2324 DI 10.1128/JB.188.7.2309-2324.2006 PG 16 WC Microbiology SC Microbiology GA 027GP UT WOS:000236403300003 PM 16547017 ER PT J AU Diaz, PI Slakeski, N Reynolds, EC Morona, R Rogers, AH Kolenbrander, PE AF Diaz, PI Slakeski, N Reynolds, EC Morona, R Rogers, AH Kolenbrander, PE TI Role of oxyR in the oral anaerobe Porphyromonas gingivalis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID OXIDATIVE STRESS-RESPONSE; DISULFIDE BOND FORMATION; BACTEROIDES-FRAGILIS; HYDROGEN-PEROXIDE; GENE-EXPRESSION; OBLIGATE ANAEROBIOSIS; SUPEROXIDE-DISMUTASE; TRANSCRIPTION FACTOR; PERIODONTAL POCKETS; ESCHERICHIA-COLI AB Porphyromonas gingivalis is an anaerobic microorganism that inhabits the oral cavity, where oxidative stress represents a constant challenge. A putative transcriptional regulator associated with oxidative stress, an oxyR homologue, is known from the P. gingivalis W83 genome sequence. We used microarrays to characterize the response of P. gingivalis to H2O2 and examine the role of oxyR in the regulation of this response. Most organisms in which oxyR has been investigated are facultative anaerobes or aerobes. In contrast to the OxyR-regulated response of these microorganisms to H2O2 the main feature of the response in P. gingivalis was a concerted up-regulation of insertion sequence elements related to IS1 transposases. Common OxyR-regulated genes such as dps and ahpFC were not positively regulated in P. gingivalis in response to H2O2. However, their expression was dependent on the presence of a functional OxyR, as revealed by microarray comparison of an oxyR mutant to the wild type. Phenotypic characterization of the oxyR mutant showed that OxyR plays a role in both the resistance to H2O2 and the aerotolerance of P. gingivalis. Escherichia coli and other bacteria with more complex respiratory requirements use OxyR for regulating resistance to H2O2 and use a separate regulator for aerotolerance. In P. gingivalis, the presence of a single protein combining the two functions might be related to the comparatively smaller genome size of this anaerobic microorganism. In conclusion, these results suggest that OxyR does not act as a sensor of H2O2 in P. gingivalis but constitutively activates transcription of oxidative-stress-related genes under anaerobic growth. C1 NIDCR, NIH, Bethesda, MD 20892 USA. Univ Melbourne, Sch Dent Sci, Melbourne, Vic 3000, Australia. Univ Adelaide, Dept Mol & Life Sci, Adelaide, SA, Australia. Univ Adelaide, Sch Dent, Oral Microbiol Lab, Adelaide, SA, Australia. RP Kolenbrander, PE (reprint author), NIDCR, NIH, Bldg 30,Room 310,30 Covent Dr, Bethesda, MD 20892 USA. EM pkolenbrander@dir.nidcr.nih.gov RI Diaz, Patricia/E-9465-2012; OI Reynolds, Eric/0000-0002-6618-4856 FU Intramural NIH HHS NR 51 TC 56 Z9 58 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2006 VL 188 IS 7 BP 2454 EP 2462 DI 10.1128/JB.188.7.2454-2462.2006 PG 9 WC Microbiology SC Microbiology GA 027GP UT WOS:000236403300018 PM 16547032 ER PT J AU Babu, MM Priya, ML Selvan, AT Madera, M Gough, J Aravind, L Sankaran, K AF Babu, MM Priya, ML Selvan, AT Madera, M Gough, J Aravind, L Sankaran, K TI A database of bacterial lipoproteins (DOLOP) with functional assignments to predicted lipoproteins SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PROLIPOPROTEIN SIGNAL PEPTIDASE; OUTER-MEMBRANE LIPOPROTEIN; HIDDEN MARKOV-MODELS; GRAM-NEGATIVE BACTERIA; HUMAN DENDRITIC CELLS; ESCHERICHIA-COLI; BORRELIA-BURGDORFERI; PSEUDOMONAS-AERUGINOSA; LIPID MODIFICATION; SECRETORY PATHWAY AB Lipid modification of the N-terminal Cys residue (N-acyl-S-diacylglyceryi-Cys) has been found to be an essential, ubiquitous, and unique bacterial posttranslational modification. Such a modification allows anchoring of even highly hydrophilic proteins to the membrane which carry out a variety of functions important for bacteria, including pathogenesis. Hence, being able to identify such proteins is of great value. To this end, we have created a comprehensive database of bacterial lipoproteins, called DOLOP, which contains information and links to molecular details for about 278 distinct lipoproteins and predicted lipoproteins from 234 completely sequenced bacterial genomes. The website also features a tool that applies a predictive algorithm to identify the presence or absence of the lipoprotein signal sequence in a user-given sequence. The experimentally verified lipoproteins have been classified into different functional classes and more importantly functional domain assignments using hidden Markov models from the SUPERFAMILY database that have been provided for the predicted lipoproteins. Other features include the following: primary sequence analysis, signal sequence analysis, and search facility and information exchange facility to allow researchers to exchange results on newly characterized lipoproteins. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Anna Univ, Ctr Biotechnol, Madras 600025, Tamil Nadu, India. MRC, Mol Biol Lab, Cambridge CB2 2QH, England. RIKEN, Genom Sci Ctr, Tsurumi Ku, Yokohama, Kanagawa 2300045, Japan. RP Babu, MM (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM madanm@mrc-lmb.cam.ac.uk; ksankaran@annauniv.edu FU Intramural NIH HHS; Medical Research Council [MC_U105185859] NR 66 TC 139 Z9 143 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2006 VL 188 IS 8 BP 2761 EP 2773 DI 10.1128/JB.188.8.2761-2773.2006 PG 13 WC Microbiology SC Microbiology GA 032AL UT WOS:000236746200003 PM 16585737 ER PT J AU Fujigaki, H Saito, K Fujigaki, S Takemura, M Sudo, K Ishiguro, H Seishima, M AF Fujigaki, H Saito, K Fujigaki, S Takemura, M Sudo, K Ishiguro, H Seishima, M TI The signal transducer and activator of transcription 1 alpha and interferon regulatory factor 1 are not essential for the induction of indoleamine 2,3-dioxygenase by lipopolysaccharide: Involvement of p38 mitogen-activated protein kinase and nuclear Factor-kappa B pathways, and synergistic effect of several proinflammatory cytokines SO JOURNAL OF BIOCHEMISTRY LA English DT Article DE enzyme induction; indoleamine 2,3-dioxygenase; interferon regulatory factor-1; lipopolysaccharide; signal transducer and activator of transcription 1 alpha ID QUINOLINIC ACID FORMATION; T-CELL PROLIFERATION; MONONUCLEAR PHAGOCYTES; GENE-EXPRESSION; TUMOR-CELLS; DNA-BINDING; IFN-GAMMA; TRYPTOPHAN; MACROPHAGES; INHIBITION AB Indoleamine 2,3-dioxygenase (IDO) is induced by interferon (IM-gamma-mediated effects of the signal transducer and activator of transcription 1 alpha (STAT1 alpha) and interferon regulatory factor (IRF)-1. The induction of IDO can also be mediated through an IFN-gamma-independent mechanism, although the mechanism of induction has not been identified. In this study, we explored whether lipopolysaccharide (LPS) or several proinflammatory cytokines can induce IDO via an IFN-gamma-independent mechanism, and whether IDO induction by LPS requires the STAT1 alpha and IRF-1 signaling pathways. IDO was induced by LPS or IFN-gamma in peripheral blood mononuclear cells and THP-1 cells, and a synergistic IDO induction occurred when THP-1 cells were cultured in the presence of a combination of tumor necrosis factor-alpha, interleukin-6 or interleukin-1 beta. An electrophoretic mobility shift assay using STAT1 alpha and IRF-1 consensus oligonucleotide probes showed no STAT1 alpha or IRF-1 binding activities in LPS-stimulated THP-1 cells. Further, the LPS-induced IDO activity was inhibited by both p38 mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-kappa B) inhibitors. These findings suggest that the induction of IDO by LPS in THP-1 cells is not regulated by IFN-gamma via recruitment of STAT1 alpha or IRF-1 to the intracellular signaling pathway, and may be related to the activity of the p38 MAPK pathway and NF-kappa B. C1 Gifu Univ, Grad Sch Med, Dept Informat Clin Med, Gifu 5011194, Japan. NIMH, Lab Neurotoxicol, Bethesda, MD 20892 USA. Carna Biosci Inc, Kobe, Hyogo 6500047, Japan. RP Saito, K (reprint author), Gifu Univ, Grad Sch Med, Dept Informat Clin Med, 1-1 Yanagido, Gifu 5011194, Japan. EM saito@cc.gifu-u.ac.jp NR 31 TC 105 Z9 112 U1 2 U2 10 PU JAPANESE BIOCHEMICAL SOC PI TOKYO PA ISHIKAWA BLDG-3F, 25-16 HONGO-5-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0021-924X J9 J BIOCHEM JI J. Biochem. PD APR PY 2006 VL 139 IS 4 BP 655 EP 662 DI 10.1093/jb/mvj072 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 047NW UT WOS:000237887000004 PM 16672265 ER PT J AU Ramaswamy, S Wang, DA Fishbein, KW Elisseeff, JH Spencer, RG AF Ramaswamy, S Wang, DA Fishbein, KW Elisseeff, JH Spencer, RG TI An analysis of the integration between articular cartilage and nondegradable hydrogel using magnetic resonance imaging SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE magnetic resonsnce imaging (MRI); hydrogel; cartilage; integration; transverse relaxation time (T-2) ID MICROSCOPY; MATRIX AB A hydrogel is a highly hydrated polymer gel suitable for use as a scaffold for tissue engineering. One important application is to the repair of cartilage defects due to injury or osteoarthritis. Integration of the hydrogel with surrounding tissue is critical for the long-term functionality of the implant; however direct visualization of integration is difficult and invasive. Accordingly, we used MRI to noninvasively investigate the integration of hydrogel in cartilage. Two integration methods were assessed: (1) cartilage-initiated and (2) chemical, using chondroitin sulphate-methacrylate-aldehyde (CS-MA-ald) as an adhesive. These were compared to a control group, that is, standard, nonintegrated hydrogel photopolymerization. Spatial variation of the transverse relaxation time, T-2, across the transition region was used to determine the effectiveness of integration. In the CS-MA-ald group only, two interfaces were found. This provides evidence of an intermediate adhesive layer between hydrogel and cartilage. Second, the thickness of the transition region between hydrogel to cartilage in the CS-MA-ald group was 1.32 rum as compared to 1.20 nun and 1.17 mm in the tissue-initiated and nonintegrated groups, respectively. We interpret this as a more gradual transition region of hydrogel to cartilage and hence a greater degree of integration when an adhesive layer is present. (c) 2005 Wiley Periodicals, Inc. C1 NIA, NIH, Clin Invest Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Biomed Engn, Baltimore, MD 21218 USA. RP Spencer, RG (reprint author), NIA, NIH, Clin Invest Lab, Gerontol Res Ctr, Room 4D-08,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM spencer@helix.nih.gov RI Wang, Dong-an/G-6195-2010; OI Fishbein, Kenneth/0000-0002-6353-4603 NR 10 TC 26 Z9 27 U1 2 U2 13 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD APR PY 2006 VL 77B IS 1 BP 144 EP 148 DI 10.1002/jbm.b.30404 PG 5 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 025JO UT WOS:000236262000020 PM 16208691 ER PT J AU Ishima, R Torchia, DA AF Ishima, R Torchia, DA TI Accuracy of optimized chemical-exchange parameters derived by fitting CPMG R-2 dispersion profiles when R-2(0a) = R-2(0b) SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article DE chemical exchange; conformational change; NMR; R-2; relaxation ID NUCLEAR-MAGNETIC-RESONANCE; TIME-SCALE DYNAMICS; NMR-SPECTROSCOPY; TRANSVERSE-RELAXATION; CAVITY MUTANT; SIDE-CHAINS; T4 LYSOZYME; PROTEINS; MOTIONS; DEPENDENCE AB The transverse relaxation rate, R-2, measured as a function of the effective field ( R2 dispersion) using a Carr-Purcell-Meiboom-Gill (CPMG) pulse train, is well suited to detect conformational exchange in proteins. The dispersion data are commonly fitted by a two-site (sites a and b) exchange model with four parameters: the relative population, p(a), the difference in chemical shifts of the two sites, delta omega, the correlation time for exchange, tau(ex,) and the intrinsic relaxation rate (i.e., transverse relaxation rate in the absence of chemical exchange), R-2(0). Although the intrinsic relaxation rates of the two sites, R-2(0a) and R-2(0b), can differ, they are normally assumed to be the same (i.e., R-2(0a) = R-2(0b) = R-2(0)) when fitting dispersion data. The purpose of this investigation is to determine the magnitudes of the errors in the optimized exchange parameters that are introduced by the assumption that R-2(0a) = R-2(0b). In order to accomplish this goal, we first generated synthetic constant-time CPMG R-2 dispersion data assuming two-site exchange with R-2(0a) not equal R-2(0b), and then fitted the synthetic data assuming two-site exchange with R-2(0) = R-2(0a) = R-2(0b). Although all the synthetic data generated assuming R-2(0a) not equal R-2(0b) were well fitted (assuming R-0a(2) = R-2(0b)), the optimized values of pa and sex differed from their true values, whereas the optimized values of delta omega values did not. A theoretical analysis using the Carver-Richards equation explains these results, and yields simple, general equations for estimating the magnitudes of the errors in the optimized parameters, as a function of (R-2(0a) - R-2(0b)). C1 Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Biol Struct, Pittsburgh, PA 15260 USA. RP Ishima, R (reprint author), Natl Inst Dent & Craniofacial Res, Struct Mol Biol Unit, NIH, Bldg 30,Rm 109,30 Convent Dr, Bethesda, MD 20892 USA. EM ishima@pitt.edu FU Intramural NIH HHS NR 24 TC 21 Z9 22 U1 1 U2 6 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD APR PY 2006 VL 34 IS 4 BP 209 EP 219 DI 10.1007/s10858-005-6226-7 PG 11 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 038AV UT WOS:000237190800001 PM 16645811 ER PT J AU Leet, AI Wientroub, S Kushner, H Brillante, B Kelly, MH Robey, PG Collins, MT AF Leet, AI Wientroub, S Kushner, H Brillante, B Kelly, MH Robey, PG Collins, MT TI The correlation of specific orthopaedic features of polyostotic fibrous dysplasia with functional outcome scores in children SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article ID MCCUNE-ALBRIGHT-SYNDROME; BONE; GENE; DYSFUNCTION; INSTRUMENT; MUTATIONS; SCOLIOSIS AB Background: Polyostotic fibrous dysplasia has a wide clinical spectrum, with substantial variation between patients in terms of orthopaedic manifestations, including the number of fractures, the degree of deformity of the limbs, and the presence of scoliosis. Data from bone scans, skeletal surveys, and records were correlated with the Pediatric Outcomes Data Collection Instrument scales to examine whether any specific facet of orthopaedic involvement could be related to functional abilities. Methods: All patients who were sixteen years of age or younger and who were part of an ongoing natural history study of polyostotic fibrous dysplasia (including McCune-Albright syndrome) were sent an age-appropriate Pediatric Outcomes Data Collection Instrument outcomes tool. The medical records and radiographs of the patients who returned forms were reviewed. Radiographic measurements of scoliosis, the femoral neck-shaft angle, and limb deformities were then performed. The extent of skeletal involvement with polyostotic fibrous dysplasia (disease burden) was assessed on bone scans with use of a validated tool. A chart review was performed to determine the fracture rate, the use of bisphosphonates, and the endocrine status. These measurements were correlated with the Pediatric Outcomes Data Collection Instrument scores. Results: The outcomes tool was sent to twenty-seven patients and the completed instrument was returned by twenty patients, for a response rate of 74%. The parent-child form was filled out for twelve patients and the parent-adolescent form was filled out for eight patients. The mean standardized Pediatric Outcomes Data Collection Instrument scores for all twenty patients were lowest for sports (62; range, 14 to 100) and happiness (72; range, 25 to 100). Adolescents and parents disagreed with regard to sports (with adolescent scores being higher than parental scores) and pain (with parental scores being higher than adolescent scores). However, the overall global scores correlated well between the parents and the adolescents (r = 0.78, p = 0.03). The femoral neck-shaft angle correlated strongly with the Pediatric Outcomes Data Collection Instrument score for sports (r = 0.46, p = 0.03) but not for transfers. The bone scan scores for the lower extremity disease burden correlated with both the transfer scale (r = 0.76, p = 0.03) and the sports scale (r = 0.77, p = 0.02). Deformity of the limbs, the presence of scoliosis, the prevalence of endocrine dysfunction, and the number of fractures did not correlate with the Pediatric Outcomes Data Collection Instrument scores. Conclusions: In patients with polyostotic fibrous dysplasia, the loss of the normal femoral neck-shaft angle and the disease burden in the lower extremities appear to have the greatest effect on functional activity as measured with the Pediatric Outcomes Data Collection Instrument tool. C1 NIH, Bethesda, MD USA. RP Leet, AI (reprint author), Johns Hopkins Med, Dept Orthopaed Surg, 601 N Caroline St,5255, Baltimore, MD 21287 USA. EM aleet1@jhmi.edu RI Robey, Pamela/H-1429-2011 OI Robey, Pamela/0000-0002-5316-5576 NR 17 TC 12 Z9 13 U1 0 U2 2 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD APR PY 2006 VL 88A IS 4 BP 818 EP 823 DI 10.2106/JBJS.E.00259 PG 6 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 029KF UT WOS:000236560500017 PM 16595472 ER PT J AU Nie, ZZ Randazzo, PA AF Nie, ZZ Randazzo, PA TI Arf GAPs and membrane traffic SO JOURNAL OF CELL SCIENCE LA English DT Article DE ADP-ribosylation factor; GTPase-activating protein; membrane traffic; coat proteins ID ADP-RIBOSYLATION FACTOR; GTPASE-ACTIVATING PROTEIN; AMINOACYL-TRANSFER-RNA; COPI VESICLE FORMATION; CELL-FREE SYSTEM; GOLGI MEMBRANES; COATED VESICLES; BINDING-PROTEIN; LIVING CELLS; ENDOPLASMIC-RETICULUM AB The selective transfer of material between membrane-delimited organelles is mediated by protein-coated vesicles. In many instances, formation of membrane trafficking intermediates is regulated by the GTP-binding protein Arf. Binding and hydrolysis of GTP by Arf was originally linked to the assembly and disassembly of vesicle coats. Arf GTPase-activating proteins (GAPs), a family of proteins that induce hydrolysis of GTP bound to Arf, were therefore proposed to regulate the disassembly and dissociation of vesicle coats. Following the molecular identification of Arf GAPs, the roles for GAPs and GTP hydrolysis have been directly examined. GAPs have been found to bind cargo and known coat proteins as well as directly contribute to vesicle formation, which is consistent with the idea that GAPs function as subunits of coat proteins rather than simply Arf inactivators. In addition, GTP hydrolysis induced by GAPs occurs largely before vesicle formation and is required for sorting. These results are the primary basis for modifications to the classical model for the function of Arf in transport vesicle formation, including a recent proposal that Arf has a proofreading, rather than a structural, role. C1 NCI, Cellular Oncol Lab, Ctr Canc Res, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. RP Randazzo, PA (reprint author), NCI, Cellular Oncol Lab, Ctr Canc Res, Dept Hlth & Human Serv,NIH, Bethesda, MD 20892 USA. EM randazzo@helix.nih.gov FU Intramural NIH HHS NR 93 TC 84 Z9 86 U1 5 U2 5 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD APR 1 PY 2006 VL 119 IS 7 BP 1203 EP 1211 DI 10.1242/jcs.02924 PG 9 WC Cell Biology SC Cell Biology GA 032GZ UT WOS:000236763900002 PM 16554436 ER PT J AU Yang, L Reece, J Gabriel, SE Shears, SB AF Yang, L Reece, J Gabriel, SE Shears, SB TI Apical localization of ITPK1 enhances its ability to be a modifier gene product in a murine tracheal cell model of cystic fibrosis SO JOURNAL OF CELL SCIENCE LA English DT Article DE ITPK1; cystic fibrosis; inositol phosphates; CFTR; secretion; chloride channel ID INOSITOL 1,3,4-TRISPHOSPHATE 5/6-KINASE; ACTIVATED CHLORIDE CONDUCTANCE; DEPENDENT PROTEIN-KINASE; AIRWAY EPITHELIA; MYOINOSITOL 3,4,5,6-TETRAKISPHOSPHATE; LUNG-DISEASE; CALCIUM; SECRETION; CHANNELS; AGONIST AB A new aspect of research into the pathogenesis of cystic fibrosis (CF) is a genetics-based search for 'modifier genes' that may affect the severity of CF lung disease. Using an alternative, cell biological approach, we show that ITPK1 should be considered a modifier gene. ITPK1 synthesizes an intracellular signal, inositol (3,4,5,6)-tetrakisphosphate [Ins(3,4,5,6)P-4]. A bio-activatable, cell-permeable analogue of Ins(3,4,5,6)P-4 inhibited Ca2+-dependent secretion of Cl from polarized monolayers of immortalized mouse tracheal epithelial cells (MTEs). Analysis by high-pressure liquid chromatography showed endogenous Ins(3,4,5,6)P-4 levels in CF MTEs were approximately 60% below those in wildtype MTEs (P < 0.03). This adaptation, which improves purinergic activation of Ca2+-dependent Cl- secretion in CF MTEs, was exceptionally specific; there was no effect upon the cellular levels of all the other inositol phosphate signals. Real-time PCR provided the explanation: the level of ITPK1 expression in wild-type MTEs was twice as high as that in CF MTEs (P < 0.002). The biological impact of this differential gene expression is amplified by ITPK1 being concentrated at the apical membrane of MTEs, which we discovered following confocal immunofluorescence microscopy. Compartmentalization of Ins(3,4,5,6)P-4 synthesis adjacent to its site of action will enhance its regulatory capacity. C1 NIEHS, DHSS, Inositol Signaling Sect, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, DHSS, Lab Signal Transduct, NIH, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Pediat, Chapel Hill, NC 27599 USA. Univ N Carolina, Cyst Fibrosis Pulm Res & Treatment Ctr, Chapel Hill, NC 27599 USA. RP Shears, SB (reprint author), NIEHS, DHSS, Inositol Signaling Sect, NIH, Res Triangle Pk, NC 27709 USA. EM shears@niehs.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [HL 62564] NR 53 TC 10 Z9 10 U1 0 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD APR 1 PY 2006 VL 119 IS 7 BP 1320 EP 1328 DI 10.1242/jcs.02836 PG 9 WC Cell Biology SC Cell Biology GA 032GZ UT WOS:000236763900012 PM 16537650 ER PT J AU Saha, T Ghosh, S Vassilev, A DePamphilis, ML AF Saha, T Ghosh, S Vassilev, A DePamphilis, ML TI Ubiquitylation, phosphorylation and Orc2 modulate the subcellular location of Orc1 and prevent it from inducing apoptosis SO JOURNAL OF CELL SCIENCE LA English DT Article DE cell division cycle; CHO; HeLa; ORC; phosphorylation; ubiquitylation ID ORIGIN RECOGNITION COMPLEX; REPLICATION-INITIATION PROTEINS; DNA-REPLICATION; CELL-CYCLE; LARGEST SUBUNIT; ES CELLS; S-PHASE; P53; CHROMATIN; MUTANT AB Previous studies have suggested that the activity of the mammalian origin recognition complex (ORC) is regulated by cell-cycle-dependent changes in its Orc1 subunit. Here, we show that Orc1 modifications such as monoubiquitylation and hyperphosphorylation that occur normally during S and G2-M phases, respectively, can cause Orc1 to accumulate in the cytoplasm. This would suppress reassembly of pre-replication complexes until mitosis is complete. In the absence of these modifications, transient expression of Orc1 rapidly induced p53-independent apoptosis, and Orc1 accumulated perinuclearly rather than uniformly throughout the nucleus. This behavior mimicked the increased concentration and perinuclear accumulation of endogenous Orc1 in apoptotic cells that arise spontaneously in proliferating cell cultures. Remarkably, expression of Orc1 in the presence of an equivalent amount of Orc2, the only ORC subunit that did not induce apoptosis, prevented induction of apoptosis and restored uniform nuclear localization of Orc1. This would promote assembly of ORC-chromatin sites, such as occurs during the transition from M to G1 phase. These results provide direct evidence in support of the regulatory role proposed for Orc1, and suggest that aberrant DNA replication during mammalian development could result in apoptosis through the appearance of 'unmodified' Orc1. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP DePamphilis, ML (reprint author), NICHHD, NIH, Bldg 6-3A-15,9000 Rockville Pike, Bethesda, MD 20892 USA. EM depamphm@mail.nih.gov FU Intramural NIH HHS [Z01 HD000506-12] NR 47 TC 27 Z9 28 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0021-9533 J9 J CELL SCI JI J. Cell Sci. PD APR 1 PY 2006 VL 119 IS 7 BP 1371 EP 1382 DI 10.1242/jcs.02851 PG 12 WC Cell Biology SC Cell Biology GA 032GZ UT WOS:000236763900017 PM 16537645 ER PT J AU Karaczyn, A Ivanov, S Reynolds, M Zhitkovich, A Kasprzak, KS Salnikow, K AF Karaczyn, A Ivanov, S Reynolds, M Zhitkovich, A Kasprzak, KS Salnikow, K TI Ascorbate depletion mediates up-regulation of hypoxia-associated proteins by cell density and nickel SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE ascorbate; cell density; nickel; SVCT1; SVCT2; hypoxia-inducible transcription factor; carbonic anhydrase IX; NDRG1/Cap43 ID CARBONIC-ANHYDRASE-IX; VITAMIN-C; CANCER-CELLS; PROLINE HYDROXYLATION; PROLYL 4-HYDROXYLASE; INDUCIBLE FACTOR; TUMOR HYPOXIA; HIF-ALPHA; IN-VITRO; EXPRESSION AB Exposure of human lung cells to carcinogenic nickel compounds in the presence of oxygen up-regulated carbonic anhydrase IX (CA IX) and NDRG1/Cap43, both known as intrinsic hypoxia markers and cancer-associated genes. This suggests that factors other than a shortage of oxygen may be involved in this induction. Both proteins can also be induced in the presence of oxygen by culturing these cells to a high density without medium change. The intracellular ascorbate measurements revealed its rapid depletion in both metal- and density-exposed cells. Nickel exposure caused strong activation of HIF-1 alpha and HIF-2 alpha, proteins, underscoring activation of HIF-1-dependent transcription. In contrast, cell density-dependent transcription was characterized by minor induction of HIF-1 alpha or HIF-2 alpha. Moreover, the up-regulation of NDRG1/Cap43 in HIF-1 alpha deficient fibroblasts suggested the involvement of different transcription factor(s). The repletion of intracellular ascorbate reversed the induction of CA IX and NDRG1/Cap43 caused by cell density or nickel exposure. Thus, the loss of intracellular ascorbate triggered the induction of both tumor markers by two different conditions in the presence of oxygen. Ascorbate is delivered to lung cells via the SVCT2 ascorbate transporter, which was found to be sensitive to nickel or cell density. Collectively these findings establish the importance of intracellular ascorbate levels for the regulation of expression of CA IX and NDRG1/Cap43. We suggest, that, in addition to low oxygenation, insufficient supply of ascorbate or its excessive oxidation in tumors, can contribute to the induction of hypoxia-associated proteins via both HIF-dependent and independent mechanisms. C1 NCI Frederick, Comparat Carcinogenesis Lab, Ft Detrick, MD 21702 USA. NCI Frederick, Sci Applicat Int Corp, Frederick, MD USA. Brown Univ, Dept Pathol & Lab Med, Providence, RI 02912 USA. RP Salnikow, K (reprint author), NCI Frederick, Comparat Carcinogenesis Lab, Bldg 538,Room 205E, Ft Detrick, MD 21702 USA. EM salnikow@ncifcrf.gov OI Ivanov, Sergey/0000-0001-9770-7237 FU Intramural NIH HHS; NIEHS NIH HHS [ES008786, ES012915, R01 ES008786] NR 40 TC 46 Z9 50 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD APR 1 PY 2006 VL 97 IS 5 BP 1025 EP 1035 DI 10.1002/jcb.20705 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 025LE UT WOS:000236266800011 PM 16288478 ER PT J AU Mood, K Saucier, C Ishimura, A Bong, YS Lee, HS Park, M Daar, IO AF Mood, K Saucier, C Ishimura, A Bong, YS Lee, HS Park, M Daar, IO TI Oncogenic met receptor induces cell-cycle progression in Xenopus oocytes independent of direct Grb2 and shc binding or Mos synthesis, but requires phosphatidylinositol 3-kinase and Raf signaling SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID HEPATOCYTE GROWTH-FACTOR; EPITHELIAL MORPHOGENESIS DOWNSTREAM; GERMINAL VESICLE BREAKDOWN; TYROSINE KINASE RECEPTOR; PHOSPHOLIPASE C-GAMMA-1; PHOSPHORYLATION SITES; MEIOTIC MATURATION; PROTEIN-KINASE; MAP KINASE; STIMULATED MATURATION AB Biological responses of hepatocyte growth factor (HGF) are mediated by the Met receptor tyrosine kinase. Although HGF is a potent mitogen for a variety of cells, the signals required for cell-cycle progression by the Met/HGF receptor are poorly defined. In this study, we have used the Xenopus oocyte system to define the role of various Met proximal-binding partners and downstream signaling pathways in cell-cycle regulation. We show that cell-cycle progression and activation of MAPK and JNK mediated by the oncogenic Met receptor, Tpr-Met, are dependent on its kinase activity and the presence of the twin phosphotyrosine (Y482 & Y489) residues in its C-terminus, but that the recruitment of Grb2 and Shc adaptor proteins is dispensable, implicating other signaling molecules. However, using Met receptor oncoproteins engineered to recruit specific signaling proteins, we demonstrate that recruitment of Grb2 or Shc adaptor proteins is sufficient to induce cell-cycle progression and activation of MAPK and JNK, while the binding of phospholipase-C gamma or phosphatidylinositol 3-kinase alone fails to elicit these responses. Using various means to block phosphaticlylinositol 3-kinase, phospholipase-C gamma, MEK, JNK, Mos, and Raft activity, we Show that Unlike the fibroblast growth factor receptor, MEK-dependent and independent signaling contribute to Met receptor-mediated cell-cycle progression, but phospholipase-C gamma or JNK activity and Mos synthesis are not critical. Notably, we demonstrate that Raf1 and phosphatidylinositol 3-kinase signaling are required for cell-cycle progression initiated by the Met receptor, a protein frequently deregulated in human tumors. C1 NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. McGill Univ, Ctr Hlth, Mol Oncol Grp, Montreal, PQ H3A 2T5, Canada. McGill Univ, Ctr Hlth, Dept Biochem, Montreal, PQ H3A 2T5, Canada. McGill Univ, Ctr Hlth, Dept Med, Montreal, PQ H3A 2T5, Canada. McGill Univ, Ctr Hlth, Dept Oncol, Montreal, PQ H3A 2T5, Canada. RP Daar, IO (reprint author), NCI, Lab Prot Dynam & Signaling, Bldg 560,Room 22-3, Frederick, MD 21702 USA. EM daar@nciferf.gov RI Lee, Hyun-Shik/G-3555-2011; OI Daar, Ira/0000-0003-2657-526X FU Intramural NIH HHS NR 62 TC 5 Z9 5 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD APR PY 2006 VL 207 IS 1 BP 271 EP 285 DI 10.1002/jcp.20564 PG 15 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 021LE UT WOS:000235983900029 PM 16331688 ER PT J AU Kochanek, PM Vagni, VA Janesko, KL Washington, CB Crumrine, PK Garman, RH Jenkins, LW Clark, RSB Homanics, GE Dixon, CE Schnermann, J Jackson, EK AF Kochanek, PM Vagni, VA Janesko, KL Washington, CB Crumrine, PK Garman, RH Jenkins, LW Clark, RSB Homanics, GE Dixon, CE Schnermann, J Jackson, EK TI Adenosine A1 receptor knockout mice develop lethal status epilepticus after experimental traumatic brain injury SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE controlled cortical impact; head injury; head trauma; purine; seizures ID CONTROLLED CORTICAL IMPACT; TRANSIENT FOCAL ISCHEMIA; FLUID PERCUSSION INJURY; TERM CAFFEINE TREATMENT; TEMPORAL-LOBE EPILEPSY; ADENOSINE RECEPTORS; CEREBRAL-ISCHEMIA; IN-VITRO; KINDLED SEIZURES; MESSENGER-RNA AB Adenosine, acting at A1 receptors, exhibits anticonvulsant effects in experimental epilepsy - and inhibits progression to status epilepticus ( SE). Seizures after traumatic brain injury (TBI) may contribute to pathophysiology. Thus, we hypothesized that endogenous adenosine, acting via A1 receptors, mediates antiepileptic benefit after experimental TBI. We subjected A1-receptor knockout (ko) mice, heterozygotes, and wild-type (wt) littermates (n = 115) to controlled cortical impact (CCI). We used four outcome protocols in male mice: ( 1) observation for seizures, SE, and mortality in the initial 2 h, ( 2) assessment of seizure score ( electroencephalogram ( EEG)) in the initial 2 h, ( 3) assessment of mortality at 24 h across injury levels, and ( 4) serial assessment of arterial blood pressure, heart rate, blood gases, and hematocrit. Lastly, to assess the influence of gender on this observation, we observed female mice for seizures, SE, and mortality in the initial 2 h. Seizure activity was noted in 83% of male ko mice in the initial 2 h, but was seen in no heterozygotes and only 33% of wt (P<0.05). Seizures in wt were brief (1 to 2 secs). In contrast, SE involving lethal sustained ( 41 h) tonic clonic activity was uniquely seen in ko mice after CCI ( 50% incidence in males), (P<0.05). Seizure score was twofold higher in ko mice after CCI versus either heterozygote or wt (P<0.05). An injury-intensity dose - response for 24 h mortality was seen in ko mice (P<0.05). Physiologic parameters were similar between genotypes. Seizures were seen in 100% of female ko mice after CCI versus 14% of heterozygotes and 25% wt (P<0.05) and SE was restricted to the ko mice ( 83% incidence). Our data suggest a critical endogenous anticonvulsant action of adenosine at A1 receptors early after experimental TBI. C1 Univ Pittsburgh, Sch Med, Dept Crit Care Med, Pittsburgh, PA 15260 USA. Univ Pittsburgh, Sch Med, Safar Ctr Resuscitat Res, Pittsburgh, PA USA. Childrens Hosp Pittsburgh, Div Child Neurol, Pittsburgh, PA 15213 USA. Consultants Vet Pathol Inc, Murrysville, PA USA. Univ Pittsburgh, Sch Med, Dept Neurol Surg, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Anesthesiol, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15261 USA. NIDDK, NIH, Bethesda, MD USA. Univ Pittsburgh, Sch Med, Ctr Clin Pharmacol, Pittsburgh, PA USA. RP Kochanek, PM (reprint author), Univ Pittsburgh, Sch Med, Dept Crit Care Med, 3434 5th Ave,Suite 201, Pittsburgh, PA 15260 USA. EM kochanekpm@ccm.upmc.edu RI Kochanek, Patrick/D-2371-2015; OI Kochanek, Patrick/0000-0002-2627-913X; Homanics, Gregg/0000-0003-3641-8153 FU NIDDK NIH HHS [DK068575]; NINDS NIH HHS [NS30318, NS38087] NR 66 TC 83 Z9 85 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD APR PY 2006 VL 26 IS 4 BP 565 EP 575 DI 10.1038/sj.jcbfm.9600218 PG 11 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 026LM UT WOS:000236340400012 PM 16121125 ER PT J AU Saporito, RA Donnelly, MA Garraffo, HM Spande, TF Daly, JW AF Saporito, Ralph A. Donnelly, Maureen A. Garraffo, H. Martin Spande, Thomas F. Daly, John W. TI Geographic and seasonal variation in alkaloid-based chemical defenses of Dendrobates pumilio from Bocas del Toro, Panama SO JOURNAL OF CHEMICAL ECOLOGY LA English DT Article DE poison frogs; dendrobatid; Dendrobates pumilio; alkaloids; arthropods; ants; mites; chemical defense ID POISON FROGS DENDROBATIDAE; PYRROLIZIDINE ALKALOIDS; SKIN ALKALOIDS; CONVERGENT EVOLUTION; DIET SPECIALIZATION; ARTHROPOD SOURCE; DART FROGS; DRY SEASON; ANTS; DECAHYDROQUINOLINES AB Poison frogs contain an alkaloid-based chemical defense that is derived from a diet of certain alkaloid-containing arthropods, which include mites, ants, beetles, and millipedes. Variation in population-level alkaloid profiles among species has been documented, and more than 800 different alkaloids have been identified. In the present study, we examine individual alkaloid variation in the dendrobatid poison frog Dendrobates pumilio among seven populations and between two seasons on Isla Bastimentos, located in the Bocas del Toro archipelago of Panama. Alkaloid profiles vary among populations and between seasons, illustrating that chemical defense in this species can vary on a small spatial and temporal scale. Alkaloid variation among populations is marginally correlated with geographic distance, and close populations have profiles more similar to each other than to distant populations. Individuals within populations also vary in alkaloid profiles. Differences are attributed to both spatial and temporal variations in the availability of alkaloid-containing arthropods. Many of the alkaloids present in the skin of D. pumilio appear likely to be of ant origin, supporting the importance of myrmecophagy in chemical defense among poison frogs. However, a variety of frog skin alkaloids was recently detected in mites, suggesting that mites may also play an important role in chemical defense. C1 Florida Int Univ, Dept Biol Sci, Miami, FL 33199 USA. NIDDKD, Bioorgan Chem Lab, US Dept HHS, NIH, Bethesda, MD 20892 USA. RP Saporito, RA (reprint author), Florida Int Univ, Dept Biol Sci, Miami, FL 33199 USA. EM saporito@fiu.edu FU Intramural NIH HHS NR 60 TC 45 Z9 46 U1 0 U2 10 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0098-0331 EI 1573-1561 J9 J CHEM ECOL JI J. Chem. Ecol. PD APR PY 2006 VL 32 IS 4 BP 795 EP 814 DI 10.1007/s10886-006-9034-y PG 20 WC Biochemistry & Molecular Biology; Ecology SC Biochemistry & Molecular Biology; Environmental Sciences & Ecology GA 046FA UT WOS:000237795600007 PM 16718571 ER PT J AU Ortega, E Koska, J Salbe, AD Tataranni, PA Bunt, JC AF Ortega, E Koska, J Salbe, AD Tataranni, PA Bunt, JC TI Serum gamma-glutamyl transpeptidase is a determinant of insulin resistance independently of adiposity in Pima Indian children SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID NONALCOHOLIC FATTY LIVER; ARTERY RISK DEVELOPMENT; YOUNG-ADULTS CARDIA; METABOLIC SYNDROME; OXIDATIVE STRESS; TRANSFERASE; DISEASE; SENSITIVITY; AMINOTRANSFERASE; ADOLESCENTS AB Context: Elevated activities of serum enzymes, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyltransferase (GGT), have been associated with obesity and insulin resistance (IR). ALT is an independent predictor of type 2 diabetes mellitus (T2DM) in adult Pima Indians, and GGT predicts T2DM in other adult populations. Objective: Our aim was to establish whether independent relationships exist between either adiposity or IR and hepatic enzymes in a group of Pima Indian children. Subjects and Methods: In a cross-sectional study, 44 children ( 22 males and 22 females; 7 - 11 yr old) were measured for weight (WT), height, percent body fat, and serum activities of ALT, AST, and GGT. Body mass index ( kilograms per meter squared) was calculated. IR was calculated from fasting plasma concentrations of glucose and insulin using the homeostasis model assessment (HOMA-IR). Results: Hepatic enzymes were positively associated with obesity measures, fasting insulin, and HOMA-IR. GGT was additionally associated with serum lipids and white blood cell count. GGT, but not AST or ALT, was a significant determinant of HOMA-IR independently of age, sex, and WT, body mass index, or percent body fat. The model that accounted for the largest portion of the variance in HOMA-IR included WT (beta = 0.004; P = 0.008) and GGT (beta = 0.20; P = 0.004; total R(2) = 0.62; P < 0.0001). Conclusion: Significant relationships between adiposity and hepatic enzyme activities exist during childhood in Pima Indians. Whether serum GGT activity predicts the development of T2DM in these children remains to be determined in follow-up studies. C1 NIDDKD, Obes & Diabet Clin Res Sect, NIH, Phoenix, AZ 85016 USA. RP Ortega, E (reprint author), NIDDKD, Obes & Diabet Clin Res Sect, NIH, 4212 N 16th St,Room 533, Phoenix, AZ 85016 USA. EM emilioo@mail.nih.gov FU Intramural NIH HHS NR 29 TC 30 Z9 30 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2006 VL 91 IS 4 BP 1419 EP 1422 DI 10.1210/jc.2005-1783 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 029YW UT WOS:000236601300038 PM 16434459 ER PT J AU Charmandari, E Kino, T Ichijo, T Zachman, K Alatsatianos, A Chrousos, GP AF Charmandari, E Kino, T Ichijo, T Zachman, K Alatsatianos, A Chrousos, GP TI Functional characterization of the natural human glucocorticoid receptor (hGR) mutants hGR alpha R477H and hGR alpha G679S associated with generalized glucocorticoid resistance SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LIGAND-BINDING DOMAIN; NF-KAPPA-B; NUCLEAR RECEPTOR; MOLECULAR-MECHANISMS; DNA-BINDING; CLINICAL PHENOTYPE; POINT MUTATION; GENE; COACTIVATOR; HORMONE AB Background: Glucocorticoid resistance is often a result of mutations in the human glucocorticoid receptor alpha(hGR alpha) gene, which impair one or more of hGR alpha's functions. We investigated the molecular mechanisms through which two previously described mutant receptors, hGR alpha R477H and hGR alpha G679S, with amino acid substitutions in the DNA- and ligand-binding domains, respectively, affect glucocorticoid signal transduction. Methods and Results: In transient transfection assays, hGR alpha R477H displayed no transcriptional activity, whereas hGR alpha G679S showed a 55% reduction in its ability to stimulate the transcription of the glucocorticoid-responsive mouse mammary tumor virus promoter in response to dexamethasone compared with the wild-type hGR alpha. Neither hGR alpha R477H nor hGR alpha G679S exerted a dominant negative effect upon the wild-type receptor. Dexamethasone binding assays showed that hGR alpha R477H preserved normal affinity for the ligand, whereas hGR alpha G679S displayed a 2-fold reduction compared with hGR alpha. Nuclear translocation studies confirmed predominantly cytoplasmic localization of the mutant receptors in the absence of ligand. Exposure to dexamethasone resulted in slower translocation of hGR alpha R477H ( 25 min) and hGR alpha G679S ( 30 min) into the nucleus than the wild-type hGR alpha ( 12 min). In chromatin immunoprecipitation assays in cells stably transfected with the mouse mammary tumor virus promoter, hGR alpha R477H did not bind to glucocorticoid-response elements, whereas hGR alpha G679S preserved its ability to bind to glucocorticoid-response elements. Finally, in glutathione-S-transferase pull-down assays, hGR alpha G679S interacted with the glucocorticoid receptor-interacting protein 1 coactivator in vitro only through its activation function (AF)-1, unlike the hGR alpha R477H and hGR alpha, which interacted with the glucocorticoid receptor-interacting protein 1 through both their AF-1 and AF-2. Conclusions: The natural mutants hGR alpha R477H and hGR alpha G679S cause generalized glucocorticoid resistance by affecting different functions of the glucocorticoid receptor, which span the cascade of the hGR signaling system. C1 NICHHD, Pediat Endocrinol Sect, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Charmandari, E (reprint author), Great Ormond St Hosp Children, Dept Pediat Endocrinol, 9th Floor,Southwood Bldg,Great Ormond St, London WC1N 3JH, England. EM charmane@mail.nih.gov RI Charmandari, Evangelia/B-6701-2011 FU Intramural NIH HHS NR 50 TC 40 Z9 45 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2006 VL 91 IS 4 BP 1535 EP 1543 DI 10.1210/jc.2005-1893 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 029YW UT WOS:000236601300056 PM 16449337 ER PT J AU Pannacciulli, N Bunt, JC Ortega, E Funahashi, T Salbe, AD Bogardus, C Krakoff, J AF Pannacciulli, N Bunt, JC Ortega, E Funahashi, T Salbe, AD Bogardus, C Krakoff, J TI Lower total fasting plasma adiponectin concentrations are associated with higher metabolic rates SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN SENSITIVITY; ENERGY-EXPENDITURE; BODY-COMPOSITION; PIMA-INDIANS; WEIGHT-LOSS; OBESITY; EXPRESSION; RESISTANCE; HUMANS; AGE AB Context: The possible role of adiponectin, a protein uniquely produced by the adipose tissue and significantly reduced in obesity and other insulin-resistant states, in the regulation of energy expenditure (EE) is still poorly understood. Objective: The objective of the study was to investigate the relationship between total fasting plasma adiponectin concentrations and the various components of EE measured in a metabolic chamber in Pima Indians and to test whether body fat distribution may have a role in this association. Design: This was a cross-sectional study. Setting: The study was an inpatient clinical research unit. Participants: Sixty nondiabetic Pima Indians ( 45 males and 15 females), aged 18 - 45 yr, spanning a wide range of adiposity ( body mass index 19.6 - 46.2 kg/m(2)) participated in the study. Main Outcome Measures: Total fasting plasma adiponectin concentrations, EE (24-h respiratory chamber), insulin sensitivity (euglycemichyperisulinemic clamp), body composition (dual-energy x-ray absorptiometry), and body fat distribution ( waist to thigh ratio) were the main outcome measures. Results: Total fasting plasma adiponectin concentrations are negatively associated with sleep EE adjusted for sex, age, fat-free mass, and fat mass. This correlation is still significant, although attenuated, after inclusion of insulin-stimulated glucose disposal among the regressors and further attenuated when adjusted also for waist to thigh ratio. Conclusions: The decrease in total fasting plasma adiponectin concentrations that accompanies fat accumulation may be a mechanism to prevent further weight gain by decreasing insulin sensitivity and increasing energy expenditure. C1 NIDDKD, Obes & Diabet Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH,Dept HHS, Phoenix, AZ 85016 USA. Osaka Univ, Grad Sch Med, Dept Med & Mol Sci, Osaka 5650871, Japan. RP Pannacciulli, N (reprint author), NIDDKD, Obes & Diabet Clin Res Sect, Phoenix Epidemiol & Clin Res Branch, NIH,Dept HHS, 4212 N 16Th St, Phoenix, AZ 85016 USA. EM nicolap@mail.nih.gov FU Intramural NIH HHS; NIDDK NIH HHS [Z01 DK069015-23] NR 20 TC 20 Z9 21 U1 0 U2 0 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD APR PY 2006 VL 91 IS 4 BP 1600 EP 1603 DI 10.1210/jc.2005-2271 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 029YW UT WOS:000236601300067 PM 16449334 ER PT J AU Miller, FG Rosenstein, DL AF Miller, FG Rosenstein, DL TI The nature and power of the placebo effect SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article ID CLINICAL ANALGESIC TRIALS; MECHANISMS AB Progress in understanding the placebo effect and its clinical significance depends on conceptual clarification of this elusive phenomenon and critical appraisal of research bearing on the influence of placebo interventions on clinical outcomes. Here we locate the placebo effect within a typology of modes of healing, distinguish between the observed placebo response in randomized controlled trials and the placebo effect, and examine critically a recent meta-analysis of clinical trials that challenges the reality of the placebo effect. (c) 2006 Elsevier Inc. All rights reserved. C1 NIMH, Intramural Res Program, Dept Clin Bioeth, Clin Ctr,NIH, Bethesda, MD 20892 USA. NIMH, Off Clin Director, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIMH, Intramural Res Program, Dept Clin Bioeth, Clin Ctr,NIH, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 24 TC 53 Z9 54 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD APR PY 2006 VL 59 IS 4 BP 331 EP 335 DI 10.1016/j.jclinepi.2005.12.001 PG 5 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 028YC UT WOS:000236523700003 PM 16549251 ER PT J AU Miller, FG Rosenstein, DL AF Miller, FG Rosenstein, DL TI Unsubstantiated claims of large effects of placebo on pain: serious errors in meta-analysis of placebo analgesia mechanism studies - Response to commentary SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Editorial Material ID TRIALS C1 NIMH, Intramural Res Program, Dept Clin Bioeth, NIH, Bethesda, MD 20892 USA. NIMH, Off Clin Director, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Miller, FG (reprint author), NIMH, Intramural Res Program, Dept Clin Bioeth, NIH, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. NR 7 TC 1 Z9 1 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD APR PY 2006 VL 59 IS 4 BP 339 EP 339 DI 10.1016/j.jclinepi.2005.12.003 PG 1 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 028YC UT WOS:000236523700005 ER PT J AU Dillon, S Agrawal, S Banerjee, K Letterio, J Denning, TL Oswald-Richter, K Kasprowicz, DJ Kellar, K Pare, J van Dyke, T Ziegler, S Unutmaz, D Pulendran, B AF Dillon, S Agrawal, S Banerjee, K Letterio, J Denning, TL Oswald-Richter, K Kasprowicz, DJ Kellar, K Pare, J van Dyke, T Ziegler, S Unutmaz, D Pulendran, B TI Yeast zymosan, a stimulus for TLR2 and dectin-1, induces regulatory antigen-presenting cells and immunological tolerance SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TOLL-LIKE RECEPTORS; ACTIVATED PROTEIN-KINASE; BETA-GLUCAN RECEPTOR; C-TYPE LECTINS; DENDRITIC CELLS; TYROSINE KINASE; IN-VIVO; INDUCTION; RECOGNITION; RESPONSES AB Emerging evidence suggests critical roles for APCs in suppressing immune responses. Here, we show that zymosan, a stimulus for TLR2 and dectin-1, regulates cytokine secretion in DCs and macrophages to induce immunological tolerance. First, zymosan induces DCs to secrete abundant IL-10 but little IL-6 and IL-12(p70). Induction of IL-10 is dependent on TLR2- and dectin-1-mediated activation of ERK MAPK via a mechanism independent of the activation protein 1 (AP-1) transcription factor c-Fos. Such DCs stimulate antigen-specific CD4(+) T cells poorly due to IL-10 and the lack of IL-6. Second, zymosan induces F4-80(+) macrophages in the splenic red pulp to secrete TGF-beta. Consistent with these effects on APCs, injection of zymosan plus OVA into mice results in OVA-specific T cells that secrete little or no Th1 or Th2 cytokines, but secrete robust levels of IL-10, and are unresponsive to challenge with OVA plus adjuvant. Finally, coinjection of zymosan with OVA plus LPS suppresses the response to OVA via a mechanism dependent on IL-10, TGF-beta, and lack of IL-6. Together, our data demonstrate that zymosan stimulates IL-10(+)IL-12(p70)-IL-6(low) regulatory DCs and TGF-beta(+) macrophages to induce immunological tolerance. These data suggest several targets for pharmacological modulation of immune responses in various clinical settings. C1 Emory Univ, Emory Vaccine Res Ctr, Atlanta, GA 30322 USA. Emory Univ, Dept Pathol, Atlanta, GA 30322 USA. NCI, Immunoregulat Sect, Lab Cell Regulat & Carcinogenesis, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37212 USA. Benaroya Res Inst, Program Immunol, Seattle, WA USA. Ctr Dis Control & Prevent, Sci Resources Program, Natl Ctr Infect Dis, Atlanta, GA USA. Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. Boston Univ, Sch Med, Dept Periodontol & Oral Biol, Boston, MA 02215 USA. RP Pulendran, B (reprint author), Emory Vaccine Ctr, 954 Gatewood Rd, Atlanta, GA 30329 USA. EM bpulend@rmy.emory.edu RI Dillon, Stephanie/B-8469-2008; Denning, Timothy/F-2271-2011 FU NIAID NIH HHS [AI05726601, AI057157, R01 AI048638, R56 AI048638, U54 AI057157, AI048638, AI0564499, R37 AI048638]; NIDDK NIH HHS [DK057665, R01 DK057665, R37 DK057665] NR 39 TC 303 Z9 314 U1 0 U2 19 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2006 VL 116 IS 4 BP 916 EP 928 DI 10.1172/JCI27203 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 029IP UT WOS:000236556100014 PM 16543948 ER PT J AU Sibon, D Gabet, AS Zandecki, M Pinatel, C Thete, J Delfau-Larue, MN Rabaaoui, S Gessain, A Gout, O Jacobson, S Mortreux, F Wattel, E AF Sibon, D Gabet, AS Zandecki, M Pinatel, C Thete, J Delfau-Larue, MN Rabaaoui, S Gessain, A Gout, O Jacobson, S Mortreux, F Wattel, E TI HTLV-1 propels untransformed CD4(+) lymphocytes into the cell cycle while protecting CD8(+) cells from death SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID VIRUS TYPE-I; TROPICAL SPASTIC PARAPARESIS; TYPE-1 TAX PROTEIN; INFECTED CIRCULATING CELLS; TRANSFORMED T-CELLS; LYMPHOTROPIC-VIRUS; ASYMPTOMATIC CARRIERS; OLIGOCLONAL EXPANSION; CLONAL EXPANSION; HTLV-1-ASSOCIATED MYELOPATHY AB Human T cell leukemia virus type 1 (HTLV-1) infects both CD4(+) and CD8(+) lymphocytes, yet it induces adult T cell leukemia/lymphoma (ATLL) that is regularly of the CD4(+) phenotype. Here we show that in vivo infected CD4(+) and CD8(+) T cells displayed similar patterns of clonal expansion in carriers without malignancy. Cloned infected cells from individuals without malignancy had a dramatic increase in spontaneous proliferation, which predominated in CD8(+) lymphocytes and depended on the amount of tax mRNA. in fact, the clonal expansion of HTLV-1-positive CD8(+) and CD4(+) lymphocytes relied on 2 distinct mechanisms - infection prevented cell death in the former while recruiting the latter into the cell cycle. Cell cycling, but not apoptosis, depended on the level of viral-encoded tax expression. Infected tax-expressing CD4(+) lymphocytes accumulated cellular defects characteristic of genetic instability. Therefore, HTLV-1 infection establishes a preleukemic phenotype that is restricted to CD4(+) infected clones. C1 Univ Lyon 1, CNRS UMR 5537, Ctr Leon Berard, Lyon, France. Hop Edouard Herriot, Hematol Serv, Lyon, France. CHU Angers, Hematol Lab, Angers, France. CHU Henri Mondor, Immunol Lab, Creteil, France. Inst Pasteur, Unite Epidmiol & Physiopathol Virus Oncogenes, Paris, France. Fdn Adolphe De Rothschild, Serv Neurol, Paris, France. NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. RP Wattel, E (reprint author), Univ Lyon 1, CNRS UMR 5537, Ctr Leon Berard, Lyon, France. EM wattel@lyon.fnclcc.fr RI mortreux, franck/M-5944-2014 NR 79 TC 37 Z9 37 U1 0 U2 2 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD APR PY 2006 VL 116 IS 4 BP 974 EP 983 DI 10.1172/JCI27198 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 029IP UT WOS:000236556100019 PM 16585963 ER PT J AU Hardick, J Giles, J Hardick, A Hsieh, YH Quinn, T Gaydos, C AF Hardick, J Giles, J Hardick, A Hsieh, YH Quinn, T Gaydos, C TI Performance of the gen-probe transmission-mediated amplification research assay compared to that of a multitarget real-time PCR for Mycoplasma genitalium detection SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; NONGONOCOCCAL URETHRITIS; QUANTITATIVE DETECTION; DISCREPANT ANALYSIS; CLINICAL-SAMPLES; UREAPLASMA-UREALYTICUM; ASYMPTOMATIC MEN; 1ST-PASS URINE; PNEUMONIAE; ASSOCIATION AB Mycoplasma genitalium (MG) can cause nongonococcal urethritis and is potentially associated with urethritis, endometritis, and cervicitis. Several assays have been developed to detect MG. Molecular amplification assays for organism detection can be problematic due to the potential for false-positive and false-negative results. Confirmatory testing is often required in these situations, requiring additional time and resources. Use of multigene targets could integrate both detection and verification at lower cost. Utilizing two targets, the MgPa adhesion gene and the 16S rRNA gene, a multitarget real-time (MTRT) PCR for the detection of MG was developed. Samples from patients attending sexually transmitted disease clinics were collected in duplicate. Urine samples from males (n = 286) and self-collected vaginal swabs from females (n = 321) were analyzed by MTRT PCR for MG and the Gen-Probe transmission-mediated amplification (TMA) assay, which targets MG rRNA for detection (TMA-MG research use (only). Utilizing the criteria of any two targets being positively amplified, the MTRT PCR had a sensitivity and specificity of 91.8% (101 positive samples/110 samples tested) and 99.5% (495/497), respectively, with a positive predictive value (PPV) of 98.1% (101/103) and a negative predictive value (NPV) of 98.2% (495/504). The Gen-Probe TMA-MG assay had a sensitivity, specificity, PPV, and NPV of 98.1% (108/110), 98.1% (488/497), 92.3% (108/117),, and 99.5% (488/490), respectively. Comparison between the MTRT PCR and TMA-MG assay by kappa statistic analysis indicated that an overall kappa value was 0.941 (95% confidence interval, 0.907 and 0.976). Both assays demonstrated accuracy in the detection of MG from urine samples from male patients and self-collected vaginal swabs from female patients. C1 Johns Hopkins Univ, Dept Infect Dis, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Emergency Med, Baltimore, MD 21205 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Hardick, J (reprint author), Johns Hopkins Univ, Dept Infect Dis, Sch Med, Div Infect Dis, Ross Bldg,Room 1147,720 Rutland Ave, Baltimore, MD 21205 USA. EM piccalo13@hotmail.com RI Gaydos, Charlotte/E-9937-2010 NR 32 TC 39 Z9 40 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2006 VL 44 IS 4 BP 1236 EP 1240 DI 10.1128/JCM.44.4.1236-1240.2006 PG 5 WC Microbiology SC Microbiology GA 032XS UT WOS:000236810500005 PM 16597844 ER PT J AU Lin, FYC Whiting, A Adderson, E Takahashi, S Dunn, DM Weiss, R Azimi, PH Philips, JB Weisman, LE Regan, J Clark, P Rhoads, GG Frasch, CE Troendle, J Moyer, P Bohnsack, JF AF Lin, FYC Whiting, A Adderson, E Takahashi, S Dunn, DM Weiss, R Azimi, PH Philips, JB Weisman, LE Regan, J Clark, P Rhoads, GG Frasch, CE Troendle, J Moyer, P Bohnsack, JF TI Phylogenetic lineages of invasive and colonizing strains of serotype III group B streptococci from neonates: A multicenter prospective study SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID AGALACTIAE STRAINS; DISEASE; VIRULENCE; IDENTIFICATION; INFECTIONS; PATTERNS; CLONE; DNA AB This study compares the phylogenetic lineages of invasive serotype III group B streptococci (GBS) to those of colonizing strains in order to determine lineages associated with invasive disease. Isolates from 29 infants with early-onset disease (EOD) and from 196 colonized infants, collected in a prospective, multicenter study, were assigned a sequence type (ST) by multilocus sequence typing. Overall, 54.5% of the isolates were in the ST-19 complex, and 40.4% were in the ST-17 complex. Invasive strains were more likely to be in the ST-17 complex than were colonizing strains (59% versus 38%, P = 0.03). After we adjusted for potential confounders, the ST-17 complex was more likely to be associated with EOD than were other lineages (odds ratio = 2.51, 95% confidence interval = 1.02 to 6.20). These data support the hypothesis that ST-17 complex GBS are more virulent than other serotype III GBS. C1 NICHHD, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Res & Review, Bethesda, MD 20014 USA. Dept Hlth & Human Serv, Bethesda, MD 20014 USA. Univ Utah, Hlth Sci Ctr, Dept Pediat, Salt Lake City, UT USA. Univ Utah, Hlth Sci Ctr, Genome Ctr, Salt Lake City, UT USA. St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. Joshi Eiyoh Univ, Div Microbiol, Saitama, Saitama, Japan. Childrens Hosp, Med Ctr No Calif, Oakland, CA USA. Univ Alabama, Birmingham, AL USA. Baylor Coll Med, Houston, TX 77030 USA. Columbia Univ, New York, NY USA. Univ Florida, Gainesville, FL USA. Univ Med & Dent New Jersey, Piscataway, NJ 08854 USA. RP Lin, FYC (reprint author), 6100 Execut Blvd,Rm 7B03,MSC 7510, Bethesda, MD 20892 USA. EM Link@exchange.nih.gov FU Intramural NIH HHS NR 21 TC 40 Z9 40 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2006 VL 44 IS 4 BP 1257 EP 1261 DI 10.1128/JCM.44.4.1257-1261.2006 PG 5 WC Microbiology SC Microbiology GA 032XS UT WOS:000236810500009 PM 16597848 ER PT J AU Fedorko, DP Nelson, NA McAuliffe, JM Subbarao, K AF Fedorko, DP Nelson, NA McAuliffe, JM Subbarao, K TI Performance of rapid tests for detection of avian influenza a virus types H5N1 and H9N2 SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Letter ID VACCINE CANDIDATE; REASSORTANT; GENERATION; INFECTION; DIAGNOSIS; FLU C1 NIH, Microbiol Serv, Dept Lab Med, Ctr Clin,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIAID, Infect Dis Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Fedorko, DP (reprint author), NIH, Microbiol Serv, Dept Lab Med, Ctr Clin,Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. EM dfedorko@cc.nih.gov FU Intramural NIH HHS NR 14 TC 26 Z9 28 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2006 VL 44 IS 4 BP 1596 EP 1597 DI 10.1128/JCM.44.4.1596-1597.2006 PG 2 WC Microbiology SC Microbiology GA 032XS UT WOS:000236810500067 PM 16597906 ER PT J AU Lee, JJ Swain, SM AF Lee, JJ Swain, SM TI Peripheral neuropathy induced by microtubule-stabilizing agents SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Review ID METASTATIC BREAST-CANCER; PHASE-II TRIAL; QUALITY-OF-LIFE; HIGH-DOSE PACLITAXEL; EPOTHILONE-B-ANALOG; GYNECOLOGIC-ONCOLOGY-GROUP; CISPLATIN COMBINATION CHEMOTHERAPY; PROSPECTIVE RANDOMIZED-TRIAL; CLINICAL-PRACTICE GUIDELINES; REFRACTORY PROSTATE-CANCER AB Microtubule-stabilizing agents (MTSAs), including the taxanes and epothilones, are effective chemotherapeutic agents for the treatment of many cancers. Neuropathy is a major adverse effect of MTSA-based chemotherapy, with severe peripheral neuropathy (grade 3 or 4) occurring in as many as 30% of patients treated with a MTSA-induced neuropathy usually resolves gradually after cessation of the treatment. The most reliable method to accurately assess MTSA-induced neuropathy is by clinical evaluation, although additional techniques are being developed and evaluated. Among MTSA-induced neuropathy, the most extensively studied is that induced by taxanes; such a neuropathy usually presents as sensory neuropathy and is more common with paclitaxel than docetaxel. The incidence of MTSA-induced neuropathy seems to depend on the MTSA dose per treatment cycle, the schedule of treatment, and the duration of the infusion. Although there have been several small clinical trials with neuroprotective agents, early recognition and supportive care are the best approaches for prevention and management of MTSA-induced neuropathy. In the future, research should focus on elucidating the mechanism of MTSA-induced neuropathy, developing reliable in vivo and in vitro preclinical models to study MTSA-induced neuropathy, developing a more reliable grading system for MTSA-induced neuropathy, developing more reliable methods for evaluating MTSA-induced neuropathy, and evaluating the efficacy of potential neuroprotective agents in clinical trials. C1 NCI, Breast Canc Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20889 USA. RP Swain, SM (reprint author), NCI, Breast Canc Sect, Med Oncol Branch, Ctr Canc Res,NIH, Bldg 8,Rm 5101,8901 Wisonsin Ave, Bethesda, MD 20889 USA. EM swains@mail.nih.gov OI Swain, Sandra/0000-0002-1320-3830 NR 129 TC 242 Z9 243 U1 0 U2 12 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2006 VL 24 IS 10 BP 1633 EP 1642 DI 10.1200/JCO.2005.04.0543 PG 10 WC Oncology SC Oncology GA 030UK UT WOS:000236660200023 PM 16575015 ER PT J AU Loud, JT Weissman, NE Peters, JA Giusti, RM Wilfond, BS Burke, W Greene, MH AF Loud, JT Weissman, NE Peters, JA Giusti, RM Wilfond, BS Burke, W Greene, MH TI Deliberate deceit of family members: A challenge to providers of clinical genetics services SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID BRCA2 MUTATION CARRIERS; OVARIAN-CANCER RISK; BREAST-CANCER; ORAL-CONTRACEPTIVES; DISCLOSURE; SUSCEPTIBILITY; WOMEN; PREDISPOSITION; COMMUNICATION; MAMMOGRAPHY C1 NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Rockville, MD 20853 USA. US FDA, Rockville, MD USA. NHGRI, Dept Clin Bioeth, Ctr Clin, NIH, Bethesda, MD 20892 USA. NHGRI, Social Behav Res Branch, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Med Hist & Eth, Seattle, WA 98195 USA. RP Loud, JT (reprint author), NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 7028, Rockville, MD 20853 USA. EM LoudJ@mail.nih.gov NR 31 TC 9 Z9 9 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD APR 1 PY 2006 VL 24 IS 10 BP 1643 EP 1646 DI 10.1200/JCO.2005.02.6203 PG 4 WC Oncology SC Oncology GA 030UK UT WOS:000236660200024 PM 16575016 ER PT J AU Hon, YY Jusko, WJ Spratlin, VE Jann, MW AF Hon, YY Jusko, WJ Spratlin, VE Jann, MW TI Altered methylprednisolone pharmacodynamics in healthy subjects with histamine N-methyltransferase C314T genetic polymorphism SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE corticosteroids; methylprednisolone pharmacodynamics; cortisol suppression; histamine suppression; HNMT polymorphism ID CORTICOTROPIN-RELEASING HORMONE; MAST-CELLS; INTRACEREBROVENTRICULAR INJECTION; ADRENOCORTICOTROPIC HORMONE; HISTIDINE-DECARBOXYLASE; BLOOD HISTAMINE; ENZYME-ACTIVITY; RAT PITUITARY; ACTH RELEASE; SECRETION AB This study investigated the potential differences in methylprednisolone pharmacodynamics between healthy subjects with different histamine N-methyl transferase (HNMT) C314T genotypes. Six individuals with C/C genotype and 4 with C/T genotype were administered a single introvenous dose of methylprednisolone 0.6 mg/kg ideal body weight in a randomized 2-period manner. Methylprednisolone plasma concentrations were fitted with a 1-compartment model. Cortisol and whole blood histamine suppression were assessed by indirect response models, with circadian baseline cortisol analyzed by Fourier analysis. The area between the baseline and effect curve and the area under the effect versus time curve suppression ratio were used to characterize plasma histamine suppression. Methylprednisolone pharmacokinetics and plasma and whole blood histamine suppression were similar between the 2 genotype groups. Me dion nadir of cortisol and the 50% inhibitory concentration for cortisol were significantly higher in subjects with C/T genotype than those with C/C genotype (P = .031 and .033, respectively, Wilcoxon rank sum test). Subjects who are heterozygous for the T314 variant allele thus appeared less sensitive to the suppressive effects of methylprednisolone on cortisol secretion. C1 NIH, Clin Pharmacokinet Res Lab, Ctr Clin, Dept Pharm, Bethesda, MD 20892 USA. Mercer Univ, So Sch Pharm, Dept Clin & Adm Sci, Atlanta, GA USA. Mercer Univ, So Sch Pharm, Clin Res Ctr, Atlanta, GA USA. SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Dept Pharmaceut Sci, Buffalo, NY 14260 USA. RP Hon, YY (reprint author), NIH, Clin Pharmacokinet Res Lab, Ctr Clin, Dept Pharm, Bldg 10,Rm 1N-257,MSC-1196,10 Ctr Dr, Bethesda, MD 20892 USA. RI Jusko, William/G-4885-2015 FU NIGMS NIH HHS [R37 GM024211]; PHS HHS [24211] NR 45 TC 6 Z9 7 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD APR PY 2006 VL 46 IS 4 BP 408 EP 417 DI 10.1177/0091270006286434 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 027KM UT WOS:000236414500005 PM 16554448 ER PT J AU Wong, S Brown, KE AF Wong, Susan Brown, Kevin E. TI Development of an improved method of detection of infectious parvovirus B19 SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE parvovirus B19; erythrovirus infections; neutralizing antibody ID POLYMERASE-CHAIN-REACTION; BLOOD-DONORS; CELL-LINE; FETAL LIVER; VIRAL-DNA; IN-VITRO; VIRUS; ASSAY; INACTIVATION; PROPAGATION AB Background: Parvovirus B 19, the only known pathogenic human parvovirus is the aetiologic agent of erythema infectiosum, transient aplastic crisis, pure red cell aplasia, and hydrops fetalis. Transmission is either by respiratory secretions or, as it can be present at high titre in plasma, by blood and blood products. B 19 is only cultured with difficulty in vitro, and there is no readily available assay for detecting B 19 infectivity or neutralizing antibodies. Objectives: In this study, we evaluated different methods to detect viral infection for the purpose of developing automated methods for large-scale testing of viral infectivity, development of neutralizing antibody and viral inactivation assays. Study design: Different cell lines were evaluated for their ability to support B19 infection and assays tested for sensitivity and ease of performing. A high-throughput assay was validated by determining infectious virus in blood pools and for determining neutralizing antibody in sera. Results: B 19 protein production was detected by immunofluorescence (IF) staining and increased viral DNA production by dot blot hybridization and quantitative PCR. The detection of RNA transcripts by RT-PCR assay and quantitative RT-PCR (qRT-PCR) was used as an indirect marker for infection. Of the cell lines tested, the subclone UT7/Epo-S1 showed the greatest sensitivity to 1319 infection, with detection of viral transcripts by qRT-PCR the preferred assay. The assays were validated by experiments to determine the infectious titre of sera from acutely infected humans, to evaluate the presence of infectious virus in human donor plasma pools and to measure neutralizing antibodies. (C) 2006 Elsevier B.V. All rights reserved. C1 NHLBI, Hematol Branch, Bethesda, MD 20892 USA. RP Brown, KE (reprint author), Hlth Protect Agcy, Ctr Infect, Virus Reference Dept, 61 Colindale Ave, London NW9 5HT, England. EM Kevin.Brown@HPA.org.uk FU Intramural NIH HHS NR 38 TC 31 Z9 35 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD APR PY 2006 VL 35 IS 4 BP 407 EP 413 DI 10.1016/j.jcv.2005.12.008 PG 7 WC Virology SC Virology GA 070SW UT WOS:000239545300008 PM 16455300 ER PT J AU Mbulaiteye, SM Atkinson, JO Whitby, D Wohl, DA Gallant, JE Royal, S Goedert, JJ Rabkin, CS AF Mbulaiteye, Sam M. Atkinson, Jonnae O. Whitby, Denise Wohl, David A. Gallant, Joel E. Royal, Scott Goedert, James J. Rabkin, Charles S. CA ACC Study Collaborators TI Risk factors for human herpesvirus 8 seropositivity in the AIDS Cancer Cohort Study SO JOURNAL OF CLINICAL VIROLOGY LA English DT Article DE kaposi sarcoma; transmission; men who have sex with men; injection drug use; United States ID KAPOSIS-SARCOMA; SEROLOGIC ASSAYS; HOMOSEXUAL-MEN; INFECTION; EPIDEMIOLOGY; HERPESVIRUS; UGANDA; HIV; SEROPREVALENCE; POPULATION AB Background: Cigarette smoking has been associated with a decreased risk for AIDS-related and classical KS, but whether it is associated with decreased risk of human herpesvirus 8 (HHV-8) infection is unknown. Study design: We evaluated factors associated with HHV-8 seropositivity in 2795 participants (132 with KS) in the National Cancer Institute AIDS Cancer Cohort, including 1621 men who have sex with men (MSM), 660 heterosexual men and 514 women. Odds ratios (OR) and 95% confidence intervals were estimated using logistic regression models. Results: Among non-KS subjects, HHV-8 seropositivity was 6%, 13% and 29% among women, heterosexual men and MSM, respectively. HHV-8 seropositivity was decreased in heavier (>= 1/2 pack/day) compared to lighter smokers among women (5% versus 8%; adjusted OR (aOR) 0.4; 95% CI 0.2-0.8) and MSM (27% versus 32%; aOR 0.7; 95% Cl 0.6-1.0), but not among heterosexual men (12% versus 16%; aOR 0.7; 95% CI 0.4-1.2). HHV-8 seroprevalence was increased in heavier (>= 1 drink/day) compared to lighter consumers of alcohol among women (16% versus 4%; adjusted OR 5.2; 95% CI 2.3-12), but not among MSM (33% versus 28%; aOR 1.2; 95% CI 0.9-1.6) or heterosexual men (13% versus 13%; aOR 1.1; 95% CI 0.6-2.0). In analyses adjusted for smoking and drinking, HHV-8 seropositivity was positively associated with chlamydia infection (OR = 4.3; 95% CI 1.2-13) and with marital status among women p(heterogeneity)=0.03, and with hepatitis (OR= 1.6; 95% CI 1.2-2.1), gonorrhea (OR =1.5; 95% CI 1.1-1.9), genital warts (OR =1.5; 95% CI 1.1-2.0) and nitrate inhalant use (OR= 1.7; 95% CI 1.3-2.3) among MSM. Conclusions: Inverse association of HHV-8 seropositivity with cigarette smoking may indicate protective effect of tobacco smoke on HHV-8 infection, whereas positive associations with alcohol may reflect either behavioral factors or biological effects modulating susceptibility. Smoking and drinking may influence KS risk, at least in part, by altering the natural history of HHV-8 infection. (C) 2005 Elsevier B.V. All rights reserved. C1 NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD 20852 USA. NCI, Viral Epidemiol Sect, AIDS Vaccine Program, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. Univ N Carolina, Dept Med, Div Infect Dis, Chapel Hill, NC USA. Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. Res Triangle Inst, Washington, DC USA. RP Mbulaiteye, SM (reprint author), NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, 6120 Execut Blvd,Execut Plaza S Rm 8006,Mail Stop, Rockville, MD 20852 USA. EM mbulaits@mail.nih.gov FU NCI NIH HHS [N01 CO 12400, N01 CP 81017]; NCRR NIH HHS [RR 00046, M01 RR 00046-41S1]; NIAID NIH HHS [AI 25868-15] NR 25 TC 14 Z9 15 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1386-6532 J9 J CLIN VIROL JI J. Clin. Virol. PD APR PY 2006 VL 35 IS 4 BP 442 EP 449 DI 10.1016/j.jcv.2005.10.010 PG 8 WC Virology SC Virology GA 070SW UT WOS:000239545300014 PM 16414306 ER PT J AU Passeron, T Ortonne, JP AF Passeron, T Ortonne, JP TI What's new in hypochromy SO JOURNAL OF DERMATOLOGICAL TREATMENT LA English DT Review DE hypochromy; tyrosine kinase inhibitors; vitiligo ID 308-NM EXCIMER-LASER; BAND UVB PHOTOTHERAPY; TOPICAL CALCIPOTRIOL; 0.05-PERCENT CLOBETASOL; ULTRAVIOLET-B; VITILIGO; COMBINATION; TACROLIMUS; REPIGMENTATION; NM AB Hypochromy is a common dermatological disorder. However, its treatment still gives unsatisfactory results. Interesting clues into the understanding of the pathophysiology of hypochromy have been recently brought about thanks to the pigmentary side effects reported with the new tyrosine kinase inhibition treatments. New therapeutic approaches to hypochromy are further discussed. C1 Hop Archet 2, Dept Dermatol, Nice, France. RP Passeron, T (reprint author), NCI, Cell Biol Lab, NIH, 37 Convent Dr,Rm 2132, Bethesda, MD 20852 USA. EM t.passeron@free.fr OI Passeron, Thierry/0000-0002-0797-6570 NR 41 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0954-6634 J9 J DERMATOL TREAT JI J. Dermatol. Treat. PD APR PY 2006 VL 17 IS 2 BP 70 EP 73 DI 10.1080/09546630500515180 PG 4 WC Dermatology SC Dermatology GA 039BQ UT WOS:000237275000002 PM 16766328 ER PT J AU Iannotti, RJ Schneider, S Nansel, TR Haynie, DL AF Iannotti, RJ Schneider, S Nansel, TR Haynie, DL TI Self-efficacy, outcome expectations, and diabetes self-management in adolescents with type 1 diabetes SO JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS LA English DT Article DE glycemic control; adherence; social cognitive theory ID METABOLIC-CONTROL; PSYCHOMETRIC PROPERTIES; YOUNG-ADULTS; 18 COUNTRIES; MELLITUS; CARE; CHILDREN; INDEPENDENCE; METAANALYSIS; ADHERENCE AB The goal of this research was to develop and evaluate measures of adolescent diabetes management self-efficacy and outcome expectations that reflect developmentally relevant, situation-specific challenges to current diabetes regimens. Self-efficacy for diabetes management, expected outcomes of adherence, adherence to the diabetes regimen, and glycemic control were assessed in 168 adolescents (ages 10-16 years) with type 1 diabetes. Factor analyses indicated a single scale for self-efficacy and two distinct factors representing positive and negative outcome expectations. Reliability and predictive validity of the new scales were supported. In regression analyses, self-efficacy and the interaction of self-efficacy with expectations of positive outcomes were significantly associated with diabetes self-management adherence and glycemic control in older adolescents. The effect of self-efficacy was greatest when adolescents had stronger beliefs in the beneficial outcomes of adherence. These brief measures can be used to identify youths at risk of poor diabetes self-management. Interventions targeting self-efficacy may lead to improved diabetes self-management. C1 NICHD, DESPR, PRB, Bethesda, MD 20892 USA. John Hopkins Med Ctr, Dept Pediat Endocrinol, Baltimore, MD USA. Georgetown Univ, Sch Med, Dept Pediat, Washington, DC USA. RP Iannotti, RJ (reprint author), NICHD, DESPR, PRB, 6100 Execut Blvd,7B05, Bethesda, MD 20892 USA. EM iannottr@mail.nih.gov RI Schneider, Stefan/K-2815-2012; OI Nansel, Tonja/0000-0002-8298-7595; Simons-Morton, Bruce/0000-0003-1099-6617; Haynie, Denise/0000-0002-8270-6079 NR 23 TC 85 Z9 85 U1 2 U2 19 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0196-206X J9 J DEV BEHAV PEDIATR JI J. Dev. Behav. Pediatr. PD APR PY 2006 VL 27 IS 2 BP 98 EP 105 DI 10.1097/00004703-200604000-00003 PG 8 WC Behavioral Sciences; Psychology, Developmental; Pediatrics SC Behavioral Sciences; Psychology; Pediatrics GA 043OE UT WOS:000237609900003 PM 16682872 ER PT J AU Schrier, L Ferns, SP Barnes, KM Emons, JAM Newman, EI Nilsson, O Baron, J AF Schrier, L Ferns, SP Barnes, KM Emons, JAM Newman, EI Nilsson, O Baron, J TI Depletion of resting zone chondrocytes during growth plate senescence SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID ESTROGEN-RECEPTOR-ALPHA; LONGITUDINAL BONE-GROWTH; ZEALAND WHITE-RABBIT; RAT TIBIA; EPIPHYSEAL FUSION; CELL KINETICS; CARTILAGE; LOCALIZATION; EXPRESSION; BETA AB With age, the growth plate undergoes senescent changes that cause linear bone growth to slow and finally cease. Based on previous indirect evidence, we hypothesized that this senescent decline occurs because growth plate stern-like cells, located in the resting zone, have a finite proliferative capacity that is gradually depleted. Consistent with this hypothesis, we found that the proliferation rate in rabbit resting zone chondrocytes (assessed by continuous 5-bromo-2'-deoxy-uridine labeling) decreases with age, as does the number of resting zone chondrocytes per area of growth plate. Glucocorticoid excess slows growth plate senescence. To explain this effect, we hypothesized that glucocorticoid inhibits resting zone chondrocyte proliferation, thus conserving their proliferative capacity. Consistent with this hypothesis, we found that dexamethasone treatment decreased the proliferation rate of rabbit resting zone chondrocytes and slowed the numerical depletion of these cells. Estrogen is known to accelerate growth plate senescence. However, we found that estradiol cypionate treatment slowed resting zone chondrocyte proliferation. Our findings support the hypotheses that growth plate senescence is caused by qualitative and quantitative depletion of stem-like cells in the resting zone and that growth-inhibiting conditions, such as glucocorticoid excess, slow senescence by slowing resting zone chondrocyte proliferation and slowing the numerical depletion of these cells, thereby conserving the proliferative capacity of the growth plate. We speculate that estrogen might accelerate senescence by a proliferation-independent mechanism, or by increasing the loss of proliferative capacity per cell cycle. C1 NICHHD, Dev Endocrinol Branch, NIH, CRC, Bethesda, MD 20892 USA. RP Baron, J (reprint author), NICHHD, Dev Endocrinol Branch, NIH, CRC, Room 1-330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM Jeffrey.baron@nih.gov OI Nilsson, Ola/0000-0002-9986-8138 FU Intramural NIH HHS NR 27 TC 36 Z9 40 U1 2 U2 7 PU SOC ENDOCRINOLOGY PI BRISTOL PA 22 APEX COURT, WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0022-0795 J9 J ENDOCRINOL JI J. Endocrinol. PD APR PY 2006 VL 189 IS 1 BP 27 EP 36 DI 10.1677/joe.1.06489 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 038AX UT WOS:000237191000002 PM 16614378 ER PT J AU McDermott, MM Hoff, FL Criqui, M Ferrucci, L Pearce, W Guralnik, JM Tian, L Liu, K Schneider, J Sharma, L Jin, T AF McDermott, M. M. Hoff, F. L. Criqui, M. Ferrucci, L. Pearce, W. Guralnik, J. M. Tian, L. Liu, K. Schneider, J. Sharma, L. Jin, T. TI Lower extremity ischemia, calf skeletal muscle characteristics, and functional impairment in peripheral arterial disease SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Northwestern Univ, Chicago, IL 60611 USA. Univ Calif San Diego, San Diego, CA 92103 USA. NIA, Bethesda, MD 20892 USA. Evanston NW Hosp, Chicago, IL USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 82 EP 82 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000290 ER PT J AU Kahn, KL Keating, NL Landrum, MB Ayanian, JZ Boer, R Klabunde, CN Catalano, PJ AF Kahn, K. L. Keating, N. L. Landrum, M. B. Ayanian, J. Z. Boer, R. Klabunde, C. N. Catalano, P. J. TI Physicians involved in the care of patients with recently diagnosed lung and colorectal cancer SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 RAND Corp, Santa Monica, CA USA. Harvard Univ, Boston, MA 02115 USA. Natl Inst Hlth, Washington, DC USA. Dana Farber Canc Inst, Boston, MA 02115 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 102 EP 102 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000364 ER PT J AU Kronman, AC Freund, KM Ash, A Hanchate, A Emanuel, E AF Kronman, A. C. Freund, K. M. Ash, A. Hanchate, A. Emanuel, E. TI Primary care visits reduce hospital utilization of medicare beneficiaries at the end of life SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Boston Univ, Sch Med, Boston, MA 02118 USA. Boston Univ, Med Ctr, Boston, MA 02215 USA. Natl Inst Hlth, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 110 EP 110 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000392 ER PT J AU Eamranond, PP Marcantonio, E Patel, K Legedza, A Leveille, SG AF Eamranond, P. P. Marcantonio, E. Patel, K. Legedza, A. Leveille, S. G. TI The association of acculturation with prevalence of undiagnosed hypertension among older Hispanic adults SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. NIH, Bethesda, MD 20892 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 136 EP 137 PG 2 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000486 ER PT J AU Ho, P Kim, P Hong, JJ Fontelo, P AF Ho, P. Kim, P. Hong, J. J. Fontelo, P. TI Virtual evidence cart and resident use of EBM SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Washington Hosp Ctr, Washington, DC 20010 USA. Natl Lib Med, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 161 EP 161 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000573 ER PT J AU Haggstrom, DA Taplin, S AF Haggstrom, D. A. Taplin, S. TI The effect of the cancer health disparities collaborative on cancer screening and follow-up SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Meeting Abstract C1 Natl Canc Ctr, Canc Prevent Fellowship, Bethesda, MD USA. Natl Canc Ctr, Appl Res Program, Bethesda, MD 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 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 SU 4 BP 202 EP 202 PG 1 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA V43VG UT WOS:000202962000717 ER PT J AU Haas, JS Geller, B Miglioretti, DL Buist, DSM Nelson, DE Kerlikowske, K Carney, PA Breslau, ES Dash, S Canales, MK Barbash, RB AF Haas, JS Geller, B Miglioretti, DL Buist, DSM Nelson, DE Kerlikowske, K Carney, PA Breslau, ES Dash, S Canales, MK Barbash, RB TI Changes in newspaper coverage about hormone therapy with the release of new medical evidence SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hormone therapy; lay media; drug usage ID ESTROGEN PLUS PROGESTIN; SCREENING MAMMOGRAPHY; POSTMENOPAUSAL WOMEN; REPLACEMENT THERAPY; BREAST-CANCER; UNITED-STATES; NEWS MEDIA; PREVENTION; TRIAL; RISKS AB Results of 2 trials of postmenopausal hormone therapy (HT) challenged established practice patterns; 1 was not associated with changes in HT use, whereas the other was associated with substantial decline. Differential coverage by lay newspapers may have contributed to the differential impact. To examine newspaper coverage of HT before and after the publication of the Heart and Estrogen Replacement Study (HERS) in August 1998, and the main findings of the estrogen plus progestin therapy arm of the Women's Health Initiative (EPT-WHI) in July 2002. Longitudinal review of newspaper articles, 1998 to 2003 (n = 663). Twenty local and 6 regional/national newspapers. Number and content of articles about HT. The average number of articles about HT published during the month of the publication of the EPT-WHI was at least 8-fold greater than the number of articles published on the topic during any prior period. While the majority of articles in all periods presented information about the potential benefits of HT, information about harms became more common than information about benefits during the 2 months before the publication of the EPT-WHI, when the trial participants were notified of the early termination of the study. The presentation of specific health harms was more common after the publication of the EPT-WHI than after the publication of HERS. Few articles in any period used visual aids. The publication of the EPT-WHI was associated with a change in both the volume and content of newspaper coverage about HT. C1 Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, Boston, MA 02120 USA. Harvard Univ, Sch Med, Boston, MA USA. Univ Vermont, Ctr Canc, Dept Family Med, Off Hlth Promot Res, Burlington, VT USA. Univ Vermont, Ctr Canc, Dept Radiol, Burlington, VT USA. Ctr Hlth Studies, Grp Hlth Cooperat, Seattle, WA USA. Ctr Dis Control & Prevent, Off Smoking & Hlth, Hlth Commun Branch, Atlanta, GA USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Vet Affairs, Gen Internal Med Sect, San Francisco, CA 94143 USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Hanover, NH USA. NCI, Div Canc Control & Populat Sci, Bethesda, MD USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD USA. Univ Vermont, Dept Nursing, Burlington, VT USA. RP Haas, JS (reprint author), Brigham & Womens Hosp, Div Gen Med & Primary Care, Dept Med, 1620 Tremont St, Boston, MA 02120 USA. EM jhaas@partners.org FU NCI NIH HHS [R01 CA080888, U01 CA070013, U01 CA086076, U01 CA70013, U01CA86076, U01 CA86082, U01 CA063731, U01 CA063740, U01 CA086082, U01 CA63740] NR 28 TC 6 Z9 7 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 IS 4 BP 304 EP 309 DI 10.1111/j.1525-1497.2006.00342.x PG 6 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 036ZT UT WOS:000237117200004 PM 16499542 ER PT J AU Haggstrom, DA Schapira, MM AF Haggstrom, DA Schapira, MM TI Black-white differences in risk perceptions of breast cancer survival and screening mammography benefit SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article; Proceedings Paper CT 25th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 01-05, 2002 CL ATLANTA, GA SP Soc Gen Internal Med DE breast cancer; cancer screening; race & ethnicity; risk assessment ID RACIAL-DIFFERENCES; TRANSPLANTATION; STATISTICS; WOMEN; AGE AB BACKGROUND: Given differences in cancer survival by race, black women may differ from white women in breast cancer risk perceptions. OBJECTIVE: To evaluate black-white differences in risk perceptions of breast cancer survival and screening mammography benefit. DESIGN: A written survey was administered to a random sample of women attending general internal medicine clinics. PARTICIPANTS: Black and white women, ages 40 to 69. MEASUREMENTS: Risk perceptions were measured regarding ( 1) average 5-year survival after a breast cancer diagnosis and ( 2) relative risk reduction of screening mammography. Women's risk perceptions were defined as being accurate, as well as more or less pessimistic. Measured patient characteristics included race, age, family history of breast cancer, income, insurance, education, and numeracy. Unadjusted Pearson chi(2) tests and adjusted multivariable regression analyses were done. RESULTS: Black women were more likely than white women to accurately perceive breast cancer survival in both unadjusted (48% vs 26%, P <.001) and adjusted analyses (adjusted odds ratio (AOR) = 3.58; 95% confidence interval (CI) = 1.56 to 8.21). Black women were also more likely to accurately perceive the benefit of screening mammography in unadjusted (39% vs 15%, P < 0.001) and adjusted analyses (AOR = 2.70; 95% CI = 1.09 to 6.69). Black women were more likely to have a more pessimistic perception of mammography benefit in unadjusted (47% vs 15%, P < 0.0001) and adjusted analyses (AOR = 3.94; 95% CI = 1.62 to 9.56). CONCLUSIONS: Awareness of risk perceptions can help physicians to tailor patient education. Physician acknowledgment of more accurate risk perceptions among black women may serve as a basis to improve patient-physician communication. C1 NCI, Div Canc Prevent, Canc Prevent Fellowship Program, NIH, Bethesda, MD 20892 USA. Med Coll Wisconsin, Div Gen Internal Med, Milwaukee, WI USA. RP Haggstrom, DA (reprint author), NCI, Div Canc Prevent, Canc Prevent Fellowship Program, NIH, EPN Room 4009C,6130 Execut Blvd, Bethesda, MD 20892 USA. EM haggstrd@mail.nih.gov FU PHS HHS [1D14 HP001 78-01] NR 21 TC 14 Z9 14 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2006 VL 21 IS 4 BP 371 EP 377 DI 10.1111/j.1525-1497.2006.00347.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 036ZT UT WOS:000237117200017 PM 16686816 ER PT J AU Tozser, J Shulenin, S Young, MR Briggs, CJ Oroszlan, S AF Tozser, J Shulenin, S Young, MR Briggs, CJ Oroszlan, S TI Replication-dependent fitness recovery of Human Immunodeficiency virus 1 harbouring mutations of Asn17 of the nucleocapsid protein SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID INFECTIOUS-ANEMIA VIRUS; REVERSE-TRANSCRIPTASE; VIRAL REPLICATION; PROVIRAL DNA; IN-VITRO; HIV; RECOGNITION; INHIBITOR; THERAPY; TARGETS AB The genetic stability of attenuated Human immunodeficiency virus 1 (HIV-1) variants harbouring mutations (Gly or Lys) of Asn17, the protease-cleavage site of the proximal zinc finger of the nucleocapsid protein, was studied. All possible codons for the Gly mutants were tested as starting sequences. Long-term replication assays revealed that the mutants were unstable; mutations of Glyl 7 to Arg, Ala, Ser and Cys, as well as a Lys17Asn reversion, were observed. Replication kinetic assays in H9 cells revealed that the replication of Ala, Ser and Arg mutants was improved substantially compared with the Gly variant; the infectivity of Ala17 and Ser17 viruses was equal to, and that of Arg 17 was almost equal to, the infectivity of the wild-type virus. Kinetic analysis of the cleavage of oligopeptides representing the corresponding nucleocapsid-cleavage sites revealed that all mutations improved cleavability, in good agreement with the previously proposed role of nudeocapsid cleavage in HIV-1 replication. C1 NCI, Frederick, MD 21701 USA. Univ Debrecen, Res Ctr Mol Med, Dept Biochem & Mol Biol, H-4012 Debrecen, Hungary. RP Oroszlan, S (reprint author), NCI, Frederick, MD 21701 USA. EM oroszlans@mail.ncifcrf.gov RI Tozser, Jozsef/A-7840-2008; OI Tozser, Jozsef/0000-0003-0274-0056; Tozser, Jozsef/0000-0001-5076-8729 FU Intramural NIH HHS NR 27 TC 1 Z9 1 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 0022-1317 EI 1465-2099 J9 J GEN VIROL JI J. Gen. Virol. PD APR PY 2006 VL 87 BP 961 EP 965 DI 10.1099/vir.0.81473-0 PN 4 PG 5 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 027WK UT WOS:000236446400026 PM 16528046 ER PT J AU Jampel, HD Vitale, S Ding, YL Quigley, H Friedman, D Congdon, N Zeimer, R AF Jampel, HD Vitale, S Ding, YL Quigley, H Friedman, D Congdon, N Zeimer, R TI Test-retest variability in structural and functional parameters of glaucoma damage in the glaucoma imaging longitudinal study SO JOURNAL OF GLAUCOMA LA English DT Article DE glaucoma; macular thickness; optic disc; optic nerve; perimetry ID VISUAL-FIELD LOSS; OPTICAL COHERENCE TOMOGRAPHY; SCANNING LASER TOMOGRAPHY; RETINAL THICKNESS; NERVE HEAD; CLINICAL-TRIALS; POSTERIOR POLE; SITA FAST; PROGRESSION; PERIMETRY AB Purpose: To determine the test-retest variability in perimetric, optic disc, and macular thickness parameters in a cohort of treated patients with established glaucoma. Patients and Methods: In this cohort study, the authors analyzed the imaging studies and Visual field tests at the baseline and 6-month visits of 162 eyes of 162 participant in the Glaucoma Imaging Longitudinal Study (GILS). They assessed the difference, expressed as the standard error of measurement, of Humphrey field analyzer II (HFA) Swedish Interactive Threshold Algorithm fast, Heidelberg retinal tomograph (HRT) II, and retinal thickness analyzer (RTA) parameters between the two visits and assumed that this difference was due to measurement variability, not pathologic change. A statistically significant change was defined as twice the standard error of measurement. Results: In this cohort of treated glaucoma patients, it was found that statistically significant changes were 3.2 dB for mean deviation (MID), 2.2 for pattern standard deviation (PSD), 0.12 for cup shape measure, 0.26 mm(2) for rim area, and 32.8 mu m and 31.8 mu m for superior and inferior macular thickness, respectively. On the basis of these values, it was estimated that the number of potential progression events detectable in this cohort by the parameters of MD, PSD, CLIP shape measure, rim area, superior macular thickness, and inferior macular thickness was 7.5, 6.0 2.3, 5.7, 3. 1, and 3.4, respectively. Conclusions: The variability of the measurements of MD, PSD, and rim area, relative to the range of possible values, is less than the variability of cup shape measure or macular thickness measurements. Therefore, the former measurements may be more useful global measurements for assessing progressive glaucoma damage. C1 Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD USA. NEI, Div Epidemiol & Clin Res, NIH, Bethesda, MD 20892 USA. RP Jampel, HD (reprint author), Woods Wilmer 377,600 N Wolfe St, Baltimore, MD 21287 USA. EM hjampel@jhmi.edu FU NEI NIH HHS [P30 EY01765, R01 EY12295] NR 31 TC 26 Z9 27 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1057-0829 J9 J GLAUCOMA JI J. Glaucoma PD APR PY 2006 VL 15 IS 2 BP 152 EP 157 DI 10.1097/00061198-200604000-00012 PG 6 WC Ophthalmology SC Ophthalmology GA 034UZ UT WOS:000236957400012 PM 16633229 ER PT J AU Thorgeirsson, SS Lee, JS Grisham, JW AF Thorgeirsson, SS Lee, JS Grisham, JW TI Molecular prognostication of liver cancer: End of the beginning SO JOURNAL OF HEPATOLOGY LA English DT Review ID GENE-EXPRESSION PROFILES; HUMAN HEPATOCELLULAR-CARCINOMA; COMPARATIVE FUNCTIONAL GENOMICS; BREAST-CANCER; OLIGONUCLEOTIDE MICROARRAY; CLINICAL-APPLICATION; DYSPLASTIC NODULES; MYELOID-LEUKEMIA; SURVIVAL; CLASSIFICATION C1 NCI, Expt Carcinogenesis Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Canc Res Ctr, NIH, 37 Convent Dr,MSC 4262,Bldg 37,Room 4146A, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 54 TC 50 Z9 56 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD APR PY 2006 VL 44 IS 4 BP 798 EP 805 DI 10.1016/j.jhep.2006.01.008 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 030QV UT WOS:000236650300032 PM 16488507 ER PT J AU Choh, AC Czerwinski, SA Lee, M Demerath, EW Cole, SA Wilson, AF Towne, B Siervogel, RM AF Choh, AC Czerwinski, SA Lee, M Demerath, EW Cole, SA Wilson, AF Towne, B Siervogel, RM TI Quantitative genetic analysis of blood pressure reactivity to orthostatic tilt using principal components analysis SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article DE genetic epidemiology; principal components analysis; cardiovascular reactivity; blood pressure; orthostatic tilt; postural change ID CARDIOVASCULAR RISK-FACTORS; BODY-MASS INDEX; ENVIRONMENTAL CONTRIBUTIONS; ATHEROSCLEROSIS RISK; RACIAL-DIFFERENCES; MENTAL STRESS; HEART-DISEASE; HYPERTENSION; FAMILY; HERITABILITY AB Blood pressure ( BP) reactivity to orthostatic tilt may be predictive of cardiovascular disease. However, the genetic and environmental influences on BP reactivity to tilt have not been well examined. Identifying different influences on BP at rest and BP during tilt is complicated by the intercorrelation among multiple measurements. In this study, we use principal components analysis ( PCA) to reduce multivariate BP data into components that are orthogonal. The objective of this study is to characterize and examine the genetic architecture of BP at rest and during head- up tilt ( HUT). Specifically, we estimate the heritability of individual BP measures and three principal components ( PC) derived from multiple BP measurements during HUT. Additionally, we estimate covariate effects on these traits. The study sample consisted of 444 individuals,distributed across four large families. HUT consisted of 701 head- up table tilting while strapped to a tilt table. BP reactivity ( Delta BP) was defined as BP during HUT minus BP while supine. Three PC extracted from the PCA were interpreted as ` general BP' ( PC1), ` pulse pressure' ( PC2) and ` BP reactivity' ( PC3). Variance components methods were used to estimate the herit-abilities of resting BP, HUT BP, DBP, as well as the three BP PC. Significant ( P < 0.05) heritabilities were found for all BP measurements, except for systolic DBP at 1 and 3 min, and diastolic Delta BP at 2 min. Significant genetic effects were also found for the three PC. Each of these orthogonal components is significantly influenced by somewhat different sets of covariates. C1 Wright State Univ, Sch Med, Lifespan Hlth Res Ctr, Dept Community Hlth, Kettering, OH 45420 USA. SW Fdn Biomed Res, San Antonio, TX 78284 USA. NHGRI, NIH, Baltimore, MD USA. RP Choh, AC (reprint author), Wright State Univ, Sch Med, Lifespan Hlth Res Ctr, Dept Community Hlth, Kettering, OH 45420 USA. EM audrey.choh@wright.edu RI Wilson, Alexander/C-2320-2009 FU NHLBI NIH HHS [R01 HL069995, R01 HL070167, R01-HL070167, R01-HL69995] NR 43 TC 5 Z9 5 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD APR PY 2006 VL 20 IS 4 BP 281 EP 289 DI 10.1038/sj.jhh.1001975 PG 9 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 022FM UT WOS:000236040500006 PM 16437129 ER PT J AU Babu, S Blauvelt, CP Kumaraswami, V Nutman, TB AF Babu, Subash Blauvelt, Carla P. Kumaraswami, V. Nutman, Thomas B. TI Cutting edge: Diminished T cell TLR expression and function modulates the immune response in human filarial infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; LYMPHATIC FILARIASIS; PARASITES; LIPOPOLYSACCHARIDE; CYTOKINES AB Patent lymphatic filariasis is characterized by profound Ag-specific T cell hyporesponsiveness with impaired IFN-gamma and IL-2 production. Because T cells have been shown to express a number of TLR and to respond to TLR ligands, we hypothesized that diminished T cell TLR function could partially account for the T cell hyporesponsiveness in filariasis. T cells expressed TLR1, TLR2, TLR4, and TLR9, and the baseline expression of TLR1, TLR2, and TLR4, but not TLR9 was significantly lower in T cells of the filarial-infected individuals compared with the uninfected individuals (both endemic and nonendemic). TLR function was significantly diminished in the T cells of filarial-infected individuals based on decreased T cell activation/cytokine production in response to TLR ligands. Thus, diminished expression and function of T cell TLR is a novel mechanism underlying T cell immune tolerance in lymphatic filariasis. C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. TB Res Ctr, Madras, Tamil Nadu, India. RP Babu, S (reprint author), NIAID, Parasit Dis Lab, NIH, 4 Ctr Dr,Room 4-B1-05, Bethesda, MD 20892 USA. EM sbabu@niaid.nih.gov FU Intramural NIH HHS NR 14 TC 76 Z9 83 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 IS 7 BP 3885 EP 3889 PG 5 WC Immunology SC Immunology GA 059YY UT WOS:000238769300008 PM 16547219 ER PT J AU Anderson, SK Locke, SM Davies, GE Wright, PW Hanson, RJ Miller, JS AF Anderson, Stephen Kent Locke, Sarahjane M. Davies, Gareth E. Wright, Paul W. Hanson, Rebecca J. Miller, Jeffrey S. TI Identification of probabilistic switches in the human KIR genes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Natl Canc Inst, SAIC Frederick, Basic Res Program, Frederick, MD 21702 USA. NCI Frederick, Expt Immunol Lab, Frederick, MD 21702 USA. Univ Minnesota, Ctr Canc, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S238 EP S238 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102102 ER PT J AU Andersson, J Stefanova, I Stephens, GL Shevach, EM AF Andersson, John Stefanova, Irena Stephens, Geoffrey L. Shevach, Ethan M. TI CD4+CD25+regulatory T cells are activated in vivo by recognition of self SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, NIH, Immunol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S139 EP S139 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101141 ER PT J AU Antony, PA Paulos, C Akpinarli, A Palmer, D Restifo, N AF Antony, Paul Andrew Paulos, Chrystal Akpinarli, Akgul Palmer, Doug Restifo, Nicholas TI Preferential use of IL-2 by CD25+Foxp3+T regulatory cells during immunity to a tumor/self-antigen SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NCI, Ctr Canc Res, Surg Branch, Bethesda, MD 20892 USA. NIAID, Ghost Lab, Bethesda, MD 20892 USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S219 EP S219 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102011 ER PT J AU Asefa, B Durum, S AF Asefa, Benyam Durum, Scott TI Regulation of T-cell homeostasis: Investigating the possible interaction between the IL-7 and TCR signaling pathways SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NCI, Mol Immunoregulat Lab, Ft Detrick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S179 EP S179 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101323 ER PT J AU Betz, BC Jordan, KL Zullo, AJ Vinson, C Taparowsky, EJ AF Betz, Briana C. Jordan, Kimberly L. Zullo, Alfred J. Vinson, Charles Taparowsky, Elizabeth J. TI Occupancy versus vacancy: exploring the role of AP-1 DNA binding activity in T cell development SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Purdue Univ, Dept Biol Sci, W Lafayette, IN 47907 USA. Purdue Univ, Purdue Canc Ctr, W Lafayette, IN 47907 USA. NIH, Lab Metab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S241 EP S241 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102114 ER PT J AU Bhandoola, A Schwarz, BA Sambandam, A Love, P Velez, M AF Bhandoola, Avinash Schwarz, Benjamin A. Sambandam, Arivazhagan Love, Paul Velez, Marielena TI Selective thymus settling by multipotent progenitors SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S311 EP S311 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102444 ER PT J AU Bowers, E Horn, C Butts, CL Belyavskaya, E Sternberg, EM AF Bowers, Eve Horn, Cash Butts, Cherie L. Belyavskaya, Elena Sternberg, Esther M. TI Comparison of male and female rat expression of steroid hormone receptors in immune cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIH, Sect Neuroendocrine Immunol & Behav, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S240 EP S240 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102110 ER PT J AU Boyaka, PN Duverger, A Tang, WJ Fujihashi, K McGhee, JR Leppla, SH AF Boyaka, Prosper N. Duverger, Alexandra Tang, Wei-Jen Fujihashi, Kohtaro McGhee, Jerry R. Leppla, Stephen H. TI A novel method for delivery of regulatory molecules in the GI tract using Bacillus anthracis protective antigen SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Alabama, Birmingham, AL 35294 USA. Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S243 EP S243 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102125 ER PT J AU Burgess, SJ Marusina, A Borrego, F Coligan, J AF Burgess, Steven James Marusina, Alina Borrego, Francisco Coligan, John TI IL-21 down-regulates NKG2D expression and function in human NK cells and differentially regulates NKG2D and CD28 expression on CD8+T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIH, RCBS, NIAID, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S27 EP S27 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100123 ER PT J AU Butts, CL Bowers, E Horn, C Belyavskaya, E Sternberg, EM AF Butts, Cherie L. Bowers, Eve Horn, Cash Belyavskaya, Elena Sternberg, Esther M. TI Progesterone has differential effects on dendritic cells from male and female rats SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIH, Sect Neuroendocrine Immunol & Behav, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S214 EP S214 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101490 ER PT J AU Chan, AY Nguyen, CM Mooney, JM Tian, XH Schwartzberg, PL D Schatzle, J Wakeland, EK AF Chan, Alice Y. Nguyen, Charles M. Mooney, Jill M. Tian, Xiang-Hong Schwartzberg, Pamela L. D Schatzle, John Wakeland, Edward K. TI The SLAM/CD2 family mediates autoimmunity independent of SAP SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S142 EP S142 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101155 ER PT J AU Chen, KQ Iribarren, P Hu, JY Chen, JH Gong, WH Cho, EH Lockett, S Dunlop, N Wang, JM AF Chen, Keqiang Iribarren, Pablo Hu, Jinyue Chen, Jianhong Gong, Wanghua Cho, Edward H. Lockett, Stephen Dunlop, Nancy Wang, Ji Ming TI Activation of toll-like receptor 2 on microglia promotes cell uptake of Alzheimer's disease-associated amyloid beta peptide SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NCI, LMI, Ft Detrick, MD 21702 USA. Shanghai Jiao Tong Univ, Sch Agr & Biol, Shanghai 201101, Peoples R China. SAIC Frederick, LMI, Basic Res Program, Ft Detrick, MD 21702 USA. SAIC Frederick, Image Anal Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S41 EP S41 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100189 ER PT J AU Darrah, PA De Luca, PM Patel, DT Seder, RA AF Darrah, Patricia A. De Luca, Paula M. Patel, Dipti T. Seder, Robert A. TI Protection against Leishmania major following vaccination with a recombinant adenovirus is determined by the quality rather than the magnitude of the Th1 response SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S120 EP S120 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101052 ER PT J AU DiPaolo, RJ Glass, DD Shevach, EM AF DiPaolo, Richard J. Glass, Deborah D. Shevach, Ethan M. TI Polyclonal and organ specific nTregs: Mechanisms of suppressing organ specific autoimmunity in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S150 EP S150 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101191 ER PT J AU Dixit, VD Yang, H Weeraratna, A Sun, YX Smith, R Taub, D AF Dixit, Vishwa Deep Yang, Hyunwon Weeraratna, Ashani Sun, Yuxiang Smith, Roy Taub, Dennis TI Age-associated thymic involution is inhibited by ghrelin SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIA, IRP, Immunol Lab, NIH, Baltimore, MD 21224 USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S303 EP S303 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102405 ER PT J AU Duverger, A Leppla, SH Tang, WJ Fujihashi, K Kiyono, H Mcghee, JR Boyaka, PN AF Duverger, Alexandra Leppla, Stephen H. Tang, Wei-Jen Fujihashi, Kohtaro Kiyono, Hiroshi Mcghee, Jerry R. Boyaka, Prosper N. TI Bacillus anthracis edema toxin acts as an adjuvant for enhanced immunity to PA and to unrelated vaccine antigens co-administered by the nasal or the transcutaneous route SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Alabama, Birmingham, AL 35294 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Chicago, Ben May Inst Canc Res, Chicago, IL 60637 USA. Univ Tokyo, Minato Ku, Tokyo 1088639, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S115 EP S115 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101030 ER PT J AU Dzutsev, A Belyakov, I Isakov, D Margulies, D AF Dzutsev, Amiran Belyakov, Igor Isakov, Dmitry Margulies, David TI Avidity of CD8 T-cells sharpens immunodominance. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NCI, Vaccine Branch, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S117 EP S117 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101038 ER PT J AU Elkholy, S Wallace, M Chowdhury, D Berg, L Sen, R Allman, D Gerstein, R AF Elkholy, Shereen Wallace, Morgan Chowdhury, Dipanjan Berg, Leslie Sen, Ranjan Allman, David Gerstein, Rachel TI IL-7-signaling via JAK3 is required for development of bone marrow committed B cell progenitors, including activation of the V(D)J recombinase SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Massachusetts, Sch Med, Worcester, MA 01655 USA. Brandeis Univ, Waltham, MA 02454 USA. NIA, Lab Cell & Mol Biol, Baltimore, MD 21224 USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S318 EP S318 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102479 ER PT J AU Elloumi, H Holland, SM AF Elloumi, Houda Holland, Steven M. TI Regulation of human cathelicidin gene SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, LCID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S242 EP S242 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102118 ER PT J AU Espinoza-Delgado, I Wojciechowski, W Li, HF Dell'Agnola, C Lopez, NE AF Espinoza-Delgado, Igor Wojciechowski, Wojciech Li, Huifen Dell'Agnola, Chiara Lopez, Natalia E. TI Post-transcriptional regulation of B7-H1 expression in human dendritic cells occurs through an ERIK-dependent and TNF-alpha-independent pathway SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIA, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S178 EP S178 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101319 ER PT J AU Ettinger, R Robbins, R Spolski, R Leonard, WJ Lipsky, PE AF Ettinger, Rachel Robbins, Rachel Spolski, Rosanne Leonard, Warren J. Lipsky, Peter E. TI IL-21 induces plasma cell differentiation from both human and mouse marginal zone B cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAMS, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S19 EP S19 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100089 ER PT J AU Feng, C Weksberg, D Goodell, M Sher, A AF Feng, Carl Weksberg, David Goodell, Margaret Sher, Alan TI The interferon-inducible GTPase LRG-47 is required for the hematopoietic stem cell response to proliferative stimuli SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA. Baylor Coll Med, Stem Cells & Regenerat Med Ctr, Houston, TX 77030 USA. Baylor Coll Med, Ctr Cell & Gene Therapy, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S306 EP S307 PG 2 WC Immunology SC Immunology GA 060YD UT WOS:000238837102423 ER PT J AU Fiorini, C Lougaris, V Lugar, P Slota, R van der Zouwen, B Melchers, M Withers, D Fischer, R Phillips, T Plebani, A Lipsky, P Grammer, A AF Fiorini, Claudia Lougaris, Vassilios Lugar, Patricia Slota, Rebecca van der Zouwen, Boris Melchers, Mark Withers, David Fischer, Randy Phillips, Terry Plebani, Alessandro Lipsky, Peter Grammer, Amrie TI CD154 engagement on tonsillar B cells induces proximal signaling events and differentiation to plasma cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIH, Bethesda, MD 20892 USA. NIH, Ultramicro Analyt Immunochem Resource, Bethesda, MD 20892 USA. Univ Brescia, I-25123 Brescia, Italy. RI Melchers, Mark/C-1438-2008; Plebani, Alessandro/C-8593-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S210 EP S210 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101472 ER PT J AU Fischer, RT Okada, S Lugar, P Slota, R Yarboro, C Longo, N Hardin, J Illei, G Lipsky, P Grammer, AC AF Fischer, Randy Thomas Okada, Sarah Lugar, Patricia Slota, Rebecca Yarboro, Cheryl Longo, Nancy Hardin, John Illei, Gabor Lipsky, Peter Grammer, Amrie C. TI A population of IgD+CD27-B cells similar to activated splenic marginal zone B cells is found in the blood of patients with active SLE, correlates with disease, and is sensitive to IL6 receptor block SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIH, BCBG, Bethesda, MD 20892 USA. NIH, OCD, Bethesda, MD 20892 USA. NIH, RAG, NIAMS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S136 EP S137 PG 2 WC Immunology SC Immunology GA 060YD UT WOS:000238837101129 ER PT J AU Gaffen, SL Kramer, JM Jin, T AF Gaffen, Sarah L. Kramer, Jill M. Jin, Tian TI Evidence for ligand-independent multimerization of the IL-17 receptor SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 SUNY Buffalo, Dept Microbiol & Immunol, Buffalo, NY 14214 USA. NIAID, Lab Immunogenet, NIH, Twinbrook Facil 2, Bethesda, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S14 EP S14 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100065 ER PT J AU Gauduin, MC Yu, Y Piatak, M Lifson, JD Desrosiers, RC Johnson, RP AF Gauduin, Marie-Claire Yu, Y. Piatak, M. Lifson, J. D. Desrosiers, R. C. Johnson, R. P. TI Induction of a virus-specific effector memory CD4+T cell response by attenuated SIV infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Harvard Univ, New England Reg Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. NCI, SAIC, Frederick, MD 21702 USA. Massachusetts Gen Hosp, Infect Dis Unit, Boston, MA 02114 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S92 EP S93 PG 2 WC Immunology SC Immunology GA 060YD UT WOS:000238837100427 ER PT J AU Ghochikyan, A Mkrtichyan, M Loukinov, D Mamikonyan, G Ichim, T Cribbs, DH Lobanenkov, VV Agadjanyan, MG AF Ghochikyan, Anahit Mkrtichyan, Mikayel Loukinov, Dmitri Mamikonyan, Grigor Ichim, Thomas Cribbs, David H. Lobanenkov, Victor V. Agadjanyan, Michael G. TI Induction of potent tissue unrestricted cancer specific immune responses by vaccination with a novel oncoinitiating transcription factor, BORIS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Inst Mol Med, Huntington Beach, CA 92647 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Calif Irvine, Inst Brain Aging & Dementia, Gillespie Neurosci Res Facil 1226, Irvine, CA 92697 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S252 EP S252 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102165 ER PT J AU Ghosh, MC Weeraratna, AT Collins, G Taub, DD AF Ghosh, Manik C. Weeraratna, Ashani T. Collins, Gary Taub, Dennis D. TI Induction of WNT-FDZ system in human T cell by the chemokines SDF1 alpha and MIP3 beta SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIA, Immunol Lab, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S26 EP S26 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100120 ER PT J AU Golech, SA Klaewsongkram, J Godlove, J Weng, NP AF Golech, Susanne Andrea Klaewsongkram, Jettanong Godlove, Jason Weng, Nan-ping TI Role of Kruppel-like factor 4 in T cell generation and function SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIA, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S295 EP S295 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102368 ER PT J AU Hand, T Singer, A Morre, M Kaech, SM AF Hand, Timothy Singer, Alfred Morre, Michel Kaech, Susan M. TI Expression of IL-7R is necessary but not sufficient for formation of memory CD8 T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Yale Univ, Sch Med, Immunobiol Sect, New Haven, CT 06520 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. Cytheris Inc, Vanves, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S298 EP S298 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102384 ER PT J AU Hayes, S Love, P AF Hayes, Sandy Love, Paul TI Stoichiometry of the murine gamma delta T cell receptor SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 SUNY Upstate Med Univ, Syracuse, NY 13210 USA. NICHD, LMGD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S212 EP S212 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101481 ER PT J AU Houpt, ER Asgharpour, A Stroup, S Wynn, T Leiter, E Hamano, S AF Houpt, Eric Robert Asgharpour, Amon Stroup, Suzanne Wynn, Thomas Leiter, Edward Hamano, Shinjiro TI Innate resistance to amoebiasis is mediated by non-hemopoietic cells but controlled by hemopoietically-derived IL-10 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Virginia, Charlottesville, VA 22908 USA. NIAID, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. Kyushu Univ, Dept Parasitol, Higashi Ku, Fukuoka 8128582, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S222 EP S222 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102027 ER PT J AU Imani, F Sawin, DA AF Imani, Farhad Sawin, Dixie-Ann TI RSV infection of human B lymphocytes induces IgA class switching through TGF-beta signaling SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S224 EP S224 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102034 ER PT J AU Jankovic, D Kullberg, MC Caspar, P Sher, A AF Jankovic, Dragana Kullberg, Marika C. Caspar, Patricia Sher, Alan TI IL-10 production by conventional Th1 cells provides negative feedback regulation of IFN-(gamma) secretion during anti-microbial responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, Lab Parasit Dis, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S13 EP S13 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100060 ER PT J AU Jirmanova, L Jankovic, D Ashwell, J AF Jirmanova, Ludmila Jankovic, Dragana Ashwell, Jonathan TI Gadd45alpha positively regulates Th1 immune response of CD4+cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S200 EP S200 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101423 ER PT J AU Kang, TJ Chen, WH Basu, S Fenton, MJ Weiner, MA Hibbs, S Baillie, L Cross, AS AF Kang, Tae Jin Chen, Wilbur H. Basu, Subhendu Fenton, Metthew J. Weiner, Matthew A. Hibbs, Stephen Baillie, Les Cross, Alan S. TI Critical role for caspase-1 in the innate immune response to Bacillus anthracis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. NIAID, Bethesda, MD 20892 USA. USN, Biol Def Res Directorate, Med Res Ctr, Silver Spring, MD 20910 USA. Univ Maryland, Maryland Biotechnol Inst, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S98 EP S99 PG 2 WC Immunology SC Immunology GA 060YD UT WOS:000238837100454 ER PT J AU Kelly, JA Paronto, K Spolski, R Al-Sharmi, A Leonard, W AF Kelly, John A. Paronto, Kate Spolski, Rosanne Al-Sharmi, Amin Leonard, Warren TI Stat5 overexpression results in immature CD8+T-cell expansion and lymphoma SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 White River Junction VA, White River Jct, VT 05009 USA. Dartmouth Coll Sch Med, Lebanon, NH 03756 USA. NHLBI, LMI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S180 EP S181 PG 2 WC Immunology SC Immunology GA 060YD UT WOS:000238837101330 ER PT J AU Kim, IJ Burkum, C Schwartzberg, PL Woodland, DL Blackman, MA AF Kim, In-Jeong Burkum, Claire Schwartzberg, Pamela L. Woodland, David L. Blackman, Marcia A. TI Gammaherpesvirus latency in SAP-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Trudeau Inst, Saranac Lake, NY 12983 USA. NHGRI, NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S73 EP S73 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100337 ER PT J AU Kinjo, Y Tupin, E Wu, D Fujio, M Benhnia, MRE Khurana, A Ben-Menachem, G Sellati, TJ Wong, CH Kronenberg, M AF Kinjo, Yuki Tupin, Emmanuel Wu, Douglass Fujio, Masakazu Rafii-El-Idrissi Benhnia, Mohammed Khurana, Archana Ben-Menachem, Gil Sellati, Timothy J. Wong, Chi-Huey Kronenberg, Mitchell TI NKT cells recognize bacterial diacylglycerols SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 La Jolla Inst Allergy & Immunol, San Diego, CA 92121 USA. Scripps Res Inst, La Jolla, CA 92037 USA. Albany Med Coll, Albany, NY 12208 USA. NIH, Bethesda, MD 20892 USA. RI rafii el idrissi benhnia, mohammed/F-3019-2015 OI rafii el idrissi benhnia, mohammed/0000-0001-7405-9476 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S97 EP S97 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100448 ER PT J AU Klaewsongkram, J Golech, S Godlove, J Katz, J Kaestner, KH Segre, J Weng, NP AF Klaewsongkram, Jettanong Golech, Susanne Godlove, Jason Katz, Jonathan Kaestner, Klaus H. Segre, Julie Weng, Nan-ping TI Kruppel-like factor 4 regulates B cell survival and apoptosis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S164 EP S164 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101252 ER PT J AU Li, LQ Gorivodsky, M Zhao, YG Tzchori, I Grinberg, A Westphal, H Love, PE AF Li, Qi Li Gorivodsky, Marat Zhao, Yangu Tzchori, Itai Grinberg, Alexander Westphal, Heiner Love, Paul E. TI LIM domain binding protein 1 (Ldb1) is required for the maintenance of adult hematopoietic stem cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NICHD, LMGD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S310 EP S311 PG 2 WC Immunology SC Immunology GA 060YD UT WOS:000238837102443 ER PT J AU Limmon, GV Imani, F AF Limmon, Gino V. Imani, Farhad TI Kinetic profiling of inflammatory gene expression in double-stranded RNA-treated human epithelial cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIEHS, LRB, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S103 EP S103 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100474 ER PT J AU Limmon, GV Chrysovergis, K Imani, F AF Limmon, Gino V. Chrysovergis, Kaliopi Imani, Farhad TI Role of TLR3 and scavenger receptor in DsRNA induction of TNF-alpha in human epithelial cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIEHS, NIH, LRB, Durham, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S70 EP S70 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100325 ER PT J AU Liu, ZG Pesce, JT Hamed, H Alem, F Urban, JF Gause, WC AF Liu, Zhugong Pesce, John T. Hamed, Hossein Alem, Farhang Urban, Joseph F., Jr. Gause, William C. TI Presence and function of Gr-1 bright neutrophils during the initiation of Th2 response induced by N. brasiliensis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07101 USA. NIAID, NIH, Immunopathol Sect, Bethesda, MD 20814 USA. USDA, Beltsville Human Nutr Res Ctr, Nutrient Requirements & Funct Lab, Beltsville, MD 20705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S67 EP S67 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100309 ER PT J AU Lobito, AA Kimberley, F Muppidi, J Hirsch, K Kastner, D Gavin, S Richard, SM AF Lobito, Adrian A. Kimberley, Fiona Muppidi, Jagan Hirsch, Komarow Kastner, Daniel Gavin, Screaton Richard, Siegel M. TI Abnormal disulfide-linked oligomerization results in ER retention and altered signaling by TNFR1 mutants in the TNFR1 associated periodic fever syndrome (TRAPS) SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAMS, Immunoregulat Unit, NIH, Bethesda, MD 20892 USA. Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, London W12 0NN, England. NIAMS, Genet & Genom Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S37 EP S37 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100169 ER PT J AU Longo, NS Yavuz, S Krijger, P Lipsky, PE AF Longo, Nancy S. Yavuz, Sule Krijger, Peter Lipsky, Peter E. TI Analysis of somatic hypermutation in X-HIgM syndrome reveals a unique pattern consistent with targeting during DNA replication SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAMS, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S234 EP S234 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102082 ER PT J AU Lugar, PL Fischer, R Slota, R Phillips, T Lipsky, P Grammer, AC AF Lugar, Patricia Lynne Fischer, Randy Slota, Rebecca Phillips, Terry Lipsky, Peter Grammer, Amrie C. TI Gene expression, phenotypic and proteomic profile of Ig-secreting plasma cells in the periphery of patients with active SLE SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAMS, NIH, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 2 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S136 EP S136 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101128 ER PT J AU Luger, D Silver, P Cua, D Chen, Z Caspi, R AF Luger, Dror Silver, Phyllis Cua, Daniel Chen, Zoe Caspi, Rachel TI Development of experimental autoimmune uveitis requires IL-23 but not the IL-17 producing T cell effector SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. DNAX Res Inst Molec & Cellular Biol Inc, Palo Alto, CA 94304 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S158 EP S158 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101226 ER PT J AU Mangan, PR Harrington, LE Wahl, SM Hatton, RD Weaver, CT AF Mangan, Paul R. Harrington, Laurie E. Wahl, Sharon M. Hatton, Robin D. Weaver, Casey T. TI Developmental requirements for Th17 effector T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Alabama, Birmingham, AL 35294 USA. NIH, Cellular Immunol Sect, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S14 EP S14 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100063 ER PT J AU Markovic-Plese, S Sujkowski, D Tang, YN Martin, R Pinilla, C AF Markovic-Plese, Silva Sujkowski, Danuta Tang, Yunan Martin, Roland Pinilla, Clemencia TI Characterization of CD4+ cells with a high degree of TCR flexibility in patients with MS SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ N Carolina, Chapel Hill, NC 27599 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20854 USA. Univ Hosp Vall Hebron, Neuroimmunol Clin, Barcelona, Spain. Torrey Pines Inst Mol Studies, San Diego, CA 92121 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S250 EP S250 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102155 ER PT J AU Mattapallil, J Douek, D Buckler-White, A Martin, M Montefiori, D Letvin, N Nabel, G Roederer, M AF Mattapallil, Joseph Douek, Daniel Buckler-White, Alicia Martin, Malcolm Montefiori, David Letvin, Norman Nabel, Gary Roederer, Mario TI Vaccination preserves pre-existing memory CD4 T-cells during acute SIV infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Durham, NC 27710 USA. Harvard Univ, Beth Israel Deaconess Med Ctr, Sch Med, Boston, MA 02215 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S90 EP S90 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100414 ER PT J AU Mattapallil, MJ Viley, AM Chan, CC Silver, PB Cortes, LM Donoso, LA McDowell, HJ David, CS Caspi, RR AF Mattapallil, Mary Joseph Viley, Angelia M. Chan, Chi-Chao Silver, Phyllis B. Cortes, Lizette M. Donoso, Larry A. McDowell, Hugh J. David, Chella S. Caspi, Rachel R. TI HLA -DR and -DQ allele interactions control susceptibility to autoimmune retinal disease SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIH, NEI LI, Bethesda, MD 20892 USA. Wills Eye Hosp & Res Inst, Philadelphia, PA 19107 USA. Univ Florida, Dept Ophthalmol, Gainesville, FL 32610 USA. Mayo Clin, Dept Immunol, Rochester, MN 55905 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S131 EP S131 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101104 ER PT J AU Medvedev, A Shoenfelt, J Weber, M Basul, S Wahl, LM Fenton, M Vogel, SN AF Medvedev, Andrei Shoenfelt, Joanna Weber, Michelle Basul, Subhendu Wahl, Larry M. Fenton, Matthew Vogel, Stefanie N. TI Role of TLR4 tyrosine phosphorylation in signal transduction and endotoxin tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Maryland, Baltimore, MD 21201 USA. NIDCR, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S183 EP S183 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101343 ER PT J AU Meylan, F Kinder, M Jankovic, D Sher, A Boesen, A Keane-Myers, A Semnani, R Nutman, T Wang, E Deyev, V AF Meylan, Francoise Kinder, Michelle Jankovic, Dragana Sher, Alan Boesen, Agnieszka Keane-Myers, Andrea Semnani, Roshanak Nutman, Tom Wang, Eddie Deyev, Vadim TI The TNF-family ligand TL1A is induced by innate and adaptive immune stimuli and biases T cells towards Th2 differentiation SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAMS, NIH, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Wales Coll Cardiff, Cardiff, Wales. Univ Miami, Coral Gables, FL 33124 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S198 EP S198 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101412 ER PT J AU Min, B Younes, S Hu-Li, J Thornton, A Oh, K Milner, J Paul, W AF Min, Booki Younes, Souheil Hu-Li, Jane Thornton, Angela Oh, Keunhee Milner, Joshua Paul, William TI CD25+ regulatory T cells exist as naive and memory phenotype cells with different proliferative rates and inhibitory potency SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Cleveland Clin Fdn, Dept Immunol, Cleveland, OH 44195 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RI younes, souheil-antoine/G-4503-2014 OI younes, souheil-antoine/0000-0003-2186-7140 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S294 EP S294 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102363 ER PT J AU Mongini, PKA Inman, J Abramson, S Attur, M AF Mongini, Patricia K. A. Inman, John Abramson, Steven Attur, Mukundan TI APRIL and BAFF promote clonal expansion of human B2 cells via a COX-2-dependent mechanism SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NYU Med Ctr, Hosp Joint Dis, New York, NY 10003 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S190 EP S190 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101373 ER PT J AU Moutaftsi, M Peters, B Pasquetto, V Sidney, J Bui, HH Grey, H Tscharke, D Yewdell, J Sette, A AF Moutaftsi, Magdalini Peters, Bjoern Pasquetto, Valerie Sidney, John Bui, Huynh-Hoa Grey, Howard Tscharke, David Yewdell, Jonathan Sette, Alessandro TI Towards the complete account of T cell specificities directed against vaccinia virus SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 LIAI, Vaccine Discovery 1, San Diego, CA 92109 USA. Queensland Inst Med Res, Div Immunol & Infect Dis, Herston, Qld 4006, Australia. NIAID, NIH, Viral Dis Lab, Bethesda, MD 20892 USA. RI yewdell, jyewdell@nih.gov/A-1702-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S116 EP S116 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101034 ER PT J AU Pechhold, K Chakrabarty, S Zhu, XL Harlan, DM AF Pechhold, Klaus Chakrabarty, Sagarika Zhu, Xiaolong Harlan, David M. TI Alterations in cognate activation of naive CD8+T cells control differentiation in effector and central memory cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIDDK, Islet & Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S45 EP S45 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100208 ER PT J AU Pisitkun, P Deane, J Difilippantonio, MJ Tarasenko, T Satterthwaite, A Bolland, S AF Pisitkun, Prapapom Deane, Jonathan Difilippantonio, Michael J. Tarasenko, Tatyana Satterthwaite, Anne Bolland, Silvia TI TLR7 gene duplication accelerates autoimmunity and promotes nucleolar-specific B cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, Autoimmun & Funct Genom Sect, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NCI, Sect Canc Genom, Genet Branch, CCR,NIH, Bethesda, MD 20892 USA. UT Southwestern, Dept Internal Med, Dallas, TX 75390 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S154 EP S154 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101208 ER PT J AU Polley, R Kaye, P AF Polley, Rosalind Kaye, Paul TI Bystander protection in a model of chronic parasitic infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, LI, LBS, NIH, Bethesda, MD 20892 USA. Univ York, Dept Biol, York YO10 5YU, N Yorkshire, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S305 EP S305 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102415 ER PT J AU Poloso, N Roche, P AF Poloso, Neil Roche, Paul TI Domain control of MHC class II raft localization SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S53 EP S53 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100244 ER PT J AU Prots, I Skapenko, A Mattyasovszky, S Yone, CL Kalden, JR Lipsky, PE Schulze-Koops, H AF Prots, Iryna Skapenko, Alla Mattyasovszky, Stefan Yone, Clarisse L. Kalden, Joachim R. Lipsky, Peter E. Schulze-Koops, Hendrik TI The IL4R single nucleotide polymorphism 150V is associated with early erosive rheumatoid arthritis SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Erlangen Nurnberg, Clin Res Grp 3, D-91054 Erlangen, Germany. NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S141 EP S141 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101150 ER PT J AU Qian, L Hong, JS Block, M Wilson, B Flood, P AF Qian, Li Hong, Jau-Shyong Block, Michelle Wilson, Belinda Flood, Patrick TI IL-10 protects dopaminergic neurons from LPS-induced neurotoxicity in rat primary midbrain cultures SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. Natl Inst Environm Hlth Sci, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S9 EP S9 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100039 ER PT J AU Rajagopalan, S Bryceson, Y Kuppusamy, SP Geraghty, DE van der Meer, A Joosten, I Long, EO AF Rajagopalan, Sumati Bryceson, Yenan Kuppusamy, Shanmuga P. Geraghty, Daniel E. van der Meer, Arnold Joosten, Irma Long, Eric O. TI Activation of NK cells by an endocytosed receptor for soluble HLA-G SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. Radboud Univ Nijmegen, Med Ctr, Dept Blood Transfus & Transplant Immunol, Nijmegen, Netherlands. RI Long, Eric/G-5475-2011; van der Meer, Arnold/M-1693-2016 OI Long, Eric/0000-0002-7793-3728; van der Meer, Arnold/0000-0001-8274-414X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S193 EP S193 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101387 ER PT J AU Ramirez, DC Mejiba, SEG Mason, RP AF Ramirez, Dario C. Mejiba, Sandra E. Gomez Mason, Ronald P. TI Immuno-spin trapping SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIEHS, Lab Pharmacol & Chem, DHHS, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S12 EP S12 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100053 ER PT J AU Robbins, RC Sims, G Novince, R Spolski, R Leonard, W Lipsky, P Ettinger, R AF Robbins, Rachel C. Sims, Gary Novince, Ryan Spolski, Rosanne Leonard, Warren Lipsky, Peter Ettinger, Rachel TI IL-21 is essential for T cell-dependent B. cell activation, differentiation, and Ig secretion SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAMSD, Autoimmun Branch, Bethesda, MD 20892 USA. NHLBI, Lab Mol Immunol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S164 EP S164 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101253 ER PT J AU Rossman, JS Stoicheva, NG Langel, FD Patterson, GH Lippincott-Schwartz, J Schaefer, BC AF Rossman, Jeremy S. Stoicheva, Natalia G. Langel, Felicia D. Patterson, George H. Lippincott-Schwartz, Jennifer Schaefer, Brian C. TI POLKADOTS are signaling foci in the T cell receptor-mediated activation of NF-kappa B SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S199 EP S199 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101418 ER PT J AU Schiralli, GM Readinger, J August, A Schwartzberg, PL Henderson, AJ AF Schiralli, Gillian M. Readinger, Julie August, Avery Schwartzberg, Pamela L. Henderson, Andrew J. TI Itk influences the HIV life cycle in T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Penn State Univ, University Pk, PA 16802 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S91 EP S91 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100421 ER PT J AU Shin, EC Seifert, U Rice, CM Feinstone, SM Kloetzel, PM Rehermann, B AF Shin, Eui-Cheol Seifert, Ulrike Rice, Charles M. Feinstone, Stephen M. Kloetzel, Peter-M. Rehermann, Barbara TI Double-stranded RNA-induced type IIFN induces immunoproteasomes during viral infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIDDK, Immunol Sect, LDB, NIH, Bethesda, MD 20892 USA. Humboldt Univ, Charite, D-10117 Berlin, Germany. Rockefeller Univ, New York, NY 10021 USA. US FDA, CBER, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S54 EP S54 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100251 ER PT J AU Sidney, J Asabe, S Peters, B Purton, KA Chung, J Pencille, TJ Purcell, R Walker, CM Chisari, FV Sette, A AF Sidney, John Asabe, Shinichi Peters, Bjoern Purton, Kelly-Anne Chung, Josan Pencille, Timothy J. Purcell, Robert Walker, Christopher M. Chisari, Francis V. Sette, Alessandro TI Detailed characterization of the peptide binding specificity of five common Patr class I MHC molecules SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Vaccine Discovery, San Diego, CA 92109 USA. Scripps Res Inst, La Jolla, CA 92037 USA. NIAID, NIH, Bethesda, MD 20892 USA. Ohio State Univ, Columbus, OH 43210 USA. Childrens Res Inst, Columbus, OH 43210 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S50 EP S50 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100233 ER PT J AU Skapenko, A Kalden, JR Lipsky, PE Schulze-Koops, H AF Skapenko, Alla Kalden, Joachim R. Lipsky, Peter E. Schulze-Koops, Hendrik TI The IL4R alpha chain-binding cytokines, IL4 and IL13, induce Foxp3 expressing CD25+CD4+regulatory T cells from CD25-CD4+precursors SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Erlangen Nurnberg, Clin Res Grp 3, D-91054 Erlangen, Germany. NIAMS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S139 EP S139 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101140 ER PT J AU Slota, R Fischer, R Longo, N Lugar, PL Illei, G Phillips, T Lipsky, P Grammer, A AF Slota, Rebecca Fischer, Randy Longo, Nancy Lugar, Patricia Lynne Illei, Gabor Phillips, Terry Lipsky, Peter Grammer, Amrie TI Functional and phenotypic characterization of anergic B cells circulating in the periphery of patients with systemic lupus erythematosus. SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAMS, NIH, Bethesda, MD 20892 USA. NIDCR, NIH, Bethesda, MD 20892 USA. NIH, Ultramicro Analyt Immunochem Resource OD, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S156 EP S156 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101218 ER PT J AU Spolski, R Kim, HP Feng, C Sher, A Leonard, W AF Spolski, Rosanne Kim, Hyoung-Pyo Feng, Carl Sher, Alan Leonard, Warren TI IL-21 functions as both a Th1 and Th2 cytokine and mediates CD4 T cell proliferative responses SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NHLBI, LMI, Bethesda, MD 20892 USA. NIAID, LPD, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S15 EP S15 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100071 ER PT J AU Stephens, GL Andersson, J Shevach, E AF Stephens, Geoffrey Laurence Andersson, John Shevach, Ethan TI A distinct subset of FoxP3+T regulatory cells participates in the control of innate and adaptive immune responses in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S141 EP S141 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101147 ER PT J AU Stewart, TJ Greenelteh, K Schneider, M Liu, KB Abrams, S AF Stewart, Trina J. Greenelteh, Kristy Schneider, Monika Liu, Kebin Abrams, Scott TI Role of interferon consensus sequence binding protein (ICSBP) in the regulation of tumor-induced CD11b+Gr1+myeloid suppressor cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NCI, Lab Tumor Immunol & Biol, Bethesda, MD 20892 USA. RI Stewart, Trina/F-5967-2012 OI Stewart, Trina/0000-0003-3220-9231 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S275 EP S275 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102272 ER PT J AU Stulberg, MJ Wright, PW Hanson, RJ Miller, JS Anderson, SK AF Stulberg, Michael J. Wright, Paul W. Hanson, Rebecca J. Miller, Jeffrey S. Anderson, Stephen K. TI Identification of an additional upstream promoter in the human KIR genes SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NCI, Expt Immunol Lab, Frederick, MD 21702 USA. Sci Applicat Int Corp, Basic Res Program, Frederick, MD 21702 USA. Univ Minnesota, Ctr Canc, Div Hematol Oncol & Transplantat, Minneapolis, MN 55455 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S242 EP S242 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102119 ER PT J AU Su, Z Segura, M Belkaid, Y Stevenson, M AF Su, Zhong Segura, Mariela Belkaid, Yasmin Stevenson, Mary TI Mechanisms of helminth-associated modulation of immunity to malaria SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 McGill Univ, Ctr Study Host Resistance, Res Inst, Ctr Hlth, Montreal, PQ H3G 1A4, Canada. McGill Univ, Ctr Host Parasite Interact, Res Inst, Ctr Hlth, Montreal, PQ H3G 1A4, Canada. NIAID, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S68 EP S68 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100316 ER PT J AU Swindle, EJ Coleman, JW Metcalfe, DD AF Swindle, Emily J. Coleman, John W. Metcalfe, Dean D. TI Fc epsilon R1 aggregation on mast cells results in lipoxygenase-dependent production of reactive oxygen species which facilitates cytokine secretion SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, LAD, MCBS, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S322 EP S322 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102498 ER PT J AU Tang, J Zhu, W Sliver, PB So, SB Agarwal, RK Chan, CC Caspi, RR AF Tang, Jun Zhu, Wei Sliver, Phyllis B. So, Shao Bo Agarwal, Rajeev K. Chan, Chi-Chao Caspi, Rachel R. TI Characteristics of autoimmune disease model induced by in-vitro matured, Ag-pulsed DC: an essential role for IFN-gamma SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NEI, Immunol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S279 EP S279 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102290 ER PT J AU Terabe, M Swann, J Ambrosino, E Sinha, P Takaku, S Hayakawa, Y Godfrey, DI Ostrand-Rosenberg, S Smyth, MJ Berzofsky, JA AF Terabe, Masaki Swann, Jeremy Ambrosino, Elena Sinha, Pratima Takaku, Shun Hayakawa, Yoshihiro Godfrey, Dale I. Ostrand-Rosenberg, Suzanne Smyth, Mark J. Berzofsky, Jay A. TI A non-classical type IINKT cell suppresses tumor immunity SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NCI, CCR, Vaccine Branch, Bethesda, MD 20892 USA. Peter MacCallum Canc Ctr, Melbourne, Vic 3002, Australia. Univ Maryland, Baltimore, MD 21250 USA. Univ Melbourne, Parkville, Vic 3010, Australia. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S274 EP S274 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102268 ER PT J AU Thompson, BD Jin, YZ Birnbaumer, L Kochevar, IE Wu, MX AF Thompson, Brian D. Jin, Yongzhu Birnbaumer, Lutz Kochevar, Irene E. Wu, Mei X. TI Antagonism between G alpha i2 and G alpha i3 in CXCR3-mediated signaling SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Massachusetts Gen Hosp, Wellman Ctr Photomed, Boston, MA 02114 USA. Natl Inst Environm Hlth Sci, Lab Signal Transduct, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S25 EP S26 PG 2 WC Immunology SC Immunology GA 060YD UT WOS:000238837100118 ER PT J AU Tolar, P Sohn, HW Pierce, SK AF Tolar, Pavel Sohn, Hae Won Pierce, Susan K. TI The initiation of B cell receptor signaling viewed in living cells with FRET SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S192 EP S192 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101383 ER PT J AU Tvinnereim, AR Cortes, C Appella, E Sidney, J Sette, A Wizel, B AF Tvinnereim, Amy R. Cortes, Claudio Appella, Ettore Sidney, John Sette, Alessandro Wizel, Benjamin TI Analysis of HLA-A2 restricted CD8+ T cell responses to Chlamydia pneumoniae SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Univ Texas, Tyler, TX 75708 USA. NCI, Bethesda, MD 20892 USA. LIAI, San Diego, CA 92121 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S116 EP S116 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101032 ER PT J AU Vacchio, MS Olaru, A Livak, F Hodes, RJ AF Vacchio, Melanie S. Olaru, Alessandro Livak, Ferenc Hodes, Richard J. TI Abnormalities in TCR expression on DP thymocytes in ATM-deficient mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIH, Expt Immunol Branch, Bethesda, MD 20892 USA. Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. NIA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S318 EP S318 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102480 ER PT J AU Wang, HS Qi, CF Clarke, SH AF Wang, Hongsheng Qi, Chenfeng Clarke, Stephen H. TI Transitional B cells lose their receptor editing capacity but retain other positive and negative selection potentials SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, Immunopathol Lab, Rockville, MD 20852 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S161 EP S161 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101240 ER PT J AU Wang, XL Ye, YH Lencer, W Kothe, M Hansen, TH AF Wang, Xiaoli Ye, Yihong Lencer, Wayne Kothe, Michael Hansen, Ted H. TI The viral E3 ubiquitin ligase mK3 uses the Derlin/p97 ERAD pathway to mediate downregulation of MHC-I protein SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 Washington Univ, Dept Pathol & Immunol, St Louis, MO 63110 USA. NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Harvard Digest Dis Ctr, Boston, MA 02115 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63110 USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S118 EP S118 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101044 ER PT J AU Wang, Y Pierce, SK AF Wang, Yan Pierce, Susan K. TI The role of CD81 cysteines in the function of the CD19/CD21 coreceptor complex SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S175 EP S175 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101303 ER PT J AU Wuest, T Willette-Brown, J Hurwitz, AA AF Wuest, Thomas Willette-Brown, Jami Hurwitz, Arthur A. TI Influence of type-1 cytokines on Treg activation and function SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NCI, Mol Immunoregulat Lab, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S216 EP S216 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101500 ER PT J AU Yan, Y Janz, S Eckhardt, LA AF Yan, Yi Janz, Siegfried Eckhardt, Laurel A. TI Under IgH 3 ' regulatory region control, c-myc transgene becomes active at the immature B cell stage of B lineage development SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 CUNY Hunter Coll, New York, NY 10021 USA. CUNY, Grad Ctr, New York, NY 10021 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S239 EP S239 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102103 ER PT J AU Yang, YH Weng, NP AF Yang, Yinhua Weng, Nan-Ping TI Differential effects of IL-7 in regulation of homeostatic proliferation and telomerase expression in human naive and memory CD4+ T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIA, Dept Immunol, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S295 EP S295 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102367 ER PT J AU Yu, CR Mahdi, R Liu, XB Takase, H Zhang, A Egwuagu, CE AF Yu, Cheng-Rong Mahdi, Rashid Liu, Xue-Bin Takase, Hiroshi Zhang, Allen Egwuagu, Charles E. TI SOCS1 regulates CD4+T cells homeostasis and migration into secondary lymphoid tissues SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S206 EP S206 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837101451 ER PT J AU Zarember, KA Sugui, J Zerfas, P Chang, Y Kwon-Chung, J Gallin, JI AF Zarember, Kol A. Sugui, Janyce Zerfas, Patricia Chang, Yon Kwon-Chung, June Gallin, John I. TI Chronic granulomatous disease (CGD) and normal human neutrophils arrest the growth of Aspergillus fumigatus conidia: a new fungistatic role for lactoferrin SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NIAID, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S70 EP S70 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100323 ER PT J AU Zeng, R Spolski, R Casas, E Levy, DE Leonard, WJ AF Zeng, Rong Spolski, Rosanne Casas, Esther Levy, David E. Leonard, Warren J. TI An IL-21 receptor tyrosine is critical for IL-21-induced proliferation and the activation of Stat1 and Stat3 SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. NYU, Sch Med, Dept Microbiol, New York, NY 10016 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S14 EP S14 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837100066 ER PT J AU Zhang, H Chua, K Snyder, K June, C AF Zhang, Hua Chua, Kevin Snyder, Kristen June, Carl TI 4-1BB mediated costimulation enriches viral and tumor reactive memory T cells from human peripheral blood SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract CT Annual Meeting of the American-Association-of-Immunologists CY MAY 12-16, 2006 CL Boston, MA SP Amer Assoc Immunologists C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Penn, Abramson Family Canc Res Inst, Ctr Canc, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2006 VL 176 SU S BP S254 EP S254 PG 1 WC Immunology SC Immunology GA 060YD UT WOS:000238837102174 ER PT J AU Li, GQ Xia, HHX Chen, MH Gu, Q De Wang, J Peng, JZ Chan, AOO Cho, CH So, HL Lam, SK Hu, PJ Liang, YJ Lin, HL Berg, DE Feng, ZH Langenbach, R Wong, BCY AF Li, GQ Xia, HHX Chen, MH Gu, Q De Wang, J Peng, JZ Chan, AOO Cho, CH So, HL Lam, SK Hu, PJ Liang, YJ Lin, HL Berg, DE Feng, ZH Langenbach, R Wong, BCY TI Effects of cyclooxygenase-1 and -2 gene disruption on Helicobacter pylori-induced gastric inflammation SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Digestive Disease Week/105th Annual Meeting of the American-Gastroenterological-Association CY MAY 16-20, 2004 CL New Orleans, LA SP Amer Gastroenterol Assoc ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; EPITHELIAL-CELL PROLIFERATION; NITRIC-OXIDE SYNTHASE; MONGOLIAN GERBILS; PROSTAGLANDIN SYNTHESIS; INDUCED APOPTOSIS; INHIBITOR SC-236; NATURAL-HISTORY; CANCER CELLS; INFECTION AB Background. Cyclooxygenases (COXs) play important roles in inflammation and carcinogenesis. The present study aimed to determine the effects of COX-1 and COX-2 gene disruption on Helicobacter pylori-induced gastric inflammation. Methods. Wild-type (WT), COX-1 and COX-2 heterozygous ( COX-1(+/-) and COX- 2(+/-)), and homozygous COX- deficient (COX-1(-/-) and COX-2(-/-)) mice were inoculated with H. pylori strain TN2 and killed after 24 weeks of infection. Uninfected WT and COX- deficient mice were used as controls. Levels of gastric mucosal inflammation, epithelial cell proliferation and apoptosis, and cytokine expression were determined. Results. COX deficiency facilitated H. pylori-induced gastritis. In the presence of H. pylori infection, apoptosis was increased in both WT and COX- deficient mice, whereas cell proliferation was increased in WT and COX- 1 deficient, but not in COX-2-deficient, mice. Tumor necrosis factor (TNF)-alpha and interleukin-10 mRNA expression was elevated in H. pylori-infected mice, but only TNF-alpha mRNA expression was further increased by COX deficiency. Prostaglandin E-2 levels were increased in infected WT and COX-2-deficient mice but were at very low levels in infected COX-1-deficient mice. Leukotriene (LT) B-4 and LTC4 levels were increased to a similar extent in infected WT and COX- deficient mice. Conclusions. COX deficiency enhances H. pylori-induced gastritis, probably via TNF-alpha expression. COX- 2, but not COX-1, deficiency suppresses H. pylori-induced cell proliferation. C1 Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China. Univ Hong Kong, Dept Pharmacol, Hong Kong, Hong Kong, Peoples R China. Sun Yat Sen Univ, Affiliated Hosp 1, Dept Med, Guangzhou, Peoples R China. Sun Yat Sen Univ, Dept Pathol, Guangzhou, Peoples R China. Nanhua Univ, Affiliated Hosp 2, Dept Med, Hengyang, Peoples R China. Washington Univ, Dept Mol Microbiol, St Louis, MO 63110 USA. Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Wong, BCY (reprint author), Univ Hong Kong, Queen Mary Hosp, Dept Med, Hong Kong, Hong Kong, Peoples R China. EM bcywong@hku.hk RI Wong, Benjamin/C-4436-2009; Cho, Chi Hin/C-6543-2014 OI Cho, Chi Hin/0000-0002-7658-3260 NR 59 TC 13 Z9 14 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2006 VL 193 IS 7 BP 1037 EP 1046 DI 10.1086/500984 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 018PJ UT WOS:000235777000018 PM 16518767 ER PT J AU Domanski, M Waldo, AL AF Domanski, Michael Waldo, Albert L. TI Catheter ablation of atrial fibrillation: A treatment frontier SO JOURNAL OF INTERVENTIONAL CARDIAC ELECTROPHYSIOLOGY LA English DT Editorial Material ID RHYTHM MANAGEMENT; LONG-TERM; RISK; ARRHYTHMIAS; STROKE C1 NHLBI, Clin Trials Grp, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Med, Cleveland, OH 44106 USA. RP Domanski, M (reprint author), NHLBI, Clin Trials Grp, Bldg 10, Bethesda, MD 20892 USA. EM domanskm@nih.gov NR 22 TC 1 Z9 2 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1383-875X J9 J INTERV CARD ELECTR JI J. Interv. Card. Electrophysiol. PD APR PY 2006 VL 15 IS 3 BP 141 EP 143 DI 10.1007/s10840-006-9024-6 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 091EU UT WOS:000241010200001 PM 16909315 ER PT J AU Trempus, C Morris, R Elmore, A Ehinger, M Humble, M Kissling, G Ito, M Cotsarelis, G Flagler, N Bortner, C Sifre, M Tennant, R AF Trempus, C. Morris, R. Elmore, A. Ehinger, M. Humble, M. Kissling, G. Ito, M. Cotsarelis, G. Flagler, N. Bortner, C. Sifre, M. Tennant, R. TI CD34 expression by hair follicle stem cells is required for skin tumor development in mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NIEHS, NCT, Res Triangle Pk, NC USA. Columbia Univ, New York, NY 10027 USA. Integrated Lab Syst Inc, Durham, NC USA. NIEHS, Biostat Branch, Res Triangle Pk, NC USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NIEHS, LEP, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 107 BP 18 EP 18 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500106 ER PT J AU Li, S Wang, J Darling, TN AF Li, S. Wang, J. Darling, T. N. TI Proteome analysis of skin tumors in tuberous sclerosis complex SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NHLBI, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 118 BP 20 EP 20 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500120 ER PT J AU Darwiche, N Ryscavage, A Nolan, L Hennings, H Yuspa, S Glick, AB AF Darwiche, N. Ryscavage, A. Nolan, L. Hennings, H. Yuspa, S. Glick, A. B. TI Identification of a gene expression signature for benign precursor lesions to cutaneous squamous cell carcinoma SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Amer Univ Beirut, Beirut, Lebanon. NCI, LCCTP, Bethesda, MD 20892 USA. Penn State Univ, Ctr Mol Toxicol & Carcinogenesis, University Pk, PA 16802 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 122 BP 21 EP 21 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500125 ER PT J AU Morris, RI Li, S Trempus, C Cotsarelis, G AF Morris, R. I. Li, S. Trempus, C. Cotsarelis, G. TI Hair follicle stem cells: Targets in carcinogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Columbia Univ, Med Ctr, New York, NY 10027 USA. NIEHS, Res Triangle Pk, NC USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 127 BP 22 EP 22 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500128 ER PT J AU Neutzner, M Feng, X Glick, AB Yuspa, SH Cannon, R Tennant, RW Udey, MC AF Neutzner, M. Feng, X. Glick, A. B. Yuspa, S. H. Cannon, R. E. Tennant, R. W. Udey, M. C. TI Promotion of cutaneous neoplasia in mice by MFG-E8 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Penn State Univ, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NIEHS, Natl Ctr Toxicogenom, NIH, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 131 BP 22 EP 22 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500130 ER PT J AU Patel, GK Ohyama, M Graham, RL Yee, CL Terunuma, A Montemarano, A Maggio, K Vogel, JC AF Patel, G. K. Ohyama, M. Graham, R. L. Yee, C. L. Terunuma, A. Montemarano, A. Maggio, K. Vogel, J. C. TI Characterization of keratinocyte subpopulations in non-melanoma skin cancer using "stem cell" markers derived from microarray analysis of human hair follicles. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NCI, Bethesda, MD 20892 USA. Univ Tokyo, Sch Med, Dept Dermatol, Tokyo, Japan. Rockledge Skin Canc Clin, Bethesda, MD USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 128 BP 22 EP 22 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500131 ER PT J AU Ermilov, A Brown, J Roessler, E Wang, A Grachtchouk, M Silva, ND Ramirez, A Jorcano, J Muenke, M Dlugosz, AA AF Ermilov, A. Brown, J. Roessler, E. Wang, A. Grachtchouk, M. Silva, N. D. Ramirez, A. Jorcano, J. Muenke, M. Dlugosz, A. A. TI Constitutive hedgehog signaling activity, via GLI2 expression, is sufficient for salivary gland tumorigenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Univ Michigan, Dept Oral Med Pathol & Oncol, Ann Arbor, MI 48109 USA. NIH, Bethesda, MD 20892 USA. CIEMAT, E-28040 Madrid, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 137 BP 23 EP 23 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500136 ER PT J AU Lee, C Kakinuma, T Wang, J Zhang, H Jaber, S Palmer, D Restifo, N Hwang, S AF Lee, C. Kakinuma, T. Wang, J. Zhang, H. Jaber, S. Palmer, D. Restifo, N. Hwang, S. TI A peptide antagonist of CXCR4 restores sensitivity of B16 murine melanoma cells to killing by GP100-specific cytolytic T cells and increases the efficacy of cyclophosphamide in treating established lung metastases SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NCI, Dermatol Branch, Bethesda, MD USA. NCI, Surg Branch, Bethesda, MD USA. RI Restifo, Nicholas/A-5713-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 222 BP 37 EP 37 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500223 ER PT J AU Segre, J Djalilian, A Seo, E McGaughey, D Cheng, J Tomic, M Ishida-Yamamoto, A AF Segre, J. Djalilian, A. Seo, E. McGaughey, D. Cheng, J. Tomic, M. Ishida-Yamamoto, A. TI Connexin 26 regulates epidermal barrier, wound remodeling and promotes psoriatic progression SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NHGRI, NIH, Bethesda, MD 20892 USA. NEI, NIH, Bethesda, MD 20892 USA. NICHD, NIH, Bethesda, MD USA. Asahikawa Med Coll, Asahikawa, Hokkaido 078, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 367 BP 62 EP 62 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500366 ER PT J AU Stimpson, S Radoja, N Blumenberg, M Morasso, MI AF Stimpson, S. Radoja, N. Blumenberg, M. Morasso, M. I. TI Potential upregulation of cyclin-dependent kinase inhibitors by the Dlx3 homeodomain transcription factor SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NIH, Dev Skin Biol Unit, NIAMS, Bethesda, MD 20892 USA. NYU, Dept Dermatol, New York, NY 10016 USA. NYU, Dept Biochem, New York, NY 10016 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 374 BP 63 EP 63 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500375 ER PT J AU Terunuma, A Kapoor, V Telford, WG Udey, MC Vogel, JC AF Terunuma, A. Kapoor, V. Telford, W. G. Udey, M. C. Vogel, J. C. TI alpha 6 integrin bright/CD71-dim human keratinocytes exhibit stem cell activity in a long-term in vivo competitive repopulation assay while "Side Population" (SP) keratinocytes resembling hematopoietic SP stem cells do not SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 380 BP 64 EP 64 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500381 ER PT J AU Buchau, AS Kukova, G Lewerenz, V Wolf, R Ruzicka, T Walz, M AF Buchau, A. S. Kukova, G. Lewerenz, V. Wolf, R. Ruzicka, T. Walz, M. TI Human S100A15 is regulated by calcium, cytokines, and bacterial compounds SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Univ Dusseldorf, D-4000 Dusseldorf, Germany. NIH, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 412 BP 69 EP 69 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500412 ER PT J AU Hwang, J Kalinin, O Hwang, M Anderson, E Kim, MJ Lee, SH Morasso, MI AF Hwang, J. Kalinin, O. Hwang, M. Anderson, E. Kim, M. J. Lee, S. H. Morasso, M. I. TI Skin-specific calcium-binding protein, Scarf and its roles during epidermal differentiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD USA. NIDDK, Proteom & Mass Spectrometry Facil, OD, NIH, Bethesda, MD USA. Yonsei Univ, Coll Med, Dept Dermatol, Seoul, South Korea. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 417 BP 70 EP 70 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500415 ER PT J AU Emmert, S Ueda, T Zumsteg, U Khan, SG Laspe, P Zachmann, K Leibeling, D Bircher, A Kraemer, KH AF Emmert, S. Ueda, T. Zumsteg, U. Khan, S. G. Laspe, P. Zachmann, K. Leibeling, D. Bircher, A. Kraemer, K. H. TI The common C2125T rather than a new del2084G mutation in the XPD gene determines the xeroderma pigmentosum phenotype in a 15y old boy SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Univ Gottingen, D-3400 Gottingen, Germany. NCI, Basic Res Lab, Bethesda, MD 20892 USA. Univ Basel Hosp, CH-4031 Basel, Switzerland. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 437 BP 73 EP 73 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500434 ER PT J AU Pasmooij, AM Pas, H Jonkman, MF AF Pasmooij, A. M. Pas, H. H. Jonkman, M. F. TI Development of genetically-modified Human Skin Equivalents (HSE) for systemic in vivo delivery of Atrial Natriuretic Peptide (ANP) for the treatment of hypertension. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Keio Univ, Sch Med, Dept Dermatol, Tokyo, Japan. RI Pasmooij, Anna/H-2419-2011 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 444 BP 74 EP 74 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500443 ER PT J AU Imoto, K Oh, K Boyle, J Inui, H Nadem, C Ueda, T Busch, DB Gozukara, E Khan, S Tamura, D DiGiovanna, J Kraemer, KH AF Imoto, K. Oh, K. Boyle, J. Inui, H. Nadem, C. Ueda, T. Busch, D. B. Gozukara, E. Khan, S. Tamura, D. DiGiovanna, J. Kraemer, K. H. TI Twelve novel mutations in 14 xeroderma pigmentosum group A families: Phenotype-genotype correlation and haplotype analysis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NIH, Basic Res Lab, Bethesda, MD 20892 USA. Inonu Univ, Sch Med, Malatya, Turkey. Brown Med Sch, Providence, RI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 464 BP 78 EP 78 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500465 ER PT J AU Oh, K Khan, SG Imoto, K Jaspers, N Raams, A Ueda, T Lehmann, A Friedmann, P Emmert, S Gratchev, A Lachlan, K Lucassan, A Kraemer, KH AF Oh, K. Khan, S. G. Imoto, K. Jaspers, N. Raams, A. Ueda, T. Lehmann, A. Friedmann, P. Emmert, S. Gratchev, A. Lachlan, K. Lucassan, A. Kraemer, K. H. TI Sequential assembly of nucleotide excision repair factors at sites of DNA damage in XP-B cells SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. Erasmus Univ, Rotterdam, Netherlands. Univ Sussex, Brighton, E Sussex, England. Univ Southampton, Southampton, Hants, England. Univ Gottingen, D-3400 Gottingen, Germany. Univ Heidelberg, D-6800 Mannheim, Germany. RI Gratchev, Alexei/J-3170-2013 NR 0 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 468 BP 78 EP 78 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500467 ER PT J AU Boyle, J Ueda, T Gonzalez, V Oh, K Imoto, K Inui, H Busch, DB Khan, S Tamura, D DiGiovanna, JJ Kraemer, KH AF Boyle, J. Ueda, T. Gonzalez, V. Oh, K. Imoto, K. Inui, H. Busch, D. B. Khan, S. Tamura, D. DiGiovanna, J. J. Kraemer, K. H. TI Splice mutations in the XPD gene and absence of neurological symptoms SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. Brown Med Sch, Providence, RI USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 469 BP 79 EP 79 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500468 ER PT J AU Khan, SG Boyle, J Imoto, K Oh, K Armstrong, N Tamura, D DiGiovanna, JJ Kraemer, KH AF Khan, S. G. Boyle, J. Imoto, K. Oh, K. Armstrong, N. Tamura, D. DiGiovanna, J. J. Kraemer, K. H. TI Differential expression of XPC protein and localization at UV damage is associated with severe or mild clinical phenotypes in xeroderma pigmentosum group C patients SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. Brown Med Sch, Providence, RI USA. NR 0 TC 1 Z9 2 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 470 BP 79 EP 79 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500471 ER PT J AU Radoja, N Guerrini, L Lolacono, N Costanzo, A LaMantia, G Calabro, V Morasso, MI AF Radoja, N. Guerrini, L. Lolacono, N. Costanzo, A. LaMantia, G. Calabro, V. Morasso, M. I. TI Dlx3 as a downstream target of p63 SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD USA. Univ Milan, Dept Biomol & Biotechnol Sci, Milan, Italy. Dulbecco Telethon Inst, Milan, Italy. Univ Roma Tor Vergata, Dept Dermatol, I-00161 Rome, Italy. Univ Naples, Dept Struct & Funct Biol, Naples, Italy. RI Costanzo, Antonio/D-3896-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 475 BP 80 EP 80 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500474 ER PT J AU Eller, MS Backvall, H Reddy, K Opresko, PL Bohr, VA Gilchrest, BA AF Eller, M. S. Backvall, H. Reddy, K. Opresko, P. L. Bohr, V. A. Gilchrest, B. A. TI WRN-mediated DNA damage responses localize to telomeres SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Boston Univ, Sch Med, Boston, MA 02215 USA. Univ Pittsburgh, Pittsburgh, PA USA. NIA, Baltimore, MD 21224 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 483 BP 81 EP 81 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500481 ER PT J AU Li, AG Siddiqui, Y Deng, C Wang, X AF Li, A. G. Siddiqui, Y. Deng, C. Wang, X. TI Differential role of Smad2 and Smad3 in mediating TGF beta 1 overexpression induced psoriasis-like skin inflammation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Oregon Hlth Sci Univ, Portland, OR 97201 USA. NIDDK, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 560 BP 94 EP 94 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500560 ER PT J AU Cui, C Hashimoto, T Grivennikov, SI Piao, Y Nedospasov, SA Schlessinger, D AF Cui, C. Hashimoto, T. Grivennikov, S. I. Piao, Y. Nedospasov, S. A. Schlessinger, D. TI Ectodysplasin regulates lymphotoxin, Wnt, BMP and SHH pathways for hair follicle formation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NIA, Genet Lab, Baltimore, MD 21224 USA. NCI, Basic Res Lab, Canc Res Ctr, Frederick, MD 21701 USA. RI Nedospasov, Sergei/J-5936-2013; Nedospasov, Sergei/L-1990-2015; Nedospasov, Sergei/Q-7319-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 572 BP 96 EP 96 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500571 ER PT J AU Hwang, J Morasso, MI AF Hwang, J. Morasso, M. I. TI Analysis of Dlx3 gene expression in lacZ knock-in mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 637 BP 107 EP 107 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500633 ER PT J AU Miyagawa, F Kim, BS Patel, HJ Tagaya, Y Waldmann, TA Katz, SI AF Miyagawa, F. Kim, B. S. Patel, H. J. Tagaya, Y. Waldmann, T. A. Katz, S. I. TI Exogenous administration of IL-15 breaks peripheral tolerance towards low dose antigen in experimental graft vs. host disease (GvHD) SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Natl Inst Hlth, Dermatol Branch, Bethesda, MD USA. Natl Inst Hlth, Metab Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 650 BP 109 EP 109 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500648 ER PT J AU Kakinuma, T Nadiminti, H Murakami, T Perez, BA Kobayashi, H Finkelstein, SE Hwang, ST AF Kakinuma, T. Nadiminti, H. Murakami, T. Perez, B. A. Kobayashi, H. Finkelstein, S. E. Hwang, S. T. TI Small numbers of residual tumor cells at the site of primary inoculation are critical for antitumor immunity following challenge at a secondary location SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. NCI, Metab Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 694 BP 116 EP 116 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500690 ER PT J AU Fang, L Hwang, ST AF Fang, L. Hwang, S. T. TI CCR7-dependent lymph node metastasis is associated with tumor development and striking alterations in the composition of immune cells within B16 melanoma tumors SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 701 BP 117 EP 117 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500694 ER PT J AU Takeuchi, S Takeuchi, F Furue, M Katz, SI AF Takeuchi, S. Takeuchi, F. Furue, M. Katz, S. I. TI Langerhans cells preferentially develop from c-kit positive hematopoietic progenitors through thymic-independent pathways SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Kyushu Univ, Grad Sch Med Sci, Fukuoka 812, Japan. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 706 BP 118 EP 118 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500702 ER PT J AU Kim, BS Miyagawa, F Bennett, CL Clausen, BE Katz, SI AF Kim, B. S. Miyagawa, F. Bennett, C. L. Clausen, B. E. Katz, S. I. TI Elimination of epidermal Langerhans cells or impairment of dermal dendritic cells does not abrogate the induction of localized graft-versus-host-disease-like skin disease SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NIH, Dermatol Branch, Bethesda, MD 20892 USA. HHMI, NIH, Res Scholars Program, Bethesda, MD USA. Univ Amsterdam, Dept Cell Biol & Histol, Amsterdam, Netherlands. RI bennett, clare/J-5249-2013 OI bennett, clare/0000-0001-9146-2347 NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 709 BP 119 EP 119 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500704 ER PT J AU Nograles, KE Miyagawa, F Kim, BS Katz, SI AF Nograles, K. E. Miyagawa, F. Kim, B. S. Katz, S. I. TI Induction of a fulminant T-cell mediated autoimmune disease after adoptive transfer of OT-IT cells into K14-sOVA transgenic mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NCI, NIH, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 723 BP 121 EP 121 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500717 ER PT J AU Lopez Kostka, S Dinges, S Knop, J Udey, MC Iwakura, Y von Stebut, E AF Lopez Kostka, S. Dinges, S. Knop, J. Udey, M. C. Iwakura, Y. von Stebut, E. TI Interleukin-17 in cutaneous leishmaniasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Univ Mainz, Dept Dermatol, D-6500 Mainz, Germany. NCI, Dermatol Branch, Bethesda, MD 20892 USA. Univ Tokyo, Ctr Expt Med, Tokyo, Japan. RI Iwakura, Yoichiro/E-5457-2011 OI Iwakura, Yoichiro/0000-0002-9934-5775 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 777 BP 130 EP 130 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500771 ER PT J AU Moelle, K Tada, Y Shibagaki, N Knop, J Udey, MC von Stebut, E AF Moelle, K. Tada, Y. Shibagaki, N. Knop, J. Udey, M. C. von Stebut, E. TI TAT-fusion protein-transduced Dendritic Cells (DC) efficiently induce CD8(+) T Cells (TC) and vaccinate against leishmaniasis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Univ Mainz, Dept Dermatol, D-6500 Mainz, Germany. NCI, NIH, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 776 BP 130 EP 130 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500773 ER PT J AU Altiner, A Tock, CL Turner, LR Terunuma, A Miller, S Beer, J Yee, CL Udey, MC Vogel, JC AF Altiner, A. Tock, C. L. Turner, L. R. Terunuma, A. Miller, S. Beer, J. Yee, C. L. Udey, M. C. Vogel, J. C. TI Identifying biosensor genes that quantify human epidermal response to UV radiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NIH, Dermatol Branch, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Bethesda, MD 20817 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 857 BP 143 EP 143 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500850 ER PT J AU Tormo, D Ferrer, A Gaffal, E Wenzel, J Steitz, J Heukamp, L Gutgemann, I Buttner, R Malumbres, M Barbacid, M Merlino, G Tuting, T AF Tormo, D. Ferrer, A. Gaffal, E. Wenzel, J. Steitz, J. Heukamp, L. Gutgemann, I. Buttner, R. Malumbres, M. Barbacid, M. Merlino, G. Tuting, T. TI Rapid growth of invasive metastatic melanoma in carcinogen-treated HGF/SF-transgenic mice carrying an oncogenic CDK4 mutation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Univ Bonn, Lab Expt Dermatol, D-5300 Bonn, Germany. Univ Bonn, Inst Pathol, D-5300 Bonn, Germany. CNIO, Madrid, Spain. NCI, Lab Cell Regulat & Carcionogenesis, Bethesda, MD 20892 USA. RI Heukamp, Lukas/A-8338-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 874 BP 146 EP 146 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500870 ER PT J AU Florell, SR Thomas, J Merlino, G Noonan, F Grossman, D AF Florell, S. R. Thomas, J. Merlino, G. Noonan, F. Grossman, D. TI Dermal melanocytomas are predominant tumor type induced in UV-irradiated HGF/B6xC3H mice SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 Univ Utah, Salt Lake City, UT USA. NCI, Bethesda, MD 20892 USA. George Washington Univ, Med Ctr, Washington, DC 20037 USA. Huntsman Canc Inst, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 885 BP 148 EP 148 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500879 ER PT J AU Wang, Y DiGiovanna, JJ Stern, J Hornyak, TJ Raffeld, M Kraemer, KH AF Wang, Y. DiGiovanna, J. J. Stern, J. Hornyak, T. J. Raffeld, M. Kraemer, K. H. TI Laser capture microdissection and DNA sequencing analysis of melanoma biopsies from Xeroderma Pigmentosum patients SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NCI, Basic Res Lab, Bethesda, MD 20892 USA. Brown Univ, Sch Med, Providence, RI 02912 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 890 BP 149 EP 149 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500887 ER PT J AU Jiang, S Kahn, SA Trepel, JB Neckers, LM Hornyak, TJ AF Jiang, S. Kahn, S. A. Trepel, J. B. Neckers, L. M. Hornyak, T. J. TI Interaction of BRAF and BRAF(V600E) with HSP90 in melanoma cells and inhibition of RAF-dependent signaling by the geldanamycin analog 17-AAG SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NCI, Dermatol Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Med Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 912 BP 152 EP 152 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500907 ER PT J AU Chung, N Longo, L Achebe, E Hornyak, T AF Chung, N. Longo, L. Achebe, E. Hornyak, T. TI Increased expression of Bmi-1 in human melanoma cell lines SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NCI, Dermatol Branch, CCR, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 913 BP 153 EP 153 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500908 ER PT J AU Achebe, E Longo, L Chung, N Hornyak, T AF Achebe, E. Longo, L. Chung, N. Hornyak, T. TI Comparison of the transduction efficiency of primary human melanocytes by lentivirus produced using different transfection reagents. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 67th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 03-06, 2006 CL Philadelphia, PA SP Soc Investigat Dermatol C1 NCI, CCR, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 SU 1 MA 920 BP 154 EP 154 PG 1 WC Dermatology SC Dermatology GA 117RU UT WOS:000242891500917 ER PT J AU Udey, MC AF Udey, Mark C. TI Langerhans cells on guard in the epidermis: Poised to dSEARCH and...? SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Editorial Material ID DENDRITIC CELLS; IN-VIVO; CONTACT HYPERSENSITIVITY AB Langerhans cells have long been considered to be prototypic immature dendritic cells. Results of experiments involving genetically engineered mice provide surprising new insights into Langerhans cell function in vivo. Nishibu and colleagues illustrate how these approaches can be used to visualize Langerhans cells in vivo in real time, and to assess aspects of their behavior in unperturbed skin and after activation. C1 NCI, Dermatol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Udey, MC (reprint author), NCI, Dermatol Branch, Canc Res Ctr, NIH, Bldg 10,Room 12N238, Bethesda, MD 20892 USA. EM udey@helix.nih.gov NR 10 TC 5 Z9 5 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2006 VL 126 IS 4 BP 705 EP 707 DI 10.1038/sj.jid.5700222 PG 4 WC Dermatology SC Dermatology GA 062TX UT WOS:000238968600004 PM 16541095 ER PT J AU Kwan, J Yeom, BW Jones, M Qin, JX Zetts, AD Thomas, JD Shiota, T AF Kwan, J Yeom, BW Jones, M Qin, JX Zetts, AD Thomas, JD Shiota, T TI Acute geometric changes of the mitral annulus after coronary occlusion: A real-time 3D echocardiographic study SO JOURNAL OF KOREAN MEDICAL SCIENCE LA English DT Article DE mitral valve; mitral annulus; echocardiography; coronary disease ID LEFT-VENTRICULAR DYSFUNCTION; 3-DIMENSIONAL ECHOCARDIOGRAPHY; ANIMAL-MODEL; DILATED CARDIOMYOPATHY; REGURGITATION; VALVE; MECHANISM; SHAPE; RECONSTRUCTION; DETERMINANTS AB We performed real-time 3D echocardiography in sixteen sheep to compare acute geometric changes in the mitral annulus after left anterior descending coronary artery (LAD, n=8) ligation and those after left circumflex coronary artery (LCX, n=8) ligation. The mitral regurgitation (MR) was quantified by regurgitant volume (RV) using the proximal isovelocity surface area method. The mitral annulus was reconstructed through the hinge points of the annulus traced on 9 rotational apical planes (angle increment=20 degrees). Mitral annular area (MAA) and the ratio of antero-posterior (AP) to commissure-commissure (CC) dimension of the annulus were calculated. Non-planar angle (NPA) representing non-planarity of the annulus was measured. After LCX occlusion, there were significant increases of the MAA during both early and late systole (p < 0.01) with significant MR (RV: 30 +/- 14 mL), while there was neither a significant increase of MAA, nor a significant MR (RV: 4 5 mL) after LAD occlusion. AP/CC ratio (p < 0.01) and NPA (p < 0.01) also significantly increased after LCX occlusion during both early and late systole. The mitral annulus was significantly enlarged in the antero-posterior direction with significant decrease of non-planarity compared to LAD occlusion immediately after LCX occlusion. C1 Inha Univ Hosp, Dept Cardiol, Inchon 400711, South Korea. Korea Univ, Coll Med, Dept Pathol, Seoul 136701, South Korea. Cleveland Clin Fdn, Dept Cardiol, Cardiovasc Imaging Ctr, Cleveland, OH 44195 USA. NHLBI, Bethesda, MD 20892 USA. RP Kwan, J (reprint author), Inha Univ Hosp, Dept Cardiol, 7-206 3-ga,Shinheung Dong, Inchon 400711, South Korea. EM kuonmd@inha.ac.kr NR 31 TC 6 Z9 9 U1 0 U2 0 PU KOREAN ACAD MEDICAL SCIENCES PI SEOUL PA 302 75 DONG DU ICHON, DONG YONGSAN KU, SEOUL 140 031, SOUTH KOREA SN 1011-8934 J9 J KOREAN MED SCI JI J. Korean Med. Sci. PD APR PY 2006 VL 21 IS 2 BP 217 EP 223 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 038NQ UT WOS:000237229900007 PM 16614504 ER PT J AU Ravert, HT Zhang, Y Horti, A Dannals, RF AF Ravert, Hayden T. Zhang, Yi Horti, Andrew Dannals, Robert F. TI Radiosynthesis of the alpha 4 beta 2 nicotinic acetylcholine receptor ligand: 5-((1-[C-11]-methyl-2-(S)pyrrolidinyl)methoxy)-2-chloro-3-((E)-2-(2-fluo ropyridin-4-yl)vinyl)pyridine SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE alpha 4 beta 2 nicotinic acetylcholine receptor; carbon-11; positron emission tomography AB 5-((1-[C-11]-methyl-2-(S)-pyrrolidinyl)methoxy)-2-chloro-3-((E)-2-(2-fluoropyridin-4-yl)vinyl)pyridine ([C-11]-FPVC) was synthesized from [C-11]-methyl iodide and the corresponding normethyl precursor. The average time of synthesis, purification, and formulation was 42 min with an average non-decay-corrected radiochemical yield of 19%. The average specific radioactivity was 359 GBq/mu Mol (9691 mCi/mu mole) at end of synthesis (EOS). Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Johns Hopkins Med Inst, Div Nucl Med, Dept Radiol, Baltimore, MD 21287 USA. NIDA, Neuroimaging Res Branch, Intramural Res Program, US Dept HHS,NIH, Baltimore, MD 21224 USA. RP Ravert, HT (reprint author), Johns Hopkins Med Inst, Div Nucl Med, Dept Radiol, 600 N Wolfe St, Baltimore, MD 21287 USA. EM htr@jhu.edu NR 4 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD APR PY 2006 VL 49 IS 5 BP 459 EP 462 DI 10.1002/jlcr.1064 PG 4 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 050WV UT WOS:000238121100006 ER PT J AU Zezula, J Wang, HYJ Woods, AS Wise, RA Jacobson, AE Rice, KC AF Zezula, Josef Wang, Hay-Yan J. Woods, Amina S. Wise, Roy A. Jacobson, Arthur E. Rice, Kenner C. TI The high specific activity tritium labeling of the ganglion-blocking nicotinic antagonist chlorisondamine SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE chlorisondamine; nicotinic antagonist; tritiation ID QUATERNARY AMMONIUM; RAT-BRAIN; IN-VIVO; BLOCKADE AB Chlorisondamine is a bisquaternary ganglion-blocking nicotinic antagonist that accumulates in dopaminergic, serotonergic, and noradrenergic cell bodies; the mechanism of uptake and time-course of retrograde transport are not known. Chlorisondamine could possibly be taken into monoaminergic neurons when blocked nicotinic receptors on those cells are internalized. In order to more easily study the mechanism of the capture and recycling of chlorisondamine, a ligand is needed that has high specific activity. For that purpose, we now report the preparation of H-3-labeled chlorisondamine (4,5,6,7-tetrachloro-2-[H-3]methyl-2-(2-trimethylammoniumethyl)-isoindolinium diiodide) of high specific activity (94CI/mmol). The compound was synthesized by quarternization of 4,5,6,7-tetrachloro-2-(2-trimethylammoniumethyl-isoindolinium iodide with pertritiated methyl iodide in dimethylformamide at high temperature in a sealed vessel. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 NIDDKD, Med Chem Lab, US Dept HHS, NIH, Bethesda, MD 20892 USA. NIDA, Behav Neurosci Branch, Intramural Res Program, US Dept HHS,NIH, Baltimore, MD 21224 USA. RP Rice, KC (reprint author), NIDDKD, Med Chem Lab, US Dept HHS, NIH, Bldg 8,Room B1-23,8 Ctr Dr,MSC 0815, Bethesda, MD 20892 USA. EM kr21f@nih.gov RI Wise, Roy/A-6465-2012 NR 13 TC 1 Z9 1 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD APR PY 2006 VL 49 IS 5 BP 471 EP 478 DI 10.1002/jlcr.1069 PG 8 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 050WV UT WOS:000238121100008 ER PT J AU Kakinuma, T Hwang, ST AF Kakinuma, Takashi Hwang, Sam T. TI Chemokines, chemokine receptors, and cancer metastasis SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE PI-3K; Akt; carcinoma; melanoma ID LYMPH-NODE METASTASIS; CELLS IN-VITRO; MONOCYTE CHEMOATTRACTANT PROTEIN-1; SKIN-ASSOCIATED CHEMOKINE; ENDOTHELIAL GROWTH-FACTOR; MALIGNANT-MELANOMA-CELLS; HUMAN OVARIAN-CANCER; REGULATORY T-CELLS; BREAST-CANCER; LUNG-CANCER AB It is clear from large clinical studies that selected chemokine receptors are often upregulated in a large number of common human cancers, including those of the breast, lung, prostate, colon, and melanoma. Chemokine receptors and their corresponding chemokine ligands have been demonstrated to play a number of nonredundant roles in cancer metastasis to vital organs as well as regional lymph nodes, the most frequent site of cancer metastasis. Chemokine receptors may potentially facilitate tumor dissemination at several key steps of metastasis, including adherence of tumor cells to endothelium, extravasation from blood vessels, metastatic colonization, angiogenesis, proliferation, and protection from the host response via activation of key survival pathways such as phosphatidylinositol-3 kinase and Akt. It is interesting that many of these roles are reminiscent of their functions in leukocyte and stem cell trafficking. Lastly, we discuss therapeutic applications for chemokine receptor antagonists in cancer therapy. C1 NCI, Dermatol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. RP Hwang, ST (reprint author), NCI, Dermatol Branch, Canc Res Ctr, Bldg 10 Rm 12N238,10 Ctr Dr, Bethesda, MD 20892 USA. EM hwangs@mail.nih.gov FU Intramural NIH HHS NR 122 TC 176 Z9 194 U1 1 U2 17 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD APR PY 2006 VL 79 IS 4 BP 639 EP 651 DI 10.1189/jlb.1105633 PG 13 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 119LZ UT WOS:000243015100001 PM 16478915 ER PT J AU Nofer, JR Remaley, AT Feuerborn, R Wolinska, I Engel, T von Eckardstein, A Assmann, G AF Nofer, JR Remaley, AT Feuerborn, R Wolinska, I Engel, T von Eckardstein, A Assmann, G TI Apolipoprotein A-I activates Cdc42 signaling through the ABCA1 transporter SO JOURNAL OF LIPID RESEARCH LA English DT Article DE ATP binding cassette transporter A1; high density lipoproteins; cholesterol efflux ID HIGH-DENSITY-LIPOPROTEINS; PROTEIN-KINASE-C; CHOLESTEROL EFFLUX; APOA-I; LIPID EFFLUX; CELLULAR CHOLESTEROL; HELICAL PEPTIDES; TANGIER-DISEASE; BINDING; PHOSPHORYLATION AB It has been suggested that the signal transduction initiated by apolipoprotein A-I ( apoA-I) activates key proteins involved in cholesterol efflux. ABCA1 serves as a binding partner for apoA-I, but its participation in apoAI-induced signaling remains uncertain. We show that the exposure of human fibroblasts to ABCA1 ligands ( apolipo-proteins and amphipathic helical peptides) results in the generation of intracellular signals, including activation of the small G-protein Cdc42, protein kinases ( PAK-1 and p54(JNK)), and actin polymerization. ApoA-I-induced signaling was abrogated by glyburide, an inhibitor of the ABC transporter family, and in fibroblasts from patients with Tangier disease, which do not express ABCA1. Conversely, induction of ABCA1 expression with the liver X receptor agonist, T0901317, and the retinoid X receptor agonist, R0264456, potentiated apoA-I-induced signaling. Similar effects were observed in HEK293 cells overexpressing ABCA1-green fluorescent protein ( GFP) fusion protein, but not ABCA1-GFP ( K939M), which fails to hydrolyze ATP, or a nonfunctional ABCA1-GFP with a truncated C terminus. We further found that Cdc42 coimmunoprecipitates with ABCA1 in ABCA1-GFP-expressing HEK293 cells exposed to apoA-I but not in cells expressing ABCA1 mutants. We conclude that ABCA1 transduces signals from apoA-I by complexing and activating Cdc42 and downstream kinases and, therefore, acts as a full apoA-I receptor. C1 Univ Munster, Inst Klin Chem & Lab Med, D-4400 Munster, Germany. Univ Munster, Leibniz Inst Arterioskleroseforsch, D-4400 Munster, Germany. NIH, Dept Lab Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. Univ Spital Zurich, Inst Klin Chem, Zurich, Switzerland. RP Nofer, JR (reprint author), Univ Munster, Inst Klin Chem & Lab Med, D-4400 Munster, Germany. EM nofer@uni-muenster.de NR 39 TC 38 Z9 39 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD APR PY 2006 VL 47 IS 4 BP 794 EP 803 DI 10.1194/jlr.M500502-JLR200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 024VF UT WOS:000236223700013 PM 16443932 ER PT J AU Quine, JR Achuthan, S Asbury, T Bertram, R Chapman, MS Hu, J Cross, TA AF Quine, JR Achuthan, S Asbury, T Bertram, R Chapman, MS Hu, J Cross, TA TI Intensity and mosaic spread analysis from PISEMA tensors in solid-state NMR SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE PISEMA tensors; solid-state NMR; powder pattern intensity; mosaic spread; lineshapes ID ORIENTATIONAL CONSTRAINTS; MEMBRANE-PROTEINS; ANISOTROPIC ENVIRONMENTS; LIPID-BILAYERS; CHEMICAL-SHIFT; SPIN-EXCHANGE; CLOSED STATE; GRAMICIDIN-A; M2 PROTEIN; CHANNEL AB The solid-state NMR experiment PISEMA, is a technique for determining structures of proteins, especially membrane proteins, from oriented samples. One method for determining the structure is to find orientations of local molecular frames (peptide planes) with respect to the unit magnetic field direction, B-0. This is done using equations that compute the coordinates of this vector in the frames. This requires an analysis of the PISEMA function and its degeneracies. As a measure of the sensitivity of peptide plane orientations to the data, we use these equations to derive a formula for the intensity function in the powder pattern. With this function and other measures, we investigate the effect of small changes in peptide plane orientations depending on the location of the resonances in the powder pattern spectrum. This gives us an indication of the change in lineshape due to mosaic spread and a way to interpret these in terms of an orientational error bar. (c) 2005 Elsevier Inc. All rights reserved. C1 Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Natl High Magnet Field Lab, Tallahassee, FL 32310 USA. Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. Florida State Univ, Dept Chem & Biochem, Tallahassee, FL 32306 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Quine, JR (reprint author), Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. EM quine@math.fsu.edu FU NIGMS NIH HHS [1P01 GM64676] NR 26 TC 19 Z9 19 U1 0 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD APR PY 2006 VL 179 IS 2 BP 190 EP 198 DI 10.1016/j.jmr.2005.12.002 PG 9 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 035VQ UT WOS:000237030200003 PM 16413215 ER PT J AU Koay, CG Basser, PJ AF Koay, CG Basser, PJ TI Analytically exact correction scheme for signal extraction from noisy magnitude MR signals SO JOURNAL OF MAGNETIC RESONANCE LA English DT Article DE magnitude MR noise; rician; noise; Gaussian; signal-to-noise; SNR fixed point ID MAXIMUM-LIKELIHOOD-ESTIMATION; MAGNETIC-RESONANCE IMAGES; RICIAN DISTRIBUTION; RECONSTRUCTION; ARRAY AB An analytically exact method is proposed to extract the signal intensity and the noise variance simultaneously from noisy magnitude MR signals. This method relies on a fixed point formula of signal-to-noise ratio (SNR) and a correction factor. The correction factor, which is a function of SNR, establishes a fundamental link between the variance of the magnitude MR signal and the variance of the underlying Gaussian noise in the two quadrature channels. A more general but very similar method is developed for parallel signal acquisitions with multiple receiver coils. In the context of M R imaging, the proposed method can be carried out on a pixel-by-pixel basis if the mean and the standard deviation of the magnitude signal are available. Published by Elsevier Inc. C1 NICHHD, NIH, Bethesda, MD 20892 USA. RP Koay, CG (reprint author), NICHHD, NIH, Bethesda, MD 20892 USA. EM guankoac@mail.nih.gov RI Basser, Peter/H-5477-2011 FU Intramural NIH HHS NR 28 TC 117 Z9 119 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1090-7807 J9 J MAGN RESON JI J. Magn. Reson. PD APR PY 2006 VL 179 IS 2 BP 317 EP 322 DI 10.1016/j.jmr.2006.01.016 PG 6 WC Biochemical Research Methods; Physics, Atomic, Molecular & Chemical; Spectroscopy SC Biochemistry & Molecular Biology; Physics; Spectroscopy GA 035VQ UT WOS:000237030200019 PM 16488635 ER PT J AU Demos, SG Vogel, AJ Gandjbakhche, AH AF Demos, Stavros G. Vogel, Abby J. Gandjbakhche, Amir H. TI Advances in optical spectroscopy and imaging of breast lesions SO JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA LA English DT Article DE optical imaging; spectroscopy; optical mammography; optical biopsy; breast imaging; functional imaging ID NEAR-INFRARED TOMOGRAPHY; INDUCED FLUORESCENCE SPECTROSCOPY; ELECTRICAL-IMPEDANCE TOMOGRAPHY; ELASTIC-SCATTERING SPECTROSCOPY; TUMORS IN-VIVO; RAMAN-SPECTROSCOPY; MAGNETIC-RESONANCE; CANCER DIAGNOSIS; OXYGEN-SATURATION; REFLECTANCE SPECTROSCOPY AB A review is presented of recent advances in optical imaging and spectroscopy and the use of light for addressing breast cancer issues. Spectroscopic techniques offer the means to characterize tissue components and obtain functional information in real time. Three-dimensional optical imaging of the breast using various illumination and signal collection schemes in combination with image reconstruction algorithms may provide a new tool for cancer detection and treatment monitoring. C1 Lawrence Livermore Natl Lab, Livermore, CA 94551 USA. Univ Calif Davis, Sch Med, Ctr Med, Sacramento, CA 95817 USA. NIH, Lab Integrat & Med Biophys, Bethesda, MD 20892 USA. RP Demos, SG (reprint author), Lawrence Livermore Natl Lab, 7000 East Ave, Livermore, CA 94551 USA. EM demos1@llnl.gov FU Intramural NIH HHS NR 99 TC 29 Z9 30 U1 1 U2 3 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1083-3021 J9 J MAMMARY GLAND BIOL JI J. Mammary Gland Biol. Neoplasia PD APR PY 2006 VL 11 IS 2 BP 165 EP 181 DI 10.1007/s10911-006-9022-4 PG 17 WC Oncology; Endocrinology & Metabolism; Physiology SC Oncology; Endocrinology & Metabolism; Physiology GA 111OP UT WOS:000242463000007 PM 17091396 ER PT J AU Bianchi, DW Hanson, J AF Bianchi, DW Hanson, J TI Sharpening the Tools: A summary of a National Institutes of Health workshop on new technologies for detection of fetal cells in maternal blood for early prenatal diagnosis SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE fetal cells in maternal blood; cell-free fetal DNA; prenatal diagnosis; NIFTY trial; nucleated erythrocyte; trophoblast ID REAL-TIME PCR; MESSENGER-RNA; PLASMA; SERUM; MICRODISSECTION; IDENTIFICATION; PREGNANCY; WOMEN; DNA AB In 2003 the National Institute of Child Health and Human Development (NICHD) sponsored a workshop entitled "Sharpening the Tools'', which was designed to explore the then current state of prenatal diagnosis and screening using fetal cells in maternal blood. The goals of the workshop were to: review the then current state of the field and assess present capabilities, identify future research needs and challenges in this area, identify promising new and innovative approaches for future exploration, and provide a written summary of the conference for public distribution. The workshop featured brief presentations by experts from a wide range of scientific fields and by innovative bioengineering and technology leaders from academic centers and private industry. The workshop was divided into presentations on target cells, target approaches for separation, genetic and protein analysis, and 'out of the box' ( bioengineering) approaches. The passage of time since the workshop has allowed an objective assessment of where the research has progressed. A 2006 update on the field is included at the end of the summary. C1 Tufts Univ, New England Med Ctr, Div Genet, Dept Pediat, Boston, MA 02111 USA. Tufts Univ, New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. NICHHD, Ctr Dev Biol & Perinatal Med, NIH, Bethesda, MD 20892 USA. RP Bianchi, DW (reprint author), Tufts Univ, New England Med Ctr, Div Genet, Dept Pediat, 750 Washington St,Box 394, Boston, MA 02111 USA. EM DBianchi@Tufts-nemc.org NR 28 TC 17 Z9 17 U1 2 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD APR PY 2006 VL 19 IS 4 BP 199 EP 207 DI 10.1080/14767050600676851 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 054XN UT WOS:000238412000002 PM 16854692 ER PT J AU Santolaya-Forgas, J Romero, R Mehendale, R AF Santolaya-Forgas, J Romero, R Mehendale, R TI The effect of continuous morphine administration on maternal plasma oxytocin concentration and uterine contractions after open fetal surgery SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE tocolytics; oxytocin; fetal surgery; opioids in pregnancy; morphine; stress response; prematurity ID CORTICOTROPIN-RELEASING HORMONE; HUMAN-PREGNANCY; HUMAN PARTURITION; PRETERM LABOR; MYOMETRIAL CONTRACTILITY; VENTRICULAR MYOCYTES; STRESS-RESPONSE; AMNIOTIC-FLUID; HUMAN NEONATE; BABOON AB Objective. A major complication of open fetal surgery is prematurity. We propose that fetal and maternal stress/pain after surgery may affect the concentration of circulating oxytocin and the frequency of uterine contractions, thus increasing the risk of preterm delivery. The objective of this study was to test whether continuous morphine sulfate administration after open fetal surgery has an effect on maternal plasma oxytocin concentration and the frequency of uterine contractions. Methods. An established time-pregnant primate model for open fetal surgery was used. From the time of surgery until the end of the three-day study period, three animals received prophylactic antibiotics, a bolus of indomethacin, and a bolus of morphine sulfate ( group I). Three other animals received the same prophylactic antibiotics and an i.v. bolus of indomethacin, as well as a continuous i.v. infusion of morphine sulfate throughout the entire study period ( group II). Maternal blood samples were collected to determine oxytocin plasma concentrations. Oxytocin was measured by radioimmunoassay. Uterine activity was continuously recorded through an amniotic fluid catheter and quantified as number of contractions ( >= 10 mmHg increase from base line in intrauterine pressure) per hour (UCs/h). Results. The mean maternal plasma oxytocin concentration was higher (p<0.01) and the number of uterine contractions more frequent (p<0.05) in the group of animals with intermittent doses of morphine than in the group that received morphine continuously. Conclusions. These data suggest that maternal plasma oxytocin concentration and uterine activity after open fetal surgery may be related to inadequate maternal/fetal analgesia/sedation. C1 NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Univ Illinois, Dept Obstet & Gynecol, Chicago, IL 60612 USA. RP Santolaya-Forgas, J (reprint author), Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Div Maternal Fetal Med, Box 4,3990 John R, Detroit, MI 48201 USA. EM jsantol@med.wayne.edu OI Mehendale, Ramkrishna/0000-0003-2127-9613 NR 70 TC 13 Z9 14 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1476-7058 J9 J MATERN-FETAL NEO M JI J. Matern.-Fetal Neonatal Med. PD APR PY 2006 VL 19 IS 4 BP 231 EP 238 DI 10.1080/14767050600593387 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 054XN UT WOS:000238412000007 PM 16854697 ER PT J AU Wendler, DS AF Wendler, DS TI Assent in paediatric research: theoretical and practical considerations SO JOURNAL OF MEDICAL ETHICS LA English DT Article ID PARENTAL PERMISSION; INFORMED CONSENT; CLINICAL-TRIALS; CHILDREN AB Guidelines around the world require children to provide assent for their participation in most research studies. Yet, little further guidance is provided on how review committees should implement this requirement, including which children are capable of providing assent and when the requirement for assent may be waived on the grounds that the research offers participating children the potential for important clinical benefit. The present paper argues that the assent requirement is supported by the importance of allowing children who are capable to make their own decisions. This suggests children are capable of assent when they become able to understand the research in question. While development varies across individual children, existing data suggest most children develop this ability by approximately age 14. Until instruments are developed to assess the assent capacity of individual children, this age should be used as the threshold for assent. In addition, the importance of protecting children from harm suggests that the sustained dissent of all children, including those who are unable to provide assent, should be respected. While the assent requirement may be waived when research participation offers the potential for important medical benefit that is unavailable outside the research context, analysis suggests that children's sustained dissent should be respected in all cases. C1 NIH, Ctr Clin, Dept Clin Bioeth, Bethesda, MD 20892 USA. RP Wendler, DS (reprint author), NIH, Ctr Clin, Dept Clin Bioeth, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM dwendler@nih.gov NR 25 TC 45 Z9 46 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0306-6800 J9 J MED ETHICS JI J. Med. Ethics PD APR 1 PY 2006 VL 32 IS 4 BP 229 EP 234 DI 10.1136/jme.2004.011114 PG 6 WC Ethics; Medical Ethics; Social Issues; Social Sciences, Biomedical SC Social Sciences - Other Topics; Medical Ethics; Social Issues; Biomedical Social Sciences GA 027HU UT WOS:000236406800010 PM 16574878 ER PT J AU Yang, X Pfeiffer, RM Goldstein, AM AF Yang, X Pfeiffer, RM Goldstein, AM TI Influence of glutathione-S-transferase (GSTM1, GSTP1, GSTT1) and cytochrome p450 (CYP1A1, CYP2D6) polymorphisms on numbers of basal cell carcinomas (BCCs) in families with the naevoid basal cell carcinoma syndrome SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID CATALYTIC EFFICIENCY; GORLIN SYNDROME; HUMAN HOMOLOG; HIGH-RISK; CANCER; PHENOTYPE; VARIANTS; SKIN; ASSOCIATION; CONJUGATION AB Background: The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant multisystem disorder with variable expression. NBCCS patients have variable susceptibility to development of basal cell carcinoma (BCC). Previous studies have shown that polymorphisms of some metabolic genes encoding the cytochrome p450 (CYP) and glutathione-S- transferase (GST) enzymes influenced the numbers of BCCs in sporadic BCC cases. Objective: To determine whether allelic variants of these genes contribute to the variation in numbers of BCCs observed in NBCCS families. Methods: Genotyping and analysis was carried out in 152 members ( 69 affected and 83 unaffected) of 13 families with NBCCS for seven polymorphisms in five metabolic genes including CYP1A1, CYP2D6, GSTM1, GSTP1, and GSTT1. Results: GSTP1 Val(105) and GSTP1 Val(114) alleles were significantly associated with fewer BCC numbers ( odds ratio (OR)(105) = 0.55 ( 95% confidence interval, 0.35 to 0.88); OR114 = 0.20 (0.05 to 0.88)). The Val(105) allele showed a dose dependent effect (ORIle/Val = 0.58 (0.34 to 0.88); ORVal/Val = 0.34 (0.14 to 0.78)). In addition, fewer jaw cysts were observed in carriers of the three p450 polymorphisms (CYP1A1m1, CYP1A1m2, and CYP2D6*4) (ORCYP1A1m1 = 0.27 (0.12 to 0.58); ORCYP1A1m2 = 0.25 (0.08 to 0.78); ORCYP2D6* 4 = 0.33 (0.18 to 0.60)). Conclusions: Genetic variants might contribute to the variation in numbers of BCCs and jaw cysts observed in NBCCS families. C1 NCI, Genet Epidemiol Branch, DCEG, NIH,DHHS, Rockville, MD 20852 USA. RP Yang, X (reprint author), NCI, Genet Epidemiol Branch, DCEG, NIH,DHHS, 6120 Execut Blvd,Rm 7014, Rockville, MD 20852 USA. EM royang@mail.nih.gov NR 28 TC 11 Z9 11 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-2593 J9 J MED GENET JI J. Med. Genet. PD APR PY 2006 VL 43 IS 4 AR e16 DI 10.1136/jmg.2005.035006 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 028EO UT WOS:000236469900016 ER PT J AU Rothstein, EC Nauman, M Chesnick, S Balaban, RS AF Rothstein, EC Nauman, M Chesnick, S Balaban, RS TI Multi-photon excitation microscopy in intact animals SO JOURNAL OF MICROSCOPY-OXFORD LA English DT Article DE collagen; kidney; mitochondria; mouse; optical coupling; rabbit; skeletal muscle ID IN-VIVO; SKELETAL-MUSCLE; BLOOD-FLOW; LIGHT; SCATTERING; TISSUE AB Two-photon excitation fluorescence microscopy and backscattered-second harmonic generation microscopy permit the investigation of the subcellular events within living animals but numerous aspects of these experiments need to be optimized to overcome the traditional microscope geometry, motion and optical coupling to the subject. This report describes a stable system for supporting a living instrumented mouse or rabbit during endogenous reduced nicotinamide adenine dinucleotide and exogenous dye two-photon excitation fluorescence microscopy measurements, and backscattered-second harmonic generation microscopy measurements. The system was a modified inverted LSM510 microscope (Carl Zeiss, Inc., Thornwood, NY, U.S.A.) with a rotating periscope that converted the inverted scope to an upright format, with the objective located approximately, 15 cm from the centre of the microscope base, allowing easy placement of an instrumented animal. An Olympus 20x water immersion objective was optically coupled to the tissue, without a cover glass, via a saline bath or custom hydrated transparent gel. The instrumented animals were held on a specially designed holder that poised the animal under the objective as well as permitted different ventilation schemes to minimize motion. Using this approach, quality images were routinely collected in living animals from both the peripheral and body cavity organs. The remaining most significant issue for physiological studies using this approach is motion on the micrometre scale. Several strategies for motion compensation are described and discussed. C1 NHLBI, Cardiac Energet Lab, NIH, Dept Human Hlth Serv, Bethesda, MD 20892 USA. RP Rothstein, EC (reprint author), NHLBI, Cardiac Energet Lab, NIH, Dept Human Hlth Serv, Bldg 10,Room B1D416,9000 Rockville Pike, Bethesda, MD 20892 USA. EM emilyr@nih.gov FU NHLBI NIH HHS [Z01 HL004601-18] NR 13 TC 32 Z9 32 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-2720 J9 J MICROSC-OXFORD JI J. Microsc.-Oxf. PD APR PY 2006 VL 222 BP 58 EP 64 DI 10.1111/j.1365-2818.2006.01570.x PN 1 PG 7 WC Microscopy SC Microscopy GA 045KE UT WOS:000237740200008 PM 16734715 ER PT J AU Inoue, Y Peters, LL Yim, SH Inoue, J Gonzalez, FJ AF Inoue, Y Peters, LL Yim, SH Inoue, J Gonzalez, FJ TI Role of hepatocyte nuclear factor 4 alpha in control of blood coagulation factor gene expression SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE HNF4 alpha; coagulation factors; knockout mice; gene expression ID DEFICIENT MOUSE MODEL; FACTOR-XII GENE; HEMOPHILIA-B; FACTOR-V; TRANSCRIPTION FACTORS; FACTOR-X; IN-VIVO; PROMOTER; RECEPTOR; MICE AB Hepatocyte nuclear factor 4 alpha (HNF4 alpha) plays an important role in the maintenance of many liver-specific functions. Liver-specific HNF alpha-null mice were used to determine whether hepatic HNF4 alpha regulates blood coagulation in vivo. These mice exhibited reduced expression of hepatic coagulation factors V, IX, XI, XII, and XIIIB and a prolonged activated partial thromboplastin time but not prothrombin time. Promoter analysis of the mouse FXII and FXIIIB genes was performed to determine whether HNF4 alpha directly regulates the genes encoding these coagulation factors. Sequence analysis revealed the presence of one and two HNF4 alpha binding sites in the mouse FXII and FXIIIB genes, respectively. Using transient transfection and electrophoretic mobility shift analyses with the mouse FXII and FXIIIB promoters, it was established that the high levels of promoter activity were dependent on HNF4a binding sites and the expression of HNF4 alpha. In conclusion, HNF4 alpha has a critical role in blood coagulation homeostasis by directing transcription of the FXII and XIIIB genes. C1 NCI, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Jackson Lab, Bar Harbor, ME 04609 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, Ctr Canc Res, NIH, 9000 Rockville Pike,Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov FU Intramural NIH HHS; NHLBI NIH HHS [HL66611, U01 HL066611] NR 45 TC 33 Z9 33 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD APR PY 2006 VL 84 IS 4 BP 334 EP 344 DI 10.1007/s00109-005-0013-5 PG 11 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 042VU UT WOS:000237559500009 PM 16389552 ER PT J AU Stefano, L Al Sarraj, J Rossler, OG Vinson, C Thiel, G AF Stefano, L Al Sarraj, J Rossler, OG Vinson, C Thiel, G TI Up-regulation of tyrosine hydroxylase gene transcription by tetradecanoylphorbol acetate is mediated by the transcription factors Ets-like protein-1 (Elk-1) and Egr-1 SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE CATH.a cells; Egr-1; Ets-like protein-1; tyrosine hydroxylase ID CATECHOLAMINERGIC IMMORTALIZED NEURON; CORTICOTROPIN-RELEASING-FACTOR; SIGNAL-TRANSDUCTION PATHWAYS; EPIDERMAL GROWTH-FACTOR; TERNARY COMPLEX FACTORS; CAMP RESPONSE ELEMENT; PHORBOL ESTER; BIOLOGICAL-ACTIVITY; TRANSGENIC MICE; CELL-LINES AB Tyrosine hydroxylase is the rate-limiting enzyme in the biosynthesis of catecholamines. Expression of the tyrosine hydroxylase gene is regulated at the transcriptional level by extracellular signalling molecules, including epidermal growth factor (EGF), nerve growth factor (NGF) and glucocorticoids. We have analysed the stimulation of tyrosine hydroxylase gene transcription by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in noradrenergic locus coeruleus-like CATH.a cells and observed a striking enhancement of the transcriptional activation potential of the ternary complex factor Ets-like protein-1 (Elk-1), a key transcriptional regulator of serum response element-driven gene transcription. Likewise, TPA strongly up-regulated the biosynthesis of the transcription factor Egr-1 via distal serum response elements within the Egr-1 5'-flanking region. Subsequently, enhancement of the transcriptional activation potential of Egr-1 was observed. Overexpression of Egr-1 was sufficient to activate transcription of a tyrosine hydroxylase promoter/reporter gene, corroborating the view that the tyrosine hydroxylase gene is a target gene of Egr-1. Expression of dominant-negative mutants of Elk-1 or Egr-1 impaired TPA-induced stimulation of a tyrosine hydroxylase promoter/reporter gene transcription. In contrast, dominant-negative mutants of the transcription factors activating transcription factor (ATF)-2, ATF4, cAMP response element-binding protein, c-Jun and CCAAT/enhancer binding protein (C/EBP) did not change TPA-induced tyrosine hydroxylase promoter activity, indicating that these proteins are not part of the TPA-mediated signalling cascade directed towards the tyrosine hydroxylase gene. C1 Univ Saarland, Med Ctr, Dept Med Biochem & Mol Biol, D-66421 Homburg, Germany. NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. RP Thiel, G (reprint author), Univ Saarland, Med Ctr, Dept Med Biochem & Mol Biol, Bldg 44, D-66421 Homburg, Germany. EM gerald.thiel@uniklinik-saarland.de NR 40 TC 34 Z9 36 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2006 VL 97 IS 1 BP 92 EP 104 DI 10.1111/j.1471-4159.2006.03749.x PG 13 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 021LZ UT WOS:000235986000009 PM 16515541 ER PT J AU Rath, MF Munoz, E Ganguly, S Morin, F Shi, Q Klein, DC Moller, M AF Rath, MF Munoz, E Ganguly, S Morin, F Shi, Q Klein, DC Moller, M TI Expression of the Otx2 homeobox gene in the developing mammalian brain: embryonic and adult expression in the pineal gland SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE brain development; cone-rod homeobox; homeobox; Otx2; pineal gland ID HYDROXYINDOLE-O-METHYLTRANSFERASE; SEROTONIN N-ACETYLTRANSFERASE; RETINOID-BINDING PROTEIN; CONE-ROD HOMEOBOX; RAT PINEAL; MESSENGER-RNA; ANTERIOR NEUROECTODERM; TRANSCRIPTION FACTORS; CIRCADIAN EXPRESSION; HOMEODOMAIN PROTEIN AB Otx2 is a vertebrate homeobox gene, which has been found to be essential for the development of rostral brain regions and appears to play a role in the development of retinal photoreceptor cells and pinealocytes. In this study, the temporal expression pattern of Otx2 was revealed in the rat brain, with special emphasis on the pineal gland throughout late embryonic and postnatal stages. Widespread high expression of Otx2 in the embryonic brain becomes progressively restricted in the adult to the pineal gland. Crx (cone-rod homeobox), a downstream target gene of Otx2, showed a pineal expression pattern similar to that of Otx2, although there was a distinct lag in time of onset. Otx2 protein was identified in pineal extracts and found to be localized in pinealocytes. Total pineal Otx2 mRNA did not show day-night variation, nor was it influenced by removal of the sympathetic input, indicating that the level of Otx2 mRNA appears to be independent of the photoneural input to the gland. Our results are consistent with the view that pineal expression of Otx2 is required for development and we hypothesize that it plays a role in the adult in controlling the expression of the cluster of genes associated with phototransduction and melatonin synthesis. C1 Univ Copenhagen, Panum Inst, Inst Med Anat, DK-2200 Copenhagen, Denmark. NICHHD, Sect Neuroendocrinol, NIH, Bethesda, MD 20892 USA. RP Rath, MF (reprint author), Univ Copenhagen, Panum Inst, Inst Med Anat, Blegdamsvej 3, DK-2200 Copenhagen, Denmark. EM m.rath@mai.ku.dk OI Munoz, Estela/0000-0002-6701-1535; Rath, Martin/0000-0002-4047-6324 NR 61 TC 40 Z9 41 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2006 VL 97 IS 2 BP 556 EP 566 DI 10.1111/j.1471-4159.2006.03773.x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 026GU UT WOS:000236328200023 PM 16539656 ER PT J AU Zhang, PS Furukawa, K Opresko, PL Xu, XR Bohr, VA Mattson, MP AF Zhang, PS Furukawa, K Opresko, PL Xu, XR Bohr, VA Mattson, MP TI TRF2 dysfunction elicits DNA damage responses associated with senescence in proliferating neural cells and differentiation of neurons SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE astrocytes; ataxia telangiectasia mutated; hippcampal neurons; senescence; telomeric DNA damage; tumor cells ID DOUBLE-STRAND BREAKS; AMYLOID-PRECURSOR PROTEIN; ATAXIA-TELANGIECTASIA; TELOMERE DYSFUNCTION; HIPPOCAMPAL-NEURONS; INDUCED NEUROTOXICITY; CATALYTIC SUBUNIT; WERNER-SYNDROME; RETINOIC ACID; GROWTH ARREST AB TTelomeres are specialized structures at the ends of chromosomes that consist of tandem repeats of the DNA sequence TTAGGG and several proteins that protect the DNA and regulate the plasticity of the telomeres. The telomere-associated protein TRF2 (telomeric repeat binding factor 2) is critical for the control of telomere structure and function; TRF2 dysfunction results in the exposure of the telomere ends and activation of ATM (ataxia telangiectasin mutated)-mediated DNA damage response. Recent findings suggest that telomere attrition can cause senescence or apoptosis of mitotic cells, but the function of telomeres in differentiated neurons is unknown. Here, we examined the impact of telomere dysfunction via TRF2 inhibition in neurons ( primary embryonic hippocampal neurons) and mitotic neural cells (astrocytes and neuroblastoma cells). We demonstrate that telomere dysfunction induced by adenovirus-mediated expression of dominant-negative TRF2 (DN-TRF2) triggers a DNA damage response involving the formation of nuclear foci containing phosphorylated histone H2AX and activated ATM in each cell type. In mitotic neural cells DN-TRF2 induced activation of both p53 and p21 and senescence (as indicated by an up-regulation of beta-galactosidase). In contrast, in neurons DN-TRF2 increased p21, but neither p53 nor beta-galactosidase was induced. In addition, TRF2 inhibition enhanced the morphological, molecular and biophysical differentiation of hippocampal neurons. These findings demonstrate divergent molecular and physiological responses to telomere dysfunction in mitotic neural cells and neurons, indicate a role for TRF2 in regulating neuronal differentiation, and suggest a potential therapeutic application of inhibition of TRF2 function in the treatment of neural tumors. C1 Natl Inst Aging Intramural Res Program, Neurosci Lab, Baltimore, MD 21224 USA. Natl Inst Aging Intramural Res Program, Lab Mol Gerontol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), Natl Inst Aging Intramural Res Program, Neurosci Lab, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012; OI Opresko, Patricia/0000-0002-6470-2189 FU Intramural NIH HHS NR 74 TC 15 Z9 21 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 2006 VL 97 IS 2 BP 567 EP 581 DI 10.1111/j.1471-4159.2006.03779.x PG 15 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 026GU UT WOS:000236328200024 PM 16539655 ER PT J AU Ponzio, TA Ni, Y Montana, V Parpura, V Hatton, GI AF Ponzio, TA Ni, Y Montana, V Parpura, V Hatton, GI TI Vesicular glutamate transporter expression in supraoptic neurones suggests a glutamatergic phenotype SO JOURNAL OF NEUROENDOCRINOLOGY LA English DT Article DE VGLUT; hypothalamus; dendritic release; oxytocin; vasopressin; astrocytes; meninges ID HYPOTHALAMIC MAGNOCELLULAR NEURONS; MAIN OLFACTORY-BULB; RAT HYPOTHALAMUS; NUCLEUS AFFERENTS; EXCITATORY NEURONS; OXYTOCIN NEURONS; SYNAPTIC INPUTS; LOCALIZATION; VASOPRESSIN; RELEASE AB Magnocellular neuroendocrine cells of the supraoptic nucleus (SON) release the peptides oxytocin (OT) and vasopressin (VP) from their dendrites and terminals. In addition to peptide-containing large dense-core vesicles, axon terminals from these cells contain clear microvesicles that have been shown to contain glutamate. Using multilabelling confocal microscopy, we investigated the presence of vesicular glutamate transporters (VGLUTs) in astrocytes as well as VP and OT neurones of the SON. Simultaneous probing of the SON with antibodies against VGLUT isoforms 1-3, OT, VP and glial fibrillary acidic protein (GFAP) revealed the presence of VGLUT-2 in somata and dendrites of SON neurones. Immunoreactivity (-ir) for VGLUT-3 was also detected in both OT and VP neurones as well as in GFAP-ir astrocytes and other cells of the ventral glial lamina. Colocalisation of VGLUT-2 and VGLUT-3 in individual SON neurones was also examined and VGLUT-ir with both antibodies could be detected in both types of SON neurones. Although VGLUT-1-ir was strong lateral to the SON, only sparse labelling was apparent within the nucleus, and no colocalisation with either SON neurones or astrocytes was observed. The SON or the SON plus its surrounding perinuclear zone was probed using the reverse transcriptase-polymerase chain reaction and the presence of mRNA for all three VGLUT isoforms was detected. These results suggest that similar arrangements of transmitters exist in SON neuronal dendrites and their neurohypophysial terminals and that magnocellular neuroendocrine somata and dendrites may be capable of glutamatergic transmission. C1 Univ Calif Riverside, Dept Cell Biol & Neurosci, Riverside, CA 92521 USA. RP Ponzio, TA (reprint author), NINDS, NIH, 49-5C68, Bethesda, MD 20892 USA. EM ponziot@mail.nih.gov RI Parpura, Vladimir/A-1242-2010 OI Parpura, Vladimir/0000-0002-4643-2197 FU NINDS NIH HHS [NS009140, R01 NS009140] NR 46 TC 21 Z9 21 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0953-8194 J9 J NEUROENDOCRINOL JI J. Neuroendocrinol. PD APR PY 2006 VL 18 IS 4 BP 253 EP 265 DI 10.1111/j.1365-2826.2006.01410.x PG 13 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 015GB UT WOS:000235538800003 PM 16503920 ER PT J AU Kelly, MP Lee, FT Smyth, FE Brechbiel, MW Scott, AM AF Kelly, MP Lee, FT Smyth, FE Brechbiel, MW Scott, AM TI Enhanced efficacy of Y-90-radiolabeled anti-Lewis Y humanized monoclonal antibody hu3S193 and paclitaxel combined-modality radioimmunotherapy in a breast cancer model SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE humanized monoclonal antibody; breast cancer; combined-modality radioimmunotherapy ID NUDE-MOUSE MODEL; IN-VIVO; CARCINOMA XENOGRAFT; SOLID TUMORS; APOPTOSIS; TAXOL; BIODISTRIBUTION; THERAPY; IN-111; 3S193 AB Radioimmunotherapy (RIT) of solid tumor is often limited in efficacy because of restrictions in achieved tumor dose. In an effort to overcome this, the combination of RIT with other therapeutic modalities was investigated in an animal model of breast carcinoma. The rationale for this combined-modality RIT (CMRIT) was to increase the therapeutic efficacy of RIT through the use of paclitaxel to arrest cells in the radiosensitive G(2)/M phase of the cell cycle. Methods: In this study, the biodistribution and therapeutic efficacy of Y-90-radiolabeled humanized anti-Lewis Y hu3S193 monoclonal antibody (Y-90-hu3S193) RIT in combination with paclitaxel chemotherapy was explored in a Lewis Y-expressing MCF-7 tumor xenografted BALB/c nude mouse model of breast cancer. Results: Biodistribution studies demonstrated excellent tumor targeting and limited normal tissue uptake by Y-90-hu3S193. A therapeutic study with established tumors assessed Y-90-hu3S193 as a single agent and demonstrated significant antitumor effects in all animals receiving a single intravenous 1.85 or 3.70 MBq dose of this treatment compared with phosphate-buffered saline placebo controls (P = 0.0008 vs. P < 0.0001). Complete responses were observed in all animals in the 3.70 MBq study arm for the duration of the study. Single-dose 90Y-hu3S193 plus paclitaxel (600 mu g) CMRIT displayed improved efficacy over single-modality therapies, with a significant difference (P < 0.0001) between the mean percentage change in tumor volume in mice receiving 0.46 MBq Y-90-hu3S193 alone and when combined with 600 mu g paclitaxel. Conclusion: The significant efficacy of Y-90-hu3S193 and paclitaxel CMRIT at low radiation doses in this model of breast carcinoma indicates its therapeutic potential and warrants further investigation into this promising therapeutic approach. C1 Austin Hosp, Ludwig Inst Canc Res, Tumour Targeting Program, Heidelberg, Vic 3084, Australia. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Scott, AM (reprint author), Austin Hosp, Ludwig Inst Canc Res, Tumour Targeting Program, Studley Rd, Heidelberg, Vic 3084, Australia. EM andrew.scott@ludwig.edu.au FU Intramural NIH HHS NR 40 TC 31 Z9 31 U1 0 U2 2 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD APR PY 2006 VL 47 IS 4 BP 716 EP 725 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 029VX UT WOS:000236593600035 PM 16595507 ER PT J AU Tamura, T Picciano, MF AF Tamura, T Picciano, MF TI Folate determination in human milk SO JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY LA English DT Letter C1 Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Tamura, T (reprint author), Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. NR 12 TC 4 Z9 5 U1 0 U2 0 PU CENTER ACADEMIC PUBL JAPAN PI TOKYO PA 2-4-16 YAYOI, BUNKYO-KU, TOKYO, 113-0032, JAPAN SN 0301-4800 J9 J NUTR SCI VITAMINOL JI J. Nutr. Sci. Vitaminol. PD APR PY 2006 VL 52 IS 2 BP 161 EP 161 DI 10.3177/jnsv.52.161 PG 1 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 038IX UT WOS:000237214200013 PM 16802699 ER PT J AU Warburton, G Brahim, JS AF Warburton, G Brahim, JS TI Intraorbital hematoma after removal of upper third molar: A case report SO JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY LA English DT Article ID SPONTANEOUS SUBPERIOSTEAL HEMATOMA; ORBITAL HEMORRHAGE; FRACTURES; SURGERY; DISEASE; TRAUMA C1 NIDCR, NIH, Bethesda, MD 20892 USA. RP Brahim, JS (reprint author), NIDCR, NIH, Bldg 10,Room 1N-112,10 Ctr Dr, Bethesda, MD 20892 USA. EM jbrahim@mail.nih.gov NR 22 TC 2 Z9 3 U1 0 U2 0 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0278-2391 J9 J ORAL MAXIL SURG JI J. Oral Maxillofac. Surg. PD APR PY 2006 VL 64 IS 4 BP 700 EP 704 DI 10.1016/j.joms.2004.10.014 PG 5 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 031CT UT WOS:000236682400021 PM 16546653 ER PT J AU Raimondi, AR Molinolo, AA Itoiz, ME AF Raimondi, AR Molinolo, AA Itoiz, ME TI Fibroblast growth factor-2 expression during experimental oral carcinogenesis. Its possible role in the induction of pre-malignant fibrosis SO JOURNAL OF ORAL PATHOLOGY & MEDICINE LA English DT Article DE fibroblastic growth factor-2; hamster cheek pouch model; oral cancer ID SQUAMOUS-CELL CARCINOMA; HAMSTER BUCCAL POUCH; SUBMUCOUS FIBROSIS; FACTOR RECEPTOR; FACTOR-ALPHA; TGF-ALPHA; FACTOR-I; CANCER; TUMOR; CANCERIZATION AB Background: The fibroblastic growth factor (FGF)-2 has been shown to induce angiogenesis in several tumor types. To date, the activity of FGF during the development of oral pre-cancerous lesions has not been analyzed. We herein evaluated the role of FGF-2 in the pre-cancerous and cancerous lesions in the hamster cheek pouch oral cancer model. Methods: Expression of FGF-2 and its receptors FGFR-2 and FGFR-3 was assessed by immunohistochemistry at different stages of the carcinogenesis protocol. Activity of FGF-2 isoforms was analyzed by Western blots. Results: Increase and abnormal localization of FGF-2 expression was evident in cancerized epithelium before it was possible to detect morphologic alterations. The changes in FGF-2 are concomitant with the evolution of subepithelial fibrosis. Immunolabeling of carcinomas was faint or completely negative. Increases of FGF-2 activity are mainly due to the increase in the 18 kDa isoform. Receptors 2 and 3 of FGF are present in epithelium, fibroblasts, and vascular endothelia of control samples and in all stages of malignant transformation. Conclusions: Our results would suggest a role for FGF-2 in the epithelium-connective interactions and a deregulation of its expression in the early stages of oral cancerization. In pre-cancerous tissue FGF-2 would play a central role in the development of fibrosis and a more collateral role in the induction of angiogenesis. The data would indicate its involvement in the process via the 18 kDa isoform. C1 Univ Buenos Aires, Fac Dent, Dept Oral Pathol, RA-1122 Buenos Aires, DF, Argentina. Natl Inst Dent & Craniofacial Res, Oral & Pharingeal Canc Branch, NIH, Bethesda, MD USA. RP Itoiz, ME (reprint author), Univ Buenos Aires, Fac Dent, Dept Oral Pathol, MT de Alvear 2142, RA-1122 Buenos Aires, DF, Argentina. EM postmast@cyt.odon.uba.ar NR 28 TC 9 Z9 12 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0904-2512 J9 J ORAL PATHOL MED JI J. Oral Pathol. Med. PD APR PY 2006 VL 35 IS 4 BP 212 EP 217 DI 10.1111/j.1600-0714.2006.00394.x PG 6 WC Dentistry, Oral Surgery & Medicine; Pathology SC Dentistry, Oral Surgery & Medicine; Pathology GA 019MY UT WOS:000235842200005 PM 16519768 ER PT J AU Farrar, JT Dworkin, RH Max, MB AF Farrar, JT Dworkin, RH Max, MB TI Use of the cumulative proportion of responders analysis graph to present pain data over a range of cut-off points Making clinical trial data more understandable SO JOURNAL OF PAIN AND SYMPTOM MANAGEMENT LA English DT Article DE pain measurement; data interpretation; statistical; clinical trials; research design; treatment outcome; pain ID TRANSMUCOSAL FENTANYL CITRATE; RANDOMIZED CONTROLLED-TRIALS; DICHOTOMOUS OUTCOME MEASURES; PLACEBO-CONTROLLED TRIAL; QUALITY-OF-LIFE; IMPORTANT DIFFERENCE; ANALGESICS; INTENSITY; PATIENT; SCALES AB In randomized controlled trials, no single definition of response is ideal for all purposes. We propose a method to present in a simple fashion the likelihood of response over a full range of response levels, which will facilitate a better understanding of clinical trial data. We present the technique called the cumulative Proportion of responders analysis (CPRA) and its application to four pain clinical trial data sets as examples. The CPRA can be used to present the Proportion of responders over the entire range of possible cut-off points as a graph. This allows the reader to compare treatment groups at any responder level that is valid for their patient population. Whether as a primary or secondary approach to a clinical trial of pain therapy, the display of data in a CPRA format may be useful in the understanding of,results and applicability to patient care. C1 Univ Penn, Dept Biostat & Epidemiol, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Ctr Educ & Res Therapeut, Philadelphia, PA 19104 USA. Univ Rochester, Dept Anesthesiol, Rochester, NY USA. Natl Inst Dental & Craniofacial Res, NIH, Bethesda, MD USA. RP Farrar, JT (reprint author), 423 Guardian Dr,Room 816,Blockley Hall, Philadelphia, PA 19104 USA. EM jfarrar@cceb.med.upenn.edu RI Farrar, John/A-1037-2007 OI Farrar, John/0000-0001-8656-5157 FU NCI NIH HHS [R01-CA73797]; NINDS NIH HHS [KO8-NS01865] NR 22 TC 57 Z9 57 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0885-3924 J9 J PAIN SYMPTOM MANAG JI J. Pain Symptom Manage. PD APR PY 2006 VL 31 IS 4 BP 369 EP 377 DI 10.1016/j.jpainsymman.2005.08.018 PG 9 WC Health Care Sciences & Services; Medicine, General & Internal; Clinical Neurology SC Health Care Sciences & Services; General & Internal Medicine; Neurosciences & Neurology GA 041UN UT WOS:000237481900010 PM 16632085 ER PT J AU Gulmann, C Sheehan, KM Kay, EW Liotta, LA Petricoin, EF AF Gulmann, C Sheehan, KM Kay, EW Liotta, LA Petricoin, EF TI Array-based proteomics: mapping of protein circuitries for diagnostics, prognostics, and therapy guidance in cancer SO JOURNAL OF PATHOLOGY LA English DT Review DE proteomics; protein microarrays; biomarker discovery; bioinformatics; cancer ID ROLLING-CIRCLE AMPLIFICATION; TISSUE MICROARRAYS; ANTIBODY MICROARRAYS; GENE-EXPRESSION; SIGNALING NETWORK; BREAST-CANCER; CARCINOMA; PATHOLOGY; TUMORS; IMMUNOHISTOCHEMISTRY AB The human proteome, due to the enormity of post-translational permutations that result in large numbers of isoforms, is much more complex than the genome and alterations in cancer can occur in ways that are not predictable by translational analysis alone. Proteomic analysis therefore represents a more direct way of investigating disease at the individual patient level. Furthermore, since most novel therapeutic targets are proteins, proteomic analysis potentially has a central role in patient care. At the same time, it is becoming clear that mapping entire networks rather than individual markers may be necessary for robust diagnostics as well as tailoring of therapy. Consequently, there is a need for high-throughput multiplexed proteomic techniques, with the capability of scanning multiple cases and analysing large numbers of endpoints. New types of protein arrays combined with advanced bioinformatics are currently being used to identify molecular signatures of individual tumours based on protein pathways and signalling cascades. It is envisaged that analysing the cellular 'circuitry' of ongoing molecular networks will become a powerful clinical tool in patient management. Copyright (c) 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. C1 Beaumont Hosp, Dept Pathol, Dublin 9, Ireland. Royal Coll Surgeons Ireland, Dublin 2, Ireland. NCI, FDA, Clin Prote Program, Pathol Lab, Bethesda, MD 20892 USA. George Mason Univ, Ctr Appl Prote & Mol Med, Manassas, VA USA. RP Gulmann, C (reprint author), Beaumont Hosp, Dept Pathol, Beaumont Rd, Dublin 9, Ireland. EM cgulmann@rcsi.ie NR 65 TC 74 Z9 78 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0022-3417 J9 J PATHOL JI J. Pathol. PD APR PY 2006 VL 208 IS 5 BP 595 EP 606 DI 10.1002/path.1958 PG 12 WC Oncology; Pathology SC Oncology; Pathology GA 028HT UT WOS:000236478500001 PM 16518808 ER PT J AU Shneider, BL Brown, MB Haber, B Whitington, PF Schwarz, K Squires, R Bezerra, J Shepherd, R Rosenthal, P Hoofnagle, JH Sokol, RJ AF Shneider, Benjamin L. Brown, Morton B. Haber, Barbara Whitington, Peter F. Schwarz, Kathleen Squires, Robert Bezerra, Jorge Shepherd, Ross Rosenthal, Philip Hoofnagle, Jay H. Sokol, Ronald J. CA Biliary Atresia Res Consortium TI A multicenter study of the outcome of biliary atresia in the United States, 1997 to 2000 SO JOURNAL OF PEDIATRICS LA English DT Article ID HEPATOPORTOENTEROSTOMY; PORTOENTEROSTOMY; PROGNOSIS; SURGERY; LIVER AB Objective To determine the prognostic factors and optimal approaches to the diagnosis and management of biliary atresia, the leading indication for liver transplantation in children. Study design A retrospective study was performed of all children who underwent hepatoportoenterostoiny (HPE) for biliary atresia between 1997 and 2000 at 9 centers in the United States. Outcome at age 24 months was correlated with demographic and clinical parameters. Results A total of 104 children underwent HPE; 25% had congenital anomalies, and outcome was worse in those with biliary atresia splenic malformation syndrome. Diagnostic and clinical approaches varied, although specific approaches did not appear to correlate with outcome. The average age at referral was 53 days. and the average age at HPE was 61. days. At age 24 months, 58 children were alive with their native liver, 42 had undergone liver transplantation (37 alive, 5 dead), and 4 had died without undergoing transplantation. Kaplan-Meier analysis of survival without liver transplantation revealed markedly improved survival in children with total bilirubin level < 2 mg/dL at 3 months after HPE (84% vs 16%; P < .0001). Conclusions Outcome in the study centers was equivalent to that reported in other countries. Total bilirubin in early follow-up after HPE was highly predictive of outcome. Efforts to improve bile flow after HPE may lead to improved outcome in children with biliary atresia. C1 Mt Sinai Med Ctr, Dept Pediat, New York, NY 10029 USA. Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA. Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. Childrens Mem Hosp, Dept Pediat, Chicago, IL 60614 USA. Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD USA. Childrens Hosp Pittsburgh, Dept Pediat, Pittsburgh, PA 15213 USA. Childrens Hosp, Med Ctr, Dept Pediat, Cincinnati, OH 45229 USA. Washington Univ, Dept Pediat, Sch Med, St Louis, MO 63130 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. NIDDK, Bethesda, MD USA. Univ Colorado, Dept Pediat, Sch Med, Denver, CO 80202 USA. Childrens Hosp, Denver, CO 80218 USA. RP Shneider, BL (reprint author), Mt Sinai Med Ctr, Dept Pediat, Box 1656,1 Gustave L Levy Pl, New York, NY 10029 USA. EM Benjamin.Shneider@mssm.edu FU NIDDK NIH HHS [U01DK062453, U01DK 062445, U01DK 062481, U01DK062436, U01DK062452, U01DK062456, U01DK062466, U01DK062497, U01DK062500, U01DK062503] NR 18 TC 142 Z9 154 U1 1 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD APR PY 2006 VL 148 IS 4 BP 467 EP 474 DI 10.1016/j.jpeds.2005 PG 8 WC Pediatrics SC Pediatrics GA 040VO UT WOS:000237409100011 PM 16647406 ER PT J AU Kozak, MN Marsh, AA Wegner, DM AF Kozak, MN Marsh, AA Wegner, DM TI What do I think you're doing? Action identification and mind attribution SO JOURNAL OF PERSONALITY AND SOCIAL PSYCHOLOGY LA English DT Article DE mind attribution; dehumanization; mentalizing; mind perception; theory of mind ID LINGUISTIC INTERGROUP BIAS; OTHERS; PERSPECTIVE; KNOWLEDGE; EMOTIONS; BEHAVIOR; PEOPLE; MOTION; AGENCY; SELF AB The authors examined how a perceiver's identification of a target person's actions covaries with attributions of mind to the target. The authors found in Study 1 that the attribution of intentionality and cognition to a target was associated with identifying the target's action in terms of high-level effects rather than low-level details. In Study 2, both action identification and mind attribution were greater for a liked target, and in Study 3, they were reduced for a target suffering misfortune. In Study 4, it was again found that action identification and mind attribution were greater for a liked target, but like that for the self or a liked other, positive actions were identified at higher levels than negative actions, with the reverse being true for disliked others. In Study 5, the authors found that instructing participants to adopt the target's perspective did not affect mind attribution but did lead to higher level identifications of the target's actions. C1 Harvard Univ, Dept Psychol, Cambridge, MA 02138 USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Kozak, MN (reprint author), Roosevelt Univ, Dept Psychol, 430 S Michigan Ave, Chicago, IL 60605 USA. EM mkozak@roosevelt.edu FU NIMH NIH HHS [MH-067332, MH-49127] NR 41 TC 71 Z9 74 U1 3 U2 29 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0022-3514 EI 1939-1315 J9 J PERS SOC PSYCHOL JI J. Pers. Soc. Psychol. PD APR PY 2006 VL 90 IS 4 BP 543 EP 555 DI 10.1037/0022-3514.90.4.543 PG 13 WC Psychology, Social SC Psychology GA 040HV UT WOS:000237370500002 PM 16649854 ER PT J AU Lee, YS Wan, J Kim, BJ Bae, MA Song, BJ AF Lee, YS Wan, J Kim, BJ Bae, MA Song, BJ TI Ubiquitin-dependent degradation of p53 protein despite phosphorylation at its N terminus by acetaminophen SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID MOUSE-LIVER PROTEINS; C6 GLIOMA-CELLS; CYTOCHROME P4502E1; COVALENT BINDING; DNA-BINDING; HEPATOTOXICITY; APOPTOSIS; DEHYDROGENASE; CYTOTOXICITY; PROTECTION AB We previously reported that acetaminophen (APAP, 4-hydroxyacetanilide) caused apoptosis of C6 glioma cells. Therefore, we hypothesized that the level of p53, which usually stimulates apoptosis, might be increased after APAP exposure. However, APAP exposure for 24 h markedly decreased the p53 content and its downstream target p21 in a concentration-dependent manner. Reduction of p53 was not accompanied by a decrease in p53 mRNA in C6 glioma cells, suggesting that p53 was mainly affected at the protein level. Unexpectedly, APAP stimulated phosphorylation of p53 at Ser15, Ser20, and Ser37, which usually elevates p53 content. However, phosphorylation of these residues did not prevent APAP-induced decrease in p53. The p53 reduction was independent from the level of phospho-Akt, which is known to promote p53 degradation. Immunoblot analysis of the immunoprecipitated p53 revealed that increased amounts of murine double minute 2 (mdm2) and ubiquitin were bound to p53 during its degradation. Lactacystin and N-benzoyloxycarbonyl (Z)-Leu-Leu-leucinal (MG132), inhibitors of proteasomal proteolysis, prevented the decrease, supporting the proteasomal degradation of p53 upon APAP exposure. Pretreatment with chlormethiazole, an inhibitor of ethanol- inducible CYP2E1, significantly lowered the CYP2E1 enzyme activity and the rate of APAP-induced cell death while it prevented the reduction of p53 and p21 in C6 glioma cells. A nontoxic analog of APAP, 3-hydroxyacetanilde, did not reduce p53 and p21 contents in C6 glioma cells and LLC-PK1 porcine kidney cells. Taken together, our results show that APAP or its reactive metabolite(s) can directly reduce the p53 content through mdm2-mediated ubiquitin conjugation, despite phosphorylation of p53 at its N terminus. C1 NIAAA, Lab Membrane Biochem & Biophys, Bethesda, MD 20892 USA. RP Song, BJ (reprint author), NIAAA, Lab Membrane Biochem & Biophys, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bjs@mail.nih.gov FU Intramural NIH HHS; NIAAA NIH HHS [Z01 AA000036-19] NR 40 TC 15 Z9 16 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 2006 VL 317 IS 1 BP 202 EP 208 DI 10.1124/jpet.105.096719 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 024DT UT WOS:000236175900024 PM 16330492 ER PT J AU Yasar, S Justinova, Z Lee, SH Stefanski, R Goldberg, SR Tanda, G AF Yasar, S Justinova, Z Lee, SH Stefanski, R Goldberg, SR Tanda, G TI Metabolic transformation plays a primary role in the psychostimulant-like discriminative-stimulus effects of selegiline [(R)-(-)-deprenyl] SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID L-DEPRENYL SELEGILINE; AMINO-ACID DECARBOXYLASE; PLACEBO-CONTROLLED TRIAL; MONOAMINE OXIDASE-B; MAO-B; BETA-PHENYLETHYLAMINE; DRUG DISCRIMINATION; DOUBLE-BLIND; AMPHETAMINE; DOPAMINE AB l-Deprenyl [selegiline, (R)-(-)-deprenyl] is a selective inhibitor of monoamine oxidase B (MAO-B) used in the treatment of Parkinson's disease and proposed as an antidepressant and an aid for cigarette-smoking cessation and treatment of psychostimulant abuse. Beneficial therapeutic effects of (R)-(-)-deprenyl may also result from indirect actions. Brain levels of dopamine and beta-phenylethylamine (beta-PEA), a behaviorally active endogenous trace amine, increase after (R)-(-)-deprenyl treatment due to MAO-B blockade and (R)-(-)-deprenyl is metabolized to (R)-(-)-methamphetamine and (R)-(-)-amphetamine, suggesting that (R)-(-)-deprenyl may have psychostimulant-like behavioral effects. Indeed, (R)-(-)-deprenyl produces psychostimulant-like discriminative-stimulus effects in experimental animals. Here, we tested the hypothesis that psychostimulant-like behavioral effects of (R)-(-)-deprenyl are mainly mediated by its metabolites. Male Fisher F344 rats were trained to discriminate i.p. injection of 1.0 mg/kg (S)-(-)-methamphetamine or 10.0 mg/kg cocaine from injection of saline using two-lever choice schedules of food delivery or stimulus shock termination. When (R)-(-)-deprenyl was tested by substitution, it had (S)-(-)-methamphetamine- and cocaine-like discriminative-stimulus effects, but only at doses of 10 to 30 mg/kg, doses 10 to 20 times higher than those selective for MAO-B inhibition. Ro 16-6491 [N-(2-aminoethyl)-4-chlorobenzamide hydrochloride], a selective inhibitor of MAO-B enzyme activity without psychoactive metabolites, had no psychostimulant-like discriminative effects. In addition, blockade of (R)-(-)-deprenyl's metabolism with SKF 525A (beta-DEAE-diphenylpropylacetate hydrochloride; 50 mg/kg i.p.) reduced or eliminated (R)-(-)-deprenyl's psychostimulant-like discriminative effects. When beta-PEA synthesis was blocked by NSD 1015 (m-hydroxy-benzyl-hydrazine; 30 mg/kg i.p.), there was a modest reversal of (R)-(-)-deprenyl's psychostimulant-like discriminative effects under some conditions, indicating a facilitatory modulation of the psychostimulant-like discriminative effects of (R)-(-)-deprenyl metabolites by elevated levels of beta-PEA under certain conditions. C1 Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Dept Hlth & Human Serv,NIH, Baltimore, MD USA. Natl Inst Drug Abuse, Psychobiol Sect, Medicat Dev Res Branch,Intramural Res Program, Dept Hlth & Human Serv,NIH, Baltimore, MD USA. RP Yasar, S (reprint author), Johns Hopkins Univ, Sch Med, Div Geriatr Med & Gerontol, 5505 Johns Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM syasar@jhmi.edu RI Tanda, Gianluigi/B-3318-2009; Justinova, Zuzana/A-9109-2011 OI Tanda, Gianluigi/0000-0001-9526-9878; Justinova, Zuzana/0000-0001-5793-7484 FU Intramural NIH HHS NR 47 TC 8 Z9 9 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 2006 VL 317 IS 1 BP 387 EP 394 DI 10.1124/jpet.105.096263 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 024DT UT WOS:000236175900046 PM 16352699 ER PT J AU Brill, SS Furimsky, AM Ho, MN Furniss, MJ Li, Y Green, AG Bradford, WW Green, CE Kapetanovic, IM Iyer, LV AF Brill, SS Furimsky, AM Ho, MN Furniss, MJ Li, Y Green, AG Bradford, WW Green, CE Kapetanovic, IM Iyer, LV TI Glucuronidation of trans-resveratrol by human liver and intestinal microsomes and UGT isoforms SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article ID BILIRUBIN UDP-GLUCURONOSYLTRANSFERASE; NATURAL-PRODUCT PRESENT; IN-VITRO; RED WINE; ACTIVE METABOLITE; INHIBITION; EXPRESSION; IDENTIFICATION; RATS; 1A1 AB Resveratrol (trans-resveratrol, trans-3,5,4'-trihydroxystilbene) is a naturally occurring stilbene analogue found in high concentrations in red wine. There is considerable research interest to determine the therapeutic potential of resveratrol, as it has been shown to have tumour inhibitory and antioxidant properties. This study was performed to investigate the glucuronidation of resveratrol and possible drug interactions via glucuronidation. Two glucuronide conjugates, resveratrol 3-O-glucuronide and resveratrol 4'-O-glucuronide, were formed by human liver and intestinal microsomes. UGT1A1 and UGT1A9 were predominantly responsible for the formation of the 3-O-glucuronide (K-m = 149 mu m) and 4'-O-glucuronide (K-m = 365 mu m), respectively. The glucuronide conjugates were formed at higher levels (up to 10-fold) by intestinal rather than liver microsomes. Resveratrol was co-incubated with substrates of UGT1A1 (bilirubin and 7-ethyl-10-hydroxycamptothecin (SN-38)) and UGT1A9 (7-hydroxytrifluoromethyl coumarin (7-HFC)). No major changes were noted in bilirubin glucuronidation in the presence of resveratrol. Resveratrol significantly inhibited the glucuronidation of SN-38 (K-i = 6.2 +/- 2.1 mu m) and 7-HFC (K-i =0.6 0.2 mu m). Hence, resveratrol has the potential to inhibit the glucuronidation of concomitantly administered therapeutic drugs or dietary components that are substrates of UGT1A1 and UGT1A9. C1 SRI Int, Toxicol & Metab Biosci Div, Menlo Pk, CA 94025 USA. SRI Int, Dept Med Chem, Biosci Div, Menlo Pk, CA 94025 USA. NCI, Chemoprevent Agent Dev Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Iyer, LV (reprint author), SRI Int, Toxicol & Metab Biosci Div, 333 Ravenswood Ave,PS347, Menlo Pk, CA 94025 USA. EM lalitha.iyer@sri.com FU NCI NIH HHS [CA102405, N01-CN-25135] NR 60 TC 38 Z9 42 U1 0 U2 5 PU PHARMACEUTICAL PRESS-ROYAL PHARMACEUTICAL SOC GREAT BRITIAN PI LONDON PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD APR PY 2006 VL 58 IS 4 BP 469 EP 479 DI 10.1211/jpp.58.4.0006 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 034AC UT WOS:000236895300006 PM 16597364 ER PT J AU Woods, AS Kaminski, R Oz, M Wang, Y Hauser, K Goody, R Wang, HYJ Jackson, SN Zeitz, P Zeitz, KP Zolkowska, D Schepers, R Nold, M Danielson, J Graslund, A Vukojevic, V Bakalkin, G Basbaum, A Shippenberg, T AF Woods, AS Kaminski, R Oz, M Wang, Y Hauser, K Goody, R Wang, HYJ Jackson, SN Zeitz, P Zeitz, KP Zolkowska, D Schepers, R Nold, M Danielson, J Graslund, A Vukojevic, V Bakalkin, G Basbaum, A Shippenberg, T TI Decoy peptides that bind dynorphin noncovalently prevent NMDA receptor-mediated neurotoxicity SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE NMDA receptor; dynorphin; neurotoxicity; paralysis; noncovalent interaction ID RAT HINDLIMB PARALYSIS; SPINAL-CORD NEURONS; ELECTROSTATIC INTERACTION; NONOPIOID MECHANISMS; A 1-13; INJURY; PHOSPHATE; IMMUNOREACTIVITY; ALLODYNIA; INDUCTION AB Prodynorphin-derived peptides elicit various pathological effects including neurological dysfunction and cell death. These actions are reduced by N-methyl-D-aspartate receptor (NMDAR) but not opioid receptor antagonists suggesting NMDAR-mediation. Here, we show that a conserved epitope (KVNSEEEEEDA) of the NR1 subunit of the NMDAR binds dynorphin peptides (DYNp) noncovalently. Synthetic peptides containing this epitope form stable complexes with DYNp and prevent the potentiation of NMDAR-gated currents produced by DYNp. They attenuate DYNp-evoked cell death in spinal cord and prevent, as well as reverse, DYNp-induced paralysis and allodynia. The data reveal a novel mechanism whereby prodynorphin-derived peptides facilitate NMDAR function and produce neurotoxicity. Furthermore, they suggest that synthetic peptides that bind DYNp, thus preventing their interaction with NMDAR, may be novel therapeutic agents for the treatment of spinal cord injury. C1 NIDA, NIH, IRP, Baltimore, MD 21224 USA. Univ Kentucky, Coll Med, Dept Anat, Lexington, KY 40536 USA. Univ Kentucky, Coll Med, Dept Neurobiol, Lexington, KY 40536 USA. Univ Calif San Francisco, Dept Anat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Physiol, San Francisco, CA 94143 USA. Univ Calif San Francisco, WM Keck Fdn Ctr Integrat Neurosci, San Francisco, CA 94143 USA. Waters Corp, Milford, MA 01757 USA. Stockholm Univ, S-10691 Stockholm, Sweden. Karolinska Inst, S-10401 Stockholm, Sweden. RP Woods, AS (reprint author), 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov RI Oz, Murat/E-2148-2012; OI Bakalkin, Georgy/0000-0002-8074-9833; Vukojevic, Vladana/0000-0003-0873-5653 FU Intramural NIH HHS [Z99 DA999999] NR 29 TC 25 Z9 25 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1535-3893 J9 J PROTEOME RES JI J. Proteome Res. PD APR PY 2006 VL 5 IS 4 BP 1017 EP 1023 DI 10.1021/pr060016+ PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 032ZS UT WOS:000236816100033 PM 16602711 ER PT J AU Bybee, RW Fuchs, B AF Bybee, RW Fuchs, B TI Preparing the 21st century workforce: A new reform in science and technology education SO JOURNAL OF RESEARCH IN SCIENCE TEACHING LA English DT Editorial Material C1 BSCS, Colorado Springs, CO 80918 USA. NIH, Off Sci Educ, Bethesda, MD 20892 USA. RP Bybee, RW (reprint author), BSCS, 5415 Mark Dabling Blvd, Colorado Springs, CO 80918 USA. NR 3 TC 42 Z9 44 U1 1 U2 20 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-4308 J9 J RES SCI TEACH JI J. Res. Sci. Teach. PD APR PY 2006 VL 43 IS 4 BP 349 EP 352 DI 10.1002/tea.20147 PG 4 WC Education & Educational Research SC Education & Educational Research GA 028YP UT WOS:000236525000001 ER PT J AU Williams, SK Scahill, L Vitiello, B Aman, MG Arnold, LE McDougle, CJ McCracken, JT Tierney, E Ritz, L Posey, DJ Swiezy, NB Hollway, J Cronin, P Ghuman, J Wheeler, C Cicchetti, D Sparrow, S AF Williams, SK Scahill, L Vitiello, B Aman, MG Arnold, LE McDougle, CJ McCracken, JT Tierney, E Ritz, L Posey, DJ Swiezy, NB Hollway, J Cronin, P Ghuman, J Wheeler, C Cicchetti, D Sparrow, S TI Risperidone and adaptive behavior in children with autism SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Association-for-the-Advancement-of-Behavior-Therapy CY NOV, 2004 CL New Orleans, LA SP Assoc Advancement Behav Therapy DE autism; risperidone; Vineland Adaptive Behavior Scales ID PERVASIVE DEVELOPMENTAL DISORDER; INTENSIVE EARLY INTERVENTION; MENTAL-RETARDATION; CLINICAL-TRIALS; YOUNG-CHILDREN; CHECKLIST; INDIVIDUALS; DOMAINS; SCORES; NORMS AB Objective: To evaluate the impact of risperidone on adaptive behavior in children with autistic disorder who have serious behavior problems and to examine different methods of scoring the Vineland Adaptive Behavior Scales to measure change. Method: Forty-eight children (5 years to 16 years, 5 months) who showed behavioral improvement during acute treatment with risperidone were followed for 6 months and assessed with the Vineland Scales. Results: Raw scores, age-equivalents, and special norm percentile scores all showed significant increases in adaptive behavior in the areas of communication, daily living skills, and socialization (p < .01). During a period of 6 to 8 months, children gained an average of 7.8 age-equivalent months in the area of socialization, a > 6% improvement beyond what would be expected based on baseline growth rates. Conclusions: Although limited by the absence of a control group, these results suggest that risperidone may improve adaptive skills in children with autistic disorder accompanied by serious behavioral problems. Vineland age-equivalent scores appear to be most useful in assessing change with treatment over time. C1 Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Ohio State Univ, Columbus, OH 43210 USA. Indiana Univ, Indianapolis, IN 46204 USA. Yale Univ, Ctr Child Study, New Haven, CT 06520 USA. Kennedy Krieger Inst, Baltimore, MD USA. NIMH, Bethesda, MD 20892 USA. RP Scahill, L (reprint author), Yale Univ, Ctr Child Study, POB 207900, New Haven, CT 06520 USA. EM lawrence.scahill@yale.edu OI Scahill, Lawrence/0000-0001-5073-1707 FU NIMH NIH HHS [N01MH80011, N01MH70010, K23 MH001883-04, N01MH70001, N01MH70009] NR 37 TC 39 Z9 40 U1 5 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD APR PY 2006 VL 45 IS 4 BP 431 EP 439 DI 10.1097/01.chi.0000196423.80717.32 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 027NC UT WOS:000236421300010 PM 16601648 ER PT J AU Zancanaro, PCQ McGirt, LY Mamelak, AJ Nguyen, RHN Martins, CR AF Zancanaro, PCQ McGirt, LY Mamelak, AJ Nguyen, RHN Martins, CR TI Cutaneous manifestations of HIV in the era of highly active antiretroviral therapy: An institutional urban clinic experience SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; IMMUNE RESTORATION DISEASE; AIDS-DEFINING ILLNESSES; CD4 LYMPHOCYTE COUNTS; SKIN-DISEASE; DERMATOLOGICAL FINDINGS; PROTEASE INHIBITORS; INFECTED PATIENTS; PREVALENCE; DISORDERS AB Background: Widespread introduction of highly active antiretroviral therapy (HAART) in the mid 1990s has altered the presentation of the cutaneous manifestations associated with HIV infection. Objective: Our purpose was to evaluate the use of HAART on the prevalence and spectrum of cutaneous manifestations in HIV-infected patients. Methods: A study of the initial visits of 897 HIV-infected patients at an urban dermatology clinic between 1996 and 2002 was performed. Results: Folliculitis was the most common cutaneous disorder identified. Patients with CN-positive cell counts less than 200 cells/mm(3) had an increased prevalence of folliculitis and prurigo nodularis, whereas those with HIV viral loads higher than 55,000 copies/mL, had a higher prevalence of idiopathic pruritus and candidiasis. Patients not receiving HAART had increased rates Of folliculitis and prurigo nodularis. Patients receiving HAART had increased rates of photosensitivity and molluscum contagiosum. Limitations: This was a cross-sectional study in which temporality was Linable to be determined. Conclusion: With ongoing therapeutic advancements, the cutaneous manifestations associated with HIV infection will continue to evolve. C1 Johns Hopkins Univ, Sch Med, Dept Dermatol, Baltimore, MD 21205 USA. Univ Brasilia, Fac Med, BR-70910900 Brasilia, DF, Brazil. NIEHS, Durham, NC USA. RP Martins, CR (reprint author), Johns Hopkins Univ, Sch Med, Dept Dermatol, 550 N Broadway,Suite 1002, Baltimore, MD 21205 USA. EM crmartin@jhmi.edu NR 48 TC 34 Z9 35 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD APR PY 2006 VL 54 IS 4 BP 581 EP 588 DI 10.1016/j.jaad.2005.12.030 PG 8 WC Dermatology SC Dermatology GA 027HC UT WOS:000236404800002 PM 16546578 ER PT J AU Dionne, RA Yagiela, JA Cote, CJ Donaldson, M Edwards, M Greenblatt, DJ Haas, D Malviya, S Milgrom, P Moore, PA Shampaine, G Silverman, M Williams, RL Wilson, S AF Dionne, RA Yagiela, JA Cote, CJ Donaldson, M Edwards, M Greenblatt, DJ Haas, D Malviya, S Milgrom, P Moore, PA Shampaine, G Silverman, M Williams, RL Wilson, S TI Balancing efficacy and safety in the use of oral sedation in dental outpatients SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE triazolam; conscious sedation; anxiety; dental pain control ID CHLORAL HYDRATE SEDATION; CONSCIOUS SEDATION; PEDIATRIC-PATIENTS; ADULT-POPULATION; NITROUS-OXIDE; TRIAZOLAM; ANXIETY; PREVALENCE; FEAR; CHILDREN AB Background. Concerns about the safety of pediatric oral sedation and the incremental use of triazolam in adults prompted a workshop cosponsored by several professional organizations. Overview. There is a strong need and demand for adult and pediatric sedation services. Using oral medication to achieve anxiolysis in adults appears to have a wide margin of safety. Mortality and serious morbidity, however, have been reported with oral conscious sedation, especially in young children. Most serious adverse events are related to potentially avoidable respiratory complications. Conclusions. Clinical trials are needed to evaluate oral sedative drugs and combinations, as well as to develop discharge criteria with objective quantifiable measures of home readiness. Courses devoted to airway management should be developed for dentists who provide conscious sedation services. State regulation of enteral administration of sedatives to achieve conscious sedation is needed to ensure safety. Practice Implications. Safety in outpatient sedation is of paramount concern, with enteral administration of benzodiazepines appearing safe but poorly documented in the office setting. Conscious sedation by the enteral route, including incremental triazolam, necessitates careful patient evaluation, monitoring, documentation, facilities, equipment and personnel as described in American Dental Association and American Academy of Pediatric Dentistry guidelines. C1 Univ Calif Los Angeles, Sch Dent, Div Diagnost & Surg Sci, Los Angeles, CA 90024 USA. Childrens Mem Hosp, Dept Pediat Anesthesiol, Chicago, IL 60614 USA. Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. Univ Alabama, Sch Dent, Birmingham, AL 35294 USA. Tufts Univ, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. Univ Toronto, Fac Dent, Toronto, ON, Canada. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Dent Fears Res Clin, Seattle, WA USA. Univ Washington, Seattle, WA 98195 USA. Univ Pittsburgh, Sch Dent Med, Pittsburgh, PA 15260 USA. US Pharmacoeial Convent, Rockville, MD USA. Univ Colorado, Dept Pediat Dent, Denver, CO 80202 USA. RP Dionne, RA (reprint author), NINR, NIH, 10 Ctr Dr,Room 2-C-1339, Bethesda, MD 20892 USA. EM dionner@mail.nih.gov OI Donaldson, Mark/0000-0002-7231-7395; Milgrom, Peter/0000-0003-0784-9181 NR 67 TC 12 Z9 14 U1 0 U2 5 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD APR PY 2006 VL 137 IS 4 BP 502 EP 513 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 033PU UT WOS:000236862000029 PM 16637480 ER PT J AU Cesari, M Leeuwenburgh, C Lauretani, F Onder, G Bandinelli, S Maraldi, C Guralnik, JM Pahor, M Ferrucci, L AF Cesari, M Leeuwenburgh, C Lauretani, F Onder, G Bandinelli, S Maraldi, C Guralnik, JM Pahor, M Ferrucci, L TI Frailty syndrome and skeletal muscle - Results from the InCHIANTI study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Univ Florida, Dept Aging & Geriatr Res, Gainesville, FL USA. Univ Sacred Heart, Dept Gerontol Geriatr & Psychiat, I-00168 Rome, Italy. Tuscany Hlth Reg Agcy, Florence, Italy. Azienda Sanitaria Firenze, Geriatr Rehabil Unit, Florence, Italy. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Bethesda, MD 20892 USA. RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S18 EP S18 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300050 ER PT J AU Di Bari, M Pecchioli, A Mazzaglia, G Marini, M Maciocco, G Marchionni, N Ferrucci, L AF Di Bari, M Pecchioli, A Mazzaglia, G Marini, M Maciocco, G Marchionni, N Ferrucci, L TI Severity of disability and care available to older community-dwellers, Italy. The "Assistenza Socio-Sanitaria in Italia" project. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Univ Florence, Dept Crit Care Med, Florence, Italy. Univ Florence, Dept Publ Hlth, Florence, Italy. Tuscany Reg Agcy Healthcare Serv, Florence, Italy. NIA, Longitudinal Studies Sect, Clin Res Branch, Baltimore, MD 21224 USA. RI DI BARI, MAURO/J-1524-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S90 EP S90 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300261 ER PT J AU Ganesh, S Hoenig, H Taylor, D Pieper, C Guralnik, J Fried, L AF Ganesh, S Hoenig, H Taylor, D Pieper, C Guralnik, J Fried, L TI Compensatory strategies used for mobility impairment in elderly women. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Duke Univ, Med Ctr, Durham, NC USA. PM&RS, Durham VA Med Ctr, Durham, NC USA. NIA, Bethesda, MD 20892 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S200 EP S200 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300581 ER PT J AU Houston, DK Cesari, M Ferrucci, L Cherubini, A Maggio, D Bartali, B Johnson, M Schwartz, GG Kritchevsky, SB AF Houston, DK Cesari, M Ferrucci, L Cherubini, A Maggio, D Bartali, B Johnson, M Schwartz, GG Kritchevsky, SB TI Association between vitamin D status and physical performance: The InCHIANTI study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Univ Florida, Gainesville, FL USA. NIA, Bethesda, MD 20892 USA. Univ Perugia, I-06100 Perugia, Italy. Cornell Univ, Ithaca, NY USA. Univ Georgia, Athens, GA 30602 USA. RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 NR 0 TC 0 Z9 0 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S28 EP S28 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300080 ER PT J AU Inzitari, M Pozzi, C Ferrucci, L Chiarantini, D Crovetti, B Marchionni, N Masotti, G Di Bari, M AF Inzitari, M Pozzi, C Ferrucci, L Chiarantini, D Crovetti, B Marchionni, N Masotti, G Di Bari, M TI Subtle abnormal neurological findings and geriatric syndromes. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Dept Med & Surg, Unit Gerontol & Geriatr, Florence, Italy. Natl Inst Aging, Longitudinal Studies Sect, Baltimore, MD USA. RI DI BARI, MAURO/J-1524-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S189 EP S189 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300552 ER PT J AU Kim, D Lipsitz, L Ferrucci, L Varadhan, R Guralnik, J Carlson, M Fleisher, L Fried, L Chaves, P AF Kim, D Lipsitz, L Ferrucci, L Varadhan, R Guralnik, J Carlson, M Fleisher, L Fried, L Chaves, P TI Association of heart rate variability with cognitive impairment in older disabled women in the community. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Jefferson Med Coll, Philadelphia, PA USA. Hebrew Rehabil Ctr Aged, Boston, MA USA. NIA, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Ctr Aging & Hlth, Baltimore, MD USA. Johns Hopkins Univ, Sch Publ Hlth, Ctr Aging & Hlth, Baltimore, MD USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S8 EP S8 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300022 ER PT J AU Lee, R Abbott, RD Masaki, KH Chen, R Ross, W White, LR Petrovitch, H Curb, DJ Yano, K Rodriguez, BL Launer, LJ AF Lee, R Abbott, RD Masaki, KH Chen, R Ross, W White, LR Petrovitch, H Curb, DJ Yano, K Rodriguez, BL Launer, LJ TI High endogenous estrogen levels predict incident stroke in elderly Japanese-American men: The Honolulu Heart Program. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Univ Hawaii, Honolulu, HI 96822 USA. Pacific Hlth Res Inst, Honolulu, HI USA. Dept Vet Affairs, Honolulu, HI USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S13 EP S13 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300036 ER PT J AU Maraldi, C Volpato, S Kritchevsky, SB Cesari, M Andresen, E Leeuwenburgh, C Harris, TB Newman, AB Kanaya, A Johnson, KC Rodondi, N Pahor, M AF Maraldi, C Volpato, S Kritchevsky, SB Cesari, M Andresen, E Leeuwenburgh, C Harris, TB Newman, AB Kanaya, A Johnson, KC Rodondi, N Pahor, M TI Alcohol intake, mortality and inflammation among older people. The health, aging, and body composition (Health-ABC) study. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Univ Florida, Inst Aging, Gainesville, FL USA. Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy. Wake Forest Univ, Sticht Ctr Aging, Winston Salem, NC 27109 USA. NIA, Lab Epidemiol Demog & Biometry, IRP, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Tennessee, Dept Prevent Med, Memphis, TN 38163 USA. Univ Lausanne, CH-1015 Lausanne, Switzerland. RI Cesari, Matteo/A-4649-2008 OI Cesari, Matteo/0000-0002-0348-3664 NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S126 EP S126 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300369 ER PT J AU Mehta, KM Yaffe, K Brenes, G Newman, AB Schorr, RI Simonsick, EM Ayonayon, HA Rubin, SM Covinsky, KE AF Mehta, KM Yaffe, K Brenes, G Newman, AB Schorr, RI Simonsick, EM Ayonayon, HA Rubin, SM Covinsky, KE TI Anxiety symptoms and decline in physical function over 5 years in the health, aging and body composition study (Health ABC). SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Univ Calif San Francisco, Div Geriatr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Neurol, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. Wake Forest Univ, Sch Med, Dept Psychiat & Behav Med, Winston Salem, NC 27109 USA. Univ Pittsburgh, Sch Med, Div Geriatr Med, Pittsburgh, PA USA. Univ Tennessee, Ctr Hlth Sci, Coll Med, Dept Prevent Med, Memphis, TN 38163 USA. NIA, Clin Res Branch, Baltimore, MD 21224 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S128 EP S128 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300374 ER PT J AU Newman, AB Naydeck, BL Boudreau, RM Fried, LF Fried, LP Harris, TB AF Newman, AB Naydeck, BL Boudreau, RM Fried, LF Fried, LP Harris, TB TI Multi-system physiologic integrity - Relationship to mortality in older adults. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Univ Pittsburgh, Pittsburgh, PA USA. Johns Hopkins Univ, Baltimore, MD USA. NIA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S15 EP S15 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300041 ER PT J AU Patel, R McDermott, M Nishida, T Sufit, R Liu, K Tian, L Guralnik, J Criqui, M Ferrucci, L AF Patel, R McDermott, M Nishida, T Sufit, R Liu, K Tian, L Guralnik, J Criqui, M Ferrucci, L TI Neuropathy in patients with lower extremity peripheral arterial disease. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NIA, Bethesda, MD 20892 USA. Univ Calif San Diego, San Diego, CA 92103 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S28 EP S28 PG 1 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300079 ER PT J AU Roti, L Corsini, G Colombini, A Mazzaglia, G Maciocco, G Marchionni, N Di Bari, M Ferrucci, L AF Roti, L Corsini, G Colombini, A Mazzaglia, G Maciocco, G Marchionni, N Di Bari, M Ferrucci, L TI A screening instrument to identify older community-dwellers at risk for death and hospitalization in Tuscany, Italy. The "Assistenza Socio-Sanitaria in Italia" project. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Tuscany Reg Agcy Healthcare Serv, Florence, Italy. Univ Florence, Dept Publ Hlth, Florence, Italy. Univ Florence, Dept Crit Med & Surg Geriatr, Florence, Italy. NIA, Clin Res Branch, Longitudinal Studies Serv, Baltimore, MD 21224 USA. RI DI BARI, MAURO/J-1524-2012 NR 0 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S90 EP S91 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300262 ER PT J AU Terry, DF Evans, JC Pencina, MJ Murabito, JM D'Agostino, RB Benjamin, EJ AF Terry, DF Evans, JC Pencina, MJ Murabito, JM D'Agostino, RB Benjamin, EJ TI Clinical characteristics of Framingham offspring participants with long lived parents. SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Meeting Abstract CT Annual Meeting of the American-Geriatrics-Society CY MAY 03-07, 2006 CL Chicago, IL SP Amer Geriatr Soc C1 Boston Univ, Sch Med, Boston Med Ctr, Boston, MA 02215 USA. NHLBI, Framingham Heart Study, Framingham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD APR PY 2006 VL 54 IS 4 SU S BP S28 EP S29 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 036KF UT WOS:000237069300081 ER PT J AU Xue, JL Daniels, F Star, RA Kimmel, PL Eggers, PW Molitoris, BA Himmelfarb, J Collins, AJ AF Xue, Jay L. Daniels, Frank Star, Robert A. Kimmel, Paul L. Eggers, Paul W. Molitoris, Bruce A. Himmelfarb, Jonathan Collins, Allan J. TI Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID INTENSIVE-CARE; UNITED-STATES; EPIDEMIOLOGY; SEPSIS; INSUFFICIENCY; SURGERY; COMORBIDITY; INFORMATION; PROGNOSIS; LENGTH AB This study's objective was to determine the incidence and mortality of acute renal failure (ARF) in Medicare beneficiaries. Data were from hospitalized Medicare beneficiaries (5,403,015 discharges) between 1992 and 2001 from the 5% sample of Medicare claims. For 1992 to 2001, the overall incidence rate of ARF was 23.8 cases per 1000 discharges, with rates increasing by approximately 11% per year. Older age, male gender, and black race were strongly associated (P < 0.0001) with ARF. The overall in-hospital death rate was 4.6% in discharges without ARF, 15.2% in discharges with ARF coded as the principal diagnosis, and 32.6% in discharges with ARF as a secondary diagnosis. In-hospital death rates were 32.9% in discharges with ARF that required renal dialysis and 27.5% in those with ARF that did not require dialysis. Death within 90 d after hospital admission was 13.1% in discharges without ARF, 34.5% in discharges with ARF coded as the principal diagnosis, and 48.6% in discharges with ARF as a secondary diagnosis. Discharges with ARF were more (P < 0.0001) likely to have intensive care and other acute organ dysfunction than those without ARF. For discharges both with and without ARF, rates for death within 90 d after hospital admission showed a declining trend. In conclusion, the incidence rate of ARF in Medicare beneficiaries has been increasing. Those of older age, male gender, and black race are more likely to have ARF. These data show ARF to be a major contributor to morbidity and mortality in hospitalized patients. C1 Univ Minnesota, Sch Med, US Renal Data Syst Coordinating Ctr, Minneapolis, MN 55404 USA. Univ Minnesota, Sch Med, Dept Med, Minneapolis, MN 55455 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Div Nephrol, Indianapolis, IN USA. Maine Med Ctr, Div Nephrol, Portland, ME 04102 USA. RP Xue, JL (reprint author), Univ Minnesota, Sch Med, US Renal Data Syst Coordinating Ctr, 914 S 8th St,Suite D-206, Minneapolis, MN 55404 USA. EM jxue@usrds.org FU NIDDK NIH HHS [N01 DK 92343] NR 33 TC 371 Z9 396 U1 1 U2 6 PU AMERICAN SOCIETY NEPHROLOGY PI WASHINGTON PA 1725 I ST, NW STE 510, WASHINGTON, DC 20006 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD APR PY 2006 VL 17 IS 4 BP 1135 EP 1142 DI 10.1681/ASN.2005060668 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 106SH UT WOS:000242120600027 PM 16495381 ER PT J AU Bowden, VM Wood, FB Warner, DG Olney, CA Olivier, ER Siegel, ER AF Bowden, VM Wood, FB Warner, DG Olney, CA Olivier, ER Siegel, ER TI Health information Hispanic outreach in the Texas Lower Rio Grande Valley SO JOURNAL OF THE MEDICAL LIBRARY ASSOCIATION LA English DT Article ID MEXICO AB Purpose: This paper provides an overview of the two-year Texas Lower Rio Grande Valley Health Information Hispanic Outreach (HI 110) project. The project included a needs assessment, four pilot projects, and focus groups on the use of MedlinePlus and MedlinePlus en espanol. The needs assessment included a survey of physicians' information usage and a review of the circuit librarian program that had been established in 1989. The pilot projects were located at a high school, a rural health clinic, an urban health clinic, and a community center. Diffusion of innovation theory provided a framework for interpreting the results of the pilot projects. Methods: The survey of physicians' information usage partially replicated a similar 1990 survey. The review of the circuit librarian program included usage statistics, interviews of administrators, and a survey of participants. Pilot project methodology varied by site. At the high school, four students were trained to instruct their peers in the use of MedlinePlus. At the two clinics, a computer workstation was installed for patients to access MedlinePlus. At the community center, staff were trained to use MedlinePlus en espanol to train community residents. Project evaluation included surveys, focus groups, and interviews. Indicators of success included increased level of consumer use of MedlinePlus, reports by key informants and consumers of how MedlinePlus was used, reports about training, and development of self-sustaining activity. Results: The physician survey documented usage of health information resources in 2002 compared to 1990. The review of the circuit librarian program documented the change in program usage between 1989 and 2003. The pilot project at the high school was the most successful of the four pilot projects in introducing MedlinePlus to a large number of people, followed by the community center project. In the high school and community center projects, the participating institutions had reinforcing educational missions and paid staff who were highly motivated to achieve the project goals. The computer workstations projects at the two clinics were less successful, due in part to limited staff commitment and conflicting priorities. Conclusions: The HI HO project tested methods of reaching the Hispanic community in the Lower Rio Grande Valley region of Texas. The four HI HO pilot projects varied in achieving their stated objectives. But taken as a whole, the HI HO project significantly contributed to a better understanding of health information outreach to the Hispanic community, knowledge that should be useful to others with similar outreach activities. C1 Univ Texas, Hlth Sci Ctr, Canyon Lake, TX 78133 USA. Natl Lib Med, Off Hlth Informat Program Dev, Bethesda, MD 20894 USA. Univ Texas, Hlth Sci Ctr, Harlingen, TX 78550 USA. Evaluat Consulting LLC, Greensboro, NC 27403 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. RP Bowden, VM (reprint author), Univ Texas, Hlth Sci Ctr, POB 2968, Canyon Lake, TX 78133 USA. EM bowdenv@sbcglobal.net; fredwood@mail.nih.gov; debiwarner@ev1.net; olneyc@triad.rr.com; olivier@uthscsa.edu; siegel@nlm.nih.gov FU NLM NIH HHS [N0-1-LM-1-3515] NR 4 TC 4 Z9 4 U1 0 U2 2 PU MEDICAL LIBRARY ASSOC PI CHICAGO PA 65 EAST WACKER PLACE, STE 1900, CHICAGO, IL 60601-7298 USA SN 1536-5050 J9 J MED LIBR ASSOC JI J. Med. Libr. Assoc. PD APR PY 2006 VL 94 IS 2 BP 180 EP 189 PG 10 WC Information Science & Library Science SC Information Science & Library Science GA 058BS UT WOS:000238639800011 PM 16636711 ER PT J AU Whitfield, KE Brandon, DT Robinson, E Bennett, G Merritt, M Edwards, C AF Whitfield, KE Brandon, DT Robinson, E Bennett, G Merritt, M Edwards, C TI Sources of variability in John Henryism SO JOURNAL OF THE NATIONAL MEDICAL ASSOCIATION LA English DT Article DE John Henryism; twins; genetics; environment; aging ID BLOOD-PRESSURE DIFFERENCES; JOHN-HENRYISM; SOCIAL SUPPORT; ENVIRONMENTAL-INFLUENCES; SOCIOECONOMIC-STATUS; AFRICAN-AMERICANS; BLACK ADULTS; STRESS; TWIN; HYPOTHESIS AB Objectives: To decompose sources of individual differences in coping as measured by John Henryism among African Americans. Methods: Analyses described in this study are based on the pairwise responses from 180 pairs of some-sex, African-American twin pairs who participated in the Carolina African-American Twins Study of Aging (CAATSA).(21) The sample consisted of 85 monozygotic (MZ) and 95 dizygotic (DZ) twin pairs. Results: Environmental factors account for most of the variance (65%) in John Henryism scores, with the remaining variance attributable to additive genetic factors (35%). The test of the genetic component suggested that the 35% represented a statistically significant proportion of variance. Conclusions: The vast majority of recent studies on African Americans and health outcomes have focused on the impact of psychosocial factors on diseases such as hypertension and diabetes, with relatively little attention to possible genetic contributors. Previous research on psychosocial indices and their relationship to cardiovascular health among African Americans has focused on assessment and epidemiological explorations rather than understanding the etiology of variability in such measures. C1 Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. Johns Hopkins Univ, Ctr Hlth Disparities Solut, Bloomberg Sch Publ Hlth, Baltimore, MD 21218 USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. N Carolina Cent Univ, Dept Psychol, Raleigh, NC 27695 USA. Duke Univ, Div Hematol, Dept Med, Dept Psychiat & Behav Sci,Med Ctr, Durham, NC USA. Harvard Univ, Dept Society Human Dev & Hlth, Boston, MA 02115 USA. RP Whitfield, KE (reprint author), Penn State Univ, Dept Biobehav Hlth, 315 E HHD, University Pk, PA 16802 USA. EM kew5@psu.edu FU NIA NIH HHS [1R01-AG13662-01A2] NR 37 TC 10 Z9 10 U1 2 U2 7 PU NATL MED ASSOC PI WASHINGON PA 1012 10TH ST, N W, WASHINGON, DC 20001 USA SN 0027-9684 J9 J NATL MED ASSOC JI J. Natl. Med. Assoc. PD APR PY 2006 VL 98 IS 4 BP 641 EP 647 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 028YG UT WOS:000236524100029 PM 16623079 ER PT J AU Bourdon, DM Mahanty, SK Jacobson, KA Boyer, JL Harden, TK AF Bourdon, DM Mahanty, SK Jacobson, KA Boyer, JL Harden, TK TI (N)-methanocarba-2MeSADP (MRS2365) is a subtype-specific agonist that induces rapid desensitization of the P2Y(1) receptor of human platelets SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Article DE adenosine diphosphate; desensitization; MRS2365; P2Y(1) receptor; P2Y(12) receptor; platelets ID ADENINE-NUCLEOTIDE ANALOGS; ADENOSINE-DIPHOSPHATE; ANTITHROMBOTIC DRUGS; MOLECULAR-BASIS; ADP RECEPTORS; P2Y1 RECEPTOR; SHAPE CHANGE; AGGREGATION; ANTAGONISTS; IDENTIFICATION AB Adenosine diphosphate (ADP) initiates and maintains sustained aggregation of platelets through simultaneous activation of both the G(q)-coupled P2Y(1) receptor and the G(i)-coupled P2Y(12) receptor. We recently described the synthesis and P2Y(1) receptor-specific agonist activity of (N)-methanocarba-2MeSADP (MRS2365). Consequences of selective activation of the P2Y(1) receptor by MRS2365 have been further examined in human platelets. Whereas MRS2365 alone only induced shape change, addition of MRS2365 following epinephrine treatment, which activates the G(i/z)-linked, alpha(2A)-adrenergic receptor, resulted in sustained aggregation that was indistinguishable from that observed with ADP. Conversely, the platelet shape change promoted by ADP in the presence of the GP(IIb/IIIa) antagonist eptifibatide was similar to that promoted by MRS2365. Preaddition of the high affinity P2Y(1) receptor antagonist MRS2500 inhibited the effect of MRS2365, whereas addition of MRS2500 subsequent to MRS2365 reversed the MRS2365-induced shape change. Preactivation of the P2Y(1) receptor with MRS2365 for 2 min resulted in marked loss of capacity of ADP to induce aggregation as evidenced by a greater than 20-fold rightward shift in the concentration effect curve of ADP. This inhibitory effect of P2Y(1) receptor activation was dependent on the concentration of MRS2365 (EC50 = 34 nM). The inhibitory effect of preincubation with MRS2365 was circumvented by activation of the G(q)-coupled 5-HT2A receptor suggesting that MRS2365 induces loss of the ADP response as a consequence of desensitization of the G(q)-coupled P2Y(1) receptor. The time course of MRS2365-induced loss of aggregation response to epinephrine was similar to that observed with ADP. These results further demonstrate the P2Y(1) receptor selectivity of MRS2365 and illustrate the occurrence of agonist-induced desensitization of the P2Y(1) receptor of human platelets studied in the absence of P2Y(12) receptor activation . C1 Univ N Carolina, Dept Pharmacol, Sch Med, Chapel Hill, NC 27599 USA. Inspire Pharmaceut Inc, Durham, NC USA. NIDDK, Mol Recognit Sect, NIH, Bethesda, MD USA. RP Harden, TK (reprint author), Univ N Carolina, Dept Pharmacol, Sch Med, CB 7365, Chapel Hill, NC 27599 USA. EM tkh@med.unc.edu RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031116-20]; NHLBI NIH HHS [HL54889, HL57391, R01 HL054889, R29 HL054889]; NIGMS NIH HHS [GM38213, R01 GM038213] NR 41 TC 14 Z9 16 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1538-7933 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD APR PY 2006 VL 4 IS 4 BP 861 EP 868 DI 10.1111/j.1538-7836.2006.01866.x PG 8 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 020US UT WOS:000235938700024 PM 16634757 ER PT J AU Krewski, D Lubin, JH Zielinski, JM Alavanja, M Catalan, VS Field, RW Klotz, JB Letourneau, EG Lynch, CF Lyon, JL Sandler, DP Schoenberg, JB Steck, DJ Stolwijk, JA Weinberg, C Wilcox, HB AF Krewski, D Lubin, JH Zielinski, JM Alavanja, M Catalan, VS Field, RW Klotz, JB Letourneau, EG Lynch, CF Lyon, JL Sandler, DP Schoenberg, JB Steck, DJ Stolwijk, JA Weinberg, C Wilcox, HB TI A combined analysis of North American case-control studies of residential radon and lung cancer SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID INDOOR RADON; EXPOSURE ASSESSMENT; GAS EXPOSURE; NONDIFFERENTIAL MISCLASSIFICATION; NONSMOKING WOMEN; RN-222 EXPOSURE; RISK; PO-210; GLASS; CANADA AB Cohort studies have consistently shown underground miners exposed to high levels of radon to be at excess risk of lung cancer, and extrapolations based on those results indicate that residential radon may be responsible for nearly 10-75% of all lung cancer deaths per year in the United States. However, case-control studies of residential radon and lung cancer have provided ambiguous evidence of radon lung cancer risks. Regardless, alpha-particle emissions from the short-lived radioactive radon decay products can damage cellular DNA. The possibility that a demonstrated lung carcinogen may be present in large numbers of homes raises a serious public health concern. Thus, a systematic analysis of pooled data from all North American residential radon studies was undertaken to provide a more direct characterization of the public health risk posed by prolonged radon exposure. To evaluate the risk associated with prolonged residential radon exposure, a combined analysis of the primary data from seven large scale case-control studies of residential radon and lung cancer risk was conducted. The combined data set included a total of 4081 cases and 5281 controls, representing the largest aggregation of data on residential radon and lung cancer conducted to date. Residential radon concentrations were determined primarily by a-track detectors placed in the living areas of homes of the study subjects in order to obtain an integrated 1-yr average radon concentration in indoor air. Conditional likelihood regression was used to estimate the excess risk of lung cancer due to residential radon exposure, with adjustment for attained age, sex, study, smoking factors, residential mobility, and completeness of radon measurements. Although the main analyses were based on the combined data set as a whole, we also considered subsets of the data considered to have more accurate radon dosimetry. This included a subset of the data involving 3662 cases and 4966 controls with a-track radon measurements within the exposure time window (ETW) 5-30 yr prior to the index date considered previously by Krewski et al. (2005). Additional restrictions focused on subjects for which a greater proportion of the ETW was covered by measured rather than imputed radon concentrations, and on subjects who occupied at most two residences. The estimated odds ratio (OR) of lung cancer generally increased with radon concentration. The OR trend was consistent with linearity (p =.10), and the excess OR (EOR) was 0.10 per Bq/m(3) with 95% confidence limits (-0.01, 0.26). For the subset of the data considered previously by Krewski et al. (2005), the EOR was 0.11 (0.00, 0.28). Further limiting subjects based on our criteria (residential stability and completeness of radon monitoring) expected to improve radon dosimetry led to increased estimates of the EOR. For example, for subjects who had resided in only one or two houses in the 5-30 ETW and who had alpha-track radon measurements for at least 20 yr of this 25-yr period, the EOR was 0.18 (0.02, 0.43) per 100 Bq/m(3). Both estimates are compatible with the EOR of 0.12 (0.02, 0.25) per 100 Bq/m(3) predicted by downward extrapolation of the miner data. Collectively, these results provide direct evidence of an association between residential radon and lung cancer risk, a finding predicted by extrapolation of results from occupational studies of radon-exposed underground miners. C1 Univ Ottawa, Inst Populat Hlth, McLaughlin Ctr Populat Hlth Risk Assessment, Ottawa, ON K1N 6N5, Canada. Univ Ottawa, Fac Med, Dept Epidemiol & Community Med, Ottawa, ON, Canada. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Washington, DC USA. Hlth Canada, Healthy Environm & Consumer Safety Branch, Ottawa, ON K1A 0L2, Canada. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Washington, DC USA. Univ Manitoba, Fac Med, Winnipeg, MB, Canada. Univ Iowa, Coll Publ Hlth, Dept Epidemiol, Dept Environm & Occupat Hlth, Iowa City, IA USA. Dept Hlth & Senior Serv, Trenton, NJ USA. Hlth Canada, Radiat Protect Bur, Hlth Protect Branch, Ottawa, ON K1A 0L2, Canada. Univ Utah, Dept Family & Prevent Med, Salt Lake City, UT USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. St Johns Univ, Dept Phys, Collegeville, MN 56321 USA. Yale Univ, Sch Med, New Haven, CT USA. Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. RP Krewski, D (reprint author), Univ Ottawa, Inst Populat Hlth, McLaughlin Ctr Populat Hlth Risk Assessment, 1 Stewart St,Room 320, Ottawa, ON K1N 6N5, Canada. EM dkrewski@uottawa.ca OI Sandler, Dale/0000-0002-6776-0018 FU NCI NIH HHS [R01 CA85942]; NIEHS NIH HHS [P30 ES05605, R01 ES05653] NR 84 TC 146 Z9 158 U1 3 U2 27 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD APR 1 PY 2006 VL 69 IS 7-8 BP 533 EP 597 DI 10.1080/15287390500260945 PG 65 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 030AI UT WOS:000236605100003 PM 16608828 ER PT J AU Field, RW Krewski, D Lubin, JH Zielinski, JM Alavanja, M Catalan, VS Klotz, JB Letourneau, EG Lynch, CF Lyon, JL Sandler, DP Schoenberg, JB Steck, DJ Stolwijk, JA Weinberg, C Wilcox, HB AF Field, RW Krewski, D Lubin, JH Zielinski, JM Alavanja, M Catalan, VS Klotz, JB Letourneau, EG Lynch, CF Lyon, JL Sandler, DP Schoenberg, JB Steck, DJ Stolwijk, JA Weinberg, C Wilcox, HB TI An overview of the North American residential radon and lung cancer case-control studies SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID WOMEN UNITED-STATES; TERM EX-SMOKERS; NONSMOKING WOMEN; GAS EXPOSURE; INDOOR RADON; LIFETIME NONSMOKERS; PAST EXPOSURE; JERSEY WOMEN; RED MEAT; RISK AB Lung cancer has held the distinction as the most common cancer type worldwide since 1985 (Parkin et al., 1993). Recent estimates suggest that lung cancer accounted for 1.2 million deaths worldwide in 2002, which represents 17.6% of the global cancer deaths (Parkin et al., 2005). During 2002, the highest lung cancer rates for men worldwide reportedly occurred in North America and Eastern Europe, whereas the highest rates in females occurred in North America and Northern Europe (Parkin et al., 2005). While tobacco smoking is the leading risk factor for lung cancer, because of the magnitude of lung cancer mortality, even secondary causes of lung cancer present a major public health concern (Field, 2001). Extrapolations from epidemiologic studies of radon-exposed miners project that approximately 18,600 lung cancer deaths per year (range 3000 to 41,000) in the United States alone are attributable to residential radon progeny exposure (National Research Council, 1999). Because of differences between the mines and the home environment, as well as differences (such as breathing rates) between miners and the general public, there was a need to directly evaluate effects of radon in homes. Seven major residential case-control radon studies have been conducted in North America to directly examine the association between prolonged radon progeny (radon) exposure and lung cancer. Six of the studies were performed in the United States including studies in New Jersey, Missouri (two studies), Iowa, and the combined states study (Connecticut, Utah, and southern Idaho). The seventh study was performed in Winnipeg, Manitoba, Canada. The residential case-control studies performed in the United States were previously reviewed elsewhere (Field, 2001). The goal of this review is to provide additional details regarding the methodologies and findings for the individual studies. Radon concentration units presented in this review adhere to the types (pCi/L or Bq/ m(3)) presented in the individual studies. One picocurie per liter is equivalent to 37 Bq/m(3). Because the Iowa study calculated actual measures of exposure (concentration x time), its exposures estimates are presented in the form WLM5-19 (Field et al., 2000a). WLM5-19 represents the working level months for exposures that occurred 5-79 yr prior to diagnosis for cases or time of interview for control. Eleven WLM5-19 is approximately equivalent to an average residential radon exposure of 4 pCi/L for 75 yr, assuming a 70% home occupancy. C1 Univ Iowa, Coll Publ Hlth, Dept Environm & Occupat Hlth, Dept Epidemiol, Iowa City, IA 52242 USA. Univ Ottawa, Fac Med, Dept Epidemiol & Community Med, Ottawa, ON, Canada. Univ Ottawa, McLaughlin Ctr Populat Hlth Risk Assessment, Ottawa, ON, Canada. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Washington, DC USA. Hlth Canada, Healthy Environm & Consumer Safety Branch, Ottawa, ON K1A 0L2, Canada. NCI, Occupat Epidemiol Branch, Div Canc Epidemiol & Genet, Washington, DC USA. Univ Manitoba, Fac Med, Winnipeg, MB, Canada. Dept Hlth & Senior Serv, Trenton, NJ USA. Hlth Canada, Radiat Protect Bur, Hlth Protect Branch, Ottawa, ON K1A 0L2, Canada. Univ Utah, Dept Family & Prevent Med, Salt Lake City, UT USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC USA. St Johns Univ, Dept Phys, Collegeville, MN 56321 USA. Yale Univ, Sch Med, New Haven, CT USA. Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC USA. RP Field, RW (reprint author), Univ Iowa, Coll Publ Hlth, Dept Environm & Occupat Hlth, Dept Epidemiol, 104 IREH, Iowa City, IA 52242 USA. EM bill-field@uiowa.edu OI Sandler, Dale/0000-0002-6776-0018 FU NCI NIH HHS [R01 CA85942]; NIEHS NIH HHS [R01 ES05653, P30 ES05605] NR 54 TC 26 Z9 27 U1 3 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD APR 1 PY 2006 VL 69 IS 7-8 BP 599 EP 631 DI 10.1080/15287390500260960 PG 33 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 030AI UT WOS:000236605100004 PM 16608829 ER PT J AU Sandler, DP Weinberg, CR Shore, DL Archer, VE Stone, MB Lyon, Jl Rothney-Kozlak, L Shepherd, M Stolwijk, JAJ AF Sandler, DP Weinberg, CR Shore, DL Archer, VE Stone, MB Lyon, Jl Rothney-Kozlak, L Shepherd, M Stolwijk, JAJ TI Indoor radon and lung cancer risk in Connecticut and Utah SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID RESIDENTIAL RADON; EXPOSURE; MINERS; WOMEN; SMOKING; DESIGN; SWEDEN AB Radon is a well-established cause of lung cancer in miners. Residents of homes with high levels of radon are potentially also at risk. Although most individual studies of indoor radon have failed to demonstrate significant risks, results have generally been consistent with estimates from studies of miners. We studied 1474 incident lung cancer cases aged 40-79 yr in Connecticut, Utah, and southern Idaho. Population controls (n = 1811) were identified by random telephone screening and from lists of Medicare recipients, and were selected to be similar to cases on age, gender, and smoking 70 yr before diagnosis/interview using randomized recruitment. Complete residential histories and information on known lung cancer risk factors were obtained by in-person and telephone interviews. Radon was measured on multiple levels of past and current homes using 12-mo alpha-track etch detectors. Missing data were imputed using mean radon concentrations for informative subgroups of controls. Average radon exposures were lower than anticipated, with median values of 23 Bq/m(3) in Connecticut and 45 Bq/m(3) in Utah/southern Idaho. Overall, there was little association between time-weighted average radon exposures 5 to 25 yr prior to diagnosis/interview and lung cancer risk. The excess relative risk (ERR) associated with a 100-Bq/m(3) increase in radon level was 0.002 (95% Cl -0.27, 0.21) in the overall population, 0.134 (95% Cl -0.23, 0.50) in Connecticut, and -0.112 (95% CI -0.34, 0.11) in Utah/Idaho. ERRS were higher for some subgroups less prone to misclassification, but there was no group with a statistically significant linear increase in risk. While results were consistent with the estimates from studies of miners, this study provides no evidence of an increased risk for lung cancer at the exposure levels observed. C1 NIH, Res Triangle Pk, NC USA. Westat Corp, Durham, NC USA. Univ Utah, Salt Lake City, UT USA. Maine Ctr Publ Hlth, Augusta, ME USA. Yale Univ, Sch Publ Hlth, New Haven, CT USA. RP Sandler, DP (reprint author), NIEHS, Epidemiol Branch, Mail Drop A3-05,POB 12233,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM sandler@niehs.nih.gov OI Sandler, Dale/0000-0002-6776-0018 NR 30 TC 14 Z9 17 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD APR 1 PY 2006 VL 69 IS 7-8 BP 633 EP 654 DI 10.1080/15287390500261117 PG 22 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 030AI UT WOS:000236605100005 PM 16608830 ER PT J AU Kusanovic, JP Soto, E Espinoza, J Stites, S Goncalves, LF Santolaya, J Nien, JK Erez, O Sorokin, Y Romero, R AF Kusanovic, JP Soto, E Espinoza, J Stites, S Goncalves, LF Santolaya, J Nien, JK Erez, O Sorokin, Y Romero, R TI Cervical varix as a cause of vaginal bleeding during pregnancy - Prenatal diagynosis by color Doppler ultrasonography SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article ID UNITED-STATES; PLACENTA PREVIA; VARICOSE-VEINS; EMBOLIZATION; MORTALITY AB Vaginal bleeding during pregnancy is a risk factor for adverse pregnancy outcome. Beyond 20 weeks of gestation, the most frequent causes of bleeding associated with maternal and perinatal morbidity and mortality are placenta previa and placental abruption. Cervical varix during pregnancy is a rare condition. To our knowledge, only 6 cases have been reported in the literature. Most of these cases are associated with preterm birth and high maternal morbidity. The optimal management and mode of delivery remain undetermined. We report a case of cervical varix diagnosed by transvaginal ultrasonography at 21 weeks of gestation. The pregnancy was complicated by several episodes of vaginal bleeding, and the patient delivered at 32 weeks. Color and power Doppler examination of the cervix played a key role in establishing the diagnosis. C1 Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI 48201 USA. NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, Perinatol Res Branch, NICHHD, 3990 John R,Box 4, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov FU Intramural NIH HHS; NICHD NIH HHS [Z01 HD002401-13] NR 18 TC 7 Z9 8 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD APR PY 2006 VL 25 IS 4 BP 545 EP 549 PG 5 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 032PB UT WOS:000236785600019 PM 16567447 ER PT J AU Crawford, ED Pinsky, PF Chia, D Kramer, BS Fagerstrom, RM Andriole, G Reding, D Gelmann, EP Levin, DL Gohagan, JK AF Crawford, ED Pinsky, PF Chia, D Kramer, BS Fagerstrom, RM Andriole, G Reding, D Gelmann, EP Levin, DL Gohagan, JK TI Prostate specific antigen changes as related to initial prostate specific antigen: Data from prostate, lung, colorectal and ovarian cancer screening trial SO JOURNAL OF UROLOGY LA English DT Article DE prostatic neoplasms; prostate-specific antigen; mass screening ID DIGITAL RECTAL EXAMINATION; NG/ML; MEN; GUIDELINES; INTERVALS; LESS AB Purpose: Annual screening with PSA, although of unproven benefit, is currently used for prostate cancer early detection. A large fraction of screened men have low (less than 2 ng/ml) initial PSA. The yield over time of positive PSA screens (ie more than 4 ng/ml) in these men has not been well characterized in large cohorts in the United States. Materials and Methods: Men in the screening arm of the PLCO received baseline PSA and annual tests for 5 years. 30,495 of these men had baseline PSA 4 ng/ml or less. We estimated the cumulative probability of converting to PSA greater than 4 at years 1 through 5 as a function of baseline PSA. Results: Among men with baseline PSA less than 1 ng/ml, 1.5% converted by year 5 (95% CI 1.2-1.7). Among men with baseline PSA of 1.0 to 1.99 ng/ml, 1.2% (95% CI 0.9-1.3) and 7.4% (95% CI 6.8-8.1) converted by year I and 5, respectively. A total of 33.5% and 79% of men with initial PSA of 2.0 to 2.99 and 3.0 to 4.0, respectively, converted by year 5. Of men with baseline PSA less than 1 ng/ml converting to PSA more than 4 ng/ml, 8% were diagnosed with cancer within 2 years of conversion. About 10% of men with baseline PSA less than 1 ng/ml and negative baseline DRE had a positive DRE within 3 years. Conclusions: For men choosing PSA screening, screening every 5 years for baseline PSA less than 1 ng/ml and every 2 years for PSA I to 2 ng/ml could result in a 50% reduction in PSA tests and in less than 1.5% of men missing earlier positive screens, but with an unknown effect on prostate cancer mortality. C1 Univ Colorado, Hlth Sci Ctr, Dept Urol Oncol, Denver, CO 80262 USA. Georgetown Univ, Div Canc Prevent, Natl Canc Inst, NIH,Dept Hlth & Human Serv, Washington, DC 20057 USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC 20057 USA. Univ Calif Los Angeles, Tissue Typing Lab, Los Angeles, CA 90024 USA. Natl Inst Hlth, Off Dis Prevent, Bethesda, MD USA. Washington Univ, Div Urol, St Louis, MO 63130 USA. Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA. RP Crawford, ED (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Urol Oncol, Box C324,4200 E 9th Ave, Denver, CO 80262 USA. EM david.crawford@uchsc.edu NR 20 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2006 VL 175 IS 4 BP 1286 EP 1290 DI 10.1016/S0022-5347(05)00706-8 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 022EX UT WOS:000236038900027 PM 16515981 ER PT J AU Crawford, ED Wilson, SS McConnell, JD Slawin, KM Lieber, MC Smith, JA Meehan, AG Bautista, OM Noble, WR Kusek, JW Nyberg, LM Roehrborn, CG AF Crawford, ED Wilson, SS McConnell, JD Slawin, KM Lieber, MC Smith, JA Meehan, AG Bautista, OM Noble, WR Kusek, JW Nyberg, LM Roehrborn, CG CA MTOPS RES Grp TI Baseline factors as predictors of clinical progression of benign prostatic hyperplasia in men treated with placebo SO JOURNAL OF UROLOGY LA English DT Article DE prostatic hyperplasia; disease progression; causality ID ACUTE URINARY RETENTION; NATURAL-HISTORY; RISK-FACTORS; FLOW-RATE; SYMPTOMS; FINASTERIDE; VOLUME; ANTIGEN; TRIALS AB Purpose: We analyzed data from the placebo arm of the MTOPS trial to determine clinical predictors of BPH progression. Materials and Methods: A total of 3,047 patients with LUTS were randomized to either placebo, doxazosin (4 to 8 mg), finasteride (5 mg), or a combination of doxazosin and finasteride. Average length of followup was 4.5 years. The primary outcome was time to overall clinical progression of BPH, defined as either a confirmed 4-point or greater increase in AUA SS, acute urinary retention, incontinence, renal insufficiency, or recurrent urinary tract infection. We analyzed BPH progression event data from the 737 men who were randomized to placebo. Results: The rate of overall clinical progression of BPH events in the placebo group was 4.5 per 100 person-years, for a cumulative incidence (among men who had at least 4 years of followup data) of 17%. The risk of BPH progression was significantly greater in patients on placebo with a baseline TPV of 31 ml or greater vs less than 31 ml (p < 0.0001), a baseline PSA of 1.6 ng/dl or greater vs PSA less than 1.6 ng/dl (p = 0.0009), a baseline Qmax of less than 10.6 ml per second vs 10.6 ml per second or greater (p = 0.011), a baseline PVR of 39 ml or greater vs less than 39 ml (p = 0.0008) and baseline age 62 years or older vs younger than 62 years (p = 0.0002). Conclusions: Among men in the placebo arm, baseline TPV, PSA, Qmax, PVR and age were important predictors of the risk of clinical progression of BPH. C1 Univ Colorado, Hlth Sci Ctr, Dept Urol Oncol, Aurora, CO 80010 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Mayo Clin Rochester, Rochester, MN USA. Baylor Coll Med, Houston, TX 77030 USA. Vanderbilt Univ, Nashville, TN USA. Merck Res Labs, Rahway, NJ USA. George Washington Univ, Washington, DC 20052 USA. NIDDK, Bethesda, MD USA. RP Crawford, ED (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Urol Oncol, POB 6510,Mail Stop F710, Aurora, CO 80010 USA. EM david.crawford@uchsc.edu FU NIDDK NIH HHS [U01 DK46416, U01 DK49971, U01 DK49977, U01 DK41418, U01 DK46437, U01 DK46431, U01 DK49951, U01 DK49954, U01 DK 49912, U01 DK49963, U01 DK46429, U01 DK46468, U01 DK49960, U01 DK49921, U01 DK49964, U01 DK46472, U01 DK49880, U01 DK49961] NR 18 TC 100 Z9 105 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD APR PY 2006 VL 175 IS 4 BP 1422 EP 1426 DI 10.1016/S0022-5347(05)00708-1 PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 022EX UT WOS:000236038900061 PM 16516013 ER PT J AU Hoover, SE Cohrs, RJ Rangel, ZG Gilden, DH Munson, P Cohen, JI AF Hoover, SE Cohrs, RJ Rangel, ZG Gilden, DH Munson, P Cohen, JI TI Downregulation of varicella-zoster virus (VZV) immediate-early ORF62 transcription by VZV ORF63 correlates with virus replication in vitro and with latency SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN TRIGEMINAL GANGLIA; HUMAN HELA-CELLS; GENE-EXPRESSION; EARLY PROTEIN; LYTIC INFECTION; IE63 PROTEIN; LOCALIZATION; ADENOVIRUS; PROMOTER; HSP70 AB Varicella-zoster virus (VZV) open reading frame 63 (ORF63) protein is expressed during latency in human sensory ganglia. Deletion of ORF63 impairs virus replication in cell culture and establishment of latency in cotton rats. We found that cells infected with a VZV ORF63 deletion mutant yielded low titers of cell-free virus and produced very few enveloped virions detectable by electron microscopy compared with those infected with parental virus. Microarray analysis of cells infected with a recombinant adenovirus expressing ORF63 showed that transcription of few human genes was affected by ORF63; a heat shock 70-kDa protein gene was downregulated, and several histone genes were upregulated. In experiments using VZV transcription arrays, deletion of ORF63 from VZV resulted in a fourfold increase in expression of ORF62, the major viral transcriptional activator. A threefold increase in ORF62 protein was observed in cells infected with the ORF63 deletion mutant compared with those infected with parental virus. Cells infected with ORE63 mutants impaired for replication and latency (J. 1. Cohen, T. Krogmann, S. Bontems, C. Sadzot-Delvaux, and L. Pesnicalk, J. Virol. 79:5069-5077, 2005) showed an increase in ORF62 transcription compared with those infected with parental virus. In contrast, cells infected with an ORF63 mutant that is not impaired for replication or latency showed ORF62 RNA levels equivalent to those in cells infected with parental virus. The ability of ORF63 to downregulate ORF62 transcription may play an important role in virus replication and latency. C1 NIH, Med Virol Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Neurol, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Microbiol, Denver, CO 80262 USA. NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Med Virol Sect, Lab Clin Infect Dis, Bldg 10,10 Ctr Dr,Room 11N228, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov RI Hoover, Susan/F-8580-2015 FU Intramural NIH HHS; NIA NIH HHS [R01 AG006127, AG06127, R37 AG006127]; NINDS NIH HHS [P01 NS032623, NS 32623] NR 53 TC 16 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2006 VL 80 IS 7 BP 3459 EP 3468 DI 10.1128/JVI.80.7.3459.3468.2006 PG 10 WC Virology SC Virology GA 025ZB UT WOS:000236305200033 PM 16537613 ER PT J AU Pal, R Venzon, D Santra, S Kalyanaraman, VS Montefiori, DC Hocker, L Hudacik, L Rose, N Nacsa, J Edghill-Smith, Y Moniuszko, M Hel, Z Belyakov, IM Berzofsky, JA Parks, RW Markham, PD Letvin, NL Tartaglia, J Franchini, G AF Pal, R Venzon, D Santra, S Kalyanaraman, VS Montefiori, DC Hocker, L Hudacik, L Rose, N Nacsa, J Edghill-Smith, Y Moniuszko, M Hel, Z Belyakov, IM Berzofsky, JA Parks, RW Markham, PD Letvin, NL Tartaglia, J Franchini, G TI Systemic immunization with an ALVAC-HIV-1/protein boost vaccine strategy protects rhesus macaques from CD4(+) T-cell loss and reduces both systemic and mucosal simian-human immunodeficiency virus SHIVKU2 RNA levels SO JOURNAL OF VIROLOGY LA English DT Article ID CYNOMOLGUS MONKEYS; CANARYPOX VACCINE; IMMUNE-RESPONSES; 89.6P CHALLENGE; TAT PROTEIN; VIRAL LOAD; INFECTION; TYPE-1; IMMUNOGENICITY; HIV-1 AB Transmission of human immunodeficiency virus type 1 (HIV-1) occurs primarily via the mucosal route, suggesting that HIV-1 vaccines may need to elicit mucosal immune responses. Here, we investigated the immunogenicity and relative efficacy of systemic immunization with two human ALVAC-HIV-1 recombinant vaccines expressing Gag, Pol, and gp120 (vCP250) or Gag, Pol, and gp160 (vCP1420) in a prime-boost protocol with their homologous vaccine native Env proteins. The relative efficacy was measured against a high-dose mucosal exposure to the pathogenic neutralization-resistant variant SHIVKU2 (simian-human immunodeficiency virus). Systemic immunization with both vaccine regimens decreased viral load levels not only in blood but unexpectedly also in mucosal sites and protected macaques from peripheral CD4(+) T-cell loss. This protective effect was stronger when the gp120 antigen was included in the vaccine. Inclusion of recombinant Tat protein in the boosting phase along with the Env protein did not contribute further to the preservation of CD4(+) T cells. Thus, systemic immunization with ALVAC-HIV-1 vaccine candidates elicits anti-HIV-1 immune responses able to contain virus replication also at mucosal sites in macaques. C1 NCI, Anim Models & Retroviral Vaccines Sect, Vaccine Branch, Bethesda, MD 20892 USA. Adv Biosci Labs Inc, Kensington, MD 20895 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Div Viral Pathogenesis, Beth Israel Deaconess Med Ctr,Dept Med, Boston, MA 02215 USA. Duke Univ, Med Ctr, Dept Surg, Ctr AIDS Res, Durham, NC 27710 USA. Med Univ Bialystok, Dept Allergol & Internal Dis, PL-15276 Bialystok, Poland. So Res Inst, Frederick, MD 21701 USA. Univ Alabama, Dept Pathol, Ctr AIDS Res, Birmingham, AL 35249 USA. NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Bethesda, MD 20892 USA. Sanofi Pasteur, Toronto, ON M2R 3T4, Canada. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, Vaccine Branch, 41-D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov OI Hel, Zdenek/0000-0002-4923-4794 FU Intramural NIH HHS; NIAID NIH HHS [N01-AI-55271] NR 56 TC 54 Z9 56 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2006 VL 80 IS 8 BP 3732 EP 3742 DI 10.1128/JVI.80.8.3732-3742.2006 PG 11 WC Virology SC Virology GA 031DZ UT WOS:000236685600005 PM 16571790 ER PT J AU Roelke, ME Pecon-Slattery, J Taylor, S Citino, S Brown, E Packer, C VandeWoude, S O'Brien, SJ AF Roelke, M. E. Pecon-Slattery, J. Taylor, S. Citino, S. Brown, E. Packer, C. VandeWoude, S. O'Brien, S. J. TI T-lymphocyte profiles in FIV-infected wild lions and pumas reveal CD4 depletion SO JOURNAL OF WILDLIFE DISEASES LA English DT Article DE CD4 T-cells; Felidae; FIV; flow cytometry; immune depletion; lion; lymphocytes; puma ID FELINE IMMUNODEFICIENCY VIRUS; DOMESTIC CATS; AFRICAN LIONS; PANTHERA-LEO; LENTIVIRUS INFECTION; PHYLOGENETIC ASPECTS; GENETIC DIVERSITY; CELLS; POPULATION; DIVERGENCE AB Feline immunodeficiency virus (FIV) is a lentivirus related to human immunodeficiency virus (HIV) that causes feline AIDS in the domestic cat (Felis catus). Serological surveys indicate that at least 25 other species of cat possess antibodies that cross-react with domestic cat FIV. Most infected nondomestic cat species are without major symptoms of disease. Long-term studies of FIV genome variation and pathogenesis reveal patterns consistent with coadaptation of virus and host in free-ranging FIV-Ple-infected African lions (Panthera leo) and FIV-Pco-infected pumas (Puma concolor) populations. This report examined correlates of immunodeficiency in wild and captive lions and pumas by quantifying CD5+, CD4+, and CD8+ T-cell subsets. Free-ranging FIV-Ple-infected lions had immunofluorescence flow cytometry (IFC) profiles marked b a dramatic decline in CD4+ subsets, a reduction of the CD4+/CD8+ ratio, reduction of CD8+beta(high) cells, and expansion of the CD8+beta(low) subset relative to uninfected lions. An overall significant depletion in CD5+ T-cells in seropositive lions was linked with a compensatory increase in total CD5- lymphocytes. The IFC profiles were altered significantly in 50% of the seropositive individuals examined. The FIV-Pco-infected pumas had a more generalized response of lymphopenia expressed as a significant decline in total lymphocytes, CD5+ T-cells, and CD5-lymphocytes as well as a significant reduction in CD4+ T-cells. Like lions, seropositive pumas had a significant decline in CD8+beta(high) cells but differed by not having compensatory expansion of CD8+beta(low) cells relative to controls. Results from FIV-infected lions and pumas parallel human and Asian monkey CD4+ diminution in HIV and SIV infection, respectively, and suggest there may be unrecognized immunological consequences of FIV infection in these two species of large cats. C1 NCI, Lab Genom Divers, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. US EPA, Res Triangle Pk, NC 27711 USA. White Oak Conservat Ctr, Yulee, FL 32097 USA. Univ Minnesota, Dept Ecol Evolut & Behav, St Paul, MN 55108 USA. Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. RP Pecon-Slattery, J (reprint author), NCI, Lab Genom Divers, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. EM slattery@mail.ncifcrf.gov FU NCI NIH HHS [N01-CO-12400] NR 44 TC 40 Z9 41 U1 3 U2 6 PU WILDLIFE DISEASE ASSN, INC PI LAWRENCE PA 810 EAST 10TH ST, LAWRENCE, KS 66044-8897 USA SN 0090-3558 J9 J WILDLIFE DIS JI J. Wildl. Dis. PD APR PY 2006 VL 42 IS 2 BP 234 EP 248 PG 15 WC Veterinary Sciences SC Veterinary Sciences GA 071EC UT WOS:000239580000003 PM 16870846 ER PT J AU Stone, J Pinn, VW Rudick, J Lawrence, M Carlyn, M AF Stone, J Pinn, VW Rudick, J Lawrence, M Carlyn, M TI Evaluation of the first 10 years of the Office of Research on Women's Health at the National Institutes of Health: Selected findings SO JOURNAL OF WOMENS HEALTH LA English DT Article C1 NIH, Off Res Womens Hlth, DHHS, Bethesda, MD 20892 USA. RP Pinn, VW (reprint author), NIH, Off Res Womens Hlth, DHHS, Bldg 1,Room 201, Bethesda, MD 20892 USA. EM ORWH-Research@od.nih.gov NR 8 TC 8 Z9 8 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD APR PY 2006 VL 15 IS 3 BP 234 EP 247 DI 10.1089/jwh.2006.15.234 PG 14 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 045PP UT WOS:000237754400003 PM 16620182 ER PT J AU Stone, J Pinn, VW Lawrence, M Lynch, BS AF Stone, J Pinn, VW Lawrence, M Lynch, BS TI Public roundtable on future directions in Women's Health Research at the National Institutes of Health SO JOURNAL OF WOMENS HEALTH LA English DT Article C1 NIH, Off Res Womens Hlth, DHHS, Bethesda, MD 20892 USA. RP Pinn, VW (reprint author), NIH, Off Res Womens Hlth, DHHS, Bldg 1,Room 201, Bethesda, MD 20892 USA. EM ORWH-Research@od.nih.gov NR 3 TC 1 Z9 1 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD APR PY 2006 VL 15 IS 3 BP 248 EP 250 DI 10.1089/jwh.2006.15.248 PG 3 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 045PP UT WOS:000237754400004 PM 16620183 ER PT J AU McDermott, MM Liu, KA Guralnik, JM Ferrucci, L Green, D Greenland, P Tian, L Criqui, MH Lo, C Rifai, N Ridker, PM Zheng, J Pearce, W AF McDermott, MM Liu, KA Guralnik, JM Ferrucci, L Green, D Greenland, P Tian, L Criqui, MH Lo, C Rifai, N Ridker, PM Zheng, J Pearce, W TI Functional decline in patients with and without peripheral arterial disease: Predictive value of annual changes in levels of C-reactive protein and D-dimer SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID NECROSIS-FACTOR-ALPHA; ANKLE BRACHIAL INDEX; SKELETAL-MUSCLE; CARDIOVASCULAR HEALTH; LONGITUDINAL DATA; 6-MINUTE WALK; INTERLEUKIN-6; DISABILITY; CRITERIA; MARKERS AB Background. Inflammation may be a potential mechanism of aging-related functional decline. We determined whether greater annual increases in levels of high sensitivity C-reactive protein (hsCRP) and D-dimer predicted greater decline in functioning among persons with and without lower extremity peripheral arterial disease (PAD). Methods. We prospectively studied 296 men and women with PAD and 191 without PAD. Objective measures of functioning, hsCRP. and D-dimer were obtained at baseline and annually for 3 years (mean follow-up = 36.3 +/- 6.4 months). Results. Among PAD participants, greater annual increases in hsCRP were associated with greater annual declines in 6-minute walk performance (-2.63 ft/mg/L p =.039) but not in other functional outcomes. Higher prior year absolute hsCRP levels were associated with greater declines in 6-minute walk (-2.93 ft/mg/L, p =.022), summary performance score (-0.038/mg/L, p =.017), and rapid paced 4-meter walk (-0.29 cm/mg/L, p =.026) during the subsequent year. Among participants without PAD, greater annual increases in hsCRP were associated with greater annual declines in 6-minute walk (-7.47 ft/mg/L, p =.002). usual-pace 4-meter walk (-0.33 cm/s/mg/L, p <.001), fast paced 4-meter walk (-0.56 cm/s/mg/L, p =.003), and the summary performance score (-0.029 mg/L, p <.001). There were no consistent associations between D-dimer levels and functional decline. Conclusion. These findings Suggest that inflammation may play a role in functional decline in persons with and without PAD. C1 Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. NIA, Lab Epidemiol Demog & Biometry, NIH, Bethesda, MD 20892 USA. NIA, Clin Res Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Diego, San Diego, CA 92103 USA. Harvard Univ, Sch Med, Boston, MA USA. RP McDermott, MM (reprint author), 675 N St Clair,Suite 18-200, Chicago, IL 60611 USA. EM mdm608@northwestern.edu FU NCRR NIH HHS [RR-00048]; NHLBI NIH HHS [R01-HL58099, R01-HL64739] NR 34 TC 26 Z9 26 U1 0 U2 1 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD APR PY 2006 VL 61 IS 4 BP 374 EP 379 PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 035OI UT WOS:000237010500009 PM 16611704 ER PT J AU Zhou, H Yuen, PST Pisitkun, T Gonzales, PA Yasuda, H Dear, JW Gross, P Knepper, MA Star, RA AF Zhou, H Yuen, PST Pisitkun, T Gonzales, PA Yasuda, H Dear, JW Gross, P Knepper, MA Star, RA TI Collection, storage, preservation, and normalization of human urinary exosomes for biomarker discovery SO KIDNEY INTERNATIONAL LA English DT Article DE storage; urine; exosome; biomarker; NHE3; TSG101; ALIX; AQP2; NSE; MDH; Na-K-Cl cotransporter isoform 2 ID PROTEIN; SAMPLES AB Urinary exosomes containing apical membrane and intracellular fluid are normally secreted into the urine from all nephron segments, and may carry protein markers of renal dysfunction and structural injury. We studied methods for collection, storage, and preservation of urinary exosomal proteins. We collected urine from healthy volunteers, added protease inhibitors, and stored urine samples at 4, - 20, and - 80 degrees C for 1 week or 7 months. Samples were thawed with and without extensive vortexing, and three fractions were isolated: urinary sediment, supernatant, and exosome fraction. Protein concentration, electrophoresis patterns, and abundance of seven exosome-associated proteins were measured. Exosome-associated proteins were not detected in sediment or supernatant fractions. Protease inhibitors prevented degradation of exosome-associated proteins. Freezing at - 20 degrees C caused a major loss in exosomes compared to fresh urine. In contrast, recovery after freezing at - 80 degrees C was almost complete. Extensive vortexing after thawing markedly increased exosome recovery in urine frozen at - 20 or - 80 degrees C, even if frozen for 7 months. The recovery from first and second morning urine was similar. The abundance of cytosolic exosome-associated proteins did not decrease during long-term storage. We concluded: ( 1) protease inhibitors are essential for preservation; ( 2) storage at - 80 degrees C with extensive vortexing after thawing maximizes the recovery of urinary exosomes; ( 3) the difference between first and second morning urine exosome-associated protein was small, suggesting minimal protein degradation in the urinary tract/bladder; ( 4) urinary exosomes remain intact during long-term storage. These urine collection, storage, and processing conditions may be useful for future biomarker discovery efforts. C1 NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Univ Med Ctr Carl Gustav Carus, Dept Med, Div Nephrol, Dresden, Germany. RP Star, RA (reprint author), NIDDK, Renal Diagnost & Therapeut Unit, NIH, 10 Ctr Dr,Bldg 10,Room 3N108, Bethesda, MD 20892 USA. EM Robert_Star@nih.gov RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 FU Intramural NIH HHS [Z01 DK043400-08, Z01 HL001285-21, Z99 HL999999] NR 13 TC 201 Z9 216 U1 3 U2 35 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD APR PY 2006 VL 69 IS 8 BP 1471 EP 1476 DI 10.1038/sj.ki.5000273 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 035NR UT WOS:000237008600032 PM 16501490 ER PT J AU Gipson, C Wigglesworth, C AF Gipson, Chester Wigglesworth, Carol TI A word from OLAW and USDA SO LAB ANIMAL LA English DT Editorial Material C1 USDA, APHIS, AC, Washington, DC 20250 USA. NIH, Off Lab Anim Welf, OER, OD,HHS, Bethesda, MD 20892 USA. RP Gipson, C (reprint author), USDA, APHIS, AC, Washington, DC 20250 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD APR PY 2006 VL 35 IS 4 BP 17 EP 17 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 070TD UT WOS:000239546100005 PM 16582893 ER PT J AU Leverich, GS Post, RM AF Leverich, GS Post, RM TI Course of bipolar illness after history of childhood trauma SO LANCET LA English DT Editorial Material ID DISORDER; ABUSE; ADOLESCENTS C1 NIMH, Biol Psychiat Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Leverich, GS (reprint author), NIMH, Biol Psychiat Branch, NIH, DHHS, Bethesda, MD 20892 USA. EM levericg@mail.nih.gov NR 15 TC 66 Z9 67 U1 2 U2 4 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 1 PY 2006 VL 367 IS 9516 BP 1040 EP 1042 DI 10.1016/S0140-6736(06)68450-X PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 030ZF UT WOS:000236673200010 PM 16581389 ER PT J AU Stapleton, JT Xiang, JH Williams, CF AF Stapleton, JT Xiang, JH Williams, CF TI HIV and GB virus C coinfection SO LANCET INFECTIOUS DISEASES LA English DT Letter ID T-LYMPHOCYTE; INFECTION; INHIBITION; SURVIVAL C1 Iowa City VA Med Ctr, Iowa City, IA USA. Univ Iowa, Iowa City, IA 52242 USA. NIAID, Div AIDS, Bethesda, MD 20892 USA. RP Stapleton, JT (reprint author), Univ Iowa Hosp & Clin, Dept Internal Med SW54, GH, 200 Hawkins Dr, Iowa City, IA 52242 USA. EM jack-stapleton@uiowa.edu NR 12 TC 5 Z9 5 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1473-3099 J9 LANCET INFECT DIS JI Lancet Infect. Dis. PD APR PY 2006 VL 6 IS 4 BP 187 EP 188 DI 10.1016/S1473-3099(06)70419-4 PG 2 WC Infectious Diseases SC Infectious Diseases GA 025MW UT WOS:000236271400003 PM 16554239 ER PT J AU Khorashad, JS Anand, M Marin, D Sauders, S Al-Jabary, T Iqbal, A Margerison, S Melo, JV Goldman, JM Apperley, JF Kaeda, J AF Khorashad, JS Anand, M Marin, D Sauders, S Al-Jabary, T Iqbal, A Margerison, S Melo, JV Goldman, JM Apperley, JF Kaeda, J TI The presence of a BCR-ABL mutant allele in CML does not always explain clinical resistance to imatinib SO LEUKEMIA LA English DT Article DE CML; imatinib; kinase mutants; BCR-ABL mutants ID CHRONIC MYELOID-LEUKEMIA; CHRONIC MYELOGENOUS LEUKEMIA; TYROSINE KINASE INHIBITOR; POLYMERASE-CHAIN-REACTION; CHRONIC-PHASE; RESIDUAL DISEASE; DOMAIN MUTATIONS; BLAST CRISIS; MESYLATE; GENE AB The expansion of a leukemia clone bearing a Bcr-Abl kinase domain mutation is associated with acquired resistance to imatinib and may also predict disease progression in patients with Philadelphia-positive chronic myeloid leukemia (CML). Here we report results of pyrosequencing to quantitate the non-mutated and mutant alleles in 12 CML patients monitored over periods ranging from 11 to 58 months, and describe three contrasting kinetic patterns: Group 1 - in four patients total BCR-ABL transcript numbers remained high with the mutant allele predominating; Group 2 - in four patients the total number of BCR-ABL transcripts fell to low levels but the mutant allele predominated; and Group 3 - in four other patients the total level of transcripts remained high (n = 2) or fell (n = 2) but the mutant clone persisted at relatively low level. In Group 2 the mutant leukemia clone was presumably still relatively sensitive to imatinib but in Group 1 the leukemia could be classified as resistant. In Group 3 patients the imatinib sensitivity of the leukemia was variable. We conclude that a mutant clone does not necessarily have a proliferative advantage and its presence does not always account for resistance to imatinib. Other mechanisms underlie resistance in at least some patients. C1 Hammersmith Hosp Trust, Dept Haematol, Imperial Coll London, London, England. Biotage Ltd, Hertford, England. RP Goldman, JM (reprint author), NHLBI, Hematol Branch, Bldg 10,Room 3-5140,10 Ctr Dr, Bethesda, MD 20892 USA. EM goldmanj2@nhlbi.nih.gov OI Iqbal, Ahmed/0000-0002-5648-0539 NR 30 TC 105 Z9 109 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD APR PY 2006 VL 20 IS 4 BP 658 EP 663 DI 10.1038/sj.leu.2404137 PG 6 WC Oncology; Hematology SC Oncology; Hematology GA 038QW UT WOS:000237239100015 PM 16467863 ER PT J AU Hao, XP Shin, MS Zhou, JX Lee, CH Qi, CF Naghashfar, Z Hartley, JW Fredrickson, TN Ward, JM Morse, HC AF Hao, XP Shin, MS Zhou, JX Lee, CH Qi, CF Naghashfar, Z Hartley, JW Fredrickson, TN Ward, JM Morse, HC TI Histologic and molecular characterizations of megakaryocytic leukemia in mice SO LEUKEMIA RESEARCH LA English DT Article DE megakaryocytic leukemia; mouse; microarray; immunohistochemistry; molecular profiling ID ACUTE MYELOID-LEUKEMIA; ACUTE MEGAKARYOBLASTIC LEUKEMIA; TRANSCRIPTION FACTOR GATA-1; VON-WILLEBRAND-FACTOR; DOWN-SYNDROME; INTRACELLULAR DOMAIN; ACQUIRED MUTATIONS; ALPHA-ENHANCER; STEM-CELLS; GENE AB Six cases of megakaryocytic leukemia (MKL) were identified and analyzed for morphology and molecular features. MKL were composed of megakaryocyte lineage cells ranging from immature to quite mature cells. VWF, GATA1 and RUNX1 were strongly expressed in megakaryocytes in both normal spleen and MKL as analyzed by immunohistochemistry (IHC). Altered expression of Meis1, Pbx1 and Psen2 and Lef1 in MKL detected with oligonucleotide microarrays was confirmed by qPCR and IHC. This is the first report of spontaneous MKL in mice, defining VWF as a biomarker for diagnosis and suggesting possible involvement of a series of genes in disease pathogenesis. (C) 2005 Elsevier Ltd. All rights reserved. C1 NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. NIAID, Comparat Med Branch, NIH, Rockville, MD 20852 USA. RP Hao, XP (reprint author), NIAID, Immunopathol Lab, NIH, Rockville, MD 20852 USA. EM xhao@niaid.nih.gov OI Morse, Herbert/0000-0002-9331-3705 FU Intramural NIH HHS NR 61 TC 7 Z9 7 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2006 VL 30 IS 4 BP 397 EP 406 DI 10.1016/j.leukres.2005.08.021 PG 10 WC Oncology; Hematology SC Oncology; Hematology GA 022WG UT WOS:000236086200006 PM 16219351 ER PT J AU Tucker, CA Bebb, G Klasa, RJ Chhanabhai, M Lestou, V Horsman, DE Gascoyne, RD Wiestner, A Masin, D Bally, M Williams, ME AF Tucker, CA Bebb, G Klasa, RJ Chhanabhai, M Lestou, V Horsman, DE Gascoyne, RD Wiestner, A Masin, D Bally, M Williams, ME TI Four human t(11;14)(q13;q32)-containing cell lines having classic and variant features of Mantle Cell Lymphoma SO LEUKEMIA RESEARCH LA English DT Article DE MCL; cell line; cyclin D1; p16; mRNA isoforms ID CHRONIC LYMPHOCYTIC-LEUKEMIA; IN-SITU HYBRIDIZATION; NON-HODGKINS-LYMPHOMA; CYCLIN D1 EXPRESSION; CDK INHIBITORS; MESSENGER-RNA; BREAST-CANCER; GENE; ESTABLISHMENT; ABNORMALITIES AB The objectives of this study were foremost to further characterize pre-existing cell lines containing the t(11;14)(q13;q32) translocation. This translocation along with cyclin D1 overexpression is characteristic of Mantle Cell Lymphoma (MCL), an aggressive B cell neoplasm. Considerable variation in the abundance of cyclin D1 expression was observed. mRNA levels were examined by RT-PCR as differences in cyclin D1 mRNA abundance have been shown to synergize with INK4A/Arf deletions to dictate proliferation rate and survival in MCL patient samples. In this study, the cell lines, Z-138 and HBL-2, which exhibited the fastest growth rates and the shortest survival times in Rag2-M mice, had high expression of either one or both cyclin D1 mRNA isoforms and had negligible expression of p16. On the other hand, NCEB-1 and JVM-2 had low expression of both mRNA isoforms, retained p 16 expression, and had slower growth rates and exhibited longer survival times in Rag2-M mice. Furthermore, JVM-2, which was found to have the lowest expression of cyclin D1, was the only cell line that expressed cyclin D2. The results of the characterization of Z-138, HBL-2, NCEB-1 and JVM-2 reveal that this group of cell lines represents both classic and variant features of MCL. (C) 2005 Elsevier Ltd. All rights reserved. C1 British Columbia Canc Res Ctr, Dept Adv Therapeut, Vancouver, BC V5Z 1L3, Canada. Univ British Columbia, Dept Pathol & Lab Med, Vancouver, BC V5Z 1M9, Canada. British Columbia Canc Agcy, Div Med Oncol, Vancouver, BC V5Z 4E6, Canada. British Columbia Canc Agcy, Div Pathol, Vancouver, BC V5Z 4E6, Canada. NCI, Metab Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Virginia, Ctr Canc, Div Hematol Oncol, Charlottesville, VA 22908 USA. Univ Virginia, Ctr Canc, Hematol Malignancy Program, Charlottesville, VA 22908 USA. Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. RP Tucker, CA (reprint author), British Columbia Canc Res Ctr, Dept Adv Therapeut, 675 W 10th Ave,5th Floor, Vancouver, BC V5Z 1L3, Canada. EM ctucker@bccrc.ca NR 41 TC 20 Z9 20 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0145-2126 J9 LEUKEMIA RES JI Leuk. Res. PD APR PY 2006 VL 30 IS 4 BP 449 EP 457 DI 10.1016/j.leukres.2005.08.016 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 022WG UT WOS:000236086200011 PM 16183118 ER PT J AU Aringer, M Stamm, TA Pisetsky, DS Yarboro, CH Cieza, A Smolen, JS Stucki, G AF Aringer, M Stamm, TA Pisetsky, DS Yarboro, CH Cieza, A Smolen, JS Stucki, G TI ICF Core Sets: how to specify impairment and function in systemic lupus erythematosus SO LUPUS LA English DT Article DE impairment; quality of life; systemic lupus erythematosus; World Health Organization ID CONSENSUS-STUDY-GROUP; DISEASE-ACTIVITY; INTERNATIONAL CLASSIFICATION; RHEUMATOLOGY RESEARCH; EUROPEAN WORKSHOP; HEALTH; INDEX; DISABILITY AB The World Health Organization's International Classification of Function (ICF) is a tool to characterize and illuminate better the full of array of problems a patient faces when affected by disease. Specifying these problems is a particular challenge in a disease like systemic lupus erythematosus (SLE) because of the wide variety in organ systems involved, its variable activity and severity, and considerable ethnic and local differences. The authors of this manuscript believe, however, that a broader understanding will prove essential for optimal patient care, and that there is sufficient experience now in defining ICF Core Sets to successfully complete core sets for SLE. Therefore, we will embark on an international project for developing ICF Core Sets for SLE, which we here delineate. This development will include two versions: 1) The Brief ICF Core Set for SLE will be a very focused list of categories essential for SLE clinical trials; and 2) The Comprehensive ICF Core Set will be much broader and useful for guiding multidisciplinary assessment in patients with SLE. Both Core Sets will be developed in a formal decision-making and consensus process of health professionals integrating evidence gathered from preliminary studies. The final definition of the Core Sets will occur at a consensus conference which will integrate: i) a systematic review of the literature regarding the outcome measures used in clinical trials and selected observational studies; ii) focus groups or semi-structured interviews with SLE patients; iii) a Delphi exercise with world wide involvement of experts; and iv) the evidence from empirical studies. The development of these SLE ICF Core Sets is designed to be an inclusive, open, worldwide process. We therefore invite both SLE clinical experts and SLE patients to participate actively. C1 Med Univ Vienna, Dept Rheumatol, AKH, A-1090 Vienna, Austria. German Inst Med Documentat & Informat DIMDI, WHO Collaborating Ctr Family Int Classificat, ICF Res Branch, IMBK, Munich, Germany. Univ Munich, Dept Phys Med & Rehabil, Munich, Germany. Durham VA Hosp, Med Res Serv, Durham, NC USA. Duke Univ, Med Ctr, Div Rheumatol & Immunol, Durham, NC USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Lainz Hosp, Dept Med 2, Vienna, Austria. RP Aringer, M (reprint author), Med Univ Vienna, Dept Rheumatol, AKH, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM Martin.Aringer@meduniwien.ac.at OI Aringer, Martin/0000-0003-4471-8375 NR 23 TC 12 Z9 14 U1 1 U2 6 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PD APR PY 2006 VL 15 IS 4 BP 248 EP 253 DI 10.1191/0961203306lu2298xx PG 6 WC Rheumatology SC Rheumatology GA 034BV UT WOS:000236900400011 PM 16686267 ER PT J AU Forbes, JG Morris, HD Wang, K AF Forbes, JG Morris, HD Wang, K TI Multimodal imaging of the sonic organ of Porichthys notatus, the singing midshipman fish SO MAGNETIC RESONANCE IMAGING LA English DT Article DE sonic muscle; sarcomere; wide Z-bands; striated muscle; MRI; CT ID SKELETAL-MUSCLE ARCHITECTURE; FIBER ARCHITECTURE; T-2 RELAXATION; MOUSE; SOUND; MRI; RELAXOMETRY; TOADFISH; EXERCISE; HEARTS AB The sonic midshipman fish, Porichthys notatus, is a bottom-dwelling species whose swim bladder has evolved into a highly specialized, sound-producing organ. The males of this species exist in two distinct morphs with different physical characteristics and sexual strategies. The Type I males have a much larger sound organ and are capable of generating a loud similar to 100 Hz tone continuously for over an hour to attract females. This sound is produced by sonic muscle and represents one of the most superfast and super-enduring striated muscles found in nature. Each fiber contains a hollow, tubular contractile apparatus composed of radially arranged myofibrils with extremely broad Z-bands that are supported by a desmin-rich cytoskeleton. We have used micro computed tomography (CT) imaging and magnetic resonance (MR) imaging to visualize the location of the sonic organ in an intact male fish. We have also obtained high-resolution MR images of the excised swim bladders from both male types. The images of the Type I sonic organ are strikingly detailed and high-contrast, revealing both the internal organization of the bladder and the crisscrossing muscle fibers and their mode of attachment to the underlying bladder. The high-contrast variation in these images is due to different T, values for fiber bundles and the spaces between the bundles. Direct MR imaging of intact Type I sonic organ in Type I midshipman fish is a powerful approach to understanding the contraction of this superfast muscle and the oscillation of its bladder to produce mating calls, and how placement of the sonic organ in the body of the fish sheds light on its prodigious ability to produce and transmit its loud mating call. (C) 2006 Elsevier Inc. All rights reserved. C1 NIAMSD, Muscle Prote & Nanotechnol Sect, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. NINDS, NIH, MRI Res Facil, Bethesda, MD 20892 USA. RP Wang, K (reprint author), NIAMSD, Muscle Prote & Nanotechnol Sect, Muscle Biol Lab, NIH, Bethesda, MD 20892 USA. EM wangk@exchange.nih.gov NR 36 TC 7 Z9 7 U1 0 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0730-725X J9 MAGN RESON IMAGING JI Magn. Reson. Imaging PD APR PY 2006 VL 24 IS 3 BP 321 EP 331 DI 10.1016/j.mri.2005.10.036 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 030SY UT WOS:000236656100014 PM 16563962 ER PT J AU Vignaud, A Rodriguez, I Ennis, DB DeSilva, R Kellman, P Taylor, J Bennett, E Wen, H AF Vignaud, A Rodriguez, I Ennis, DB DeSilva, R Kellman, P Taylor, J Bennett, E Wen, H TI Detection of myocardial capillary orientation with intravascular iron-oxide nanoparticles in spin-echo MRI SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE magnetic susceptibility; cardiac MRI; USPIO; Ferumoxtran-10; T-2 tensor; capillary; myofiber; microvascular structure; diffusion; helical ID FIBER-ORIENTATION; CONTRAST AGENTS; SUSCEPTIBILITY; BLOOD AB in mammalian hearts the capillaries are closely aligned with the muscle fibers. We report our observation of a main-field direction-dependent contrast in MR spin-echo (SE) images of the heart in the presence of Ferumoxtran-10, an intravascular iron-oxide nanoparticle contrast agent (CA). We describe a novel MRI method for mapping the preferential orientation of capillaries in the myocardial wall. The eigenvector corresponding to the minimum eigen value of the R-2 relaxation rate tensor is consistent with the expected orientation of the capillary network. Preliminary results also demonstrate the feasibility of this method for in vivo application to rodent imaging. C1 NHLBI, Imaging Phys Sect, Cardiac Energet Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. NHLBI, Cardiovasc Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. Stanford Univ, Dept Radiol, Palo Alto, CA 94304 USA. RP Wen, H (reprint author), NHLBI, Imaging Phys Sect, Cardiac Energet Lab, Div Intramural Res,NIH, Bldg 10,Room B1D416 MSC 1061, Bethesda, MD 20892 USA. EM wenh@nhlbi.nih.gov RI Rodriguez, Ignacio/B-1006-2015; Wen, Han/G-3081-2010 OI Rodriguez, Ignacio/0000-0002-4262-2516; Wen, Han/0000-0001-6844-2997 FU Intramural NIH HHS [ZIA HL004606-13] NR 16 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD APR PY 2006 VL 55 IS 4 BP 725 EP 730 DI 10.1002/mrm.20827 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 029ZK UT WOS:000236602700003 PM 16506158 ER PT J AU Matsumoto, K Kawai, S Chignell, CF Utsumi, H AF Matsumoto, K Kawai, S Chignell, CF Utsumi, H TI Location of anthralin radical generation in mouse skin by UV-A irradiation: An estimation using microscopic EPR spectral-spatial imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE electron paramagnetic resonance; spectral-spatial imaging; skin; anthralin; antioxidant ID ELECTRON-PARAMAGNETIC-RESONANCE; DITHRANOL ANTHRALIN; FIELD GRADIENT; RECONSTRUCTION; 9-ANTHRONES; IRRITATION; ANALOGS; MICE AB In vivo location of the anthralin radical generated in mouse skin by ultraviolet A (UV-A) irradiation was estimated by microscopic electron paramagnetic resonance (EPR) spectral-spatial imaging. An X-band EPR spectrometer equipped with specially designed high-power imaging coils and a TE-mode cavity was employed. The maximum field gradient used in this study was 6.77 mT/mm. Anthralin was applied to the dorsal skin of live mice, which were then exposed to UV-A irradiation. A broad singlet EPR spectrum (peak-to-peak line width = 0.6 mT and g = 2.004) was obtained. Microscopic EPR spectral-spatial imaging of the skin tissue showed that the anthralin radical was located mainly in the epidermis (27 mu m from the skin surface). This result was consistent with the finding that the proportions of the radical in the dermis and epidermis were about 15% and 85%, respectively. C1 Kyushu Univ, Fac Pharmaceut Sci, Dept Biofunct Sci, Higashi Ku, Fukuoka 8128582, Japan. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. RP Utsumi, H (reprint author), Kyushu Univ, Fac Pharmaceut Sci, Dept Biofunct Sci, Higashi Ku, Fukuoka 8128582, Japan. EM utsumi@pch.phar.kyushu-u.ac.jp NR 30 TC 8 Z9 8 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD APR PY 2006 VL 55 IS 4 BP 738 EP 742 DI 10.1002/mrm.20862 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 029ZK UT WOS:000236602700005 PM 16528709 ER PT J AU Nezafat, R Stuber, M Ouwerkerk, R Gharib, AM Desai, MY Pettigrew, RI AF Nezafat, R Stuber, M Ouwerkerk, R Gharib, AM Desai, MY Pettigrew, RI TI B-1-insensitive T-2 preparation for improved coronary magnetic resonance angiography at 3 T SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE coronary MR angiography; T-2 prep; adiabatic pulses; 3 T cardiac MR; contrast enhancement ID MR-ANGIOGRAPHY; ADIABATIC PULSES; PLANE ROTATIONS; CONTRAST AGENT; CARDIAC MRI; BREATH-HOLD; ARTERIES; FIELDS; NMR; COILS AB At 3 T, the effective wavelength of the RF field is comparable to the dimension of the human body, resulting in B-1 standing wave effects and extra variations in phase. This effect is accompanied by an increase in B-0 field inhomogeneity compared to 1.5 T. This combination results in nonuniform magnetization preparation by the composite MLEV weighted T-2 preparation (T-2 Prep) sequence used for coronary magnetic resonance angiography (MRA). A new adiabatic refocusing T-2 Prep sequence is presented in which the magnetization is tipped into the transverse plane with a hard RF pulse and refocused using a pair of adiabatic fast-passage RF pulses. The isochromats are subsequently returned to the longitudinal axis using a hard RF pulse. Numerical simulations predict an excellent suppression of artifacts originating from B, inhomogeneity while achieving good contrast enhancement between coronary arteries and surrounding tissue. This was confirmed by an in vivo study, in which coronary MR angiograms were obtained without a T-2 Prep, with an MLEV weighted T-2 Prep and the proposed adiabatic T-2 Prep. Improved quantitative and qualitative coronary MRA image measurement was achieved using the adiabatic T-2 Prep at 3 T. C1 Johns Hopkins Univ, Sch Med, Dept Biomed Engn, Baltimore, MD 21287 USA. NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Russell H Morgan Dept Radiol & Radiol Sci, Baltimore, MD 21287 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21287 USA. Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21287 USA. RP Stuber, M (reprint author), Johns Hopkins Univ, Sch Med, Dept Radiol, JHOC 4223 601 N Carolina St, Baltimore, MD 21287 USA. EM mstuber@mri.jhu.edu RI Stuber, Matthias/B-2949-2010; Gharib, Ahmed/O-2629-2016 OI Stuber, Matthias/0000-0001-9843-2028; Gharib, Ahmed/0000-0002-2476-481X NR 35 TC 60 Z9 64 U1 2 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD APR PY 2006 VL 55 IS 4 BP 858 EP 864 DI 10.1002/mrm.20835 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 029ZK UT WOS:000236602700019 PM 16538606 ER PT J AU Koay, CG Carew, JD Alexander, AL Basser, PJ Meyerand, ME AF Koay, CG Carew, JD Alexander, AL Basser, PJ Meyerand, ME TI Investigation of anomalous estimates of tensor-derived quantities in diffusion tensor imaging SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE diffusion tensor imaging; negative diffusivity; fractional anisotropy; constrained optimization; diffusion tensor estimation ID NOISE; MRI; FEATURES; TISSUES AB The diffusion tensor is typically assumed to be positive definite. However, noise in the measurements may cause the eigenvalues of the tensor estimate to be negative, thereby violating this assumption. Negative eigenvalues in diffusion tensor imaging (DTI) data occur predominately in regions of high anisotropy and may cause the fractional anisotropy (FA) to exceed unity. Two constrained least squares methods for eliminating negative eigenvalues are explored. These methods, the constrained linear least squares method (CLLS) and the constrained nonlinear least squares method (CNLS), are compared with other commonly used algebraic constrained methods. The CLLS tensor estimator can be shown to be equivalent to the linear least squares (LLS) tensor estimator when the LLS tensor estimate is positive definite. Similarly, the CNLS tensor estimator can be shown to be equivalent to the nonlinear least squares (NLS) tensor estimator when the NLS tensor estimate is positive definite. The constrained least squares methods for eliminating negative eigenvalues are evaluated with both simulations and in vivo human brain DTI data. Simulation results show that the CNLS method is, in terms of mean squared error for estimating trace and FA, the most effective method for correcting negative eigenvalues. C1 NICHD, STBB, LIMB, NIH, Bethesda, MD 20892 USA. Univ Wisconsin, Dept Phys, Madison, WI 53706 USA. Univ Wisconsin, Dept Stat, Madison, WI 53706 USA. Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. RP Koay, CG (reprint author), NICHD, STBB, LIMB, NIH, Bldg 13,Room 3W16,13 S Dr, Bethesda, MD 20892 USA. EM guankoac@mail.nih.gov RI Basser, Peter/H-5477-2011 FU NEI NIH HHS [EY07119]; NIBIB NIH HHS [EB002012]; NIMH NIH HHS [MH062015] NR 20 TC 44 Z9 44 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGN RESON MED JI Magn. Reson. Med. PD APR PY 2006 VL 55 IS 4 BP 930 EP 936 DI 10.1002/mrm.20832 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 029ZK UT WOS:000236602700028 PM 16526013 ER PT J AU Henke, RT Kim, SE Maitra, A Paik, S Wellstein, A AF Henke, RT Kim, SE Maitra, A Paik, S Wellstein, A TI Expression analysis of mRNA in formalin-fixed, paraffin-embedded archival tissues by mRNA in situ hybridization SO METHODS LA English DT Article DE cytokines; gene expression analysis; formalin-fixed tissues; growth factors; in situ hybridization; mRNA; paraffin-embedded tissue; tissue microarray ID FACTOR-BINDING-PROTEIN; LASER CAPTURE MICRODISSECTION; GROWTH-FACTOR PLEIOTROPHIN; BREAST-CANCER; GENE-EXPRESSION; COACTIVATOR AIB1; UP-REGULATION; MICROARRAY; TUMOR; OVEREXPRESSION AB Gene expression in diseased tissues can indicate the contribution to a disease process and potentially guide therapeutic decision-making. Archival tissues with associated clinical Outcome may be useful to discover or validate the role of a candidate gene in a disease process or the response to therapy. Such archival tissues are commonly formalin-fixed and paraffin-embedded, restricting the methods available for gene expression analysis. Obviously, the detection of proteins in tissues requires adaptation for each protein and the detection of secreted proteins can prove difficult or of reduced value since the protein detected may not reflect the total amount produced. Thus. we describe here a reliable method for the detection of mRNA in archival tissues. The method for mRNA in situ hybridization (ISH) was adapted by us for > 15 different genes and applied to several hundred tissue microarrays (TMAs) and full sections generating > 10,000 expression data points. We also discuss the utility of TMAs to simultaeneously analyze several hundred tissue samples on one slide to minimize variability and preserve valuable tissue samples. Experimental protocols are provided that can be implemented without major hurdles in a typical molecular pathology laboratory and we discuss quantitative analysis as well as advantages and limitations of ISH with a special focus on secreted proteins. We conclude that ISH is a reliable and cost effective approach to gene expression analysis in archival tissues that is amenable to screening of series Of tissues or of genes of interest. (c) 2006 Elsevier Inc. All rights reserved. C1 Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC 20057 USA. Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21218 USA. NSABP, Div Pathol, Pittsburgh, PA USA. RP Wellstein, A (reprint author), Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC 20057 USA. EM wellstea@georgetown.edu OI Wellstein, Anton/0000-0002-0570-4950 NR 35 TC 17 Z9 18 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 1046-2023 J9 METHODS JI Methods PD APR PY 2006 VL 38 IS 4 BP 253 EP 262 DI 10.1016/j.ymeth.2005.11.013 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 029YA UT WOS:000236599100003 PM 16513366 ER PT J AU Elshal, MF McCoy, JP AF Elshal, MF McCoy, JP TI Multiplex bead array assays: Performance evaluation and comparison of sensitivity to ELISA SO METHODS LA English DT Article DE cytokine; lumnex; X-map; multiplex; ELISA ID HUMAN CYTOKINES; SINGLE-SAMPLE; SIMULTANEOUS QUANTIFICATION; FLOW-CYTOMETRY; HUMAN PLASMA; VALIDATION; IMMUNOASSAY; VOLUMES; SYSTEM; PANEL AB The measurement of soluble cytokines and other analytes in serum and plasma is becoming increasingly important in the study and management of many diseases. As a result, there is a growing demand for rapid, precise, and cost-effective measurement of such analytes in both clinical and research laboratories. Multiplex bead array assays provide quantitative measurement of large numbers of analytes using an automated 96-well plate format. Enzyme-linked immunosorbent assay (ELISAs) have long been the standard for quantitative analysis of cytokines and other biomarkers, but are not well suited for high throughput multiplex analyses. However, prior to replacement of ELISA assays with multiplex bead array assays, there is a need to know how comparable these two methods are for quantitative analyses. A number of published studies have compared these two methods and it is apparent that certain elements of these assays, such as the clones of monoclonal antibodies used for detection and reporting, are pivotal in obtaining similar results front both assays. By careful consideration of these variables, it should be possible to utilize multiplex bead array assays in lieu of ELISAs for studies requiring high throughput analysis of numerous analytes. Crown copyright (c) 2006 Published by Elsevier Inc. All rights reserved. C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP McCoy, JP (reprint author), NHLBI, NIH, Bethesda, MD 20892 USA. EM mccoyjp@mail.nih.gov RI Elshal, Mohamed/H-7953-2012 FU Intramural NIH HHS [Z99 HL999999] NR 26 TC 241 Z9 249 U1 1 U2 39 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD APR PY 2006 VL 38 IS 4 BP 317 EP 323 DI 10.1016/j.ymeth.2005.11.010 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 029YA UT WOS:000236599100010 PM 16481199 ER PT J AU Doffinger, R Patel, SY Kumararatne, DS AF Doffinger, R Patel, SY Kumararatne, DS TI Host genetic factors and mycobacterial infections: lessons from single gene disorders affecting innate and adaptive immunity SO MICROBES AND INFECTION LA English DT Review DE primary immunodeficiency; mycobacteria ID SEVERE COMBINED IMMUNODEFICIENCY; DISSEMINATED BCG INFECTION; ANHIDROTIC ECTODERMAL DYSPLASIA; BONE-MARROW-TRANSPLANTATION; INTERFERON-GAMMA-RECEPTOR; CALMETTE-GUERIN INFECTION; HYPER-IGM SYNDROME; CYSTIC-FIBROSIS LUNG; HYPERIMMUNOGLOBULIN-E SYNDROME; ESSENTIAL MODULATOR MUTATION AB This review summarizes the association of increased susceptibility to mycobacterial disease in patients with genetic defects affecting innate and adaptive immunity. The optimum function of CD4 T-cell and macrophage function is critically important for immunity against mycobacteria. Antibody, complement and neutrophil function is not required for effective anti-mycobacterial immunity. (c) 2006 Elsevier SAS. All rights reserved. C1 Addenbrookes Hosp, Dept Clin Biochem & Immunol, Cambridge CB2 2QQ, England. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Kumararatne, DS (reprint author), Addenbrookes Hosp, Dept Clin Biochem & Immunol, Box 109,Hills Rd, Cambridge CB2 2QQ, England. EM dsk22@cam.ac.uk NR 122 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD APR PY 2006 VL 8 IS 4 BP 1141 EP 1150 DI 10.1016/j.micinf.2005.10.028 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 045PM UT WOS:000237754100022 PM 16520078 ER PT J AU Haverkamp, MH van Dissel, JT Holland, SM AF Haverkamp, MH van Dissel, JT Holland, SM TI Human host genetic factors innontuberculous mycobacterial infection: lessons from single gene disorders affecting innate and adaptive immunity and lessons from molecular defects in interferon-gamma-dependent signaling SO MICROBES AND INFECTION LA English DT Article DE interferon-gamma; interferon-gamma receptor; Stat-1; mycobacterium; mutation ID RECEPTOR 1 DEFICIENCY; STEM-CELL TRANSPLANTATION; NECROSIS-FACTOR-ALPHA; TOLL-LIKE RECEPTOR-2; IFN-GAMMA; AVIUM INFECTION; SELECTIVE SUSCEPTIBILITY; MOUSE MACROPHAGES; HUMAN MONOCYTES; MESSENGER-RNA AB Mendelian defects in interferon-gamma (IFN-gamma) signaling most commonly lead to infection with nontuberculous mycobacteria. Mutations have been identified in the genes encoding IFN-gamma-receptor-1, IFN-gamma-receptor-2 and Stat-1. Partial and complete deficiencies in signaling are found, leading to parallel clinical, pathological, and cellular phenotypes. These rare defects have led to better molecular and mechanistic understanding of the role of IFN-gamma in the human immune system. (c) 2006 Elsevier SAS. All rights reserved. C1 NIH, Lab Clin Infect Dis, Bethesda, MD 20892 USA. Leiden Univ, Ctr Med, Dept Infect Dis, NL-2300 RC Leiden, Netherlands. RP Haverkamp, MH (reprint author), NIH, Lab Clin Infect Dis, Bldg 10-CRC,Rm B3-4233,MSC 1684,10 Ctr Dr, Bethesda, MD 20892 USA. EM mhaverkamp@niaid.nih.gov NR 42 TC 42 Z9 42 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD APR PY 2006 VL 8 IS 4 BP 1157 EP 1166 DI 10.1016/j.micinf.2005.10.029 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 045PM UT WOS:000237754100024 PM 16520075 ER PT J AU Yap, GS Shaw, MH Ling, Y Sher, A AF Yap, GS Shaw, MH Ling, Y Sher, A TI Genetic analysis of host resistance to intracellular pathogens: lessons from studies of Toxoplasma gondii infection SO MICROBES AND INFECTION LA English DT Article DE Toxoplasma gondii; innate immunity; cytokine ID INDUCIBLE NITRIC-OXIDE; IFN-GAMMA; IL-12 PRODUCTION; B10.Q/J MICE; INTERFERON; IMMUNITY; MACROPHAGES; MECHANISMS; ABSENCE; LRG-47 AB Cell-mediated immunity to Toxoplasma gondii establishes and maintains a balanced host-pathogen relationship. Recent analyses using spontaneous and genetically engineered mouse mutants have yielded a clearer picture of factors positively and negatively regulating the host immune response and a better understanding of cytokine-inducible intracytoplasmic mechanisms that lead to intracellular pathogen suppression and demise. (c) 2006 Elsevier SAS. All rights reserved. C1 Brown Univ, Dept Mol Microbiol & Immunol, Providence, RI 02912 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Yap, GS (reprint author), Brown Univ, Dept Mol Microbiol & Immunol, Providence, RI 02912 USA. EM george_yap@brown.edu FU NCRR NIH HHS [RR015578]; NIAID NIH HHS [AI50618] NR 30 TC 24 Z9 26 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD APR PY 2006 VL 8 IS 4 BP 1174 EP 1178 DI 10.1016/j.micinf.2005.10.031 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 045PM UT WOS:000237754100026 PM 16513380 ER PT J AU Shianna, KV Marchuk, DA Strand, MK AF Shianna, KV Marchuk, DA Strand, MK TI Genomic characterization of POS5, the Saccharomyces cerevisiae mitochondrial NADH kinase SO MITOCHONDRION LA English DT Article DE Pos5; NAD kinase; NADH kinase; Friedreich's ataxia; oxidative stress; mitochondria; iron-sulfur cluster assembly ID REDUCTASE HOMOLOG ARH1P; IRON HOMEOSTASIS; FRIEDREICH ATAXIA; YEAST; MOUSE; EXPRESSION; IDENTIFICATION; ENZYMES; STRESS; CELLS AB Disruption of the Saccharomyces cerevisiae mitochondrial NADH kinase POS5 increases the mitochondrial mutation rate 50-fold. Whereas most multicellular eukaryotic genomes have one NADH kinase gene, the yeast genome contains three distinct genes encoding NAD/H kinase activity. To determine if all three genes are essential for viability we constructed combinations of gene knockouts. We show that only the pos5 Delta utrl Delta combination is synthetically lethal, demonstrating an essential overlapping function, and showing that NAD/H kinase activity is essential for eukaryotic viability. The single human NAD/H kinase gene can rescue the lethality of the double knockout in yeast, demonstrating that the single human gene can fill the various functions provided by the three yeast genes. The human NAD/H kinase gene harbors very common sequence variants, but all of these equally complement the synthetic lethality in yeast, illustrating that each of these are functionally wild-type. To understand the molecular mechanism of the mitochondrial genome instability of pos5 mutation we performed gene expression analysis on the pos5 Delta. The pos5 Delta resulted in an increase in expression of most of the iron transport genes including key genes involved in iron-sulfur cluster assembly. Decreased expression occurred in many genes involved in the electron transport chain. We show that the pos5 Delta expression pattern is similar to the frataxin homolog knockout (yfh1 Delta), the yeast model for Friedreich's ataxia. These combined data show that the POS5 NAD/H kinase is an important protein required for a variety of essential cellular pathways and that deficient iron-sulfur cluster assembly may play a critical role in the mitochondrial mutator phenotype observed in the pos5 Delta. (c) 2006 Elsevier B.V. and Mitochondria Research Society. All rights reserved. C1 Natl Inst Environm Hlth Sci, Mol Genet Lab, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. RP Strand, MK (reprint author), Natl Inst Environm Hlth Sci, Mol Genet Lab, POB 12233,MD E3-01, Res Triangle Pk, NC 27709 USA. EM strand@niehs.nih.gov NR 30 TC 11 Z9 11 U1 2 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD APR PY 2006 VL 6 IS 2 BP 94 EP 101 DI 10.1016/j.mito.2006.02.003 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 058JC UT WOS:000238660300006 PM 16621727 ER PT J AU Mbuchi, M Bates, PA Ilg, T Coe, JE Raynes, JG AF Mbuchi, M Bates, PA Ilg, T Coe, JE Raynes, JG TI C-reactive protein initiates transformation of Leishmania donovani and L-mexicana through binding to lipophosphoglycan SO MOLECULAR AND BIOCHEMICAL PARASITOLOGY LA English DT Article DE pentraxin; amastigote; promastigote; hamster female protein ID AMASTIGOTE-LIKE FORMS; HAMSTER FEMALE PROTEIN; AXENIC AMASTIGOTES; DIFFERENTIATION; PROMASTIGOTES; TRANSMISSION; TEMPERATURE; CULTIVATION; MACROPHAGES; PENTRAXIN C1 Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, Immunol Unit, London WC1E 7HT, England. Univ Liverpool, Liverpool Sch Trop Med, Mol & Biochem Parasitol Grp, Liverpool L3 5QA, Merseyside, England. Max Planck Inst Biol, Abt Membranbiochem, D-72076 Tubingen, Germany. NIAID, Rocky Mt Lab, Hamilton, MT 59840 USA. RP Raynes, JG (reprint author), Univ London London Sch Hyg & Trop Med, Dept Infect & Trop Dis, Immunol Unit, Keppel St, London WC1E 7HT, England. EM john.raynes@lshtm.ac.uk RI Raynes, John/G-7932-2011; OI Raynes, John/0000-0002-8536-1328; Bates, Paul/0000-0001-6861-5421 NR 27 TC 0 Z9 1 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-6851 J9 MOL BIOCHEM PARASIT JI Mol. Biochem. Parasitol. PD APR PY 2006 VL 146 IS 2 BP 259 EP 264 DI 10.1016/j.molbiopara.2005.12.003 PG 6 WC Biochemistry & Molecular Biology; Parasitology SC Biochemistry & Molecular Biology; Parasitology GA 026EQ UT WOS:000236320700014 PM 16417933 ER PT J AU Budd, ME Reis, CC Smith, S Myung, K Campbell, JL AF Budd, ME Reis, CC Smith, S Myung, K Campbell, JL TI Evidence suggesting that Pif1 helicase functions in DNA replication with the DNA2 helicase/nuclease and DNA polymerase delta SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID OKAZAKI FRAGMENT MATURATION; GROSS CHROMOSOMAL REARRANGEMENTS; SACCHAROMYCES-CEREVISIAE; FISSION YEAST; FLAP ENDONUCLEASE-1; GENOME INSTABILITY; FORK PROGRESSION; LIGATABLE NICK; RIBOSOMAL DNA; IN-VIVO AB The precise machineries required for two aspects of eukaryotic DNA replication, Okazaki fragment processing (OFP) and telomere maintenance, are poorly understood. In this work, we present evidence that Saccharomyces cerevisiae Pif1 helicase plays a wider role in DNA replication than previously appreciated and that it likely functions in conjunction with Dna2 helicase/nuclease as a component of the OFP machinery. In addition, we show that Dna2, which is known to associate with telomeres in a cell-cycle-specific manner, may be a new component of the telomere replication apparatus. Specifically, we show that deletion of PIF1 suppresses the lethality of a DNA2-null mutant. The pif1 Delta dna2 Delta strain remains methylmethane sulfonate sensitive and temperature sensitive; however, these phenotypes can be suppressed by further deletion of a subunit of poll delta, POL32. Deletion of PIF1 also suppresses the cold-sensitive lethality and hydroxyurea sensitivity of the pol32 Delta strain. Dna2 is thought to function by cleaving long flaps that arise during OFP due to excessive strand displacement by pol delta and/or by an as yet unidentified helicase. Thus, suppression of dna2 Delta can be rationalized if deletion of POL32 and/or PIF1 results in a reduction in long flaps that require Dna2 for processing. We further show that deletion of DNA2 suppresses the long-telomere phenotype and the high rate of formation of gross chromosomal rearrangements in pif1 Delta mutants, suggesting a role for Dna2 in telomere elongation in the absence of Pif1. C1 CALTECH, Braun Labs, Pasadena, CA 91125 USA. Natl Human Genome Res Inst, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Gulbenkian Ph D Program Biomed, P-2780156 Oeiras, Portugal. RP Campbell, JL (reprint author), CALTECH, Braun Labs, 147-75, Pasadena, CA 91125 USA. EM jcampbel@caltech.edu FU Intramural NIH HHS; NIGMS NIH HHS [GM25508, R01 GM025508] NR 50 TC 111 Z9 117 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2006 VL 26 IS 7 BP 2490 EP 2500 DI 10.1128/MCB.26.7.2490-2500.2006 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 026BR UT WOS:000236312200003 PM 16537895 ER PT J AU Liu, H Mulholland, N Fu, HQ Zhao, K AF Liu, H Mulholland, N Fu, HQ Zhao, K TI Cooperative activity of BRG1 and Z-DNA formation in chromatin remodeling SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID SWI-SNF COMPLEX; TRANSCRIPTIONAL REGULATION; HISTONE MODIFICATIONS; SWI/SNF COMPLEXES; FORMING SEQUENCES; HUMAN GENOME; BAF COMPLEX; BINDING; GENE; ACETYLATION AB The mammalian genome contains tens of thousands of CG and TG repeat sequences that have high potential to form the nonclassical left-handed double-helical Z-DNA structure. Previously we showed that activation of the colony-stimulating factor 1 (CSF1) gene by the chromatin remodeling enzyme, BRG1, results in formation of Z-DNA at the TG repeat sequence located within the promoter. In this report, we show that the TG repeats are assembled in a positioned nucleosome in the silent CSF1 promoter and that activation by BRG1 disrupts this nucleosome and results in Z-DNA formation. Active transcription is not required for the formation of Z-DNA but does result in an expanded region of Z-DNA. Formation of sequences by both BRG1 and the Z-DNA is required for effective chromatin remodeling of the CSF1 promoter. We propose the Z-DNA formation induced by BRG1 promotes a transition from a transient and partial remodeling to a more extensive disruption of the canonical nucleosomal structure. The data presented in this report establish that Z-DNA formation is an important mechanism in modulating chromatin structure, in similarity to the activities of ATP-dependent remodelers and posttranslational histone modifications. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. RP Zhao, K (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Room 7N311,9000 Rockville Pike, Bethesda, MD 20892 USA. EM zhaok@nhlbi.nih.gov FU Intramural NIH HHS NR 45 TC 59 Z9 64 U1 2 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2006 VL 26 IS 7 BP 2550 EP 2559 DI 10.1128/MCB.26.7.2550-2559.2006 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 026BR UT WOS:000236312200009 PM 16537901 ER PT J AU Sadagurski, M Yakar, S Weingarten, G Holzenberger, M Rhodes, CJ Breitkreutz, D LeRoith, D Wertheimer, E AF Sadagurski, M Yakar, S Weingarten, G Holzenberger, M Rhodes, CJ Breitkreutz, D LeRoith, D Wertheimer, E TI Insulin-like growth factor 1 receptor signaling regulates skin development and inhibits skin keratinocyte differentiation SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR-I; INSULIN-RECEPTOR; PROTEIN-KINASE; PHOSPHATIDYLINOSITOL 3-KINASE; ADIPOCYTE DIFFERENTIATION; BROWN ADIPOCYTES; EPIDERMAL-GROWTH; EXPRESSION; MICE; CELLS AB The insulin-like growth factor 1 receptor (IGF-1R) is a multifunctional receptor that mediates signals for cell proliferation, differentiation, and survival. Genetic experiments showed that IGF-1R inactivation in skin results in a disrupted epidermis. However, because IGF-1R-null mice die at birth, it is difficult to study the effects of IGF-1R on skin. By using a combined approach of conditional gene ablation and a three-dimensional organotypic model, we demonstrate that IGF-1R-deficient skin cocultures show abnormal maturation and differentiation patterns. Furthermore, IGF-1R-null keratinocytes exhibit accelerated differentiation and decreased proliferation. Investigating the signaling pathway downstream of IGF-1R reveals that insulin receptor substrate 2 (IRS-2) overexpression compensates for the lack of IGF-1R, whereas IRS-1 overexpression does not. We also demonstrate that phosphatidylinositol 3-kinase and extracellular signal-regulated kinase 1 and 2 are involved in the regulation of skin keratinocyte differentiation and take some part in mediating the inhibitory signal of IGF-1R on differentiation. In addition, we show that mammalian target of rapamycin plays a specific role in mediating IGF-1R impedance of action on keratinocyte differentiation. In conclusion, these results reveal that IGF-1R plays an inhibitory role in the regulation of skin development and differentiation. C1 Tel Aviv Univ, Dept Pathol, Sackler Sch Med, IL-69978 Tel Aviv, Israel. NIDDKD, Diabet Branch, NIH, Bethesda, MD 20892 USA. St Antonius Hosp, INSERM, U515, Paris, France. German Canc Res Ctr, D-6900 Heidelberg, Germany. Pacific NW Res Inst, Seattle, WA USA. German Canc Res Ctr, Div A080, Heidelberg, Germany. RP Wertheimer, E (reprint author), Tel Aviv Univ, Dept Pathol, Sackler Sch Med, IL-69978 Tel Aviv, Israel. EM effy@patholog.tau.ac.il NR 44 TC 57 Z9 59 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2006 VL 26 IS 7 BP 2675 EP 2687 DI 10.1128/MCB.26.7.2675-2687.2006 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 026BR UT WOS:000236312200019 PM 16537911 ER PT J AU Mazan-Mamczarz, K Lal, A Martindale, JL Kawai, T Gorospe, M AF Mazan-Mamczarz, K Lal, A Martindale, JL Kawai, T Gorospe, M TI Translational repression by RNA-binding protein TIAR SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AU-RICH ELEMENT; MAMMALIAN STRESS GRANULES; ANTIGEN-RELATED PROTEIN; MESSENGER-RNA; GENE-EXPRESSION; POSTTRANSCRIPTIONAL REGULATION; EUKARYOTIC TRANSLATION; INHIBITS TRANSLATION; INITIATION-FACTORS; HUR AB The RNA-binding protein TIAR has been proposed to inhibit protein synthesis transiently by promoting the formation of translationally silent stress granules. Here, we report the selective binding of TIAR to several mRNAs encoding translation factors such as eukaryotic initiation factor 4A (eIF4A) and eIF4E (translation initiation factors), eEF1B (a translation elongation factor), and c-Myc (which transcriptionally controls the expression of numerous translation regulatory proteins). TIAR bound the 3'-untranslated regions of these mRNAs and potently suppressed their translation, particularly in response to low levels of short-wave length LTV (UVC) irradiation. The UVC-imposed global inhibition of the cellular translation machinery was significantly relieved after silencing of TIAR expression. We propose that the TIAR-mediated inhibition of translation factor expression elicits a sustained repression of protein biosynthesis in cells responding to stress. C1 NIA, LCMB, IRP, NIH, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, LCMB, IRP, NIH, Box 12, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov FU Intramural NIH HHS NR 47 TC 86 Z9 90 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2006 VL 26 IS 7 BP 2716 EP 2727 DI 10.1128/MCB.26.7.2716-2727.2006 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 026BR UT WOS:000236312200022 PM 16537914 ER PT J AU Nielsen, KH Valasek, L Sykes, C Jivotovskaya, A Hinnebusch, AG AF Nielsen, KH Valasek, L Sykes, C Jivotovskaya, A Hinnebusch, AG TI Interaction of the RNP1 motif in PRT1 with HCR1 promotes 40S binding of eukaryotic initiation factor 3 in yeast SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID TRANSLATION INITIATION; IN-VIVO; PREINITIATION COMPLEX; MULTIFACTOR COMPLEX; SACCHAROMYCES-CEREVISIAE; MESSENGER-RNA; RIBOSOMAL-SUBUNITS; ESCHERICHIA-COLI; AUG RECOGNITION; CODON SELECTION AB We found that mutating the RNP1 motif in the predicted RRM domain in yeast eukaryotic initiation factor 3 (eIF3) subunit b/PRT1 (prt1-rnp1) impairs its direct interactions in vitro with both eIF3a/TIF32 and eIF3j/HCR1. The rnp1 mutation in PRT1 confers temperature-sensitive translation initiation in vivo and reduces 40S-binding of eIF3 to native preinitiation complexes. Several findings indicate that the rnp1 lesion decreases recruitment of eIF3 to the 40S subunit by HCR1: (i) rnp1 strongly impairs the association of HCR1 with PRT1 without substantially disrupting the eIF3 complex; (ii) rnp1 impairs the 40S binding of eIF3 more so than the 40S binding of HCR1; (iii) overexpressing HCR1-R215I decreases the Ts- phenotype and increases 40S-bound eIF3 in rnp1 cells; (iv) the rnp1 Ts- phenotype is exacerbated by tif32-Delta 6, which eliminates a binding determinant for HCR1 in TIF32; and (v) hcr1 Delta impairs 40S binding of eIF3 in otherwise wild-type cells. Interestingly, rnp1 also reduces the levels of 40S-bound eIF5 and eIF1 and increases leaky scanning at the GCN4 uORF1. Thus, the PRT1 RNP1 motif coordinates the functions of HCR1 and TIF32 in 40S binding of eIF3 and is needed for optimal preinitiation complex assembly and AUG recognition in vivo. C1 NICHHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NICHHD, Lab Gene Regulat & Dev, NIH, Bldg 6A-Rm,BIA-13, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov RI Valasek, Leos/I-5743-2014 FU Intramural NIH HHS NR 46 TC 41 Z9 48 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2006 VL 26 IS 8 BP 2984 EP 2998 DI 10.1128/MCB.26.8.2984-2998.2006 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 030TM UT WOS:000236657600011 PM 16581774 ER PT J AU Qiu, HF Hu, CH Wong, CM Hinnebusch, AG AF Qiu, HF Hu, CH Wong, CM Hinnebusch, AG TI The Spt4p subunit of yeast DSIF stimulates association of the Paf1 complex with elongating RNA polymerase II SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID HISTONE H2B MONOUBIQUITINATION; REGULATES H3 METHYLATION; CARBOXYL-TERMINAL DOMAIN; TRANSCRIPTION ELONGATION; SACCHAROMYCES-CEREVISIAE; IN-VIVO; KINASE-I; PROTEIN; PHOSPHORYLATION; RECRUITMENT AB The Paf1 complex (Paf1C) interacts with RNA polymerase II (Pol II) and promotes histone methylation of transcribed coding sequences, but the mechanism of Paf1C recruitment is unknown. We show that Paf1C is not recruited directly by the activator Gcn4p but is dependent on preinitiation complex assembly and Ser5 carboxy-terminal domain phosphorylation for optimal association with ARG1 coding sequences. Importantly, Spt4p is required for Paf1C occupancy at ARG1 (and other genes) and for Paf1C association with Ser5-phosphorylated Pol II in cell extracts, whereas Spt4p-Pol II association is independent of Paf1C. Since spt4 Delta does not reduce levels of Pol II at ARG1, Ser5 phosphorylation, or Paf1C expression, it appears that Spt4p (or its partner in DSIF, Spt5p) provides a platform on Pol II for recruiting Paf1C following Ser5 phosphorylation and promoter clearance. spt4 Delta reduces trimethylation of Lys4 on histone H3, demonstrating a new role for yeast DSIF in promoting a Paf1C-dependent function in elongation. C1 NICHHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. RP Hinnebusch, AG (reprint author), NIH, Bldg 6A,Room B1A-13, Bethesda, MD 20892 USA. EM ahinnebusch@nih.gov RI Wong, Chi-Ming/A-7627-2013 OI Wong, Chi-Ming/0000-0002-0025-7135 FU Intramural NIH HHS NR 53 TC 46 Z9 46 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2006 VL 26 IS 8 BP 3135 EP 3148 DI 10.1128/MCB.26.8.3135-3148.2006 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 030TM UT WOS:000236657600025 PM 16581788 ER PT J AU Kawai, T Lal, A Yang, XL Galban, S Mazan-Mamczarz, K Gorospe, M AF Kawai, T Lal, A Yang, XL Galban, S Mazan-Mamczarz, K Gorospe, M TI Translational control of cytochrome c by RNA-binding proteins TIA-1 and HuR SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID AU-RICH ELEMENT; RETICULUM STRESS-RESPONSE; ANTIGEN-RELATED PROTEIN; MESSENGER-RNA; GENE-EXPRESSION; CDNA ARRAYS; APOPTOSIS; GRANULES; ALPHA; IDENTIFICATION AB Stresses affecting the endoplasmic reticulum (ER) globally modulate gene expression patterns by altering posttranscriptional processes such as translation. Here, we use tunicamycin (Tn) to investigate ER stress-triggered changes in the translation of cytochrome c, a pivotal regulator of apoptosis. We identified two RNA-binding proteins that associate with its similar to 900-bp-long, adenine- and uridine-rich 3' untranslated region (UTR): HuR, which displayed affinity for several regions of the cytochrome c 3'UTR, and T-cell-restricted intracellular antigen I (TIA-1), which preferentially bound the segment proximal to the coding region. HuR did not appear to influence the cytochrome c mRNA levels but instead promoted cytochrome c translation, as HuR silencing greatly diminished the levels of nascent cytochrome c protein. By contrast, TIA-1 functioned as a translational repressor of cytochrome c, with interventions to silence TIA-1 dramatically increasing cytochrome c translation. Following treatment with Tn, HuR binding to cytochrome c mRNA decreased, and both the presence of cytochrome c mRNA within actively translating polysomes and the rate of cytochrome c translation declined. Taken together, our data suggest that the translation rate of cytochrome c is determined by the opposing influences of HuR and TIA-1 upon the cytochrome c mRNA. Under unstressed conditions, cytochrome c mRNA is actively translated, but in response to ER stress agents, both HuR and TIA-1 contribute to lowering its biosynthesis rate. We propose that HuR and TIA-1 function coordinately to maintain precise levels of cytochrome c production under unstimulated conditions and to modify cytochrome c translation when damaged cells are faced with molecular decisions to follow a prosurvival or a prodeath path. C1 NIA, IRP, LCMB, NIH, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, IRP, LCMB, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov FU Intramural NIH HHS NR 52 TC 123 Z9 124 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD APR PY 2006 VL 26 IS 8 BP 3295 EP 3307 DI 10.1128/MCB.26.8.3295-3307.2006 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 030TM UT WOS:000236657600038 PM 16581801 ER PT J AU Campbell, JL Lorenz, A Witkin, KL Hays, T Loidl, L Cohen-Fix, O AF Campbell, JL Lorenz, A Witkin, KL Hays, T Loidl, L Cohen-Fix, O TI Yeast nuclear envelope subdomains with distinct abilities to resist membrane expansion SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID SACCHAROMYCES-CEREVISIAE; BUDDING YEAST; PORE COMPLEX; CELL-CYCLE; GENE; ORGANIZATION; NUCLEOLUS; PROTEINS; DYNAMICS; ARCHITECTURE AB Little is known about what dictates the round shape of the yeast Saccharomyces cerevisiae nucleus. In spo7 Delta mutants, the nucleus is misshapen, exhibiting a single protrusion. The Spo7 protein is part of a phosphatase complex that represses phospholipid biosynthesis. Here, we report that the nuclear protrusion of spo7 Delta mutants colocalizes with the nucleolus, whereas the nuclear compartment containing the bulk of the DNA is unaffected. Using strains in which the nucleolus is not intimately associated with the nuclear envelope, we show that the single nuclear protrusion of spo7 Delta mutants is not a result of nucleolar expansion, but rather a property of the nuclear membrane. We found that in spo7 Delta mutants the peripheral endoplasmic reticulum (ER) membrane was also expanded. Because the nuclear membrane and the ER are contiguous, this finding indicates that in spo7 Delta mutants all ER membranes, with the exception of the membrane surrounding the bulk of the DNA, undergo expansion. Our results suggest that the nuclear envelope has distinct domains that differ in their ability to resist membrane expansion in response to increased phospholipid biosynthesis. We further propose that in budding yeast there is a mechanism, or structure, that restricts nuclear membrane expansion around the bulk of the DNA. C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Vienna, Dept Chromosome Biol, A-1030 Vienna, Austria. RP Cohen-Fix, O (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. EM ornacf@helix.nih.gov RI Lorenz, Alexander/B-4735-2008 OI Lorenz, Alexander/0000-0003-1925-3713 FU Intramural NIH HHS NR 42 TC 44 Z9 44 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD APR PY 2006 VL 17 IS 4 BP 1768 EP 1778 DI 10.1091/mbc.E05-09-0839 PG 11 WC Cell Biology SC Cell Biology GA 030TP UT WOS:000236657900025 PM 16467382 ER PT J AU Bussey, KJ Chin, K Lababidi, S Reimers, M Reinhold, WC Kuo, WL Gwadry, F Jain, A Kouros-Mehr, H Fridlyand, J Jain, A Collins, C Nishizuka, S Tonon, G Roschke, A Gehlhaus, K Kirsch, I Scudiero, DA Gray, JW Weinstein, JN AF Bussey, KJ Chin, K Lababidi, S Reimers, M Reinhold, WC Kuo, WL Gwadry, F Jain, A Kouros-Mehr, H Fridlyand, J Jain, A Collins, C Nishizuka, S Tonon, G Roschke, A Gehlhaus, K Kirsch, I Scudiero, DA Gray, JW Weinstein, JN TI Integrating data on DNA copy number with gene expression levels and drug sensitivities in the NCI-60 cell line panel SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID COMPARATIVE GENOMIC HYBRIDIZATION; HUMAN BREAST-CANCER; MOLECULAR PHARMACOLOGY; LUNG-CANCER; OVARIAN ADENOCARCINOMAS; MICROARRAY ANALYSIS; L-ASPARAGINASE; TUMORS; HETEROZYGOSITY; IDENTIFICATION AB Chromosome rearrangement, a hallmark of cancer, has profound effects on carcinogenesis and tumor phenotype. We used a panel of 60 human cancer cell lines (the NCl-60) as a model system to identify relationships among DNA copy number, mRNA expression level, and drug sensitivity. For etch of 64 cancer-relevant genes, we calculated all 4,096 possible Pearson's correlation coefficients relating DNA copy number (assessed by comparative genomic hybridization using bacterial artificial chromosome microarrays) and mRNA expression level (determined using both cDNA and Affymetrix oligonucleotide microarrays). The analysis identified an association of ERB82 overexpression with 3p copy number, a finding supported by data from human tumors and a mouse model of ER882-induced carcinogenesis. When we examined the correlation between DNA copy number for all 353 unique loci on the bacterial artificial chromosome microarray and drug sensitivity for 118 drugs with putatively known mechanisms of action, we found a striking negative correlation (-0.983; 95% bootstrap confidence interval, -0.999 to -0.899) between activity of the enzyme drug L-asparaginase and DNA copy number of genes near asparagine synthetase in the ovarian cancer cells. Previous analysis of drug sensitivity and mRNA expression had suggested an inverse relationship between mRNA levels of asparagine synthetase and L-asparaginase sensitivity in the NCl-60. The concordance of pharmacogenomic findings at the DNA and mRNA levels strongly suggests further study of L-asparaginase for possible treatment of a low-synthetase subset of clinical ovarian cancers. The DNA copy number database presented here will enable other investigators to explore DNA transcript-drug relationships in their own domains of research focus. C1 NCI, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NCI, Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Lab Med, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Anat, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Biopharmaceut Sci, Ctr Comprehens Canc, San Francisco, CA 94143 USA. Univ Calif San Francisco, Inst Canc Res, San Francisco, CA 94143 USA. Natl Canc Inst, Sci Applicat Int Corp Frederick Canc Res & Dev Ct, Frederick, MD USA. RP Weinstein, JN (reprint author), NCI, Mol Pharmacol Lab, NIH, Bldg 37,Room 5056,MSC 4255,9000 Rockville Pike, Bethesda, MD 20892 USA. EM weinstein@dtpax2.ncifcrf.gov OI Bussey, Kimberly/0000-0003-1001-8207 FU Intramural NIH HHS; NCI NIH HHS [P01 CA 64602, P01 CA064602, P50 CA 58207, P50 CA058207, U54 CA112970-02, U54 CA112970] NR 54 TC 106 Z9 111 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD APR PY 2006 VL 5 IS 4 BP 853 EP 867 DI 10.1158/1535-7163.MCT-05-0155 PG 15 WC Oncology SC Oncology GA 041LU UT WOS:000237458500008 PM 16648555 ER PT J AU Jin, H Kim, TH Hwang, SK Chang, SH Kim, HW Anderson, HK Lee, HW Lee, KH Colburn, NH Yang, HS Cho, MH Cho, CS AF Jin, H Kim, TH Hwang, SK Chang, SH Kim, HW Anderson, HK Lee, HW Lee, KH Colburn, NH Yang, HS Cho, MH Cho, CS TI Aerosol delivery of urocanic acid-modified chitosan/programmed cell death 4 complex regulated apoptosis, cell cycle, and angiogenesis in lungs of K-ras null mice SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID CYSTIC-FIBROSIS PATIENTS; NONVIRAL GENE DELIVERY; CANCER CELLS; IN-VITRO; RECOMBINANT ADENOVIRUS; PLASMID DNA; CHITOSAN; EXPRESSION; CFTR; SUPPRESSOR AB The low efficiency of conventional therapies in achieving long-term survival of patients with lung cancer calls for development of novel treatment options. Although several genes have been investigated for their antitumor activities through gene delivery, problems surrounding the methods used, such as efficiency, specificity, and toxicity, hinder application of such therapies in clinical settings. Aerosol gene delivery as nonviral and noninvasive method for gene therapy may provide an alternative for a safer and more effective treatment for lung cancer. In this study, imidazole ring-containing urocanic acid-modified chitosan (UAC) designed in previous study was used as a gene carrier. The efficiency of UAC carrier in lungs was confirmed, and the potential effects of the programmed cell death protein 4 (PDCD4) tumor suppressor gene on three major pathways (apoptosis, cell cycle, and angiogenesis) were evaluated. Aerosol containing UAC/PDCD4 complexes was delivered into K-ras null lung cancer model mice through the nose-only inhalation system developed by our group. Delivered UAC/PDCD4 complex facilitated apoptosis, inhibited pathways important for cell proliferation, and efficiently suppressed pathways important for tumor angiogenesis. In summary, results obtained by Western blot analysis, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated nick end labeling assay suggest that our aerosol gene delivery technique is compatible with in vivo gene delivery and can be applied as a noninvasive gene therapy. C1 Seoul Natl Univ, Toxicol Lab, Coll Vet Med, Seoul 151742, South Korea. Seoul Natl Univ, Lab Biomed Polymer & Tissue Engn, Sch Agr Biotechnol, Seoul 151742, South Korea. Korea Inst Radiol & Med Sci, Mol Oncol Lab, Seoul, South Korea. Sungkyunkwan Univ, Dept Mol Cell Biol, Sch Med, Samsung Biomed Res Inst, Suwon, South Korea. Natl Canc Inst, Lab Canc Prevent, Frederick, MD USA. Univ Kentucky, Grad Ctr Toxicol, Markey Canc Ctr, Coll Med, Lexington, KY USA. RP Cho, CS (reprint author), Seoul Natl Univ, Toxicol Lab, Coll Vet Med, Seoul 151742, South Korea. EM chocs@snu.ac.kr RI Yang, Hsin-Sheng/A-6419-2008; CHO, Myung-Haing/B-7362-2014 NR 34 TC 68 Z9 74 U1 0 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD APR PY 2006 VL 5 IS 4 BP 1041 EP 1049 DI 10.1158/1535-7163.MCT-05-0433 PG 9 WC Oncology SC Oncology GA 041LU UT WOS:000237458500029 PM 16648576 ER PT J AU Wang, Y Yao, RS Maciag, A Grubbs, CJ Lubet, RA You, M AF Wang, Y Yao, RS Maciag, A Grubbs, CJ Lubet, RA You, M TI Organ-specific expression profiles of rat mammary gland, liver, and lung tissues treated with targretin, 9-cis retinoic acid, and 4-hydroxyphenylretinamide SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID X-RECEPTOR; BREAST-CANCER; 9-CIS-RETINOIC ACID; GENE-EXPRESSION; PREVENTION; CELLS; CARCINOMA; N-(4-HYDROXYPHENYL)RETINAMIDE; DIFFERENTIATION; CHEMOPREVENTION AB A rexinoid, targretin, and two retinoids, 9-cis retinoic acid (9cRA) and 4-hydroxyphenylretinamide (4HPR), were examined for their effects on gene expression in rat mammary gland, liver, and lung tissues. The chemopreventive effects of these agents have largely been attributed to their ability to interact with retinoic acid receptors (RAR) and/or retinoid X receptors (RXR). Targretin interacts with the RXR receptors. 9cRA interacts with both the RAR and RXR receptors, whereas 4HPR has a moderate affinity primarily for RAR gamma. Based on previous studies on mammary chemoprevention, targretin (150 mg/ kg diet), 9cRA (100 mg/kg diet), and 4HPR (782 mg/kg diet), were administered to rats continually in their diet for 7 days. Tissue- and agent-specific expression differences were determined by comparing tissues from treated rats with those from rats given a control diet. There were significantly more changes associated with targretin than 9cRA or 4HPR. Only a limited number of expression changes were found with 4HPR treatment. For each organ, targretin- and 9cRA-treated tissues clustered closely together, whereas 4HPR-treated tissues clustered with the tissues from the control diet group. In contrast to 9cRA treatment, targretin treatment altered genes that involved fatty acid metabolism and modulation of various cytochromes P450 in the liver, clearly demonstrating the very disparate nature of these two retinoids. These expression signatures could provide useful pharmacodynamic biomarkers for retinoid treatment and chemoprevention. C1 Washington Univ, Sch Med, Dept Surg, St Louis, MO 63110 USA. Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. Univ Alabama, Chemoprevent Ctr, Birmingham, AL USA. NCI, Chemoprevent Agent Dev Res Grp, Bethesda, MD 20892 USA. RP You, M (reprint author), Washington Univ, Sch Med, Dept Surg, 660 S Euclid Ave,Campus Box 8109, St Louis, MO 63110 USA. EM youm@wustl.edu FU NCI NIH HHS [N01-CN-25018-72] NR 36 TC 18 Z9 18 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD APR PY 2006 VL 5 IS 4 BP 1060 EP 1072 DI 10.1158/1535-7163.MCT-05-0322 PG 13 WC Oncology SC Oncology GA 041LU UT WOS:000237458500031 PM 16648578 ER PT J AU Lubet, RA Christov, K You, M Yao, R Steele, VE End, DW Juliana, MM Grubbs, CJ AF Lubet, RA Christov, K You, M Yao, R Steele, VE End, DW Juliana, MM Grubbs, CJ TI Effects of the farnesyl transferase inhibitor R115777 (Zarnestra) on mammary carcinogenesis: prevention, therapy, and role of HaRas mutations SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID MURINE SARCOMA VIRUS; HUMAN-BREAST-CANCER; FARNESYLTRANSFERASE INHIBITORS; TRANSGENIC MICE; FOCUS FORMATION; CARCINOMAS; PROTEIN; EXPRESSION; VOROZOLE; TUMORS AB The ability of the farnesyl transferase inhibitor R115777 to act as a cancer therapeutic/preventive agent and to modulate proliferation/apoptosis markers was determined in the methylnitrosourea-induced model of mammary carcinogenesis. Female Sprague-Dawley rats were given methylnitrosourea at 50 days of age. In the prevention study, R115777 15, 16, or 50 mg/kg body weight/d, beginning 5 days after methylnitrosourea treatment, decreased the formation of mammary cancers by 6%, 42%, and 75%, respectively. Approximately 50% of the mammary cancers that developed had HaRas mutations. Only 1 of 15 tumors that grew out in the presence of 8115777 (16 or 50 mg/kg body weight/d) had a HaRas mutation. In the therapeutic study, a surgical biopsy of a mammary cancer was done to determine HaRas status, and growth of the cancer was then followed during treatment of the rat with R115777. Virtually every cancer with a HaRas mutation underwent complete regression within 3 weeks, whereas tumors without a HaRas mutation had variable responses to the inhibitor. Both of these studies implied a high sensitivity of tumors with HaRas mutations to the effects of R115777. In order to understand the preferential susceptibility of tumors with HaRas mutations, rats with a palpable cancer were treated with R115777 for a period of 36 or 96 hours prior to sacrifice, and the proliferation and apoptosis levels in the cancers were determined. The proliferative index was significantly (> 85%) decreased in all mammary cancers with HaRas mutations, whereas variable responses were observed in cancers without HaRas mutations. Apoptosis was also measured and a 5-fold increase was observed in HaRas mutant tumors, again with varying responses in the HaRas wild-type cancers. Thus, R115777 was active in the prevention and therapy of these chemically induced mammary cancers, but was strikingly more effective in cancers with HaRas mutations. C1 Natl Canc Inst, Div Canc Prevent, Bethesda, MD 20852 USA. Univ Illinois, Dept Surg Oncol, Chicago, IL 60680 USA. Washington Univ, Dept Surg, Sch Med, St Louis, MO USA. Johnson & Johnson Pharmaceut, Res & Dev, Spring House, PA USA. Univ Alabama Birmingham, Dept Genet, Birmingham, AL USA. Univ Alabama Birmingham, Dept Surg, Birmingham, AL 35294 USA. RP Lubet, RA (reprint author), Natl Canc Inst, Div Canc Prevent, Execut Plaza N,Suite 2110,6130 Execut Blvd, Bethesda, MD 20852 USA. EM lubetr@mail.nih.gov NR 23 TC 10 Z9 10 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD APR PY 2006 VL 5 IS 4 BP 1073 EP 1078 DI 10.1158/1535-7163.MCT-05-0398 PG 6 WC Oncology SC Oncology GA 041LU UT WOS:000237458500032 PM 16648579 ER PT J AU Burlak, C Whitney, AR Mead, DJ Hackstadt, T DeLeo, FR AF Burlak, C Whitney, AR Mead, DJ Hackstadt, T DeLeo, FR TI Maturation of human neutrophil phagosomes includes incorporation of molecular chaperones and endoplasmic reticulum quality control machinery SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID HUMAN POLYMORPHONUCLEAR LEUKOCYTES; ER-MEDIATED PHAGOCYTOSIS; MHC CLASS-I; CROSS-PRESENTATION; RESPIRATORY BURST; PLASMA-MEMBRANE; DENDRITIC CELLS; ANNEXIN-I; PROTEIN; MACROPHAGES AB Human neutrophils are an essential component of the innate immune response. Although significant progress has been made toward understanding mechanisms of phagocytosis and microbicidal activity, a comprehensive analysis of proteins comprising neutrophil phagosomes has not been conducted. To that end, we used subcellular proteomics to identify proteins associated with human neutrophil phagosomes following receptor-mediated phagocytosis. Proteins (n = 411 spots) resolved from neutrophil phagosome fractions were identified by MALDI-TOF MS and/or LC-MS/MS analysis. Those associated with phagocytic vacuoles originated from multiple subcellular compartments, including the cytosol, plasma membrane, specific and azurophilic granules, and cytoskeleton. Unexpectedly several enzymes typically associated with mitochondria were identified in phagosome fractions. Furthermore proteins characteristic of the endoplasmic reticulum, including 11 molecular chaperones, were resolved from phagosome preparations. Confocal microscopy confirmed that proteins representing these major subcellular compartments were enriched on phagosomes of intact neutrophils. Notably calnexin and glucose-regulated protein 78 co-localized with gp91(phox) in human neutrophils and were thus likely delivered to phagosomes by fusion of specific granules. We conclude that neutrophil phagosomes have heretofore unrecognized complexity and function, which includes potential for antigen processing events. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. NIAID, Lab Intracellular Parasites, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. RP DeLeo, FR (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59840 USA. EM fdeleo@niaid.nih.gov OI DeLeo, Frank/0000-0003-3150-2516 FU Intramural NIH HHS NR 56 TC 40 Z9 41 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD APR PY 2006 VL 5 IS 4 BP 620 EP 634 DI 10.1074/mcp.M500336-MCP200 PG 15 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 030QE UT WOS:000236648600004 PM 16415295 ER PT J AU Kayser, MA AF Kayser, MA TI IEM Digest - Disorders of ketone production and utilization SO MOLECULAR GENETICS AND METABOLISM LA English DT Editorial Material ID SYNTHASE DEFICIENCY; LYASE DEFICIENCY; BODY METABOLISM; COA; CLONING C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Kayser, MA (reprint author), NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM mkayser@mail.nih.gov NR 15 TC 2 Z9 2 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 2006 VL 87 IS 4 BP 281 EP 283 DI 10.1016/j.ymgme.2006.02.009 PG 3 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 031FS UT WOS:000236690500001 ER PT J AU O'Leary, VB Pangilinan, F Cox, C Parle-McDermott, A Conley, M Molloy, AM Kirke, PN Mills, JL Brody, LC Scott, JM AF O'Leary, VB Pangilinan, F Cox, C Parle-McDermott, A Conley, M Molloy, AM Kirke, PN Mills, JL Brody, LC Scott, JM TI Reduced folate carrier polymorphisms and neural tube defect risk SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE reduced folate carrier; H27R; 61 bp tandem repeat; folate; neural tube defect ID SPINA-BIFIDA; GENE; TRANSPORT; VITAMIN; PREVENTION; REDUCTASE AB The reduced folate carrier (RFCI) is essential for folate transport into cells. Low folate is an important cause of neural tube defects (NTDs), and a single-nucleotide polymorphism (H27R) (80G -> A) in the RFCI gene has been reported to be a NTD risk factor. We investigated H27R and a 61bp tandem repeat polymorphism as potential risk factors for NTDs, using a large homogeneous Irish population by case/control comparison, log-linear analysis, and transmission disequilibrium testing. No association was found between NTDs and H27R in mothers [p = 0.23, odds ratio (OR) 0.87, 95% confidence interval (CI) 0.69-1.09], fathers (p = 0.11, OR 0.83, 95% CI 0.66-1.04), or cases (p = 0.36, OR 0.9, 95% Cl 0.72-1.12) when compared to controls or through log-linear modeling for dominant or recessive effects or with the transmission disequilibrium test for preferential allele transmission. Using log-linear models, a significant protective case effect was seen for the 61 bp polymorphism (p = 0.0039, OR 0.21, 95% CI 0.05-0.85). When analyzed by genotype, individuals homozygous for a single copy of the 61 bp sequence were underrepresented in cases as compared to controls, although these results did not reach statistical significance (p = 0.081, OR 0.5, 95% Cl 0.23-1.09, goodness of fit p = 0.42). We compared the frequencies of H27R and the 61 bp polymorphism in African-Americans and American-Caucasians. The frequencies of H27R polymorphism differed significantly between the two populations (p = 0.0001). This large study does not confirm previous reports that H27R is a risk factor for NTDs. The previously unstudied 61 bp tandem repeat, however, has a possible protective NTD effect in our Irish population. This requires confirmation in other studies. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. Univ Dublin Trinity Coll, Dept Clin Med, Dublin 2, Ireland. NHGRI, Genome Technol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NICHHD, Genome Technol Branch, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Hlth Res Board, Child Hlth Epidemiol Div, Dublin, Ireland. RP O'Leary, VB (reprint author), Univ Dublin Trinity Coll, Dept Biochem, Dublin 2, Ireland. EM olearyv@tcd.ie OI Molloy, Anne/0000-0002-1688-9049; O'Leary, Valerie/0000-0003-1171-9830 NR 24 TC 29 Z9 30 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 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 2006 VL 87 IS 4 BP 364 EP 369 DI 10.1016/j.ymgme.2005.09.024 PG 6 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 031FS UT WOS:000236690500013 PM 16343969 ER PT J AU Kulka, A Metcalfe, DD AF Kulka, A Metcalfe, DD TI TLR3 activation inhibits human mast cell attachment to fibronectin and vitronectin SO MOLECULAR IMMUNOLOGY LA English DT Article DE mast cells; adhesion; toll-like receptors; integrins ID TOLL-LIKE RECEPTOR-3; DOUBLE-STRANDED-RNA; MONOCLONAL-ANTIBODY; PROINFLAMMATORY CYTOKINES; MIGRATION; MOUSE AB Mastcells are involved in both the genesis of allergic inflammation and in host defense; and reside in tissues where their location and responsiveness is regulated in part by adhesion to extracellular matrix proteins (ECM). We have reported that human mast cells (huMC) express TLR 1-7, and 9 and respond to toll-like receptors (TLR) ligands by releasing cytokines and leukotriene C4. To determine if TLR ligation could similarly affect mast cells via an influence on adhesion, we employed huMC; and as substrates, fibronectin (FN) and vitronectin (VN). huMC were thus treated with double-stranded RNA (dsRNA) and adhesion to ECM was quantified. Fc epsilon RI dependent mast cell deggranulation was assessed. Adhesion molecule expression and activation was measured by flow cytornetry. Activation of huMC through TLR3 with increasing amounts of polyl:C inhibited mast cell adhesion in a dose-dependent manner. This decrease in adhesion was accompanied by a similar decrease in IgE-mediated mast cell degranulation. Activation of TLR3 on huMC resulted in a change in the conformation of CD29, the receptor for FN, to an inactive form. Thus, TLR3 activation decreases mast cell attachment to VN and FN through an active process and one. which would abrogate mast cell attachment dependent potentiation of IgE-mediated responses. Published by Elsevier Ltd. C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. Northwestern Univ, Feinberg Sch Med, Allergy Immunol Div, Chicago, IL 60611 USA. RP Metcalfe, DD (reprint author), NIAID, Lab Allerg Dis, NIH, Bldg 10,Room 11C205,10 Ctr Dr,MSC 1881, Bethesda, MD 20892 USA. EM dmetcalfe@niaid.nih.gov NR 17 TC 7 Z9 7 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0161-5890 J9 MOL IMMUNOL JI Mol. Immunol. PD APR PY 2006 VL 43 IS 10 BP 1579 EP 1586 DI 10.1016/j.molimm.2005.09.019 PG 8 WC Biochemistry & Molecular Biology; Immunology SC Biochemistry & Molecular Biology; Immunology GA 027XZ UT WOS:000236450900009 ER PT J AU Hosseinpour, F Moore, R Negishi, M Sueyoshi, T AF Hosseinpour, F Moore, R Negishi, M Sueyoshi, T TI Serine 202 regulates the nuclear translocation of constitutive active/androstane receptor SO MOLECULAR PHARMACOLOGY LA English DT Article ID ARYL-HYDROCARBON RECEPTOR; PREGNANE-X-RECEPTOR; ANDROSTANE RECEPTOR; MOUSE-LIVER; GLUCOCORTICOID-RECEPTOR; HEPG2 CELLS; CAR; PROTEIN; GENE; IMMUNOPHILIN AB The constitutive active receptor (CAR) in mouse primary hepatocytes undergoes okadaic acid (OA)-sensitive nuclear translocation after activation by xenobiotics such as phenobarbital (PB) and 1,4 bis[2-(3,5-dichloropyridyloxy)]benzene (TCPOBOP). We have now mimicked this TCPOBOP-dependent and OA-sensitive translocation of mouse CAR (mCAR) in HepG2 cells and have demonstrated that protein phosphatase 2A regulates this nuclear translocation. Site-directed mutagenesis analysis of various Ser and Thr residues delineated the translocation activity to Ser-202. Mutation of Ser-202 to Asp (S202D) prevented mCAR translocation into the nucleus of TCPOBOP-treated HepG2 cells. In addition, in the livers of Car(-/-) mice, the YFP-tagged S202D mutant did not translocate into the nucleus after PB treatment. To examine whether Ser-202 can be phosphorylated, flag-tagged wild-type mCAR or flag-tagged S202A mutant was expressed in HepG2 cells and subjected to Western blot analysis using an antibody specific to a peptide containing phospho-Ser-202. A high molecular weight phosphorylated form of CAR was detected only with the wild-type mCAR. These results are consistent with the conclusion that the dephosphorylation of Ser-202 is a required step that regulates the xenobiotic-dependent nuclear translocation of mCAR. C1 NIEHS, Pharmacogenet Sec, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Negishi, M (reprint author), NIEHS, Pharmacogenet Sec, Reprod & Dev Toxicol Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM negishi@niehs.nih.gov NR 25 TC 48 Z9 53 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 2006 VL 69 IS 4 BP 1095 EP 1102 DI 10.1124/mol.105.019505 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 023YR UT WOS:000236162600004 PM 16377764 ER PT J AU Uno, S Dalton, TP Dragin, N Curran, CP Derkenne, S Miller, ML Shertzer, HG Gonzalez, FJ Nebert, DW AF Uno, S Dalton, TP Dragin, N Curran, CP Derkenne, S Miller, ML Shertzer, HG Gonzalez, FJ Nebert, DW TI Oral benzo[a]pyrene in Cyp1 knockout mouse lines: CYP1A1 important in detoxication, CYP1B1 metabolism required for immune damage independent of total-body burden and clearance rate SO MOLECULAR PHARMACOLOGY LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Society-of-Toxicology CY MAR, 2005 CL New Orleans, LA SP Soc Toxicol ID ARYL-HYDROCARBON RECEPTOR; POLYCYCLIC AROMATIC-HYDROCARBONS; BONE-MARROW CYTOTOXICITY; NULL MUTANT MICE; MESSENGER-RNA; INDUCIBLE CYTOCHROME-P450; MEDIATED INDUCTION; EXPRESSION; ACTIVATION; CELLS AB CYP1A1 and CYP1B1 metabolically activate many polycyclic aromatic hydrocarbons (PAHs), including benzo[a] pyrene, to reactive intermediates associated with toxicity, mutagenesis, and carcinogenesis. Paradoxically, however, Cyp1a1(-/-) knockout mice are more sensitive to oral benzo[ a] pyrene exposure, compared with wild-type Cyp1a1(-/-) mice ( Mol Pharmacol 65: 1225, 2004). To further investigate the mechanism for this enhanced sensitivity, Cyp1a1(-/-), Cyp1a2(-/-), and Cyp1b1(-/-) single-knockout, Cyp1a1/1b1(-/-) and Cyp1a2/1b1(-/-) double-knockout, and Cyp1(-/-) wild-type mice were analyzed. After administration of oral benzo[ a] pyrene ( 125 mg/kg/day) for 18 days, Cyp1a1(-/-) mice showed marked wasting, immunosuppression, and bone marrow hypocellularity, whereas the other five genotypes did not. After 5 days of feeding, steady-state blood levels of benzo[ a] pyrene were similar to 25 and similar to 75 times higher in Cyp1a1(-/-) and Cyp1a1/1b1(-/-) mice, respectively, than in wild-type mice. Benzo[ a] pyrene-DNA adduct levels were highest in liver, spleen, and marrow of Cyp1a1(-/-) and Cyp1a1/1b1(-/-) mice. Many lines of convergent data obtained with oral benzo[ a] pyrene dosing suggest that: 1) inducible CYP1A1, probably in both intestine and liver, is most important in detoxication; 2) CYP1B1 in spleen and marrow is responsible for metabolic activation of benzo[a] pyrene, which results in immune damage in the absence of CYP1A1; 3) both thymus atrophy and hepatocyte hypertrophy are independent of CYP1B1 metabolism but rather may reflect long-term activation of the aryl hydrocarbon receptor; and 4) the magnitude of immune damage in Cyp1a1(-/-) and Cyp1a1/1b1(-/-) mice is independent of plasma benzo[a] pyrene and total-body burden and clearance. Thus, a balance between tissue-specific expression of the CYP1A1 and CYP1B1 enzymes governs sensitivity of benzo[a] pyrene toxicity and, possibly, carcinogenicity. C1 Univ Cincinnati, Med Ctr, Dept Environm Hlth, Cincinnati, OH 45267 USA. Univ Cincinnati, Med Ctr, Ctr Environm Genet, Cincinnati, OH 45267 USA. Nihon Univ, Sch Med, Dept Biochem, Tokyo, Japan. NIH, Lab Metab, Ctr Canc Res, NIH, Bethesda, MD USA. RP Nebert, DW (reprint author), Univ Cincinnati, Med Ctr, Dept Environm Hlth, POB 670056, Cincinnati, OH 45267 USA. EM dan.nebert@uc.edu FU NIEHS NIH HHS [R01-ES10133, R01-ES08147] NR 51 TC 131 Z9 136 U1 1 U2 8 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 2006 VL 69 IS 4 BP 1103 EP 1114 DI 10.1124/mol.105.021501 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 023YR UT WOS:000236162600005 PM 16377763 ER PT J AU Couch, RD Ganem, NJ Zhou, M Popov, VM Honda, T Veenstra, TD Sporn, MB Anderson, AC AF Couch, RD Ganem, NJ Zhou, M Popov, VM Honda, T Veenstra, TD Sporn, MB Anderson, AC TI 2-cyano-3,12-dioxooleana-1,9(11)-diene-28-oic acid disrupts microtubule polymerization: A possible mechanism contributing to apoptosis SO MOLECULAR PHARMACOLOGY LA English DT Article ID NITRIC-OXIDE PRODUCTION; CDDO INDUCES APOPTOSIS; ACTIVATED RECEPTOR-GAMMA; MYELOID-LEUKEMIA CELLS; MOUSE MACROPHAGES; 2-CYANO-3,12-DIOXOOLEAN-1,9-DIEN-28-OIC ACID; SYNTHETIC OLEANANE; TRITERPENOID CDDO; URSANE TRITERPENOIDS; CANCER-CHEMOTHERAPY AB The semisynthetic triterpenoid 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO) has several biological activities, including the induction of apoptosis in many cancer cell lines. To identify potential protein targets, immobilized biotinylated CDDO was used to screen the proteome of a human lymphoma cell line (U937) sensitive to CDDO-induced apoptosis. Tubulin was identified as one of several putative targets of CDDO. CDDO was shown to selectively bind to tubulin, with a dissociation constant of similar to 7 mu M, and to disrupt microtubules both in vivo and in vitro. CDDO inhibits tubulin polymerization in vitro, possibly through interactions with a hydrophobic site on beta-tubulin. The CDDO-tubulin interaction may also involve a reversible 1,4-addition with a protein sulfhydryl group. Unlike other known spindle poisons, CDDO does not result in a temporal increase in the mitotic index. Rather, CDDO seems to initiate apoptosis early in M phase. C1 Dartmouth Coll, Dept Chem, Hanover, NH 03755 USA. Dartmouth Coll Sch Med, Dept Biochem, Hanover, NH USA. Dartmouth Coll Sch Med, Dept Pharmacol & Toxicol, Hanover, NH USA. NCI, SAIC Federick Inc, Lab Proteom & Analyt Technol, Frederick, MD 21701 USA. RP Anderson, AC (reprint author), Univ Connecticut, Sch Pharm, Dept Med Chem, 69 N Eagleville Rd, Storrs, CT 06269 USA. EM amy.anderson@uconn.edu FU NCI NIH HHS [CA78814] NR 50 TC 13 Z9 15 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 2006 VL 69 IS 4 BP 1158 EP 1165 DI 10.1124/mol.105.018572 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 023YR UT WOS:000236162600010 PM 16407469 ER PT J AU Lazar, J Braun, DC Toth, A Wang, Y Pearce, LV Pavlyukovets, VA Blumberg, PM Garfield, SH Wincovitch, S Choi, HK Lee, J AF Lazar, J Braun, DC Toth, A Wang, Y Pearce, LV Pavlyukovets, VA Blumberg, PM Garfield, SH Wincovitch, S Choi, HK Lee, J TI Kinetics of penetration influence the apparent potency of vanilloids on TRPV1 SO MOLECULAR PHARMACOLOGY LA English DT Article ID H-3 RESINIFERATOXIN BINDING; ROOT GANGLION MEMBRANES; ACTIVATED ION-CHANNEL; PROTEIN-KINASE-C; IODO-RESINIFERATOXIN; RECEPTOR ANTAGONIST; ADULT-RATS; IN-VITRO; CAPSAICIN; AGONISTS AB Evidence that the ligand binding site of TRPV1 lies on the inner face of the plasma membrane and that much of the TRPV1 itself is localized to internal membranes suggests that the rate of ligand entry into the cell may be an important determinant of the kinetics of ligand action. In this study, we synthesized a BODIPY TR-labeled fluorescent capsaicin analog (CHK-884) so that we could directly measure ligand entry. We report that CHK-884 penetrated only slowly into Chinese hamster ovary (CHO) cells expressing rat TRPV1, with a t(1/2) of 30 +/- 4 min, and localized in the endoplasmic reticulum and Golgi. Although CHK-884 was only weakly potent for TRPV1 binding (K-i = 6400 +/- 230 nM), it was appreciably more potent when assayed by intracellular calcium imaging and was 3.2-fold more potent with a 1-h incubation time ( 37 nM) than with a 5-min incubation time. Olvanil, a highly lipophilic vanilloid, yielded an EC50 of 4.3 nM upon intracellular calcium imaging with an incubation time of 1 h, compared with an EC50 value of 29.5 nM for calcium imaging assayed at 5 min. Likewise, the antagonist 5-iodoresiniferatoxin (5-iodo-RTX) displayed a K-i of 4.2 pM if incubated with CHO-TRPV1 cells for 2 h before addition of capsaicin compared with 1.5 nM if added simultaneously. We conclude that some vanilloids may have slow kinetics of uptake; this slow uptake may affect assessment of structure activity relations and may represent a significant factor for vanilloid drug design. C1 NCI, Lab Cellular Carcinogenesis & Tumor Promot, NIH, Bethesda, MD 20892 USA. NCI, Expt Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Gallaudet Univ, Dept Biol, Washington, DC 20002 USA. Seoul Natl Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul, South Korea. RP Blumberg, PM (reprint author), NCI, Lab Cellular Carcinogenesis & Tumor Promot, NIH, Bldg 37,Room 4048,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. EM blumberp@dc37a.nci.nih.gov RI Toth, Attila/F-4859-2010 OI Toth, Attila/0000-0001-6503-3653 FU Intramural NIH HHS NR 38 TC 24 Z9 25 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 2006 VL 69 IS 4 BP 1166 EP 1173 DI 10.1124/mol.105.019158 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 023YR UT WOS:000236162600011 PM 16418338 ER PT J AU Shen, DW Liang, XJ Suzuki, T Gottesman, MM AF Shen, DW Liang, XJ Suzuki, T Gottesman, MM TI Identification by functional cloning from a retroviral cDNA library of cDNAs for ribosomal protein L36 and the 10-kDa heat shock protein that confer cisplatin resistance SO MOLECULAR PHARMACOLOGY LA English DT Article ID MULTIDRUG-RESISTANCE; CELL-LINES; ANTICANCER DRUGS; GENE-EXPRESSION; CANCER CELLS; APOPTOSIS; SENSITIVITY AB Based on analyses of two-dimensional gel and cDNA microarrays, our laboratory and others have demonstrated that a number of genes show altered expression during the development of cisplatin resistance (CP-r) in human cancer cells, including genes associated with DNA damage repair, proto-oncogenes, apoptosis, stress-response, and transcription factors. To verify these results and find genes that are directly responsible for CP-r, as opposed to those reflecting a secondary response induced by cisplatin treatment or resulting from CP-r, we constructed a retroviral cDNA library in the vector pLNCX2 from KB-CP. 5 ( KCP.5), a cell line selected in one step after exposure to cisplatin at 0.5 mu g/ml. Using a library of cDNAs (1.8 x 10(6) cDNA clones) and an intermittent cisplatin selection system to allow more effective functional cloning, 11 expressed cDNAs were identified in a primary pool of 93,000 transfected cell clones. Metallothionein 2A, a known CP-r gene, was among these 11 genes found in the transfectants after CP selection. Several other genes, including those encoding ribosomal proteins (e.g., RPL36) and heat shock protein (e.g., HSP10), were also found among the cisplatin-selected clones. Transfection of either the RPL36 cDNA or HSP10 cDNA conferred on KB-3-1 cells 2.5- to 3-fold resistance to cisplatin by clonogenic assays. A subsequent transfection also identified RPL36 as a CP-r gene. The finding that a ribosomal protein gene, RPL36, contributes to CP-r should stimulate study of the role of ribosomal proteins in multifactorial mechanisms of cisplatin resistance. C1 NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, NIH, 37 Convent Dr,Room 2108, Bethesda, MD 20892 USA. EM mgottesman@nih.gov FU Intramural NIH HHS; NCI NIH HHS [Z01 BC005598-16] NR 21 TC 18 Z9 19 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 2006 VL 69 IS 4 BP 1383 EP 1388 DI 10.1124/mol.105.017525 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 023YR UT WOS:000236162600035 PM 16394183 ER PT J AU Kim, H Jeon, H Kong, H Yang, Y Choi, B Kim, YM Neckers, L Jung, Y AF Kim, H Jeon, H Kong, H Yang, Y Choi, B Kim, YM Neckers, L Jung, Y TI A molecular mechanism for the anti-inflammatory effect of taurine-conjugated 5-aminosalicylic acid in inflamed colon SO MOLECULAR PHARMACOLOGY LA English DT Article ID NF-KAPPA-B; INFLAMMATORY-BOWEL-DISEASE; NITRIC-OXIDE SYNTHASE; P65 SUBUNIT; TRANSCRIPTIONAL ACTIVITY; ULCERATIVE-COLITIS; GENE-EXPRESSION; KINASE ALPHA; INHIBITION; ACTIVATION AB In previous reports, a novel colon-specific prodrug, 5-amino-salicyltaurine (5-ASA-Tau) administered orally, is successfully delivered to and liberates 5-aminosalicylic acid (5-ASA) and taurine in the inflamed large intestine of rats. Furthermore, the prodrug ameliorates the 2,4,6-trinitrobenzene-sulfonic acid-induced colitis, and taurine acts not only as a carrier but also as an active therapeutic agent. In this study, we investigated the anti-inflammatory properties of the prodrug at a molecular level. After rectal administration of taurine, formation of taurine chloramine (TauCl) in the inflamed colonic tissue was examined using high-performance liquid chromatography. In human colon epithelial cell lines, nuclear factor-kappa B (NF-kappa B) activity was accessed using an NF-kappa B-dependent luciferase reporter gene. Protein levels were monitored by Western blotting. DNA binding activity of the NF-kappa B subunit p65 was determined using a DNA binding assay kit. A millimolar level of TauCl was formed in the inflamed tissue. TauCl inhibited tumor necrosis factor (TNF)-dependent NF-kappa B activation by modifying thiol(s) on p65 and blocking DNA binding. In addition, 5-ASA inhibited phosphorylation of p65 at serine 536, which is critical for transcriptional activity of NF-kappa B. Furthermore, combined TauCl/5-ASA treatment additively inhibited TNF-dependent NF-kappa B activation. Together, our data suggest that the colon-specific carrier taurine contributes to the clinical effect of the prodrug by potentiating the inhibitory effect of the active ingredient 5-ASA on a major proinflammatory signal, TNF-dependent NF-kappa B activation in the inflamed large intestine. C1 Pusan Natl Univ, Coll Pharm, Lab Biomed Chem, Pusan 609735, South Korea. NCI, Urol Oncol Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Jung, Y (reprint author), Pusan Natl Univ, Coll Pharm, Lab Biomed Chem, Pusan 609735, South Korea. EM jungy@pusan.ac.kr NR 40 TC 25 Z9 25 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 2006 VL 69 IS 4 BP 1405 EP 1412 DI 10.1124/mol.105.020578 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 023YR UT WOS:000236162600038 PM 16407467 ER PT J AU Semenova, EA Johnson, AA Marchand, C Davis, DA Yarchoan, R Pommier, Y AF Semenova, EA Johnson, AA Marchand, C Davis, DA Yarchoan, R Pommier, Y TI Preferential inhibition of the magnesium-dependent strand transfer reaction of HIV-1 integrase by alpha-hydroxytropolones SO MOLECULAR PHARMACOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HINOKITIOL-RELATED COMPOUNDS; TYPE-1 INTEGRASE; IN-VITRO; REVERSE-TRANSCRIPTASE; BIOLOGICAL-ACTIVITY; GAMMA-THUJAPLICIN; CATALYTIC DOMAIN; BETA-THUJAPLICIN; RNASE-H AB Integration is a crucial step in the life cycle of human immunodeficiency virus type 1 (HIV-1); therefore, inhibitors of HIV-1 integrase are candidates for antiretroviral therapy. Two 7-hydroxytropolone derivatives (alpha-hydroxytropolones) were found to inhibit HIV-1 integrase. A structure-activity relationship investigation with several tropolone derivatives from The National Cancer Institute compound repository demonstrated that the 7-hydroxy group is essential for integrase inhibition. alpha-Hydroxytropolones preferentially inhibit strand transfer and are inhibitory both in the presence of magnesium or manganese. Lack of inhibition of disintegration in the presence of magnesium coupled with results from different cross-linking assays suggests alpha-hydroxytropolones as interfacial inhibitors. We propose that alpha-hydroxytropolones chelate the divalent metal (Mg2+ or Mn2+) in the enzyme active site. The most active compound against HIV-1 integrase in biochemical assays [ 2,4,6-cycloheptatrien-1-one, 2,7-dihydroxy-4-isopropyl (NSC 18806) IC50 = 4.8 +/- 2.5 mu M] exhibits weak cytoprotective activity against HIV-1(IIIB) in a cell-based assay. alpha-Hydroxytropolones represent a new family of inhibitors for the development of novel drugs against HIV infection. C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, HIV & AIDS Malignancy Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH, Bldg 37,Room 5068, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Marchand, Christophe/D-8559-2016 FU Intramural NIH HHS NR 45 TC 43 Z9 47 U1 0 U2 5 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X EI 1521-0111 J9 MOL PHARMACOL JI Mol. Pharmacol. PD APR PY 2006 VL 69 IS 4 BP 1454 EP 1460 DI 10.1124/mol.105.020321 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 023YR UT WOS:000236162600043 PM 16418335 ER PT J AU Woo, SLC Skarlatos, SI Joyce, MM Croxton, TL Qasba, P AF Woo, SLC Skarlatos, SI Joyce, MM Croxton, TL Qasba, P TI Critical resources for gene therapy in heart, lung, and blood diseases working group SO MOLECULAR THERAPY LA English DT Article C1 NHLBI, NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Gene & Cell Med, New York, NY 10029 USA. RP Skarlatos, SI (reprint author), NHLBI, NIH, Bldg 10, Bethesda, MD 20892 USA. EM skarlats@uhlbi.nih.gov NR 0 TC 6 Z9 6 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 1525-0016 J9 MOL THER JI Mol. Ther. PD APR PY 2006 VL 13 IS 4 BP 641 EP 643 DI 10.1016/j.ymthe.2005.12.007 PG 3 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 033HX UT WOS:000236838900004 PM 16649254 ER PT J AU Hadjigeorgiou, GM Xiromerisiou, G Gourbali, V Aggelakis, K Scarmeas, N Papadimitriou, A Singleton, A AF Hadjigeorgiou, GM Xiromerisiou, G Gourbali, V Aggelakis, K Scarmeas, N Papadimitriou, A Singleton, A TI Association of alpha-synuclein ReP1 polymorphism and Parkinson's disease: Influence of Rep1 on age at onset SO MOVEMENT DISORDERS LA English DT Article DE Parkinson's disease; alpha-synuclein; Rep1; polymorphism; association study ID ALLELIC VARIATION; GENE; NACP-REP1; SUSCEPTIBILITY; MUTATION; RISK; METAANALYSIS; VARIABILITY; REPLICATION; HAPLOTYPES AB The alpha-synuclein Rep1 polymorphism was studied in patients and controls in an ethnic Greek population. There was an association of allele 2 with risk of Parkinson's disease (PD: adjusted odd ratio = 3.25; 95% Cl = 1.80-5.87). Survival analyses (Cox proportional hazards models) were employed to explore the influence of genotypes on age at onset of PD. Age at onset of carriers of at least one Rep I allele 2 was earlier (3.6 years) compared to noncarriers (adjusted hazard ratio = 2.21 95% CI = 1.58-3.10). Kaplan-Meier analysis also Supported a dosage effect of Rep1 allele 2 on age at onset. For Rep1 allele 1. there was neither association with risk of PD nor influence on age at onset. This is the first stud showing an influence of Rep1 polymorphism on age at onset of PD. (C) 2005 Movement Disorder Society. C1 Univ Thessaloniki, Sch Med, Dept Neurol, Neurogenet Unit, Larisa 41222, Greece. Columbia Univ, Dept Neurol, Med Ctr, Cognit Neurosci Div,Taub Inst, New York, NY USA. NIH, Mol Genet Sect, Neurogenet Lab, Bethesda, MD 20892 USA. RP Hadjigeorgiou, GM (reprint author), Univ Thessaloniki, Sch Med, Dept Neurol, Neurogenet Unit, Papakyriazi 22 St, Larisa 41222, Greece. EM gmhadji@med.uth.gr RI Singleton, Andrew/C-3010-2009 NR 31 TC 30 Z9 31 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2006 VL 21 IS 4 BP 534 EP 539 DI 10.1002/mds.20752 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 036UV UT WOS:000237102300016 PM 16250025 ER PT J AU Daumer, M Griffith, LM Meister, W Nash, RA Wolinsky, JS AF Daumer, M Griffith, LM Meister, W Nash, RA Wolinsky, JS TI Survival, and time to an advanced disease state or progression, of untreated patients with moderately severe multiple sclerosis in a multicenter observational database: relevance for design of a clinical trial for high dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation SO MULTIPLE SCLEROSIS LA English DT Article DE autologous hematopoietic cell transplantation; immunosuppressive therapy; multiple; sclerosis; survival; time-to-progression ID NATURAL-HISTORY; IMMUNOABLATIVE THERAPY; IMPORTANT DIFFERENCE; AUTOIMMUNE-DISEASE; FOLLOW-UP; MS; DISABILITY; LESIONS; COHORT AB Despite prolonged survival, patients with multiple sclerosis ( MS) experience considerable morbidity, which adversely impacts quality of life. To assess the risk - benefit of a clinical trial of high dose immunosuppressive therapy with autologous hematopoietic stem cell transplantation for MS, we sought to determine the natural history of the disease in a comparison group of untreated patients. We identified 285 individuals with 2132 combined observation years ( median: 5.6 years; 5th to 95th percentile: 1 - 21 years), with Expanded Disability Status Scale (EDSS) scores of 3.0 - 5.5 at baseline observation. Disease-related mortality was zero at five years, 5.4% at 10 years, and 22% at 15 years ( 40 patients contributing to the data point; 95% confidence interval: 4 - 32%). Risk for progression to advanced disability, defined as an EDSS score of 8, was very low for the subgroup with a baseline EDSS score of 3 - 3.5; however, for those with a baseline EDSS score of 4 - 5.5, 3% had advanced disability after two years, 5% after three years, 6% after four years, 12% after five years, and 40% after 10 years. The estimated probability of disease progression, defined as an increase in EDSS score by >= 1.0 sustained for at least 180 days, was 5% after one year, 14% after two years, 22% after three years, 38% after five years, 57% after 10 years, and > 80% after 20 years of observation. The relevance of these features to the design of the clinical trial is discussed. C1 Sylvia Lawry Ctr MS Res, D-81677 Munich, Germany. NIAID, Div Allergy Immunol & Transplantat, NIH, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. Univ Texas, Hlth Sci Ctr, Dept Neurol, Houston, TX 77225 USA. RP Daumer, M (reprint author), Sylvia Lawry Ctr MS Res, Hohenlindenerstr 1, D-81677 Munich, Germany. EM daumer@slcmsr.org NR 36 TC 15 Z9 15 U1 1 U2 3 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD APR PY 2006 VL 12 IS 2 BP 174 EP 179 DI 10.1191/135248506ms1256oa PG 6 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 033OG UT WOS:000236857700006 PM 16629420 ER PT J AU Wu, CJ Conze, DB Li, T Srinivasula, SM Ashwell, JD AF Wu, CJ Conze, DB Li, T Srinivasula, SM Ashwell, JD TI NEMO is a sensor of Lys 63-linked polyubiquitination and functions in NF-kappa B activation SO NATURE CELL BIOLOGY LA English DT Article ID DEATH DOMAIN KINASE; GAMMA IKK-GAMMA; UBIQUITINATION; PROTEIN; COMPLEX; RIP; OLIGOMERIZATION; RECRUITMENT; PATHWAY; CHAINS AB The transcription factor NF-kappa B is sequestered in the cytoplasm in a complex with I kappa B-1. Almost all NF-kappa B activation pathways converge on I kappa B kinase (IKK), which phosphorylates I kappa B resulting in Lys 48-linked polyubiquitination of I kappa B and its degradation. This allows migration of NF-kappa B to the nucleus where it regulates gene expression(2). IKK has two catalytic subunits, IKK alpha and IKK beta, and a regulatory subunit, IKK gamma or NEMO. NEMO is essential for NF-kappa B activation, and NEMO dysfunction in humans is the cause of incontinentia pigmenti and hypohidrotic ectodermal dysplasia and immunodeficiency (HED-ID)(3). The recruitment of IKK to occupied cytokine receptors, and its subsequent activation, are dependent on the attachment of Lys 63-linked polyubiquitin chains to signalling intermediates such as receptor-interacting protein ( RIP). Here, we show that NEMO binds to Lys 63-but not Lys 48-linked polyubiquitin, and that single point mutations in NEMO that prevent binding to Lys 63-linked polyubiquitin also abrogates the binding of NEMO to RIP in tumour necrosis factor ( TNF)alpha- stimulated cells, the recruitment of IKK to TNF receptor (TNF-R) 1, and the activation of IKK and NF-kappa B. RIP is also destabilized in the absence of NEMO binding and undergoes proteasomal degradation in TNF-alpha-treated cells. These results provide a mechanism for NEMO's critical role in IKK activation, and a key to understanding the link between cytokine-receptor proximal signalling and IKK and NF-kappa B activation. C1 NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. EM jda@pop.nci.nih.gov FU Intramural NIH HHS NR 35 TC 407 Z9 414 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD APR PY 2006 VL 8 IS 4 BP 398 EP U58 DI 10.1038/ncb1384 PG 15 WC Cell Biology SC Cell Biology GA 029KA UT WOS:000236560000019 PM 16547522 ER PT J AU Dalakas, MC AF Dalakas, MC TI Mechanisms of Disease: signaling pathways and immunobiology of inflammatory myopathies SO NATURE CLINICAL PRACTICE RHEUMATOLOGY LA English DT Review DE cell stress; dermatomyositis; major histocompatibility complex; polymyositis; sporadic inclusion body myositis ID INCLUSION-BODY MYOSITIS; MHC CLASS-I; ENDOPLASMIC-RETICULUM STRESS; CELL-ADHESION MOLECULES; GENE-EXPRESSION; COSTIMULATORY MOLECULE; MUSCLE-FIBERS; T-CELLS; INFILTRATING LYMPHOCYTES; DIFFERENTIAL EXPRESSION AB The signaling pathways involved in the irnmunobiology of polymyositis, dermatomyositis, and inclusion-body myositis are outlined in this Review, which is based oil research performed during the past 10 years. In dermatomyositis, the complement cascade is activated and the expression of cytokines and chemokines is upregulated. In polymyositis and inclusion-body myositis, autoinvasive CD8(+) T cells are clonally expanded. This T-cell subset possesses conserved amino-acid sequences in complementarity-determining region 3 of the T-cell receptor and, via the perforin pathway, exerts a myotoxic effect oil muscle fibers that express major histocompatibility complex (MHC) class I molecules. In all inflammatory myopathies, molecules associated with T-cell transmigration and cytokine signaling, as well as chemokines and their receptors, are strongly expressed by endothelial and inflammatory cells. Early in the pathogenesis of polymyositis and inclusion-body myositis, expression of MHC class I molecules oil muscle fibers is upregulated, even in the absence of autoinvasive CD8(+) T cells. Emerging data indicate that such continuous upregulation of the expression of MHC class I molecules oil muscle fibers leads to all endoplasmic reticulum stress response, intracellular accumulation of misfolded glycoproteins, and activation of nuclear factor kappa B pathways, which call further stimulate formation of MHC class I-CD8 complexes, resulting in a self-sustaining inflammatory response. Advances in our understanding of the signaling pathways involved in the pathogenesis of these inflammatory myopathies are expected to result in the identification of novel therapeutic targets for these diseases. C1 Natl Inst Neurol Disorders & Stroke, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC USA. RP Dalakas, MC (reprint author), Natl Inst Neurol Disorders & Stroke, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov FU Intramural NIH HHS NR 50 TC 61 Z9 67 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1745-8382 J9 NAT CLIN PRACT RHEUM JI Nat. Clin. Pract. Rheumatol. PD APR PY 2006 VL 2 IS 4 BP 219 EP 227 DI 10.1038/ncprheum0140 PG 9 WC Rheumatology; Social Issues SC Rheumatology; Social Issues GA 026IJ UT WOS:000236332300007 PM 16932688 ER PT J AU Kleta, R AF Kleta, R TI A key stone cop regulates oxalate homeostasis SO NATURE GENETICS LA English DT Editorial Material ID INTESTINAL TRANSPORT; CALCIUM; RISK AB A new study shows that Slc26a6-null mice manifest calcium-oxalate nephrolithiasis accompanied by enhanced net intestinal oxalate absorption. These findings point to a critical role for Slc26a6 in gastrointestinal oxalate secretion and suggest a genetic explanation for a common form of renal stone disease in humans. C1 NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20982 USA. RP Kleta, R (reprint author), NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, 10 Ctr Dr, Bethesda, MD 20982 USA. EM kletar@mail.nih.gov NR 15 TC 4 Z9 4 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2006 VL 38 IS 4 BP 403 EP 404 DI 10.1038/ng0406-403 PG 3 WC Genetics & Heredity SC Genetics & Heredity GA 026LN UT WOS:000236340500009 PM 16570061 ER PT J AU Palmer, CNA Irvine, AD Terron-Kwiatkowski, A Zhao, YW Liao, HH Lee, SP Goudie, DR Sandilands, A Campbell, LE Smith, FJD O'Regan, GM Watson, RM Cecil, JE Bale, SJ Compton, JG DiGiovanna, JJ Fleckman, P Lewis-Jones, S Arseculeratne, G Sergeant, A Munro, CS El Houate, B McElreavey, K Halkjaer, LB Bisgaard, H Mukhopadhyay, S McLean, WHI AF Palmer, CNA Irvine, AD Terron-Kwiatkowski, A Zhao, YW Liao, HH Lee, SP Goudie, DR Sandilands, A Campbell, LE Smith, FJD O'Regan, GM Watson, RM Cecil, JE Bale, SJ Compton, JG DiGiovanna, JJ Fleckman, P Lewis-Jones, S Arseculeratne, G Sergeant, A Munro, CS El Houate, B McElreavey, K Halkjaer, LB Bisgaard, H Mukhopadhyay, S McLean, WHI TI Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis SO NATURE GENETICS LA English DT Article ID PARTY DIAGNOSTIC-CRITERIA; ICHTHYOSIS VULGARIS; CORNIFIED ENVELOPE; SKIN; GENE; DIFFERENTIATION; ASTHMA; HYPERRESPONSIVENESS; EPIDEMIOLOGY; POPULATION AB Atopic disease, including atopic dermatitis (eczema), allergy and asthma, has increased in frequency in recent decades(1) and now affects similar to 20% of the population in the developed world. Twin and family studies have shown that predisposition to atopic disease is highly heritable(2). Although most genetic studies have focused on immunological mechanisms, a primary epithelial barrier defect has been anticipated(3). Filaggrin is a key protein that facilitates terminal differentiation of the epidermis and formation of the skin barrier. Here we show that two independent loss-of-function genetic variants (R510X and 2282del4) in the gene encoding filaggrin (FLG) are very strong predisposing factors for atopic dermatitis. These variants are carried by similar to 9% of people of European origin. These variants also show highly significant association with asthma occurring in the context of atopic dermatitis. This work establishes a key role for impaired skin barrier function in the development of atopic disease. C1 Univ Dundee, Ninewells Hosp & Med Sch, Div Pathol & Neurosci, Epithelial Genet Grp, Dundee DD1 9SY, Scotland. Univ Dundee, Ninewells Hosp & Med Sch, Biomed Res Ctr, Populat Pharmacogenet Grp, Dundee DD1 9SY, Scotland. Our Ladys Hosp Sick Children, Dept Paediat Dermatol, Dublin 12, Ireland. Univ Dundee, Ninewells Hosp & Med Sch, Tayside Univ Hosp NHS Trust, Dundee DD1 9SY, Scotland. Univ St Andrews, Bute Med Sch, St Andrews, Fife, Scotland. GeneDx, Gaithersburg, MD 20877 USA. Brown Med Sch, Dept Dermatol, Div Dermatopharmacol, Providence, RI 02903 USA. Rhode Isl Hosp, Providence, RI 02903 USA. NCI, Basic Res Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Washington, Dept Med, Div Dermatol, Seattle, WA 98195 USA. Univ Dundee, Ninewells Hosp & Med Sch, Tayside Univ Hosp NHS Trust, Dundee DD1 9SY, Scotland. S Glasgow Univ Hosp NHS Trust, Dept Dermatol, Glasgow G51 4TF, Lanark, Scotland. Inst Pasteur, F-75724 Paris, France. Copenhagen Univ Hosp, Danish Paediat Asthma Ctr, DK-2900 Copenhagen, Denmark. Univ Dundee, Ninewells Hosp & Med Sch, Childrens Asthma & Allergy Res Unit, Dundee DD1 9SY, Scotland. RP McLean, WHI (reprint author), Univ Dundee, Ninewells Hosp & Med Sch, Div Pathol & Neurosci, Epithelial Genet Grp, Dundee DD1 9SY, Scotland. EM w.h.i.mclean@dundee.ac.uk RI Palmer, Colin/C-7053-2008; McLean, William/C-6352-2009; Cecil, Joanne/A-3071-2010; Kronow, Joern/B-1054-2011; Osborne, Nicholas/N-4915-2015; Bisgaard, Hans/N-4761-2016; OI Palmer, Colin/0000-0002-6415-6560; Osborne, Nicholas/0000-0002-6700-2284; Bisgaard, Hans/0000-0003-4131-7592; Irvine, Alan/0000-0002-9048-2044; McLean, William Henry Irwin/0000-0001-5539-5757 FU Medical Research Council [G0700314] NR 30 TC 1254 Z9 1297 U1 10 U2 97 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2006 VL 38 IS 4 BP 441 EP 446 DI 10.1038/ng1767 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 026LN UT WOS:000236340500016 PM 16550169 ER PT J AU Gold, B Merriam, JE Zernant, J Hancox, LS Taiber, AJ Gehrs, K Cramer, K Neel, J Bergeron, J Barile, GR Smith, RT Dean, M Allikmets, R AF Gold, B Merriam, JE Zernant, J Hancox, LS Taiber, AJ Gehrs, K Cramer, K Neel, J Bergeron, J Barile, GR Smith, RT Dean, M Allikmets, R CA AMD Genetics Clin Study Grp TI Variation in factor B (BF) and complement component 2 (C2) genes is associated with age-related macular degeneration SO NATURE GENETICS LA English DT Article ID FACTOR-H POLYMORPHISM; DISEASE; DRUSEN; MACULOPATHY; DEFICIENCY; SUSCEPTIBILITY; EPIDEMIOLOGY; HAPLOTYPE; ETIOLOGY; VARIANT AB Age-related macular degeneration (AMD) is the most common form of irreversible blindness in developed countries(1,2). Variants in the factor H gene (CFH, also known as HF1), which encodes a major inhibitor of the alternative complement pathway, are associated with the risk for developing AMD(3-8). Here we test the hypothesis that variation in genes encoding other regulatory proteins of the same pathway is associated with AMD. We screened factor B (BF) and complement component 2 (C2) genes, located in the major histocompatibility complex class III region, for genetic variation in two independent cohorts comprising similar to 900 individuals with AMD and similar to 400 matched controls. Haplotype analyses identify a statistically significant common risk haplotype (H1) and two protective haplotypes. The L9H variant of BF and the E318D variant of C2 (H10), as well as a variant in intron 10 of C2 and the R32Q variant of BF (H7), confer a significantly reduced risk of AMD (odds ratio=0.45 and 0.36, respectively). Combined analysis of the C2 and BF haplotypes and CFH variants shows that variation in the two loci can predict the clinical outcome in 74% of the affected individuals and 56% of the controls. These data expand and refine our understanding of the genetic risk for AMD. C1 Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Univ Iowa, Ctr Macular Degenerat, Dept Ophthalmol & Visual Sci, Iowa City, IA 52240 USA. Sapio Sci LLC, York, PA 17402 USA. SAIC Frederick, Frederick, MD 21702 USA. Columbia Univ, Dept Pathol & Cell Biol, New York, NY 10032 USA. RP Allikmets, R (reprint author), Columbia Univ, Dept Ophthalmol, New York, NY 10032 USA. EM dean@ncifcrf.gov; rla22@columbia.edu RI Dean, Michael/G-8172-2012; OI Dean, Michael/0000-0003-2234-0631; smith, theodore/0000-0002-1693-943X FU Intramural NIH HHS; NCI NIH HHS [N01-CO-124000]; NEI NIH HHS [EY11515, EY13435, R01 EY011515, R01 EY013435, R01 EY015520, R01 EY015520-01A2, R01 EY015520-02, R01 EY015520-03, R01 EY015520-04, R01 EY015520-05] NR 30 TC 674 Z9 699 U1 0 U2 27 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD APR PY 2006 VL 38 IS 4 BP 458 EP 462 DI 10.1038/ng1750 PG 5 WC Genetics & Heredity SC Genetics & Heredity GA 026LN UT WOS:000236340500019 PM 16518403 ER PT J AU Liu, J Finkel, T AF Liu, J Finkel, T TI Stem cell aging: what bleach can teach SO NATURE MEDICINE LA English DT Editorial Material ID OXIDATIVE STRESS; ATM AB Intracellular oxidants may contribute to overall lifespan, in part by affecting stem cells. The connection between oxidants and aging now gains strength in a study of hematopoietic stem cells, which respond to oxidants by activating a pathway leading to stem cell exhaustion (pages 446-451). C1 NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. RP Liu, J (reprint author), NHLBI, Cardiol Branch, Bethesda, MD 20892 USA. EM finkelt@nih.gov NR 12 TC 10 Z9 13 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2006 VL 12 IS 4 BP 383 EP 384 DI 10.1038/nm0406-383 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 029RE UT WOS:000236581300013 PM 16598279 ER PT J AU Maudsley, S Mattson, MP AF Maudsley, S Mattson, MP TI Protein twists and turns in Alzheimer disease SO NATURE MEDICINE LA English DT Editorial Material ID PROLYL ISOMERASE PIN1; PHOSPHORYLATION; ISOMERIZATION; ACTIVATION; NEURONS AB An enzyme that modifies protein structure seems to help keep Alzheimer disease at bay. The enzyme affects two proteins thought to be key to disease pathology: amyloid precursor protein (APP) and the microtubule-binding protein tau. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. RP Maudsley, S (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM maudsleyst@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 13 TC 17 Z9 17 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2006 VL 12 IS 4 BP 392 EP 393 DI 10.1038/nm0406-392 PG 2 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 029RE UT WOS:000236581300019 PM 16598285 ER PT J AU Ott, MG Schmidt, M Schwarzwaelder, K Stein, S Siler, U Koehl, U Glimm, H Kuhlcke, K Schilz, A Kunkel, H Naundorf, S Brinkmann, A Deichmann, A Fischer, M Ball, C Pilz, I Dunbar, C Du, Y Jenkins, NA Copeland, NG Luthi, U Hassan, M Thrasher, AJ Hoelzer, D von Kalle, C Seger, R Grez, M AF Ott, MG Schmidt, M Schwarzwaelder, K Stein, S Siler, U Koehl, U Glimm, H Kuhlcke, K Schilz, A Kunkel, H Naundorf, S Brinkmann, A Deichmann, A Fischer, M Ball, C Pilz, I Dunbar, C Du, Y Jenkins, NA Copeland, NG Luthi, U Hassan, M Thrasher, AJ Hoelzer, D von Kalle, C Seger, R Grez, M TI Correction of X-linked chronic granulomatous disease by gene therapy, augmented by insertional activation of MDS1-EVI1, PRDM16 or SETBP1 SO NATURE MEDICINE LA English DT Article ID SEVERE COMBINED IMMUNODEFICIENCY; NADPH OXIDASE ACTIVITY; ASPERGILLUS-FUMIGATUS; HEMATOPOIETIC-CELLS; CD34(+) CELLS; HOST-DEFENSE; LIPOSOMAL BUSULFAN; CORD BLOOD; NEUTROPHILS; GP91(PHOX) AB Gene transfer into hematopoietic stem cells has been used successfully for correcting lymphoid but not myeloid immunodeficiencies. Here we report on two adults who received gene therapy after nonmyeloablative bone marrow conditioning for the treatment of X-linked chronic granulomatous disease (X-CGD), a primary immunodeficiency caused by a defect in the oxidative antimicrobial activity of phagocytes resulting from mutations in gp91(phox). We detected substantial gene transfer in both individuals' neutrophils that lead to a large number of functionally corrected phagocytes and notable clinical improvement. Large-scale retroviral integration site-distribution analysis showed activating insertions in MDS1-EVI1, PRDM16 or SETBP1 that had influenced regulation of long-term hematopoiesis by expanding gene-corrected myelopoiesis three- to four-fold in both individuals. Although insertional influences have probably reinforced the therapeutic efficacy in this trial, our results suggest that gene therapy in combination with bone marrow conditioning can be successfully used to treat inherited diseases affecting the myeloid compartment such as CGD. C1 Inst Biomed Res, D-60596 Frankfurt, Germany. Univ Hosp, Dept Hematol Oncol, D-60590 Frankfurt, Germany. Univ Hosp, Dept Internal Med 1, D-79106 Freiburg, Germany. Univ Freiburg, Inst Mol Med & Cell Res, D-79104 Freiburg, Germany. Natl Ctr Tumor Dis, D-69120 Heidelberg, Germany. Univ Freiburg, Fac Biol, D-79104 Freiburg, Germany. Univ Childrens Hosp, Div Hematol Immunol, CH-8032 Zurich, Switzerland. Univ Hosp, D-60590 Frankfurt, Germany. EUFETS AG, D-55743 Idar Oberstein, Germany. NHLBI, Hematol Branch, Bethesda, MD 20892 USA. NCI, Mouse Canc Genet Program, Ctr Canc Res, Frederick, MD 21702 USA. Univ Zurich, Cent Lab Electron Microscopy, CH-8006 Zurich, Switzerland. Karolinska Inst, Div Hematol, Dept Med, SE-17177 Stockholm, Sweden. Inst Child Hlth, Mol Immunol Unit, London WC1H 1EH, England. Cincinnati Childrens Res Fdn, Mol & Gene Therapy Program, Cincinnati, OH 45229 USA. RP Grez, M (reprint author), Inst Biomed Res, Georg Speyer Haus,Paul Ehrlich Str 42, D-60596 Frankfurt, Germany. EM christof.kalle@nct-heidelberg.de; grez@em.uni-frankfurt.de RI Hassan, Moustapha/H-9260-2015; OI Hassan, Moustapha/0000-0003-1927-5859; Koehl, Ulrike/0000-0002-8159-9160; Ball, Claudia/0000-0002-1749-3791; Stein, Stefan/0000-0003-1473-9706 FU Wellcome Trust NR 47 TC 688 Z9 711 U1 2 U2 32 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2006 VL 12 IS 4 BP 401 EP 409 DI 10.1038/nm1393 PG 9 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 029RE UT WOS:000236581300028 PM 16582916 ER PT J AU Lee, JS Heo, J Libbrecht, L Chu, IS Kaposi-Novak, P Calvisi, DF Mikaelyan, A Roberts, LR Demetris, AJ Sun, ZT Nevens, F Roskams, T Thorgeirsson, SS AF Lee, JS Heo, J Libbrecht, L Chu, IS Kaposi-Novak, P Calvisi, DF Mikaelyan, A Roberts, LR Demetris, AJ Sun, ZT Nevens, F Roskams, T Thorgeirsson, SS TI A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells SO NATURE MEDICINE LA English DT Article ID COMPARATIVE FUNCTIONAL GENOMICS; GENE-EXPRESSION; HUMAN CANCER; SIGNALING PATHWAY; LIVER-TUMOR; STEM-CELLS; C-JUN; METASTASIS; CLASSIFICATION; EZRIN AB The variability in the prognosis of individuals with hepatocellular carcinoma (HCC) suggests that HCC may comprise several distinct biological phenotypes. These phenotypes may result from activation of different oncogenic pathways during tumorigenesis and/or from a different cell of origin. Here we address whether the transcriptional characteristics of HCC can provide insight into the cellular origin of the tumor. We integrated gene expression data from rat fetal hepatoblasts and adult hepatocytes with HCC from human and mouse models. Individuals with HCC who shared a gene expression pattern with fetal hepatoblasts had a poor prognosis. The gene expression program that distinguished this subtype from other types of HCC included markers of hepatic oval cells, suggesting that HCC of this subtype may arise from hepatic progenitor cells. Analyses of gene networks showed that activation of AP-1 transcription factors in this newly identified HCC subtype might have key roles in tumor development. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, Bethesda, MD 20892 USA. Katholieke Univ Leuven, Dept Morphol, B-3000 Louvain, Belgium. Katholieke Univ Leuven, Dept Mol Pathol, B-3000 Louvain, Belgium. Korea Res Inst Biosci & Biotechnol, Natl Genome Informat Ctr, Taejon 305333, South Korea. Mayo Clin, Div Gastroenterol & Hepatol, Rochester, MN 55905 USA. Univ Pittsburgh, Med Ctr, Thomas E Starzl Transplant Inst, Pittsburgh, PA 15213 USA. Chinese Acad Med Sci, Inst Canc, Natl Lab Mol Oncol, Beijing 100021, Peoples R China. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, 37 Convent Dr,Room 4146, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov OI Roberts, Lewis/0000-0001-7885-8574 FU Intramural NIH HHS NR 40 TC 510 Z9 539 U1 7 U2 36 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 2006 VL 12 IS 4 BP 410 EP 416 DI 10.1038/nm1377 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 029RE UT WOS:000236581300029 PM 16532004 ER PT J AU Hobson, JP Liu, SH Rono, B Leppla, SH Bugge, TH AF Hobson, JP Liu, SH Rono, B Leppla, SH Bugge, TH TI Imaging specific cell-surface proteolytic activity in single living cells SO NATURE METHODS LA English DT Article ID ANTHRAX TOXIN; PLASMINOGEN-ACTIVATOR; BETA-LACTAMASE; UROKINASE; PROTEASES; CANCER; FURIN AB We describe a simple, sensitive and noninvasive assay that uses nontoxic, reengineered anthrax toxin-beta-lactamase fusion proteins with altered protease cleavage specificity to visualize specific cell-surface proteolytic activity in single living cells. The assay could be used to specifically image endogenous cell-surface furin, urokinase plasminogen activator and metalloprotease activity. We have adapted the assay for fluorescence microscopy, flow cytometry and fluorescent plate reader formats, and it is amenable for automation and high-throughput analysis. C1 NIAID, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Proteases & Tissue Remodeling Unit, NIH, Bethesda, MD 20892 USA. Rigshosp, Finsen Lab, DK-2100 Copenhagen, Denmark. RP Leppla, SH (reprint author), NIAID, Microbial Pathogenesis Sect, NIH, 30 Convent Dr, Bethesda, MD 20892 USA. EM leppla@nih.gov; thomas.bugge@nih.gov FU Intramural NIH HHS NR 18 TC 34 Z9 36 U1 0 U2 10 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD APR PY 2006 VL 3 IS 4 BP 259 EP 261 DI 10.1038/NMETH862 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 028PX UT WOS:000236501400011 PM 16554829 ER PT J AU Wang, GG Calvo, KR Pasillas, MP Sykes, DB Hacker, H Kamps, MP AF Wang, GG Calvo, KR Pasillas, MP Sykes, DB Hacker, H Kamps, MP TI Quantitative production of macrophages or neutrophils ex vivo using conditional Hoxb8 SO NATURE METHODS LA English DT Article ID STEM-CELL EXPANSION; NF-KAPPA-B; MYELOID-LEUKEMIA; C-MYC; V-MYB; DIFFERENTIATION; GENES; HOXA9; HEMATOPOIESIS; TRANSCRIPTION AB Differentiation mechanisms and inflammatory functions of neutrophils; and macrophages are usually studied by genetic and biochemical approaches that require costly breeding and time-consuming purification to obtain phagocytes for functional analysis. Because Hox oncoproteins enforce self-renewal of factor-dependent myeloid progenitors, we queried whether estrogen-regulated Hoxb8 (ER-Hoxb8) could immortalize macrophage or neutrophil progenitors that would execute normal differentiation and normal innate immune function upon ER-Hoxb8 inactivation. Here we describe methods to derive unlimited quantities of mouse macrophages or neutrophils by immortalizing their respective progenitors with ER-Hoxb8 using different cytokines to target expansion of different committed progenitors. ER-Hoxb8 neutrophils and macrophages are functionally superior to those produced by many other ex vivo differentiation models, have strong inflammatory responses and can be derived easily from embryonic day 13 (e13) fetal Liver of mice exhibiting embryonic-lethal phenotypes. Using knockout or small interfering RNA (siRNA) technologies, this ER-Hoxb8 phagocyte maturation system represents a rapid analytical toot for studying macrophage and neutrophil biology. C1 Univ Calif San Diego, Sch Med, Dept Pathol, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Mol Pathol Grad Program, La Jolla, CA 92093 USA. Univ Calif San Diego, Sch Med, Biomed Sci Grad Program, La Jolla, CA 92093 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Harvard Univ, Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA. St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. RP Kamps, MP (reprint author), Univ Calif San Diego, Sch Med, Dept Pathol, 9500 Gilman Dr, La Jolla, CA 92093 USA. EM mkamps@ucsd.edu RI Calvo, Katherine/A-8109-2009; Haecker, Hans/F-6826-2013; Wang, G Greg/L-6666-2014; OI Wang, G Greg/0000-0002-7210-9940; Calvo, Katherine/0000-0002-0771-4191 FU NCI NIH HHS [CA56876] NR 30 TC 86 Z9 86 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1548-7091 J9 NAT METHODS JI Nat. Methods PD APR PY 2006 VL 3 IS 4 BP 287 EP 293 DI 10.1038/NMETH865 PG 7 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 028PX UT WOS:000236501400016 PM 16554834 ER PT J AU Kerr, MA Belluscio, L AF Kerr, MA Belluscio, L TI Olfactory experience accelerates glomerular refinement in the mammalian olfactory bulb SO NATURE NEUROSCIENCE LA English DT Article ID ODORANT RECEPTORS; CREB AB Primary olfactory sensory neurons (OSNs) impart both molecular and functional organization to the olfactory bulb. Because OSNs can be selectively activated by odorants in vivo, we sought to determine whether odorant experience alters the cellular dynamics of specific OSNs or their axonal projections. Using mice, we found that odorant stimulation associated with behavioral conditioning influenced OSN wiring by accelerating glomerular refinement independent of OSN number; furthermore, this wiring was strongly associated with olfactory learning. C1 NINDS, Dev Neural Plast Unit, NIH, Bethesda, MD 20892 USA. RP Belluscio, L (reprint author), NINDS, Dev Neural Plast Unit, NIH, Bethesda, MD 20892 USA. EM belluscl@ninds.nih.gov FU Intramural NIH HHS NR 15 TC 49 Z9 49 U1 0 U2 7 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD APR PY 2006 VL 9 IS 4 BP 484 EP 486 DI 10.1038/nn1673 PG 3 WC Neurosciences SC Neurosciences & Neurology GA 026BC UT WOS:000236310700013 PM 16547509 ER PT J AU Siegel, RM AF Siegel, RM TI Caspases at the crossroads of immune-cell life and death SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID NF-KAPPA-B; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; RECEPTOR-INDUCED APOPTOSIS; TUMOR-NECROSIS-FACTOR; MATURE T-LYMPHOCYTES; LONG FORM; C-FLIP; INDUCED PROLIFERATION; NEGATIVE SELECTION; SIGNALING COMPLEX AB Caspases are responsible for crucial aspects of inflammation and immune-cell death that are disrupted in a number of genetic autoimmune and autoinflammatory diseases. The caspase family of proteases can be divided into pro-apoptotic and pro-inflammatory members based on their substrate specificity and participation in separate signalling cascades. However, as discussed here, evidence has emerged over the past few years that a number of the caspases thought to be involved solely in apoptosis also contribute to specific aspects of immune-cell development, activation and differentiation, and can even protect cells from some forms of cell death. C1 NIAMS, Immunoregulat Unit, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. RP Siegel, RM (reprint author), NIAMS, Immunoregulat Unit, Autoimmun Branch, NIH, Bldg 10,Room 9N238, Bethesda, MD 20892 USA. EM rsiegel@nih.gov RI Siegel, Richard/C-7592-2009 OI Siegel, Richard/0000-0001-5953-9893 FU Intramural NIH HHS NR 85 TC 201 Z9 209 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD APR PY 2006 VL 6 IS 4 BP 308 EP 317 DI 10.1038/nri1809 PG 10 WC Immunology SC Immunology GA 025YJ UT WOS:000236303200019 PM 16557262 ER PT J AU Sternberg, EM AF Sternberg, EM TI Neural regulation of innate immunity: a coordinated nonspecific host response to pathogens SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID GENE-RELATED PEPTIDE; VASOACTIVE-INTESTINAL-PEPTIDE; CORTICOTROPIN-RELEASING HORMONE; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; GLUCOCORTICOID-RECEPTOR GENE; TOLL-LIKE RECEPTORS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; MELANOCYTE-STIMULATING HORMONE; SYSTEMIC-LUPUS-ERYTHEMATOSUS AB The central nervous system (CNS) regulates innate immune responses through hormonal and neuronal routes. The neuroendocrine stress response and the sympathetic and parasympathetic nervous systems generally inhibit innate immune responses at systemic and regional levels, whereas the peripheral nervous system tends to amplify local innate immune responses. These systems work together to first activate and amplify local inflammatory responses that contain or eliminate invading pathogens, and subsequently to terminate inflammation and restore host homeostasis. Here, I review these regulatory mechanisms and discuss the evidence indicating that the CNS can be considered as integral to acute-phase inflammatory responses to pathogens as the innate immune system. C1 NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Rockville, MD 20852 USA. RP Sternberg, EM (reprint author), NIMH, Sect Neuroendocrine Immunol & Behav, NIH, 5625 Fishers Lane,Room 4N-13,MSC-9401, Rockville, MD 20852 USA. EM sternbee@mail.mih.gov FU NIMH NIH HHS [Z01 MH002585-15] NR 140 TC 432 Z9 449 U1 9 U2 53 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD APR PY 2006 VL 6 IS 4 BP 318 EP 328 DI 10.1038/nri1810 PG 11 WC Immunology SC Immunology GA 025YJ UT WOS:000236303200020 PM 16557263 ER PT J AU Margolis, L Shattock, R AF Margolis, L Shattock, R TI Selective transmission of CCR5-utilizing HIV-1: the 'gatekeeper' problem resolved? SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN LYMPHOID-TISSUE; CD4(+) T-CELLS; CHEMOKINE RECEPTOR EXPRESSION; SYNCYTIUM-INDUCING HIV-1; HUMAN LANGERHANS CELLS; HUMAN CERVICAL TISSUE; DENDRITIC CELLS; TYPE-1 INFECTION; ENVELOPE GLYCOPROTEIN AB Understanding the mechanisms of HIV-1 transmission is crucial for the development of effective preventive microbicides and vaccine strategies, and remains one of the main goals of HIV research. Over the past decade, many studies have focused on trying to identify the 'gatekeeping' mechanism that restricts the transmission of CXCR4-utilizing HIV-1 more efficiently than CCR5-utilizing HIV-1. However, to date, no study has explained the almost perfect negative selection of the former in vivo. Here, we propose that there is no single gatekeeper and that, instead, the selective transmission of R5 HIV-1 depends on the superimposition of multiple imperfect gatekeepers. C1 Natl Inst Child Hlth & Human Dev, NIH, Bethesda, MD 20895 USA. Univ London, St Georges Med Sch, London SW17 0RE, England. RP Shattock, R (reprint author), Natl Inst Child Hlth & Human Dev, NIH, Bethesda, MD 20895 USA. EM shattock@sghms.ac.uk NR 67 TC 165 Z9 168 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD APR PY 2006 VL 4 IS 4 BP 312 EP 317 DI 10.1038/nrmicro1387 PG 7 WC Microbiology SC Microbiology GA 022FJ UT WOS:000236040200017 PM 16541138 ER PT J AU Mattson, MP Magnus, T AF Mattson, MP Magnus, T TI Ageing and neuronal vulnerability SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID AMYOTROPHIC-LATERAL-SCLEROSIS; GROWTH-FACTOR-I; SELECTIVE MOTONEURON VULNERABILITY; PERTURBED CALCIUM HOMEOSTASIS; UBIQUITIN-PROTEASOME SYSTEM; HUNTINGTIN MUTANT MICE; ISCHEMIC BRAIN-INJURY; AMYLOID BETA-PEPTIDE; ALZHEIMERS-DISEASE; PARKINSONS-DISEASE AB Everyone ages, but only some will develop a neurodegenerative disorder in the process. Disease might occur when cells fail to respond adaptively to age-related increases in oxidative, metabolic and ionic stress, thereby resulting in the accumulation of damaged proteins, DNA and membranes. Determinants of neuronal vulnerability might include cell size and location, metabolism of disease-specific proteins and a repertoire of signal transduction pathways and stress resistance mechanisms. Emerging evidence on protein interaction networks that monitor and respond to the normal ageing process suggests that successful neural ageing is possible for most people, but also cautions that cures for neurodegenerative disorders are unlikely in the near future. C1 NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Neurosci, Baltimore, MD 21205 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 FU Intramural NIH HHS [Z01 AG000314-07, Z01 AG000312-07, Z01 AG000313-07, Z01 AG000317-07, Z01 AG000331-01] NR 225 TC 401 Z9 415 U1 3 U2 55 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD APR PY 2006 VL 7 IS 4 BP 278 EP 294 DI 10.1038/nrn1886 PG 17 WC Neurosciences SC Neurosciences & Neurology GA 024BR UT WOS:000236170400014 PM 16552414 ER PT J AU Zimmerberg, J Akimov, SA Frolov, V AF Zimmerberg, J Akimov, SA Frolov, V TI Synaptotagmin: fusogenic role for calcium sensor? SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Editorial Material ID MEMBRANE-FUSION; C2 DOMAINS; BINDING; VESICLES; BILAYERS; ENERGY; MODEL AB Two recent studies focusing on synaptotagmin-1' s role in synaptic vesicle fusion suggest that it may be key in bringing vesicle and target membranes together and in promoting SNARE assembly. The highly positive electrostatic potential of the synaptotagmin surface could catalyze fusion. C1 US Natl Inst Hlth, Natl Inst Child & Hlth & Human Dev, Lab Cellular & Mol Biophys, Bethesda, MD 20892 USA. RP Zimmerberg, J (reprint author), US Natl Inst Hlth, Natl Inst Child & Hlth & Human Dev, Lab Cellular & Mol Biophys, 10-10D14 MSC 1855, Bethesda, MD 20892 USA. EM joshz@helix.nih.gov RI Akimov, Sergey/L-2001-2013; Akimov, Sergey/I-6432-2015; OI Frolov, Vadim/0000-0002-0653-5669 NR 22 TC 25 Z9 26 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD APR PY 2006 VL 13 IS 4 BP 301 EP 303 DI 10.1038/nsmb0406-301 PG 3 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 029RF UT WOS:000236581400005 PM 16715046 ER PT J AU Catez, F Ueda, T Bustin, M AF Catez, F Ueda, T Bustin, M TI Determinants of histone H1 mobility and chromatin binding in living cells SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Review ID 4-WAY JUNCTION DNA; EXPRESSION IN-VIVO; C-TERMINAL DOMAIN; LINKER-HISTONE; GENE-EXPRESSION; DYNAMIC INTERACTION; NUCLEAR TRANSFER; PROTEINS; PHOSPHORYLATION; TRANSCRIPTION AB The dynamic interaction of chromatin-binding proteins with their nucleosome binding sites is an important element in regulating the structure and function of chromatin in living cells. Here we review the major factors regulating the intranuclear mobility and chromatin binding of the linker histone H1, the most abundant family of nucleosome-binding proteins. The information available reveals that multiple and diverse factors modulate the interaction of H1 with chromatin at both a local and global level. This multifaceted mode of modulating the interaction of H1 with nucleosomes is part of the mechanism that regulates the dynamics of the chromatin fiber in living cells. C1 NCI, Lab Metab, US Natl Inst Hlth, Bethesda, MD 20892 USA. RP Bustin, M (reprint author), Univ Lyon 1, CNRS, UMR 5534, Ctr Genet Mol & Cellulaire, F-69622 Villeurbanne, France. EM bustinm@mail.nih.gov RI Bustin, Michael/G-6155-2015 FU Intramural NIH HHS [Z01 BC004496-30] NR 66 TC 101 Z9 105 U1 0 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD APR PY 2006 VL 13 IS 4 BP 305 EP 310 DI 10.1038/nsmb1077 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 029RF UT WOS:000236581400010 PM 16715048 ER PT J AU Jin, CY Kato, K Chimura, T Yamasaki, T Nakade, K Murata, T Li, HJ Pan, JZ Zhao, MJ Sun, KL Chiu, R Ito, T Nagata, K Horikoshi, M Yokoyama, KK AF Jin, CY Kato, K Chimura, T Yamasaki, T Nakade, K Murata, T Li, HJ Pan, JZ Zhao, MJ Sun, KL Chiu, R Ito, T Nagata, K Horikoshi, M Yokoyama, KK TI Regulation of histone acetylation and nucleosome assembly by transcription factor JDP2 SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID JUN DIMERIZATION PROTEIN-2; ACETYLTRANSFERASE ACTIVITY; RETINOIC ACID; ONCOPROTEIN E1A; AP-1 REPRESSOR; F9 CELLS; CHROMATIN; DIFFERENTIATION; DNA; PHOSPHORYLATION AB Jun dimerization protein-2 ( JDP2) is a component of the AP-1 transcription factor that represses transactivation mediated by the Jun family of proteins. Here, we examine the functional mechanisms of JDP2 and show that it can inhibit p300-mediated acetylation of core histones in vitro and in vivo. Inhibition of histone acetylation requires the N-terminal 35 residues and the DNA-binding region of JDP2. In addition, we demonstrate that JDP2 has histone-chaperone activity in vitro. These results suggest that the sequence-specific DNA-binding protein JDP2 may control transcription via direct regulation of the modification of histones and the assembly of chromatin. C1 China Med Univ, Dept Med Genet, Shenyang 110001, Peoples R China. Univ Tsukuba, Inst Basic Med Sci, Dept Infect Biol, Tsukuba, Ibaraki 3058575, Japan. Univ Tokyo, Inst Mol & Cellular Biosci, Bunkyo Ku, Tokyo 1130032, Japan. Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Biochem & Cell Biol, Shanghai 20031, Peoples R China. Univ Calif Los Angeles, Sch Med, Dent Res Inst, Los Angeles, CA 90095 USA. Nagasaki Univ, Sch Med, Dept Biochem, Nagasaki 8528523, Japan. RIKEN, Dept Biol Syst, BioResouce Ctr, Gene Engn Div, Tsukuba, Ibaraki 3050074, Japan. RP Yokoyama, KK (reprint author), Natl Inst Diabet & Digest & Kidney Dis, Lab Mol Biol, US Natl Inst Hlth, Bethesda, MD 20892 USA. EM kazu@brc.riken.jp NR 38 TC 43 Z9 46 U1 0 U2 5 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD APR PY 2006 VL 13 IS 4 BP 331 EP 338 DI 10.1038/nsmb1063 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 029RF UT WOS:000236581400014 PM 16518400 ER PT J AU Zofall, M Persinger, J Kassabov, SR Bartholomew, B AF Zofall, M Persinger, J Kassabov, SR Bartholomew, B TI Chromatin remodeling by ISW2 and SWI/SNF requires DNA translocation inside the nucleosome SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID CORE PARTICLE; TARGET SITES; MECHANISM; RSC; DISTINCT; COMPLEX; BINDING; MOBILIZATION; RESOLUTION; PROTEINS AB Chromatin-remodeling complexes regulate access to nucleosomal DNA by mobilizing nucleosomes in an ATP-dependent manner. In this study, we find that chromatin remodeling by SWI/SNF and ISW2 involves DNA translocation inside nucleosomes two helical turns from the dyad axis at superhelical location-2. DNA translocation at this internal position does not require the propagation of a DNA twist from the site of translocation to the entry/exit sites for nucleosome movement. Nucleosomes are moved in 9- to 11- or B50-base-pair increments by ISW2 or SWI/SNF, respectively, presumably through the formation of DNA loops on the nucleosome surface. Remodeling by ISW2 but not SWI/SNF requires DNA torsional strain near the site of translocation, which may work in conjunction with conformational changes of ISW2 to promote nucleosome movement on DNA. The difference in step size of nucleosome movement by SWI/SNF and ISW2 demonstrates how SWI/SNF may be more disruptive to nucleosome structure than ISW2. C1 So Illinois Univ, Sch Med, Dept Biochem & Mol Biol, Carbondale, IL 62901 USA. Columbia Univ, Ctr Neurobiol & Behav, New York, NY 10032 USA. RP Bartholomew, B (reprint author), NCI, US Natl Inst Hlth, Covenant Dr,Bldg 37,Room 6050, Bethesda, MD 20892 USA. EM bbartholomew@siumed.edu FU NIGMS NIH HHS [GM 48413, GM 70864] NR 39 TC 141 Z9 142 U1 2 U2 8 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD APR PY 2006 VL 13 IS 4 BP 339 EP 346 DI 10.1038/nsmb1071 PG 8 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 029RF UT WOS:000236581400015 PM 16518397 ER PT J AU Truglio, JJ Karakas, E Rhau, B Wang, H DellaVecchia, MJ Van Houten, B Kisker, C AF Truglio, JJ Karakas, E Rhau, B Wang, H DellaVecchia, MJ Van Houten, B Kisker, C TI Structural basis for DNA recognition and processing by UvrB SO NATURE STRUCTURAL & MOLECULAR BIOLOGY LA English DT Article ID NUCLEOTIDE EXCISION-REPAIR; ESCHERICHIA-COLI; CRYSTAL-STRUCTURE; DAMAGE RECOGNITION; (A)BC EXCINUCLEASE; THERMUS-THERMOPHILUS; PREINCISION COMPLEX; PROTEIN COMPLEX; POLYMERASE-I; ACTIVE-SITE AB DNA-damage recognition in the nucleotide excision repair ( NER) cascade is a complex process, operating on a wide variety of damages. UvrB is the central component in prokaryotic NER, directly involved in DNA-damage recognition and guiding the DNA through repair synthesis. We report the first structure of a UvrB-double-stranded DNA complex, providing insights into the mechanism by which UvrB binds DNA, leading to formation of the preincision complex. One DNA strand, containing a 3' overhang, threads behind a beta-hairpin motif of UvrB, indicating that this motif inserts between the strands of the double helix, thereby locking down either the damaged or undamaged strand. The nucleotide directly behind the beta-hairpin is flipped out and inserted into a small, highly conserved pocket in UvrB. C1 SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. Natl Inst Environm Hlth Sci, Lab Mol Genet, US Natl Inst Hlth, Res Triangle Pk, NC 27709 USA. Univ Wurzburg, Inst Struct Biol, Rudolf Virchow Ctr Expt Biomed, D-97078 Wurzburg, Germany. RP Kisker, C (reprint author), SUNY Stony Brook, Dept Pharmacol Sci, Stony Brook, NY 11794 USA. EM caroline.kisker@virchow.uni-wuerzburg.de RI Wang, Hong/F-3164-2014 OI Wang, Hong/0000-0003-0165-3559 FU Intramural NIH HHS; NIGMS NIH HHS [GM 070873] NR 39 TC 68 Z9 70 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1545-9985 J9 NAT STRUCT MOL BIOL JI Nat. Struct. Mol. Biol. PD APR PY 2006 VL 13 IS 4 BP 360 EP 364 DI 10.1038/nsmb1072 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 029RF UT WOS:000236581400018 PM 16532007 ER PT J AU De Roos, AJ Rothman, N Brown, M Bell, DA Pittman, GS Shapiro, WR Selker, RG Fine, HA Black, PM Inskip, PD AF De Roos, AJ Rothman, N Brown, M Bell, DA Pittman, GS Shapiro, WR Selker, RG Fine, HA Black, PM Inskip, PD TI Variation in genes relevant to aromatic hydrocarbon metabolism and the risk of adult brain tumors SO NEURO-ONCOLOGY LA English DT Article DE acoustic neuroma; aromatic hydrocarbons; brain tumors; gene-environment interaction; glioma; meningioma ID GLUTATHIONE-S-TRANSFERASE; MICROSOMAL EPOXIDE HYDROLASE; LUNG-CANCER RISK; PROSTATE-CANCER; BREAST-CANCER; INCREASED SUSCEPTIBILITY; ESOPHAGEAL-CARCINOMA; JAPANESE POPULATION; CIGARETTE-SMOKING; CELL CARCINOMA AB Genes involved in phase I and phase 11 regulation of aromatic hydrocarbon-induced effects exhibit sequence variability that may mediate the risk of adult brain tumors. We evaluated associations between gene variants in CYP1A1, CYP1B1, GSTM3, EPHX1, and NQO1 and adult brain tumor incidence. Cases were patients with glioma (n = 489), meningioma (n = 197), or acoustic neuroma (n = 96) diagnosed from 1994 to 1998 at three U.S. hospitals. Controls were 799 patients admitted to the same hospitals for nonmalignant conditions. DNA was extracted from blood samples collected from 1277 subjects, and genotyping was conducted for CYP1A1 1462V, CYP1B1 V432L, EPHX1 Y113H, GSTM3 *A/"B (intron 6 deletion), and NQO1 P187S. The CYP1B1 V432L homozygous variant was associated with decreased risk of meningioma (odds ratio [OR] = 0.6; 95% CI, 0.3-1.0) but not the other tumor types. The GSTM3 *B/*B genotype was associated with increased risk of glioma (OR = 2.3; 95% CI, 1.0-5.2) and meningioma (OR = 3.6; 95% CI, 1.3-9.8). Increased risks associated with GSTM3 *B/*B were observed in younger subjects (age < 50) and older subjects (age >= 50), in men and women, and within each study site. The magnitude of association for GSTM3 with glioma and meningioma was greater among ever-smokers than among those who had never smoked. None of the other genotypes showed consistent associations with any tumor type. The association with the GSTM3 *B allele, while intriguing, requires replication, and additional research is needed to clarify the function of the GSTM3 alleles studied here. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98109 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, Canc Res Ctr, Frederick, MD 20877 USA. NIEHS, Lab Computat Biol & Risk Anal, Res Triangle Pk, NC 27709 USA. St Josephs Hosp, Phoenix, AZ 85013 USA. Western Penn Hosp, Pittsburgh, PA 15243 USA. NCI, Neurooncol Branch, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RP De Roos, AJ (reprint author), Fred Hutchinson Canc Res Ctr, 1100 Fairview Ave N,M4-B874, Seattle, WA 98109 USA. EM deroos@u.washington.edu FU Intramural NIH HHS NR 71 TC 25 Z9 25 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2006 VL 8 IS 2 BP 145 EP 155 DI 10.1215/15228517-2005-003 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 031MG UT WOS:000236708100007 PM 16598069 ER PT J AU Prados, MD Lamborn, K Yung, WKA Jaeckle, K Robins, HI Mehta, M Fine, HA Wen, PY Cloughesy, T Chang, S Nicholas, MK Schiff, D Greenberg, H Junck, L Fink, K Hess, K Kuhn, J AF Prados, MD Lamborn, K Yung, WKA Jaeckle, K Robins, HI Mehta, M Fine, HA Wen, PY Cloughesy, T Chang, S Nicholas, MK Schiff, D Greenberg, H Junck, L Fink, K Hess, K Kuhn, J TI A phase 2 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: A North American Brain Tumor Consortium study SO NEURO-ONCOLOGY LA English DT Article DE clinical trial; irinotecan; phase 2; recurrent malignant glioma ID CHEMOTHERAPY; GLIOBLASTOMA; METABOLITE; ADULTS AB The purpose of this study was to determine the response to CPT-11 administered every three weeks to adults with progressive malignant glioma, treated with or without enzyme-inducing antiepileptic drug (EIAED) therapy, at the recommended phase 2 dose determined from a previous phase 1 study. Adult patients age 18 or older with a KPS of 60 or higher who had measurable recurrent grade III anaplastic glioma (AG) or grade IV glioblastoma multiforme (GBM) were eligible. No more than one prior chemotherapy was allowed, either as adjuvant therapy or for recurrent disease. The CPT-11 dose was 350 mg/m(2) i.v. every three weeks in patients not on EIAED and 750 mg/m(2) in patients on EIAED therapy. Patients with stable or responding disease could be treated until tumor progression or a total of 12 months of therapy. The primary end point of the study was to determine whether CPT-11. could significantly delay tumor progress on, using the rate of six-month progression-free survival (PFS-6). The trial was sized to be able to discriminate between a 15% and 35% rate for the GBM group alone and between a 20% and 40% rate for the entire cohort. There were 51 eligible patients, including 38 GBM and 13 AG patients, enrolled. The median age was 52 and 42 years, respectively. PFS-6 for the entire cohort was 1.7.6%. PFS-6 was 15.7% (95% confidence interval [CI], 0.07-0.31) for the GBM patients and 23% (95% CI, 0.07-0.52) for AG patients. Toxicity for the group included diarrhea and myelosuppression. We conclude that the recommended phase 2 dose of CPT-11 for patients with or without EIAED was ineffective on this schedule, in this patient population. C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Wisconsin, Med Ctr, Madison, WI 53792 USA. Natl Inst Hlth, Bethesda, MD 20892 USA. Dana Farber Brigham & Womens Canc Ctr, Boston, MA 02115 USA. Univ Calif Los Angeles, Los Angeles, CA 90095 USA. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA 22908 USA. Univ Michigan, Ctr Med, Ann Arbor, MI 48109 USA. Univ Texas, SW Med Ctr, Dallas, TX 75390 USA. Univ Texas, Hlth Sci Ctr, San Antonio, TX 78229 USA. RP Prados, MD (reprint author), Univ Calif San Francisco, 400 Parnassus Ave,Room A808, San Francisco, CA 94143 USA. EM pradosm@neurosurg.ucsf.edu OI mehta, minesh/0000-0002-4812-5713 FU NCI NIH HHS [CA 62399, U01 CA062399] NR 12 TC 126 Z9 129 U1 0 U2 5 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2006 VL 8 IS 2 BP 189 EP 193 DI 10.1215/15228517-2005-010 PG 5 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 031MG UT WOS:000236708100012 PM 16533878 ER PT J AU Greig, NH Sambamurti, K Giordano, T Utsuki, T Ingram, DK Yu, QS Holloway, HW Brossi, A Chen, DM Lahiri, DK AF Greig, NH Sambamurti, K Giordano, T Utsuki, T Ingram, DK Yu, QS Holloway, HW Brossi, A Chen, DM Lahiri, DK TI Cholinesterase inhibitors decrease beta-amyloid in brain SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy CY APR 19-22, 2006 CL Geneva, SWITZERLAND C1 NIA, NIH, Baltimore, MD 21224 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Louisiana State Univ, Hlth Sci Ctr, Shreveport, LA 71105 USA. Univ N Carolina, Chapel Hill, NC USA. Indiana Univ, Med Ctr, Inst Psychiat Res, Indianapolis, IN USA. EM greign@grc.nia.nih.gov; sambak@musc.edu; dlahiri@iupui.edu 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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD APR PY 2006 VL 27 SU 1 MA 38 BP S9 EP S9 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 024PJ UT WOS:000236208100039 ER PT J AU Launer, LJ AF Launer, LJ TI Blood pressure lowering: Is there enough evidence to call it a prevention strategy for dementia? SO NEUROBIOLOGY OF AGING LA English DT Meeting Abstract CT 9th International Geneva/Springfield Symposium on Advances in Alzheimer Therapy CY APR 19-22, 2006 CL Geneva, SWITZERLAND C1 NIA, Bethesda, MD 20892 USA. EM launerl@nia.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 0197-4580 J9 NEUROBIOL AGING JI Neurobiol. Aging PD APR PY 2006 VL 27 SU 1 MA 51 BP S12 EP S12 PG 1 WC Geriatrics & Gerontology; Neurosciences SC Geriatrics & Gerontology; Neurosciences & Neurology GA 024PJ UT WOS:000236208100052 ER PT J AU Gu, H Lu, HZ Ye, FQ Stein, EA Yang, YH AF Gu, H Lu, HZ Ye, FQ Stein, EA Yang, YH TI Noninvasive quantification of cerebral blood volume in humans during functional activation SO NEUROIMAGE LA English DT Article DE cerebral blood volume; brain activation; functional MRI; BOLD; VASO ID SENSORY STIMULATION; NEURONAL-ACTIVITY; MAGNETIC-FIELDS; SIGNAL CHANGES; BRAIN; FLOW; OXYGENATION; PERFUSION; CONTRAST; CORTEX AB Like cerebral blood flow (CBF), cerebral blood volume (CB%r) is an important physiological parameter closely associated with brain activity and thus, noninvasive quantification of CBV during brain activation provides another opportunity to investigate the relationship between neuronal activity and hemodynamic changes. In this paper, a new method is presented that is able to quantify CBV at rest and during activation. Specifically, using an inversion recovery pulse sequence, a set of brain images was collected at various inversion times (TIs). At each TI, functional images were acquired with a block-design visual stimulation paradigm. A biophysical model comprised of multiple tissue components was developed and was utilized for the determination of CBV using the visual stimulation data. MRI experiments on five healthy volunteers showed that CBV was 5.0 +/- 1.5 ml blood/100 ml brain during rest and increased to 6.6 +/- 1.8 ml blood/100 ml brain following visual stimulation. Furthermore, experiments with visual stimulation at two frequencies (2 and 8 Hz) showed that the increases in CBV correlated with the strength of stimulation. This technique with its ability to measure quantitative CBV values noninvasively, provides a valuable too] for quantifying hemodynamic signals associated with brain activation. Published by Elsevier Inc. C1 Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, Baltimore, MD 21042 USA. NYU, Dept Radiol, New York, NY 10016 USA. NIMH, Neurophysiol Imaging Facil, NIH, Bethesda, MD 20892 USA. RP Yang, YH (reprint author), Natl Inst Drug Abuse, Neuroimaging Res Branch, NIH, 5500 Nathan Shock Dr,Bldg C,Room 383, Baltimore, MD 21042 USA. EM yihongyang@intra.nida.nih.gov RI Stein, Elliot/C-7349-2008 NR 39 TC 29 Z9 29 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 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 1 PY 2006 VL 30 IS 2 BP 377 EP 387 DI 10.1016/j.neuroimage.2005.09.057 PG 11 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 031CR UT WOS:000236682200004 PM 16278086 ER PT J AU Nugent, AC Milham, MP Bain, EE Mah, L Cannon, DM Marrett, S Zarate, CA Pine, DS Price, JL Drevets, WC AF Nugent, AC Milham, MP Bain, EE Mah, L Cannon, DM Marrett, S Zarate, CA Pine, DS Price, JL Drevets, WC TI Cortical abnormalities in bipolar disorder investigated with MRI and voxel-based morphometry SO NEUROIMAGE LA English DT Article DE morphometry; bipolar depression; magnetic resonance imaging ID GRAY-MATTER VOLUME; POSITRON-EMISSION-TOMOGRAPHY; ANTERIOR CINGULATE CORTEX; MAJOR-DEPRESSIVE-DISORDER; MOOD DISORDERS; HUMAN BRAIN; PREFRONTAL CORTEX; FUNCTIONAL NEUROANATOMY; UNIPOLAR DEPRESSION; GLUCOSE-METABOLISM AB Bipolar disorder (BD) has been associated with abnormalities of brain structure. Specifically, in vivo volumetric MRI and/or post mortern studies of BID have reported abnormalities of gray matter (GM) volume in the medial prefrontal cortex (PFC), amygdala, hippocampal subiculum and ventral striatum. These structures share anatomical connections with each other and form part of a "visceromotor" network modulating emotional behavior. Areas of the lateral orbital, superior temporal and posterior cingulate cortices project to this network, but morphometric abnormalities in these areas have not been established in BD. The current study assessed tissue volumes within these areas in 131) using MRI and voxel-based morphometry (VBM). MRI images were obtained from 36 BD subjects and 65 healthy controls. To account for possible neurotrophic and neuroprotective effects of psychotropic medications, BID subjects were divided into medicated and unmedicated groups. Images were segmented into tissue compartments, which were examined on a voxel-wise basis to determine the location and extent of morphometric changes. The GM was reduced in the posterior cingulate/retrosplenial cortex and superior temporal gyrus of unmedicated BD subjects relative to medicated BD subjects and in the lateral orbital cortex of medicated BD subjects relative to controls. White matter (WM) was increased in the orbital and posterior cingulate cortices, which most likely reflected alterations in gyral morphology resulting from the reductions in the associated GM. The morphometric abnormalities in the posterior cingulate, superior temporal and lateral orbital cortices in BD support the hypothesis that the extended network of neuroanatomical structures subserving visceromotor regulation contains structural alterations in BID. Additionally, localization of morphometric abnormalities to areas known to exhibit increased metabolism in depression supports the hypothesis that repeated stress and elevated glucocorticoid secretion may result in neuroplastic changes in BD. (c) 2005 Elsevier Inc. All rights reserved. C1 NIMH, Sect Neuroimaging Mood & Anxiety Disorders Progra, NIH, Bethesda, MD 20892 USA. Univ Illinois, Beckman Inst, Urbana, IL 61810 USA. NIMH, Funct Neuroimaging Facil, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA. RP Nugent, AC (reprint author), NIMH, Sect Neuroimaging Mood & Anxiety Disorders Progra, NIH, 1 Ctr Dr,MSC 0135, Bethesda, MD 20892 USA. EM nugenta@intra.nimh.nih.gov RI Cannon, Dara/C-1323-2009; OI Cannon, Dara/0000-0001-7378-3411; Marrett, Sean/0000-0001-8179-6511; Nugent, Allison/0000-0003-2569-2480 FU Intramural NIH HHS NR 78 TC 136 Z9 139 U1 2 U2 9 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD APR 1 PY 2006 VL 30 IS 2 BP 485 EP 497 DI 10.1016/j.neuroimage.2005.09.029 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 031CR UT WOS:000236682200014 PM 16256376 ER PT J AU Fritz, DA Dwyer, MG Bagnato, F Watts, KL Bratina, A Zorzon, M Durastanti, V Locatelli, L Millefiorini, E Zivadinov, R AF Fritz, DA Dwyer, MG Bagnato, F Watts, KL Bratina, A Zorzon, M Durastanti, V Locatelli, L Millefiorini, E Zivadinov, R TI Effect of MRI coregistration on serial short-term brain volume changes in multiple sclerosis SO NEUROLOGICAL RESEARCH LA English DT Article DE magnetic resonance imaging; coregistration; brain atrophy; multiple sclerosis ID ATROPHY; ACCURATE; ROBUST; OPTIMIZATION; REGISTRATION; IMAGES AB Objective: To test the effect of serial magnetic resonance (MR) coregistration on short-term brain volume changes using different semiautomated and automated brain volume techniques in patients with relapsing-remitting (RR) multiple sclerosis (MS). Coregistration is frequently used to increase precision in serial MR imaging (MRI) analyses. However, the effect of coregistration on measurement of whole brain volume changes from serial scans in the short term has not been tested in MS patients. Methods: Twenty-eight patients with RR MS [mean disease duration: 4.9 years, mean age: 34.4 years and mean expanded disability status scale (EDSS): 1.4] were scanned at baseline and monthly for a period of 3 months with 2D spin-echo T1-weighted sequences obtained with non-gapped 3 mm axial slices. Percent brain parenchymal fraction change (PBPFC) was calculated by a semiautomated (Buffalo) and, separately, by two automated (Buffalo automated and SIENAX) techniques, whereas percent brain volume change (PBVC) was calculated by the SIENA technique. For coregistration of serial images we used a robust, fully automated linear image coregistration tool. PBPFC and PBVC were calculated before and after coregistration, comparing scans from the following time periods: (1) baseline to month 3; (2) baseline to month 1; (3) month 1 to 2 and (4) month 2 to 3. Results: The highest median PBPFCs measured on non-coregistered images were detected for the baseline-to-month-3 time period and ranged from -0.11% for Buffalo semiautomated to -0.45% for Buffalo automated (p=ns). On coregistered images, the highest PBPFCs were detected for the baseline-to-month-3 time period and ranged from 0.3% for Buffalo semiautomated, -0.3% for Buffalo automated, 0.02% for SIENAX and -0.02% for SIENA (PBVC). At all time points of the study, no significant differences of median volume changes were measured on coregistered and non-coregistered images when comparing the results among the segmentation algorithms. Conclusions: Over a 3 month period we did not detect short-term changes in normalized brain volumes using different measurement techniques. A longer observation period is needed to assess whether coregistration can affect the measurement of long-term brain volume changes. C1 SUNY Buffalo, Jacobs Neurol Inst, Sch Med & Biomed Sci, Dept Neurol,Buffalo Neuroimaging Anal Ctr, Buffalo, NY 14203 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Univ Trieste, Dept Clin Morphol & Technol Sci, I-34127 Trieste, Italy. Univ Roma La Sapienza, Dept Neurol Sci, I-00185 Rome, Italy. RP Zivadinov, R (reprint author), SUNY Buffalo, Jacobs Neurol Inst, Sch Med & Biomed Sci, Dept Neurol,Buffalo Neuroimaging Anal Ctr, 100 High St, Buffalo, NY 14203 USA. EM rzivadinov@thejni.org OI millefiorini, enrico/0000-0001-5318-3849; Dwyer, Michael/0000-0003-4684-4658 NR 14 TC 5 Z9 5 U1 0 U2 0 PU MANEY PUBLISHING PI LEEDS PA HUDSON RD, LEEDS LS9 7DL, ENGLAND SN 0161-6412 J9 NEUROL RES JI Neurol. Res. PD APR PY 2006 VL 28 IS 3 BP 275 EP 279 DI 10.1179/016164106X98152 PG 5 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 038LZ UT WOS:000237223500009 PM 16687053 ER PT J AU Dalakas, MC AF Dalakas, MC TI Therapeutic targets in patients with inflammatory myopathies: Present approaches and a look to the future SO NEUROMUSCULAR DISORDERS LA English DT Review ID INCLUSION-BODY MYOSITIS; INFILTRATING T-CELLS; AUTOIMMUNE NEUROMUSCULAR DISEASES; INTRAVENOUS IMMUNOGLOBULIN; REFRACTORY POLYMYOSITIS; COSTIMULATORY MOLECULE; MUSCLE-CELLS; DIFFERENTIAL EXPRESSION; MONOCLONAL-ANTIBODY; CYTOKINE EXPRESSION C1 NINDS, Neuromuscular Dis Sect, NIH, Bethesda, MD 20892 USA. RP Dalakas, MC (reprint author), NINDS, Neuromuscular Dis Sect, NIH, Bldg 10,Room 4N248,10 Ctr Dr MSC 1382, Bethesda, MD 20892 USA. EM dalakasm@ninds.nih.gov FU Intramural NIH HHS NR 95 TC 31 Z9 33 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0960-8966 J9 NEUROMUSCULAR DISORD JI Neuromusc. Disord. PD APR PY 2006 VL 16 IS 4 BP 223 EP 236 DI 10.1016/j.nmd.2005.12.008 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 038XM UT WOS:000237262800001 PM 16542836 ER PT J AU Andringa, G Bol, JGJM Wang, X Boekel, A Bennett, MC Chase, TN Drukarch, B AF Andringa, G Bol, JGJM Wang, X Boekel, A Bennett, MC Chase, TN Drukarch, B TI Changed distribution pattern of the constitutive rather than the inducible HSP70 chaperone in neuromelanin-containing neurones of the Parkinsonian midbrain SO NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY LA English DT Article DE heat shock protein 70; immunohistochemistry; Lewy body; neuromelanin; neuroprotection; Parkinson's disease ID HEAT-SHOCK-PROTEIN; ALPHA-SYNUCLEIN; MOLECULAR CHAPERONES; ALZHEIMERS-DISEASE; SUBSTANTIA-NIGRA; PC12 CELLS; BRAIN; EXPRESSION; LOCALIZATION; INDUCTION AB Aberrant protein aggregation has been recognized as an important factor in the degeneration of melanized dopaminergic neurones in Parkinson's disease (PD). The constitutive (HSP73) and (heat)-inducible (HSP72) proteins of the heat shock 70 family form a major defence system against pathological protein aggregation. However, the distribution patterns of these chaperones in nigral neuromelanin-laden neurones are largely unknown. The present study determined the distribution of HSP72 and HSP73 in control and Parkinsonian substantia nigra, using immunohistochemistry. In the neuromelanin-laden neurones of controls, HSP72 was nondetectable, whereas HSP73 was weakly expressed in both the cytosol and the nucleus. Surprisingly, in PD subjects, marked nuclear HSP73, but not HSP72 immunoreactivity was observed, while cytosolic immunoreactivity of the two chaperones resembled the labelling pattern observed in controls. Furthermore, HSP73 immunoreactivity was observed in a subset of the Lewy bodies (LBs) detected in the substantia nigra of PD subjects, whereas only few of these LBs were labelled with HSP72. Interestingly, HSP72 and to a lesser extent HSP73 immunoreactivity was much stronger in nonmelanized neurones as compared with melanized neurones in this area. Thus, we conclude that the distribution pattern of HSP73 rather than HSP72 is changed in the nigral neuromelanin-laden neurones of PD subjects as compared with control subjects. The impaired ability of aged, dopaminergic neurones to express high levels of chaperones, may contribute to the preferential vulnerability of the latter cells in PD. C1 VU Univ Med Ctr, ICEN, Dept Med Pharmacol, NL-1081 BT Amsterdam, Netherlands. VU Univ Med Ctr, ICEN, Dept Anat, NL-1081 BT Amsterdam, Netherlands. Natl Inst Neurol Disorders & Stroke, Expt Therapeut Branch, NIH, Bethesda, MD 20892 USA. RP Andringa, G (reprint author), VU Univ Med Ctr, ICEN, Dept Med Pharmacol, Van der Boechorststr 7, NL-1081 BT Amsterdam, Netherlands. EM G.andringa@vumc.nl NR 43 TC 12 Z9 12 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0305-1846 J9 NEUROPATH APPL NEURO JI Neuropathol. Appl. Neurobiol. PD APR PY 2006 VL 32 IS 2 BP 157 EP 169 DI 10.1111/j.1365-2990.2006.00714.x PG 13 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 021MH UT WOS:000235986800005 PM 16599944 ER PT J AU Kim, T Loh, YP AF Kim, T Loh, YP TI Secretory granule biogenesis in neuroendocrine cells SO NEUROPEPTIDES LA English DT Meeting Abstract C1 NICHD, Sect Cellular Neurobiol, Off Sci Director, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 2006 VL 40 IS 2 BP 139 EP 139 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 046WU UT WOS:000237842600012 ER PT J AU Aguilera, G Young, S Volpi, S Liu, Y Subburaju, S AF Aguilera, G Young, S Volpi, S Liu, Y Subburaju, S TI Vasopressin and chronic stress adaptation SO NEUROPEPTIDES LA English DT Meeting Abstract C1 NICHHD, Sect Endocrine Physiol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 2006 VL 40 IS 2 BP 141 EP 142 PG 2 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 046WU UT WOS:000237842600018 ER PT J AU Chrousos, G Contoreggi, C Rice, KC AF Chrousos, G Contoreggi, C Rice, KC TI Nonpeptide corticotropin-releasing hormone receptor type 1 antagonists and their applications in stress-related psychosomatic disorders SO NEUROPEPTIDES LA English DT Meeting Abstract C1 Natl Inst Drug Abuse, Intramural Res Program, Baltimore, MD USA. NIDDK, Intramural Res Program, Bethesda, MD USA. NICHHD, Intramural Res Program, Bethesda, MD 20892 USA. NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 2006 VL 40 IS 2 BP 141 EP 141 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 046WU UT WOS:000237842600017 ER PT J AU Saavedra, JM Pavel, J AF Saavedra, JM Pavel, J TI Central and peripheral angiotensin II AT1 receptor blockade prevents the stress-induced decrease in cortical CRH1 receptor and benzodiazepine binding and is anxiolytic SO NEUROPEPTIDES LA English DT Meeting Abstract C1 NIMH, Pharmacol Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 2006 VL 40 IS 2 BP 142 EP 142 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 046WU UT WOS:000237842600019 ER PT J AU Shippenberg, TS Kivell, B Bolan, E Kurguntula, D Chefer, VI AF Shippenberg, TS Kivell, B Bolan, E Kurguntula, D Chefer, VI TI Regulation of dopamine transport by kappa opioid systems: Implications for the treatment of drug addiction SO NEUROPEPTIDES LA English DT Meeting Abstract C1 NIDA, Integrat Neurosci Sect, DHHS, NIH,Intramural Res Program, Baltimore, MD 21220 USA. RI Kivell, Bronwyn/P-3140-2014 OI Kivell, Bronwyn/0000-0001-9699-553X NR 0 TC 0 Z9 0 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 2006 VL 40 IS 2 BP 149 EP 150 PG 2 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 046WU UT WOS:000237842600037 ER PT J AU Crawley, JN AF Crawley, JN TI Neuropeptides and behavior: The trouble with galanin in Alzheimer's disease SO NEUROPEPTIDES LA English DT Meeting Abstract C1 NIMH, Lab Behav Neurosci, Intramural Res Program, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 2006 VL 40 IS 2 BP 150 EP 151 PG 2 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 046WU UT WOS:000237842600040 ER PT J AU Rustay, NR Tolu, SG Sullivan, TL Crawley, JN AF Rustay, NR Tolu, SG Sullivan, TL Crawley, JN TI The galanin antagonist M40 rescues the deficit in emotional memory in galanin overexpressing mice SO NEUROPEPTIDES LA English DT Meeting Abstract C1 NIMH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 2006 VL 40 IS 2 BP 152 EP 153 PG 2 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 046WU UT WOS:000237842600045 ER PT J AU Moody, TW Nakagawa, T Kang, Y Jakowlew, S Chan, D Jensen, RT AF Moody, TW Nakagawa, T Kang, Y Jakowlew, S Chan, D Jensen, RT TI Bombesin/GRP receptor antagonists and HDAC inhibitors are synergistic at inhibiting lung cancer proliferation SO NEUROPEPTIDES LA English DT Meeting Abstract C1 NCI, DHHS, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD USA. NCI, Rockville, MD USA. Univ Colorado, Hlth Sci Ctr, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD APR PY 2006 VL 40 IS 2 BP 157 EP 157 PG 1 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 046WU UT WOS:000237842600053 ER PT J AU Powell, KJ Binder, TL Hori, S Nakabeppu, Y Weinberger, DR Lipska, BK Robertson, GS AF Powell, KJ Binder, TL Hori, S Nakabeppu, Y Weinberger, DR Lipska, BK Robertson, GS TI Neonatal ventral hippocampal lesions produce an elevation of Delta FosB-like protein(s) in the rodent neocortex SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE schizophrenia; neurodevelopment; immediate-early genes; neonatal lesion; hippocampus; cerebral cortex ID IMMEDIATE-EARLY GENES; LASTING AP-1 COMPLEX; PREFRONTAL CORTEX; NERVOUS-SYSTEM; C-FOS; NUCLEUS-ACCUMBENS; CHRONIC COCAINE; CORTICAL DEVELOPMENT; ANTIPSYCHOTIC-DRUGS; ENTORHINAL CORTEX AB Rats that have sustained bilateral excitotoxic lesions of the ventral hippocampus (VH) as neonates develop behavioral abnormalities as adults (hyper-responsiveness to stress, diminished prepulse inhibition, and increased sensitivity to dopamine agonists), which resemble certain aspects of schizophrenia. Although this behavioral profile is thought to reflect dysregulation of the mesolimbic dopamine system, the precise neuroanatomical and neurochemical substrates that mediate the emergence of these abnormalities during brain maturation are unclear. In order to identify putative sites responsible for the development of behavioral abnormalities following neonatal lesions of the VH, we utilized the chronic neuronal activity marker Delta FosB. By comparison to sham lesioned animals, bilateral destruction of the VH elevated Delta FosB expression throughout the caudate putamen and neocortex of animals lesioned as neonates. These increases were not observed in rats lesioned as young-adults, suggesting that Delta FosB induction in the cortex of neonatally lesioned rats may be related to altered cortical neurodevelopment. Accumulating evidence implicates Delta FosB in mediation of the long-lasting effects of altered dopaminergic neurotransmission on behavior. The present findings are consistent with this proposal and suggest that elevated expression of Delta FosB identifies overactive neurons that may contribute to the enhanced sensitivity to stress and dopaminergic agonists of rats that have sustained bilateral ventral hippocampal lesions as neonates. C1 Dalhousie Univ, Fac Med, Dept Psychiat, Halifax, NS B3H 1X5, Canada. Dalhousie Univ, Fac Med, Dept Pharmacol, Halifax, NS B3H 1X5, Canada. Beth Israel Deaconess Med Ctr, Dept Psychiat, Boston, MA 02215 USA. Kyushu Univ, Med Inst Bioregulat, Dept Immunobiol & Neurosci, Div Neurofunct Genom,Higashi Ku, Fukuoka 812, Japan. NIMH, Clin Brain Disorders Branch, Intramural Res Program, NIH, Bethesda, MD 20892 USA. RP Robertson, GS (reprint author), Dalhousie Univ, Fac Med, Dept Psychiat, Sir Charles Tupper Med Bldg,5850 Coll St, Halifax, NS B3H 1X5, Canada. EM George.Robertson@dal.ca RI Nakabeppu, Yusaku/A-8902-2011 NR 62 TC 15 Z9 17 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD APR PY 2006 VL 31 IS 4 BP 700 EP 711 DI 10.1038/sj.npp.1300883 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 023QQ UT WOS:000236141700002 PM 16132062 ER PT J AU Colwell, B Ramirez, N Koehly, L Stevens, S Smith, DW Creekmur, S AF Colwell, B Ramirez, N Koehly, L Stevens, S Smith, DW Creekmur, S TI Seasonal variations in the initiation of smoking among adolescents SO NICOTINE & TOBACCO RESEARCH LA English DT Article ID CIGARETTES; TOBACCO; SCHOOL AB Numerous studies have identified a variety of reasons that youths give for starting smoking. Few efforts have been made, however, to identify seasonal variations in initiation. This study was an attempt to fill that void. We examined data from 342 youths participating in a mandated smoking education and cessation program in Texas. Data were collected based on responses to questions in participant workbooks, including an item asking participants about the month in which they started smoking. A total of 47% of the participants indicated that they started smoking in May through August (chi(2)=91.42, df=3). Post-hoc analyses indicated that significantly more youths than expected began smoking in May and June, whereas significantly fewer youths than expected began smoking in September and November. Unsupervised time out of school during the first months of summer vacation is a period of increased danger for smoking initiation. The significantly lower rates during September seem to be related to the beginning of school. C1 Texas A&M Sch Rural Publ Hlth, Dept Social & Behav Hlth, College Stn, TX 77843 USA. NHGRI, NIH, Bethesda, MD USA. Texas Dept State Hlth Serv, Austin, TX USA. Univ Houston, Dept Hlth & Human Performance, Houston, TX USA. RP Colwell, B (reprint author), Texas A&M Sch Rural Publ Hlth, Dept Social & Behav Hlth, 1266 TAMU, College Stn, TX 77843 USA. EM colwell@srph.tamhsc.edu NR 25 TC 8 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1462-2203 J9 NICOTINE TOB RES JI Nicotine Tob. Res. PD APR PY 2006 VL 8 IS 2 BP 239 EP 243 DI 10.1080/14622200600576503 PG 5 WC Substance Abuse; Public, Environmental & Occupational Health SC Substance Abuse; Public, Environmental & Occupational Health GA 043UW UT WOS:000237628700009 PM 16766416 ER PT J AU Jones, CE Wolf, RL Detre, JA Das, B Saha, PK Wang, J Zhang, Y Song, HK Wright, AC Mohler, EM Fairman, RM Zager, EL Velazquez, OC Golden, MA Carpenter, JP Wehrli, FW AF Jones, CE Wolf, RL Detre, JA Das, B Saha, PK Wang, J Zhang, Y Song, HK Wright, AC Mohler, EM Fairman, RM Zager, EL Velazquez, OC Golden, MA Carpenter, JP Wehrli, FW TI Structural MRI of carotid artery burden and characterization of atherosclerotic lesion hemispheric cerebral blood flow before and after carotid endarterectomy SO NMR IN BIOMEDICINE LA English DT Article DE carotid artery disease; cerebral hypoperfusion; stroke; perfusion imaging; arterial spin labeling; MRI ID CEREBROVASCULAR-DISEASE; IMAGING TECHNIQUES; BRAIN PERFUSION; SPIN INVERSION; CONTRAST; STENOSIS; CIRCULATION; IMPLEMENTATION; HEMODYNAMICS; ANGIOGRAPHY AB Collateral circulation plays a major role in maintaining cerebral blood flow (CBF) in patients with internal carotid artery (ICA) stenosis. CBF can remain normal despite severe ICA stenosis, making the benefit of carotid endarterectomy (CEA) or stenting difficult to assess. Before and after surgery, we assessed CBF supplied through the ipsilateral (stenotic) or contralateral ICA individually with a novel hemisphere-selective arterial spin-labeling (ASL) perfusion MR technique. We further explored the relationship between CBF and ICA obstruction ratio (OR) acquired with a multislice black-blood imaging sequence. For patients With unilateral ICA stenosis (n=19), conventional bilateral labeling did not reveal interhemispheric differences. With unilateral labeling, CBF in the middle cerebral artery (MCA) territory on the surgical side from the ipsilateral Supply (53.7 +/- 3.3 ml/100g/min) was lower than CBF in the contralateral MCA territory from the contralateral supply (58.5 +/- 2.7ml/100g/min), although not statistically significant (p=0.09). The ipsilateral MCA territory received significant (p=0.02) contralateral supply (7.0 +/- 2.7ml/100g/min), while ipsilateral supply to the contralateral side was not reciprocated. After surgery (n=11), ipsilateral supply to the MCA territory increased from 57.3 +/- 5.7 to 67.3 +/- 5.4ml/100g/min (p=0.03), and contralateral Supply to the ipsilateral MCA territory decreased. The best predictor of increased CBF on the side of surgery was normalized presurgical ipsilateral supply (r(2)=0.62 p=0.004). OR was less predictive of change, although the change in normalized contralateral supply was negatively correlated with ORexcess ( ORipsilateral - ORcontralaterale) (r(2)=0.58, p=0.006). The results demonstrate the effect of carotid artery stenosis oil blood Supply to the cerebral hemispheres, as well as the relative role of collateral pathways before surgery and redistribution of blood flow through these pathways after surgery. Unilateral ASL may better predict hemodynamic surgical outcome (measured by improved perfusion) than ICA OR. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Univ Penn, Med Ctr, Dept Radiol, Neuroradiol Sect, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Dept Neurol, Philadelphia, PA USA. Natl Inst Mental Hlth, Bethesda, MD USA. Univ Penn, Ctr Med, Dept Cardiol, Philadelphia, PA USA. Univ Penn, Med Ctr, Dept Vasc Surg, Philadelphia, PA USA. Univ Penn, Med Ctr, Dept Neurosurg, Philadelphia, PA USA. RP Wolf, RL (reprint author), Univ Penn, Med Ctr, Dept Radiol, Neuroradiol Sect, 3400 Spruce St, Philadelphia, PA 19104 USA. EM Ronald.wolf@uphs.upenn.edu RI Saha, Punam /F-8833-2011 NR 47 TC 19 Z9 21 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD APR PY 2006 VL 19 IS 2 BP 198 EP 208 DI 10.1002/nbm.1017 PG 11 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 030EW UT WOS:000236618000004 PM 16475206 ER PT J AU Shen, J Xu, S AF Shen, J Xu, S TI Theoretical analysis of carbon-13 magnetization transfer for in vivo exchange between alpha-ketoglutarate and glutamate SO NMR IN BIOMEDICINE LA English DT Article DE Bloch-McConnell equations; off-resonance effect; quasi-steady-state assumption; magnetization transfer; carbon-13 magnetic resonance spectroscopy; glutamate; aspartate; transamination ID TRANSFER KINETIC MEASUREMENTS; OFF-RESONANCE IRRADIATION; NMR SATURATION-TRANSFER; CHEMICAL-EXCHANGE; RAT-BRAIN; INCOMPLETE SATURATION; RELAXATION-TIMES; CREATINE-KINASE; 11.7 TESLA; SPECTROSCOPY AB Many enzymes catalyze fast exchange between a small pool and a large pool in vivo. For example, aspartate aminotransferase catalyzes fast exchanges between alpha-ketoglutarate and glutamate and between oxaloacetate and aspartate, which can be detected using in vivo C-13 MRS while saturating alpha-carbons of the keto acids. Unlike in the traditional saturation transfer experiments studied using (31)p MRS, the tricarboxylic acid cycle intermediates alpha-ketoglutarate and oxaloacetate are below the detection limit of in vivo NMR. In this work, a theoretical analysis of the saturation transfer between alpha-ketoglutarate and glutamate catalyzed by aspartate aminotransferase was presented to examine the requirements for complete saturation of the rapidly turning over alpha-ketoglutarate pool without affecting the longitudinal magnetization of glutamate. The fast turnover of the small alpha-ketoalutarate pool also allows a quasi-steady-state approximation of its dynamic longitudinal relaxation. The theoretical analysis provides a useful guide for designing experimental methods to characterize saturation transfer processes associated with fast turning over small pools in vivo. Copyright (c) 2006 John Wiley & Sons, Ltd. C1 Natl Inst Mental Hlth, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Shen, J (reprint author), Natl Inst Mental Hlth, Mol Imaging Branch, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov FU Intramural NIH HHS NR 34 TC 8 Z9 8 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0952-3480 J9 NMR BIOMED JI NMR Biomed. PD APR PY 2006 VL 19 IS 2 BP 248 EP 254 DI 10.1002/nbm.1021 PG 7 WC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy SC Biophysics; Radiology, Nuclear Medicine & Medical Imaging; Spectroscopy GA 030EW UT WOS:000236618000010 PM 16521093 ER PT J AU Creinin, MD Huang, XK Westhoff, C Barnhart, K Gilles, JM Zhang, J AF Creinin, Mitchell D. Huang, Xiangke Westhoff, Carolyn Barnhart, Kurt Gilles, Jerry M. Zhang, Jun CA Natl Inst Child Hlth Human Dev Man TI Factors related to successful misoprostol treatment for early pregnancy failure SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID SPONTANEOUS-ABORTION; EXPECTANT MANAGEMENT; SURGICAL EVACUATION; RANDOMIZED-TRIAL; MISSED ABORTION; ENDOMETRIAL THICKNESS; VAGINAL MISOPROSTOL; MEDICAL-MANAGEMENT; MISCARRIAGE; MIFEPRISTONE AB OBJECTIVE: To identify potential predictors for treatment success in medical management with misoprostol for early pregnancy failure. METHODS: We conducted a planned secondary analysis of data from a multicenter trial that compared medical and surgical management of early pregnancy failure. Medical management consisted of misoprostol 800 mu g vaginally on study day 1, with a repeat dose if indicated on day 3. Women returned on days 3 and 15, and a telephone interview was conducted on day 30. Failure was defined as suction aspiration for any reason within 30 days. Demographic, historical, and outcome variables were included in univariable analyses of success. Multivariable analyses were conducted using clinical site, gestational age, and variables for which the univariable analysis resulted in a P <.1 to determine predictors of overall treatment success and first-dose success. RESULTS: Of the 491 women who received misoprostol, 485 met the criteria for this secondary analysis. Lower abdominal pain or vaginal bleeding within the last 24 hours, Rh-negative blood type, and nulliparity were predictive of overall success. However, only vaginal bleeding within the last 24 hours and parity of 0 or 1 were predictive of first-dose success. Overall success exceeds 92% in women who have localized abdominal pain within the last 24 hours, Rh-negative blood type, or the combination of vaginal bleeding in the past 24 hours and nulliparity. CONCLUSION: Misoprostol treatment for early pregnancy failure is highly successful in select women, primarily those with active bleeding and nulliparity. Clinicians and patients should be aware of these differences when considering misoprostol treatment. C1 Univ Pittsburgh, Sch Med, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15260 USA. Magee Womens Res Inst, Pittsburgh, PA USA. Clin Trials & Surveys Corp, Baltimore, MD USA. Columbia Univ, Dept Obstet & Gynecol, New York, NY USA. Univ Penn, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Univ Miami, Dept Obstet & Gynecol, Miami, FL 33152 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Creinin, MD (reprint author), Magee Womens Hosp, 300 Halket St, Pittsburgh, PA 15213 USA. EM mcreinin@upmc.edu FU NCRR NIH HHS [M01RR000056, M01 RR000056]; NICHD NIH HHS [N01-HD-1-3323, N01-HD-1-3324, N01-HD-1-3322, N01-HD-1-3325, N01-HD-1-3321] NR 31 TC 30 Z9 32 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2006 VL 107 IS 4 BP 901 EP 907 DI 10.1097/01.AOG.0000206737.68709.3e PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 095GM UT WOS:000241296200024 PM 16582130 ER PT J AU Villanueva, CM Cantor, KP Grimalt, JO Castano-Vinyals, G Malats, N Silverman, D Tardon, A Garcia-Closas, R Serra, C Carrato, A Rothman, N Real, FX Dosemeci, M Kogevinas, M AF Villanueva, CM Cantor, KP Grimalt, JO Castano-Vinyals, G Malats, N Silverman, D Tardon, A Garcia-Closas, R Serra, C Carrato, A Rothman, N Real, FX Dosemeci, M Kogevinas, M TI Assessment of lifetime exposure to trihalomethanes through different routes SO OCCUPATIONAL AND ENVIRONMENTAL MEDICINE LA English DT Article ID CHLORINATION BY-PRODUCTS; DRINKING-WATER SOURCE; TAP WATER; BLADDER-CANCER; CHLOROFORM; WOMEN AB Objectives: To evaluate lifetime exposure to trihalomethanes ( THM) through ingestion, inhalation, and dermal absorption in a hospital based case- control study of bladder cancer conducted between 1998 and 2001 in five areas of Spain. The study base was comprised of subjects living in the catchment areas of the participating hospitals. Methods: Individual information on water related habits was obtained from personal interviews of 1219 cases and 1271 controls: residential and occupational history, drinking water source at each residence and job, amount of water consumption, frequency and duration of showering, bathing, and swimming pool attendance. THM levels, water source history, and year when chlorination started in study areas were ascertained through measurements in drinking water samples and questionnaires to water companies and local authorities. Estimates of THM levels covered 79% of the subjects' person- years of exposure. Results: Current and historical average THM levels in water were correlated. Control subjects reported that drinking water source in the last residence was municipal for 63%, bottled for 22%, private well for 2%, and other sources for 13%. For the time window between age 15 and the time of interview, average residential THM level was 32.2 mu g/ l. THM exposure through ingestion was 23.7 mu g/ day on average, and was correlated with the ingestion THM level in the workplace. Overall, 79% usually took showers, 16% usually took baths, and 13% had ever attended a swimming pool. Between 21% and 45% of controls unexposed to THM through ingestion were evaluated as moderately or highly exposed through showering or bathing, and 5 - 10% were exposed through swimming in pools. Conclusion: The importance of evaluating different routes is underscored by findings from experimental studies showing substantial differences in THM uptake and internal distribution by route. C1 IMIM, Resp & Environm Hlth Res Unit, Barcelona 08003, Spain. NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. CSIC, Inst Chem & Environm Res, Dept Environm Chem, Barcelona, Catalonia, Spain. Univ Oviedo, Oviedo, Spain. Catalan Inst Oncol, Dept Epidemiol, Barcelona, Spain. Univ Pompeu Fabra, Dept Ciencias Expt Salut, Unit Res Occupat Hlth, Barcelona, Spain. Hosp Gen Elche, Elche, Spain. IMIM, Unitat Biol Cellular & Mol, Barcelona, Spain. RP Villanueva, CM (reprint author), IMIM, Resp & Environm Hlth Res Unit, Doctor Aiguader 80, Barcelona 08003, Spain. EM cvillanueva@imim.es RI Grimalt, Joan/E-2073-2011; Serra, C/E-6879-2014; Villanueva, Cristina/N-1942-2014; Kogevinas, Manolis/C-3918-2017; Real, Francisco X/H-5275-2015 OI Grimalt, Joan/0000-0002-7391-5768; Malats, Nuria/0000-0003-2538-3784; Serra, C/0000-0001-8337-8356; Villanueva, Cristina/0000-0002-0783-1259; Castano-Vinyals, Gemma/0000-0003-4468-1816; Real, Francisco X/0000-0001-9501-498X FU Intramural NIH HHS; NCI NIH HHS [N02-CP-11015] NR 16 TC 28 Z9 28 U1 2 U2 8 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1351-0711 J9 OCCUP ENVIRON MED JI Occup. Environ. Med. PD APR PY 2006 VL 63 IS 4 BP 273 EP 277 DI 10.1136/oem.2005.023069 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 024VL UT WOS:000236224300010 PM 16556748 ER PT J AU Kump, LI Cervantes-Castaneda, RA Androudi, SN Foster, CS Christen, WG AF Kump, LI Cervantes-Castaneda, RA Androudi, SN Foster, CS Christen, WG TI Patterns of exacerbations of chronic non-infectious uveitis in pregnancy and puerperium SO OCULAR IMMUNOLOGY AND INFLAMMATION LA English DT Article DE uveitis; pregnancy; puerperium ID VOGT-KOYANAGI-HARADA; NEUROPEPTIDE ALPHA-MSH; MULTIPLE-SCLEROSIS; RHEUMATOID-ARTHRITIS; BEHCETS-DISEASE; FETOPROTEIN; MODULATION; CYTOKINES; RELAPSE; FEVER AB Purpose: To determine patterns of exacerbations of recurrent noninfectious uveitis during pregnancy and puerperium. Design: Retrospective cohort study. Methods: The medical records of 32 women with a history of chronic non-infectious uveitis, who were pregnant during their follow-up at the Ocular Immunology and Uveitis Service of the Massachusetts Eye and Ear Infirmary, from 1983 through 2003, were reviewed. The uveitis relapse rate during pregnancy was compared to the relapse rate during pregnancy-free periods in these women and to the relapse rate in a control group of women of childbearing age with recurrent non-infectious uveitis. Results: Among the 32 women who were pregnant during follow-up ( 40 pregnancies), the rate of flare-ups during pregnancy (1.0 recurrence per year) was lower than that observed during non-pregnant periods (2.4 per year; p < 0.001) and lower than that observed in the non-pregnant control group (3.1 per year; p < 0.001). Flare-ups were most frequent in the first trimester of pregnancy and decreased markedly in the second and third trimesters (2.3, 0.5, and 0.4 recurrences per year, respectively; p < 0.001). Conclusions: Pregnancy is associated with lower numbers of flare-ups of non-infectious uveitis compared to the non-pregnant state. If flare-ups do occur during pregnancy, they happen predominantly in the first trimester. C1 Massachusetts Eye Res & Surg Inst, Cambridge, MA USA. Brigham & Womens Hosp, Div Epidemiol & Biostat, Boston, MA 02115 USA. RP Kump, LI (reprint author), NEI, NIH, 10 Ctr Dr,Bld 10,Rm 10S235C, Bethesda, MD 20892 USA. EM drkump@hotmail.com NR 51 TC 13 Z9 13 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0927-3948 J9 OCUL IMMUNOL INFLAMM JI Ocul. Immunol. Inflamm. PD APR PY 2006 VL 14 IS 2 BP 99 EP 104 DI 10.1080/09273940500557027 PG 6 WC Ophthalmology SC Ophthalmology GA 038SK UT WOS:000237243700005 PM 16597539 ER PT J AU Haller, K Kibler, KV Kasai, T Chi, YH Peloponese, JM Yedavalli, VSRK Jeang, KT AF Haller, K Kibler, KV Kasai, T Chi, YH Peloponese, JM Yedavalli, VSRK Jeang, KT TI The N-terminus of rodent and human MAD1 confers species-specific stringency to spindle assembly checkpoint SO ONCOGENE LA English DT Article DE aneuploidy; spindle assembly checkpoint; cellular transformation; chromosomal instability; mitotic arrest ID VIRUS TYPE-I; MITOTIC CHECKPOINT; SACCHAROMYCES-CEREVISIAE; CELLULAR-TRANSFORMATION; GENOMIC INSTABILITY; GENETIC INSTABILITY; RAT FIBROBLASTS; TAX PROTEIN; LEUKEMIA; CANCER AB The spindle assembly checkpoint (SAC) guards against chromosomal mis-segregation and the emergence of aneuploidy. SAC in higher eukaryotes includes at least 10 proteins including MAD1-3, BUB1-3, and Msp1. A long-standing observation has been that rodent cells are more tolerant of microtubule toxins than primate cells indicating that SAC function is more relaxed in the former than the latter. Here, we report on an unexpected functional difference between the rodent and human MAD1 component of the respective SAC. Ectopic expression of human MAD1 in mouse and hamster cells corrected a relaxed SAC to a more stringent form. Our findings posit MAD1 as a species-specific determinant which influences the stringency of cellular response to microtubule depolymerization and spindle damage. C1 NIAID, Mol Virol Sect, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIAID, Mol Virol Sect, Mol Microbiol Lab, 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 59 TC 19 Z9 19 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2006 VL 25 IS 15 BP 2137 EP 2147 DI 10.1038/sj.onc.1209259 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 029RD UT WOS:000236581200001 PM 16288203 ER PT J AU Teal, HE Ni, S Xu, J Finkelstein, LD Cheng, AM Paulson, RF Feng, GS Correll, PH AF Teal, HE Ni, S Xu, J Finkelstein, LD Cheng, AM Paulson, RF Feng, GS Correll, PH TI GRB2-mediated recruitment of GAB2, but not GAB1, to SF-STK supports the expansion of Friend virus-infected erythroid progenitor cells SO ONCOGENE LA English DT Article DE Friend virus; erythroleukemia; Fv2; Sf-Stk ID RECEPTOR TYROSINE KINASE; PLECKSTRIN HOMOLOGY DOMAIN; TERMINAL SH3 DOMAIN; EPITHELIAL MORPHOGENESIS DOWNSTREAM; GRB2 BINDING-SITE; C-MET RECEPTOR; SIGNAL-TRANSDUCTION; PHOSPHATIDYLINOSITOL 3-KINASE; ADAPTER PROTEIN; IN-VIVO AB Friend virus induces the development of erythroleukemia in mice through the interaction of a viral glycoprotein, gp55, with a truncated form of the Stk receptor tyrosine kinase, short form-Stk (Sf-Stk), and the EpoR. We have shown previously that the ability of Sf-Stk to participate in the transformation of Friend virus-infected cells requires the kinase activity and Grb2-binding site of Sf-Stk. Here we show that Grb2 heterozygous mice exhibit decreased susceptibility to Friend erythroleukemia and that expansion of erythroid progenitors in response to infection requires the C-terminal SH3 domain of Grb2. A fusion protein in which the Grb2-binding site in Sf-Stk is replaced by Gab2, supports the growth of progenitors from mice lacking Sf-Stk, whereas a Sf-Stk/Gab1 fusion protein does not. Gab2 is expressed in spleens from Friend virus-infected mice, co-immunoprecipitates with Sf-Stk and is tyrosine phosphorylated in the presence of Sf-Stk. Mice with a targeted deletion in Gab2 are less susceptible to Friend erythroleukemia and the expansion of erythroid progenitor cells in response to infection can be rescued by expression of Gab2, but not Gab1. Taken together, these data indicate that a Sf-Stk/Grb2/Gab2 complex mediates the growth of primary erythroid progenitor cells in response to Friend virus. C1 Penn State Univ, Dept Vet & Biomed Sci, Ctr Mol Immunol & Infect Dis, University Pk, PA USA. NHGRI, NIH, Bethesda, MD USA. Washington Univ, St Louis, MO USA. Burnham Inst, San Diego, CA USA. RP Correll, PH (reprint author), Dept Vet Sci, 115 Henning Bldg, University Pk, PA 16802 USA. EM phc7@psu.edu FU NHLBI NIH HHS [R01 HL066471, R01-HL66208]; PHS HHS [R01-L66471] NR 60 TC 21 Z9 21 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR PY 2006 VL 25 IS 17 BP 2433 EP 2443 DI 10.1038/sj.onc.1209288 PG 11 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 034RJ UT WOS:000236948000002 PM 16314834 ER PT J AU Ricci, MS Zong, WX AF Ricci, M. Stacey Zong, Wei-Xing TI Chemotherapeutic approaches for targeting cell death pathways SO ONCOLOGIST LA English DT Review DE chemotherapy; apoptosis; necrosis; autophagy; senescence; mitotic catastrophe ID TUMOR-NECROSIS-FACTOR; APOPTOSIS-INDUCING LIGAND; MITOCHONDRIAL PERMEABILITY TRANSITION; CYTOCHROME-C RELEASE; GROWTH IN-VIVO; CA-2&-INDUCED MEMBRANE TRANSITION; ADENINE-NUCLEOTIDE TRANSLOCATOR; SMALL-MOLECULE ANTAGONISTS; TRAIL-INDUCED APOPTOSIS; MYELOID-LEUKEMIA CELLS AB For several decades, apoptosis has taken center stage as the principal mechanism of programmed cell death in mammalian tissues. It also has been increasingly noted that conventional chemotherapeutic agents not only elicit apoptosis but other forms of nonapoptotic death such as necrosis, autophagy, mitotic catastrophe, and senescence. This review presents background on the signaling pathways involved in the different cell death outcomes. A re-examination of what we know about chemotherapy-induced death is vitally important in light of new understanding of nonapoptotic cell death signaling pathways. If we can precisely activate or inhibit molecules that mediate the diversity of cell death outcomes, perhaps we can succeed in more effective and less toxic chemotherapeutic regimens. C1 SUNY Stony Brook, Dept Mol Genet & Microbiol, Stony Brook, NY 11794 USA. NCI, Bethesda, MD 20892 USA. Food & Drug Adm Interagcy Oncol Task Force, Bethesda, MD USA. RP Zong, WX (reprint author), SUNY Stony Brook, Dept Mol Genet & Microbiol, 128 Life Sci Bldg, Stony Brook, NY 11794 USA. EM wzong@notes.cc.sunysb.edu FU NCI NIH HHS [K01 CA098092, K01 CA098092-01A2, K01 CA098092-02, K01 CA098092-03, K01 CA098092-04, K01 CA098092-05, K01 CA098092-06] NR 184 TC 189 Z9 204 U1 1 U2 7 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD APR PY 2006 VL 11 IS 4 BP 342 EP 357 DI 10.1634/theoncologist.11-4-342 PG 16 WC Oncology SC Oncology GA 085TK UT WOS:000240627100004 PM 16614230 ER PT J AU Smith, M AF Smith, M TI Double trouble: Cancer in twins SO PEDIATRIC BLOOD & CANCER LA English DT Editorial Material ID ACUTE LYMPHOBLASTIC-LEUKEMIA; CHILDHOOD-CANCER; MONOZYGOTIC TWINS; IDENTICAL-TWINS; PRENATAL ORIGIN; CHILDREN; CONCORDANCE; DEATHS; GENE; SIBS C1 NCI, Canc Therapy Evaluat Program, Rockville, MD 20852 USA. RP Smith, M (reprint author), NCI, Canc Therapy Evaluat Program, 6130 Execut Blvd,Room 7025, Rockville, MD 20852 USA. EM smithm@ctep.nci.nih.gov NR 19 TC 3 Z9 3 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD APR PY 2006 VL 46 IS 4 BP 412 EP 413 DI 10.1002/pbc.20569 PG 2 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 019DB UT WOS:000235814700003 PM 16155936 ER PT J AU Mahony, L Sleeper, LA Anderson, PAW Gersony, WM McCrindle, BW Minich, LL Newburger, JW Saul, JP Vetter, VL Pearson, GD AF Mahony, L Sleeper, LA Anderson, PAW Gersony, WM McCrindle, BW Minich, LL Newburger, JW Saul, JP Vetter, VL Pearson, GD CA Pediat Heart Network Investigators TI The Pediatric Heart Network: A primer for the conduct of multicenter studies in children with congenital and acquired heart disease SO PEDIATRIC CARDIOLOGY LA English DT Article DE clinical trials; congenital heart disease; pediatric clinical research ID RANDOMIZED CONTROLLED-TRIALS; CLINICAL-TRIALS; END-POINTS; CHALLENGES; DRUGS AB Most contemporary diagnostic and treatment strategies for pediatric patients with cardiovascular disease are not supported by evidence from clinical trials but instead are based on expert opinion, single-institution observational studies, or extrapolated from adult cardiovascular medicine. In response to this concern, the National Heart, Lung, and Blood Institute established the Pediatric Heart Disease Clinical Research Network (PHN) in 2001. The purposes of this article are to describe the initiation, structure, and function of the PHN; to review the ongoing studies; and to address current and future challenges. To date, four randomized clinical trials and two observational studies have been launched. Design and conduct of complex, multicenter studies in children with congenital and acquired heart disease must address numerous challenges, including identification of an appropriate clinically relevant primary endpoint, lack of preliminary data on which to base sample size calculations, and recruitment of an adequate number of subjects. The infrastructure is now well developed and capable of implementing complex, multicenter protocols efficiently and recruiting subjects effectively. The PHN is uniquely positioned to contribute to providing evidence-based medicine for and improving the outcomes of pediatric patients with cardiovascular disease. C1 Univ Texas, SW Med Ctr, Dallas, TX USA. New England Res Inst, Watertown, MA 02172 USA. Duke Univ, Med Ctr, Durham, NC USA. Columbia Univ, Med Ctr, New York, NY USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Primary Childrens Med Ctr, Salt Lake City, UT 84103 USA. Childrens Hosp Boston, Boston, MA USA. Med Univ S Carolina, Charleston, SC 29425 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NHLBI, US Dept HHS, NIH, Washington, DC USA. RP Mahony, L (reprint author), CMC Cardiol, 1935 Motor St, Dallas, TX 75235 USA. EM Lynn.Mahony@UTSouthwestern.edu FU NHLBI NIH HHS [U01 HL068269, U01 HL068270, U01 HL068279, U01 HL068281, U01 HL068285, U01 HL068288, U01 HL068290, U01 HL068292] NR 16 TC 40 Z9 40 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0172-0643 J9 PEDIATR CARDIOL JI Pediatr. Cardiol. PD APR PY 2006 VL 27 IS 2 BP 191 EP 198 DI 10.1007/s00246-005-1151-9 PG 8 WC Cardiac & Cardiovascular Systems; Pediatrics SC Cardiovascular System & Cardiology; Pediatrics GA 024MY UT WOS:000236200400001 PM 16261271 ER PT J AU Panicker, J Walsh, T Kamani, N AF Panicker, J Walsh, T Kamani, N TI Recurrent central nervous system blastomycosis in an immunocompetent child treated successfully with sequential liposomal amphotericin B and voriconazole SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE blastomycosis; voriconazole; amphotericin; immunocompetent ID CEREBROSPINAL-FLUID AB Central nervous system involvement in infection with Blastomyces dermatitidis is uncommon, except in immunocompromised patients. We report a case of central nervous system blastomycosis occurring 18 months after treatment of pulmonary blastomycosis in an immunocompetent child. Our patient was successfully treated sequentially with liposomal amphotericin B followed by oral voriconazole without need for surgical resection. C1 Childrens Natl Med Ctr, Div Pediat Hematol Oncol, Washington, DC 20010 USA. NCI, Pediat Branch, NIH, Bethesda, MD 20892 USA. Childrens Natl Med Ctr, Div Stem Cell Transplantat Immunol, Washington, DC 20010 USA. RP Panicker, J (reprint author), Childrens Natl Med Ctr, Div Pediat Hematol Oncol, Washington, DC 20010 USA. EM nkamani@cnmc.org NR 20 TC 19 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD APR PY 2006 VL 25 IS 4 BP 377 EP 379 DI 10.1097/01.inf.0000207475.89745.51 PG 3 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 034HR UT WOS:000236920400022 PM 16567998 ER PT J AU Zimmerman, AW Connors, SL Jyonouchi, H Milstien, S Heyes, MP AF Zimmerman, AW Connors, SL Jyonouchi, H Milstien, S Heyes, MP TI Immune activation in autism - Response SO PEDIATRIC NEUROLOGY LA English DT Letter C1 Kennedy Krieger Inst, Baltimore, MD USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. NIMH, Bethesda, MD 20892 USA. PsychoGenics Inc, Hawthorne, NY USA. RP Zimmerman, AW (reprint author), Kennedy Krieger Inst, Baltimore, MD USA. NR 2 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 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD APR PY 2006 VL 34 IS 4 BP 333 EP 333 DI 10.1016/j.pediatrneurol.2006.03.001 PG 1 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 039KS UT WOS:000237305100019 ER PT J AU Batey, JF Cole, LK AF Batey, JF Cole, LK TI A stem cell primer SO PEDIATRIC RESEARCH LA English DT Editorial Material C1 NIDCD, NIH, Bethesda, MD 20892 USA. RP Batey, JF (reprint author), NIDCD, NIH, Bldg 31,Room 3C02, Bethesda, MD 20892 USA. EM batteyj@nided.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2006 VL 59 IS 4 BP 1R EP 3R DI 10.1203/01.pdr.0000208976.01669.c8 PN 2 PG 3 WC Pediatrics SC Pediatrics GA 026RK UT WOS:000236359600001 ER PT J AU Tanofsky-Kraff, M Cohen, ML Yanovski, SZ Cox, C Theim, KR Keil, M Reynolds, JC Yanovski, JA AF Tanofsky-Kraff, M Cohen, ML Yanovski, SZ Cox, C Theim, KR Keil, M Reynolds, JC Yanovski, JA TI A prospective study of psychological predictors of body fat gain among children at high risk for adult obesity SO PEDIATRICS LA English DT Article DE child; disturbed eating behaviors; depression; adiposity; overweight ID X-RAY ABSORPTIOMETRY; EATING-DISORDERED BEHAVIORS; ADOLESCENT GIRLS; PUBERTAL CHANGES; WEIGHT PATTERNS; ENERGY-INTAKE; DEPRESSION; QUESTIONNAIRE; CHILDHOOD; HEALTH AB OBJECTIVE. Limited data suggest that psychological factors, including binge eating, dieting, and depressive symptoms, may predispose children to excessive weight gain. We investigated the relationship between baseline psychological measures and changes in body fat ( measured with dual-energy x-ray absorptiometry) over time among children thought to be at high risk for adult obesity. METHODS. A cohort study of a convenience sample of children ( age: 6 - 12 years) recruited from Washington, DC, and its suburbs was performed. Subjects were selected to be at increased risk for adult obesity, either because they were overweight when first examined or because their parents were overweight. Children completed questionnaires at baseline that assessed dieting, binge eating, disordered eating attitudes, and depressive symptoms; they underwent measurements of body fat mass at baseline and annually for an average of 4.2 years (SD: 1.8 years). RESULTS. Five hundred sixty-eight measurements were obtained between July 1996 and December 2004, for 146 children. Both binge eating and dieting predicted increases in body fat. Neither depressive symptoms nor disturbed eating attitudes served as significant predictors. Children who reported binge eating gained, on average, 15% more fat mass, compared with children who did not report binge eating. CONCLUSIONS. Children's reports of binge eating and dieting were salient predictors of gains in fat mass during middle childhood among children at high risk for adult obesity. Interventions targeting disordered eating behaviors may be useful in preventing excessive fat gain in this high-risk group. C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. NIDDKD, Div Digest Dis & Nutr, Bethesda, MD USA. NIH, Warren G Magnuson Clin Ctr, Dept Nucl Med, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, Room 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM jy15i@nih.gov FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [Z01 HD000641] NR 43 TC 127 Z9 128 U1 2 U2 14 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2006 VL 117 IS 4 BP 1203 EP 1209 DI 10.1542/peds.2005-1329 PG 7 WC Pediatrics SC Pediatrics GA 029EA UT WOS:000236540500052 PM 16585316 ER PT J AU Ehrenkranz, RA Dusick, AM Vohr, BR Wright, LL Wrage, LA Poole, WK AF Ehrenkranz, RA Dusick, AM Vohr, BR Wright, LL Wrage, LA Poole, WK CA Natl Inst Hlth Human Dev Neonatal TI Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants SO PEDIATRICS LA English DT Article DE extremely low birth weight infant; growth; neurodevelopmental outcome ID CHRONIC LUNG-DISEASE; PRETERM INFANTS; NECROTIZING ENTEROCOLITIS; NATIONAL-INSTITUTE; RESEARCH NETWORK; CHILD-HEALTH; BRONCHOPULMONARY DYSPLASIA; POSTNATAL-GROWTH; HEAD GROWTH; DEXAMETHASONE AB OBJECTIVES. The objectives of this study were to assess whether ( 1) in-hospital growth velocity is predictive of neurodevelopmental and growth outcomes at 18 to 22 months' corrected age among extremely low birth weight (ELBW) infants and ( 2) in-hospital growth velocity contributes to these outcomes after controlling for confounding demographic and clinical variables. METHODS. Infants 501 to 1000 g birth weight from a multicenter cohort study were divided into quartiles of in-hospital growth velocity rates. Variables considered for the logistic-regression models included gender, race, gestational age, small for gestational age, mother's education, severe intraventricular hemorrhage, periventricular leukomalacia, age at regaining birth weight, necrotizing enterocolitis, late-onset infection, bronchopulmonary dysplasia, postnatal steroid therapy for pulmonary disease, and center. RESULTS. Of the 600 discharged infants, 495 (83%) were evaluated at 18 to 22 months' corrected age. As the rate of weight gain increased between quartile 1 and quartile 4, from 12.0 to 21.2 g/kg per day, the incidence of cerebral palsy, Bayley II Mental Developmental Index (MDI) < 70 and Psychomotor Developmental Index (PDI) < 70, abnormal neurologic examination, neurodevelopmental impairment, and need for rehospitalization fell significantly. Similar findings were observed as the rate of head circumference growth increased. The in-hospital rate of growth was associated with the likelihood of anthropometric measurements at 18 months' corrected age below the 10th percentile values of the Centers for Disease Control and Prevention 2000 growth curve. Logistic-regression analyses, controlling for potential demographic or clinical cofounders, and adjusted for center, identified a significant relationship between growth velocity and the likelihood of cerebral palsy, MDI and PDI scores of < 70, and neurodevelopmental impairment. CONCLUSIONS. These analyses suggest that growth velocity during an ELBW infant's NICU hospitalization exerts a significant, and possibly independent, effect on neurodevelopmental and growth outcomes at 18 to 22 months' corrected age. C1 Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. Indiana Univ, Indianapolis, IN 46204 USA. Brown Univ, Dept Pediat, Providence, RI 02912 USA. NICHHD, Bethesda, MD 20892 USA. RTI Int, Res Triangle Pk, NC USA. RP Ehrenkranz, RA (reprint author), Yale Univ, Sch Med, Dept Pediat, 333 Cedar St,POB 208064, New Haven, CT 06520 USA. EM richard.ehrenkranz@yale.edu FU NCRR NIH HHS [M01 RR 02172, M01 RR 00070, M01 RR 00750, M01 RR 00997, M01 RR 01032, M01 RR 02635, M01 RR 06022, M01 RR 08084]; NICHD NIH HHS [U01 HD36790, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34167, U10 HD34216] NR 36 TC 426 Z9 463 U1 2 U2 34 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2006 VL 117 IS 4 BP 1253 EP 1261 DI 10.1542/peds.2005-1368 PG 9 WC Pediatrics SC Pediatrics GA 029EA UT WOS:000236540500058 PM 16585322 ER PT J AU Munson, S Schroth, E Ernst, M AF Munson, S Schroth, E Ernst, M TI The role of functional neuroimaging in pediatric brain injury SO PEDIATRICS LA English DT Review DE brain development; functional neuroimaging; brain injury; plasticity; vulnerability ID HEAD-INJURY; CHILDHOOD INJURIES; CORTICAL INJURY; PRACTICAL SCALE; LEFT-HEMISPHERE; UNITED-STATES; CHILDREN; REORGANIZATION; LESION; ADOLESCENTS AB The aim of this article is to review empirical studies published in the last 10 years that used various functional neuroimaging techniques to assess pediatric patients with brain injury. Overall, these studies have demonstrated the ability of functional neuroimaging to offer unique information concerning the diagnosis, clinical outcome, and recovery mechanisms after pediatric brain injury. Future research using functional neuroimaging is recommended to better understand the functional reorganization and neurodevelopmental consequences resulting from brain injury. Such research might allow clinicians to design tailored early-intervention and rehabilitation programs to maximize the recovery process for pediatric patients. Limitations and advantages associated with the use of functional neuroimaging in pediatric populations are discussed. C1 NIMH, NIH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Ernst, M (reprint author), NIMH, NIH, Mood & Anxiety Disorders Program, 15K North Dr, Bethesda, MD 20892 USA. EM ernstm@mail.nih.gov NR 52 TC 20 Z9 20 U1 1 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2006 VL 117 IS 4 BP 1372 EP 1381 DI 10.1542/peds.2005-0826 PG 10 WC Pediatrics SC Pediatrics GA 029EA UT WOS:000236540500071 PM 16585335 ER PT J AU Blakely, ML Tyson, JE Lally, KP McDonald, S Stoll, BJ Stevenson, DK Poole, WK Jobe, AH Wright, LL Higgins, RD AF Blakely, ML Tyson, JE Lally, KP McDonald, S Stoll, BJ Stevenson, DK Poole, WK Jobe, AH Wright, LL Higgins, RD CA NICHD Neonatal Res Network TI Laparotomy versus peritoneal drainage for necrotizing enterocolitis or isolated intestinal perforation in extremely low birth weight infants: Outcomes through 18 months adjusted age SO PEDIATRICS LA English DT Article DE necrotizing enterocolitis; neonatal surgery; neurodevelopmental outcomes ID LOCAL-ANESTHESIA; CLINICAL-TRIALS; RARE DISEASES; SURGERY; EXPERIENCE AB OBJECTIVE. Extremely low birth weight (ELBW; <= 1000 g) infants with necrotizing enterocolitis (NEC) or isolated intestinal perforation (IP) are treated surgically with either initial laparotomy or peritoneal drain placement. The only published data comparing these therapies are from small, retrospective, single-center studies that do not address outcomes beyond nursery discharge. The objective of this study was to conduct a prospective, multicenter, observational study to (1) develop a hypothesis about the relative effect of these 2 therapies on risk-adjusted outcomes through 18 to 22 months in ELBW infants and (2) to obtain data that would be useful in designing and conducting a successful trial of this hypothesis. METHODS. A prospective, cohort study was conducted at 16 clinical centers within the National Institute of Child Health and Human Development Neonatal Research Network. To assist in risk adjustment, the attending pediatric surgeon recorded the preoperative diagnosis and intraoperative diagnosis and identified infants who were considered to be too ill for laparotomy. Predefined measures of short-and longer-term outcome included (1) either predischarge death or prolonged parenteral nutrition (>85 days) after enrollment and (2) either death or neurodevelopmental impairment on a standardized examination at 18 to 22 months' adjusted age. RESULTS. Severe NEC or IP occurred in 156 (5.2%) of 2987 ELBW infants; 80 were treated with initial drainage, and 76 were treated with initial laparotomy. By 18 to 22 months, 78 (50%) had died; 112 (72%) had died or were shown to be impaired. Outcome was worse in the subgroup with NEC. Laparotomy was never performed in 76% (28 of 36) of drain-treated survivors. CONCLUSIONS. Drainage was commonly used, and outcome was poor. Our findings, particularly the risk-adjusted odds ratio favoring laparotomy for death or impairment, indicate the need for a large, multicenter clinical trial to assess the effect of the initial surgical therapy on outcome at >= 18 months. C1 Univ Tennessee, Div Pediat Surg, Pediat Surg Sect, Hlth Sci Ctr, Memphis, TN 38105 USA. Univ Texas, Hlth Sci Ctr, Dept Neonatol, Houston, TX USA. RTI Int, Res Triangle Pk, NC USA. Emory Univ, Dept Neonatol, Atlanta, GA 30322 USA. Stanford Univ, Sch Med, Dept Neonatol, Palo Alto, CA 94304 USA. Res Triangle Inst, Dept Neonatol, Res Triangle Pk, NC 27709 USA. Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. NICHHD, Dept Neonatol, Ctr Res Mothers & Children, Bethesda, MD USA. NICHHD, Dept Neonatol, Ctr Dev Biol & Perinatal Med, Bethesda, MD 20892 USA. RP Blakely, ML (reprint author), Univ Tennessee, Div Pediat Surg, Pediat Surg Sect, Hlth Sci Ctr, 777 Washington Ave,Suite P220, Memphis, TN 38105 USA. EM mblakely@utmem.edu FU NCRR NIH HHS [K24RR17050]; NICHD NIH HHS [U10HD27871, U10HD27880, U10HD40498, U10HD21364, U10HD27851, U10HD27856, U10HD34216, K23HD001473-04, U01HD36790, U10HD21385, U10HD27853, U10HD21397, U10HD40461, U10HD27904, U10HD21373, U10HD40689, U10HD40492, U10HD40521] NR 34 TC 80 Z9 81 U1 0 U2 3 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2006 VL 117 IS 4 BP E680 EP E687 DI 10.1542/peds.2005-1273 PG 8 WC Pediatrics SC Pediatrics GA 029EA UT WOS:000236540500010 PM 16549503 ER PT J AU Zaoutis, TE Heydon, K Chu, JH Walsh, TJ Steinbach, WJ AF Zaoutis, TE Heydon, K Chu, JH Walsh, TJ Steinbach, WJ TI Epidemiology, outcomes, and costs of invasive aspergillosis in immunocompromised children in the United States, 2000 SO PEDIATRICS LA English DT Article DE aspergillosis; fungal Infections; pediatric; Aspergillus ID FUNGAL-INFECTIONS; TRANSPLANT RECIPIENTS; CANCER; TRENDS; EXPERIENCE; CANDIDEMIA; MORTALITY; VIRUS; ADULT AB OBJECTIVE. Invasive aspergillosis (IA) is the most common filamentous fungal infection observed in immunocompromised patients. The incidence of invasive aspergillosis has increased significantly in recent decades in parallel with the increasing number and improved survival of immunocompromised patients. IA in adults has been well characterized; however, only a few small studies of IA in children have been reported. Therefore, the objective of this study was to describe the incidence and outcomes of children with IA. METHODS. We performed a retrospective cohort study using the 2000 Kids Inpatient Database, a national database of hospital inpatient stays during 2000. IA was defined as aspergillosis that occurred in a child with malignancy (solid tumor, leukemia, or lymphoma), hematologic/immunologic deficiency, or transplant (bone marrow or solid organ). Discharge weighting was applied to the data to obtain nationally representative estimates of disease. RESULTS. During 2000, there were an estimated 666 pediatric cases of IA among 152 231 immunocompromised children, yielding an annual incidence of 437/100 000 (0.4%) among hospitalized immunocompromised children. Children with malignancy accounted for the majority (74%) of cases of IA. The highest incidence of IA was seen in children who had undergone allogeneic bone marrow transplantation (4.5%) and those with acute myelogenous leukemia (4%). The overall in-hospital mortality of immunocompromised children with IA was 18%. Children with malignancy and IA were at higher risk for death than children with malignancy and without IA. Pediatric patients with IA had a significantly longer median length of hospital stay (16 days) than immunocompromised children without IA (3 days). The median total hospital charges for patients with IA were $49 309 compared with immunocompromised children without IA ($9035). CONCLUSIONS. The impact of IA on increases in mortality, length of hospital stay, and the burden of cost in the hospital setting underscores the need for improved means of diagnosis, prevention, and treatment of IA in immunocompromised children. C1 Childrens Hosp Philadelphia, Dept Pediat, Ctr Clin Epidemiol & Biostat, Sch Med,Div Infect Dis, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Pediat, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Pediat, Div Pediat Infect Dis, Durham, NC USA. RP Zaoutis, TE (reprint author), Childrens Hosp Philadelphia, Dept Pediat, Ctr Clin Epidemiol & Biostat, Sch Med,Div Infect Dis, 3535 Market St,Room 1527, Philadelphia, PA 19104 USA. EM zaoutis@email.chop.edu FU AHRQ HHS [U18-HS10399]; NIAID NIH HHS [K23 AI0629753-01] NR 20 TC 81 Z9 86 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2006 VL 117 IS 4 BP E711 EP E716 DI 10.1542/peds.2005-1161 PG 6 WC Pediatrics SC Pediatrics GA 029EA UT WOS:000236540500014 PM 16533892 ER PT J AU Devadas, K Boykins, RA Hardegen, NJ Philp, D Kleinman, HK Osa, EO Wang, J Clouse, KA Wahl, LM Hewlett, IK Rappaport, J Yamada, KM Dhawan, S AF Devadas, K Boykins, RA Hardegen, NJ Philp, D Kleinman, HK Osa, EO Wang, J Clouse, KA Wahl, LM Hewlett, IK Rappaport, J Yamada, KM Dhawan, S TI Selective side-chain modification of cysteine and arginine residues blocks pathogenic activity of HIV-1-Tat functional peptides SO PEPTIDES LA English DT Article DE HIV-Tat; peptides; AIDS; vaccination ID IMMUNODEFICIENCY-VIRUS TYPE-1; TAT-NEUTRALIZING ANTIBODIES; VASCULAR ENDOTHELIAL-CELLS; FIBROBLAST-GROWTH-FACTOR; NF-KAPPA-B; KAPOSIS-SARCOMA; T-CELLS; FLK-1/KDR RECEPTOR; IMMUNE-RESPONSES; RHESUS MACAQUES AB Extracellular Tat protein of HIV-1 activates virus replication in HIV-infected cells and induces a variety of host factors in the uninfected cells, some of which play a critical role in the progression of HIV infection. The cysteine-rich and arginine-rich basic domains represent key components of the HIV-Tat protein for pathogenic effects of the full-length Tat protein and, therefore, could be ideal candidates for the development of a therapeutic AIDS vaccine. The present study describes selective modifications of the side-chain functional groups of cysteine and arginine amino acids of these HIV-Tat peptides to minimize the pathogenic effects of these peptides while maintaining natural peptide linkages. Modification of cysteine by introducing either a methyl or t-butyl group in the free sulfhydryl group and replacing the guanidine group with a urea linkage in the side chain of arginine in the cysteine-rich and arginine-rich Tat peptide sequences completely blocked the ability of these peptides to induce HIV replication, chemokine receptor CCR-5 expression, and NF-kappa B activity in monocytes. Such modifications also inhibited angiogenesis and migration of Kaposi's sarcoma cells normally induced by Tat peptides. Such chemical modifications of the cysteine-rich and arginine-rich peptides did not affect their reactivity with antibodies against the full-length Tat protein. With an estimated 40 million HIV-positive individuals worldwide and approximately 4 million new infections emerging every year, a synthetic subunit HIV-Tat vaccine comprised of functionally inactive Tat domains could provide a safe, effective, and economical therapeutic vaccine to reduce the progression of HIV disease. Published by Elsevier Inc. C1 US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Immunopathogenesis Sect, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20852 USA. Natl Inst Dent & Craniofacial Res, Oral Infect & Immun Branch, Cellular Immunol Sect, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Cell Biol Lab, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. Temple Univ, Ctr Neurovirol & Canc Biol, Philadelphia, PA 19122 USA. RP Dhawan, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Immunopathogenesis Sect, 1401 Rockville Pike HFM-315, Rockville, MD 20852 USA. EM dhawan@cber.fda.gov OI Yamada, Kenneth/0000-0003-1512-6805 NR 56 TC 2 Z9 2 U1 1 U2 5 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD APR PY 2006 VL 27 IS 4 BP 611 EP 621 DI 10.1016/j.peptides.2005.09.013 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 036BX UT WOS:000237047000002 PM 16256245 ER PT J AU Wang, XY Xu, H Rothman, RB AF Wang, XY Xu, H Rothman, RB TI Regulation of the rat brain endothelin system by endogenous beta-endorphin SO PEPTIDES LA English DT Article DE beta-endorphin; endothelin; opioid receptors; corticotropin releasing hormone ID ANTI-OPIATE PEPTIDES; MU-OPIOID RECEPTORS; MORPHINE ANALGESIA; SITES; NOCICEPTION; ANTAGONIST; MODEL; MICE AB Several lines of evidence indicate that the central endogenous opioid and endothelin (ET) system regulate each other. To explore this idea further, we determined the effect of intracerebroventricular (i.c.v.) administration of anti-p-endorphin IgG (rabbit) on the expression level of the opioid, corticotropin-releasing hormone and endothelin receptors, and tissue concentration of ET-1. Three days after implanting cannula into the lateral ventricle, male Sprague-Dawley rats were administered 10 RI (i.c.v.) of either control rabbit IgG (2.5 mu g/mu l) or anti-beta-endorphin IgG (2.5 mu g/mu l) on days 1, 3 and 5. On day 6, animals were euthanized and caudate, cortex and hippocampus collected for Western blot analysis. Anti-beta-endorphin IgG down-regulated ET-A receptor protein expression in the caudate (51%), but had no effect on the expression of mu, delta, kappa opioid, ET-B, CRH-1 and CRH-2 receptors in any brain region. Anti-beta-endorphin IgG increased tissue ET-1 levels in the caudate by 30.3%. [S-35]GTP-gamma-S binding assays demonstrated that anti-beta-endorphin IgG increased the efficacy of [D-Ala(2)-MePhe(4), Gly-ol(5)]enkephalin without altering its potency in caudate. Control experiments showed that there was no detectable rabbit IgG in caudate, cortex and hippocampus samples. These results suggest that p-endorphin in the CSF coordinately regulates ET-1 levels and the ET-A receptor in rat caudate. These findings support the hypothesis that CSF neuropeptides have regulatory effects and further demonstrate a link between opioid and ET system. (c) 2005 Elsevier Inc. All rights reserved. C1 NIDA, Intramural Res Program, Clin Psychopharmacol Sect, Dept Hlth & Human Serv,NIH, Baltimore, MD 21224 USA. RP Rothman, RB (reprint author), NIDA, Intramural Res Program, Clin Psychopharmacol Sect, Dept Hlth & Human Serv,NIH, 333 Cassell Dr, Baltimore, MD 21224 USA. EM rrothman@intra.nida.nih.gov FU Intramural NIH HHS NR 24 TC 8 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 J9 PEPTIDES JI Peptides PD APR PY 2006 VL 27 IS 4 BP 769 EP 774 DI 10.1016/j.peptides.2005.07.014 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 036BX UT WOS:000237047000021 PM 16165252 ER PT J AU Carmel, L Efroni, S White, PD Aslakson, E Vollmer-Conna, U Rajeevan, MS AF Carmel, L Efroni, S White, PD Aslakson, E Vollmer-Conna, U Rajeevan, MS TI Gene expression profile of empirically delineated classes of unexplained chronic fatigue SO PHARMACOGENOMICS LA English DT Article DE chronic fatigue syndrome; Fisher quotient and discriminatory genes; gene expression and gene scores; interoception; latent class analysis; principal component analysis ID BIOMARKER DISCOVERY; PERIPHERAL-BLOOD; MICROARRAY DATA; IDENTIFICATION; MULTICLASS; MODEL; CLASSIFICATION; ROLES AB Objectives: To identify the underlying gene expression profiles of unexplained chronic fatigue subjects classified into five or six class solutions by principal component (PCA) and latent class analyses (LCA). Methods: Microarray expression data were available for 15,315 genes and 111 female subjects enrolled from a population-based study on chronic fatigue syndrome. Algorithms were developed to assign gene scores and threshold values that signified the contribution of each gene to discriminate the multiclasses in each LCA solution. Unsupervised dimensionality reduction was first used to remove noise or otherwise uninformative gene combinations, followed by supervised dimensionality reduction to isolate gene combinations that best separate the classes. Results: The authors' gene score and threshold algorithms identified 32 and 26 genes capable of discriminating the five and six multiclass solutions, respectively. Pair-wise comparisons suggested that some genes (zinc finger protein 350 [ZNF350], solute carrier family 1, member 6 [SLC1A6], F-box protein 7 [FBX07] and vacuole 14 protein homolog [VAC14]) distinguished most classes of fatigued subjects from healthy subjects, whereas others (patched homolog 2 [PTCH2] and T-cell leukemia/lymphoma [TCL1A]) differentiated specific fatigue classes. Conclusion: A computational approach was developed for general use to identify discriminatory genes in any multiclass problem. Using this approach, differences in gene expression were found to discriminate some classes of unexplained chronic fatigue, particularly one termed interoception. C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. NCI, Ctr Bioinformat, NIH, Bethesda, MD 20892 USA. Univ London, Dept Psychol Med, Barts London & Queen Mary Sch Med & Dent, London, England. Univ New S Wales, Sch Psychiat, Sydney, NSW, Australia. RP Rajeevan, MS (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd,MSG 41, Atlanta, GA 30333 USA. EM mor4@cdc.gov RI Carmel, Liran/A-9681-2008; Efroni, Sol/I-6752-2012; OI Efroni, Sol/0000-0001-7927-6349; White, Peter/0000-0002-8193-5355 NR 33 TC 28 Z9 28 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD APR PY 2006 VL 7 IS 3 BP 375 EP 386 DI 10.2217/14622416.7.3.375 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 036LF UT WOS:000237071900014 PM 16610948 ER PT J AU Fostel, J Boneva, R Lloyd, A AF Fostel, J Boneva, R Lloyd, A TI Exploration of the gene expression correlates of chronic unexplained fatigue using factor analysis SO PHARMACOGENOMICS LA English DT Article DE chronic fatigue; factor analysis; molecular expression; surrogate biomarker ID HEALTH SURVEY SF-36; PERIPHERAL-BLOOD; BIOMARKER DISCOVERY; CASE-DEFINITION; SYMPTOMS; DEPRESSION; IDENTIFICATION; PREVALENCE; INVENTORY AB Objective: To identify biomarkers of chronic fatigue syndrome (CFS) and related disorders through analysis of microarray data, pathology test results and self-report symptom profiles. Method: To empirically derive the symptom domains of the illnesses, factor analysis was performed on responses to self-report questionnaires (multidimensional fatigue inventory, Centers for Disease Control and Prevention (CDC) symptom inventory and Zung depression scale) before validation with independent datasets. Gene expression patterns that distinguished subjects across each factor dimension were then sought. Results: A four-factor solution was favored, featuring 'fatigue' and 'mood disturbance' factors. Scores on these factors correlated with measures of disability on the Short Form (SF)-36. A total of 57 genes that distinguished subjects along each factor dimension were identified, although the separation was significant only for subjects beyond the extreme (15th and 85th) percentiles of severity. Clustering of laboratory parameters with expression of these genes revealed associations with serum measurements of pH, electrolytes, glucose, urea, creatinine, and liver enzymes (aspartate amino transferase [AST] and alanine amino transferase [AST]); as well as hematocrit and white cell count. Conclusion: CFS is a complex syndrome that cannot simply be associated with changes in individual laboratory tests or expression levels of individual genes. No clear association with gene expression and individual symptom domains was found. However, analysis of such multifacetted datasets is likely to be an important means to elucidate the pathogenesis of CFS. C1 NIEHS, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Univ New S Wales, Sydney, NSW, Australia. RP Fostel, J (reprint author), NIEHS, Natl Ctr Toxicogenom, MD F1-05,111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM fostel@niehs.nih.gov NR 39 TC 15 Z9 15 U1 1 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD APR PY 2006 VL 7 IS 3 BP 441 EP 454 DI 10.2217/14622416.7.3.441 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 036LF UT WOS:000237071900020 PM 16610954 ER PT J AU Kim, T Gondre-Lewis, MC Arnaoutova, I Loh, YP AF Kim, T Gondre-Lewis, MC Arnaoutova, I Loh, YP TI Dense-core secretory granule biogenesis SO PHYSIOLOGY LA English DT Review ID TRANS-GOLGI NETWORK; PATHWAY-SORTING RECEPTOR; PROTEIN-KINASE-D; TYROSINE-HYDROXYLASE GENE; ADRENAL CHROMAFFIN CELLS; PANCREATIC BETA-CELLS; AP-1 ADAPTER COMPLEX; LEMLI-OPITZ-SYNDROME; CHROMOGRANIN-A; CARBOXYPEPTIDASE E AB The dense-core secretory granule is a key organelle for secretion of hormones and neuropeptides in endocrine cells and neurons, in response to stimulation. Cholesterol and granins are critical for the assembly of these organelles at the trans-Golgi network, and their biogenesis is regulated quantitatively by posttranscriptional and posttranslational mechanisms. C1 NICHHD, Sect Cellular Neurobiol, NIH, Bethesda, MD 20892 USA. RP Kim, T (reprint author), NICHHD, Sect Cellular Neurobiol, NIH, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov NR 90 TC 84 Z9 90 U1 1 U2 8 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1548-9213 J9 PHYSIOLOGY JI Physiology PD APR PY 2006 VL 21 BP 124 EP 133 DI 10.1152/physiol.00043.2005 PG 10 WC Physiology SC Physiology GA 033BT UT WOS:000236822000006 PM 16565478 ER PT J AU Tsai, CJ Zheng, J Nussinov, R AF Tsai, Chung-Jung Zheng, Jie Nussinov, Ruth TI Designing a nanotube using naturally occurring protein building blocks SO PLOS COMPUTATIONAL BIOLOGY LA English DT Article ID ASSEMBLED PEPTIDE NANOTUBES; SURFACTANT-LIKE PEPTIDES; HIV-1 CAPSID PROTEIN; TUBULES; NANOSTRUCTURES; ARCHITECTURE; ENERGY AB Here our goal is to carry out nanotube design using naturally occurring protein building blocks. Inspection of the protein structural database reveals the richness of the conformations of proteins, their parts, and their chemistry. Given target functional protein nanotube geometry, our strategy involves scanning a library of candidate building blocks, combinatorially assembling them into the shape and testing its stability. Since self-assembly takes place on time scales not affordable for computations, here we propose a strategy for the very first step in protein nanotube design: we map the candidate building blocks onto a planar sheet and wrap the sheet around a cylinder with the target dimensions. We provide examples of three nanotubes, two peptide and one protein, in atomistic model detail for which there are experimental data. The nanotube models can be used to verify a nanostructure observed by low-resolution experiments, and to study the mechanism of tube formation. C1 Natl Canc Inst, Basic Res Program, SAIC Frederick Inc, Canc Res Ctr,Nanobiol Program, Frederick, MD USA. Tel Aviv Univ, Sch Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), Natl Canc Inst, Basic Res Program, SAIC Frederick Inc, Canc Res Ctr,Nanobiol Program, Frederick, MD USA. EM ruthn@ncifcrf.gov RI Zheng, Jie/B-5057-2013 OI Zheng, Jie/0000-0003-1547-3612 FU Intramural NIH HHS; NCI NIH HHS [N01-CO-12400, N01CO12400] NR 33 TC 25 Z9 27 U1 2 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-734X J9 PLOS COMPUT BIOL JI PLoS Comput. Biol. PD APR PY 2006 VL 2 IS 4 BP 311 EP 319 AR e42 DI 10.1371/journal.pcbi.0020042 PG 9 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 070AX UT WOS:000239493800010 PM 16683021 ER PT J AU Scacheri, PC Davis, S Odom, DT Crawford, GE Perkins, S Halawi, MJ Agarwal, SK Marx, SJ Spiegel, AM Meltzer, PS Collins, FS AF Scacheri, Peter C. Davis, Sean Odom, Duncan T. Crawford, Gregory E. Perkins, Stacie Halawi, Mohamad J. Agarwal, Sunita K. Marx, Stephen J. Spiegel, Allen M. Meltzer, Paul S. Collins, Francis S. TI Genome-wide analysis of menin binding provides insights into MEN1 tumorigenesis SO PLOS GENETICS LA English DT Article ID MULTIPLE ENDOCRINE NEOPLASIA; HISTONE METHYLTRANSFERASE COMPLEX; DEPENDENT KINASE INHIBITORS; TUMOR-SUPPRESSOR GENE; HOMEOBOX GENE; PANCREATIC DEVELOPMENT; PARATHYROID TUMORS; CURRARINO-SYNDROME; EXPRESSION; MICE AB Multiple endocrine neoplasia type I ( MEN1) is a familial cancer syndrome characterized primarily by tumors of multiple endocrine glands. The gene for MEN1 encodes a ubiquitously expressed tumor suppressor protein called menin. Menin was recently shown to interact with several components of a trithorax family histone methyltransferase complex including ASH2, Rbbp5, WDR5, and the leukemia proto-oncoprotein MLL. To elucidate menin's role as a tumor suppressor and gain insights into the endocrine-specific tumor phenotype in MEN1, we mapped the genomic binding sites of menin, MLL1, and Rbbp5, to approximately 20,000 promoters in HeLa S3, HepG2, and pancreatic islet cells using the strategy of chromatin-immunoprecipitation coupled with microarray analysis. We found that menin, MLL1, and Rbbp5 localize to the promoters of thousands of human genes but do not always bind together. These data suggest that menin functions as a general regulator of transcription. We also found that factor occupancy generally correlates with high gene expression but that the loss of menin does not result in significant changes in most transcript levels. One exception is the developmentally programmed transcription factor, HLXB9, which is overexpressed in islets in the absence of menin. Our findings expand the realm of menin- targeted genes several hundred- fold beyond that previously described and provide potential insights to the endocrine tumor bias observed in MEN1 patients. C1 NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Whitehead Inst, Cambridge, MA 02142 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Bethesda, MD USA. RP Collins, FS (reprint author), NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. EM francisc@mail.nih.gov RI Agarwal, Sunita/D-1428-2016; OI Agarwal, Sunita/0000-0002-7557-3191; Odom, Duncan/0000-0001-6201-5599; Davis, Sean/0000-0002-8991-6458 FU Intramural NIH HHS; NIDDK NIH HHS [K25 DK070813, K25-DK070813, R01 DK068655, R01-DK068655] NR 40 TC 123 Z9 124 U1 1 U2 7 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD APR PY 2006 VL 2 IS 4 BP 406 EP 419 AR e51 DI 10.1371/journal.pgen.0020051 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 070BE UT WOS:000239494500004 PM 16604156 ER PT J AU Feng, YQ Desprat, R Fu, H Olivier, E Lin, CM Lobell, A Gowda, SN Aladjem, MI Bouhassira, EE AF Feng, Yong-Qing Desprat, Romain Fu, Haiqing Olivier, Emmanuel Lin, Chii Mei Lobell, Amanda Gowda, Shilpa N. Aladjem, Mirit I. Bouhassira, Eric E. TI DNA methylation supports intrinsic epigenetic memory in mammalian cells SO PLOS GENETICS LA English DT Article ID MEDIATED CASSETTE EXCHANGE; LOCUS-CONTROL REGION; H3 LYSINE 9; HISTONE H3; GENE-EXPRESSION; CHROMATIN; HP1; REPLICATION; TRANSGENE; METHYLTRANSFERASES AB We have investigated the role of DNA methylation in the initiation and maintenance of silenced chromatin in somatic mammalian cells. We found that a mutated transgene, in which all the CpG dinucleotides have been eliminated, underwent transcriptional silencing to the same extent as the unmodified transgene. These observations demonstrate that DNA methylation is not required for silencing. The silenced CpG- free transgene exhibited all the features of heterochromatin, including silencing of transcriptional activity, delayed DNA replication, lack of histone H3 and H4 acetylation, lack of H3- K4 methylation, and enrichment in tri- methyl- H3- K9. In contrast, when we tested for transgene reactivation using a Cre recombinase- mediated inversion assay, we observed a marked difference between a CpG- free and an unmodified transgene: the CpG- free transgene resumed transcription and did not exhibit markers of heterochromatin whereas the unmodified transgene remained silenced. These data indicate that methylation of CpG residues conferred epigenetic memory in this system. These results also suggest that replication delay, lack of histone H3 and H4 acetylation, H3- K4 methylation, and enrichment in tri- methyl- H3- K9 are not sufficient to confer epigenetic memory. We propose that DNA methylation within transgenes serves as an intrinsic epigenetic memory to permanently silence transgenes and prevent their reactivation. C1 Albert Einstein Coll Med, Dept Med, Div Hematol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Dept Cell Biol, Bronx, NY 10467 USA. NCI, Mol Pharmacol Lab, Bethesda, MD 20892 USA. RP Bouhassira, EE (reprint author), Albert Einstein Coll Med, Dept Med, Div Hematol, Bronx, NY 10467 USA. EM bouhassi@aecom.yu.edu RI Aladjem, Mirit/G-2169-2010; OI Aladjem, Mirit/0000-0002-1875-3110; Olivier, Emmanuel/0000-0001-9288-1746 FU Intramural NIH HHS; NHLBI NIH HHS [HL55435, P01 HL055435]; NIDDK NIH HHS [DK061799, DK56845, R01 DK056845] NR 37 TC 44 Z9 52 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1553-7390 J9 PLOS GENET JI PLoS Genet. PD APR PY 2006 VL 2 IS 4 BP 461 EP 470 AR e65 DI 10.1371/journal.pgen.0020065 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 070BE UT WOS:000239494500009 PM 16683039 ER PT J AU Viboud, C Alonso, WJ Simonsen, L AF Viboud, Cecile Alonso, Wladimir J. Simonsen, Lone TI Influenza in tropical regions SO PLOS MEDICINE LA English DT Editorial Material ID UNITED-STATES; HONG-KONG; MORTALITY; HOSPITALIZATIONS; CHILDREN; VACCINATION; PNEUMONIA; VIRUS C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Origem Sci Consultancy, Florianopolis, SC, Brazil. NIAID, NIH, Bethesda, MD 20892 USA. RP Viboud, C (reprint author), NIH, Fogarty Int Ctr, Bldg 10, Bethesda, MD 20892 USA. EM viboudc@mail.nih.gov OI Simonsen, Lone/0000-0003-1535-8526 NR 23 TC 221 Z9 235 U1 1 U2 10 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD APR PY 2006 VL 3 IS 4 BP 468 EP 471 AR e89 DI 10.1371/journal.pmed.0030089 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 042RX UT WOS:000237548200013 PM 16509764 ER PT J AU Spong, CY AF Spong, Catherine Y. TI Protection against prenatal alcohol-induced damage SO PLOS MEDICINE LA English DT Editorial Material ID PREVENTION; ETHANOL; DISORDER; GROWTH; BRAIN; MODEL C1 NICHHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. RP Spong, CY (reprint author), NICHHD, Pregnancy & Perinatol Branch, NIH, Bethesda, MD 20892 USA. EM spongc@mail.nih.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD APR PY 2006 VL 3 IS 4 BP 474 EP 475 AR e196 DI 10.1371/journal.pmed.0030196 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 042RX UT WOS:000237548200015 PM 16605309 ER PT J AU Greenberg, DE Ding, L Zelazny, AM Stock, F Wong, A Anderson, VL Miller, G Kleiner, DE Tenorio, AR Brinster, L Dorward, DW Murray, PR Holland, SM AF Greenberg, David E. Ding, Li Zelazny, Adrian M. Stock, Frida Wong, Alexandra Anderson, Victoria L. Miller, Georgina Kleiner, David E. Tenorio, Allan R. Brinster, Lauren Dorward, David W. Murray, Patrick R. Holland, Steven M. TI A novel bacterium associated with lymphadenitis in a patient with chronic granulomatous disease SO PLOS PATHOGENS LA English DT Article AB Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte NADPH oxidase system causing defective production of toxic oxygen metabolites, impaired bacterial and fungal killing, and recurrent life-threatening infections. We identified a novel gram-negative rod in excised lymph nodes from a patient with CGD. Gram-negative rods grew on charcoal-yeast extract, but conventional tests could not identify it. The best 50 matches of the 16S rRNA (using BLAST) were all members of the family Acetobacteraceae, with the closest match being Gluconobacter sacchari. Patient serum showed specific band recognition in whole lysate immunoblot. We used mouse models of CGD to determine whether this organism was a genuine CGD pathogen. Intraperitoneal injection of gp91(phox-/)-(X-linked) and p47(phox-/)-(autosomal recessive) mice with this bacterium led to larger burdens of organism recovered from knockout compared with wild-type mice. Knockout mouse lymph nodes had histopathology that was similar to that seen in our patient. We recovered organisms with 16S rRNA sequence identical to the patient's original isolate from the infected mice. We identified a novel gram-negative rod from a patient with CGD. To confirm its pathogenicity, we demonstrated specific immune reaction by high titer antibody, showed that it was able to cause similar disease when introduced into CGD, but not wild-type mice, and we recovered the same organism from pathologic lesions in these mice. Therefore, we have fulfilled Koch's postulates for a new pathogen. This is the first reported case of invasive human disease caused by any of the Acetobacteraceae. Polyphasic taxonomic analysis shows this organism to be a new genus and species for which we propose the name Granulobacter bethesdensis. C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NIH, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Diagnost & Res Serv Branch, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Rush Natl Coll, Dept Med, Infect Dis Sect, Chicago, IL USA. NIAID, Microscopy Branch, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Holland, SM (reprint author), NIAID, Lab Clin Infect Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM smh@nih.gov OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS NR 1 TC 42 Z9 43 U1 0 U2 3 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2006 VL 2 IS 4 BP 260 EP 267 AR e28 DI 10.1371/journal.ppat.0020028 PG 8 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA V42VG UT WOS:000202894400003 PM 16617373 ER PT J AU Grant, C Oh, U Fugo, K Takenouchi, N Griffith, C Yao, K Newhook, TE Ratner, L Jacobson, S AF Grant, Christian Oh, Unsong Fugo, Kazunori Takenouchi, Norihiro Griffith, Caitlin Yao, Karen Newhook, Timothy E. Ratner, Lee Jacobson, Steven TI Foxp3 represses retroviral transcription by targeting both NF-kappa B and CREB pathways SO PLOS PATHOGENS LA English DT Article AB Forkhead box (Fox)/winged-helix transcription factors regulate multiple aspects of immune responsiveness and Foxp3 is recognized as an essential functional marker of regulatory T cells. Herein we describe downstream signaling pathways targeted by Foxp3 that may negatively impact retroviral pathogenesis. Overexpression of Foxp3 in HEK 293T and purified CD4(+) T cells resulted in a dose-dependent and time-dependent decrease in basal levels of nuclear factor-kappa B (NF-kappa B) activation. Deletion of the carboxyl-terminal forkhead (FKH) domain, critical for nuclear localization and DNA-binding activity, abrogated the ability of Foxp3 to suppress NF-kappa B activity in HEK 293T cells, but not in Jurkat or primary human CD4(+) T cells. We further demonstrate that Foxp3 suppressed the transcription of two human retroviral promoters (HIV-1 and human T cell lymphotropic virus type I [ HTLV-I]) utilizing NF-kappa B-dependent and NF-kappa B-independent mechanisms. Examination of the latter identified the cAMP-responsive element binding protein (CREB) pathway as a target of Foxp3. Finally, comparison of the percent Foxp3(+)CD4(+)CD25(+) T cells to the HTLV-I proviral load in HTLV-I-infected asymptomatic carriers and patients with HTLV-I-associated myelopathy/tropical spastic paraparesis suggested that high Foxp3 expression is associated with low proviral load and absence of disease. These results suggest an expanded role for Foxp3 in regulating NF-kappa B-and CREB-dependent cellular and viral gene expression. C1 NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Pathol, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Mol Microbiol, St Louis, MO 63110 USA. RP Jacobson, S (reprint author), NINDS, Viral Immunol Sect, Neuroimmunol Branch, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. EM jacobsons@ninds.nih.gov FU Intramural NIH HHS NR 0 TC 7 Z9 7 U1 0 U2 1 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7366 EI 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2006 VL 2 IS 4 BP 303 EP 314 AR e33 DI 10.1371/journal.ppat.0020033 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA V42VG UT WOS:000202894400007 PM 16652169 ER PT J AU Rivera, S Vernon, SW Tiro, JA Coan, S del Junco, D Chan, W Coker, A AF Rivera, S Vernon, SW Tiro, JA Coan, S del Junco, D Chan, W Coker, A TI Test-retest reliability of self-reported mammography in women veterans SO PREVENTIVE MEDICINE LA English DT Article DE mammography/utilization; self-reports; reproducibility of results ID FECAL OCCULT BLOOD; COLORECTAL-CANCER; REPEAT MAMMOGRAPHY; PARTICIPATION; PREVALENCE; COHORT AB Background. Mammography self-report is used to monitor screening and evaluate intervention trends; however, few studies have examined reliability. Methods. Reliability of self-reported lifetime number of mammograms, most recent mammogram date, and predictors of reliability were assessed using data from Project H.O.M.E. The study population was 2494 women 52 years and over, listed in the U.S. National Registry of Women Veterans, with no history of breast cancer, who completed both baseline (2000-2002) and year 1 (2002-2003) surveys. Results. Reliability of lifetime number of mammograms was 60.9% for exact consistency and 79.9% for consistency within one mammogram. Thirty-five percent was exactly consistent in reporting mammogram date; 55.6% was consistent within 3 months. Completing both surveys by mail and reporting fewer lifetime mammograms at baseline were positively associated with consistency of reporting lifetime number. White race/ethnicity, having a Bachelor's degree, reporting a healthcare provider's recommendation for a mammogram, having a screening mammogram, completing both surveys by mail, and being in the maintenance or action stages of change were associated with consistency in reporting date. Conclusions. Reliability varies with the measure of self-reported mammography. Likewise, predictors show different patterns of association with different definitions. Our findings call attention to the need for explicit definitions and measures of mammography use. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Texas, Sch Publ Hlth, Div Hlth Promot & Behav Sci, Houston, TX 77225 USA. NCI, Div Canc Prevent, Canc Prevent Fellowship Program, Bethesda, MD 20892 USA. Texas A&M Univ, Sch Rural Publ Hlth, College Stn, TX 77843 USA. RP Vernon, SW (reprint author), 7000 Fannin,Suite 2560, Houston, TX 77030 USA. EM Sally.W.Vernon@uth.tmc.edu OI Tiro, Jasmin/0000-0001-8300-0441 FU NCI NIH HHS [R01 CA766330] NR 26 TC 9 Z9 9 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 0091-7435 J9 PREV MED JI Prev. Med. PD APR PY 2006 VL 42 IS 4 BP 320 EP 326 DI 10.1016/j.ypmed.2005.12.001 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 037MO UT WOS:000237151200014 PM 16442154 ER PT J AU Bu, B Ashwood, P Harvey, D King, IB Van de Water, J Jin, LW AF Bu, B Ashwood, P Harvey, D King, IB Van de Water, J Jin, LW TI Fatty acid compositions of red blood cell phospholipids in children with autism SO PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS LA English DT Article ID SCHIZOPHRENIC-PATIENTS; SPECTRUM DISORDERS; LIPID-PEROXIDATION; OXIDATIVE STRESS; METABOLISM; OMEGA-3-FATTY-ACIDS; SUPPLEMENTATION; QUESTIONNAIRE; DEFICIENCY; MEMBRANES AB We compared the compositions of fatty acids including n-3, n-6 polyunsaturated fatty acids, trans- and cis-monounsaturated fatty acids, and saturated fatty acids in the red blood cell membranes of 40 children with autism (20 with early onset autism and 20 with developmental regression) and age-matched, 20 typically developing controls and 20' subjects with non-autistic developmental disabilities. The main findings include increased levels of eicosenoic acid (20:1n9) and erucic acid (22:1n9) in autistic subjects with developmental regression when compared with typically developing controls. In addition, an. increase in 20:2n6 and a decrease in 16:1 n7t were observed in children with clinical regression compared to those with early onset autism. Our results do not provide strong evidence for the hypothesis that abnormal fatty acid metabolism plays a role in the pathogenesis of autism spectrum disorder, although they suggest Borne metabolic or dietary abnormalities in the regressive form of autism., (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Calif Davis, Dept Pathol, MIND Inst, Sacramento, CA 95817 USA. NIEHS, Dept Med Microbiol & Immunol, MIND Inst, Ctr Childrens Environm Hlth, Res Triangle Pk, NC 27709 USA. Univ Calif Davis, Div Biostat, Dept Publ Hlth Sci, Davis, CA 95616 USA. Univ Calif Davis, NIEHS Ctr Childrens Environm Hlth, Dept Internal Med, Div Rheumatol Allergy & Clin Imunol,MIND Inst, Davis, CA 95616 USA. Fred Hutchinson Canc Res Ctr, Publ Hlth Sci Lab, Seattle, WA 98104 USA. RP Jin, LW (reprint author), Univ Calif Davis, Dept Pathol, MIND Inst, 2805 50th St, Sacramento, CA 95817 USA. EM lee-way.jin@ucdmc.ucdavis.edu FU NIEHS NIH HHS [1 P01 ES11269-01] NR 39 TC 34 Z9 36 U1 0 U2 4 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0952-3278 J9 PROSTAG LEUKOTR ESS JI Prostaglandins Leukot. Essent. Fatty Acids PD APR PY 2006 VL 74 IS 4 BP 215 EP 221 DI 10.1016/j.plefa.2006.02.001 PG 7 WC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Cell Biology; Endocrinology & Metabolism GA 035HT UT WOS:000236992300001 PM 16581239 ER PT J AU Xiong, CY O'Keefe, BR Botos, I Wlodawer, A McMahon, JB AF Xiong, CY O'Keefe, BR Botos, I Wlodawer, A McMahon, JB TI Overexpression and purification of scytovirin, a potent, novel anti-HIV protein from the cultured cyanobacterium Scytonema varium SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE scytovirin, SVN; microbicide; HIV; anti-HIV; cyanobacterium; recombinant expression ID DISULFIDE BOND FORMATION; CYANOVIRIN-N; INACTIVATING PROTEIN; ESCHERICHIA-COLI; CYTOPLASM; GP120 AB Scytovirin (SVN) is a novel anti-human immunodeficiency virus (HIV) protein isolated from aqueous extracts of the cultured cyanobacterium Scytonema varium. The protein consists of a single 95-amino acid chain with significant internal sequence duplication and 10 cysteines forming five intrachain disulfide bonds. A synthetic gene that encodes scytovirin was constructed, and expressed in Escherichia coli, with thioredoxin (TRX) fused to its N-terminus (TRX-SVN). Most of the expressed protein was in soluble form, which was purified by a polyhistidine tag affinity purification step. SVN was then cleaved from TRX with enterokinase and separated from the TRX partner by C18 reversed-phase HPLC. This production method has proven superior to earlier synthetic attempts and recombinant procedures using a standard expression system. The current system resulted in yields of 5-10 mg/L of purified SVN for structural studies and for preclinical development of SVN as a topical microbicide for HIV prophylaxis. Published by Elsevier Inc. C1 NCI, Mol Targets Dev Program, NIH, Frederick, MD 21701 USA. NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21701 USA. RP O'Keefe, BR (reprint author), NCI, Mol Targets Dev Program, NIH, Frederick, MD 21701 USA. EM okeefe@ncifcrf.gov FU Intramural NIH HHS NR 12 TC 23 Z9 27 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD APR PY 2006 VL 46 IS 2 BP 233 EP 239 DI 10.1016/j.pep.2005.09.019 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 033DZ UT WOS:000236828100008 PM 16289703 ER PT J AU Zhao, Q Chen, PL Manson, ME Liu, YS AF Zhao, Q Chen, PL Manson, ME Liu, YS TI Production of active recombinant mitogen-activated protein kinases through transient transfection of 293T cells SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE MAP kinase; signal transduction; phosphorylation; recombinant protein; stress-activated protein kinase; JNK; p38; expression; purification ID MAP KINASE; STIMULATED MACROPHAGES; CYTOKINE BIOSYNTHESIS; CELLULAR-RESPONSE; HUMAN GENOME; C-JUN; STRESS; PATHWAYS; EXPRESSION; PHOSPHATASE-1 AB Mitogen-activated protein (MAP) kinases are a family of serine/threonine protein kinases that play an important role in a myriad of cellular processes, including cell proliferation, differentiation, and apoptosis. Abnormal activation of MAP kinases has been shown to participate in a variety of human diseases which include cancer, septic shock, rheumatoid arthritis, diabetes, and cardiovascular diseases. Active MAP kinase enzymes are not only valuable for basic biomedical research but are also critical for the development of pharmacological inhibitors as therapeutic drugs in the treatment of relevant human diseases. MAP kinases produced in a bacterial system are poorly active due to a lack of proper phosphorylation at their characteristic threonine and tyrosine residues. To overcome these limitations, we have developed a mammalian expression system for high level expression and one-step purification of enzymatically MAP kinases. We cloned JNK1, p38, and p38-regulated MAP kinase-activated protein kinase-2 into the mammalian expression vector pEBG, and expressed these protein kinases as glutathione S-transferase fusion proteins in human embryonic kidney 293T cells through transient transfection. The protein kinases were activated in vivo through treating the transfected cells with sodium arsenite and affinity-purified using glutathione-Sepharose beads. The enzymatic activities of these protein kinases were demonstrated by Western blot analysis and in vitro kinase assays. Our results indicate that this system is an extremely powerful tool for generating valuable reagents, and could be very valuable for proteomic studies. (c) 2005 Elsevier Inc. All rights reserved. C1 Ohio State Univ, Childrens Hosp, Childrens Res Inst, Dept Pediat, Columbus, OH 43205 USA. NIA, Intramural Res Program, Cellular & Mol Biol Lab, Baltimore, MD 21224 USA. RP Liu, YS (reprint author), Ohio State Univ, Childrens Hosp, Childrens Res Inst, Dept Pediat, 700 Childrens Dr, Columbus, OH 43205 USA. EM liuy@pediatrics.ohio-state.edu RI Liu, Yusen/E-3527-2011 NR 33 TC 5 Z9 5 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 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD APR PY 2006 VL 46 IS 2 BP 468 EP 474 DI 10.1016/j.pep.2005.09.011 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 033DZ UT WOS:000236828100037 PM 16256366 ER PT J AU Chill, JH Louis, JM Miller, C Bax, A AF Chill, JH Louis, JM Miller, C Bax, A TI NMR study of the tetrameric KcsA potassium channel in detergent micelles SO PROTEIN SCIENCE LA English DT Article DE backbone assignment; detergent; global fold; membrane protein; NMR; NOE; potassium channel; secondary chemical shifts ID LARGE BIOLOGICAL MACROMOLECULES; PROTEIN-STRUCTURE DETERMINATION; K+ CHANNEL; MEMBRANE-PROTEIN; CHEMICAL-SHIFTS; LIPID INTERACTIONS; ESCHERICHIA-COLI; SPECTROSCOPY; ASSIGNMENTS; DYNAMICS AB Nuclear magnetic resonance (NMR) studies of large membrane-associated proteins are limited by the difficulties in preparation of stable protein-detergent mixed micelles and by line broadening, which is typical of these macroassemblies. We have used the 68-kDa homotetrameric KcsA, a thermostable N-terminal deletion mutant of a bacterial potassium channel from Streptomyces lividans, as a model system for applying NMR methods to membrane proteins. Optimization of measurement conditions enabled us to perform the backbone assignment of KcsA in SDS micelles and establish its secondary structure, which was found to closely agree with the KcsA crystal structure. The C-terminal cytoplasmic domain, absent in the original structure, contains a 14-residue helix that could participate in tetramerization by forming an intersubunit four-helix bundle. A quantitative estimate of cross-relaxation between detergent and KcsA backbone amide protons, together with relaxation and light scattering data, suggests SDS-KcsA mixed micelles form an oblate spheroid with similar to 180 SDS molecules per channel. K+ ions bind to the micelle-solubilized channel with a K-D of 3 +/- 0.5 mM, resulting in chemical shift changes in the selectivity filter. Related pH-induced changes in chemical shift along the "outer" transmembrane helix and the cytoplasmic membrane interface hint at a possible structural explanation for the observed pH-gating of the potassium channel. C1 NIDDK, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Brandeis Univ, Howard Hughes Med Inst, Dept Biochem, Waltham, MA 02454 USA. RP Bax, A (reprint author), NIDDK, Phys Chem Lab, NIH, Bldg 5,Room 126,9000 Rockville Pike, Bethesda, MD 20892 USA. EM bax@nih.gov FU Intramural NIH HHS NR 62 TC 122 Z9 125 U1 1 U2 15 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD APR PY 2006 VL 15 IS 4 BP 684 EP 698 DI 10.1110/ps.051954706 PG 15 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 031WA UT WOS:000236734200003 PM 16522799 ER PT J AU Wang, XN Zhu, W Pradhan, K Ji, C Ma, YM Semmes, OJ Glimm, J Mitchell, J AF Wang, XN Zhu, W Pradhan, K Ji, C Ma, YM Semmes, OJ Glimm, J Mitchell, J TI Feature extraction in the analysis of proteomic mass spectra SO PROTEOMICS LA English DT Article DE feature extraction; mass spectrometry; noise filtration; peak alignment; peak calibration ID BIOMARKER DISCOVERY; CANCER; SERUM; SPECTROMETRY; PATTERNS; PROSTATE; HEAD AB Feature extraction or biomarker selection is a critical step in disease diagnosis and knowledge discovery based on protein MS. Many studies have discussed the classification methods applied in proteomics; however, few could be found to address feature extraction in detail. In this paper, we developed a systematic approach for the extraction of mass spectrum peak apex and peak area with special emphasis on noise filtration and peak calibration. Application to a head and neck cancer data generated at the Eastern Virginia Medical School [Wadsworth, J.T., Somers, K. D., Cazares, L.H., Malik, G. et al., Clin. Cancer Res. 2004, 10, 1625-1632] revealed that the new feature extraction method would yield consistent and highly discriminatory biomarkers. C1 SUNY Stony Brook, Stony Brook, NY 11794 USA. NIAAA, Bethesda, MD USA. Eastern Virginia Med Sch, Norfolk, VA 23501 USA. RP Zhu, W (reprint author), SUNY Stony Brook, Nicholls Rd, Stony Brook, NY 11794 USA. EM zhu@ams.sunysb.edu FU NCRR NIH HHS [3 M01 RR010710-06S1]; NIA NIH HHS [2 P30 AG08051-11] NR 18 TC 16 Z9 16 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9853 J9 PROTEOMICS JI Proteomics PD APR PY 2006 VL 6 IS 7 BP 2095 EP 2100 DI 10.1002/pmic.200500459 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 033EL UT WOS:000236829300008 PM 16502467 ER PT J AU Kasai, S Han, WH Ide, S Hata, H Takamatsu, Y Yamamoto, H Uhl, GR Sora, I Ikeda, K AF Kasai, S Han, WH Ide, S Hata, H Takamatsu, Y Yamamoto, H Uhl, GR Sora, I Ikeda, K TI Involvement of the 3 ' non-coding region of the mu opioid receptor gene in morphine-induced analgesia SO PSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article; Proceedings Paper CT Joint Meeting of the Japanese-Society-of-Biological-Psychiatry/Japanese-Society-of-Neuropsych opharmacology CY JUL 06-08, 2005 CL Osaka, JAPAN SP Japanese Soc Biolog Psychiatry, Japanese Soc Neuropsychopharmacol DE 3 ' untranslated region; analgesia; CXBK mice; morphine; mu opioid receptor ID MESSENGER-RNA DEGRADATION; 3' UNTRANSLATED REGION; TRANSCRIPTIONAL REGULATION; OPIATE RECEPTOR; PHARMACOLOGICAL CHARACTERIZATION; MYOTONIC-DYSTROPHY; MOLECULAR-CLONING; NEURONAL CELLS; MICE LACKING; CXBK MICE AB The mu opioid receptor (MOR) is known to play an essential role in morphine-induced analgesia. MOR-1 mRNA, the major MOR transcript, possesses a long 3' untranslated region (3'UTR) in both mouse and human species. The sequence of the MOR-1 3'UTR, especially that of its 3' end region, is conserved between mice and humans. In the MOR-1 3'UTR, AU-rich elements (AREs) are densely localized at the 3' end region, suggesting low stability of this mRNA. Numerous putative transcription factor-binding motifs are located in the 3' non-coding regions of the mouse and human MOR genes. The CXBK mouse strain, known as a MOR-deficient strain, possesses a decreased amount of MOR-1 mRNA containing an abnormally long MOR-1 3'UTR with a long nucleotide insertion. This insert might disrupt the stability of the MOR-1 mRNA or might reduce the transcription of the MOR-1 mRNA by separating the transcription factor-binding motifs in the 3' non-coding region of the MOR gene, thereby decreasing MOR-1 mRNA expression and attenuating morphine-induced analgesia in CXBK mice. These recent findings suggest that the MOR-1 3'UTR is involved in mRNA expression and in the difference in response to morphine. This possible genetic mechanism may provide a good starting point for designing effective pain treatments with opiates. C1 Tokyo Inst Psychiat, Div Psychobiol, Setagaya Ku, Tokyo 1568585, Japan. Hiroshima Int Univ, Dept Pharmaceut Sci, Neuropharmacol Lab, Kure, Japan. Tohoku Univ, Sch Med, Dept Psychobiol, Sendai, Miyagi 980, Japan. NIDA, Mol Neurobiol Branch, Int Res Program, NIH, Baltimore, MD USA. RP Ikeda, K (reprint author), Tokyo Inst Psychiat, Div Psychobiol, Setagaya Ku, 2-1-8 Kamikitazawa, Tokyo 1568585, Japan. EM ikedak@prit.go.jp RI Ide, Soichiro/D-5472-2012 NR 54 TC 8 Z9 9 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1323-1316 J9 PSYCHIAT CLIN NEUROS JI Psychiatry Clin. Neurosci. PD APR PY 2006 VL 60 SU 1 BP S11 EP S17 PG 7 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 021AN UT WOS:000235954800003 ER PT J AU Rose, EJ Simonotto, E Spencer, EP Ebmeier, KP AF Rose, EJ Simonotto, E Spencer, EP Ebmeier, KP TI The effects of escitalopram on working memory and brain activity in healthy adults during performance of the n-back task SO PSYCHOPHARMACOLOGY LA English DT Article DE escitalopram; working memory; major depression; functional MRI ID SEROTONIN-REUPTAKE INHIBITORS; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; SELECTIVE SEROTONIN; MAJOR DEPRESSION; COGNITIVE FUNCTION; GLUCOSE-METABOLISM; VOLUNTEERS; CITALOPRAM; PAROXETINE AB Rationale: Psychotropic medication affects cognition and brain function, making it a potential confounder in functional neuroimaging studies of psychiatric patients. Objective: To determine whether the sub-acute administration of an antidepressant (escitalopram) would induce differences in cognitive performance and associated brain function, which could be observed within the normal power of a functional imaging study. Materials and methods: Healthy adults (N=10) received a short course of escitalopram (10 mg/day for 7 days). Participants performed a parametric working memory (WM) task during BOLD fMRI, both while medication-free and after medication. To control for order effects, the medication-free examination was completed by half the subjects before starting medication and by the other half at least one week after medication. Results: Escitalopram had no significant effect on WM accuracy or reaction time. Preliminary analysis of the imaging data revealed no significant (p (corrected)< 0.05) differences in memory-load-dependent activation between conditions. However, small volume correction analysis of regions that were significant prior to correction for multiple comparisons highlighted between condition differences in regions likely to be susceptible to antidepressant effects (i.e. thalamus, anterior cingulate and inferior frontal gyrus). Conclusions: These results suggest that the sub-acute administration of antidepressants in healthy controls does not affect cognitive or hemodynamic function in healthy adults to a magnitude greater than one standard deviation unit. Therefore, the confounding effect of antidepressants on signal intensity in imaging studies of medicated, depressed individuals may be limited. C1 Univ Edinburgh, Dept Psychiat, Edinburgh EH10 5HF, Midlothian, Scotland. Univ Edinburgh, Western Gen Hosp, Dept Clin Neurosci, SHEFC Brain Imagiing Ctr Scotland, Edinburgh EH4 2XU, Midlothian, Scotland. NIDA, Intramural Res Program, Baltimore, MD 21224 USA. Guys & St Thomas Hosp, Med Toxicol Unit, London SE1 9RT, England. RP Ebmeier, KP (reprint author), Univ Edinburgh, Dept Psychiat, Kennedy Tower,Morningside Pk, Edinburgh EH10 5HF, Midlothian, Scotland. EM k.ebmeier@ed.ac.uk RI Rose, Emma/A-9960-2010; OI Rose, Emma/0000-0001-5365-4794; Ebmeier, Klaus/0000-0002-5190-7038 NR 48 TC 32 Z9 32 U1 3 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD APR PY 2006 VL 185 IS 3 BP 339 EP 347 DI 10.1007/s00213-006-0334-2 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 024OY UT WOS:000236206900009 PM 16525858 ER PT J AU Skopec, M Loew, M Price, JL Moscovitch, M AF Skopec, M Loew, M Price, JL Moscovitch, M TI Thermoluminescent response and the effect of exposure order from mixed photon and proton irradiations SO RADIATION MEASUREMENTS LA English DT Article ID GLOW CURVE DECONVOLUTION; RADIATION-FIELDS; DOSIMETRY AB Two types of thermoluminescent dosimeters (TLDs): Harshaw LiF:Mg,Ti (TLD-100) and CaF2:Tm (TLD-300) were investigated for their glow curve responses to separate, mixed field, and simultaneous X-ray and proton irradiations. All TLDs X-rays produced by a 30 keV, 0.2 mA electron beam. X-ray tube source. TLD-100 detectors were exposed to were exposed to 2.5 MeV protons and the TLD-300 detectors were exposed to 4MeV protons. The following five separate irradiation schemes were used: only X-ray, only proton, first X-ray then proton, first proton then X-ray, and simultaneous X-ray and proton beam exposures. Computerized glow curve deconvolution based on first order TL kinetics was used to analyze the resulting glow curves for any differences in shape and TL efficiency due to order of exposure. We found no significant differences in glow Curve shape or magnitude attributable to radiation exposure order. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. George Washington Univ, Washington, DC USA. USN, Ctr Surface Warfare, Carderock Div, Bethesda, MD 20084 USA. Georgetown Univ, Washington, DC USA. RP Skopec, M (reprint author), NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. EM marskopec@yahoo.com NR 9 TC 0 Z9 0 U1 2 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-4487 J9 RADIAT MEAS JI Radiat. Meas. PD APR PY 2006 VL 41 IS 4 BP 405 EP 409 DI 10.1016/j.radmeas.2005.09.016 PG 5 WC Nuclear Science & Technology SC Nuclear Science & Technology GA 026AV UT WOS:000236310000004 ER PT J AU Frenkel, V Oberoi, J Stone, MJ Park, M Deng, C Wood, BJ Neeman, Z Horne, M Li, KCP AF Frenkel, V Oberoi, J Stone, MJ Park, M Deng, C Wood, BJ Neeman, Z Horne, M Li, KCP TI Pulsed high-intensity focused ultrasound enhances thrombolysis in an in vitro model SO RADIOLOGY LA English DT Article ID SHOCK-WAVE LITHOTRIPSY; EXTERNAL ULTRASOUND; FISH SKIN; FIBRINOLYSIS; THERAPY; VIVO; ACCELERATION; MICROBUBBLES; FEASIBILITY; DISRUPTION AB Purpose: To evaluate the use of pulsed high-intensity focused Ultrasound exposures to improve tissue plasminogen activator (tPA)-mediated thrombolysis in an in vitro model. Materials and Methods: All experimental work was compliant with institutional guidelines and HIPAA. Clots were formed by placing 1. mL of human blood ill closed-off sections of pediatric Penrose tubes. Four experimental groups were evaluated: control (nontreated) clots, clots treated with pulsed high-intensity focused ultrasound only, clots treated with tPA only, and clots treated with pulsed high-intensity focused ultrasound plus tPA. The focused ultrasound exposures (real or sham) were followed by incubations of the clots in tPA with saline or in saline only. Thrombolysis was measured as the relative reduction in the mass or the clot. D-Dimer assays also were performed. Two additional experiments were performed and yielded dose-response curves for two exposure parameters: number or pulses per raster point and total acoustic power. Radiation force-induced displacements Caused by focused ultrasound exposures were simulated in the clots. A Tukey-Kramer honestly significant difference test was performed for comparisons between all pairs of experimental groups. Results: The clots treated with h focused ultrasound alone did not show significant, increases in thrombolysis compared with the control clots. The clots treated with focused ultrasound plus tPA showed a 50% ([30.2/20.1]/20.1) increase in the degree of thrombolysis compared with the clots treated with tPA only (P <.001), further corroborating the D-dimer assay results (P <.001). Additional experiments revealed how increasing both the number of pulses per raster point, and the total acoustic power yielded corresponding increases in the thrombolysis rate. In the latter experiment, simulations performed at a range of power settings revealed a direct correlation between increased displacement and observed thrombolysis rate. Conclusions: The race of tPA-mediated thrombolysis can be enhanced by using pulsed high-intensity focused ultrasound exposure in Vitro. C1 NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Ctr Clin, Bethesda, MD 20892 USA. Case Western Reserve Univ, Dept Biomed Engn, Cleveland, OH 44106 USA. RP Frenkel, V (reprint author), NIH, Dept Diagnost Radiol, 10 Ctr Dr,Bldg 10,Room 1C657, Bethesda, MD 20892 USA. EM vfrenkel@cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 37 TC 68 Z9 70 U1 0 U2 4 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD APR PY 2006 VL 239 IS 1 BP 86 EP 93 DI 10.1148/radiol.2391042181 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 030XQ UT WOS:000236669100012 PM 16493016 ER PT J AU Doerge, DR Twaddle, NC Churchwell, MI Newbold, RR Delclos, KB AF Doerge, DR Twaddle, NC Churchwell, MI Newbold, RR Delclos, KB TI Lactational transfer of the soy isoflavone, genistein, in Sprague-Dawley rats consuming dietary genistein SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE genistein; soy; lactation; neonatal; mass spectrometry ID NEONATAL EXPOSURE; FEMALE RATS; PHYTOESTROGEN GENISTEIN; F-1 GENERATIONS; BIOAVAILABILITY; HYPOTHALAMUS; NONYLPHENOL; EXPRESSION; VOLUME AB Exposures of Sprague-Dawley rats to the soy isoflavone, genistein, throughout the entire lifespan have produced a number of effects on reproductive tissues, immune function, neuroendocrine function and behavior. Our previous studies investigated pharmacokinetics and disposition of genistein during adult and fetal periods and this study describes the internal exposures of post-natal day 10 (PND10) rat pups due to lactational transfer of genistein. Conjugated and aglycone forms of genistein were measured by using LC/MS/MS in serum (PND10) and milk (PND7) from lactating dams consuming a genistein-fortified soy-free diet, and in serum from their pups at a time when milk was the only food source (PND10). This study shows that limited lactational transfer of genistein to rat pups occurs and that internal exposures to the active aglycone form of genistein are generally lower than those measured previously in the fetal period. These results suggest that developmental effects attributable to genistein exposure in our chronic and multi-generation studies are more likely to result from fetal exposures because of the higher levels of the active estrogenic aglycone form of genistein in utero, although the possibility of neonatal responses cannot be excluded. (c) 2005 Elsevier Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Dev Endocrinol & Endorcine Disrupter Sect, Mol Toxicol Lab, NIH DHHS, Res Triangle Pk, NC 27709 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM ddoerge@nctr.fda.gov FU PHS HHS [224-93-0001] NR 32 TC 43 Z9 43 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD APR PY 2006 VL 21 IS 3 BP 307 EP 312 DI 10.1016/j.reprotox.2005.09.007 PG 6 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 023VG UT WOS:000236153700014 PM 16257506 ER PT J AU Azhikina, T Gvozdevsky, N Botvinnik, A Fushan, A Shemyakin, I Stepanshina, V Lipin, M Barry, CB Sverdlov, E AF Azhikina, T Gvozdevsky, N Botvinnik, A Fushan, A Shemyakin, I Stepanshina, V Lipin, M Barry, CB Sverdlov, E TI A genome-wide sequence-independent comparative analysis of insertion-deletion polymorphisms in multiple Mycobacterium tuberculosis strains SO RESEARCH IN MICROBIOLOGY LA English DT Article DE Mycobacterium tuberculosis strains; subtractive hybridization; comparative genomics ID SUBTRACTIVE HYBRIDIZATION; NEISSERIA-MENINGITIDIS; GENETIC-DIFFERENCES; VIRULENCE; COMPLEX; LIBRARIES; MARKERS; IDENTIFICATION; BIOSYNTHESIS; DIVERSITY AB We applied an enhanced version of subtractive hybridization for comparative analyses of indel differences between genomes of several Mycobacterium tuberculosis strains widespread in Russian regions, and the H37Rv reference strain. A number of differences were detected and partially analyzed, thus demonstrating the practicality of the approach. A majority of the insertions found were shared by all Russian strains, except for strain 1540 that revealed the highest virulence in animal tests. This strain possesses a number of genes absent from other clinical strains. Two of the differential genes were found to encode putative membrane proteins and are presumed to affect mycobacterial interaction with the host cell, thus enhancing virulent properties of the isolate. The method used is of general application, and enables the elaboration of a catalogue of indel polymorphic genomic differences between closely related strains. (c) 2005 Elsevier SAS. All rights reserved. C1 Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Lab Struct & Funct Human Genes, Moscow 117997, Russia. State Res Ctr Appl Microbiol, Obolensk 142279, Russia. NIAID, TB Res Stn, NIH, Rockville, MD 20852 USA. RP Azhikina, T (reprint author), Russian Acad Sci, Shemyakin Ovchinnikov Inst Bioorgan Chem, Lab Struct & Funct Human Genes, 16-10 Miklukho Maklaya St, Moscow 117997, Russia. EM tanya@humgen.siobc.ras.ru RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11] NR 44 TC 4 Z9 6 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0923-2508 J9 RES MICROBIOL JI Res. Microbiol. PD APR PY 2006 VL 157 IS 3 BP 282 EP 290 DI 10.1016/j.resmic.2005.08.002 PG 9 WC Microbiology SC Microbiology GA 030MQ UT WOS:000236639100013 PM 16239096 ER PT J AU Graves, E Ramsay, E McCarthy, DO AF Graves, E Ramsay, E McCarthy, DO TI Inhibitors of COX activity preserve muscle mass in mice bearing the Lewis lung carcinoma, but not the B16 melanoma SO RESEARCH IN NURSING & HEALTH LA English DT Article DE mice; cachexia; B16 melanoma; Lewis lung carcinoma; tumor necrosis factor-alpha; indomethacin; cyclooxygenase ID EXPERIMENTAL CANCER CACHEXIA; KAPPA-B ACTIVATION; SKELETAL-MUSCLE; SYSTEMIC INFLAMMATION; GASTROCNEMIUS-MUSCLE; TNF-ALPHA; TUMOR; CYCLOOXYGENASE-2; EXPRESSION; CYTOKINES AB Tumor-induced skeletal muscle wasting (SMW) contributes to the fatigue and weakness experienced by persons with cancer cachexia. Tumor necrosis factor-alpha (TNFa) and cyclooxygenase (COX) activity have been implicated in SMW in some animal models of cancer cachexia. We report that indomethacin, a nonspecific inhibitor of COX, and NS398, a specific inhibitor of COX2, preserved muscle mass and reduced type 1 TNF receptors in muscles of mice bearing the Lewis lung carcinoma, but not in mice bearing the B16 melanoma. These data suggest that tumor-induced SMW can occur via a COX2-independent pathway. The COX2-dependent pathway may involve reducing the catabolic effects of TNFa in muscle. Further study is needed to understand the relationship between COX and SMW, and whether patients with cancer cachexia might benefit from COX inhibitors. (c) 2006 Wiley Periodicals, Inc. C1 Natl Inst Nursing, Lab Symptom Management, Bethesda, MD USA. RP Graves, E (reprint author), Clin Sci Ctr, 600 Highland Ave,Room K6-326, Madison, WI 53792 USA. RI McCarthy, Donna/A-3291-2013 FU Intramural NIH HHS NR 24 TC 17 Z9 17 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD APR PY 2006 VL 29 IS 2 BP 87 EP 97 DI 10.1002/nur.20114 PG 11 WC Nursing SC Nursing GA 028YQ UT WOS:000236525100003 PM 16532483 ER PT J AU McCarthy, DO Graves, E AF McCarthy, DO Graves, E TI Conjugated linoleic acid preserves muscle mass in mice bearing the Lewis lung carcinoma, but not the B16 melanoma SO RESEARCH IN NURSING & HEALTH LA English DT Article DE cancer cachexia; tumor necrosis factor-alpha; Lewis lung carcinoma; B16 melanoma; mice; conjugated linoleic acid ID NF-KAPPA-B; EXPERIMENTAL CANCER CACHEXIA; SKELETAL-MUSCLE; COLON-26 ADENOCARCINOMA; SYSTEMIC INFLAMMATION; CYTOKINES; ALPHA; PROTEIN; DEGRADATION; EXPRESSION AB Conjugated linoleic acid (CLA), which is found in dairy products, reduces synthesis of tumor necrosis factor-alpha (TNFa), a pro-inflammatory cytokine that plays a major role in tumor-induced skeletal muscle wasting (SMW). The B16 melanoma expresses TNFa mRNA, and induced SMW with no change in muscle levels of TNFa type 1 receptor (TNFR1) protein. A diet containing .5% CLA had no effect on SMW or TNFR1 in mice bearing B16 tumors. In contrast, the Lewis lung carcinoma expresses low levels of TNFa mRNA, induced SMW, and increased muscle levels of TNFR1. A diet containing .5% CLA reduced SMW, but had no effect on muscle levels of TNFR1. We conclude that that tumor-induced SMW can occur independent of muscle levels of TNFR1. Further study is needed before CLA can be tested in persons with cancer cachexia. (c) 2006 Wiley Periodicals, Inc. C1 Natl Inst Nursing, Lab Sympton Management, NIH, Bethesda, MD USA. RP McCarthy, DO (reprint author), Univ Wisconsin, Sch Nursing, 600 Highland Ave, Madison, WI 53792 USA. RI McCarthy, Donna/A-3291-2013 FU Intramural NIH HHS NR 30 TC 9 Z9 9 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0160-6891 J9 RES NURS HEALTH JI Res. Nurs. Health PD APR PY 2006 VL 29 IS 2 BP 98 EP 104 DI 10.1002/nur.20115 PG 7 WC Nursing SC Nursing GA 028YQ UT WOS:000236525100004 PM 16532476 ER PT J AU Lodde, BM Sankar, V Kok, MR Leakan, RA Tak, PP Pillemer, SR AF Lodde, BM Sankar, V Kok, MR Leakan, RA Tak, PP Pillemer, SR TI Serum lipid levels in Sjogren's syndrome SO RHEUMATOLOGY LA English DT Article DE Sjogren's syndrome; cholesterol; HDL; inflammation; cardiovascular disease ID ACTIVE RHEUMATOID-ARTHRITIS; CHRONIC INFLAMMATORY ARTHRITIDES; DENSITY-LIPOPROTEIN CHOLESTEROL; ACUTE-PHASE RESPONSE; C-REACTIVE PROTEIN; CARDIOVASCULAR-DISEASE; SALIVARY-GLANDS; SICCA SYNDROME; PROFILES; DYSLIPOPROTEINEMIA AB Objectives. Altered lipid levels may occur in autoimmune diseases, for example low cholesterol levels have been described in rheumatoid arthritis (RA). Serum lipid profiles in patients with Sjogren's syndrome (SS) have not been investigated. We hypothesized decreased lipid levels in SS patients and an inverse relationship with disease activity. Methods. Serum lipid levels [total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides] and additional data regarding disease measures (clinical immunology parameters, focus score from labial salivary gland biopsy, salivary flow and ophthalmological measures) were available for 46 primary SS patients and 12 xerostomic controls. Results. Significant differences between SS patients and controls means (s.d.) were seen for HDL (P = 0.04) and total cholesterol (P = 0.02). LDL (P = 0.12) and triglyceride (P = 0.08) levels were not different. In SS patients, but not in controls, total cholesterol (P = 0.003) and HDL cholesterol (P = 0.003) predicted immunoglobulin G levels. Anti-SSA antibodies were related to a lower total cholesterol (P = 0.02) and anti-SSB antibodies to a lower HDL cholesterol level (P = 0.0497). Conclusions. Significant differences were seen in serum lipid levels of primary SS patients and these were associated with serological measures of inflammation. Our results are comparable to earlier findings in RA patients and raise questions related to adverse cardiovascular consequences in SS. C1 NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. Univ Amsterdam, Acad Med Ctr, Div Clin Immunol & Rheumatol, NL-1012 WX Amsterdam, Netherlands. RP Lodde, BM (reprint author), NIDCR, GTTB, NIH, 10 Ctr Dr,Room 1N114,MSC 1190, Bethesda, MD 20892 USA. EM blodde@mail.nih.gov NR 37 TC 34 Z9 35 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD APR PY 2006 VL 45 IS 4 BP 481 EP 484 DI 10.1093/rheumatology/kei190 PG 4 WC Rheumatology SC Rheumatology GA 025GD UT WOS:000236252400022 PM 16303821 ER PT J AU Kirkpatrick, B Fenton, WS Carpenter, WT Marder, SR AF Kirkpatrick, B Fenton, WS Carpenter, WT Marder, SR TI The NIMH-MATRICS consensus statement on negative symptoms SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; methods; clinical trials; rating scales; antipsychotics ID QUALITY-OF-LIFE; DEFICIT SYNDROME; SCHIZOPHRENIA; SCALE C1 Med Coll Georgia, Dept Psychiat & Hlth Behav, Augusta, GA 30912 USA. NIMH, Div Adult Translat Res & Dev, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Univ Maryland, Maryland Psychiat Res Ctr, Dept Psychiat, College Pk, MD 20742 USA. Univ Calif Los Angeles, VA Desert Pacific, Mental Illness Res Educ & Clin Ctr, Dept Psychiat,David Geffen Sch Med, Los Angeles, CA USA. RP Kirkpatrick, B (reprint author), Med Coll Georgia, Dept Psychiat & Hlth Behav, Augusta, GA 30912 USA. EM bkirkpatrick2@aol.com NR 24 TC 408 Z9 416 U1 3 U2 26 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD APR PY 2006 VL 32 IS 2 BP 214 EP 219 DI 10.1093/schbul/sbj053 PG 6 WC Psychiatry SC Psychiatry GA 023DV UT WOS:000236106600006 PM 16481659 ER PT J AU Yang, JC Abad, J Sherry, R AF Yang, JC Abad, J Sherry, R TI Treatment of oligometastases after successful immunotherapy SO SEMINARS IN RADIATION ONCOLOGY LA English DT Article ID HIGH-DOSE INTERLEUKIN-2; RENAL-CELL CARCINOMA; ACTIVATED KILLER-CELLS; METASTATIC MELANOMA; CLASS-I; RECOMBINANT INTERLEUKIN-2; BOLUS INTERLEUKIN-2; CANCER; IDENTIFICATION; ANTIGEN C1 NCI, Surg Branch, Bethesda, MD 20892 USA. RP Yang, JC (reprint author), NCI, Surg Branch, Bldg 10,Room 2B37, Bethesda, MD 20892 USA. NR 19 TC 16 Z9 16 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 1053-4296 J9 SEMIN RADIAT ONCOL JI Semin. Radiat. Oncol. PD APR PY 2006 VL 16 IS 2 BP 131 EP 135 DI 10.1016/j.semradonc.2005.12.008 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 032QA UT WOS:000236788200008 PM 16564448 ER PT J AU Kalantaridou, SN Calis, KA AF Kalantaridou, SN Calis, KA TI Testosterone therapy in premenopausal women SO SEMINARS IN REPRODUCTIVE MEDICINE LA English DT Article DE premenopausal women; androgen insufficiency; testosterone therapy ID PREMATURE OVARIAN FAILURE; HUMAN-IMMUNODEFICIENCY-VIRUS; HYPOACTIVE SEXUAL DESIRE; SURGICALLY MENOPAUSAL WOMEN; HORMONE-BINDING GLOBULIN; POSTMENOPAUSAL WOMEN; YOUNG-WOMEN; ANDROGEN DEFICIENCY; CIRCULATING ANDROGENS; ESTERIFIED ESTROGENS AB Testosterone therapy for postmenopausal women and women with surgical menopause, albeit controversial, is becoming more widespread. However, only limited data are available to support its use in premenopausal women. Androgens have important biological roles in young women, influencing bone and muscle mass, mood and well-being, and libido. Pathophysiological states affecting ovarian and adrenal function or both may result in androgen deficiency in premenopausal women. Young women with hypothalamic amenorrhea, premature ovarian failure, oophorectomy, premenstrual syndrome, acquired immunodeficiency wasting syndrome, adrenal insufficiency, and hypopituitarism may have testosterone deficiency. Young women with loss of libido may also have testosterone deficiency. Medications that may lead to testosterone insufficiency include oral estrogen, oral contraceptives, and corticosteroids. Testosterone deficiency in young women may be underdiagnosed because the symptoms generally are nonspecific and the measurement of total and free testosterone is inaccurate with commonly used techniques. Only a few studies investigating the effects of testosterone therapy have been performed thus far in premenopausal women. Long-term trials evaluating safety and effectiveness of testosterone therapy in premenopausal women are lacking. Common adverse effects include hirsutism and acne, which reverse with discontinuation of treatment. The availability of testosterone regimens specifically designed for women is expected to help maintain testosterone levels within the normal range and clarify whether the apparent beneficial effects of testosterone therapy are physiological or pharmacological. C1 Univ Ioannina, Sch Med, Dept Obstet & Gynecol, GR-45110 Ioannina, Greece. NIH, Mark O Hatfield Clin Res Ctr, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. RP Kalantaridou, SN (reprint author), Univ Ioannina, Sch Med, Dept Obstet & Gynecol, Panepistimiou Ave, GR-45110 Ioannina, Greece. EM sophia_kalantaridou@hotmail.com NR 64 TC 8 Z9 9 U1 3 U2 3 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 1526-8004 J9 SEMIN REPROD MED JI Semin. Reprod. Med. PD APR PY 2006 VL 24 IS 2 BP 106 EP 114 DI 10.1055/s-2006-939569 PG 9 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 037QN UT WOS:000237162100007 PM 16633984 ER PT J AU Reynolds, SJ Risbud, AR Shepherd, ME Rompalo, AM Ghate, MV Godbole, SV Joshi, SN Divekar, AD Gangakhedkar, RR Bollinger, RC Mehendale, SM AF Reynolds, SJ Risbud, AR Shepherd, ME Rompalo, AM Ghate, MV Godbole, SV Joshi, SN Divekar, AD Gangakhedkar, RR Bollinger, RC Mehendale, SM TI High rates of syphilis among STI patients are contributing to the spread of HIV-1 in India SO SEXUALLY TRANSMITTED INFECTIONS LA English DT Article; Proceedings Paper CT 15th Congress of the International-Society-for-Sexually-Transmitted-Diseases-Research CY JUL 27-30, 2003 CL Ottawa, CANADA SP Int Soc Sexually Transmitted Dis Res ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUALLY-TRANSMITTED-DISEASES; GENITAL ULCER DISEASE; FEMALE SEX WORKERS; DAR-ES-SALAAM; RISK-FACTORS; NORTHERN THAILAND; HAEMOPHILUS-DUCREYI; HIV-1-INFECTED MEN; HOMOSEXUAL MEN AB Background: Recent syphilis outbreaks have raised concern regarding the potential enhancement of HIV transmission. The incidence of syphilis and its association with HIV-1 infection rates among a cohort of sexually transmitted infection (STI) clinic attendees was investigated. Methods: 2732 HIV-1 seronegative patients attending three STI and one gynaecology clinic, were enrolled from 1993 - 2000 in an ongoing prospective cohort study of acute HIV-1 infection in Pune, India. At screening and quarterly follow up visits, participants underwent HIV-1 risk reduction counselling, risk behaviour assessment and HIV/STI screening that included testing for serological evidence of syphilis by RPR with TPHA confirmation. Patients with genital ulcers were screened with dark field microscopy. Results: Among 2324 participants who were HIV-1 and RPR seronegative at baseline, 172 participants were found to have clinical or laboratory evidence of syphilis during follow up (5.4 per 100 person years, 95% CI 4.8 to 6.5 per 100 person years). Independent predictors of syphilis acquisition based on a Cox proportional hazards model included age less than 20 years, lack of formal education, earlier calendar year of follow up, and recent HIV-1 infection. Based on a median follow up time of 11 months, the incidence of HIV-1 was 5.8 per 100 person years ( 95% CI 5.0 to 6.6 per 100 person years). Using a Cox proportional hazards model to adjust for known HIV risk factors, the adjusted hazard ratio of HIV-1 infection associated with incident syphilis was 4.44 ( 95% CI 2.96 to 6.65; p< 0.001). Conclusions: A high incidence rate of syphilis was observed among STI clinic attendees. The elevated risk of HIV-1 infection that was observed among participants with incident syphilis supports the hypothesis that syphilis enhances the sexual transmission of HIV-1 and highlights the importance of early diagnosis and treatment of syphilis. C1 Johns Hopkins Univ, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. Natl AIDS Res Inst, Pune, Maharashtra, India. RP Reynolds, SJ (reprint author), American Embassy Kampala, POB 7007, Kampala, Uganda. EM sjr@jhmi.edu FU FIC NIH HHS [5 D43 TW00010-AITRP]; NIAID NIH HHS [AI 01633, AI 35173, AI 41369, K24 AI001633, N01 AI035173] NR 44 TC 59 Z9 65 U1 0 U2 4 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1368-4973 J9 SEX TRANSM INFECT JI Sex. Transm. Infect. PD APR 1 PY 2006 VL 82 IS 2 BP 121 EP 126 DI 10.1136/sti.2005.015040 PG 6 WC Infectious Diseases SC Infectious Diseases GA 031TT UT WOS:000236727700009 PM 16581736 ER PT J AU Kuwata, K Yamada, S Kinuwaki, E Naito, M Mitsuya, H AF Kuwata, K Yamada, S Kinuwaki, E Naito, M Mitsuya, H TI Peripheral hemophagocytosis: An early indicator of advanced systemic inflammatory response syndrome/hemophagocytic syndrome SO SHOCK LA English DT Article DE peripheral hemophagocytosis; systemic inflammatory response syndrome; hemophagocytic syndrome; inflammation; macrophage; early diagnosis ID DIFFERENTIATION ANTIGEN; MONOCLONAL-ANTIBODY; SCAVENGER RECEPTORS; BINDING-PROTEIN; CENTENARIANS; MACROPHAGES; PHAGOCYTES; GUIDELINES; MONOCYTES; INFECTION AB Peripheral hemophagocytosis (PHP) is seen in patients with hemophagocytic syndrome (HPS), a clinical status in which activated macrophages play a role in its pathogenesis. The inflammatory state, systemic inflammatory response syndrome (SIRS), is also associated with activated macrophages. However, the link between HPS and SIRS and the clinical implications of PHP remain to be determined. In the present work, we examined the clinical utility and impact of the detection of PHP and the link between HPS and SIRS. We studied the clinical and laboratory profiles of 322 SIRS patients (174 men; mean age, 68 +/- 22 years; range, 16-99 years) who visited an urban hospital specializing in respiratory, cardiovascular, digestive, renal diseases, general surgery, and orthopedics in Japan. Peripheral hemophagocytosis was detected in 40 (23 men; mean age, 81.3 +/- 8.7 years; range, 63-98 years) of 322 patients on 3 +/- 2 days after SIRS diagnosis as determined with a "blunt-edged-smear" method differing from the conventional "feather-edged smear" method. The incidence of advanced SIRS and ensuing death in the SIRS+PHP+ group (37 and 21 of 40, respectively) was significantly greater than in the SIRS+PHP- group (82 and 17 of 282) (P < 0.01). The duration from SIRS diagnosis to recovery in 19 SIRS+PHP+ surviving patients (26 18 days) was longer than that in 19 age-matched SIRS+PHP- surviving patients who initially presented comparable clinical profiles (6 +/- 3 days) (P < 0.001). Bone marrow analysis in all 7 patients having PHP and SIRS showed no HIPS initially (< 3% hemophagocytes), but all subsequently developed HPS at 7 +/- 1 days after the diagnosis, confirmed by the presence of 9% +/- 13% hemophagocytes in the bone marrow. Electron microscopic and immunohistochemical analyses revealed that PHP was derived from hemophagocytes in the bone marrow. The present data strongly suggest that PHP detection could serve as an early indicator for advanced SIRS and/or HPS and that the use of the blunt-edged method is preferable for PHP detection. C1 Kumamoto Univ, Grad Sch Med, Dept Hematol, Kumamoto 8608556, Japan. Kumamoto Univ, Grad Sch Med, Dept Infect Dis, Kumamoto 8608556, Japan. Konan Hosp, Kyouninkai Inc, Kumamoto, Japan. Niigata Univ, Dept Cellular Funct, Div Cellular & Mol Pathol, Grad Sch Med & Dent Sci, Niigata, Japan. NCI, Expt Retrovirol Sect, HIV & AIDS Malignancy Branch, Bethesda, MD 20892 USA. RP Mitsuya, H (reprint author), Kumamoto Univ, Sch Med, Dept Hematol & Infect Dis, 1-1-1 Honjo, Kumamoto 8608556, Japan. EM hmitsuya@helix.nih.gov NR 37 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1073-2322 J9 SHOCK JI Shock PD APR PY 2006 VL 25 IS 4 BP 344 EP 350 DI 10.1097/01.shk.0000209520.82377.41 PG 7 WC Critical Care Medicine; Hematology; Surgery; Peripheral Vascular Disease SC General & Internal Medicine; Hematology; Surgery; Cardiovascular System & Cardiology GA 030RN UT WOS:000236652100005 PM 16670635 ER PT J AU Gooding, HC Organista, K Burack, J Biesecker, BB AF Gooding, HC Organista, K Burack, J Biesecker, BB TI Genetic susceptibility testing from a stress and coping perspective SO SOCIAL SCIENCE & MEDICINE LA English DT Article DE genetic testing; stress and coping; adaptation; health behavior; genetic counseling ID BREAST-CANCER SUSCEPTIBILITY; NONPOLYPOSIS COLORECTAL-CANCER; HEREDITARY COLON-CANCER; AFRICAN-AMERICAN WOMEN; HUNTINGTONS-DISEASE; OVARIAN-CANCER; PSYCHOLOGICAL DISTRESS; ALZHEIMERS-DISEASE; DECISION-MAKING; FOLLOW-UP AB Four theories of health behavior and of stress and coping are reviewed for their ability to illuminate interest in uptake and outcomes of genetic testing for adult-onset diseases. These theories are the Health Belief Model, the Theory of Planned Behavior (TPB), the Common Sense Model of Self-regulation (CSM), and the Transactional Model of Stress and Coping (TMSC). Basic concepts of each theory are discussed, followed by evidence from the literature supporting the relevance of these concepts to the understanding of genetic testing for four adult-onset diseases: Huntington's disease, Alzheimer's disease, hereditary breast/ovarian cancer, and hereditary colorectal cancer. Emphasis is placed on the finding that a decision to undergo genetic testing may be considered as a way to cope with both the cognitive and affective concerns that arise from living at increased risk of developing a disease in the future. The potential value of genetic testing for reducing uncertainty about and gaining a sense of control over one's risk of developing a chronic disease is highlighted. We argue that theories which focus on stress and coping provide a useful framework for future studies of genetic testing decisions for adult-onset disease risk. Published by Elsevier Ltd. C1 NHRGI, NIH, Bethesda, MD 20892 USA. Univ Calif Berkeley, Sch Publ Hlth, Div Hlth & Med Sci, Berkeley, CA 94720 USA. Univ Calif Berkeley, Sch Social Welf, Berkeley, CA 94720 USA. Univ Calif Berkeley, Div Community Hlth & Human Dev, Sch Publ Hlth, Berkeley, CA 94720 USA. RP Biesecker, BB (reprint author), NHRGI, NIH, Bethesda, MD 20892 USA. EM holly.gooding@ucsf.edu; barbarab@mail.nih.gov NR 83 TC 41 Z9 41 U1 3 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0277-9536 J9 SOC SCI MED JI Soc. Sci. Med. PD APR PY 2006 VL 62 IS 8 BP 1880 EP 1890 DI 10.1016/j.socscimed.2005.08.041 PG 11 WC Public, Environmental & Occupational Health; Social Sciences, Biomedical SC Public, Environmental & Occupational Health; Biomedical Social Sciences GA 037QD UT WOS:000237161000005 PM 16198036 ER EF