FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hirshberg, B Cochran, C Skarulis, MC Libutti, SK Alexander, HR Wood, BJ Chang, R Kleiner, DE Gorden, P AF Hirshberg, B Cochran, C Skarulis, MC Libutti, SK Alexander, HR Wood, BJ Chang, R Kleiner, DE Gorden, P TI Malignant insulinoma - Spectrum of unusual clinical features SO CANCER LA English DT Article DE insulinoma; beta-cell tumor; neoplasia; endocrine ID ISLET-CELL-CARCINOMA; HEPATIC ARTERIAL CHEMOEMBOLIZATION; METASTATIC INSULINOMA; ENDOCRINE TUMORS; LIVER METASTASES; PANCREAS; HYPOGLYCEMIA; SOMATOSTATIN; SURVIVAL; PATIENT AB BACKGROUND. Malignant insulinoma occurs in a few patients with insulinoma. Due to the small sample of patients, there are little data regarding their clinical manifestation as well as the preferred treatment modalities. The aims of the current study were to summarize the National Institutes of Health experience during the last two decades and to conduct a critical review of the current literature. METHODS. The authors identified 10 patients with metastatic insulmoma. RESULTS. The patients presented with four patterns of clinical behavior. First, four patients presented with lymph node metastasis and, after surgical excision, maintained a prolonged tumor-free survival. Second, four patients presented with metastatic disease to the liver, which appeared years after the initial diagnosis and presumed curative surgery. Third, one patient presented with a large alpha-fetoprotein-secreting liver mass. Finally, 9 of the 10 patients had a prolonged survival. Various treatment modalities were used to control hypoglycernia. Short-term benefits were most often achieved with embolization and diazoxide. Less successful modalities included radiofrequency ablation, radical debulking surgery, verapamil therapy, octreotide therapy, and chemotherapy. CONCLUSIONS. The current study, as well as others, suggested that metastatic insulinoma may have a variable natural history. After the initial surgical resection, the biology of the tumor, rather than any treatment modality, was most likely the major determinant of long-term survival. Published 2005 by the American Cancer Society. C1 NIDDKD, Div Intramural Res, NIH, Bethesda, MD 20892 USA. NCI, Surg Metab Branch, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Anat Pathol, Bethesda, MD 20892 USA. RP Hirshberg, B (reprint author), Pfizer Inc, Eastern Point Rd,MS 8260-2502, Groton, CT 06340 USA. EM Boaz.Hirshberg@pfizer.com OI Kleiner, David/0000-0003-3442-4453 FU Intramural NIH HHS [Z99 CL999999] NR 39 TC 68 Z9 72 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUL 15 PY 2005 VL 104 IS 2 BP 264 EP 272 DI 10.1002/cncr.21179 PG 9 WC Oncology SC Oncology GA 943CZ UT WOS:000230331000007 PM 15937909 ER PT J AU Rao, VK Wangsa, D Robey, RW Huff, L Honjo, Y Hung, J Knutsen, T Ried, T Bates, SE AF Rao, VK Wangsa, D Robey, RW Huff, L Honjo, Y Hung, J Knutsen, T Ried, T Bates, SE TI Characterization of ABCG2 gene amplification manifesting as extrachromosomal DNA in mitoxantrone-selected SF295 human glioblastoma cells SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID DOUBLE-MINUTE CHROMOSOMES; IN-SITU HYBRIDIZATION; DIHYDROFOLATE-REDUCTASE GENE; CANCER RESISTANCE PROTEIN; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; MULTIDRUG-RESISTANCE; MYELODYSPLASTIC SYNDROME; MICROSATELLITE INSTABILITY; N-MYC AB The human ABCG2 gene, located on chromosome 4, encodes an ATP-binding cassette half-transporter that has been shown to confer resistance to chemotherapeutic agents. Relatively little is known about the mechanisms controlling expression of ABCG2. In previous studies, we had shown that overexpression of ABCG2 can result from rearrangement or gene amplification involving chromosome 4. To better characterize the mechanisms of ABCG2 overexpression, SF295 glioblastoma cells were exposed to increasing amounts of mitoxantrone to generate the SF295 MX50, MX100, MX250, and MX500 sublines, maintained in mitoxantrone concentrations ranging from 50 to 500 nmol/L. Northern blot analysis confirmed overexpression of ABCG2 mRNA, and immunoblot analysis demonstrated increased protein expression in the selected cell lines. Efflux of BODIPY-prazosin confirmed a functional protein. ABCG2 gene amplification was observed in all resistant sublines, as determined by Southern blot analysis. Fluorescence in situ hybridization (FISH) revealed amplification of ABCG2 via double minute chromosomes (dmins) detected in metaphase chromosome spreads in the SF295 MX50 and MX100 sublines. At higher levels of drug selection, in the MX250 and MX500 sublines, fewer dmins were observed but homogeneously staining regions (hsr) were visible with FISH analysis, revealing reintegration of the ABCG2 gene into multiple chromosomes. Spectral karyotyping (SKY) demonstrated multiple clonal and nonclonal rearrangements of chromosome 4, including hsrs. These results suggest that amplification of ABCG2 occurred initially in the form of dmins, followed by chromosomal reintegration of the amplicon at multiple sites. This occurred with increasing drug-selection pressure, generating a more stable genotype. (D 2005 Elsevier Inc. All rights reserved. C1 NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Bates, SE (reprint author), NCI, Canc Res Ctr, NIH, Bldg 10,Room 12C103,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sebates@helix.nih.gov NR 37 TC 14 Z9 15 U1 1 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JUL 15 PY 2005 VL 160 IS 2 BP 126 EP 133 DI 10.1016/j.cancergencyto.2004.12.013 PG 8 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 947OY UT WOS:000230656900003 PM 15993268 ER PT J AU Jansen, AP Camalier, CE Colburn, NH AF Jansen, AP Camalier, CE Colburn, NH TI Epidermal expression of the translation inhibitor programmed cell death 4 suppresses tumorigenesis SO CANCER RESEARCH LA English DT Article ID INITIATION-FACTOR 4A; NF-KAPPA-B; NEGATIVE C-JUN; MESSENGER-RNA; TRANSFORMATION SUPPRESSOR; MALIGNANT TRANSFORMATION; ANCHORAGE INDEPENDENCE; AP-1 TRANSACTIVATION; TUMOR PROMOTION; CELL-DEATH AB Programmed cell death 4 (Pdcd4) is a novel repressor of in vitro transformation. Pdcd4 directly inhibits the helicase activity of eukaryotic translation initiation factor 4A, a component of the translation initiation complex. To ascertain whether Pdcd4 suppresses tumor development in vivo, we have generated transgenic mice that overexpress Pdcd4 in the epidermis (K14-Pdcd4). K14-regulated Pdcd4 expression caused a neonatal short-hair phenotype due to early catagen entry compared with matched wild-type siblings. In response to the 7,12-dimethylbenz(a)anthracene (DMBA)/12-O-tetradecanoylphorbol-13-acetate (TPA) mouse skin carcinogenesis protocol, K14-Pdcd4 mice showed significant reductions in papilloma formation, carcinoma incidence, and papilloma-to-carcinoma conversion frequency compared with wild-Lype mice. The translational efficiency of an mRNA engineered to form a structured 5' untranslated region (UTR) was attenuated in primary keratinocytes when Pdcd4 was overexpressed. Pdcd4 inhibited by 46% TPA-induced activator protein-1 (AP-1)-dependent transcription, an event required for tumorigenesis. CDK4 and ornithine decarboxylase (ODC) are candidates for Pdcd4-regulated translation as their mRNAs contain 5' structured UTRs. In K14-Pdcd4 primary keratinocytes expressing activated Ha-Ras to mimic DMBA-initiated epidermis, ODC and CDK4 protein levels were decreased by 40% and 46%, respectively. Expression of a protein encoded by 5' unstructured mRNA showed no change. These results extend to an in vivo model the observations that Pdcd4 inhibits both translation initiation and AP-1 activation while decreasing benign tumor development and malignant progression. The K14-Pdcd4 mice seem to validate translation initiation as a novel target for cancer prevention. C1 Natl Canc Inst Frederick, Canc Res Ctr, Lab Canc Prevent, Gene Regulat Sect, Ft Detrick, MD 21702 USA. RP Jansen, AP (reprint author), Natl Canc Inst Frederick, Canc Res Ctr, Lab Canc Prevent, Gene Regulat Sect, Bldg 567,Room 187, Ft Detrick, MD 21702 USA. EM ajansen@nciferf.gov NR 48 TC 159 Z9 169 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2005 VL 65 IS 14 BP 6034 EP 6041 DI 10.1158/0008-5472.CAN-04-2119 PG 8 WC Oncology SC Oncology GA 947HG UT WOS:000230633400011 PM 16024603 ER PT J AU Goodison, S Yuan, G Sloan, D Kim, R Li, C Popescu, NC Urquidi, V AF Goodison, S Yuan, G Sloan, D Kim, R Li, C Popescu, NC Urquidi, V TI The RhoGAP protein DLC-1 functions as a metastasis suppressor in breast cancer cells SO CANCER RESEARCH LA English DT Article ID GTPASE-ACTIVATING PROTEIN; POLYMERASE-CHAIN-REACTION; HEPATOCELLULAR-CARCINOMA; GENE-EXPRESSION; PLASMINOGEN-ACTIVATOR; TUMOR-METASTASIS; IN-VIVO; GROWTH; MODEL; LINES AB The identification of molecular signatures characteristic of tumor cells that are capable of metastatic spread is required for the development of therapeutic interventions to abrogate this lethal process. To facilitate this, we have previously characterized an experimental system in which the role of candidate metastasis-related genes can be screened and tested. Monoclonal cell lines M4A4 and NM2C5 are spontaneously occurring sublines of the MDA-MB-435 cell breast tumor cell line that exhibit phenotypic differences in growth, invasion, and metastatic efficiency in athymic mice. In this study, transcriptional profiles of these cell lines were created using oligonucleotide microarrays representing over 12,000 genes. Intensity modeling and hierarchical clustering analysis identified a 171-gene expression signature that correlated with metastatic phenotype and highlighted several GTPase signaling components. Restoration of one of these GTPases, deleted in liver cancer-1 (DLC-1), in metastatic M4A4 cells to levels observed in the nonmetastatic NM2C5 cell line resulted in the inhibition of migration and invasion in vitro and a significant reduction in the ability of these cells to form pulmonary metastases in athymic mice. These studies show the utility of expression profiling, in an appropriate experimental system, to identify genetic determinants of metastatic sufficiency. The finding that DLC-1 can act as a metastasis-suppressor gene supports an influential role for GTPase signaling in tumor progression. C1 Univ Florida, Dept Pathol, Jacksonville, FL USA. Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA. Univ Calif San Diego, Rebecca & John Moores Canc Ctr, La Jolla, CA USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Natl Canc Inst, Canc Res Ctr, Expt Carcinogenesis Lab, Bethesda, MD USA. RP Goodison, S (reprint author), Univ Florida, Hlth Sci Ctr, Shands Hosp, Dept Pathol, 655 W 8th St, Jacksonville, FL 32209 USA. EM steve.goodison@jax.ufl.edu FU NCI NIH HHS [CA R01 108597, R01 CA108597, R01 CA108597-02] NR 53 TC 111 Z9 119 U1 1 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2005 VL 65 IS 14 BP 6042 EP 6053 DI 10.1158/0008-5472.CAN-04-3043 PG 12 WC Oncology SC Oncology GA 947HG UT WOS:000230633400012 PM 16024604 ER PT J AU Hodge, DR Xiao, WH Peng, BJ Cherry, PC Munroe, DJ Farrar, WL AF Hodge, DR Xiao, WH Peng, BJ Cherry, PC Munroe, DJ Farrar, WL TI Enforced expression of superoxide dismutase 2/manganese superoxide dismutase disrupts autocrine interleukin-6 stimulation in human multiple myeloma cells and enhances dexamethasone-induced apoptosis SO CANCER RESEARCH LA English DT Article ID NF-KAPPA-B; AP-1 TRANSCRIPTION FACTOR; BREAST-CANCER CELLS; GROWTH-FACTOR; CARCINOMA-CELLS; IN-VITRO; GLUCOCORTICOID-RECEPTOR; IONIZING-RADIATION; OXIDATIVE STRESS; GENE-EXPRESSION AB Autocrine pathways of proliferative and antiapoptotic growth factors represent a serious impediment to the treatment of many types of tumors. In particular, interleukin-6 (IL-6), a pleiotropic cytokine known to play a critical role in the survival and growth of multiple myeloma cells, participates in an autocrine. stimulation loop that serves to inhibit the induction of apoptosis during chemotherapy. Manganese syperoxide dismutase (MnSOD) is an important antioxidant enzyme encoded by the SOD2 gene that attenuates oxidative free radicals in the mitochondria by catalyzing the formation of hydrogen peroxide from superoxide radicals. Transcription factor activity and binding is influenced by the oxidative state of cells, and dysregulation of MnSOD levels can result in abnormal patterns of gene expression. In the human multiple myeloma cell line IM-9, an autocrine IL-6 loop exists, which enables the cell to resist the effects of dexamethasone, a common treatment for multiple myeloma. Here, we show that SOD2 expression is epigenetically silenced in IM-9 cells, and replacement of MnSOD reduces cell proliferation and partially restores susceptibility to dexamethasone. The restoration of MnSOD also serves to decrease the expression levels of IL-6 by reducing the ability of activator protein-1, an important mediator of IL-6 expression in multiple myeloma cells, to bind to its enhancer site. These results show the importance of free radical-mediated dysregulation of autocrine growth factor loops in tumor cells and their effect on cell growth and response to chemotherapy. C1 NCI, Lab Mol Immunoregulat, Cytokine Mol Mech Sect, Ctr Canc Res, Frederick, MD 21701 USA. NCI, Lab Mol Technol, Frederick, MD 21701 USA. Sci Applicat Int Corp Frederick, Intramural Res Support Program, Basic Res Program, Frederick, MD USA. RP Hodge, DR (reprint author), NCI, Lab Mol Immunoregulat, Cytokine Mol Mech Sect, Ctr Canc Res, 1050 Boyles St,Bldg 560,Room 31-76, Frederick, MD 21701 USA. EM hodje@mail.ncifcrf.gov RI Xiao, Weihua/N-2775-2013 OI Xiao, Weihua/0000-0001-9102-6326 NR 53 TC 23 Z9 23 U1 2 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 15 PY 2005 VL 65 IS 14 BP 6255 EP 6263 DI 10.1158/0008-5472.CAN-04-4482 PG 9 WC Oncology SC Oncology GA 947HG UT WOS:000230633400035 PM 16024627 ER PT J AU Muanza, TM Cotrim, AP McAuliffe, M Sowers, AL Baum, BJ Cook, JA Feldchtein, F Amazeen, P Coleman, CN Mitchell, JB AF Muanza, TM Cotrim, AP McAuliffe, M Sowers, AL Baum, BJ Cook, JA Feldchtein, F Amazeen, P Coleman, CN Mitchell, JB TI Evaluation of radiation-induced oral mucositis by optical coherence tomography SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-III; CHALLENGING COMPLICATION; CONCURRENT CHEMOTHERAPY; RANDOMIZED-TRIAL; SOFT-TISSUE; RADIOTHERAPY; CANCER; DIAGNOSIS; BIOPSY; CHEMORADIOTHERAPY AB Purpose: Optical coherence tomography (OCT) imaging was evaluated to determine if radiation-induced mucosal damage could be noninvasively monitored in real time and correlated with histopathologic findings. Experimental Design: Female C3H mice, ages 7 to 9 weeks, four per group, were immobilized in a custom-made Lucite jig and received 0, 15, 22.5, and 25 Gy in a single fraction to their oral cavity. OCT images were acquired of proximal, middle, and distal aspects of the dorsum of the tongue on days 0, 1, 3, 5, and 7 post-irradiation. Animals were sacrificed on day 7 and samples taken for histologic evaluation. OCT images were visually examined and also quantified by image analysis and compared with histologic findings. Results: Tongues removed 7 days post-irradiation showed no visible damage; however, upon staining with toluidine blue, ulcers at the base of the tongue became visible (100% for 25 Gy, 75% after 22.5 Gy, and 0% after 15 Gy). Visual inspection of OCT images qualitatively compared with histologic findings and quantitative image analysis of the OCT images (effective light penetration depth) revealed significant changes 7 days post-irradiation compared with unirradiated controls for the base of the tongue. Conclusions: OCT allows for direct noninvasive real-time acquisition of digitally archivable images of oral mucosa and can detect radiation-induced changes in the mucosa before visual manifestation. OCT may be a useful technique to quantify subclinical radiation-induced mucosal injury in experimental chemoradiation clinical trials. C1 Natl Inst Dent & Craniofacial Res, Radiat Oncol Branch, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, Radiat Biol Branch, NCI, Bethesda, MD USA. Natl Inst Dent & Craniofacial Res, Gene Therapy & Therapeut Branch, Bethesda, MD USA. McGill Univ, Hlth Ctr, Montreal, PQ H3A 2T5, Canada. CIT, Biomed Imaging Res Serv Stn, NIH, Cleveland, OH USA. Imalux Corp, Cleveland, OH USA. RP Mitchell, JB (reprint author), NCI, Radiat Biol Branch, Room B3-B69,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jbm@helix.nih.gov NR 35 TC 23 Z9 26 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 15 PY 2005 VL 11 IS 14 BP 5121 EP 5127 DI 10.1158/1078-0432.CCR-05-0403 PG 7 WC Oncology SC Oncology GA 945VG UT WOS:000230529800010 PM 16033826 ER PT J AU Diallo, DA Doumbo, OK Plowe, CV Wellems, TE Emanuel, EJ Hurst, SA AF Diallo, DA Doumbo, OK Plowe, CV Wellems, TE Emanuel, EJ Hurst, SA TI Community permission for medical research in developing countries SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID PROTECTING COMMUNITIES; INFORMED-CONSENT; CLINICAL-RESEARCH; MALARIA; AFRICA; TRIAL; MALI AB The realization of the need for community consent, or more accurately community permission, for research has occurred relatively recently. Practical experience with it is scarce. This article describes the Malian experience at a malaria vaccine study site. We describe a process that we used to obtain community permission. The process had 6 steps: (1) a study of the community, (2) an introductory meeting with leaders, (3) formal meetings with leaders, (4) personal visits with leaders, (5) meetings with traditional health practitioners, and (6) recognition that obtaining permission is a dynamic process. We discuss documentation of community permission for research and outline the reasons why the community-level process we used was practically necessary and ethically appropriate. Far from competing with the individual informed consent process, the process of obtaining community permission both initiated and facilitated the process of disclosure for individual informed consent. C1 Univ Bamako, Fac Med Pharm & Dent, Dept Hematol, Malaria Res & Training Ctr, Bamako, Mali. Univ Bamako, Fac Med Pharm & Dent, Dept Parasitol, Malaria Res & Training Ctr, Bamako, Mali. Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Diallo, DA (reprint author), Univ Bamako, Fac Med Pharm & Dent, Dept Hematol, Malaria Res & Training Ctr, Bamako, Mali. EM dadiallo@mrtcbko.org NR 19 TC 52 Z9 52 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 15 PY 2005 VL 41 IS 2 BP 255 EP 259 DI 10.1086/430707 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 936YF UT WOS:000229890800019 PM 15983925 ER PT J AU Robertson, SM Penzak, SR Lane, J Pau, AK Mican, JM AF Robertson, SM Penzak, SR Lane, J Pau, AK Mican, JM TI A potentially significant interaction between efavirenz and phenytoin: A case report and review of the literature SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID HUMAN CYP2B6 GENE; HUMAN HEPATOCYTES; PLASMA-LEVELS; PHARMACOKINETICS; INDUCTION AB Although it has not been demonstrated yet, phenytoin is expected to reduce efavirenz exposure through coinduction of cytochrome P450 (CYP) 3A4 and CYP2B6. Conversely, efavirenz has been shown in vitro to inhibit the enzymes responsible for phenytoin metabolism, CYP2C9 and CYP2C19. We report a case in which a potential bidirectional drug interaction between phenytoin and efavirenz resulted in lower-than-expected efavirenz concentrations and elevated phenytoin levels. Therapeutic drug monitoring was used in this case to ensure adequate efavirenz exposure. C1 NIAID, Clin Pharmacokinet Res Lab, Ctr Clin, Dept Pharm,NIH, Bethesda, MD 20892 USA. NIAID, Off Clin Res, NIH, Bethesda, MD 20892 USA. RP Robertson, SM (reprint author), NIAID, Clin Pharmacokinet Res Lab, Ctr Clin, Dept Pharm,NIH, Bldg 10,Rm 1 N 257, Bethesda, MD 20892 USA. EM robertsonsa@cc.nih.gov NR 19 TC 12 Z9 12 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 15 PY 2005 VL 41 IS 2 BP E15 EP E18 DI 10.1086/431208 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 936YF UT WOS:000229890800033 PM 15983905 ER PT J AU Sun, X Lewandoski, M Deng, CX Harfe, B Verheyden, J AF Sun, X Lewandoski, M Deng, CX Harfe, B Verheyden, J TI Conditional inactivation of Fgfr1 in mouse defines its role in limb bud establishment, outgrowth and digit patterning. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 Univ Wisconsin, Genet Lab, Madison, WI 53706 USA. NCI, Ft Detrick, MD 21702 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Univ Florida, Gainesville, FL 32610 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 76 BP 590 EP 590 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800097 ER PT J AU Itoh, M Ishitani, T Matsumoto, K Chitnis, AB AF Itoh, M Ishitani, T Matsumoto, K Chitnis, AB TI Nrarp functions to modulate neural crest cell differentiation by regulating LEF1 protein stability. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NIH, Bethesda, MD 20892 USA. Nagoya Univ, Aichi 4648602, Japan. NR 0 TC 0 Z9 0 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 128 BP 601 EP 601 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800149 ER PT J AU Cohen, TV Stewart, CL AF Cohen, TV Stewart, CL TI The nuclear envelope protein Man1 is required for angiogenesis in the embryonic yolk sac. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 Natl Canc Inst, Frederick, MD 21702 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 134 BP 602 EP 602 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800155 ER PT J AU Fernandez-Diaz, LC Fiorenza, MT Jenkins, NA Copeland, NG Blasi, F AF Fernandez-Diaz, LC Fiorenza, MT Jenkins, NA Copeland, NG Blasi, F TI A Prep-1 null mutation is embryonic lethal at E7.5. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 Univ Viat Salute San Raffaele, Milan, Italy. FIRC Inst Mol Oncol, IFOM, Milan, Italy. Natl Canc Inst, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 140 BP 603 EP 603 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800161 ER PT J AU Rong, Q Pfeifer, K AF Rong, Q Pfeifer, K TI Regulatory mechanisms of H19 DMR at the heterologous Afp locus. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NICHHD, Sect Genom Imprinting, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 BP 603 EP 603 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800162 ER PT J AU Brody, T Kuzin, A Odenwald, WF AF Brody, T Kuzin, A Odenwald, WF TI Transcription regulation of drosophila neuroblast temporal determinants. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 167 BP 609 EP 609 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800188 ER PT J AU Kuzin, A Brody, T Odenwald, W AF Kuzin, A Brody, T Odenwald, W TI Analysis of nerfin-1 transcriptional and post-transcriptional regulation. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NINDS, Neural Cell Fate Determinants Sect, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 167 BP 609 EP 609 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800189 ER PT J AU Palmer, MB Boss, JM Wade, PA AF Palmer, MB Boss, JM Wade, PA TI Regulation of snail transcription: A chromatin structure approach. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 Emory Univ, Atlanta, GA 30322 USA. NIEHS, Res Triangle Pk, NC 27709 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 170 BP 609 EP 610 PG 2 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800191 ER PT J AU Das, B Cai, L Carter, MG Sharov, AA Piao, YL Ko, MS Brown, DD AF Das, B Cai, L Carter, MG Sharov, AA Piao, YL Ko, MS Brown, DD TI Genome-wide expression profiling of Xenopus laevis metamorphosis programs. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 Carnegie Inst Washington, Dept Embryol, Baltimore, MD 21210 USA. NIA, Dev Genom & Aging Sect, Genet Lab, NIH, Baltimore, MD 21224 USA. RI Ko, Minoru/B-7969-2009; Carter, Mark/B-5089-2010 OI Ko, Minoru/0000-0002-3530-3015; 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 178 BP 611 EP 611 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800199 ER PT J AU Hong, SK Haldin, CE Ulanch, PE Lawson, ND Weinstein, BM Dawid, IB Hukriede, NA AF Hong, SK Haldin, CE Ulanch, PE Lawson, ND Weinstein, BM Dawid, IB Hukriede, NA TI The zebrafish kohtalo/trap230 gene is required for the development of the brain, neural crest and pronephric kidney. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 176 BP 611 EP 611 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800197 ER PT J AU Angerer, LM Newman, LA Angerer, RC AF Angerer, LM Newman, LA Angerer, RC TI Differential protein turnover, negative autoregulation, and transcriptional repression precisely regulate SoxB1 levels in the early sea urchin embryo. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NIDCR, NIH, Bethesda, MD 20892 USA. Univ Rochester, Rochester, NY 14634 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 196 BP 615 EP 615 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800216 ER PT J AU Pei, WH Feldman, B AF Pei, WH Feldman, B TI Morpholino knockdown uncovers a requirement for FoxH1/Schmalspur for normal morphogenesis and survival during gastrulation. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NHGRI, Med Genet Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 218 BP 619 EP 619 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800238 ER PT J AU Castranio, T Mishina, Y AF Castranio, T Mishina, Y TI Neural tube patterning and the role of BMP2. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NIEHS, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 237 BP 623 EP 623 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800257 ER PT J AU Miura, S Mishina, Y AF Miura, S Mishina, Y TI Requirement of the anterior visceral endoderm for the establishment of anterior-posterior axis and mesoderm patterning. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 240 BP 624 EP 624 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800260 ER PT J AU Nakaya, M Tessarollo, L Habas, R He, X Yamaguchi, TP AF Nakaya, M Tessarollo, L Habas, R He, X Yamaguchi, TP TI Role of Daam genes in the regulation of cell polarity during mammalian embryogenesis. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NCI, NIH, Ft Detrick, MD 21702 USA. Univ Med & Dent New Jersey, Piscataway, NJ 08854 USA. Harvard Univ, Sch Med, Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 248 BP 625 EP 626 PG 2 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800268 ER PT J AU Park, JM Kohn, MJ Bruinsma, M Vech, C Mukherjee, I Fuhrmann, S Grinberg, A Love, PE Latham, KE Intine, RV DePamphilis, M Maraia, RJ AF Park, JM Kohn, MJ Bruinsma, M Vech, C Mukherjee, I Fuhrmann, S Grinberg, A Love, PE Latham, KE Intine, RV DePamphilis, M Maraia, RJ TI Disruption of the mouse La gene leads to failure to develop beyond blastocyst and prohibits embryonic stem cell development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NICHD, NIH, Bethesda, MD 20892 USA. Temple Univ, Sch Med, Philadelphia, PA 19140 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 250 BP 626 EP 626 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800270 ER PT J AU McMains, VC Kreppel, L Kimmel, AR AF McMains, VC Kreppel, L Kimmel, AR TI Regulation of Dictyostelium development by presenilin and GSK3 signaling. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NIDDK, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 256 BP 627 EP 627 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800276 ER PT J AU Driver, EC Pryor, SP Hill, P Turner, J Ruther, U Biesecker, LG Griffith, AJ Kelley, MW AF Driver, EC Pryor, SP Hill, P Turner, J Ruther, U Biesecker, LG Griffith, AJ Kelley, MW TI A role for hedgehog signaling in development of the mammalian cochlear sensory epithelium. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NIDCD, NIH, Bethesda, MD USA. NIDCD, NIH, Rockville, MD USA. Univ Dusseldorf, D-4000 Dusseldorf, Germany. NHGRI, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 276 BP 631 EP 632 PG 2 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800296 ER PT J AU Jacques, BE Layman, EM Lewandoski, M Kelley, MW AF Jacques, BE Layman, EM Lewandoski, M Kelley, MW TI The FGF8 signaling pathway regulates differentiation during the development of the cochlear sensory epithelium. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NIDCD, NIH, Bethesda, MD 20892 USA. NCI, NIH, Ft Detrick, MD 21702 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 275 BP 631 EP 631 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800295 ER PT J AU Chalasani, K John, K Yeo, SY Chitnis, A Brewster, R AF Chalasani, K John, K Yeo, SY Chitnis, A Brewster, R TI Role of N-Cadherin-mediated cell adhesion in regulating neurogenesis. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 UMBC, Baltimore, MD USA. CSHL, Watson Sch Biol Sci, New York, NY USA. NICHD, NIH, Bethesda, MD 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 281 BP 632 EP 633 PG 2 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800301 ER PT J AU Mathers, P Voronina, V Kozhemyakina, E Bennett, V Zamora, B Lewandoski, M AF Mathers, P Voronina, V Kozhemyakina, E Bennett, V Zamora, B Lewandoski, M TI Induction and cell fate specification in early eye development. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 W Virginia Univ, Sensory Neurosci Res Ctr, Morgantown, WV 26506 USA. NCI, Genet Vertebrate Dev Sect, Frederick, MD 21701 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 291 BP 634 EP 635 PG 2 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800311 ER PT J AU Mukhopadhyay, M Morasso, M Ma, C Westphal, H AF Mukhopadhyay, M Morasso, M Ma, C Westphal, H TI Role of Dkk2 in the maintenance of ocular surface morphology. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NICHD, Lab Mamallian Genes & Dev, NIH, Bethesda, MD USA. NIAMS, Dev Skin Biol Unit, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 292 BP 635 EP 635 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800312 ER PT J AU Ohsugi, M Hess, S Dean, J AF Ohsugi, M Hess, S Dean, J TI Oocyte-specific MATER affects microtubule formation and may suppress protein secretion. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 363 BP 649 EP 649 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800381 ER PT J AU Underwood, SP Wilson, CW Mishina, Y Lewandoski, M AF Underwood, SP Wilson, CW Mishina, Y Lewandoski, M TI BMP signals control interdigital programmed cell death by regulating FGF signaling. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NCI, CCR, NIH, Frederick, MD 21701 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 401 BP 657 EP 657 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800419 ER PT J AU Zhu, JJ Nguyen, MT Mackem, S AF Zhu, JJ Nguyen, MT Mackem, S TI Temporal requirements of sonic hedgehog expression for specifying different digits. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NCI, Pathol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 434 BP 664 EP 664 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800451 ER PT J AU Bok, J Wu, DK AF Bok, J Wu, DK TI Multiple roles of Gli3 in mouse inner ear patterning. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 Natl Inst Deafness & Other Commun Disorders, Rockville, MD 20850 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 447 BP 666 EP 666 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800464 ER PT J AU Waters, ST Wilson, C Lewandoski, M AF Waters, ST Wilson, C Lewandoski, M TI A requirement for Gbx1 in normal locomotion. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NCI, Canc & Dev Biol Lab, NIH, Frederick, MD 21702 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 448 BP 666 EP 667 PG 2 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800465 ER PT J AU Lewandoski, M Timofeeva, O Naillat, F Richman, C Pajni-Underwood, S Wilson, C Vainio, S Perantoni, AO AF Lewandoski, M Timofeeva, O Naillat, F Richman, C Pajni-Underwood, S Wilson, C Vainio, S Perantoni, AO TI The mouse Fgf8 gene is required for nephrogenesis but not for somitogenesis. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 NCI, Canc & Dev Biol Lab, Frederick, MD 21702 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. Univ Oulu, Bioctr, Fac Sci & Med, FIN-90014 Oulu, Finland. Univ Oulu, Dept Biochem, Fac Sci & Med, FIN-90014 Oulu, Finland. 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 529 BP 683 EP 683 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800545 ER PT J AU Harrington, MJ Tsang, M Dawid, I Halpern, M Brewster, R AF Harrington, MJ Tsang, M Dawid, I Halpern, M Brewster, R TI Role of desmosomal cadherins in zebrafish vascular morphogenesis. SO DEVELOPMENTAL BIOLOGY LA English DT Meeting Abstract CT 64th Annual Meeting of the Society-for-Development-Biology CY JUL 27-AUG 01, 2005 CL San Francisco, CA SP Soc Dev Biol C1 Univ Maryland Baltimore Cty, Baltimore, MD 21250 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15261 USA. NICHD, NIH, Bethesda, MD 20892 USA. Carnegie Inst Washington, Baltimore, MD 21210 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 0012-1606 J9 DEV BIOL JI Dev. Biol. PD JUL 15 PY 2005 VL 283 IS 2 MA 556 BP 689 EP 689 PG 1 WC Developmental Biology SC Developmental Biology GA 947YS UT WOS:000230683800572 ER PT J AU Manne, U Srivastava, RG Srivastava, S AF Manne, U Srivastava, RG Srivastava, S TI Recent advances in biomakers for cancer diagnosis and treatment SO DRUG DISCOVERY TODAY LA English DT Review ID SURROGATE END-POINTS; PROSTATE-SPECIFIC ANTIGEN; METASTATIC BREAST-CANCER; DRUG DEVELOPMENT; OVARIAN-CANCER; LUNG-CANCER; PROMOTER HYPERMETHYLATION; HEPATOCELLULAR-CARCINOMA; MONOCLONAL-ANTIBODY; PROTEOMIC PATTERNS AB With the availability of new technologies and the increased interest of medical practitioners to use molecular biomarkers in early detection and diagnosis, and in the prediction of therapeutic treatment efficacy and clinical outcomes, the academic and research institutions, as well as the pharmaceutical industry have increased their efforts to develop novel molecular biomarkers for several human diseases, including cancer. The identification of molecular biomarkers also enables the development of a new generation of diagnostic products and to integrate diagnostics and therapeutics. This integrated approach will aid in 'individualizing' the medical practice. Here, we address issues related to the development of biomarkers, novel technological platforms used for drug development, future technologies and strategies for validating biomarkers for their clinical utility. C1 Univ Alabama, Dept Pathol, Tuscaloosa, AL 35487 USA. Natl Canc Inst, Organ Syst Branch, Bethesda, MD 20892 USA. Natl Canc Inst, Canc Biomarkers Res Grp, Bethesda, MD 20892 USA. RP Manne, U (reprint author), Univ Alabama, Dept Pathol, Tuscaloosa, AL 35487 USA. EM srivasts@mail.nih.gov RI Manne, Upender/D-5613-2009 NR 78 TC 44 Z9 47 U1 0 U2 13 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6446 J9 DRUG DISCOV TODAY JI Drug Discov. Today PD JUL 15 PY 2005 VL 10 IS 14 BP 965 EP 976 DI 10.1016/S1359-6446(05)03487-2 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 942AB UT WOS:000230254200008 PM 16023055 ER PT J AU Lee, J Jung, ID Chang, WK Park, CG Cho, DY Shin, EY Seo, DW Kim, YK Lee, HW Han, JW Lee, HY AF Lee, J Jung, ID Chang, WK Park, CG Cho, DY Shin, EY Seo, DW Kim, YK Lee, HW Han, JW Lee, HY TI p85 beta-PIX is required for cell motility through phosphorylations of focal adhesion kinase and p38 MAP kinase SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE p85 beta-PIX; lysophosphatidic acid; p38 MAP kinase; focal adhesion kinase ID WISKOTT-ALDRICH SYNDROME; INTERACTING EXCHANGE FACTOR; PROTEIN-COUPLED RECEPTOR; LYSOPHOSPHATIDIC ACID; P21-ACTIVATED KINASE; GROWTH-FACTOR; ENDOTHELIAL-CELLS; ACTIN REORGANIZATION; NEURITE OUTGROWTH; SIGNALING PATHWAY AB Lysophosphatidic acid (LPA) mediates diverse biological responses, including cell migration, through the activation of G-protein-coupled receptors. Recently, we have shown that LPA stimulates p2l-activated kinase (PAK) that is critical for focal adhesion kinase (FAK) phosphorylation and cell motility. Here, we provide the direct evidence that p85 beta-PIX is required for cell motility of NIH-3T3 cells by LPA through FAK and p38 MAP kinase phosphorylations. LPA induced p85 beta-PIX binding to FAK in NIH-3T3 cells that was inhibited by pretreatment of the cells with phosphomositide 3-kinase inhibitor, LY294002. Furthermore, the similar inhibition of the complex formation was also observed, when the cells were transfected with either p85 beta-PIX mutant that cannot bind GIT or dominant negative mutants of Rac1 (N17Rac1) and PAK (PAK-PID). Transfection of the cells with specific p85 beta-PIX siRNA led to drastic inhibition of LPA-induced FAK phosphorylation, peripheral redistribution of p85 beta-PIX with FAK and GIT1, and cell motility. p85 [ PTX was also required for p38 MAP kinase phosphorylation induced by LPA. Finally, dominant negative mutant of Rho (N19Rho)-transfected cells did not affect PAK activation, while the cells stably trainsfected with p85 beta-PIX siRNA or N17Rac1 showed the reduction of LPA-induced PAK activation. Taken together, the present data suggest that p85 beta-PIX, located downstream of Rac1, is a key regulator for the activations of FAK or p38 MAP kinase and plays a pivotal role in focal complex formation and cell motility induced by LPA. (c) 2005 Elsevier Inc. All rights reserved. C1 Konyang Univ, Coll Med, Dept Pharmacol, Nonsan 320711, South Korea. Chungbuk Natl Univ, Coll Med, Dept Biochem, Cheongju 361763, South Korea. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Kwandong Univ, Coll Med, Gangneung 210701, South Korea. Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea. RP Lee, HY (reprint author), Konyang Univ, Coll Med, Dept Pharmacol, Nonsan 320711, South Korea. EM hoi@konyang.ac.kr NR 62 TC 39 Z9 39 U1 0 U2 3 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 15 PY 2005 VL 307 IS 2 BP 315 EP 328 DI 10.1016/j.yexcr.2005.03.028 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 939JM UT WOS:000230068800004 PM 15893751 ER PT J AU Yan, ZJ Cui, KR Murray, DM Ling, C Xue, YT Gerstein, A Parsons, R Zhao, KJ Wang, WD AF Yan, ZJ Cui, KR Murray, DM Ling, C Xue, YT Gerstein, A Parsons, R Zhao, KJ Wang, WD TI PBAF chromatin-remodeling complex requires a novel specificity subunit, BAF200, to regulate expression of selective interferon-responsive genes SO GENES & DEVELOPMENT LA English DT Article DE SWI/SNF; BAF; PBAF; RSC; chromatin remodeling; interferon ID YEAST SWI/SNF COMPLEX; MULTISUBUNIT COMPLEX; NUCLEOSOME; RSC; ENHANCEMENT; LOCALIZES; PRODUCTS; PROTEINS; PROMOTER; BINDING AB PBAF and BAF are two chromatin-remodeling complexes of the SWI/SNF family essential for mammalian transcription and development. Although these complexes share eight identical subunits, only PBAF can facilitate transcriptional activation by nuclear receptors in vitro. Here we show that these complexes have selectivity in mediating transcription of different interferon-responsive genes. The selectivity by PBAF requires a novel subunit, BAF200, but not the previously described PBAF-specificity subunit, BAF180 (Polybromo). Our study provides in vivo evidence that PBAF and BAF regulate expression of distinct genes, and suggests that BAF200 plays a key role in PBAF function. C1 NIA, Genet Lab, Baltimore, MD 21224 USA. NHLBI, Lab Blood Immunol, NIH, Bethesda, MD 20892 USA. Columbia Univ, Inst Canc Genet, New York, NY 10032 USA. RP Wang, WD (reprint author), NIA, Genet Lab, Baltimore, MD 21224 USA. EM wangw@grc.nia.nih.gov FU NCI NIH HHS [R01 CA082783, R01 CA082783-06] NR 29 TC 110 Z9 115 U1 0 U2 12 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 JUL 15 PY 2005 VL 19 IS 14 BP 1662 EP 1667 DI 10.1101/gad.1323805 PG 6 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 946AO UT WOS:000230544500003 PM 15985610 ER PT J AU Inga, A Reamon-Buettner, SM Borlak, J Resnick, MA AF Inga, A Reamon-Buettner, SM Borlak, J Resnick, MA TI Functional dissection of sequence-specific NKX2-5 DNA binding domain mutations associated with human heart septation defects using a yeast-based system SO HUMAN MOLECULAR GENETICS LA English DT Article ID CARDIAC CONDUCTION SYSTEM; TRANSCRIPTION FACTOR; CSX/NKX2.5 HOMEOPROTEIN; GENE NKX2-5; DISEASE; P53; GATA-4; OLIGONUCLEOTIDES; PATHWAYS; LINEAGE AB Human heart development requires an orderly coordination of transcriptional programs, with the homeodomain protein NKX2-5 being one of the key transcription factors required for the differentiation of mesodermal progenitor cells. Indeed, lack of Nkx2-5 in mice arrests heart development prior to looping, resulting in embryonic lethality. There are 28 germline NKX2-5 mutations identified in humans that are associated with congenital heart disease, and we recently reported multiple somatic mutations in patients with complex cardiac malformations. To address the functional consequences of single and multiple mutations of NKX2-5, we developed a functional assay in the budding yeast Saccharomyces cerevisiae, which could determine transactivation capacity and specificity of expressed NKX2-5 alleles towards targeted response element (RE) sequences. We focused on mutants of the third helix, which provides DNA binding specificity, and characterized mutations that were highly associated with either ventricular (VSD) or atrioventricular (AVSD) septal defects. Individual mutants exhibited partial to complete loss of function and differences in transactivation capacity between the various REs. The mutants also exhibited gene dosage rather than dominant effects on transcription. Surprisingly, all AVSD patients (22/23) had a single K183E mutation in the DNA binding domain, which resulted in transcriptional inactivation. None of the VSD patients had this mutation; yet 14/29 had at least one mutation in the third helix leading to either inactivation or reduction of NKX2-5 transactivation. Therefore, mutations of somatic origin in the binding domains of NKX2-5 were associated specifically with AVSD or VSD and resulted in loss of protein function. C1 NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. Fraunhofer Inst Toxicol & Expt Med, Dept Drug Res & Med Biotechnol, D-30625 Hannover, Germany. RP Resnick, MA (reprint author), NIEHS, Chromosome Stabil Sect, Mol Genet Lab, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM Juergen.Borlak@item.fraunhofer.de; resnick@niehs.nih.gov NR 43 TC 24 Z9 30 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL 15 PY 2005 VL 14 IS 14 BP 1965 EP 1975 DI 10.1093/hmg/ddi202 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 941HL UT WOS:000230205800006 PM 15917268 ER PT J AU Lim, JH Booker, AB Luo, T Williams, T Furuta, Y Lagutin, O Oliver, G Sargent, TD Fallon, JR AF Lim, JH Booker, AB Luo, T Williams, T Furuta, Y Lagutin, O Oliver, G Sargent, TD Fallon, JR TI AP-2 alpha selectively regulates fragile X mental retardation-1 gene transcription during embryonic development SO HUMAN MOLECULAR GENETICS LA English DT Article ID TISSUE-SPECIFIC EXPRESSION; FACTOR AP-2; FMR1 PROMOTER; XENOPUS-LAEVIS; NEURAL CREST; TRANSGENIC MICE; DNA-BINDING; IN-VIVO; SP1; MORPHOGENESIS AB Fragile X syndrome (FXS) is almost always caused by silencing of the FMR1 gene. The defects observed in FXS indicate that the normal FMR1 gene has a range of functions and plays a particularly prominent role during development. However, the mechanisms regulating FMR1 expression in vivo are not known. Here, we have tested the role of the transcription factor AP-2 alpha in regulating Fmr1 expression. Chromatin immunoprecipitation showed that AP-2 alpha associates with the Fmr1 promoter in vivo. Furthermore, Fmr1 transcript levels are reduced > 4-fold in homozygous null AP-2 alpha mutant mice at embryonic day 18.5 when compared with normal littermates. Notably, AP-2 alpha exhibits a strong gene dosage effect, with heterozygous mice showing similar to 2-fold reduction in Fmr1 levels. Examination of conditional AP-2 alpha mutant mice indicates that this transcription factor plays a major role in regulating Fmr1 expression in embryos, but not in adults. We further investigated the role of AP-2 alpha in the developmental regulation of Fmr1 expression using the Xenopus animal cap assay. Over-expression of a dominant-negative AP-2 alpha in Xenopus embryos led to reduced Fmr1 levels. Moreover, exogenous wild-type AP-2 alpha rescued Fmr1 expression in embryos where endogenous AP-2 alpha had been suppressed. We conclude that AP-2 alpha associates with the Fmr1 promoter in vivo and selectively regulates Fmr1 transcription during embryonic development. C1 Brown Univ, Dept Neurosci, Providence, RI 02912 USA. NICHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. Univ Colorado, Hlth Sci Ctr, Dept Craniofacial Biol & Cell & Dev Biol, Denver, CO 80262 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biochem & Mol Biol, Houston, TX 77030 USA. St Jude Childrens Res Hosp, Dept Genet, Memphis, TN 38105 USA. RP Fallon, JR (reprint author), Brown Univ, Dept Neurosci, POB 1953,190 Thayer St, Providence, RI 02912 USA. EM justin_fallon@brown.edu FU NCRR NIH HHS [P20 RR015578-060002, RR15578, P20 RR015578]; NEI NIH HHS [EY12162]; NIDCR NIH HHS [DE12728]; NIMH NIH HHS [MH065094]; NINDS NIH HHS [P01 NS039321, NS39321, P01 NS039321-050002] NR 46 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL 15 PY 2005 VL 14 IS 14 BP 2027 EP 2034 DI 10.1093/hmg/ddi207 PG 8 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 941HL UT WOS:000230205800011 PM 15930016 ER PT J AU Ottolenghi, C Omari, S Garcia-Ortiz, JE Uda, M Crisponi, L Forabosco, A Pilia, G Schlessinger, D AF Ottolenghi, C Omari, S Garcia-Ortiz, JE Uda, M Crisponi, L Forabosco, A Pilia, G Schlessinger, D TI Foxl2 is required for commitment to ovary differentiation SO HUMAN MOLECULAR GENETICS LA English DT Article ID TRANSCRIPTION FACTOR FOXL2; GERMLINE STEM-CELLS; SEX DETERMINATION; MAMMALIAN OVARY; INVERSUS SYNDROME; TRANSGENIC MICE; MOUSE; FAILURE; TESTIS; EXPRESSION AB Genetic control of female sex differentiation from a bipotential gonad in mammals is poorly understood. We find that mouse XX gonads lacking the forkhead transcription factor Foxl2 form meiotic prophase oocytes, but then activate the genetic program for somatic testis determination. Pivotal Foxl2 action thus represses the male gene pathway at several stages of female gonadal differentiation. This suggests the possible continued involvement of sex-determining genes in maintaining ovarian function throughout female reproductive life. C1 NIA, Genet Lab, Baltimore, MD 21224 USA. George Washington Univ, Grad Program Genet, Washington, DC 20052 USA. Osped Microcitem, Consiglio Nazl Ric, Ist Neurogenet & Neurofarmacol, I-09100 Cagliari, Italy. Univ Modena & Reggio Emilia, Dipartimento Maternoinfantile, Policlin, I-41100 Modena, Italy. RP Schlessinger, D (reprint author), NIA, Genet Lab, Baltimore, MD 21224 USA. EM schlessingerd@grc.nia.nih.gov FU Telethon [GP0049Y01] NR 46 TC 161 Z9 167 U1 2 U2 13 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD JUL 15 PY 2005 VL 14 IS 14 BP 2053 EP 2062 DI 10.1093/hmg/ddi210 PG 10 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 941HL UT WOS:000230205800014 PM 15944199 ER PT J AU D'Souza, T Agarwal, R Morin, PJ AF D'Souza, T Agarwal, R Morin, PJ TI Phosphorylation of claudin-3 at threonine 192 by cAMP-dependent protein kinase regulates tight junction barrier function in ovarian cancer cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EPITHELIAL-CELLS; GENE-EXPRESSION; CYCLIC-AMP; MOLECULAR PHYSIOLOGY; MAP KINASE; C ISOFORMS; PATHOPHYSIOLOGY; OVEREXPRESSION; IDENTIFICATION; DISRUPTION AB Claudins are integral membrane proteins essential in the formation and function of tight junctions (TJs). Disruption of TJs, which have essential roles in cell permeability and polarity, is thought to contribute to epithelial tumorigenesis. Claudin-3 and -4 are frequently overexpressed in ovarian cancer, but the molecular pathways involved in the regulation of these proteins are unclear. Interestingly, several studies have demonstrated a role for phosphorylation in the regulation of TJ complexes, although evidence for claudin phosphorylation is scarce. Here, we showed that claudin-3 and -4 can be phosphorylated in ovarian cancer cells. In vitro phosphorylation assays using glutathione S-transferase fusion constructs demonstrated that the C terminus of claudin-3 is an excellent substrate for cAMP-dependent protein kinase (PKA). Using site-directed mutagenesis, we identified a PKA phosphorylation site at amino acid 192 in the C terminus of claudin-3. Overexpression of the protein containing a T192D mutation, mimicking the phosphorylated state, resulted in a decrease in TJ strength in ovarian cancer cell line OVCA433. Our results suggest that claudin-3 phosphorylation by PKA, a kinase frequently activated in ovarian cancer, may provide a mechanism for the disruption of TJs in this cancer. In addition, our findings may have general implications for the regulation of TJs in normal epithelial cells. C1 NIA, Cellular & Mol Biol Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21287 USA. RP Morin, PJ (reprint author), NIA, Cellular & Mol Biol Lab, Ctr Gerontol Res, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM morinp@grc.nia.nih.gov NR 36 TC 126 Z9 131 U1 0 U2 7 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 15 PY 2005 VL 280 IS 28 BP 26233 EP 26240 DI 10.1074/jbc.M502003200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 943WT UT WOS:000230386800038 PM 15905176 ER PT J AU Su, D Novoselov, SV Sun, QA Moustafa, ME Zhou, Y Oko, R Hatfield, DL Gladyshev, VN AF Su, D Novoselov, SV Sun, QA Moustafa, ME Zhou, Y Oko, R Hatfield, DL Gladyshev, VN TI Mammalian selenoprotein thioredoxin-glutathione reductase - Roles in disulfide bond formation and sperm maturation SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXPRESSION PATTERN; ESCHERICHIA-COLI; REDOX REGULATION; MESSENGER-RNA; PEROXIDASE; PROTEIN; CELLS; GENE; IDENTIFICATION; SELENOCYSTEINE AB Thioredoxin reductases (TRs) are important redox regulatory enzymes, which control the redox state of thioredoxins. Mammals have cytosolic and mitochondrial TRs, which contain an essential selenocysteine residue and reduce cytosolic and mitochondrial thioredoxins. In addition, thioredoxin/glutathione reductase (TGR) was identified, which is a fusion of an N-terminal glutaredoxin domain and the TR module. Here we show that TGR is expressed at low levels in various tissues but accumulates in testes after puberty. The protein is particularly abundant in elongating spermatids at the site of mitochondrial sheath formation but is absent in mature sperm. We found that TGR can catalyze isomerization of protein and interprotein disulfide bonds and localized this function to its thiol domain. TGR targets include proteins that form structural components of the sperm, including glutathione peroxidase GPx4/PHGPx. Together, TGR and GPx4 can serve as a novel disulfide bond formation system. Both enzymes contain a catalytic selenocysteine consistent with the role of selenium in male reproduction. C1 Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. Univ Nebraska, Ctr Biotechnol, Lincoln, NE 68588 USA. NCI, NIH, Bethesda, MD 20892 USA. Queens Univ, Dept Anat & Cell Biol, Kingston, ON K7L 3N6, Canada. RP Gladyshev, VN (reprint author), Univ Nebraska, Dept Biochem, Lincoln, NE 68588 USA. EM vgladyshev1@unl.edu RI Su, Dan/B-1972-2010; Gladyshev, Vadim/A-9894-2013 FU NIGMS NIH HHS [GM065204] NR 39 TC 93 Z9 98 U1 2 U2 11 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 15 PY 2005 VL 280 IS 28 BP 26491 EP 26498 DI 10.1074/jbc.M503638200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 943WT UT WOS:000230386800065 PM 15901730 ER PT J AU Wieland, GD Nehmann, N Muller, D Eibel, H Siebenlist, U Suhnel, J Zipfel, PF Skerka, C AF Wieland, GD Nehmann, N Muller, D Eibel, H Siebenlist, U Suhnel, J Zipfel, PF Skerka, C TI Early growth response proteins EGR-4 and EGR-3 interact with immune inflammatory mediators NF-kappa B p50 and p65 SO JOURNAL OF CELL SCIENCE LA English DT Article DE EGR; NF-kappa B; IL-2; TNF-alpha; ICAM-1 ID NF-KAPPA-B; RESONANCE ENERGY-TRANSFER; NECROSIS-FACTOR-ALPHA; ACTIVATED T-CELLS; TRANSCRIPTION FACTORS; NGFI-A; LIGAND PROMOTER; BINDING-SITE; GENE; EXPRESSION AB Here, we characterize the basis for the T-cell-specific activity of the human zinc-finger protein early growth response factor 4 (EGR-4). A yeast two-hybrid screen showed interaction of EGR-4 with NF-kappa B p50. Using recombinant proteins, stable physical complex formation was confirmed for EGR-4 and EGR-3 with p50 and with p65 using glutathione-S-transferase pull-down assays and surface-plasmon-resonance and peptide-spot analyses. In vivo interaction of EGR-4 and EGR-3 with NF-kappa B p65 was demonstrated by immunoprecipitation experiments and fluorescence-resonance-energy transfer (FRET) analysis showing interaction in the nucleus of transfected Jurkat T cells. In transfection assays, EGR-p50 complexes were transcriptionally inactive and EGR-p65 complexes strongly activated transcription of the promoters of the human genes encoding the cytokines interleukin 2, tissue necrosis factor alpha and ICAM-1. The EGR-p65 complexes increased reporter-gene activity about 100-fold and thus exceeded the transcriptional activities of the p65 homodimer and the p65/p50 heterodimers. The major interaction domain for p65 was localized within the third zinc finger of EGR-4 using deletion mutants for pull-down assays and peptide-spot assays. By computer modeling, this interaction domain was localized to an cc-helical region and shown to have the central amino acids surface exposed and thus accessible for interaction. In summary, in T cells, the two zinc-finger proteins EGR-4 and EGR-3 interact with the specific nuclear mediator NF-kappa B and control transcription of genes encoding inflammatory cytokines. C1 Leibniz Inst Nat Prod Res & Infect Biol, Hans Knoell Inst, Dept Infect Biol, D-07745 Jena, Germany. Univ Freiburg, Res Grp Rheumatol, D-79106 Freiburg, Germany. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Inst Mol Biotechnol, Biocomp Grp, D-07745 Jena, Germany. RP Skerka, C (reprint author), Leibniz Inst Nat Prod Res & Infect Biol, Hans Knoell Inst, Dept Infect Biol, Butenbergstr 11A, D-07745 Jena, Germany. EM christine.skerka@hki-jena.de NR 36 TC 29 Z9 30 U1 1 U2 4 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 JUL 15 PY 2005 VL 118 IS 14 BP 3203 EP 3212 DI 10.1242/jcs.02445 PG 10 WC Cell Biology SC Cell Biology GA 955DF UT WOS:000231204700020 PM 16014385 ER PT J AU Ortaldo, JR Winkler-Pickett, RT Bere, EW Watanabe, M Murphy, WJ Wiltrout, RH AF Ortaldo, JR Winkler-Pickett, RT Bere, EW Watanabe, M Murphy, WJ Wiltrout, RH TI In vivo hydrodynamic delivery of cDNA encoding IL-2: Rapid, sustained redistribution, activation of mouse NK cells, and therapeutic potential in the absence of NKT cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; T-CELLS; TUMOR-IMMUNITY; IFN-GAMMA; CANCER-IMMUNOTHERAPY; METASTATIC MELANOMA; DOSE INTERLEUKIN-2; ANTITUMOR; INDUCTION; CYTOKINE AB In the present study, we have tested the ability of hydrodynamically delivered IL-2 cDNA to modulate the number and function of murine leukocyte subsets in different organs and in mice of different genetic backgrounds, and we have evaluated effects of this mode of gene delivery on established murine tumor metastases. Hydrodynamic administration of the IL-2 gene resulted in the rapid and transient production of up to 160 ng/ml IL-2 in the serum. The appearance of IL-2 was followed by transient production of IFN-gamma and a dramatic and sustained increase in NK cell numbers and NK-mediated cytolytic activity in liver and spleen leukocytes. In addition, significant increases in other lymphocyte subpopulations (e.g., NKT, T, and B cells) that are known to be responsive to IL-2 were observed following IL-2 cDNA plasmid delivery. Finally, hydrodynamic delivery of only 4 mu g of the IL-2 plasmid to mice bearing established lung and liver metastases was as effective in inhibiting progression of metastases as was the administration of large amounts (100,000 IU/twice daily) of IL-2 protein. Studies performed in mice bearing metastatic renal cell tumors demonstrated that the IL-2 cDNA plasmid was an effective treatment against liver metastasis and moderately effective against lung metastasis. Collectively, these results demonstrate that hydrodynamic delivery of relatively small amounts of IL-2 cDNA provides a simple and inexpensive method to increase the numbers of NK and NKT cells, to induce the biological effects of IL-2 in vivo for use in combination with other biological agents, and for studies of its antitumor activity. C1 NCI, Canc Res Ctr, Expt Immunol Lab, Frederick, MD 21702 USA. Univ Nevada, Sch Med, Dept Microbiol, Reno, NV 89557 USA. RP Ortaldo, JR (reprint author), NCI, Canc Res Ctr, Expt Immunol Lab, Bldg 560,Room 31-93, Frederick, MD 21702 USA. EM ortaldo@ncifcrf.gov FU NCI NIH HHS [N01 CO 12400] NR 32 TC 26 Z9 27 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 JUL 15 PY 2005 VL 175 IS 2 BP 693 EP 699 PG 7 WC Immunology SC Immunology GA 989BJ UT WOS:000233647600008 PM 16002664 ER PT J AU Correale, P Cusi, MG Del Vecchio, MT Aquino, A Prete, S Tsang, KY Micheli, L Nencini, C La Placa, M Montagnani, F Terrosi, C Caraglia, M Formica, V Giorgi, G Bonmassar, E Francini, G AF Correale, P Cusi, MG Del Vecchio, MT Aquino, A Prete, S Tsang, KY Micheli, L Nencini, C La Placa, M Montagnani, F Terrosi, C Caraglia, M Formica, V Giorgi, G Bonmassar, E Francini, G TI Dendritic cell-mediated cross-presentation of antigens derived from colon carcinoma cells exposed to a highly cytotoxic multidrug regimen with gemcitabine, oxaliplatin, 5-fluorouracil, and leucovorin, elicits a powerful human antigen-specific CTL response with antitumor activity in vitro SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEAT-SHOCK PROTEINS; THYMIDYLATE SYNTHASE; COLORECTAL-CANCER; CARCINOEMBRYONIC ANTIGEN; T-CELLS; IMMUNE-RESPONSES; SOLID TUMORS; CHEMOIMMUNOTHERAPY; IMMUNOTHERAPY; CHEMOTHERAPY AB Gemcitabine, oxaliplatin, leucovorin, and 5-fluorouracil (GOLF) is a novel multidrug regimen inducing high levels of necrosis and apoptosis in colon carcinoma cells. This regimen is also able to promote a process of Ag remodeling including up-regulation of immunotherapy targets like carcinoembryonic Ag (CEA), thymidylate synthase (TS). We have conducted a preclinical study aimed to investigate whether these drug-induced modifications would also enhance colon cancer cell immunogenicity. Several CTL lines were thus generated by in vitro stimulating human HLA-A(*)02.01(+) PBMCs, from normal donors and colon cancer patients, with autologous dendritic cells cross-primed with cell lysates of colon cancer cells untreated, irradiated, or previously exposed to different drug treatments including the GOLF regimen. Class I HLA-restricted cytolytic activity of these CTL lines was tested against colon cancer cells and CEA and TS gene transfected target cells. These experiments revealed that CTLs sensitized with GOLF-treated cancer cells were much more effective than those sensitized with the untreated colon carcinoma cells or those exposed to the other treatments. CTL lines sensitized against the GOLF-treated colon cancer cells, also expressed a greater percentage of T-lymphocyte precursors able to recognize TS- and CEA-derived peptides. These results suggest that GOLF regimen is a powerful antitumor and immunomodulating regimen that can make the tumor cells a suitable means to induce an Ag-specific CTL response. These results suggest that a rationale combination of GOLF chemotherapy with cytokine-based immunotherapy could generate a chemotherapy-modulated Ag-specific T-lymphocyte response in cancer patients able to destroy the residual disease survived to the cytotoxic drugs. C1 Univ Siena, Sch Med, Dept Human Pathol & Oncol, Oncol Sect, I-53100 Siena, Italy. Univ Siena, Sch Med, Dept Human Pathol & Oncol, Sect Pathol, I-53100 Siena, Italy. Univ Siena, Sch Med, Sect Virol, Dept Mol Biol, I-53100 Siena, Italy. Univ Siena, Sch Med, Giorgio Segre Dept Pharmacol, I-53100 Siena, Italy. Natl Canc Inst, Fdn Pascale, Expt Oncol Unit, Naples, Italy. Univ Roma Tor Vergata, Dept Neurosci, Med Oncol & Pharmacol Sect, Rome, Italy. NCI, Expt Oncol Sect, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. RP Francini, G (reprint author), Univ Siena, Sch Med, Dept Human Pathol & Oncol, Oncol Sect, Viale Bracci 11, I-53100 Siena, Italy. EM correale@unisi.it; Bonmasse@yahoo.com RI Caraglia, Michele/N-5670-2015; Correale, Pierpaolo/K-1640-2016 OI Caraglia, Michele/0000-0003-2408-6091; Correale, Pierpaolo/0000-0003-2154-6734 NR 49 TC 52 Z9 57 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 15 PY 2005 VL 175 IS 2 BP 820 EP 828 PG 9 WC Immunology SC Immunology GA 989BJ UT WOS:000233647600023 PM 16002679 ER PT J AU Babu, S Blauvelt, CP Kumaraswami, V Nutman, TB AF Babu, S Blauvelt, CP Kumaraswami, V Nutman, TB TI Diminished expression and function of TLR in lymphatic filariasis: A novel mechanism of immune dysregulation SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN DENDRITIC CELLS; TOLL-LIKE RECEPTORS; HUMAN MONOCYTES; BRUGIA-MALAYI; TETANUS VACCINATION; HELMINTH-PARASITES; TRYPANOSOMA-CRUZI; GENE-EXPRESSION; B-CELLS; RESPONSES AB Lymphatic filariasis is a disease characterized by immune dysregulation involving APC and T cell populations. To assess the contribution of TLR in mediating this dysregulation, we examined the expression of TLR1, TLR2, TLR4, and TLR9 on B cells and monocytes of filaria-infected and uninfected individuals. Baseline expression of TLR was significantly lower in B cells but not in monocytes of the filaria-infected group compared with the uninfected group. Upon stimulation with filarial Ag, a diminished up-regulation of TLR was observed in both B cells and monocytes of infected individuals. Finally, stimulation of B cells and monocytes with TLR ligands resulted in decreased B cell and monocyte activation/cytokine production, indicating a state of immune tolerance. This dysregulation is associated with diminished CD4(+) T cell production of IFN-gamma and IL-5. The diminished expression and function of TLR is thus a likely consequence of chronic Ag stimulation and could serve as a novel mechanism underlying the dysfunctional immune response in 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 NR 34 TC 68 Z9 72 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 JUL 15 PY 2005 VL 175 IS 2 BP 1170 EP 1176 PG 7 WC Immunology SC Immunology GA 989BJ UT WOS:000233647600063 PM 16002719 ER PT J AU Viboud, C Grais, RF Lafont, BAP Miller, MA Simonsen, L AF Viboud, C Grais, RF Lafont, BAP Miller, MA Simonsen, L CA Multinational Influenza Seasonal M TI Multinational impact of the 1968 Hong Kong influenza pandemic: Evidence for a smoldering pandemic SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID EXCESS MORTALITY; RESPIRATORY ILLNESS; ANTIGENIC VARIATION; ANTIBODY PATTERNS; AGE DISTRIBUTION; UNITED-STATES; EPIDEMIOLOGY; PNEUMONIA; TECUMSEH; VIRUS AB Background. The first pandemic season of A/H3N2 influenza virus (1968/1969) resulted in significant mortality in the United States, but it was the second pandemic season of A/H3N2 influenza virus (1969/1970) that caused the majority of deaths in England. We further explored the global pattern of mortality caused by the pandemic during this period. Methods. We estimated the influenza-related excess mortality in 6 countries (United States, Canada, England and Wales, France, Japan, and Australia) using national vital statistics by age for 1967-1978. Geographical and temporal pandemic patterns in mortality were compared with the genetic drift of the influenza viruses by analyzing hemagglutinin and neuraminidase sequences from GenBank. Results. In North America, the majority of influenza-related deaths in 1968/1969 and 1969/1970 occurred during the first pandemic season (United States, 70%; Canada, 54%). Conversely, in Europe and Asia, the pattern was reversed: 70% of deaths occurred during the second pandemic season. The second pandemic season coincided with a drift in the neuraminidase antigen. Conclusion. We found a consistent pattern of mortality being delayed until the second pandemic season of A/H3N2 circulation in Europe and Asia. We hypothesize that this phenomenon may be explained by higher preexisting neuraminidase immunity (from the A/H2N2 era) in Europe and Asia than in North America, combined with a subsequent drift in the neuraminidase antigen during 1969/1970. C1 NCI, Fogarty Int Ctr, Bethesda, MD 20892 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Viboud, C (reprint author), NCI, Fogarty Int Ctr, 16 Ctr Dr, Bethesda, MD 20892 USA. EM viboudc@mail.nih.gov RI Lafont, Bernard/B-7236-2014; OI Simonsen, Lone/0000-0003-1535-8526 NR 52 TC 102 Z9 107 U1 1 U2 8 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 15 PY 2005 VL 192 IS 2 BP 233 EP 248 DI 10.1086/431150 PG 16 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 943WX UT WOS:000230387300007 PM 15962218 ER PT J AU Kovacs, A Montepiedra, G Carey, V Pahwa, S Weinberg, A Frenkel, L Capparelli, E Mofenson, L Smith, E McIntosh, K Burchett, SK AF Kovacs, A Montepiedra, G Carey, V Pahwa, S Weinberg, A Frenkel, L Capparelli, E Mofenson, L Smith, E McIntosh, K Burchett, SK CA Pediat AIDS Clinical Trials Grp 366 Study Grp TI Immune reconstitution after receipt of highly active antiretroviral therapy in children with advanced or progressive HIV disease and complete or partial viral load response SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 8th Conference on Retroviruses and Opportunistic Infections CY FEB 04-08, 2001 CL CHICAGO, IL ID HUMAN-IMMUNODEFICIENCY-VIRUS; COMBINATION THERAPY; INFECTION; ADOLESCENTS; MORTALITY; FAILURE; COUNT AB We assessed CD4 cell recovery in 175 children with advanced human immunodeficiency virus disease who had received a 4-drug antiretroviral regimen and were categorized as viral load (VL) responders (VLRs), partial VLRs, or non-VLRs. Median CD4 cell counts increased from baseline to week 48, and, among children with maximal follow-up, increases in CD4 cell counts were sustained to week 96 among VLRs and partial VLRs but not among non-VLRs. For VL rebounders still in the study, CD4 cell counts remained increased for 32 weeks after VL rebound. Sustained immunologic benefits can be achieved even with partial VL response in children with advanced disease. C1 Univ So Calif, Maternal Child & Adolescent Ctr Infect Dis & Viro, Keck Sch Med, LAC&USC Med Ctr, Los Angeles, CA 90033 USA. Univ Calif San Diego, Pediat Pharmacol Unit, San Diego, CA 92103 USA. Univ Miami, Sch Med, Miami, FL USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. Univ Washington, Childrens Hosp & Med Ctr, Seattle, WA USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, Ctr Res Mothers & Children, Bethesda, MD 20892 USA. NIAID, Pediat Med Branch, Therapeut Res Plan, Div AIDS, Bethesda, MD 20892 USA. RP Kovacs, A (reprint author), Univ So Calif, Maternal Child & Adolescent Ctr Infect Dis & Viro, Keck Sch Med, LAC&USC Med Ctr, 1640 Marengo St, Los Angeles, CA 90033 USA. EM akovacs@usc.edu OI Mofenson, Lynne/0000-0002-2818-9808 FU NCRR NIH HHS [M01RR00043] NR 15 TC 16 Z9 18 U1 0 U2 0 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 JUL 15 PY 2005 VL 192 IS 2 BP 296 EP 302 DI 10.1086/430922 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 943WX UT WOS:000230387300013 PM 15962224 ER PT J AU McKenzie, FE Prudhomme, WA Magill, AJ Forney, JR Permpanich, B Lucas, C Gasser, RA Wongsrichanalai, C AF McKenzie, FE Prudhomme, WA Magill, AJ Forney, JR Permpanich, B Lucas, C Gasser, RA Wongsrichanalai, C TI White blood cell counts and malaria SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID FALCIPARUM-MALARIA; PARASITE DENSITY; DIAGNOSIS; MICROSCOPY; DEVICES AB White blood cells (WBCs) were counted in 4697 individuals who presented to outpatient malaria clinics in Maesod, Tak Province, Thailand, and Iquitos, Peru, between 28 May and 28 August 1998 and between 17 May and 9 July 1999. At each site and in each year, WBC counts in the Plasmodium falciparum-infected patients were lower than those in the Plasmodium vivax-infected patients, which, in turn, were lower than those in the uninfected patients. In Thailand, one-sixth of the P. falciparum-infected patients had WBC counts of < 4000 cells/mu L. Leukopenia may confound population studies that estimate parasite densities on the basis of an assumed WBC count of 8000 cells/mu L. For instance, in the present study, use of this conventional approach would have overestimated average asexual parasite densities in the P. falciparum-infected patients in Thailand by nearly one-third. C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Silver Spring, MD USA. Armed Forces Res Inst Med Sci, Bangkok 10400, Thailand. USN, Med Res Ctr Detachment, Lima, Peru. USN, Med Res Unit 2, Jakarta, Indonesia. RP McKenzie, FE (reprint author), NIH, Fogarty Int Ctr, Bldg 16, Bethesda, MD 20892 USA. EM em225k@nih.gov FU Intramural NIH HHS [Z99 TW999999] NR 29 TC 59 Z9 59 U1 2 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 JUL 15 PY 2005 VL 192 IS 2 BP 323 EP 330 DI 10.1086/431152 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 943WX UT WOS:000230387300017 PM 15962228 ER PT J AU Pan, YP Ma, BY Nussinov, R AF Pan, YP Ma, BY Nussinov, R TI CD4 binding partially locks the bridging sheet in gp120 but leaves the beta 2/3 strands flexible SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE HIV-1; gp120; bridging sheet; potential mean force; molecular dynamics ID HUMAN-IMMUNODEFICIENCY-VIRUS; INDUCED CONFORMATIONAL-CHANGES; TYPE-1 GP120; ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODIES; RECEPTOR-BINDING; HIV-1 ENTRY; NEUTRALIZATION; ENERGY; DOMAIN AB The structure of the free form HIV gp120, critical for therapeutic agent development, is unavailable due to its high flexibility Previous thermodynamic data, structural analysis and simulation results have suggested a large conformational change in the core domain upon CD4 binding. The bridging sheet, which consists of four beta-strands with beta 20/21 nestling against the inner/outer domains and beta 2/3 facing outward, more exposed to the solvent, was proposed to be unfolded in the native state. In order to test this proposition and to characterize the native conformations, we performed potential mean force (PMF) molecular dynamics (MD) simulations on the CD4-bound crystal structure. We Pushed the bridging sheet away from the inner and outer domain to explore the accessible conformational space for the bridging sheet. In addition, we performed conventional MD simulations on structures with the bridging sheet partially unfolded to investigate the stability of the association between the inner and outer domains. Based on the free energy profiles, we find that the whole bridging sheet is unlikely to unfold without other concurrent conformational changes. On the other hand, the partial bridging sheet, 0 strands 2/3, can switch its conformation from the folded to the unfolded state. Furthermore, relaxation of conformation with partially unfolded bridging sheet through MD simulations leads to a conformation with strands 20/21 quickly re-anchoring against the inner and outer domains. Such a conformation, although lacking some of the hydrophobic interactions present in the CD4-bound structure, displayed high stability as further indicated by other restrained MD simulations. The relevance of this conformation to the free form structure and the pathway for conformational change from the free form to the CD4-bound structure is discussed in detail in light of the available unliganded SIV gp120 crystal structure. (c) 2005 Elsevier Ltd. All rights reserved. C1 NCI, Basic Res Program, SAIC Frederick, Inc Lab Expt & Computat Biol, Ft Detrick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP NCI, Basic Res Program, SAIC Frederick, Inc Lab Expt & Computat Biol, Ft Detrick, MD 21702 USA. EM ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-12400] NR 40 TC 23 Z9 24 U1 0 U2 5 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 EI 1089-8638 J9 J MOL BIOL JI J. Mol. Biol. PD JUL 15 PY 2005 VL 350 IS 3 BP 514 EP 527 DI 10.1016/j.jmb.2005.05.009 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 942QK UT WOS:000230296700010 PM 15946678 ER PT J AU Fueger, PT Shearer, J Krueger, TM Posey, KA Bracy, DP Heikkinen, S Laakso, M Rottman, JN Wasserman, DH AF Fueger, PT Shearer, J Krueger, TM Posey, KA Bracy, DP Heikkinen, S Laakso, M Rottman, JN Wasserman, DH TI Hexokinase II protein content is a determinant of exercise endurance capacity in the mouse SO JOURNAL OF PHYSIOLOGY-LONDON LA English DT Article ID MUSCLE GLUCOSE-UPTAKE; RAT SKELETAL-MUSCLE; MCARDLES-DISEASE; WORKING MUSCLES; INSULIN; MICE; GLYCOGEN; OVEREXPRESSION; PHOSPHORYLATION; TRANSLOCATION AB Hexokinase (HK) II content is elevated in fatigue resistant muscle fibres and exercise trained muscle. The aim of this study was to determine if exercise capacity is dependent on muscle HK protein content. C57Bl/6 mice with a 50% HK knockout (HK+/-), no genetic manipulation (wild-type, WT) and an similar to 3-fold HK overexpression (HKTg) were tested. Mice (n = 12/group) completed both a maximal oxygen consumption ((V) over dot (o2,max)) test and an endurance capacity test (run at similar to 75% (V) over dot (o2,max)) on an enclosed treadmill equipped to measure gas exchange. Arterial and venous catheters were surgically implanted into separate groups of mice (n=9-11/group) in order to measure an index of muscle glucose uptake (R-g) during 30 min of treadmill exercise. Maximum work rate (0.95 +/- 0.05, 1.00 +/- 0.04 and 1.06 +/- 0.07 kg m min(-1)), (V) over dot (o2,max) (137 +/- 3, 141 +/- 4 and 141 +/- 5 ml kg(-1) min(-1)) and maximal respiratory exchange ratio (1.04 +/- 0.02, 1.00 +/- 0.03 and 1.04 +/- 0.04) were similar in HK+/-, WT and HKTg, respectively. Exercise endurance capacity (measured as time to exhaustion) increased as HK content increased (55 +/- 11, 77 +/- 5 and 98 +/- 9 min) and this was related to R-g measured in mice during 30 min of exercise (13 +/- 2,24 +/- 5 and 42 +/- 5 mu mol (100 g)(-1) min(-1)). Muscle glycogen in sedentary HK+/- mice and HK+/- mice following 30 min of exercise were significantly lower than in HKTg and WT mice. However, the net exercise-induced muscle glycogen breakdown was equal in the three genotypes. In summary, HK protein content within the range studied (a) was not associated with a difference in the capacity to perform maximal intensity exercise, (b) was a powerful determinant of the ability to sustain moderate intensity exercise, as reducing HK content impaired endurance and increasing HK content enhanced endurance, and (c) although directly related to exercise endurance, was not a determinant of net muscle glycogen usage during exercise. In conclusion, adaptations that increase HK protein content and/or functional activity such as regular exercise contribute to increased muscular endurance. C1 Vanderbilt Univ, Sch Med, Dept Mol Biol & Biophys, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Mouse Metab Phenotyping Ctr, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. Univ Kuopio, Dept Med, SF-70210 Kuopio, Finland. Univ Kuopio, AI Virtanen Inst Mol Sci, SF-70210 Kuopio, Finland. Univ Kuopio, Dept Biotechnol & Mol Med, SF-70210 Kuopio, Finland. RP Fueger, PT (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, 4321 Med Pk Dr,Suite 200, Durham, NC 27704 USA. EM patrick.fueger@duke.edu RI Heikkinen, Sami/L-1460-2013 OI Heikkinen, Sami/0000-0002-6083-2402 FU NIDDK NIH HHS [R01 DK-54902, U24 DK-59637, R01 DK054902, U24 DK059637] NR 42 TC 38 Z9 38 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3751 J9 J PHYSIOL-LONDON JI J. Physiol.-London PD JUL 15 PY 2005 VL 566 IS 2 BP 533 EP 541 DI 10.1113/jphysiol.2005.085043 PG 9 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 951DL UT WOS:000230909200019 PM 15878951 ER PT J AU Pozzilli, C Bagnato, F AF Pozzilli, C Bagnato, F TI Letter to the editor - Response to letter to the editor SO JOURNAL OF THE NEUROLOGICAL SCIENCES LA English DT Letter ID MULTIPLE-SCLEROSIS; CLINICAL-TRIALS; OPTIC NEURITIS; METHYLPREDNISOLONE C1 Univ Roma La Sapienza, Dept Neurol Sci, MS Clin, I-00185 Rome, Italy. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD USA. RP Pozzilli, C (reprint author), Univ Roma La Sapienza, Dept Neurol Sci, MS Clin, Vle Univ 30, I-00185 Rome, Italy. EM Carlo.pozzilli@uniroma1.it; bagnatof@ninds.nih.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-510X J9 J NEUROL SCI JI J. Neurol. Sci. PD JUL 15 PY 2005 VL 234 IS 1-2 BP 119 EP 120 DI 10.1016/j.jns.2005.03.044 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 946ZL UT WOS:000230611700021 ER PT J AU Risinger, RC Salmeron, BJ Ross, TJ Amen, SL Sanfilipo, M Hoffmann, RG Bloom, AS Garavan, H Stein, EA AF Risinger, RC Salmeron, BJ Ross, TJ Amen, SL Sanfilipo, M Hoffmann, RG Bloom, AS Garavan, H Stein, EA TI Neural correlates of high and craving during cocaine self-administration using BOLD fMRI SO NEUROIMAGE LA English DT Article DE functional magnetic resonance imaging; self-administration; cocaine; neurobiology; reinforcement; drug abuse ID CEREBRAL-BLOOD-FLOW; DOPAMINE TRANSPORTER OCCUPANCY; ORBITOFRONTAL CORTEX; INTRAVENOUS COCAINE; HUMAN BRAIN; INCENTIVE-SENSITIZATION; BASOLATERAL AMYGDALA; NUCLEUS-ACCUMBENS; SMOKED COCAINE; SPATIAL EXTENT AB Modern theories of drug dependence hold the hedonic effects of drug-taking central to understanding the motivation for compulsive drug use. Previous neuroimaging studies have begun to identify brain regions associated with acute drug effects after passive delivery. In this study, a more naturalistic model of cocaine self-administration (SA) was employed in order to identify those sites associated with drug-induced high and craving as measures of reward and motivation. Non-treatment seeking cocaine-dependent subjects chose both when and how often i.v. cocaine administration occurred within a medically supervised SA procedure. Both functional magnetic resonance imaging (fMRI) data and real-time behavioral ratings were acquired during the 1-h SA period. Drug-induced HIGH was found to correlate negatively with activity, in limbic, paralimbic, and mesocortical regions including the nucleus accumbens (NAc), inferior frontal/orbitofrontal gyrus (OFC), and anterior cingulate (AC), while CRAVING correlated positively with activity in these regions. This study provides the first evidence in humans that changes in subjective state surrounding cocaine self-administration reflect neural activity of the endogenous reward system. (c) 2005 Elsevier Inc. All rights reserved. C1 Med Coll Wisconsin, Dept Psychiat & Behav Med, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Biophys, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Biostat, Milwaukee, WI 53226 USA. Med Coll Wisconsin, Dept Pharmacol & Toxicol, Milwaukee, WI 53226 USA. NIDA, Neuroimaging Res Branch, IRP Baltimore, Baltimore, MD USA. RP Risinger, RC (reprint author), Med Coll Wisconsin, Dept Psychiat & Behav Med, 8701 Watertown Plank Rd, Milwaukee, WI 53226 USA. EM risinger@mcw.edu RI Ross, Thomas/B-7469-2008; Stein, Elliot/C-7349-2008; Salmeron, Betty Jo/M-1793-2016 OI Ross, Thomas/0000-0002-7745-3572; Salmeron, Betty Jo/0000-0003-1699-9333 FU NCRR NIH HHS [5M01 RR 00058]; NIDA NIH HHS [DA 09465, K23 DA 00486, R01 DA 11326] NR 57 TC 100 Z9 109 U1 5 U2 8 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 JUL 15 PY 2005 VL 26 IS 4 BP 1097 EP 1108 DI 10.1016/j.neuroimage.2005.03.030 PG 12 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 939KK UT WOS:000230071300013 PM 15886020 ER PT J AU Knight, DC Nguyen, HT Bandettini, PA AF Knight, DC Nguyen, HT Bandettini, PA TI The role of the human amygdala in the production of conditioned fear responses SO NEUROIMAGE LA English DT Article DE amygdala; conditioned fear responses; skin conductance response; fMRI; emotion; arousal; Pavlovian conditioning; learning and memory ID SKIN-CONDUCTANCE RESPONSES; ELECTRODERMAL ACTIVITY; PREFRONTAL CORTEX; FUNCTIONAL MRI; HUMAN BRAIN; FMRI; REPRESENTATION; VISUALIZATION; ACTIVATION; SOFTWARE AB The amygdala plays a central role in the acquisition and expression of fear memories. Laboratory animal studies indicate that the amygdala both receives sensory information and produces learned behavioral and autonomic fear responses. However, prior functional imaging research in humans has largely focused on amygdala activity elicited by fearful stimuli giving less attention to this region's role in the production of fear responses. In contrast, the present study used functional magnetic resonance imaging to investigate the amygdala's influence on the generation of conditional fear responses. Significant increases in amygdala activity were observed during the production of conditioned (learning-related), but not orienting, nonspecific, and unconditioned (nonlearning-related) skin conductance responses. Further, greater amygdala activity was demonstrated during conditioned response production than during conditioned stimulus presentation. These results suggest the amygdala not only responds to fearful stimuli, but also generates learning-related changes in human autonomic fear expression. Published by Elsevier Inc. C1 NIMH, Unit Funct Imaging Methods, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Knight, DC (reprint author), NIMH, Unit Funct Imaging Methods, Lab Brain & Cognit, Bldg 10,Room 1D80, Bethesda, MD 20892 USA. EM knightd@mail.nih.gov NR 38 TC 91 Z9 91 U1 2 U2 10 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 JUL 15 PY 2005 VL 26 IS 4 BP 1193 EP 1200 DI 10.1016/j.neuroimage.2005.03.020 PG 8 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 939KK UT WOS:000230071300023 PM 15961053 ER PT J AU Fujita, M Zoghbi, SS Creseenzo, MS Hong, J Musachio, JL Lu, JQ Liow, JS Seneca, N Tipre, DN Cropley, VL Imaizumi, M Gee, AD Seidel, J Green, MV Pike, VW Innis, RB AF Fujita, M Zoghbi, SS Creseenzo, MS Hong, J Musachio, JL Lu, JQ Liow, JS Seneca, N Tipre, DN Cropley, VL Imaizumi, M Gee, AD Seidel, J Green, MV Pike, VW Innis, RB TI Quantification of brain phosphodiesterase 4 in rat with (R)-[C-11]Rolipram-PET SO NEUROIMAGE LA English DT Article DE pharmacokinetics; plasma metabolites; cyclic AMP; small; animal PET; compartment analysis ID ADENOSINE-MONOPHOSPHATE PHOSPHODIESTERASE; CYCLIC-AMP PHOSPHODIESTERASE; ANIMAL PET SCANNER; IN-VIVO; ROLIPRAM; BINDING; INHIBITORS; PDE4; EXPRESSION; RECEPTORS AB Objective: Phosphodiesterase 4 (PDE4) catabolizes the second messenger 3', 5'-cyclic adenosine monophosphate and may play a critical role in brain diseases. Our aim was to quantity PDE4 in rats with positron emission tomography (PET). Methods: High (n = 6) and low specific activity (SA) (n = 2) higher affinity ((R)-[C-11]rolipram) and high SA lower affinity ((S)-[C-11]rolipram) (n = 2) enantiomers were intravenously administered to Sprague-Dawley rats. Brain data were acquired using the ATLAS PET scanner and reconstructed using, the 3D-ordered subset expectation maximization algorithm. Arterial samples were taken to measure unmetabolized [C-11]rolipram. Total distribution volumes (V'(T)) were calculated using a 1-tissue compartment (1C) and an unconstrained 2-tissue compartment (2C) model. Results: High SA R experiments showed later and greater brain uptake, and slower washout than low SA R and S experiments. In all regions and in all experiments, the 2C model gave significantly better fitting than the 1C model. The poor fitting by the latter caused underestimation of V'(T) by 19-31%. The 2C model identified V'(T) reasonably well with coefficients of variation less than 10%. V'(T) values by this model were 16.4-29.2 mL/cm(3) in high SA R, 2.9-3.5 in low SA R, and 3.1-3.7 in S experiments. Conclusions: Specific binding of (R)-[C-11]rolipram was accurately measured in living rats. In high SA R experiments. similar to 86% of V'(T) was specific binding. Distribution and changes of PDE4 in animal models can now be studied by measuring V'(T) of high SA (R)-[C-11]rolipram. Published by Elsevier Inc. C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. GlaxoSmithKline, Addenbrookes Hosp, PET Div, Cambridge, England. NIH, Bethesda, MD 20892 USA. RP Fujita, M (reprint author), NIMH, Mol Imaging Branch, Bldg 1,Room B3-10,1 Ctr Dr,MSC-0135, Bethesda, MD 20892 USA. EM FujitaM@intra.nimh.nih.gov NR 41 TC 35 Z9 35 U1 2 U2 3 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 JUL 15 PY 2005 VL 26 IS 4 BP 1201 EP 1210 DI 10.1016/j.neuroimage.2005.03.017 PG 10 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 939KK UT WOS:000230071300024 PM 15961054 ER PT J AU Silva, PJS Hashimoto, RF Kim, SC Barrera, J Brandao, LO Suh, E Dougherty, ER AF Silva, PJS Hashimoto, RF Kim, SC Barrera, J Brandao, LO Suh, E Dougherty, ER TI Feature selection algorithms to find strong genes SO PATTERN RECOGNITION LETTERS LA English DT Article DE feature selection; strong genes; gene expression analysis; high-dimensional problem; small sample size ID FLOATING SEARCH METHODS; EXPRESSION PROFILES; CLASSIFICATION; MICROARRAY; PREDICTION; CANCER; IDENTIFICATION; SETS AB The cDNA microarray technology allows us to estimate the expression of thousands of genes of a given tissue. It is natural then to use such information to classify different cell states, like healthy or diseased, or one particular type of cancer or another. However, usually the number of microarray samples is very small and leads to it classification problem with only tens of samples and thousands of features. Recently, Kim et al, proposed to use it parameterized distribution based on the original sample set as a way to attenuate such difficulty. Genes that contribute to good classifiers in such setting are called strong. In this paper, we investigate how to Use feature selection techniques to speed up the quest for strong genes. The idea is to use a feature selection algorithm to filter the gene set considered before the original strong feature technique, that is based on a combinatorial search. The filtering helps its, to find very good strong gene sets, without resorting to super computers. We have tested several filter options and compared the strong genes obtained with the ones got by the original full combinatorial search. (c) 2004 Elsevier B.V. All rights reserved. C1 Univ Sao Paulo, Inst Math Stat, Dept Comp Sci, BR-05508090 Sao Paulo, Brazil. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. NIH, Div Computat Biol, Ctr Informat Technol, Bethesda, MD 20892 USA. Texas A&M Univ, Dept Elect Engn, College Stn, TX 77840 USA. RP Silva, PJS (reprint author), Univ Sao Paulo, Inst Math Stat, Dept Comp Sci, Rua Matao 1010, BR-05508090 Sao Paulo, Brazil. EM pjssilva@ime.usp.br RI Silva, Paulo/D-1938-2012; Hashimoto, Ronaldo/B-6544-2013 OI Silva, Paulo/0000-0003-1340-965X; Hashimoto, Ronaldo/0000-0002-6399-8790 NR 22 TC 17 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-8655 J9 PATTERN RECOGN LETT JI Pattern Recognit. Lett. PD JUL 15 PY 2005 VL 26 IS 10 BP 1444 EP 1453 DI 10.1016/j.patrec.2004.11.017 PG 10 WC Computer Science, Artificial Intelligence SC Computer Science GA 938MF UT WOS:000230006800005 ER PT J AU Woodard, GE Li, XH Rosado, JA AF Woodard, GE Li, XH Rosado, JA TI Receptor subtypes for vasonatrin peptide in renal glomeruli and arteries SO REGULATORY PEPTIDES LA English DT Article DE vasonatrin; NPR-C; NPR-A; renal glomeruli; ANP; CNP ID NATRIURETIC-PEPTIDE; C-RECEPTOR; RAT; ATRIAL; PROTEINS AB Vasonatrin peptide (VNP) is a synthetic new member of the natriuretic peptide family. VNP is a chimera of CNP and ANP, which possesses the 22-amino acid ringed structure of CNP and the COOH terminus of ANP. VNP shares properties with ANP and CNP but also shows functional characteristics distinct from those induced by the original natriuretic peptides. This study investigates VNP binding to specific sites in the kidney and femoral artery, in order to clarify the nature of the receptors through which VNP exerts its effects. Using autoradiographic techniques we have found that VNP binds to renal and arterial tissue sections. VNP binding was displaced by incubation in the presence of 1 mu M ANP(1-28), CNP1-22 and C-ANP, which suggests that VNP mostly binds to NPR-C. Cross-linking studies performed in rat glomerular membranes confirmed that VNP mainly binds to the 67 kDa-NPR-C-like protein and also to NPR-A. Consistent with this, our results indicate that VNP inhibits cAMP synthesis stimulated by the physiological agonist histamine in a concentration-dependent manner, without having any effect on basal cAMP production. Finally, we have found that VNP increases cGMP production in rat renal glomeruli, suggesting that this peptide functionally binds to NPR-A. (c) 2005 Elsevier B.V. All rights reserved. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. Mt Sinai Sch Med, Dept Med, New York, NY 10029 USA. Univ Extremadura, Dept Physiol, Caceres, Spain. RP Woodard, GE (reprint author), NIDDKD, NIH, Bldg 10,Rm 8C-208,10 Ctr Dr,MSC 1752, Bethesda, MD 20892 USA. EM Geoffrey@intra.niddk.nih.gov RI Woodard, Geoffrey/A-8608-2009; rosado, juan/H-3488-2015 OI rosado, juan/0000-0002-9749-2325 NR 25 TC 8 Z9 8 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-0115 J9 REGUL PEPTIDES JI Regul. Pept. PD JUL 15 PY 2005 VL 129 IS 1-3 BP 183 EP 189 DI 10.1016/j.regpep.2005.02.006 PG 7 WC Endocrinology & Metabolism; Physiology SC Endocrinology & Metabolism; Physiology GA 939KU UT WOS:000230072400025 PM 15927715 ER PT J AU Dupuy, AJ Akagi, K Largaespada, DA Copeland, NG Jenkins, NA AF Dupuy, AJ Akagi, K Largaespada, DA Copeland, NG Jenkins, NA TI Mammalian mutagenesis using a highly mobile somatic Sleeping Beauty transposon system SO NATURE LA English DT Article ID CHROMOSOMAL TRANSPOSITION; MLV INTEGRATION; HUMAN-CELLS; GENE; MOUSE; DROSOPHILA; GENOME; MICE; DISRUPTION; EXPRESSION AB Transposons have provided important genetic tools for functional genomic screens in lower eukaryotes but have proven less useful in higher eukaryotes because of their low transposition frequency. Here we show that Sleeping Beauty (SB), a member of the Tc1/mariner class of transposons, can be mobilized in mouse somatic cells at frequencies high enough to induce embryonic death and cancer in wild-type mice. Tumours are aggressive, with some animals developing two or even three different types of cancer within a few months of birth. The tumours result from SB insertional mutagenesis of cancer genes, thus facilitating the identification of genes and pathways that induce disease. SB transposition can easily be controlled to mutagenize any target tissue and can therefore, in principle, be used to induce many of the cancers affecting humans, including those for which little is known about the aetiology. The uses of SB are also not restricted to the mouse and could potentially be used for forward genetic screens in any higher eukaryote in which transgenesis is possible. C1 NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. Univ Minnesota, Ctr Canc, Dept Genet Cell Biol & Dev, Arnold & Mabel Beckman Ctr Transposon Res, Minneapolis, MN 55455 USA. RP Jenkins, NA (reprint author), NCI, Ctr Canc Res, Mouse Canc Genet Program, Frederick, MD 21702 USA. EM jenkins@ncifcrf.gov RI Largaespada, David/C-9832-2014 NR 24 TC 316 Z9 328 U1 2 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 14 PY 2005 VL 436 IS 7048 BP 221 EP 226 DI 10.1038/nature03691 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 944VR UT WOS:000230459500032 PM 16015321 ER PT J AU Garrison, JL Kunkel, EJ Hegde, RS Taunton, J AF Garrison, JL Kunkel, EJ Hegde, RS Taunton, J TI A substrate-specific inhibitor of protein translocation into the endoplasmic reticulum SO NATURE LA English DT Article ID SIGNAL SEQUENCE RECOGNITION; ER MEMBRANE; NASCENT PREPROLACTIN; SEC PROTEINS; POLYPEPTIDE; TRANSPORT; COMPLEX; COMPONENTS; HUN-7293; PARTICLE AB The segregation of secretory and membrane proteins to the mammalian endoplasmic reticulum is mediated by remarkably diverse signal sequences that have little or no homology with each other(1,2). Despite such sequence diversity, these signals are all recognized and interpreted by a highly conserved protein-conducting channel composed of the Sec61 complex(3,4). Signal recognition by Sec61 is essential for productive insertion of the nascent polypeptide into the translocation site(5), channel gating(6) and initiation of transport. Although subtle differences in these steps can be detected between different substrates(7,8), it is not known whether they can be exploited to modulate protein translocation selectively. Here we describe cotransin, a small molecule that inhibits protein translocation into the endoplasmic reticulum. Cotransin acts in a signal-sequence-discriminatory manner to prevent the stable insertion of select nascent chains into the Sec61 translocation channel. Thus, the range of substrates accommodated by the channel can be specifically and reversibly modulated by a cell-permeable small molecule that alters the interaction between signal sequences and the Sec61 complex. C1 NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Chem & Chem Biol Grad Program, San Francisco, CA 94107 USA. Univ Calif San Francisco, Dept Mol & Cellular Pharmacol, San Francisco, CA 94107 USA. Bioseek Inc, Burlingame, CA 94010 USA. RP Hegde, RS (reprint author), NICHD, Cell Biol & Metab Branch, NIH, Bethesda, MD 20892 USA. EM hegder@mail.nih.gov; taunton@cmp.ucsf.edu OI Hegde, Ramanujan/0000-0001-8338-852X NR 28 TC 79 Z9 81 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 14 PY 2005 VL 436 IS 7048 BP 285 EP 289 DI 10.1038/nature03821 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 944VR UT WOS:000230459500047 PM 16015336 ER PT J AU Doroshow, JH AF Doroshow, JH TI Targeting EGFR in non-small-cell lung cancer SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID GEFITINIB; MUTATIONS; KINASE; TRIAL C1 NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Doroshow, JH (reprint author), NCI, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NR 12 TC 20 Z9 22 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 14 PY 2005 VL 353 IS 2 BP 200 EP 202 DI 10.1056/NEJMe058113 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 944OP UT WOS:000230438800013 PM 16014890 ER PT J AU Demidenko, ZN Rapisarda, A Garayoa, M Giannakakou, P Melillo, G Blagosklonny, MV AF Demidenko, ZN Rapisarda, A Garayoa, M Giannakakou, P Melillo, G Blagosklonny, MV TI Accumulation of hypoxia-inducible factor-1 alpha is limited by transcription-dependent depletion SO ONCOGENE LA English DT Article DE HIF-1; hypoxia; p53; the proteasome; degradation ID TUMOR-SUPPRESSOR PROTEIN; HIPPEL-LINDAU PROTEIN; PROLYL HYDROXYLASES; TOPOISOMERASE-I; HIF-ALPHA; HIF-1-ALPHA; OXYGEN; P53; INHIBITION; PATHWAY AB In the presence of oxygen and iron, hypoxia- inducible factor (HIF-1 alpha) is rapidly degraded via the prolyl hydroxylases (PHD)/VHL pathways. Given striking similarities between p53 and HIF-1 alpha regulation, we previously suggested that HIF-1 transcriptionally initiates its own degradation and therefore inhibitors of transcription must induce HIF-1 alpha. Under normoxia, while inducing p53, inhibitors of transcription did not induce HIF-1 alpha. Under hypoxia or low iron (DFX), inhibitors of transcription dramatically super- induced HIF-1 alpha. Removal of inhibitors resulted in outburst of the HIF-1-dependent transcription followed by depletion of HIF-1 alpha. Although hypoxia/ DFX induced PHD3, we excluded the PHD/VHL pathway in the regulation of HIF-1 alpha under hypoxia/DFX. The transcription-dependent degradation of HIF-1 alpha under hypoxia occurs via the proteasome and is accelerated by protein acetylation. Thus, HIF-1 alpha is regulated by two distinct mechanisms. Under normoxia, HIF-1 alpha is degraded via the classic PHD/VHL pathway, is expressed at low levels and therefore does not activate the feedback loop. But under hypoxia, HIF-1 alpha accumulates and transcriptionally activates its own degradation that is independent from the PHD/VHL pathway. C1 New York Med Coll, Brander Canc Res Inst, Valhalla, NY USA. SAID Frederick Inc, NCI, Tumor Hypoxia Lab, Frederick, MD USA. Univ Navarra, Fac Med & Ciencias, Dept Histol & Anat Patol, Navarra, Spain. Emory Univ, Sch Med, Winship Canc Inst, Atlanta, GA 30322 USA. RP Blagosklonny, MV (reprint author), Ordway Res Inst, Ctr Canc, 150 New Scotland Ave, Albany, NY 12208 USA. EM Blagosklonny@hotmail.com OI Giannakakou, Paraskevi/0000-0001-7378-262X NR 42 TC 44 Z9 47 U1 0 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 JUL 14 PY 2005 VL 24 IS 30 BP 4829 EP 4838 DI 10.1038/sj.onc.1208636 PG 10 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 945CC UT WOS:000230477900010 PM 15897903 ER PT J AU Wang, QW Lu, HL Song, CC Liu, H Xu, CG AF Wang, Qing-Wei Lu, Hui-Lan Song, Chang-Cheng Liu, Hong Xu, Cong-Gao TI Radiosensitivity of human colon cancer cell enhanced by immunoliposomal docetaxel SO WORLD JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Radiosensitivity; Human colon cancer cell; Docetaxel; Immunoliposomes AB AIM: To enhance the radiosensitivity of human colon cancer cells by docetaxel. METHODS: Immunoliposomal docetaxel was prepared by coupling monoclonal antibody against carcinoembryonic antigen to cyanuric chloride at the PEG terminus of liposome. LoVo adenocarcinoma cell line was treated with immunoliposomal docetaxel or/and irradiation. MTT colorimetric assay was used to estimate cytotoxicity of immunoliposomal docetaxel and radiotoxicity. Cell cycle redistribution and apoptosis were determined with flow cytometry. Survivin expression in LoVo cells was verified by immunohistochemistry. D801 morphologic analysis system was used to semi-quantify immunohistochemical staining of survivin. RESULTS: Cytotoxicity was induced by immunoliposomal docetaxel alone in a dose-dependent manner. Immunoliposomal docetaxel yielded a cytotoxicity effect at a low dose of 2 nmol/L. With a single dose irradiation, the relative surviving fraction of LoVo cells showed a dose-dependent response, but there were no significant changes as radiation delivered from 4 to 8 Gy. Compared with liposomal docetaxel or single dose irradiation, strongly radiopotentiating effects of immunoliposomal docetaxel on LoVo cells were observed. A low dose of immunoliposomal docetaxel could yield sufficient radiosensitivity. Immunoliposomal docetaxel were achieved both specificity of the conjugated antibody and drug radiosensitization. Combined with radiation, immunoliposomal docetaxel significantly increased the percentage of G(2)/M cells and induced apoptosis, but significantly decreased the percentage of cells in G(2)/G(1) and S phase by comparison with liposomal docetaxel. Immunohistochemical analysis showed that the brown stained survivin was mainly in cytoplasm of LoVo cells. Semi-quantitative analysis of the survivin immunostaining showed that the expression of survivin in LoVo cells under irradiation with immunoliposomal docetaxel was significantly decreased. CONCLUSION: Immunoliposomal docetaxel is strongly effective for target radiosensitation in LoVo colon carcinoma cells, and may offer the potential to improve local radiotherapy. (C) 2005 The WJG Press and Elsevier Inc. All rights reserved. C1 [Wang, Qing-Wei; Lu, Hui-Lan; Liu, Hong; Xu, Cong-Gao] Shandong Univ, Canc Res Ctr, Qilu Hosp, Jinan 250012, Shandong, Peoples R China. [Song, Chang-Cheng] NCI, Basic Res Program, Lab Canc Prevent, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Wang, QW (reprint author), Shandong Univ, Canc Res Ctr, Qilu Hosp, Jinan 250012, Shandong, Peoples R China. EM wangqingwei@csco.org.cn FU Department of Science and Technology of Shandong Province FX Supported by the Department of Science and Technology of Shandong Province NR 31 TC 18 Z9 21 U1 0 U2 0 PU BAISHIDENG PUBL GRP CO LTD PI BEIJING PA RM 903, BLDG D, OCEAN INTERNATIONAL CTR, NO 62 DONGSIHUAN ZHONGLU, BEIJING, CHAOYANG DISTRICT 100025, PEOPLES R CHINA SN 1007-9327 J9 WORLD J GASTROENTERO JI World J. Gastroenterol. PD JUL 14 PY 2005 VL 11 IS 26 BP 4003 EP 4007 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA V23BG UT WOS:000208317700006 PM 15996023 ER PT J AU Sharifi, N Gulley, JL Dahut, WL AF Sharifi, N Gulley, JL Dahut, WL TI Androgen deprivation therapy for prostate cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; UNFAVORABLE-PROGNOSIS CARCINOMA; SUPPRESSION PLUS RADIATION; PREVENT BONE LOSS; HOT FLASHES; RADICAL PROSTATECTOMY; MEGESTROL-ACETATE; HORMONAL-THERAPY; PILOT EVALUATION AB Context Prostate cancer is the most common nonskin cancer and second most common cause of cancer mortality in US men. Androgen deprivation therapy (ADT), specifically surgical or medical castration, is the first line of treatment against advanced prostate cancer and is also used as an adjuvant to local treatment of high-risk disease. Objective To review systematically the evidence on the risks and benefits of ADT for prostate cancer as well as clinical management of its adverse effects. Evidence Acquisition We performed MEDLINE searches of English-language literature (1966 to March 2005) using the terms androgen deprivation therapy, hormone treatment, and prostate cancer. We reviewed bibliographies of literature to extract other relevant articles. Studies were selected based on clinical pertinence, with an emphasis on controlled study design. Evidence Synthesis Androgen deprivation therapy is effective for palliation in many patients with advanced prostate cancer and improves outcomes for high-risk patients treated with radiation therapy for localized disease. Although patients with increasing prostate-specific antigen levels after local treatment without metastatic disease frequently undergo ADT, the benefits of this strategy are not clear. Adverse effects of ADT include decreased libido, impotence, hot flashes, osteopenia with increased fracture risk, metabolic alterations, and changes in cognition and mood. Conclusions Androgen deprivation therapy has clear roles in the management of advanced prostate cancer and high-risk localized disease. The benefits of ADT in other settings need to be weighed carefully against substantial risks and adverse effects on quality of life. C1 NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. NCI, Cytokine Mol Mech Sect, Mol Immunoregulat Lab, Frederick, MD 21701 USA. RP Gulley, JL (reprint author), NCI, Tumor Immunol & Biol Lab, Ctr Canc Res, 10 Ctr Dr,8B09 MSC 1750, Bethesda, MD 20892 USA. EM gul-leyj@mail.nih.gov RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 59 TC 474 Z9 482 U1 21 U2 58 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 13 PY 2005 VL 294 IS 2 BP 238 EP 244 DI 10.1001/jama.294.2.238 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 944DO UT WOS:000230406100028 PM 16014598 ER PT J AU Kruman, II Mouton, PR Emokpae, R Cutler, RG Mattson, MP AF Kruman, II Mouton, PR Emokpae, R Cutler, RG Mattson, MP TI Folate deficiency inhibits proliferation of adult hippocampal progenitors SO NEUROREPORT LA English DT Article DE diet; hippocampus; metabolism; neuronal progenitor cells; proliferation; suppression ID ALZHEIMERS-DISEASE; DENTATE GYRUS; HOMOCYSTEINE; NEUROGENESIS; CELL; DNA; STRESS; MODELS; REPAIR; MICE AB Neurogenesis in the adult hippocampus may play important roles in learning and memory, and in recovery from injury. As recent findings suggest, the perturbance of homocysteine/folate or one-carbon metabolism can adversely affect both the developing and the adult brain, and increase the risk of neural tube defects and Alzheimer's disease. We report that dietary folic acid deficiency dramatically increased blood homocysteine levels and significantly reduced the number of proliferating cells in the dentate gyrus of the hippocampus in adult mice. In vitro, the perturbance of one-carbon metabolism repressed proliferation of cultured embryonic mu tipotent neuroepithelial progenitor cells and affected cell cycle distribution. Our results suggest that dietary folate deficiency inh bits proliferation of neuronal progenitor cells in the adult brain and thereby affects neurogenesis. C1 Sun Hlth Res Inst, Sun City, AZ 85351 USA. NIA, Lab Expt Gerontol, Intramural Res Program, Baltimore, MD 21224 USA. NIA, Neurosci Lab, Intramural Res Program, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA. RP Kruman, II (reprint author), Sun Hlth Res Inst, 10515 W Santa Fe Dr, Sun City, AZ 85351 USA. EM inna.kruman@sunhealth.org RI Mattson, Mark/F-6038-2012 NR 25 TC 55 Z9 60 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 13 PY 2005 VL 16 IS 10 BP 1055 EP 1059 DI 10.1097/00001756-200507130-00005 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 949GC UT WOS:000230772100005 PM 15973147 ER PT J AU Schaefer, M Heinze, HJ Rotte, M AF Schaefer, M Heinze, HJ Rotte, M TI Seeing the hand being touched modulates the primary somatosensory cortex SO NEUROREPORT LA English DT Article DE cross-modal; magnetoencephalography; multisensory; somatosensory cortex; touch; vision ID INFLUENCES TACTILE PERCEPTION; HUMANS; REPRESENTATION; ORGANIZATION; ENHANCEMENT; ATTENTION; NEURONS; SPACE AB Recent behavioral studies have shown that viewing the stimulated body part can enhance tactile acuity. We examined effects of viewing the stimulated body part by using neuromagnetic source imaging. Study participants were covertly stimulated on their first digit (D1) while watching a video that showed a hand where D1 was stimulated. The video hand appeared in the region where the real hand would be expected. In addition, participants were stimulated on D1 without watching the video. The results demonstrated a shift of D1 to a more inferior position and an increase of the dipole strength of D1 during the observation of tactile stimulation. We discuss these cross-modal interactions with recent studies on visuotactile enhancement. C1 NINDS, Human Cortical Physiol Sect, NIH, Bethesda, MD 20892 USA. Otto Von Guericke Univ, Dept Neurol 2, D-39120 Magdeburg, Germany. RP Schaefer, M (reprint author), NINDS, Human Cortical Physiol Sect, NIH, Bethesda, MD 20892 USA. EM schaefem@ninds.nih.gov NR 23 TC 32 Z9 32 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD JUL 13 PY 2005 VL 16 IS 10 BP 1101 EP 1105 DI 10.1097/00001756-200507130-00014 PG 5 WC Neurosciences SC Neurosciences & Neurology GA 949GC UT WOS:000230772100014 PM 15973156 ER PT J AU Majone, F Luisetto, R Zamboni, D Iwanaga, Y Jeang, KT AF Majone, F Luisetto, R Zamboni, D Iwanaga, Y Jeang, KT TI Ku protein as a potential human T-cell leukemia virus type 1 (HTLV-1) Tax target in clastogenic chromosomal instability of mammalian cells SO RETROVIROLOGY LA English DT Article ID STRAND BREAK REPAIR; POLY(ADP-RIBOSE) POLYMERASE; DNA-REPAIR; TRANSCRIPTIONAL ACTIVATION; TELOMERASE ACTIVITY; GENOMIC INTEGRITY; I TAX; IDENTIFICATION; TUMORIGENESIS; ONCOPROTEIN AB The HTLV-1 Tax oncoprotein rapidly induces cytogenetic damage which can be measured by a significant increase in the number of micronuclei (MN) in cells. Tax is thought to have both aneuploidogenic and clastogenic effects. To examine the cellular target for Tax which might mechanistically explain the clastogenic phenomenon, we tested the ability of Tax to induce MN in rodents cells genetically defective for either the Ku80 protein or the catalytic subunit of DNA protein kinase (DNAPKcs). We found that cells genetically mutated in Ku80 were refractory to Tax's induction of MN while cells knocked-out for DNAPKcs showed increased number of Tax-induced MN. Using a cytogenetic method termed FISHI (Fluorescent In Situ Hybridization and Incorporation) which measures the number of DNA-breaks in cells that contained unprotected 3'-OH ends, we observed that Tax increased the prevalence of unprotected DNA breaks in Ku80-intact cells, but not in Ku80-mutated cells. Taken together, our findings suggest Ku80 as a cellular factor targeted by Tax in engendering clastogenic DNA damage. C1 Univ Padua, Dept Biol, Padua, Italy. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Majone, F (reprint author), Univ Padua, Dept Biol, Padua, Italy. EM majone@mail.bio.unipd.it; roberto.luisetto@unipd.it; daniela.zamboni@unipd.it; yoichiiwanaga@hotmail.com; kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 31 TC 34 Z9 34 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JUL 13 PY 2005 VL 2 AR 45 DI 10.1186/1742-4690-2-45 PG 10 WC Virology SC Virology GA 033DO UT WOS:000236826900001 PM 16014171 ER PT J AU Luo, S Kim, G Levine, RL AF Luo, S Kim, G Levine, RL TI Mutation of the adenylylated tyrosine of glutamine synthetase alters its catalytic properties SO BIOCHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; INHIBITION; MECHANISM; PROTEINS AB Glutamine synthetase is central to nitrogen metabolism in the Gram-negative bacteria. The amount of glutamine synthetase in the cell and its catalytic activity are tightly regulated by multiple, sophisticated mechanisms. Reversible covalent modification of Tyr-397 is central to the regulation of glutamine synthetase activity, via esterification of the hydroxyl group to AMP in a process termed adenylylation. As expected, site-specific mutation of this surface-exposed Tyr-397 to Phe, Ala, or Ser was found to prevent adenylylation. Unexpectedly, these mutations had major effects on the catalytic characteristics of glutamine synthetase. The specific activities of each mutant were approximately doubled, the pH-activity profiles changed, and divalent-cation specificity was altered. Overall, Tyr397Phe behaved as if it were unadenylylated, while both Tyr397Ala and Tyr397Ser behaved as if they were adenylylated. Thus, subtle modifications in the environment of residue 397 are sufficient to induce changes previously thought to require adenylylation. C1 NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP Levine, RL (reprint author), NHLBI, Biochem Lab, Bldg 3, Bethesda, MD 20892 USA. EM rlevine@nih.gov RI Levine, Rodney/D-9885-2011 NR 20 TC 7 Z9 8 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUL 12 PY 2005 VL 44 IS 27 BP 9441 EP 9446 DI 10.1021/bi050554k PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 944YA UT WOS:000230465900005 PM 15996098 ER PT J AU Mitchell, GF DeStefano, AL Larson, MG Benjamin, EJ Chen, MH Vasan, RS Vita, JA Levy, D AF Mitchell, GF DeStefano, AL Larson, MG Benjamin, EJ Chen, MH Vasan, RS Vita, JA Levy, D TI Heritability and a genome-wide linkage scan for arterial stiffness, wave reflection, and mean arterial pressure - The Framingham Heart Study SO CIRCULATION LA English DT Article DE genetics; blood pressure; arteries; arteriosclerosis; elasticity ID BLOOD-PRESSURE; PULSE PRESSURE; AORTIC STIFFNESS; CARDIOVASCULAR MORTALITY; ESSENTIAL-HYPERTENSION; SYSTOLIC HYPERTENSION; MYOCARDIAL-INFARCTION; INDEPENDENT PREDICTOR; PROTEIN EXPRESSION; MEXICAN-AMERICANS AB Background - Arterial stiffness and mean arterial pressure variably contribute to systolic hypertension and increased cardiovascular risk. However, few prior community-based studies have evaluated the genetics of arterial stiffness and separate mean and pulsatile components of blood pressure. Methods and Results - Using arterial tonometry, we evaluated heritability and linkage of forward and reflected wave amplitude, mean arterial pressure, and carotid-femoral pulse wave velocity (CFPWV) in 1480 participants representing 817 pedigrees in the Framingham Study offspring cohort. In 204 families with tonometry data, a genome-wide scan was performed with microsatellite markers that covered the genome at 10-cM intervals. Heritability estimates were moderate for reflected wave amplitude ( h(2) = 0.48), forward wave amplitude (h(2) = 0.21), CFPWV (h(2) = 0.40), and mean arterial pressure (h(2) = 0.33). Variance components linkage analysis identified 2 regions of linkage for reflected wave amplitude: chromosome 4 at 181 cM ( logarithm of odds [LOD] = 4.93, permuted P = 0.002) and chromosome 8 at 33 cM (LOD = 3.27, permuted P = 0.058). There was 1 region of linkage for forward wave amplitude on chromosome 7 at 174 cM (LOD = 2.88, permuted P = 0.017). There were several regions of suggestive linkage for CFPWV: chromosome 2 at 94 cM (LOD = 2.46), chromosome 7 at 29 cM (LOD = 2.50), chromosome 13 at 108 cm (LOD = 2.10), and chromosome 15 at 108 cM (LOD = 2.48). There was 1 region of suggestive linkage for mean arterial pressure on chromosome 1 at 192 cM ( LOD = 2.18). Conclusions - Arterial stiffness measures and mean and pulsatile components of blood pressure are heritable and appear to have genetic determinants that may be linked to separate genetic loci in humans. C1 Cardiovasc Engn Inc, Holliston, MA 01746 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. Boston Univ, Dept Math & Stat, Boston, MA USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Sect Prevent Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Evans Dept Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Whitaker Cardiovasc Inst, Boston, MA 02118 USA. NHLBI, Framingham, MA USA. RP Cardiovasc Engn Inc, 327 Fiske St, Holliston, MA 01746 USA. EM GaryFMitchell@mindspring.com OI Vita, Joseph/0000-0001-5607-1797; Larson, Martin/0000-0002-9631-1254; Ramachandran, Vasan/0000-0001-7357-5970; Benjamin, Emelia/0000-0003-4076-2336 FU NHLBI NIH HHS [1R01-HL70100, 1R01-HL60040, N01-HC-25195] NR 47 TC 88 Z9 89 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0009-7322 EI 1524-4539 J9 CIRCULATION JI Circulation PD JUL 12 PY 2005 VL 112 IS 2 BP 194 EP 199 DI 10.1161/CIRCULATIONAHA.104.530675 PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 944KQ UT WOS:000230427300009 PM 15998672 ER PT J AU Wright, VL Olan, W Dick, B Yu, H Alberts-Grill, N Latour, LL Baird, AE AF Wright, VL Olan, W Dick, B Yu, H Alberts-Grill, N Latour, LL Baird, AE TI Assessment of CE-MRA for the rapid detection of supra-aortic vascular disease SO NEUROLOGY LA English DT Article; Proceedings Paper CT 5th World Stroke Conference CY JUN 26, 2004 CL Vancouver, CANADA ID MAGNETIC-RESONANCE ANGIOGRAPHY; DIGITAL-SUBTRACTION-ANGIOGRAPHY; CAROTID-ENDARTERECTOMY; CT ANGIOGRAPHY; ACUTE STROKE; BREATH-HOLD; STENOSIS; ARTERIES; ATHEROSCLEROSIS; EPIDEMIOLOGY AB Background: Contrast-enhanced MR angiography (CE-MRA) using a combined head and neck coil permits non-invasive imaging of the vasculature from the aortic arch through to the Circle of Willis in less than 2 minutes. Objective: To determine the accuracy of CE-MRA for the detection of vascular pathology, in particular vascular stenoses, using digital subtraction angiography (DSA) as the gold standard. Methods: In a prospective study of 81 patients referred for DSA, CE-MRA and DSA studies were performed within 72 hours of each other. CE-MRA was performed on a 1.5 Tesla clinical MRI scanner using a five-channel neurovascular array ( head and neck coil), with dynamic tracking of the IV gadolinium bolus. CE-MRAs and DSA films were read by two interventional neuroradiologists blinded to the clinical presentation of the patient. Results: On DSA, there were 77 vascular stenoses >= 50% identified, 51 extracranial and 26 intracranial. The overall sensitivity of CE-MRA using the neurovascular array for the detection of vascular stenoses >= 50% was 57% ( 95% CI: 46 to 68%) with a specificity of 98% ( 97 to 99%). The sensitivity for the detection of extracranial vascular stenoses >= 50% was 82% ( 72 to 93%) with a specificity of 97% ( 96 to 98%). However, the sensitivity for the detection of intracranial vascular stenoses >= 50% was only 8% ( 0 to 18%), with a specificity of 99% ( 98 to 100%). Conclusions: At this stage Contrast-enhanced MR angiography using a neurovascular coil shows promise as a rapid, specific, and noninvasive screening method for extracranial vascular disease, but not for intracranial vascular disease. C1 NINDS, Stroke Neurosci Unit, NIH, Bethesda, MD 20892 USA. NINDS, Sect Stroke Diagnost & Therapeut, NIH, Bethesda, MD 20892 USA. Suburban Hosp, Bethesda, MD USA. RP Baird, AE (reprint author), NINDS, Stroke Neurosci Unit, NIH, 10 Ctr Dr,MSC 1294,Room 3N258, Bethesda, MD 20892 USA. EM bairda@ninds.nih.gov NR 25 TC 21 Z9 27 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 12 PY 2005 VL 65 IS 1 BP 27 EP 32 DI 10.1212/01.wnl.0000167606.81882.68 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 944KP UT WOS:000230427200008 PM 16009882 ER PT J AU Peckham, EL Giblen, G Kim, AK Sirdofsky, MD AF Peckham, EL Giblen, G Kim, AK Sirdofsky, MD TI Bilateral extraocular muscle metastasis from primary breast cancer SO NEUROLOGY LA English DT Editorial Material C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Peckham, EL (reprint author), NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. EM peckhame@ninds.nih.gov NR 2 TC 5 Z9 5 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JUL 12 PY 2005 VL 65 IS 1 BP 74 EP 74 DI 10.1212/01.WNL.0000156359.93206.99 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 944KP UT WOS:000230427200015 PM 16009888 ER PT J AU Schumacher, AJ Nissley, DV Harris, RS AF Schumacher, AJ Nissley, DV Harris, RS TI APOBEC3G hypermutates genomic DNA and inhibits Ty1 retrotransposition in yeast SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE APOBEC3F; endogenous retrotransposon Ty1; hypermutation; cytodeamination; Saccharomyces cerevisiae ID IMMUNODEFICIENCY-VIRUS TYPE-1; EDITING ENZYME APOBEC3G; SACCHAROMYCES-CEREVISIAE; HIV-1 VIRIONS; VIF PROTEIN; ANTIRETROVIRAL FACTOR; ANTIVIRAL ACTIVITY; GAG PROTEINS; SOCS-BOX; T-CELLS AB Human cells harbor a variety of factors that function to block the proliferation of foreign nucleic acid. The APOBEC3G enzyme inhibits the replication of retroviruses by deaminating nascent retroviral cDNA cytosines to uracils, lesions that can result in lethal levels of hypermutation. Here, we demonstrate that APOBEC3G is capable of deaminating genomic cytosines in Saccharomyces cerevisiae. APOBEC3G expression caused a 20-fold increase in frequency of mutation to canavanine-resistance, which was further elevated in a uracil DNA glycosylase-deficient background. All APOBEC3G-induced base substitution mutations mapped to the nuclear CAN1 gene and were exclusively C/G -> T/A transition mutations within a 5'-CC consensus. The APOBEC3G preferred sites were found on both strands of the DNA duplex, but were otherwise located in hotspots nearly identical to those found previously in retroviral cDNA. This unique genetic system further enabled us to show that expression of APOBEC3G or its homolog APOBEC3F was able to inhibit the mobility of the retrotransposon Ty1 by a mechanism that involves the deamination of cDNA cytosines. Thus, these data expand the range of likely APOBEC3 targets to include nuclear DNA and endogenous retroelements, which have pathological and physiological implications, respectively. We postulate that the APOBEC3-dependent innate cellular defense constitutes a tightly regulated arm of a conserved mobile nucleic acid restriction mechanism that is poised to limit internal as well as external assaults. C1 Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. Univ Minnesota, Inst Mol Virol, Minneapolis, MN 55455 USA. NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. RP Harris, RS (reprint author), Univ Minnesota, Dept Biochem Mol Biol & Biophys, Minneapolis, MN 55455 USA. EM rsh@umn.edu FU NCI NIH HHS [N01 CO 12400, N01CO12400] NR 54 TC 108 Z9 110 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 12 PY 2005 VL 102 IS 28 BP 9854 EP 9859 DI 10.1073/pnas.0501694102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 946AU UT WOS:000230545100023 PM 16000409 ER PT J AU Zhang, YX Wang, XW Jelovac, D Nakanishi, T Yu, MH Akinmade, D Goloubeva, O Ross, DD Brodie, A Hamburger, AW AF Zhang, YX Wang, XW Jelovac, D Nakanishi, T Yu, MH Akinmade, D Goloubeva, O Ross, DD Brodie, A Hamburger, AW TI The ErB3-binding protein Ebp1 suppresses androgen receptor-mediated gene transcription and tumorigenesis of prostate cancer cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ErbB receptors; transcriptional corepressors; androgen independence ID ERBB-3 BINDING-PROTEIN; MOLECULAR-CLONING; CARCINOMA-CELLS; EXPRESSION; GROWTH; LNCAP; HEREGULIN; DOMAIN; REPRESSION; DIFFERENTIATION AB Down-regulation of the androgen receptor (AR) is being evaluated as an effective therapy for the advanced stages of prostate cancer. We report that Ebp1, a protein identified by its interactions with the ErbB3 receptor, down-regulates expression of AR and AR-regulated genes in the LNCaP prostate cancer cell line. Using microarray analysis, we identified six endogenous AR target genes, including the AR itself, that are down-regulated by ebp1 overexpression. Chromatin immunoprecipitation assays revealed that Ebp1 was recruited to the prostate-specific antigen gene promoter in response to the androgen antagonist bicalutamide, suggesting that Ebp1 directly affected the expression of AR-regulated genes in response to androgen antagonists. Ebp1 expression was reduced in cells that had become androgen-independent. Androgens failed to stimulate either the growth of ebp1 transfectants or transcription of AR-regulated reporter genes in these cells. The agonist activity of the antiandrogen cyproterone acetate was abolished in ebp1 transfectants. In severe combined immunodeficient mice, Ebp1 overexpression resulted in a reduced incidence of LNCaP tumors and slower tumor growth. These findings suggest that Ebp1 is a previously unrecognized therapeutic target for treatment of hormone refractory prostate cancer. C1 Univ Maryland, Greenebaum Canc Ctr, Sch Med, Baltimore, MD 21201 USA. Univ Maryland, Dept Pathol, Sch Med, Baltimore, MD 21201 USA. Univ Maryland, Dept Pharmacol, Sch Med, Baltimore, MD 21201 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. Baltimore Vet Affairs Med Ctr, Baltimore, MD 21201 USA. RP Hamburger, AW (reprint author), Univ Maryland, Greenebaum Canc Ctr, Sch Med, 655 W Baltimore St, Baltimore, MD 21201 USA. EM ahamburg@som.umaryland.edu RI Wang, Xin/B-6162-2009; Nakanishi, Takeo/C-3891-2015 OI Nakanishi, Takeo/0000-0002-6561-7138 FU NCI NIH HHS [R01 CA 76047, R01 CA076047]; PHS HHS [R21 088882-01] NR 45 TC 62 Z9 70 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 12 PY 2005 VL 102 IS 28 BP 9890 EP 9895 DI 10.1073/pnas.0503829102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 946AU UT WOS:000230545100029 PM 15994225 ER PT J AU Carney, RM Blumenthal, JA Freedland, KE Stein, PK Howells, WB Berkman, LF Watkins, LL Czajkowski, SM Hayano, J Domitrovich, PP Jaffe, AS AF Carney, RM Blumenthal, JA Freedland, KE Stein, PK Howells, WB Berkman, LF Watkins, LL Czajkowski, SM Hayano, J Domitrovich, PP Jaffe, AS TI Low heart rate variability and the effect of depression on post-myocardial infarction mortality SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY-DISEASE; FREQUENCY-DOMAIN MEASURES; PERIOD VARIABILITY; RISK-FACTOR; ASSOCIATION; RECOVERY; MECHANISMS; MORBIDITY; DEATH AB Background: Depression is associated with an increased risk for mortality after acute myocardial infarction (MI). The purpose of this study was to determine whether low heart rate variability (HRV) mediates the effect of depression on mortality. Methods: Twenty-four-hour ambulatory electrocardiograms were obtained from 311 depressed patients with a recent acute MI who were enrolled in the Enhancing Recovery in Coronary Heart Disease (ENRICHD) clinical trial and from 367 nondepressed patients who met the ENRICHD medical inclusion criteria. Standard HRV indexes were extracted from the recordings. Results: The log of very low-frequency (LnVLF) power, an index of HRV derived from power spectral analysis of the electrocardiogram signal (0.0033-0.04 Hz [in milliseconds squared]), was lower in the depressed than in the nondepressed patients (P <.001). There were 47 deaths (6.1%) during a 30-month follow-up. After adjusting for potential confounders, the depressed patients remained at higher risk for all-cause mortality compared with the nondepressed patients (hazard ratio, 2.8; 95% confidence interval [CI], 1.4-5.4-1 P <.003). When LnVLF power was entered into the model, the hazard ratio for depression dropped to 2.1 (95% CI, 1.1-4.2; P=.03). The proportion of the risk for depression attributable to LnVLF power was 0.27 (95% CI, 0.23-0.3 1; P <.001). Conclusions: Low HRV partially mediates the effect of depression on survival after acute MI. This finding helps to clarify the physiological mechanisms underlying depression's role as a risk factor for mortality in patients with coronary heart disease. It also raises the possibility that treatments that improve both depression and HRV might also improve survival in these patients. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Harvard Univ, Dept Epidemiol, Boston, MA USA. NHLBI, Bethesda, MD 20892 USA. Nagoya City Univ, Grad Sch Med, Dept Med, Nagoya, Aichi, Japan. Mayo Clin, Dept Med, Rochester, MN USA. RP Carney, RM (reprint author), Behav Med Ctr, 4625 Lindell Blve,Suite 420, St Louis, MO 63108 USA. EM carneyr@bmc.wustl.edu FU NHLBI NIH HHS [1 RO-1HL58946] NR 33 TC 140 Z9 146 U1 1 U2 13 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 11 PY 2005 VL 165 IS 13 BP 1486 EP 1491 DI 10.1001/archinte.165.13.1486 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 944EK UT WOS:000230408900005 PM 16009863 ER PT J AU Fracasso, PM Blum, KA Ma, MK Tan, BR Wright, LP Goodner, SA Fears, CL Hou, W Arquette, MA Picus, J Denes, A Mortimer, JE Ratner, L Ivy, SP McLeod, HL AF Fracasso, PM Blum, KA Ma, MK Tan, BR Wright, LP Goodner, SA Fears, CL Hou, W Arquette, MA Picus, J Denes, A Mortimer, JE Ratner, L Ivy, SP McLeod, HL TI Phase I study of pegylated liposomal doxorubicin and the multidrug-resistance modulator, valspodar SO BRITISH JOURNAL OF CANCER LA English DT Article DE doxil; multidrug resistance; pegylated liposomal doxorubicin; PSC 833; valspodar ID STERICALLY STABILIZED LIPOSOMES; GLYCOPROTEIN ANTAGONIST PSC-833; SDZ PSC 833; SOLID TUMORS; INFUSIONAL VINBLASTINE; THERAPEUTIC-EFFICACY; CIRCULATION TIME; KAPOSIS-SARCOMA; OVARIAN-CANCER; COMBINATION AB Valspodar, a P-glycoprotein modulator, affects pharmacokinetics of doxorubicin when administered in combination, resulting in doxorubicin dose reduction. In animal models, valspodar has minimal interaction with pegylated liposomal doxorubicin (PEG-LD). To determine any pharmacokinetic interaction in humans, we designed a study to determine maximum tolerated dose, dose-limiting toxicity (DLT), and pharmacokinetics of total doxorubicin, in PEG-LD and valspodar combination therapy in patients with advanced malignancies. Patients received PEG-LD 20-25 mg m(-2) intravenously over 1 h for cycle one. In subsequent 2-week cycles, valspodar was administered as 72 h continuous intravenous infusion with PEG-LD beginning at 8 mg m(-2) and escalated in an accelerated titration design to 25 mg m(-2). Pharmacokinetic data were collected with and without valspodar. A total of 14 patients completed at least two cycles of therapy. No DLTs were observed in six patients treated at the highest level of PEG-LD 25 mg m(-2). The most common toxicities were fatigue, nausea, vomiting, mucositis, palmar plantar erythrodysesthesia, diarrhoea, and ataxia. Partial responses were observed in patients with breast and ovarian carcinoma. The mean ( range) total doxorubicin clearance decreased from 27 (10-73) ml h(-1) m(-2) in cycle 1 to 18 (3-37) ml h(-1) m(-2) with the addition of valspodar in cycle 2 (P = 0.009). Treatment with PEG-LD 25 mg m(-2) in combination with valspodar results in a moderate prolongation of total doxorubicin clearance and half-life but did not increase the toxicity of this agent. C1 Washington Univ, Sch Med, Dept Med, St Louis, MO 63110 USA. Washington Univ, Sch Med, Alvin J Siteman Canc Ctr, St Louis, MO 63110 USA. NCI, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Fracasso, PM (reprint author), Washington Univ, Sch Med, Dept Med, 660 S Euclid St,Box 8056, St Louis, MO 63110 USA. EM fracasso@wustl.edu RI Blum, Kristie/E-2768-2011 FU NCI NIH HHS [P30 CA091842] NR 32 TC 21 Z9 24 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD JUL 11 PY 2005 VL 93 IS 1 BP 46 EP 53 DI 10.1038/sj.bjc.6602653 PG 8 WC Oncology SC Oncology GA 942EF UT WOS:000230265000008 PM 15942626 ER PT J AU Carmona, GN Schindler, CW Greig, NH Holloway, HW Jufer, RA Cone, EJ Gorelick, DA AF Carmona, GN Schindler, CW Greig, NH Holloway, HW Jufer, RA Cone, EJ Gorelick, DA TI Intravenous butyrylcholinesterase levels of cocaine administration and plasma and brain levels of cocaine and metabolites in rats SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE cocaine; butyrylcholinesterase; ecgonine methylester; cymserine; benzoylecgonine; (rat) ID ECGONINE METHYL-ESTER; CHOLINESTERASE ACTIVITY; IN-VITRO; TOXICITY; INHIBITION; PROTECTS; MICE; HYDROLYSIS; MECHANISMS; RESPONSES AB Butyrylcholinesterasc is a major cocaine-metabolizing enzyme in humans and other primates, catalyzing hydrolysis to ecgonine methylester. Increasing butyrylcholinesterase activity may be a treatment for cocaine addiction. We evaluated the effect of 30-min pretreatment with horse-derived butyry1cholinesterase (5-15,000 U i.v.) or with the selective butyry1cholinesterase inhibitor cymserine (10 mg/kg i.v.) on the metabolism of cocaine (17 mg/kg i.p.) in anesthetized rats. Venous blood samples were collected for two hours after cocaine administration and later assayed for cocaine and metabolites by gas chromatography/mass spectroscopy. Whole brains were collected after the last blood sample and similarly assayed. Butyrylcholinesterase significantly increased plasma and brain ecgonine methylester levels and decreased cocaine plasma half-life from 26.2 min (saline) to 16.4 min (15,000 U). Butyrylcholinesterase had no significant effect on plasma or brain cocaine or benzoylecgonine levels. Cymserine had no effect on any variable. These findings suggest that butyry1cholinesterase treatment may have benefits in enhancing cocaine metabolism and in increasing levels of ecgonine methylester, which may have a protective action against cocaine. (c) 2005 Elsevier B.V All rights reserved. C1 NIDA, Intramural Res Program, Baltimore, MD 21224 USA. NIA, NIH, US Dept HHS, Baltimore, MD 21224 USA. RP Gorelick, DA (reprint author), NIDA, Intramural Res Program, Baltimore, MD 21224 USA. EM dgorelic@intra.nida.nih.gov FU Intramural NIH HHS NR 24 TC 17 Z9 17 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUL 11 PY 2005 VL 517 IS 3 BP 186 EP 190 DI 10.1016/j.ejphar.2005.05.013 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 948FI UT WOS:000230701000006 PM 15967428 ER PT J AU Donaldson, JG Honda, A Weigert, R AF Donaldson, JG Honda, A Weigert, R TI Multiple activities for Arf1 at the Golgi complex SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Review DE Arf1; Golgi complex; COPI; adaptor protein; membrane traffic; phosphoinositide ID ADP-RIBOSYLATION FACTOR; NUCLEOTIDE-EXCHANGE FACTOR; GTPASE-ACTIVATING PROTEIN; PHOSPHOLIPASE-D ACTIVITY; BREFELDIN-A; SACCHAROMYCES-CEREVISIAE; COPI COAT; ENDOPLASMIC-RETICULUM; CIS-GOLGI; MEMBRANE TRAFFICKING AB The Arf family of GTPases regulates membrane traffic and organelle structure. At the Golgi complex, Arf proteins facilitate membrane recruitment of many cytoplasmic coat proteins to allow sorting of membrane proteins for transport, stimulate the activity of enzymes that modulate the lipid composition of the Golgi, and assemble a cytoskeletal scaffold on the Golgi. Arf1 is the Arf family member most closely studied for its function at the Golgi complex. A number of regulators that activate and inactivate Arf1 on the Golgi have been described that localize to different regions of the organelle. This spatial distribution of Arf regulators may facilitate the recruitment of the coat proteins and other Arf effectors to different regions of the Golgi complex. (c) 2005 Elsevier B.V. All rights reserved. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Donaldson, JG (reprint author), NHLBI, Cell Biol Lab, NIH, Bldg 50,Room 2503, Bethesda, MD 20892 USA. EM jdonalds@helix.nih.gov NR 117 TC 76 Z9 77 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD JUL 10 PY 2005 VL 1744 IS 3 BP 364 EP 373 DI 10.1016/j.bbamcr.2005.03.001 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 943OI UT WOS:000230363200010 PM 15979507 ER PT J AU Purdue, MP Devesa, SS Sigurdson, AJ McGlynn, KA AF Purdue, MP Devesa, SS Sigurdson, AJ McGlynn, KA TI International patterns and trends in testis cancer incidence SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE testicular neoplasms; incidence; trends; international ID GERM-CELL CANCER; TESTICULAR CANCER; UNITED-STATES; BIRTH COHORT; BODY HEIGHT; YOUNG MEN; DENMARK; INCREASE; CRYPTORCHIDISM; SMOKING AB Although the incidence of testis cancer has risen markedly in many Western populations over the past half-century, it is not clear whether rates in other populations also have increased. To clarify this issue, we examined testis cancer incidence rates over the 25-year time period of 1973-1997 for selected populations around the world. Age-standardized incidence rates for 21 registries in the Americas, Asia, Europe and Oceania over successive 5-year time periods were obtained from volumes 4-8 of Cancer Incidence in Five Continents. Testis cancer rates rose between 1973 and 1997 in most populations worldwide, although the increases were strongest and most consistent among populations of European ancestry. Rates appear to be leveling off in some Populations. The increases in testis cancer remain unexplained, although changes in the prevalence of important risk factors for this disease may be responsible. Published 2005 Wiley-Liss, Inc. C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Purdue, MP (reprint author), NCI, Div Can Epidemiol & Biostat, EPS 8121,6120 Execut Blvd, Bethesda, MD 20892 USA. EM purduem@mail.nih.gov RI Purdue, Mark/C-9228-2016 OI Purdue, Mark/0000-0003-1177-3108 NR 44 TC 99 Z9 100 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 10 PY 2005 VL 115 IS 5 BP 822 EP 827 DI 10.1002/ijc.20931 PG 6 WC Oncology SC Oncology GA 933BC UT WOS:000229597900021 PM 15704170 ER PT J AU Yoshinaga, S Hauptmann, M Sigurdson, AJ Doody, MM Freedman, DM Alexander, BH Linet, MS Ron, E Mabuchi, K AF Yoshinaga, S Hauptmann, M Sigurdson, AJ Doody, MM Freedman, DM Alexander, BH Linet, MS Ron, E Mabuchi, K TI Nonmelanoma skin cancer in relation to ionizing radiation exposure among US radiologic technologists SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE epidemiology; occupational exposure; ionizing radiation; nonmelanoma skin cancer; ultraviolet radiation ID SQUAMOUS-CELL CARCINOMA; UNITED-STATES; RISK-FACTORS; FOLLOW-UP; MORTALITY; HEALTH; NECK; HEAD; HUMANS; TUMORS AB Ionizing radiation (IR) is an established cause of nonmelanoma skin cancer, but there is uncertainty about the risk associated with chronic occupational exposure to IR and how it is influenced by ultraviolet radiation (UVR) exposure. We studied 1,355 incident cases with basal cell carcinoma (BCC) and 270 with squamous cell carcinoma (SCC) of the skin in a cohort of 65,304 U.S. white radiologic technologists who responded to the baseline questionnaire survey in 1983-1989 and the follow-up survey in 1994-1998. Cox's proportional-hazards model was used to estimate relative risks of BCC and SCC associated with surrogate measures of occupational exposure to IR and residential UVR exposure during childhood and adulthood, adjusted for potential confounders including pigmentation characteristics. Relative risks of BCC, but not of SCC, were elevated among technologists who first worked during the 1950s (RR = 1.42; 95% CI = 1.12-1.80), 1940s (RR = 2.04; 95% CI = 1.44-2.88) and before 1940 (RR = 2.16; 95% Cl = 1.14-4.09), when IR exposures were high, compared to those who first worked after 1960 (p for trend < 0.01). The effect of year first worked on BCC risk was not modified by UVR exposure, but was significantly stronger among individuals with lighter compared to darker eye and hair color (p = 0.013 and 0.027, respectively). This study provides some evidence that chronic occupational exposure to IR at low to moderate levels can increase the risk of BCC, and that this risk may be modified by pigmentation characteristics. Published 2005 Wiley-Liss, Inc. C1 Natl Inst Radiol Sci, Res Ctr Radiat Safety, Environm Radiat Protect Res Grp, Inage Ku, Chiba 2638555, Japan. NCI, Div Can Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Minnesota, Div Environm Hlth Sci, Minneapolis, MN USA. RP Yoshinaga, S (reprint author), Natl Inst Radiol Sci, Res Ctr Radiat Safety, Environm Radiat Protect Res Grp, Inage Ku, 4-9-1,Anagawa, Chiba 2638555, Japan. EM yosinaga@nirs.go.jp FU NCI NIH HHS [N02-CP-81005, N01-CP-15673, N01-CP-51016, N02-CP-81121] NR 44 TC 31 Z9 32 U1 2 U2 7 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 10 PY 2005 VL 115 IS 5 BP 828 EP 834 DI 10.1002/ijc.20939 PG 7 WC Oncology SC Oncology GA 933BC UT WOS:000229597900022 PM 15704092 ER PT J AU Cardis, E Vrijheid, M Blettner, M Gilbert, E Hakama, M Hill, C Howe, G Kaldor, J Muirhead, CR Schubauer-Berigan, M Yoshimura, T AF Cardis, E Vrijheid, M Blettner, M Gilbert, E Hakama, M Hill, C Howe, G Kaldor, J Muirhead, CR Schubauer-Berigan, M Yoshimura, T CA Int Study Grp TI Risk of cancer after low doses of ionising radiation - retrospective cohort study in 15 countries SO BRITISH MEDICAL JOURNAL LA English DT Article ID ATOMIC-BOMB SURVIVORS; MORTALITY; EXPOSURE; SMOKING; WORKERS; ENERGY; RATES AB Objectives To provide direct estimates of risk of cancer after protracted low doses of ionising radiation and to strengthen the scientific basis of radiation protection standards for environmental, occupational, and medical diagnostic exposures. Design Multinational retrospective cohort study of cancer mortality. Setting Cohorts of workers in the nuclear industry in 15 countries. Participants 407 391 workers individually monitored for external radiation with a total follow-up of 5.2 million person years. Main outcome measurements Estimates of excess relative risks per sievert (Sv) of radiation dose for mortality from cancers other than leukaemia and from leukaemia excluding chronic lymphocytic leukaemia, the main causes of death considered by radiation protection authorities. Results The excess relative risk for cancers other than leukaemia was 0.97 per Sv, 95% confidence interval 0.14 to 1.97. Analyses of causes of death related or unrelated to smoking indicate that, although confounding by smoking may be present, it is unlikely to explain all of this increased risk. The excess relative risk for leukaemia excluding chronic lymphocytic leukaemia was 1.93 per Sv (< 0 to 8.47). On the basis of these estimates, 1-2% of deaths from cancer among workers in this cohort may be attributable to radiation. Conclusions These estimates, from the largest study of nuclear workers ever conducted, are higher than, but statistically compatible with, the risk estimates used for current radiation protection standards. The results suggest that there is a small excess risk of cancer, even at the low doses and dose rates typically received by nuclear workers in this study. C1 Int Agcy Res Canc, Radiat Grp, F-69372 Lyon, France. Univ Mainz, Inst Med Biostat Epidemiol & Informat, D-6500 Mainz, Germany. NCI, Radiat Epidemiol Branch, Div Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Tampere, FIN-33101 Tampere, Finland. Inst Gustave Roussy, Villejuif, France. Columbia Univ, Mailman Sch Publ Hlth, New York, NY USA. Natl Ctr HIV Epidemiol & Clin Res, Sydney, NSW, Australia. Hlth Protect Agcy, Radiat Protect Div, Didcot, Oxon, England. NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Industrywide Studies Branch, Cincinnati, OH 45226 USA. Fukuoka Inst Hlth & Environm Sci, Fukuoka, Japan. RP Cardis, E (reprint author), Int Agcy Res Canc, Radiat Grp, 150 Cours Albert Thomas, F-69372 Lyon, France. EM cardis@iarc.fr RI Schubauer-Berigan, Mary/B-3149-2009; Ahn, Yoon-Ok/J-5530-2012; Kaldor, John /D-4545-2011; Gulis, Gabriel/E-4505-2013; Cardis, Elisabeth/C-3904-2017; Vrijheid, M/H-2702-2014 OI Schubauer-Berigan, Mary/0000-0002-5175-924X; Vrijheid, M/0000-0002-7090-1758 FU ODCDC CDC HHS [U50/CCU011778] NR 22 TC 286 Z9 305 U1 4 U2 30 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-8146 J9 BRIT MED J JI Br. Med. J. PD JUL 9 PY 2005 VL 331 IS 7508 BP 77 EP 80B DI 10.1136/bmj.38499.599861.E0 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 945XR UT WOS:000230536800013 PM 15987704 ER PT J AU Kim, CH Braud, S Isaac, JTR Roche, KW AF Kim, CH Braud, S Isaac, JTR Roche, KW TI Protein kinase C phosphorylation of the metabotropic glutamate receptor mGluR5 on serine 839 regulates Ca(2+) oscillations SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID CALCIUM OSCILLATIONS; GENE-EXPRESSION; DESENSITIZATION; ACTIVATION; FREQUENCY; GLUTAMATE-RECEPTOR-5; DETERMINANTS; SENSITIVITY; PKC AB The activation of Group 1 metabotropic glutamate receptors, mGluR5 and mGluR1 alpha, triggers intracellular calcium release; however, mGluR5 activation is unique in that it elicits Ca(2+) oscillations. A short region of the mGluR5 C terminus is the critical determinant and differs from the analogous region of mGluR1 alpha by a single amino acid residue, Thr-840, which is an aspartic acid (Asp-854) in mGluR1 alpha. Previous studies show that mGluR5-elicited Ca(2+) oscillations require protein kinase C (PKC)-dependent phosphorylation and identify Thr-840 as the phosphorylation site. However, direct phosphorylation of mGluR5 has not been studied in detail. We have used biochemical analyses to directly investigate the phosphorylation of the mGluR5 C terminus. We showed that Ser-839 on mGluR5 is directly phosphorylated by PKC, whereas Thr-840 plays a permissive role. Although Ser-839 is conserved in mGluR1 alpha (Ser-853), it is not phosphorylated, as the adjacent residue (Asp-854) is not permissive; however, mutagenesis of Asp-854 to a permissive alanine residue allows phosphorylation of Ser-853 on mGluR1 alpha. We investigated the physiological consequences of mGluR5 Ser-839 phosphorylation using Ca(2+) imaging. Mutations that eliminate Ser-839 phosphorylation prevent the characteristic mGluR5-dependent Ca(2+) oscillations. However, mutation of Thr-840 to alanine, which prevents potential Thr-840 phosphorylation but is still permissive for Ser-839 phosphorylation, has no effect on Ca(2+) oscillations. Thus, we showed that it is phosphorylation of Ser-839, not Thr-840, that is absolutely required for the unique Ca(2+) oscillations produced by mGluR5 activation. The Thr-840 residue is important only in that it is permissive for the PKC-dependent phosphorylation of Ser-839. C1 NINDS, NIH, Bethesda, MD 20892 USA. Univ Bristol, Dept Anat, Med Res Council Ctr Synap Plast, Bristol BS8 1TD, Avon, England. RP Roche, KW (reprint author), NINDS, NIH, Bldg 35,Rm 2C903, Bethesda, MD 20892 USA. EM rochek@ninds.nih.gov OI Roche, Katherine/0000-0001-7282-6539 FU Wellcome Trust NR 28 TC 35 Z9 37 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 8 PY 2005 VL 280 IS 27 BP 25409 EP 25415 DI 10.1074/jbc.M502644200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 941IG UT WOS:000230207900015 PM 15894802 ER PT J AU Gupta, R Sharma, S Sommers, JA Jin, Z Cantor, SB Brosh, RM AF Gupta, R Sharma, S Sommers, JA Jin, Z Cantor, SB Brosh, RM TI Analysis of the DNA substrate specificity of the human BACH1 helicase associated with breast cancer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID HOLLIDAY JUNCTIONS; ESCHERICHIA-COLI; BRCT DOMAIN; PROTEIN; BINDING; REPAIR; DAMAGE; PHOSPHOPEPTIDE; RECOGNITION; MECHANISM AB We have investigated the DNA substrate specificity of BACH1 ( BRCA1- associated C- terminal helicase). The importance of various DNA structural elements for efficient unwinding by purified recombinant BACH1 helicase was examined. The results indicated that BACH1 preferentially binds and unwinds a forked duplex substrate compared with a duplex flanked by only one single-stranded DNA ( ssDNA) tail. In support of its DNA substrate preference, helicase sequestration studies revealed that BACH1 can be preferentially trapped by forked duplex molecules. BACH1 helicase requires a minimal 5' ssDNA tail of 15 nucleotides for unwinding of conventional duplex DNA substrates; however, the enzyme is able to catalytically release the third strand of the homologous recombination intermediate D- loop structure irrespective of DNA tail status. In contrast, BACH1 completely fails to unwind a synthetic Holliday junction structure. Moreover, BACH1 requires nucleic acid continuity in the 5 ' ssDNA tail of the forked duplex substrate within six nucleotides of the ssDNA- dsDNA junction to initiate efficiently DNA unwinding. These studies provide the first detailed information on the DNA substrate specificity of BACH1 helicase and provide insight to the types of DNA structures the enzyme is likely to act upon to perform its functions in DNA repair or recombination. C1 NIA, Lab Mol Gerontol, NIH, Baltimore, MD 21224 USA. Univ Massachusetts, Sch Med, Dept Canc Biol, Worcester, MA 01605 USA. RP Brosh, RM (reprint author), NIA, Lab Mol Gerontol, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM BroshR@grc.nia.nih.gov OI Sharma, Sudha/0000-0003-2765-2482 NR 32 TC 77 Z9 81 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 8 PY 2005 VL 280 IS 27 BP 25450 EP 25460 DI 10.1074/jbc.M501995200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 941IG UT WOS:000230207900019 PM 15878853 ER PT J AU Naude, B Brzostowski, JA Kimmel, AR Wellems, TE AF Naude, B Brzostowski, JA Kimmel, AR Wellems, TE TI Dictyostelium discoideum expresses a malaria chloroquine resistance mechanism upon transfection with mutant, but not wild-type, Plasmodium falciparum transporter PfCRT SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID TRANSMEMBRANE PROTEIN PFCRT; DIGESTIVE VACUOLAR PH; IN-VITRO; INFECTED ERYTHROCYTES; EFFLUX; MUTATIONS; PARASITES; PIPERAQUINE; IDENTIFICATION; ACCUMULATION AB Chloroquine resistance in Plasmodium falciparum malaria results from mutations in PfCRT, a member of a unique family of transporters present in apicomplexan parasites and Dictyostelium discoideum. Mechanisms that have been proposed to explain chloroquine resistance are difficult to evaluate within malaria parasites. Here we report on the targeted expression of wild-type and mutant forms of PfCRT to acidic vesicles in D. discoideum. We show that wild-type PfCRT has minimal effect on the accumulation of chloroquine by D. discoideum, whereas forms of PfCRT carrying a key charge-loss mutation of lysine 76 (e.g. K76T) enable D. discoideum to expel chloroquine. As in P. falciparum, the chloroquine resistance phenotype conferred on transformed D. discoideum can be reversed by the channel-blocking agent verapamil. Although intravesicular pH levels in D. discoideum show small acidic changes with the expression of different forms of PfCRT, these changes would tend to promote intravesicular trapping of chloroquine ( a weak base) and do not account for reduced drug accumulation in transformed D. discoideum. Our results instead support outward-directed chloroquine efflux for the mechanism of chloroquine resistance by mutant PfCRT. This mechanism shows structural specificity as D. discoideum transformants that expel chloroquine do not expel piperaquine, a bisquinoline analog of chloroquine used frequently against chloroquine-resistant parasites in Southeast Asia. PfCRT, nevertheless, may have some ability to act on quinine and quinidine. Transformed D. discoideum will be useful for further studies of the chloroquine resistance mechanism and may assist in the development and evaluation of new antimalarial drugs. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. NIDDKD, Cellular & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. RP Wellems, TE (reprint author), NIAID, Lab Malaria & Vector Res, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM twellems@niaid.nih.gov FU NIAID NIH HHS [Z01 AI000483-20]; NIDDK NIH HHS [Z01 DK015503-24] NR 57 TC 47 Z9 54 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 8 PY 2005 VL 280 IS 27 BP 25596 EP 25603 DI 10.1074/jbc.M503227200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 941IG UT WOS:000230207900038 PM 15883156 ER PT J AU Pan, PY Cai, Q Lin, L Lu, PH Duan, SM Sheng, ZH AF Pan, PY Cai, Q Lin, L Lu, PH Duan, SM Sheng, ZH TI SNAP-29-mediated modulation of synaptic transmission in cultured hippocampal neurons SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; SHORT-TERM PLASTICITY; NEUROTRANSMITTER RELEASE; CALCIUM-CHANNELS; N-TYPE; PRESYNAPTIC PROTEINS; CENTRAL SYNAPSES; NERVE-TERMINALS; ALPHA-SNAP; IN-VITRO AB Identifying the molecules that regulate both the recycling of synaptic vesicles and the SNARE components required for fusion is critical for elucidating the molecular mechanisms underlying synaptic plasticity. SNAP- 29 was initially isolated as a syntaxin- binding and ubiquitously expressed protein. Previous studies have suggested that SNAP- 29 inhibits SNARE complex disassembly, thereby reducing synaptic transmission in cultured superior cervical ganglion neurons in an activity-dependent manner. However, the role of SNAP- 29 in regulating synaptic vesicle recycling and short- term plasticity in the central nervous system remains unclear. In the present study, we examined the effect of SNAP- 29 on synaptic transmission in cultured hippocampal neurons by dual patch clamp whole- cell recording, FM dye imaging, and immunocytochemistry. Our results demonstrated that exogenous expression of SNAP- 29 in presynaptic neurons significantly decreased the efficiency of synaptic transmission after repetitive firing within a few minutes under low and moderate frequency stimulations ( 0.1 and 1 Hz). In contrast, SNAP- 29 did not affect the density of synapses and basal synaptic transmission. Whereas neurotransmitter release was unaffected during intensive stimulation, recovery after synaptic depression was impaired by SNAP- 29. Furthermore, knockdown of SNAP- 29 expression in neurons by small interfering RNA increased the efficiency of synaptic transmission during repetitive firing. These findings suggest that SNAP- 29 acts as a negative modulator for neurotransmitter release, probably by slowing recycling of the SNARE- based fusion machinery and synaptic vesicle turnover. C1 Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai 200031, Peoples R China. Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Neurobiol, Shanghai 200031, Peoples R China. Shanghai Med Univ 2, Dept Neurobiol, Shanghai 200025, Peoples R China. NINDS, Synapt Funct Unit, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. RP Duan, SM (reprint author), Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Neurosci, Shanghai 200031, Peoples R China. EM shumin@ion.ac.cn; shengz@ninds.nih.gov FU Intramural NIH HHS; NINDS NIH HHS [Z01 NS002946-09] NR 50 TC 35 Z9 38 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 8 PY 2005 VL 280 IS 27 BP 25769 EP 25779 DI 10.1074/jbc.M502356200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 941IG UT WOS:000230207900058 PM 15890653 ER PT J AU Winn, RM Gil-Lamaignere, C Roilides, E Simitsopoulou, M Lyman, CA Maloukou, A Walsh, TJ AF Winn, RM Gil-Lamaignere, C Roilides, E Simitsopoulou, M Lyman, CA Maloukou, A Walsh, TJ TI Effects of interleukin-15 on antifungal responses of human polymorphonuclear leukocytes against Fusarium spp. and Scedosporium spp. SO CYTOKINE LA English DT Article DE filamentous fungi; hyphal damage; interleukin-15; polymorphonuclear leukocytes; oxidative burst ID NATURAL-KILLER-CELLS; RECEPTOR-BETA-CHAIN; 10 YEARS EXPERIENCE; ASPERGILLUS-FUMIGATUS; PSEUDALLESCHERIA-BOYDII; HUMAN-NEUTROPHILS; HUMAN MONOCYTES; IL-2 RECEPTOR; INVASIVE ASPERGILLOSIS; DISSEMINATED INFECTION AB Fusarium spp. and Scedosporium spp. have emerged as important fungal pathogens that are frequently resistant to antifungal compounds. We investigated the effects of human interleukin-15 (IL-15) on human polymorphonuclear leukocyte (PMNL) activity against Fusarium solani and Fusarium oxysporum as well as Scedosporium prolificans and Scedosporium apiospermum. IL-15 (100 ng/ml) significantly enhanced PMNL-induced hyphal damage of both Fusarium spp. and S. prolificans after incubation for 22 h (P < 0.01) but not S. apiospermum. In addition, IL-15 enhanced PMNL oxidative respiratory burst evaluated as superoxide anion production in response to S. prolificans but not to the other fungi after 2 h incubation. IL-15 increased interleukin-8 (IL-8) release from PMNLs challenged with hyphae of F. solani and S. prolificans (P <= 0.04). Release of tumor necrosis factor-a was not affected. The species-dependent enhancement of hyphal damage and induction of IL-8 release suggest that IL-15 plays an important role in the immunomodulation of host response to these emerging fungal pathogens. (c) 2004 Published by Elsevier Ltd. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Aristotle Univ Thessaloniki, Hippokrat Hosp Gen, Dept Pediat 3, GR-54642 Thessaloniki, Greece. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bldg 10,Rm 13N240, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov NR 49 TC 12 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1043-4666 J9 CYTOKINE JI Cytokine PD JUL 7 PY 2005 VL 31 IS 1 BP 1 EP 8 DI 10.1016/j.cyto.2004.07.016 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 944QN UT WOS:000230444000001 PM 15935692 ER PT J AU Gaede, HC Yau, WM Gawrisch, K AF Gaede, HC Yau, WM Gawrisch, K TI Electrostatic contributions to indole-lipid interactions SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID OVERHAUSER ENHANCEMENT SPECTROSCOPY; MAGNETIC-RESONANCE SPECTROSCOPY; CROSS-RELAXATION RATES; ALPHA-HELICAL PEPTIDES; MEMBRANE-PROTEINS; GRAMICIDIN CHANNEL; TRYPTOPHAN; BILAYER; ANALOGS; WATER AB The role of electrostatic forces in indole-lipid interactions was studied by H-1 and H-2 NMR in ether- and ester-linked phospholipid bilayers with incorporated indole. Indole-ring-current-induced 1H NMR chemical shifts of lipid resonances in bilayers of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine, 1,2-dioleoyl-sn-glycero-3-phosphocholine, 1,2-di-O-octadecenyl-sn-glycero-3-phosphocholine, and 1,2-di-O-octadecenyl-sn-glycero-3-phosphomethanol show a bimodal indole distribution, with indole residing at the upper hydrocarbon chain/glycerol region of the lipid and near the choline group, when present. H-2 NMR of indole-d(7)-incorporated lipid bilayers reveals that the former site is occupied by about two-thirds of the indole, which adopts a distinct preferred orientation with respect to the bilayer normal. The results suggest that the upper hydrocarbon chain/ glycerol location is dictated by many factors, including interactions with the electric charges and dipoles, van der Waals interactions, entropic contributions, and hydrogen bonding. Indole diffusion rates are higher in lipids with ester bonds and lower in choline-containing lipids, suggesting that interactions between indole and carbonyl groups are of minor importance for lipid-indole association and that cation-pi interactions with choline drive the second indole location. Nuclear Overhauser effect spectroscopy cross-relaxation rates suggest a 30-ns lifetime for indole-lipid associations. These results may have important implications for sidedness and structural transitions in tryptophan-rich membrane proteins. C1 NIAAA, Lab Membrane Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Gawrisch, K (reprint author), NIAAA, Lab Membrane Biochem & Biophys, NIH, 5625 Fishers Lane,Room 3N07, Bethesda, MD 20892 USA. EM gawrisch@helix.nih.gov RI Gaede, Holly/B-7392-2015 OI Gaede, Holly/0000-0003-4444-4394 NR 36 TC 55 Z9 58 U1 1 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD JUL 7 PY 2005 VL 109 IS 26 BP 13014 EP 13023 DI 10.1021/jp0511000 PG 10 WC Chemistry, Physical SC Chemistry GA 941OS UT WOS:000230224700051 PM 16852615 ER PT J AU Glenn, M AF Glenn, M TI Cancer biology - The weakest link? SO NATURE LA English DT Editorial Material ID MUTATIONS; NICHE C1 NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. RP Glenn, M (reprint author), NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. EM gmerlino@helix.nih.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD JUL 7 PY 2005 VL 436 IS 7047 BP 33 EP + DI 10.1038/436033a PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 942QJ UT WOS:000230296600028 ER PT J AU Van Meurs, KP Wright, LL Ehrenkranz, RA Lemons, JA Ball, MB Poole, WK Perritt, R Higgins, RD Oh, W Hudak, ML Laptook, AR Shankaran, S Finer, NN Carlo, WA Kennedy, KA Fridriksson, JH Steinhorn, RH Sokol, GM Konduri, GG Aschner, JL Stoll, BJ D'Angio, CT Stevenson, DK Oh, W Hensman, A Gingras, D Stoll, BJ Jain, L Hale, E Seabrook, I Sokol, G Lorant, D Appel, DD Miller, L Chriscinske, D Attwood, J Steinhorn, R Sautel, M Van Meurs, K Ball, B Proud, D Carlo, WA Cosby, SS Johnson, RB Fridriksson, J Warner, B Mersmann, M Alexander, B Shively, J Mincey, H Hoover, M Sapienz, S Stephenson, E Finer, NN Rasmussen, MR Henderson, C Demetrio, C Rich, W Joseph, C Hudak, M Osbeck, S Case, E Kellum, A Hogans, L D'Angio, CT Reubens, L Hutton, G Laptook, A Madison, S Hensley, G Miller, N Metoyer, G Kennedy, K McDavid, G Emerson, D Konduri, G Paquette, M Wong, S Aschner, J O'Shea, TM Peters, N Hansell, BJ Griffin, J Adams, C Shankaran, S Bara, RA Muran, G Weekfall, W Ehrenkranz, RA Gettner, P Caldwell, A Oh, W Fanaroff, AA Goldberg, RN Stoll, BJ Lemons, JA Stevenson, DK Carlo, WA Donovan, EF Finer, NN Duara, S Phelps, DL Laptook, AR Tyson, JE O'Shea, TM Shankaran, S Ehrenkranz, RA Jobe, A Poole, WK Hastings, B Petrie, C Higgins, RD Wright, LL McClure, E Bulas, D Mertens, D Slovis, T Avery, G D'Alton, M Poole, WK Fletcher, JC Gleason, CA Redmond, C AF Van Meurs, KP Wright, LL Ehrenkranz, RA Lemons, JA Ball, MB Poole, WK Perritt, R Higgins, RD Oh, W Hudak, ML Laptook, AR Shankaran, S Finer, NN Carlo, WA Kennedy, KA Fridriksson, JH Steinhorn, RH Sokol, GM Konduri, GG Aschner, JL Stoll, BJ D'Angio, CT Stevenson, DK Oh, W Hensman, A Gingras, D Stoll, BJ Jain, L Hale, E Seabrook, I Sokol, G Lorant, D Appel, DD Miller, L Chriscinske, D Attwood, J Steinhorn, R Sautel, M Van Meurs, K Ball, B Proud, D Carlo, WA Cosby, SS Johnson, RB Fridriksson, J Warner, B Mersmann, M Alexander, B Shively, J Mincey, H Hoover, M Sapienz, S Stephenson, E Finer, NN Rasmussen, MR Henderson, C Demetrio, C Rich, W Joseph, C Hudak, M Osbeck, S Case, E Kellum, A Hogans, L D'Angio, CT Reubens, L Hutton, G Laptook, A Madison, S Hensley, G Miller, N Metoyer, G Kennedy, K McDavid, G Emerson, D Konduri, G Paquette, M Wong, S Aschner, J O'Shea, TM Peters, N Hansell, BJ Griffin, J Adams, C Shankaran, S Bara, RA Muran, G Weekfall, W Ehrenkranz, RA Gettner, P Caldwell, A Oh, W Fanaroff, AA Goldberg, RN Stoll, BJ Lemons, JA Stevenson, DK Carlo, WA Donovan, EF Finer, NN Duara, S Phelps, DL Laptook, AR Tyson, JE O'Shea, TM Shankaran, S Ehrenkranz, RA Jobe, A Poole, WK Hastings, B Petrie, C Higgins, RD Wright, LL McClure, E Bulas, D Mertens, D Slovis, T Avery, G D'Alton, M Poole, WK Fletcher, JC Gleason, CA Redmond, C CA Preemie Inhaled Nitric Oxide Study TI Inhaled nitric oxide for premature infants with severe respiratory failure SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID HYALINE-MEMBRANE DISEASE; PERSISTENT PULMONARY-HYPERTENSION; RANDOMIZED CONTROLLED-TRIAL; DISTRESS-SYNDROME; PLATELET-AGGREGATION; BLEEDING-TIME; NEWBORN; TERM; ENDOTHELIUM; PRESSURE AB Background: Inhaled nitric oxide is a controversial treatment for premature infants with severe respiratory failure. We conducted a multicenter, randomized, blinded, controlled trial to determine whether inhaled nitric oxide reduced the rate of death or bronchopulmonary dysplasia in such infants. Methods: We randomly assigned 420 neonates, born at less than 34 weeks of gestation, with a birth weight of 401 to 1500 g, and with respiratory failure more than four hours after treatment with surfactant to receive placebo (simulated flow) or inhaled nitric oxide (5 to 10 ppm). Infants with a response (an increase in the partial pressure of arterial oxygen of more than 10 mm Hg) were weaned according to protocol. Treatment with study gas was discontinued in infants who did not have a response. Results: The rate of death or bronchopulmonary dysplasia was 80 percent in the nitric oxide group, as compared with 82 percent in the placebo group (relative risk, 0.97; 95 percent confidence interval, 0.86 to 1.06; P=0.52), and the rate of bronchopulmonary dysplasia was 60 percent versus 68 percent (relative risk, 0.90; 95 percent confidence interval, 0.75 to 1.08; P=0.26). There were no significant differences in the rates of severe intracranial hemorrhage or periventricular leukomalacia. Post hoc analyses suggest that rates of death and bronchopulmonary dysplasia are reduced for infants with a birth weight greater than 1000 g, whereas infants weighing 1000 g or less who are treated with inhaled nitric oxide have higher mortality and increased rates of severe intracranial hemorrhage. Conclusions: The use of inhaled nitric oxide in critically ill premature infants weighing less than 1500 g does not decrease the rates of death or bronchopulmonary dysplasia. Further trials are required to determine whether inhaled nitric oxide benefits infants with a birth weight of 1000 g or more. C1 Stanford Univ, Sch Med, Dept Pediat, Div Neonatol & Dev Med, Palo Alto, CA 94304 USA. NICHHD, NICHD, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT USA. Indiana Univ, Sch Med, Indianapolis, IN USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Brown Univ, Women & Infants Hosp, Providence, RI USA. Univ Florida, Jacksonville, FL USA. Wayne State Univ, Detroit, MI USA. Univ Calif San Diego, San Diego, CA 92103 USA. Univ Alabama, Birmingham, AL USA. Univ Texas, Houston, TX USA. Univ Cincinnati, Coll Med, Cincinnati, OH 45221 USA. Northwestern Univ, Chicago, IL 60611 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. Emory Univ, Sch Med, Atlanta, GA USA. Univ Rochester, Rochester, NY USA. RP Van Meurs, KP (reprint author), Stanford Univ, Sch Med, Dept Pediat, Div Neonatol & Dev Med, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA. EM vanmeurs@stanford.edu RI Steinhorn, Robin/A-4248-2010 FU NCRR NIH HHS [M01 RR00039, M01 RR00044, M01 RR08084, M01 RR06022, M01 RR00750, M01 RR00070]; NICHD NIH HHS [U10 HD27853, U10 HD40461, U10 HD 21373, U10 HD27856, U10 HD40521, U01 HD36790, U10 HD27871, U10 HD40689, U10 HD21385, U10 HD27851, U10 HD34216, U10 HD27904, U10 HD40498, U10 HD27880] NR 35 TC 144 Z9 146 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 7 PY 2005 VL 353 IS 1 BP 13 EP 22 DI 10.1056/NEJMoa043927 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 942FC UT WOS:000230267300004 PM 16000352 ER PT J AU Shin, Y Fournier, JH Balachandran, R Madiraju, C Raccor, BS Zhu, G Edler, MC Hamel, E Day, BW Curran, DP AF Shin, Y Fournier, JH Balachandran, R Madiraju, C Raccor, BS Zhu, G Edler, MC Hamel, E Day, BW Curran, DP TI Synthesis and biological evaluation of (-)-16-normethyldictyostatin: A potent analogue of (-)-dictyostatin SO ORGANIC LETTERS LA English DT Article ID MICROTUBULE-STABILIZING MACROLIDE; MARINE SPONGE ORIGIN; (+)-DISCODERMOLIDE; DICTYOSTATIN-1; DESIGN; TAXOL AB (-)-16-Normethyldictyostatin has been made by total synthesis and is a potent antitumor agent in cells expressing wild-type tubulin and in one mutant cell line that is resistant to paclitaxel, but it is much less active than dictyostatin in another paclitaxel-resistant cell line where Val is substituted for Phe270. This provides strong evidence that the C16 methyl group of the dictyostatins is oriented toward Phe270 in the paclitaxel-binding site on beta-tubulin. C1 Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15261 USA. Univ Pittsburgh, Dept Pharmaceut Sci, Pittsburgh, PA 15261 USA. Natl Canc Inst, Screening Technol Branch, Dev Therapeut Program, Div Canc Treatment & Diag,NIH, Ft Detrick, MD 21702 USA. RP Shin, Y (reprint author), Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15261 USA. EM curran@pitt.edu OI ZHU, Guangyu/0000-0002-4710-7070 FU NCI NIH HHS [CA078039] NR 17 TC 51 Z9 51 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD JUL 7 PY 2005 VL 7 IS 14 BP 2873 EP 2876 DI 10.1021/ol050808u PG 4 WC Chemistry, Organic SC Chemistry GA 941KG UT WOS:000230213100018 PM 15987158 ER PT J AU Harding, WW Tidgewell, K Schmidt, M Shah, K Dersch, CM Snyder, J Parrish, D Deschamps, JR Rothman, RB Prisinzano, TE AF Harding, WW Tidgewell, K Schmidt, M Shah, K Dersch, CM Snyder, J Parrish, D Deschamps, JR Rothman, RB Prisinzano, TE TI Salvinicins A and B, new neoclerodane diterpenes from Salvia divinorum SO ORGANIC LETTERS LA English DT Article ID OPIOID RECEPTOR AGONIST; SALVINORIN-A; MINT; STEREOCHEMISTRY; HALLUCINOGEN; LSD AB Two new neoclerodane diterpenes, salvinicins A (4) and B (5), were isolated from the dried leaves of Salvia divinorum. The structures of these compounds were elucidated by spectroscopic techniques, including H-1 and C-13 NMR, NOESY, HMQC, and HMBC. The absolute stereochemistry of these compounds was assigned on the basis of single-crystal X-ray crystallographic analysis of salvinicin A (4) and a 3,4-dichlorobenzoate derivative of salvinorin B. C1 Univ Iowa, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. NIDA, IRP, DHHS,Lab Struct Matter,Code 6030, Clin Psychopharmacol Sect,NIH, Baltimore, MD 21224 USA. Naval Res Lab, Washington, DC USA. Univ Iowa, High Field NMR Facil, Iowa City, IA 52242 USA. RP Harding, WW (reprint author), Univ Iowa, Div Med & Nat Prod Chem, Iowa City, IA 52242 USA. EM thomas-prisinzano@uiowa.edu RI Prisinzano, Thomas/B-7877-2010; OI Deschamps, Jeffrey/0000-0001-5845-0010; Tidgewell , Kevin/0000-0002-0501-2604 FU NIDA NIH HHS [R01 DA018151, R01 DA018151-01A2] NR 32 TC 41 Z9 45 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD JUL 7 PY 2005 VL 7 IS 14 BP 3017 EP 3020 DI 10.1021/ol0510522 PG 4 WC Chemistry, Organic SC Chemistry GA 941KG UT WOS:000230213100054 PM 15987194 ER PT J AU Khurana, T Brzostowski, JA Kimmel, AR AF Khurana, T Brzostowski, JA Kimmel, AR TI A Rab21/LIM-only/CH-LIM complex regulates phagocytosis via both activating and inhibitory mechanisms SO EMBO JOURNAL LA English DT Article DE Dictyostelium; GTPases; phagocytosis; Rab21; vesicle formation ID DICTYOSTELIUM-DISCOIDEUM; PHAGOSOME MATURATION; LEGIONELLA-PNEUMOPHILA; MEMBRANE TRAFFICKING; FUSION PROTEIN; LIM PROTEINS; RUN FUSION; ADHESION; RAB5; CYTOSKELETON AB We have identified two LIM domain proteins, LimF and ChLim, from Dictyostelium that interact with each other and with the small, Rab5-related, Rab21 GTPase to collectively regulate phagocytosis. To investigate in vivo functions, we generated cell lines that lack or overexpress LimF and ChLim and strains that express activating or inhibiting variants of Rab21. Overexpression of LimF, loss of ChLim, or expression of constitutively active Rab21 increases the rate of phagocytosis above that of wild type. Conversely, loss of LimF, overexpression of ChLim, or expression of a dominant-negative Rab21 inhibits phagocytosis. Our studies using cells carrying multiple mutations in these genes further indicate that ChLim antagonizes the activating function of Rab21-GTP during phagocytosis; in turn, LimF is required for Rab21-GTP function. Finally, we demonstrate that ChLim and LimF localize to the phagocytic cup and phago-lysosomal vesicles. We suggest that LimF, ChLim, and activated Rab21-GTP participate as a novel signaling complex that regulates phagocytic activity. C1 NIDDK, Cellular & Dev Biol Lab, NIH, MMDS, Bethesda, MD 20892 USA. RP Kimmel, AR (reprint author), NIDDK, Cellular & Dev Biol Lab, NIH, MMDS, Bldg 6-B1-22, Bethesda, MD 20892 USA. EM ark1@helix.nih.gov NR 43 TC 29 Z9 32 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 6 PY 2005 VL 24 IS 13 BP 2254 EP 2264 DI 10.1038/sj.emboj.7600716 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 951UI UT WOS:000230956500003 PM 15962002 ER PT J AU Kwon, J Qu, CK Maeng, JS Falahati, R Lee, C Williams, MS AF Kwon, J Qu, CK Maeng, JS Falahati, R Lee, C Williams, MS TI Receptor-stimulated oxidation of SHP-2 promotes T-cell adhesion through SLP-76-ADAP SO EMBO JOURNAL LA English DT Article DE adhesion; reactive oxygen species; protein tyrosine phosphatase; signal transduction; T lymphocyte ID PROTEIN-TYROSINE-PHOSPHATASE; HYDROGEN-PEROXIDE; REVERSIBLE OXIDATION; SIGNAL-TRANSDUCTION; REDOX REGULATION; INTEGRIN ADHESION; GROWTH-FACTOR; IN-VIVO; ACTIVATION; 1B AB Receptor-stimulated generation of intracellular reactive oxygen species (ROS) modulates signal transduction, although the mechanism(s) is unclear. One potential basis is the reversible oxidation of the active site cysteine of protein tyrosine phosphatases (PTPs). Here, we show that activation of the antigen receptor of T cells (TCR), which induces production of ROS, induces transient inactivation of the SH2 domain-containing PTP, SHP-2, but not the homologous SHP-1. SHP-2 is recruited to the LAT Gads - SLP- 76 complex and directly regulates the phosphorylation of key signaling proteins Vav1 and ADAP. Furthermore, the association of ADAP with the adapter SLP- 76 is regulated by SHP-2 in a redox-dependent manner. The data indicate that TCR-mediated ROS generation leads to SHP-2 oxidation, which promotes T-cell adhesion through effects on an SLP-76-dependent signaling pathway to integrin activation. C1 Univ Maryland, Sch Med, Dept Immunol & Microbiol, Rockville, MD 20855 USA. Univ Maryland, Sch Med, Dept Pathol, Rockville, MD 20855 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Med, Dept Immunol, Washington, DC USA. Veritas Inc, Rockville, MD USA. RP Williams, MS (reprint author), Univ Maryland, Sch Med, Dept Immunol & Microbiol, 15601 Crabbs Branch Way, Rockville, MD 20855 USA. EM willmark@usa.redcross.org RI Falahati, Rustom/Q-4098-2016 NR 46 TC 76 Z9 77 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUL 6 PY 2005 VL 24 IS 13 BP 2331 EP 2341 DI 10.1038/sj.emboj.7600706 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 951UI UT WOS:000230956500009 PM 15933714 ER PT J AU Pluta, RM Gladwin, MT Oldfield, EH AF Pluta, RM Gladwin, MT Oldfield, EH TI Methodological standards in human vs animal clinical trials - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Dept Crit Care Med, Biol Chem Lab, NIH, Bethesda, MD USA. RP Pluta, RM (reprint author), NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. EM rysiek@ninds.nih.gov NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 6 PY 2005 VL 294 IS 1 BP 40 EP 41 DI 10.1001/jama.294.1.40-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 941JD UT WOS:000230210200013 ER PT J AU Thompson, IM Ankerst, DP Chi, C Lucia, MS Goodman, PJ Crowley, JJ Parnes, HL Coltman, CA AF Thompson, IM Ankerst, DP Chi, C Lucia, MS Goodman, PJ Crowley, JJ Parnes, HL Coltman, CA TI Operating characteristics of prostate-specific antigen in men with an initial PSA level of 3.0 ng/mL or lower SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID CANCER MORTALITY; TRENDS; SURVEILLANCE; VERIFICATION; PREVALENCE; SURVIVAL; DISEASE; IMPACT; BIAS AB Context Three fourths of US men older than 50 years have been screened with prostate-specific antigen (PSA) for prostate cancer. Objective To estimate the receiver operating characteristic (ROC) curve for PSA. Design, Setting, and Participants Calculation of PSA ROC curves in the placebo group of the Prostate Cancer Prevention Trial, a randomized, prospective study conducted from 1993 to 2003 at 221 US centers. Participants were 18 882 healthy men aged 55 years or older without prostate cancer and with PSA levels less than or equal to 3.0 ng/mL and normal digital rectal examination results, followed up for 7 years with annual PSA measurement and digital rectal examination. If PSA level exceeded 4.0 ng/mL or rectal examination result was abnormal, a prostate biopsy was recommended. After 7 years of study participation, an end-of-study prostate biopsy was recommended in all cancer-free men. Main Outcome Measures Operating characteristics of PSA for prostate cancer detection, including sensitivity, specificity, and ROC curve. Results Of 8575 men in the placebo group with at least 1 PSA measurement and digital rectal examination in the same year, 5587 (65.2%) had had at least 1 biopsy; of these, 1225 (21.9%) were diagnosed with prostate cancer. Of 1213 cancers with Gleason grade recorded, 250 (20.6%) were Gleason grade 7 or greater and 57 (4.7%) were Gleason grade 8 or greater. The areas under the ROC curve (AUC) for PSA to discriminate any prostate cancer vs no cancer, Gleason grade 7 or greater cancer vs no or lower-grade cancer, and Gleason grade 8 or greater cancer vs no or lower-grade cancer were 0.678 (95% confidence interval [CI], 0.666-0.689), 0.782 (95% Cl, 0.748-0.816), and 0.827 (95% Cl, 0.761-0.893), respectively (all P values <.001 for AUC vs 50%). For detecting any prostate cancer, PSA cutoff values of 1.1, 2.1, 3.1, and 4.1 ng/mL yielded sensitivities of 83.4%, 52.6%, 32.2%, and 20.5%, and specificities of 38.9%, 72.5%, 86.7%, and 93.8%, respectively. Age-stratified analyses showed slightly better performance of PSA in men younger than 70 years vs those 70 years or older with AUC values of 0.699 (SD, 0.013) vs 0.663 (SD, 0.013) (P=.03). Conclusion There is no cutpoint of PSA with simultaneous high sensitivity and high specificity for monitoring healthy men for prostate cancer, but rather a continuum of prostate cancer risk at all values of PSA. C1 SW Oncol Grp, Operat Off, San Antonio, TX 78245 USA. Univ Texas, Hlth Sci Ctr, Dept Urol, San Antonio, TX USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Colorado, Denver, CO 80202 USA. Canc Res & Biostat, Seattle, WA USA. NCI, NIH, Bethesda, MD 20892 USA. RP Thompson, IM (reprint author), SW Oncol Grp, Operat Off, 14980 Omicron Dr, San Antonio, TX 78245 USA. EM thompsoni@uthscsa.edu FU NCI NIH HHS [CA 35178, CA 37429, CA 45808, CA 86402] NR 24 TC 377 Z9 390 U1 1 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 6 PY 2005 VL 294 IS 1 BP 66 EP 70 DI 10.1001/jama.294.1.66 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 941JD UT WOS:000230210200026 PM 15998892 ER PT J AU Morris, CR Kato, GJ Poljakovic, M Wang, XD Blackwelder, WC Sachdev, V Hazen, SL Vichinsky, EP Morris, SM Gladwin, MT AF Morris, CR Kato, GJ Poljakovic, M Wang, XD Blackwelder, WC Sachdev, V Hazen, SL Vichinsky, EP Morris, SM Gladwin, MT TI Dysregulated arginine metabolism, hemolysis-associated pulmonary hypertension, and mortality in sickle cell disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article ID NITRIC-OXIDE SYNTHASE; ARGINASE ACTIVITY; P-SELECTIN; AIRWAY HYPERRESPONSIVENESS; ADHESION MOLECULES; ENDOTHELIAL-CELLS; AMINO-ACID; ANEMIA; ERYTHROCYTES; EXPRESSION AB Context Sickle cell disease is characterized by a state of nitric oxide resistance and limited bioavailability of L-arginine, the substrate for nitric oxide synthesis. We hypothesized that increased arginase activity and dysregulated arginine metabolism contribute to endothelial dysfunction, pulmonary hypertension, and patient outcomes. Objective To explore the role of arginase in sickle cell disease pathogenesis, pulmonary hypertension, and mortality. Design Plasma amino acid levels, plasma and erythrocyte arginase activities, and pulmonary hypertension status as measured by Doppler echocardiogram were prospectively obtained in outpatients with sickle cell disease. Patients were followed,up for survival up to 49 months. Setting Urban tertiary care center and community clinics in the United States between February 2001 and March 2005. Participants Two hundred twenty-eight patients with sickle cell disease, aged 18 to 74 years, and 36 control participants. Main Outcome Measures Plasma amino acid levels, plasma and erythrocyte arginase activities, diagnosis of pulmonary hypertension, and mortality. Results Plasma arginase activity was significantly elevated in patients with sickle cell disease, with highest activity found in patients with secondary pulmonary hypertension. Arginase activity correlated with the arginine-ornithine ratio, and lower ratios were associated with greater severity of pulmonary hypertension and with mortality in this population (risk ratio, 2.5; 95% confidence interval [CI] 1.2-5.2; P=.006). Global arginine bioavailability, characterized by the ratio of arginine to ornithine plus citrulline, was also strongly associated with mortality (risk ratio, 3.6; 95% Cl, 1.5-8.3; P<.001). Increased plasma arginase activity was correlated with increased intravascular hemolytic rate and, to a lesser extent, with markers of inflammation and soluble adhesion molecule levels. Conclusions These data support a novel mechanism of disease in which hemolysis contributes to reduced nitric oxide bioavailability and endothelial dysfunction via release of erythrocyte arginase, which limits arginine bioavailability, and release of erythrocyte hemoglobin, which scavenges nitric oxide. The ratios of arginine to ornithine and arginine to ornithine plus citrulline are independently associated with pulmonary hypertension and increased mortality in patients with sickle cell disease. C1 Childrens Hosp & Res Ctr Oakland, Dept Emergency Med, Oakland, CA 94609 USA. Childrens Hosp & Res Ctr Oakland, Dept Hematol Oncol, Oakland, CA 94609 USA. NHLBI, Vasc Therapeut Sect, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. NIH, Echocardiog Lab, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. Cleveland Clin Fdn, Ctr Cardiovasc Diagnost & Prevent, Dept Cell Biol, Cleveland, OH 44195 USA. Cleveland Clin Fdn, Ctr Cardiovasc Diagnost & Prevent, Dept Cardiovasc Med, Cleveland, OH 44195 USA. RP Morris, SM (reprint author), Childrens Hosp & Res Ctr Oakland, Dept Emergency Med, 747 52nd St, Oakland, CA 94609 USA. EM claudiamorris@comcast.net RI Kato, Gregory/I-7615-2014; Morris, Sidney/I-3440-2015 OI Kato, Gregory/0000-0003-4465-3217; FU Intramural NIH HHS [Z01 CL001174-07, Z99 HL999999, ZIA HL006012-01]; NCRR NIH HHS [M01 RR001271, M01-RR01271]; NHLBI NIH HHS [HL-04386-05, K23 HL004386, P01 HL076491]; NIGMS NIH HHS [R01 GM057384, R01 GM57384] NR 75 TC 345 Z9 358 U1 1 U2 12 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JUL 6 PY 2005 VL 294 IS 1 BP 81 EP 90 DI 10.1001/jama.294.1.81 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 941JD UT WOS:000230210200028 PM 15998894 ER PT J AU Hance, KW Anderson, WF Devesa, SS Young, HA Levine, PH AF Hance, KW Anderson, WF Devesa, SS Young, HA Levine, PH TI Trends in inflammatory breast carcinoma incidence and survival: The Surveillance, Epidemiology, and End Results Program at the National Cancer Institute SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID UNITED-STATES; MAMMOGRAPHIC FINDINGS; SOCIOECONOMIC-STATUS; MENOPAUSAL STATUS; AFRICAN-AMERICAN; RESULTS DATABASE; EXPRESSION; STAGE; POPULATION; DEFINITION AB Background: Inflammatory breast carcinoma (IBC) appears to be a clinicopathologic entity distinct from noninflammatory locally advanced breast cancer (LABC). We examined incidence and, survival trends for IBC in Surveillance, Epidemiology, and End Results (SEER).Program data with a case definition designed to capture many of its unique clinical and pathologic characteristics. Methods: We analyzed breast cancer cases diagnosed in the SEER 9 Registries (n = 180 224), between 1988 and 2000. Breast cancer cases were categorized using SEER's "Extent of Disease" codes in combination with International Classification of Diseases for Oncology morphology code 8530/3 and classified as IBC (n = 3648), LABC (n = 3636), and non-T4 breast cancer (n = 172 940). We compared changes in incidence rates over 3-year intervals by breast cancer subtype and race using SEER*Stat. Survival differences by breast cancer subtype and race were assessed using Kaplan-Meier curves and log-rank statistics. All statistical tests were two-sided. Results: Between 1988 and 1990 and 1997 and 1999, IBC incidence rates (per 100000 womanyears) increased from 2.0 to 2.5 (P <.001), whereas those for LABC declined (2.5 to 2.0, P =.0025), as did those for non-T4 breast cancer (108 to 101, P =.0084). IBC incidence rates were statistically significantly higher in black women (3.1) than in white women (2.2) during the study period (P <.001). Women diagnosed with IBC had statistically significantly poorer survival than women with either LABC or non-T4 breast cancer (log-rank test, P <.001). Median survival of women with IBC (2.9 years) was statistically significantly shorter than that of women with LABC (6.4 years; P <.0001) or non-T4 breast cancer (> 10 years, P <.0001). Black women with IBC or LABC had poorer survival than white women with IBC or LABC, respectively (log-rank test, P <.001). Conclusions: Throughout the 1990s, IBC incidence rose, and survival improved modestly. Substantial racial differences were noted in age at diagnosis, age-specific incidence rates, and survival outcomes. C1 NCI, Canc Prevent Fellowship Program, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Dept Epidemiol & Biostat, Washington, DC USA. NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. George Washington Univ, Inst Canc, Washington, DC USA. RP NCI, Canc Prevent Fellowship Program, Div Canc Prevent, NIH, 6120 Execut Blvd,Suite T41, Bethesda, MD 20892 USA. EM hancek@mail.nih.gov FU Intramural NIH HHS [NIH0011268250]; PHS HHS [NIH0011268250] NR 49 TC 223 Z9 234 U1 1 U2 6 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 EI 1460-2105 J9 JNCI-J NATL CANCER I JI JNCI-J. Natl. Cancer Inst. PD JUL 6 PY 2005 VL 97 IS 13 BP 966 EP 975 DI 10.1093/dji172 PG 10 WC Oncology SC Oncology GA 942QF UT WOS:000230296200009 PM 15998949 ER PT J AU Weissfeld, JL Schoen, RE Pinsky, PF Bresalier, RS Church, T Yurgalevitch, S Austin, JH Prorok, PC Gohagan, JK AF Weissfeld, JL Schoen, RE Pinsky, PF Bresalier, RS Church, T Yurgalevitch, S Austin, JH Prorok, PC Gohagan, JK CA PLCO Project Team TI Flexible sigmoidoscopy in the PLCO cancer screening trial: Results from the baseline screening examination of a randomized trial SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FECAL-OCCULT-BLOOD; PROXIMAL COLONIC NEOPLASIA; COLORECTAL-CANCER; FIBEROPTIC SIGMOIDOSCOPY; POPULATION; YIELD; RATES; POLYP; RISK AB Background. The Prostate, Lung, Colorectal and Ovarian (PLCO) cancer screening trial is a randomized clinical trial to test the effectiveness of cancer screening, including the effect of flexible sigmoidoscopy screening on colorectal cancer mortality. Here we report findings from the baseline screening flexible sigmoidoscopy examination. Methods: Analyses included 77465 men and women aged 55-74 years who were enrolled at 10 screening centers. The trial administered baseline risk factor questionnaires, offered 60-cm flexible sigmoidoscopy examinations, referred patients with screen detected colorectal polyps or masses to personal physicians, and tracked subjects with polyps or masses to determine results from diagnostic follow-up. Cochran-Mantel-Haenszel statistics and logistic regression were used to test for differences in proportions according to sex and age. Results: A total of 64658 subjects (83.5%) underwent screening flexible sigmoidoscopy, and at least one polyp or mass was identified in 15150 subjects (23.4%). Of these, 74.2% received follow-up lower endoscopic procedures. Follow-up lower endoscopy was more frequent in subjects with at least one larger ( >= 0.5 cm) polyp or mass (86.0% [95% confidence interval {CI} = 84.6% to 87.4%] and 81.0% 195% CI = 79.8% to 82.2%] in women and men, respectively) than in those with a smaller (< 0.5 cm) polyp or mass (69.1% 195% Cl = 67.5% to 70.6%] and 65.4% 195% Cl = 64.1 % to 66.7%] in women and men, respectively). The yields per 1000 screened, depending on 5-year age group, were as follows: for colorectal cancer, 1.1-2.5 in women and 2.4-5.6 in men; for advanced adenoma, 18.0-30.4 in women and 36.1-49.1 in men; and for colorectal cancer or any adenoma, 50.6-79.6 in women and 101.9-128.6 in men. Approximately 77% (130/169) of the colorectal adenocarcinoma patients were stage I or II at diagnosis. Conclusions: Acceptance of screening flexible sigmoidoseopy was high. Diagnostic follow-up varied according to polyp size, yet cancer or adenoma detection rates met expectations. C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. US Dept HHS, NCI, Div Canc Prevent, NIH, Bethesda, MD USA. Henry Ford Hosp, Detroit, MI 48202 USA. Univ Minnesota, Minneapolis, MN 55455 USA. WESTAT Corp, Rockville, MD 20850 USA. Informat Management Serv Inc, Rockville, MD USA. RP Weissfeld, JL (reprint author), UPMC Canc Pavil,POB 2,3rd Floor Ctr Med Bldg,5150, Pittsburgh, PA 15232 USA. EM jwepid@pitt.edu OI Church, Timothy R./0000-0003-3292-5035 NR 30 TC 117 Z9 121 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 6 PY 2005 VL 97 IS 13 BP 989 EP 997 DI 10.1093/jnci/dji175 PG 9 WC Oncology SC Oncology GA 942QF UT WOS:000230296200012 PM 15998952 ER PT J AU Landi, MT Kanetsky, PA Tsang, S Gold, B Munroe, D Rebbeck, T Swoyer, J Ter-Minassian, M Hedayati, M Grossman, L Goldstein, AM Calista, D Pfeiffer, RM AF Landi, MT Kanetsky, PA Tsang, S Gold, B Munroe, D Rebbeck, T Swoyer, J Ter-Minassian, M Hedayati, M Grossman, L Goldstein, AM Calista, D Pfeiffer, RM TI MC1R, ASIP, and DNA repair in sporadic and familial melanoma in a Mediterranean population SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID CUTANEOUS MALIGNANT-MELANOMA; MELANOCORTIN-1 RECEPTOR MC1R; SKIN TYPE; HUMAN MELANOCYTES; GENE VARIANTS; HUMAN PIGMENTATION; DYSPLASTIC NEVI; RISK-FACTORS; SUSCEPTIBILITY; POLYMORPHISM AB Background. Melanoma risk factors include fair pigmentation, multiple nevi, low DNA repair capacity, and CDKN2A or CDK4 mutations. Variants of the melanocortin-1 receptor (MCIR) gene have been associated with fair pigmentation and melanoma risk, and a polymorphism of the Agouti Signaling Protein (ASIP) gene has been associated with dark pigmentation. We examined MCIR and ASIP genotypes in relation to phenotypic characteristics, sporadic and familial melanoma risk, and melanoma thickness as an indicator of disease progression in a Mediterranean population. Methods: We studied 267 melanoma patients and 382 control subjects from a case-control study and a family study in northeastern Italy. Host factors were assessed by physical examination, questionnaire, spectrophotometer, and minimal erythema dose measurement. MC1R was sequenced, ASIP was genotyped, and DNA repair capacity was measured by the host-cell reactivation assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by logistic regression models. Effect modification of the association between MCIR and melanoma risk by phenotypic characteristics and DNA repair capacity was also assessed. All statistical tests were two-sided. Results: Carrying MCIR variant alleles was associated with a two- to fourfold increase in risk of both sporadic and familial melanoma compared with carrying wild-type MCIR, particularly in individuals carrying multiple variant alleles (OR 3.9; 95% CI = 3.3 to 4.6). This association was stronger in individuals with fewer additional risk factors (those with dark skin or few nevi). MC1R variant allele carriers were also three to four times more likely than were non-carriers to have thick melanomas. The ASIP polymorphism was not associated with pigmentation, nevi, or melanoma risk. Conclusions: MCIR was associated with melanoma risk and progression in a Mediterranean population, particularly in the absence of other strong risk factors, such as freckling or many nevi. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Philadelphia, PA 19104 USA. NCI, Lab Mol Technol, SAIC, DHHS,NIH, Frederick, MD USA. NCI, Lab Genom Divers, SAIC, DHHS,NIH, Frederick, MD USA. Johns Hopkins Univ, Dept Biochem, Baltimore, MD USA. Maurizio Bufalini Hosp, Dermatol Unit, Cesena, Italy. RP Landi, MT (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, DHHS,NIH, 6120 Execut Blvd,EPS 7114, Bethesda, MD 20892 USA. EM landim@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 FU NCI NIH HHS [CA 5558-01A2] NR 51 TC 103 Z9 107 U1 1 U2 5 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 6 PY 2005 VL 97 IS 13 BP 998 EP 1007 DI 10.1093/jnci/dji176 PG 10 WC Oncology SC Oncology GA 942QF UT WOS:000230296200013 PM 15998953 ER PT J AU Jeang, KT AF Jeang, KT TI Small philanthropy and big science: the RETROVIROLOGY prize and Stephen P. Goff SO RETROVIROLOGY LA English DT Editorial Material AB Stephen P. Goff wins the 2005 RETROVIROLOGY prize. C1 NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008 NR 1 TC 9 Z9 9 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JUL 6 PY 2005 VL 2 AR 43 DI 10.1186/1742-4690-2-43 PG 4 WC Virology SC Virology GA 033DJ UT WOS:000236826400001 PM 16000174 ER PT J AU Nowotny, P Hinrichs, AL Smemo, S Kauwe, JSK Maxwell, T Holmans, P Hamshere, M Turic, D Jehu, L Hollingworth, P Moore, P Bryden, L Myers, A Doil, LM Tacey, KM Gibson, AM McKeith, IG Perry, RH Morris, CM Thal, L Morris, JC O'Donovan, MC Lovestone, S Grupe, A Hardy, J Owen, MJ Williams, J Goate, A AF Nowotny, P Hinrichs, AL Smemo, S Kauwe, JSK Maxwell, T Holmans, P Hamshere, M Turic, D Jehu, L Hollingworth, P Moore, P Bryden, L Myers, A Doil, LM Tacey, KM Gibson, AM McKeith, IG Perry, RH Morris, CM Thal, L Morris, JC O'Donovan, MC Lovestone, S Grupe, A Hardy, J Owen, MJ Williams, J Goate, A TI Association studies between risk for late-onset Alzheimer's disease and variants in insulin degrading enzyme SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE LOAD; IDE; SNP; haplotype; association studies ID AMYLOID BETA-PROTEIN; BLOCK SPANNING IDE; PHENOTYPIC ASSOCIATIONS; CLADISTIC-ANALYSIS; LINKAGE DISEQUILIBRIUM; EXTRACELLULAR LEVELS; DIABETES-MELLITUS; GENETIC-VARIATION; PLASMA A-BETA-42; NO ASSOCIATION AB Linkage studies have suggested there is a susceptibility gene for late onset Alzheimer's disease (LOAD) in a broad region of chromosome 10. A strong positional and biological candidate is the gene encoding the insulin-degrading enzyme (IDE), a protease involved in the catabolism of A beta. However, previous association studies have produced inconsistent results. To systematically evaluate the role of variation in IDE in the risk for LOAD, we genotyped 18 SNPs spanning a 276 kb region in and around IDE, including three "tagging" SNPs identified in an earlier study. We used four case-control series with a total of 1,217 cases and 1,257 controls. One SNP (IDE_7) showed association in two samples (P-value = 0.0066, and P = 0.026, respectively), but this result was not replicated in the other two series. None of the other SNPs showed association with LOAD in any of the tested samples. Haplotypes, constructed from the three tagging SNPs, showed no globally significant association. In the UK2 series, the CTA haplotype was over-represented in cases (P = 0.046), and in the combined data set, the CCG haplotype was more frequent in controls (P=0.015). However, these weak associations observed in our series were in the opposite direction to the results in previous studies. Although our results are not universally negative, we were unable to replicate the results of previous studies and conclude that common variants or haplotypes of these variants in IDE are not major risk factors for LOAD. (c) 2005 Wiley-Liss, Inc. C1 Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Dept Biol, St Louis, MO 63130 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Univ Cardiff Wales, Sch Med, Dept Psychol Med, Cardiff, Wales. NIA, Bethesda, MD 20892 USA. Celera Diagnost, Alameda, CA USA. Univ Newcastle Upon Tyne, Newcastle Gen Hosp, Inst Ageing & Hlth, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. Univ Cardiff Wales, Biostat & Bioinformat Unit, Cardiff, Wales. Univ London Kings Coll, Inst Psychiat, London, England. RP Goate, A (reprint author), Washington Univ, Sch Med, Dept Psychiat, Campus Box 8134,660 S Euclid St, St Louis, MO 63110 USA. EM goate@icarus.wustl.edu RI Lovestone, Simon/E-8725-2010; Myers, Amanda/B-1796-2010; turton, miranda/F-4682-2011; Kauwe, John/B-2034-2009; Morris, John/A-1686-2012; Hardy, John/C-2451-2009; Holmans, Peter/F-4518-2015; OI Myers, Amanda/0000-0002-3100-9396; Kauwe, John/0000-0001-8641-2468; Holmans, Peter/0000-0003-0870-9412; O'Donovan, Michael/0000-0001-7073-2379 FU NIA NIH HHS [P01 AG03991, P50 AG05681, AG16208, U24 AG021886] NR 39 TC 31 Z9 33 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUL 5 PY 2005 VL 136B IS 1 BP 62 EP 68 DI 10.1002/ajmg.b.30186 PG 7 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 939DN UT WOS:000230052700010 PM 15858813 ER PT J AU Martinez, M Brice, A Vaughan, JR Zimprich, A Breteler, MMB Meco, G Filla, A Farrer, MJ Betard, C Singleton, A Hardy, J De Michele, G Bonifati, V Oostra, BA Gasser, T Wood, NW Durr, A AF Martinez, M Brice, A Vaughan, JR Zimprich, A Breteler, MMB Meco, G Filla, A Farrer, MJ Betard, C Singleton, A Hardy, J De Michele, G Bonifati, V Oostra, BA Gasser, T Wood, NW Durr, A CA French Parkinson's Disease TI Apolipoprotein E4 is probably responsible for the chromosome 19 linkage peak for Parkinson's disease SO AMERICAN JOURNAL OF MEDICAL GENETICS PART B-NEUROPSYCHIATRIC GENETICS LA English DT Article DE Parkinson's disease; genetics; apolipoprotein E ID E GENOTYPE AB Analysis of the apolipoprotein E genotype in sibpairs with Parkinson's disease showed the E4 allele was over represented in those who shared the adjacent chromosome 19 markers. This suggests that apolipoprotein E4 is responsible for the linkage peak in this region and that it is a modest risk factor for Parkinson's disease. (c) 2005 Wiley-Liss, Inc. C1 NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. INSERM, Evry, France. Hop La Pitie Salpetriere, INSERM, U289, Paris, France. Hop La Pitie Salpetriere, Dept Genet Cytogenet & Embryol, Paris, France. Charing Cross Hosp, Dept Neurol, London, England. Univ Tubingen, Hertie Inst Clin Brain Res, Dept Neurodegenerat Dis, Tubingen, Germany. Erasmus MC, Dept Epidemiol & Biostat, Rotterdam, Netherlands. Univ Roma La Sapienza, Dept Neurol Sci, Rome, Italy. Univ Naples Federico 2, Dept Neurol Sci, Naples, Italy. Mayo Clin Jacksonville, Neurogenet Lab, Jacksonville, FL USA. Ctr Natl Genotypage, Evry, France. Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands. UCL, Inst Neurol, Dept Mol Neuro, London, England. RP Hardy, J (reprint author), NIA, Neurogenet Lab, NIH, Bldg 35,Room 1A1015,35 Convent Dr,Room 1A1015,MSC, Bethesda, MD 20892 USA. EM hardyj@mail.nih.gov RI Singleton, Andrew/C-3010-2009; Hardy, John/C-2451-2009; Wood, Nicholas/C-2505-2009; Martinez, Maria/B-3111-2013 OI Wood, Nicholas/0000-0002-9500-3348; Martinez, Maria/0000-0003-2180-4537 NR 11 TC 25 Z9 25 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4841 J9 AM J MED GENET B JI Am. J. Med. Genet. B PD JUL 5 PY 2005 VL 136B IS 1 BP 72 EP 74 DI 10.1002/ajmg.b.30196 PG 3 WC Genetics & Heredity; Psychiatry SC Genetics & Heredity; Psychiatry GA 939DN UT WOS:000230052700012 PM 15924299 ER PT J AU Cutler, JA Obarzanek, E AF Cutler, JA Obarzanek, E TI Nutrition and blood pressure: Is protein one link? Toward a strategy of hypertension prevention SO ANNALS OF INTERNAL MEDICINE LA English DT Editorial Material ID DIETARY-PROTEIN; BLADDER-CANCER; INCREASED RISK; SOY PROTEIN; HEALTH C1 NHLBI, Bethesda, MD 20892 USA. RP Cutler, JA (reprint author), NHLBI, 6701 Rockledge Dr, Bethesda, MD 20892 USA. NR 13 TC 7 Z9 7 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JUL 5 PY 2005 VL 143 IS 1 BP 74 EP 75 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 941XB UT WOS:000230246400008 PM 15998756 ER PT J AU Zeeberg, BR Qin, HY Narasimhan, S Sunshine, M Cao, H Kane, DW Reimers, M Stephens, RM Bryant, D Burt, SK Elnekave, E Hari, DM Wynn, TA Cunningham-Rundles, C Stewart, DM Nelson, D Weinstein, JN AF Zeeberg, BR Qin, HY Narasimhan, S Sunshine, M Cao, H Kane, DW Reimers, M Stephens, RM Bryant, D Burt, SK Elnekave, E Hari, DM Wynn, TA Cunningham-Rundles, C Stewart, DM Nelson, D Weinstein, JN TI High-Throughput GoMiner, an 'industrial-strength' integrative gene ontology tool for interpretation of multiple-microarray experiments, with application to studies of Common Variable Immune Deficiency (CVID) SO BMC BIOINFORMATICS LA English DT Article ID PRIMARY IMMUNODEFICIENCY; SIGNAL-TRANSDUCTION; T-CELLS; B-CELLS; CANCER; EXPRESSION; SCHISTOSOMIASIS; INFORMATION; RESPONSES; DEFECTS AB Background: We previously developed GoMiner, an application that organizes lists of 'interesting' genes ( for example, under- and overexpressed genes from a microarray experiment) for biological interpretation in the context of the Gene Ontology. The original version of GoMiner was oriented toward visualization and interpretation of the results from a single microarray ( or other high-throughput experimental platform), using a graphical user interface. Although that version can be used to examine the results from a number of microarrays one at a time, that is a rather tedious task, and original GoMiner includes no apparatus for obtaining a global picture of results from an experiment that consists of multiple microarrays. We wanted to provide a computational resource that automates the analysis of multiple microarrays and then integrates the results across all of them in useful exportable output files and visualizations. Results: We now introduce a new tool, High-Throughput GoMiner, that has those capabilities and a number of others: It (i) efficiently performs the computationally-intensive task of automated batch processing of an arbitrary number of microarrays, (ii) produces a human- or computer-readable report that rank-orders the multiple microarray results according to the number of significant GO categories, (iii) integrates the multiple microarray results by providing organized, global clustered image map visualizations of the relationships of significant GO categories, (iv) provides a fast form of 'false discovery rate' multiple comparisons calculation, and ( v) provides annotations and visualizations for relating transcription factor binding sites to genes and GO categories. Conclusion: High-Throughput GoMiner achieves the desired goal of providing a computational resource that automates the analysis of multiple microarrays and integrates results across all of the microarrays. For illustration, we show an application of this new tool to the interpretation of altered gene expression patterns in Common Variable Immune Deficiency (CVID). High-Throughput GoMiner will be useful in a wide range of applications, including the study of time-courses, evaluation of multiple drug treatments, comparison of multiple gene knock-outs or knockdowns, and screening of large numbers of chemical derivatives generated from a promising lead compound. C1 NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. SRA Int, Fairfax, VA 22033 USA. NCI, Adv Biomed Comp Ctr, SAIC Frederick, Frederick, MD 21702 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. RP Weinstein, JN (reprint author), NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, NIH, Bethesda, MD 20892 USA. EM barry@discover.nci.nih.gov; qinh@mail.nih.gov; naraisms@mail.nih.gov; margots@mail.nih.gov; caohong@mail.nih.gov; David_Kane@sra.com; reimersm@mail.nih.gov; bobs@ncifcrf.gov; bryantd@ncifcrf.gov; sb314f@nih.gov; EElnekave@niaid.nih.gov; danielle@aol.com; twynn@niaid.nih.gov; charlotte.cunningham-rundles@mssm.edu; dstew@helix.nih.gov; dln@helix.nih.gov; weinstein@dtpax2.ncifcrf.gov RI Wynn, Thomas/C-2797-2011 NR 39 TC 186 Z9 193 U1 3 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUL 5 PY 2005 VL 6 AR 168 DI 10.1186/1471-2105-6-168 PG 17 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 958CP UT WOS:000231422600001 PM 15998470 ER PT J AU Cushman, M Arnold, AM Psaty, BM Manolio, TA Kuller, LH Burke, GL Polak, JF Tracy, RP AF Cushman, M Arnold, AM Psaty, BM Manolio, TA Kuller, LH Burke, GL Polak, JF Tracy, RP TI C-reactive protein and the 10-year incidence of coronary heart disease in older men and women - The cardiovascular health study SO CIRCULATION LA English DT Article DE coronary disease; epidemiology; inflammation; myocardial infarction; risk factors ID 1ST MYOCARDIAL-INFARCTION; TRADITIONAL RISK-FACTORS; SUBCLINICAL DISEASE; INDEPENDENT PREDICTOR; COMPUTED-TOMOGRAPHY; TOTAL MORTALITY; ASSOCIATION; MARKERS; INFLAMMATION; EVENTS AB Background - High C-reactive protein (CRP) is associated with increased coronary heart disease risk. Few long-term data in the elderly are available. Methods and Results - Baseline CRP was measured in 3971 men and women >= 65 years of age without prior vascular diseases; 26% had elevated concentrations ( > 3 mg/ L). With 10 years of follow-up, 547 participants developed coronary heart disease (CHD; defined as myocardial infarction or coronary death). With elevated CRP, the 10-year cumulative CHD incidences were 33% in men and 17% in women. The age-, ethnicity-, and sex-adjusted relative risk of CHD for CRP > 3 mg/ L compared with < 1 mg/ L was 1.82 (95% CI, 1.46 to 2.28). Adjusting for conventional risk factors reduced the relative risk to 1.45 ( 95% CI, 1.14 to 1.86). The population-attributable risk of CHD for elevated CRP was 11%. Risk relationships did not differ in subgroups defined by baseline risk factors. We assessed whether CRP improved prediction by the Framingham Risk Score. Among men with a 10-year Framingham-predicted risk of 10% to 20%, the observed CHD incidence was 32% for elevated CRP. Among women, CRP discriminated best among those with a 10-year predicted risk > 20%; the incidences were 31% and 10% for elevated and normal CRP levels, respectively. Conclusions - In older men and women, elevated CRP was associated with increased 10-year risk of CHD, regardless of the presence or absence of cardiac risk factors. A single CRP measurement provided information beyond conventional risk assessment, especially in intermediate-Framingham-risk men and high-Framingham-risk women. C1 Univ Vermont, Dept Med, Colchester, VT 05446 USA. Univ Vermont, Dept Pathol, Colchester, VT 05446 USA. Univ Vermont, Dept Pathol & Biochem, Colchester, VT 05446 USA. Univ Washington, Dept Biostat, Seattle, WA 98195 USA. Univ Washington, Dept Med Epidemiol & Hlth Serv, Seattle, WA 98195 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Tufts Univ, Sch Med, Dept Radiol, Boston, MA 02111 USA. RP Cushman, M (reprint author), Univ Vermont, Dept Med, 208 S Pk Dr,Suite 2, Colchester, VT 05446 USA. EM mary.cushman@uvm.edu FU NHLBI NIH HHS [N01-HC-85079, N01-HC-85086, N01-HC-35129, N01-HC-15103, HL-46696, HL-03618, HL-8329] NR 40 TC 226 Z9 240 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 5 PY 2005 VL 112 IS 1 BP 25 EP 31 DI 10.1161/CIRCULATIONAHA.104.504159 PG 7 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 941IW UT WOS:000230209500007 PM 15983251 ER PT J AU Nabel, EG AF Nabel, EG TI A vision for the future - Opportunities and challenges - Notes from the Director of the National Heart, Lung, and Blood Institute SO CIRCULATION LA English DT Article C1 NHLBI, NIH, Bethesda, MD 20892 USA. RP Nabel, EG (reprint author), NHLBI, NIH, Bldg 10-8C103,10 Ctr Dr, Bethesda, MD 20892 USA. EM enable@nih.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUL 5 PY 2005 VL 112 IS 1 BP 145 EP 146 DI 10.1161/CIRCULATIONAHA.105.564252 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 941IW UT WOS:000230209500022 PM 15998699 ER PT J AU Triola, B Olson, MB Reis, SE Rautaharju, P Merz, CNB Kelsey, SF Shaw, LJ Sharaf, BL Sopko, G Saba, S AF Triola, B Olson, MB Reis, SE Rautaharju, P Merz, CNB Kelsey, SF Shaw, LJ Sharaf, BL Sopko, G Saba, S TI Electrocardiographic predictors of cardiovascular outcome in women - The National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID QRS DURATION; QT INTERVAL; CHEST PAIN; FAILURE; MORTALITY; DYSFUNCTION; MARKER AB OBJECTIVES We sought to analyze the value of infrequently measured parameters of the 12-lead electrocardiogram (ECG) in predicting cardiovascular events in women with suspected myocardial ischemia who were referred for cardiac catheterization. BACKGROUND Routinely analyzed ECG parameters have low predictive value for cardiovascular events in women with preserved left ventricular function and suspected myocardial ischemia. The predictive value of ECG parameters for cardiovascular disease has not been fully determined. METHODS Women enrolled in the National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study who had complete digital 12-lead ECG and quantitative angiography data were studied. Clinical and ECG predictors of cardiovascular disease events, defined as death, congestive heart failure, and non-fatal myocardial infarction, were determined. RESULTS Of 143 women with ECG and angiographic data (mean age 59 +/- 13 years, left ventricular ejection fraction 64.1 +/- 8.6%), 13% had events during a mean follow-up period of 3.3 +/- 1.6 years. Independent predictors of event occurrences included a wider QRS-T angle (i.e., the spatial electrical angle between the QRS complex and the T-wave; p = 0.0005), wider QRS complex (p = 0.004), longer QTrr (i.e., age- and gender-adjusted QT interval; p = 0.0004), a more depressed ST-segment in precordial lead V-5 (p = 0.0002), and a higher coronary artery disease severity score (p = 0.02). CONCLUSIONS Several 12-lead ECG parameters, such as the QRS-T angle and the QRS and QTrr duration, are predictive of future cardiovascular events in women with suspected myocardial ischemia. (J Am Coll Cardiol 2005;46:51-6) (c) 2005 by the American College of Cardiology Foundation. C1 Univ Pittsburgh, Dept Med, Pittsburgh, PA USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA USA. Wake Forest Univ, Sch Med, Dept Community Hlth Sci, Winston Salem, NC 27109 USA. Cedars Sinai Med Ctr, Div Cardiol, Los Angeles, CA 90048 USA. Atlanta Cardiovasc Res Inst, Atlanta, GA USA. Rhode Isl Hosp, Div Cardiol, Providence, RI USA. NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. RP Saba, S (reprint author), Univ Pittsburgh, Med Ctr, Cardiovasc Inst, 200 Lothrop St,B535 PUH, Pittsburgh, PA 15213 USA. EM sabas@upmc.edu RI Reis, Steven/J-3957-2014 FU NHLBI NIH HHS [N01-HV-68164, N01-HV-68161, N01-HV-68162, N01-HV-68163, U01-HL64829-01, U01-HL64914-01, U01-HL64924-01] NR 21 TC 42 Z9 44 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD JUL 5 PY 2005 VL 46 IS 1 BP 51 EP 56 DI 10.1016/j.jacc.2004.09.082 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 941LJ UT WOS:000230216000009 PM 15992635 ER PT J AU Klebanoff, CA Gattinoni, L Torabi-Parizi, P Kerstann, K Cardones, AR Finkelstein, SE Palmer, DC Antony, PA Hwang, ST Rosenberg, SA Waldmann, TA Restifo, NP AF Klebanoff, CA Gattinoni, L Torabi-Parizi, P Kerstann, K Cardones, AR Finkelstein, SE Palmer, DC Antony, PA Hwang, ST Rosenberg, SA Waldmann, TA Restifo, NP TI Central memory self/tumor-reactive CD8(+) T cells confer superior antitumor immunity compared with effector memory T cells SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE IL-2; IL-15; homing; immunotherapy; vaccine ID IN-VIVO; TRANSFER THERAPY; METASTATIC MELANOMA; CUTTING EDGE; DIFFERENTIATION; IMMUNOTHERAPY; INFLAMMATION; DESTRUCTION; MAINTENANCE; PERSISTENCE AB Central memory CD8+ T cells (T-cm) and effector memory CD8(+) T cells (T-EM) are found in humans and mice; however, their relative contributions to host immunity have only recently been examined in vivo. Further, the ability of Tcm to treat an established tumor or infection has yet to be evaluated. To address the therapeutic potential of different tumor-reactive CD8+ T cell memory subsets, we used an established model for the in vitro generation of Tcm and TEm by using IL-15 and IL-2, respectively. Adoptively transferred Tcm exhibited a potent in vivo recall response when combined with tumor-antigen vaccination and exogenous IL-2, leading to the eradication of large established tumors. By contrast, T-EM were far less effective on a per-cell basis. Microarray analysis revealed that the signature of highly in vivo effective antitumor T cells included the overexpression of genes responsible for trafficking to secondary lymphoid tissues. This gene expression profile correctly predicted the in vitro and in vivo lymphoid-homing attributes of tumor-reactive T cells. Furthermore, we found that homing to secondary lymphoid tissue is required for optimal tumor treatment. Our findings indicated that highly in vivo effective antitumor T cells were those that initially targeted secondary lymphoid tissue, rather than tumor sites, as had previously been postulated. Thus, tumor-reactive CD8(+) T cell populations with the phenotypic and functional attributes of Tcm may be superior to T-EM/effector T cells for adoptive immunotherapies using concomitant tumor-antigen vaccination. C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Howard Hughes Med Inst, Scholars Program, NIH, Bethesda, MD 20814 USA. RP Restifo, NP (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. EM restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Restifo, Nicholas/A-5713-2008; Klebanoff, Christopher/B-8088-2008; Palmer, Douglas/B-9454-2008; Klebanoff, Christopher/D-9581-2011; OI Gattinoni, Luca/0000-0003-2239-3282; Palmer, Douglas/0000-0001-5018-5734; Restifo, Nicholas P./0000-0003-4229-4580 FU Intramural NIH HHS [Z01 BC010763-01, Z99 CA999999] NR 26 TC 405 Z9 426 U1 1 U2 16 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 2005 VL 102 IS 27 BP 9571 EP 9576 DI 10.1073/pnas.0503726102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 944DN UT WOS:000230406000025 PM 15980149 ER PT J AU Yang, QF Huang, W Jozwik, C Lin, Y Glasman, M Caohuy, H Srivastava, M Esposito, D Gillette, W Hartley, J Pollard, HB AF Yang, QF Huang, W Jozwik, C Lin, Y Glasman, M Caohuy, H Srivastava, M Esposito, D Gillette, W Hartley, J Pollard, HB TI Cardiac glycosides inhibit TNF-alpha/NF-kappa B signaling by blocking recruitment of TNF receptor-associated death domain to the TNF receptor SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE digitoxin; inflammation ID OLEANDRIN SUPPRESSES ACTIVATION; INTERLEUKIN-8 GENE-EXPRESSION; LUNG EPITHELIAL-CELLS; KINASE-ALPHA; IKK ACTIVATION; BETA; TRAF2; JNK; RIP; TRANSDUCTION AB Digitoxin and structurally related cardiac glycoside drugs potently block activation of the TNF-alpha/NF-kappa B signaling pathway. We have hypothesized that the mechanism might be discovered by searching systematically for selective inhibitory action through the entire pathway. We report that the common action of these drugs is to block the TNF-alpha-dependent binding of TNF receptor 1 to TNF receptor-associated death domain. This drug action can be observed with native cells, such as HeLa, and reconstituted systems prepared in HEK293 cells. All other antiinflammatory effects of digitoxin on NF-kappa B and c-Jun N-terminal kinase pathways appear to follow from the blockade of this initial upstream signaling event. C1 Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. Uniformed Serv Univ Hlth Sci, Inst Mol Med, Bethesda, MD 20814 USA. NCI, Canc & Cell Biol Branch, NIH, Bethesda, MD 20892 USA. NCI, Prot Express Lab, SAIC, NIH, Frederick, MD 21702 USA. RP Pollard, HB (reprint author), Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, 4301 Jones Bridge Rd,Bldg B,Room B2100, Bethesda, MD 20814 USA. EM hpollard@usuhs.mil FU NHLBI NIH HHS [N01-HV-28187, N01HV28187]; NIDDK NIH HHS [R01 DK053051, R01-DK53051-7] NR 37 TC 50 Z9 51 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 5 PY 2005 VL 102 IS 27 BP 9631 EP 9636 DI 10.1073/pnas.0504097102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 944DN UT WOS:000230406000035 PM 15983368 ER PT J AU Hu, HL Cohen, JI AF Hu, HL Cohen, JI TI Varicella-zoster virus open reading frame 47 (ORF47) protein is critical for virus replication in dendritic cells and for spread to other cells SO VIROLOGY LA English DT Article DE dendritic cells; varicella-zoster virus; varicella; shingles; zoster; ORF47 ID HUMAN-IMMUNODEFICIENCY-VIRUS; HERPES-SIMPLEX-VIRUS; HUMAN T-CELLS; VIRAL REPLICATION; HUMAN CYTOMEGALOVIRUS; SERINE KINASE; IN-VITRO; INFECTION; PHOSPHORYLATION; MATURATION AB Varicella-zoster virus infects human dendritic cells (DCs). We found that VZV infection of DCs resulted in down-regulation of Fas expression on the surface of cells. VZV ORF47 was critical for replication of virus in human immature, but not mature DCs. Immature DCs infected with a mutant virus unable to express ORF47 expressed similar levels of a VZV immediate-early protein as cells infected with parental virus; however, cells infected with the ORF47 mutant expressed lower levels of glycoprotein E. Thus, in the absence of ORF47 protein, there is a block in viral replication between immediate-early and late gene expression. VZV unable to express ORF47 was severely impaired for spread of virus from DCs to melanoma cells. Infection of DCs with parental VZV resulted in a different pattern of phosphoproteins compared with the ORF47 mutant virus. Thus, VZV ORF47 is important for replication in immature DCs and for spread to other cells. Published by Elsevier Inc. C1 NIAID, Med Virol Sect, Lab Clin Infect Div, NIH, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIAID, Med Virol Sect, Lab Clin Infect Div, NIH, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov NR 33 TC 19 Z9 20 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 0042-6822 J9 VIROLOGY JI Virology PD JUL 5 PY 2005 VL 337 IS 2 BP 304 EP 311 DI 10.1016/j.virol.2005.04.024 PG 8 WC Virology SC Virology GA 940PB UT WOS:000230155300011 PM 15913699 ER PT J AU Rutigliano, JA Rock, MT Johnson, AK Crowe, JE Graham, BS AF Rutigliano, JA Rock, MT Johnson, AK Crowe, JE Graham, BS TI Identification of an H-2D(b)-restricted CD8+ cytotoxic T lymphocyte epitope in the matrix protein of respiratory syncytial virus SO VIROLOGY LA English DT Article DE RSV; CD8+CTL; epitope; mice; immunodominance ID CELL RESPONSES; FUSION PROTEIN; INFECTION; MICE; VACCINE; EPIDEMIOLOGY; CHILDREN; DISEASE; INFANTS; PEPTIDE AB Cytotoxic T lymphocytes (CTL) play a significant role in the clearance of respiratory syncytial virus (RSV) infection in humans and mice. Identification of class 1 MHC-restricted CTL epitopes is critical in elucidating mechanisms of CTL responses against viral infections. However, only four H-2(d)-restricted epitopes have been reported in mice. Because of the diversity of transgenic and knockout mice available to study immune responses, new epitopes in additional strains of mice must be identified. We therefore attempted to discover novel CTL epitopes in C57B1/6 mice. Our efforts revealed a new H-2D(b)-restricted CTL epitope from the RSV M protein, corresponding to aa 187-195 (NAITNAKII). Also, M187-195-specific CTLs were activated with kinetics similar to the immunodominant BALB/c epitope, M2 82-90. This is the first RSV-specific CTL epitope described in a strain of mice other than BALB/c. Furthemore, identification of this H-2(b)-restricted CTL epitope provides access to genetically modified H-2(b) mice for more detailed studies of CTL mechanisms in RSV infection. Published by Elsevier Inc. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37232 USA. RP Graham, BS (reprint author), NIAID, Vaccine Res Ctr, NIH, Bldg 40,Room 2502,40 Convent Dr,MSC 3017, Bethesda, MD 20892 USA. EM bgraham@nih.gov RI Crowe, James/B-5549-2009 OI Crowe, James/0000-0002-0049-1079 FU NIAID NIH HHS [R01-AI-33933] NR 47 TC 38 Z9 39 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 0042-6822 J9 VIROLOGY JI Virology PD JUL 5 PY 2005 VL 337 IS 2 BP 335 EP 343 DI 10.1016/j.virol.2005.04.032 PG 9 WC Virology SC Virology GA 940PB UT WOS:000230155300014 PM 15916793 ER PT J AU Pastrana, DV Gambhira, R Buck, CB Pang, YYS Thompson, CD Culp, TD Christensen, ND Lowy, DR Schiller, JT Roden, RBS AF Pastrana, DV Gambhira, R Buck, CB Pang, YYS Thompson, CD Culp, TD Christensen, ND Lowy, DR Schiller, JT Roden, RBS TI Cross-neutralization of cutaneous and mucosal Papillomavirus types with anti-sera to the amino terminus of L2 SO VIROLOGY LA English DT Article DE papillomavirus; capsid protein; L2; vaccine; prophylactic; neutralizing antibody ID MINOR CAPSID PROTEIN; COTTONTAIL RABBIT PAPILLOMAVIRUS; VIRUS-LIKE PARTICLES; CERVICAL-CANCER WORLDWIDE; N-TERMINUS; BOVINE PAPILLOMAVIRUS-4; MEDIATED NEUTRALIZATION; MONOCLONAL-ANTIBODIES; LINEAR EPITOPES; INFECTION AB Vaccination with papillomavirus L2 has been shown to induce neutralizing antibodies that protect against homologous type infection and cross-neutralize a limited number of genital HPVs. Surprisingly, we found that antibodies to bovine papillomavirus (BPV1) L2 amino acids 1-88 induced similar titers of neutralizing antibodies against Human papillomavirus (HPV)16 and 18 and BPV1 pseudoviruses and also neutralized HPV11 native virions. These antibodies also neutralized each of the other pseudovirus types tested, HPV31, HPV6 and Cottontail rabbit papillomavirus (CRPV) pseudoviruses, albeit with lower titers. HPV 16, HPV 18, HPV31, HPV6 and CRPV L2 anti-sera also displayed some cross-neutralization, but the titers were lower and did not encompass all pseudoviruses tested. This study demonstrates the presence of broadly cross-neutralizing epitopes at the N-terminus of L2 that are shared by cutaneous and mucosal types and by types that infect divergent species. BPV1 L2 was exceptionally effective at inducing cross-neutralizing antibodies to these shared epitopes. (c) 2005 Elsevier Inc. All rights reserved. C1 Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21205 USA. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA. Johns Hopkins Sch Med, Dept Oncol, Baltimore, MD 21205 USA. Johns Hopkins Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA. RP Roden, RBS (reprint author), Johns Hopkins Sch Med, Dept Pathol, Ross 512B,720 Rutland Ave, Baltimore, MD 21205 USA. EM roden@jhmi.edu OI Buck, Christopher/0000-0003-3165-8094 FU NCI NIH HHS [P50 CA098252] NR 46 TC 105 Z9 112 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JUL 5 PY 2005 VL 337 IS 2 BP 365 EP 372 DI 10.1016/j.virol.2005.04.011 PG 8 WC Virology SC Virology GA 940PB UT WOS:000230155300017 PM 15885736 ER PT J AU Saksena, R Adamo, R Kovac, P AF Saksena, R Adamo, R Kovac, P TI Studies toward a conjugate vaccine for anthrax. Synthesis and characterization of anthrose [4,6-dideoxy-4-(3-hydroxy-3-methylbutanamido)2-O-methyl-d-glucopyranose] and its methyl glycosides SO CARBOHYDRATE RESEARCH LA English DT Article DE methyl alpha-anthroside; methyl beta-anthroside; thioglycoside hydrolysis; perosamine ID VIBRIO-CHOLERAE O-1; DISACCHARIDE REPEATING UNIT; SEROTYPE INABA; ALPHA-GLYCOSIDE; ANTIGENIC DETERMINANTS; O-POLYSACCHARIDE; D-MANNOSE; OGAWA; TERMINUS; LIPOPOLYSACCHARIDE AB The key step in the first chemical synthesis of anthrose (16) and its methyl alpha- (6) and P-glycoside (22) was inversion of configuration at C-2 in triffates 10, 2, and 18, respectively, obtained from the common intermediate, methyl 4-azido-3-O-benzyl-4,6-dideoxy-alpha-D -mannopyranoside (1). To prepare methyl alpha-anthroside (6), methylation at 0-2 of the gluco product 3, obtained from 2, was followed by hydrogenation/hydrogenolysis of the formed 2-methyl ether 4, to simultaneously remove the protecting benzyl group and reduce the azido function. Subsequent N-acylation of the formed amine 5 with 3-hydroxy-3-methylbutyric acid gave the target methyl alpha-glycoside 6. Synthesis of methyl beta-anthroside (22) comprised the same sequence of reactions, starting from the known methyl 4-azido-3-O-benzyl-4,6-didCOXY-beta-D-mannopyranoside (17), which was prepared from 1. In the synthesis of anthrose (16), 1-thio-beta-glucoside 11, obtained from 1 through 10, was methylated at O-2, and the azido function in the resulting benzylated 1-thioglycoside 12 was selectively reduced to give amine 13. After N-acylation with 3-hydroxy-3-methylbutyric acid, 1-thioglycoside 14 was hydrolyzed to give the corresponding reducing sugar, aldol 15, which was debenzylated to afford anthrose. Published by Elsevier Ltd. C1 NIDDK, LMC, Natl Inst Hlth, Bethesda, MD 20892 USA. RP Kovac, P (reprint author), NIDDK, LMC, Natl Inst Hlth, Bethesda, MD 20892 USA. EM kpn@helix.nih.gov NR 29 TC 29 Z9 29 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD JUL 4 PY 2005 VL 340 IS 9 BP 1591 EP 1600 DI 10.1016/j.carres.2005.04.010 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 941JL UT WOS:000230211000003 PM 15922317 ER PT J AU Khurana, S Yamada, M Wess, J Kennedy, RH Raufman, JP AF Khurana, S Yamada, M Wess, J Kennedy, RH Raufman, JP TI Deoxycholyltaurine-induced vasodilation of rodent aorta is nitric oxide- and muscarinic M-3 receptor-dependent SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE receptor subtype; vascular relaxation; cholinergic receptor; deoxycholic acid; cirrhosis ID BILE-ACIDS; HYPERDYNAMIC CIRCULATION; ARTERIAL VASODILATION; ACETYLCHOLINE-RECEPTOR; CLINICAL-IMPLICATIONS; PORTAL-HYPERTENSION; ENDOTHELIAL-CELLS; LIVER-CIRRHOSIS; SMOOTH-MUSCLE; EXHALED AIR AB Emerging evidence indicates that some secondary bile acids interact functionally with muscarinic cholinergic receptors. Using thoracic aortic rings prepared from rats and mice, we examined the mechanism of deoxycholyltaurine-induced vasorelaxation. Increasing concentrations of both acetylcholine (1 nM to 0.1 mM) and deoxycholyltaurine (0.1 mu M to 1 mM) stimulated relaxation of phenylephrine-constricted rings prepared from rat thoracic aortae. These effects were reduced by endothelial denudation and by treatment with an inhibitor of nitric oxide formation and with a synthetic acetylcholine: bile acid hybrid that acts as a muscarinic receptor antagonist. Likewise, both acetylcholine (1 nM to 0.1 mM) and deoxycholyltaurine (0.1 mu M to 0.1 mM) stimulated relaxation of phenylephrine-constricted rings prepared from mouse thoracic aortae. These effects were reduced by endothelial denudation, addition of an inhibitor of nitric oxide formation, and by muscarinic M-3 receptor knockout. We conclude that the systemic vasodilatory actions of deoxycholyltaurine are mediated in part by a nitric oxide-, muscarinic M-3 receptor-dependent mechanism. In advanced liver disease, interaction of serum bile acids with endothelial muscarinic receptors may explain nitric oxide overproduction in the systemic circulation and resulting peripheral arterial vasodilation. Published by Elsevier B.V. C1 VA Maryland Hlth Care Syst, Div Gastroenterol & Hepatol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Cent Arkansas Vet Hlth Care Syst, Div Gastroenterol & Hepatol, Little Rock, AR 72205 USA. NIDDKD, Lab Biorgan Chem, Bethesda, MD 20892 USA. Univ Arkansas Med Sci, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. RP Raufman, JP (reprint author), VA Maryland Hlth Care Syst, Div Gastroenterol & Hepatol, 22 S Greene St,N3W62, Baltimore, MD 21201 USA. EM jraufman@medicine.umaryland.edu NR 37 TC 15 Z9 16 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUL 4 PY 2005 VL 517 IS 1-2 BP 103 EP 110 DI 10.1016/j.ejphar.2005.05.037 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 944QJ UT WOS:000230443600015 PM 15964566 ER PT J AU Lee, YC Higashi, Y Luu, C Shimizu, C Strott, CA AF Lee, YC Higashi, Y Luu, C Shimizu, C Strott, CA TI Sp1 elements in SULT2B1b promoter and 5 '-untranslated region of mRNA: Sp1/Sp2 induction and augmentation by histone deacetylase inhibition SO FEBS LETTERS LA English DT Article DE sulfonation; SULT2B1 promoter; cis-element; trans-factor; chromatin structure ID HYDROXYSTEROID SULFOTRANSFERASE SULT2B1; CHOLESTEROL SULFATE; CHROMATIN-STRUCTURE; TRANSCRIPTION; GENE; KERATINOCYTES; EXPRESSION; COMPLEX; ACETYLATION; MURINE AB The steroid/sterol sulfotransferase gene (SULT2B1) encodes for two isozymes of which one (SULT2131b) sulfonates cholesterol and is selectively expressed in skin. The human SUL T2B1 gene contains neither a TATAAA nor a CCAAT motif upstream of the coding region for SULT2131b; however, this area is GC-rich. Of five Sp1 elements identified two had regulatory activity utilizing immortalized human keratinocytes: one element is located above the ostensible transcription initiation site, whereas the other is located within the 5'-untranslated region of the SULT2B1b mRNA. Sp1 and Sp2 transcription factors identified by supershift analyses induced reporter gene activity, an effect markedly augmented by histone deacetylase inhibition. Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD 20892 USA. RP Strott, CA (reprint author), NICHHD, Sect Steroid Regulat, Endocrinol & Reprod Res Branch, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM chastro@mail.nih.gov NR 29 TC 14 Z9 14 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 4 PY 2005 VL 579 IS 17 BP 3639 EP 3645 DI 10.1016/j.febslet.2005.05.041 PG 7 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 943EQ UT WOS:000230335600028 PM 15953604 ER PT J AU Clemen, CS Fischer, D Roth, U Simon, S Vicart, P Kato, K Kaminska, AM Vorgerd, M Goldfarb, LG Eymard, B Romero, NB Goudeau, B Eggermann, T Zerres, K Noegel, AA Schroder, R AF Clemen, CS Fischer, D Roth, U Simon, S Vicart, P Kato, K Kaminska, AM Vorgerd, M Goldfarb, LG Eymard, B Romero, NB Goudeau, B Eggermann, T Zerres, K Noegel, AA Schroder, R TI Hsp27-2D-gel electrophoresis is a diagnostic tool to differentiate primary desminopathies from myofibrillar myopathies SO FEBS LETTERS LA English DT Article DE hsp27; alpha B-crystallin; desmin; plectin; myofibrillar myopathies; 2D-gel electrophoresis; MALDI ID ALPHA-B-CRYSTALLIN; IMMOBILIZED PH GRADIENTS; 2-DIMENSIONAL ELECTROPHORESIS; DESMIN CYTOSKELETON; SKELETAL; PROTEINS; CELLS; METHYLATION; MUTATIONS; PLECTIN AB Small heat shock proteins prevent abnormal protein folding and accumulation. We analyzed the expression of hsp27 and alpha B-crystallin in skeletal muscle specimens of patients with desminopathies, plectinopathies, myotilinopathy, and other myofibrillar myopathies by means of differential centrifugation, 2D-gel electrophoresis, Western blotting, and mass spectrometry. Hsp27-P82 and -P15 as well as alpha B-crystallin-P59 and -P45 are the major serine phosphorylation isoforms in normal and diseased human skeletal muscle. 2D-gel-electrophoresis revealed spots of hsp27 in a range of pH 5.3-6.4 in samples of all skeletal muscle specimens, except for the seven desminopathies. They indicated a shift of the main hsp27-spot to alkaline pH degrees, which may help to differentiate primary desminopathies from other myopathies with structural pathology of the desmin cytoskeleton. (c) 2005 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 Univ Bonn, Fac Med, Dept Neurol, D-53127 Bonn, Germany. Univ Cologne, Fac Med, Ctr Biochem, Cologne, Germany. Univ Cologne, Ctr Mol Med Cologne, Cologne, Germany. Univ Paris 06, CNRS, UMR 7000, Paris, France. Univ Paris 07, UFR Biochem, Paris, France. Aichi Human Serv Ctr, Inst Dev Res, Dept Biochem, Kasugai, Aichi, Japan. Med Univ Warsaw, Dept Neurol, Warsaw, Poland. Polish Acad Sci, Med Res Ctr, Neuromuscular Unit, Warsaw, Poland. Ruhr Univ Bochum, Dept Neurol, D-4630 Bochum, Germany. NINDS, Clin Neurogenet Unit, NIH, Bethesda, MD 20892 USA. Grp Hosp Pitie Salpetriere, Inst Myol, F-75634 Paris, France. Grp Hosp Pitie Salpetriere, INSERM, U582, F-75634 Paris, France. Univ Paris 06, CNRS, UMR 7000, Lab Cytosquelette & Dev, Paris, France. Rhein Westfal TH Aachen, Inst Human Genet, D-5100 Aachen, Germany. RP Schroder, R (reprint author), Univ Bonn, Fac Med, Dept Neurol, Siegmund Freud Str 25, D-53127 Bonn, Germany. EM rolf.schroeder@ukb.uni-bonn.de RI Schroder, Rolf/B-2774-2011; simon, stephanie/A-3845-2013; Eggermann, Thomas/F-3807-2014; Clemen, Christoph/B-2761-2011 OI Clemen, Christoph/0000-0002-1291-4219 NR 20 TC 26 Z9 26 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 4 PY 2005 VL 579 IS 17 BP 3777 EP 3782 DI 10.1016/j.febslet.2005.05.051 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 943EQ UT WOS:000230335600049 PM 15978589 ER PT J AU Moon, HE Ahn, MY Park, JA Min, KJ Kwon, YW Kim, KW AF Moon, HE Ahn, MY Park, JA Min, KJ Kwon, YW Kim, KW TI Negative regulation of hypoxia inducible factor-1 alpha by necdin SO FEBS LETTERS LA English DT Article DE hypoxia; hypoxia-inducible factor-1 alpha; necdin; angiogenesis ID GROWTH SUPPRESSOR NECDIN; PRADER-WILLI-SYNDROME; FACTOR 1-ALPHA; PROLYL HYDROXYLATION/; BINDING PROTEIN; NUCLEAR-MATRIX; HIF-ALPHA; INTERACTS; STABILIZATION; DESTRUCTION AB Hypoxia-inducible factor 1 (HIF-1) is a master transcription factor that mediates cellular and systemic homeostatic responses to reduce O-2 availability, such as erythropoiesis, angiogenesis, and glycolysis. Using the yeast two-hybrid screening system, we found that the oxygen dependent degradation (ODD) domain of HIF-1 alpha interacts with necdin, a growth suppressor. The interaction of necdin with HIF-1 alpha was confirmed using coimmunoprecipitation with the overexpressed HIF-1 alpha. Biological effect of necdin on HIF-1 alpha showed that necdin reduces the transcriptional activity of HIF-1 under hypoxia. Moreover, necdin decreased the level of the HIF-1 alpha protein, but not that of mRNA, implying a possibility of necdin-mediated HIF-1 alpha degradation. Furthermore, necdin has an anti-angiogenic activity in the tube formation assay and CAM assay, which might be due to the downregulation of HIF-1 alpha. Collectively, these results suggest that necdin can be a novel negative regulator of HIF-1 alpha stability via the direct interaction. (c) 2005 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies. C1 Seoul Natl Univ, Coll Pharm, Neurovasc Coordinat Res Ctr, Seoul 151742, South Korea. Seoul Natl Univ, Coll Pharm, Res Inst Pharmaceut Sci, Seoul 151742, South Korea. Juseong Coll, Dept Biotechnol, Cheongju 363794, South Korea. NIAID, Immunopathol Lab, Rockville, MD 20852 USA. RP Kim, KW (reprint author), Seoul Natl Univ, Coll Pharm, Neurovasc Coordinat Res Ctr, Seoul 151742, South Korea. EM qwonkim@plaza.snu.ac.kr NR 28 TC 23 Z9 23 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD JUL 4 PY 2005 VL 579 IS 17 BP 3797 EP 3801 DI 10.1016/j.febslet.2005.05.072 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 943EQ UT WOS:000230335600052 PM 15978586 ER PT J AU Ali, M Emch, M von Seidlein, L Yunus, M Sack, DA Rao, M Holmgren, J Clemens, JD AF Ali, M Emch, M von Seidlein, L Yunus, M Sack, DA Rao, M Holmgren, J Clemens, JD TI Herd immunity conferred by killed oral cholera vaccines in Bangladesh: a reanalysis SO LANCET LA English DT Article ID FIELD TRIAL; B-SUBUNIT; FOLLOW-UP; IMMUNIZATION; VACCINATION; MODELS AB Background Decisions about the use of killed oral cholera vaccines, which confer moderate levels of direct protection to vaccinees, can depend on whether the vaccines also provide indirect (herd) protection when high levels of vaccine coverage are attained. We reanalysed data from a field trial in Bangladesh to ascertain whether there is evidence of indirect protection from killed oral cholera vaccines. Methods We analysed the first year of surveillance data from a placebo-controlled trial of B subunit-killed whole-cell and killed whole-cell-only oral cholera vaccines in children and adult women in Bangladesh. We calculated whether there was an inverse, monotonic trend for the relation between the level of vaccine coverage in a residential cluster and the incidence of cholera in individual vaccine recipients or placebo recipients residing in the cluster after controlling for potential confounding variables. Findings Vaccine coverage of the targeted population ranged from 4% to 65%. Incidence rates of cholera among placebo recipients were inversely related to levels of vaccine coverage (7.01 cases per 1000 in the lowest quintile of coverage vs 1.47 cases per 1000 in the highest quintile; p<0.0001 for trend). Receipt of vaccine by an individual and the level of vaccine coverage of the individual's cluster were independently related to a reduced risk of cholera. Moreover, after adjustment for the level of vaccine coverage of the cluster, vaccine protective efficacy remained significant (55% [95% CI 41-66], p<0.0001). Interpretation in addition to providing direct protection to vaccine recipients, killed oral cholera vaccines confer significant herd protection to neighbouring non-vaccinated individuals. Use of these vaccines could have a major effect on the burden of cholera in endemic settings. C1 Int Vaccine Inst, Seoul 151818, South Korea. Portland State Univ, Dept Geog, Portland, OR 97207 USA. ICDDR B, Ctr Hlth & Populat Res, Dhaka, Bangladesh. NIAID, NIH, Bethesda, MD 20892 USA. Univ Gothenburg, Dept Med Microbiol & Immunol, Gothenburg, Sweden. NICHHD, Bethesda, MD 20892 USA. RP Clemens, JD (reprint author), Int Vaccine Inst, SNU Res Pk,San 4-8 Bongcheon 7 Dong, Seoul 151818, South Korea. EM jclemens@ivi.int RI Ali, Mohammad/E-2365-2017 OI Ali, Mohammad/0000-0003-1410-388X FU NIAID NIH HHS [1R03AI53214-01] NR 21 TC 152 Z9 157 U1 2 U2 13 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUL 2 PY 2005 VL 366 IS 9479 BP 44 EP 49 DI 10.1016/S0140-6736(05)66550-6 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 942JB UT WOS:000230277600033 PM 15993232 ER PT J AU Han, PKJ Keranen, LB Lescisin, DA Arnold, RM AF Han, PKJ Keranen, LB Lescisin, DA Arnold, RM TI The Palliative Care Clinical Evaluation Exercise (CEX): An experience-based intervention for teaching end-of-life communication skills SO ACADEMIC MEDICINE LA English DT Article; Proceedings Paper CT 27th Annual Meeting of the Society-of-General-Internal-Medicine CY MAY 12-15, 2004 CL Chicago, IL SP Soc Gen Internal Med ID BREAKING-BAD-NEWS; MEDICAL-STUDENTS; TERMINALLY ILL; MINI-CEX; EDUCATION; RESIDENTS; WORKSHOP; SCHOOL; DEATH AB Purpose To pilot test the "Palliative Care Clinical Evaluation Exercise (CEX)," a new experience-based intervention to teach communication skills in giving bad news and discussing code status. The intervention allows faculty to observe, evaluate, and give feedback to housestaff in their discussions with patients and families. Method In 2002-03, the intervention was piloted among 60 first-year residents in the categorical Internal Medicine Residency Programs at the University of Pittsburgh. The authors collected feasibility measurements at the time of intervention, and interns' attitudes were measured before and one week after intervention and at the end of the intern year. Results Forty-four residents (73%) completed the intervention. Discussions averaged a total of 49.5 minutes (SD 24.1), divided among 12.7 minutes (SD 7.5) for prediscussion counseling between the resident and faculty observer, 25.6 minutes (SD 16.1) for the resident-patient discussion, and 12.1 minutes (SD 5.7) for postdiscussion feedback. Residents rated the Palliative Care CEX favorably (> 3 on a five-point scale) on ease of arranging the exercise, educational value, quality of the experience, effect on their comfort with discussions, importance to their education, and value of preceptor feedback. Self-ratings of communication competence showed improvement one week after the intervention. Conclusions The Palliative Care CEX is feasible and positively valued by residents. The findings from this initial pilot study support the value of further efforts to refine the intervention, to confirm its feasibility in other settings, and to validate its use as an educational and assessment tool. C1 NCI, Div Canc Prevent, Bethesda, MD 20852 USA. Univ Colorado, Dept Commun, Boulder, CO USA. Univ Pittsburgh, Ctr Med, Dept Med, Pittsburgh, PA USA. RP Han, PKJ (reprint author), NCI, Div Canc Prevent, Execut Plaza N,Room 4097,6130 Execut Blvd, Bethesda, MD 20852 USA. EM hanp@mail.nih.gov OI Han, Paul/0000-0003-0165-1940 NR 47 TC 36 Z9 37 U1 2 U2 10 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-2446 J9 ACAD MED JI Acad. Med. PD JUL PY 2005 VL 80 IS 7 BP 669 EP 676 DI 10.1097/00001888-200507000-00009 PG 8 WC Education, Scientific Disciplines; Health Care Sciences & Services SC Education & Educational Research; Health Care Sciences & Services GA 939FT UT WOS:000230058600008 PM 15980083 ER PT J AU Seto, B AF Seto, B TI Molecular imaging SO ACADEMIC RADIOLOGY LA English DT Editorial Material C1 Natl Inst Biomed Imaging & Bioengn, Bethesda, MD 20892 USA. RP Seto, B (reprint author), Natl Inst Biomed Imaging & Bioengn, Democracy Plaza 2 DEM 2,6707 Democracy Blvd, Bethesda, MD 20892 USA. EM setob@mail.nih.gov NR 1 TC 0 Z9 1 U1 0 U2 0 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD JUL PY 2005 VL 12 IS 7 BP 797 EP 797 DI 10.1016/j.acra.2005.06.00 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 950OU UT WOS:000230867600001 PM 16039532 ER PT J AU Hummer, G Szabo, A AF Hummer, G Szabo, A TI Free energy surfaces from single-molecule force spectroscopy SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID DYNAMICS SIMULATIONS; NONEQUILIBRIUM MEASUREMENTS; PULLING EXPERIMENTS; PROTEIN; TITIN; EQUILIBRIUM; ELASTICITY; ADHESION; EQUALITY; KINETICS AB Single-molecule force spectroscopy has the potential to provide unprecedented insights into the mechanical properties of individual molecules. The unfolding of proteins and nucleic acids, the dissociation of molecular complexes, and other molecular transitions can be induced through mechanical forces exerted, for example, by laser optical tweezers or atomic force microscopes and monitored with subnanometer resolution. Can one obtain the equilibrium free energy of the molecular system along the pulling coordinate from such nonequilibrium force measurements? Jarzynski's remarkable identity does not immediately solve this problem because it relates the nonequilibrium work to free energy differences at different times, not positions. By surmounting this difficulty, we were able to express the free energy profile in terms of the integral of the force with respect to extension. Here we present the theory in a simple way and discuss various practical aspects in the context of pulling experiments. We illustrate our rigorous free energy reconstruction procedure by applying it to force-induced RNA unfolding experiments. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Hummer, G (reprint author), NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RI Szabo, Attila/H-3867-2012; Hummer, Gerhard/A-2546-2013 OI Hummer, Gerhard/0000-0001-7768-746X NR 41 TC 159 Z9 160 U1 2 U2 61 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0001-4842 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD JUL PY 2005 VL 38 IS 7 BP 504 EP 513 DI 10.1021/ar040148d PG 10 WC Chemistry, Multidisciplinary SC Chemistry GA 948AI UT WOS:000230688000002 PM 16028884 ER PT J AU Dauter, Z Botos, I LaRonde-Leblanc, N Wlodawer, A AF Dauter, Z Botos, I LaRonde-Leblanc, N Wlodawer, A TI Pathological crystallography: case studies of several unusual macromolecular crystals SO ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY LA English DT Article ID RAY-DIFFRACTION DATA; X-RAY; MOLECULAR REPLACEMENT; STRUCTURAL GENOMICS; REFINEMENT; SYMMETRY; COLLECTION; SYSTEM; MAD AB Although macromolecular crystallography is rapidly becoming largely routine owing to advances in methods of data collection, structure solution and refinement, difficult cases are still common. To remind structural biologists about the kinds of crystallographic difficulties that might be encountered, case studies of several successfully completed structure determinations that utilized less than perfect crystals are discussed here. The structure of the proteolytic domain of Archaeoglobus fulgidus Lon was solved with crystals that contained superimposed orthorhombic and monoclinic lattices, a case not previously described for proteins. Another hexagonal crystal form of this protein exhibited an unusually high degree of non-isomorphism. Crystals of A. fulgidus Rio1 kinase exhibited both pseudosymmetry and twinning. Ways of identifying the observed phenomena and approaches to solving and refining macromolecular structures when only less than perfect crystals are available are discussed here. C1 NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. NCI, Synchrotron Radiat Res Sect, Macromol Crystallog Lab, Argonne, IL 60439 USA. Argonne Natl Lab, Biosci Div, Argonne, IL 60439 USA. RP Wlodawer, A (reprint author), NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov RI LaRonde-LeBlanc, Nicole/C-3399-2009 OI LaRonde-LeBlanc, Nicole/0000-0002-2778-8358 NR 39 TC 24 Z9 24 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0907-4449 J9 ACTA CRYSTALLOGR D JI Acta Crystallogr. Sect. D-Biol. Crystallogr. PD JUL PY 2005 VL 61 BP 967 EP 975 DI 10.1107/S0907444905011285 PN 7 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 939ZL UT WOS:000230113000016 PM 15983420 ER PT J AU Alfano, M Grivel, JC Ghezzi, S Corti, D Trimarchi, M Poli, G Margolis, L AF Alfano, M Grivel, JC Ghezzi, S Corti, D Trimarchi, M Poli, G Margolis, L TI Pertussis toxin B-oligomer dissociates T cell activation and HIV replication in CD4 T cells released from infected lymphoid tissue SO AIDS LA English DT Article DE HIV; PTX; T-cell proliferation; lymphoid tissue; latency ID IMMUNODEFICIENCY-VIRUS TYPE-1; MEK/ERK SIGNALING PATHWAY; UROKINASE RECEPTOR; LYMPHOCYTES; EXPRESSION; THERAPY; SUBUNIT; BINDING; CCR5; MACROPHAGES AB Objective: To investigate, in human lymphoid tissue infected with HIV-1 ex vivo, the immunostimulatory and HIV inhibitory properties of pertussis toxin B oligomer (PTX-B) and of the genetically modified non-toxic PT-9K/129G. Methods: Human tonsils from uninfected donors were infected ex vivo with R5 or X4 HIV-1 in the presence or absence of PTX-B. Virus replication was evaluated in culture supernatants; cells emigrated from tissue blocks were immunostained for lymphocytic and activation markers. HIV DNA and cell proliferation were evaluated with real-time PCR and [H-3]thymidine incorporation, respectively. Results: Both PTX-B and PT-9K/129G inhibited HIV-1 replication. These compounds activated and stimulated the proliferation of emigrated cells, most of which were CD4 T lymphocytes. Cells emigrated from infected tissues did not produce detectable virus in unstimulated or in PTX-B- or PT-9K/129G-stimulated cultures whereas robust virus production was triggered by phytohemagglutinin (PHA) or interleukin-2 (IL-2). Analysis of HIV DNA content indicated that infected cells were present among emigrated cells and that their number greatly increased following IL-2 stimulation, whereas it remained constant in the presence of PTX-13 or PT-9K/129G. Conclusions: PTX-13 and PT-9K/129G inhibit both R5 and X4 HIV-1 replication in human lymphoid tissue ex vivo. In contrast to PHA and IL-2, they promote the proliferation of CD4 T lymphocytes emigrated from tissue, including HIV-infected cells, without triggering virus replication. Therefore, these emigrated CD4 T cells represent a novel model of a latent inducible HIV reservoir. Thus, PTX-B and the clinically approved PT-9K/129G are potential antiretroviral agents endowed with immunostimulatory capacity. (c) 2005 Lippincott Williams & Wilkins. C1 NICHHD, Lab Mol & Cellular Biophys, NIH, Bethesda, MD 20892 USA. San Raffaele Sci Inst, Dept Immunol & Infect Dis, AIDS Immunopathogenesis Unit, I-20132 Milan, Italy. Hosp San Raffaele, Otorhinolaryngol Div, I-20132 Milan, Italy. Vita Salute San Raffaele Univ, Sch Med, Milan, Italy. RP Poli, G (reprint author), NICHHD, Lab Mol & Cellular Biophys, NIH, Bldg 10,Room 10D14, Bethesda, MD 20892 USA. EM poli.guido@hsr.it; margolis@helix.nih.gov RI Trimarchi, Matteo/I-7401-2012 OI Trimarchi, Matteo/0000-0001-6472-3484 NR 34 TC 12 Z9 14 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 1 PY 2005 VL 19 IS 10 BP 1007 EP 1014 DI 10.1097/01.aids.0000174446.40379.3b PG 8 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 944YU UT WOS:000230468000005 PM 15958831 ER PT J AU Sklar, PA Masur, H Grubb, JR Voell, J Witek, J Ono, A Freed, EO Maldarelli, F AF Sklar, PA Masur, H Grubb, JR Voell, J Witek, J Ono, A Freed, EO Maldarelli, F TI Pravastatin does not have a consistent antiviral effect in chronically HIV-infected individuals on antiretroviral therapy SO AIDS LA English DT Letter ID LIPID RAFTS; TYPE-1; CHOLESTEROL; STATINS C1 Drexel Univ, Coll Med, Div HIV AIDS Med, Philadelphia, PA 19104 USA. NIAID, NIH, Bethesda, MD USA. Dept Crit Care Med, Ctr Clin, Bethesda, MD USA. NCI, HIV Drug Resistance Program, NIH, Frederick, MD USA. RP Sklar, PA (reprint author), Drexel Univ, Coll Med, Div HIV AIDS Med, Philadelphia, PA 19104 USA. NR 8 TC 24 Z9 26 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 1 PY 2005 VL 19 IS 10 BP 1109 EP 1111 DI 10.1097/01.aids.0000174461.31794.50 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 944YU UT WOS:000230468000020 PM 15958846 ER PT J AU Egan, MA Chong, SY Megati, S Montefiori, DC Rose, NF Boyer, JD Sidhu, MK Quiroz, J Rosati, M Schadeck, EB Pavlakis, GN Weiner, DB Rose, JK Israel, ZR Udem, SA Eldridge, JH AF Egan, MA Chong, SY Megati, S Montefiori, DC Rose, NF Boyer, JD Sidhu, MK Quiroz, J Rosati, M Schadeck, EB Pavlakis, GN Weiner, DB Rose, JK Israel, ZR Udem, SA Eldridge, JH TI Priming with plasmid DNAs expressing interleukin-12 and simian immunodeficiency virus gag enhances the immunogenicity and efficacy of an experimental AIDS vaccine based on recombinant vesicular stomatitis virus SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID T-LYMPHOCYTE RESPONSES; CELLULAR IMMUNE-RESPONSES; RHESUS-MONKEYS; SERONEGATIVE VOLUNTEERS; NEUTRALIZING ANTIBODIES; MUCOSAL CHALLENGE; CANARYPOX VACCINE; TYPE-1 INFECTION; ENV GENE; REPLICATION AB Of the various approaches being developed as prophylactic HIV vaccines, those based on a heterologous; plasmid DNA prime, live vector boost vaccination regimen appear especially promising in the nonhuman primate/simian-human immunodeficiency virus (SHIV) challenge model. In this study, we sought to determine whether a series of intramuscular priming immunizations with a plasmid DNA vaccine expressing SIVgag p39, in combination with plasmid expressed rhesus IL-12, could effectively enhance the immunogenicity and postchallenge efficacy of two intranasal doses of recombinant vesicular stomatitis virus (rVSV)-based vectors expressing HIV-1 env 89.6P gp160 and SIVmac239 gag p55 in rhesus macaques. In macaques receiving the combination plasmid DNA prime, rVSV boost vaccination regimen we observed significantly increased SIVgag-specific cell-mediated and humoral immune responses and significantly lower viral loads postintravenous SHIV89.6P challenge relative to macaques receiving only the rVSV vectored immunizations. In addition, the plasmid DNA prime, rVSV boost vaccination regimen also tended to increase the preservation of peripheral blood CD4(+) cells and reduce the morbidity and mortality associated with SHIV89.6P infection. An analysis of immune correlates of protection after SHIV89.61? challenge revealed that the prechallenge SHIV-specific IFN-gamma ELISpot response elicited by vaccination and the ability of the host to mount a virus-specific neutralizing antibody response postchallenge correlated with postchallenge clinical outcome. The correlation between vaccine-elicited cell-mediated immune responses and an improved clinical outcome after SHIV challenge provides strong justification for the continued development of a cytokine-enhanced plasmid DNA prime, rVSV vector boost immunization regimen for the prevention of HIV infection. C1 Wyeth Vaccines Res, Dept Vaccine Discovery, Pearl River, NY 10965 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Yale Univ, Sch Med, Dept Pathol, New Haven, CT 06510 USA. Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Wyeth Biometr Res, Pearl River, NY 10965 USA. NCI, Human Retrovirus Sect, Basic Res Lab, Frederick, MD 21702 USA. RP Egan, MA (reprint author), Wyeth Vaccines Res, Dept Vaccine Discovery, 401 N Middletown Rd,Bldg 180-216-10, Pearl River, NY 10965 USA. EM eganm@wyeth.com RI Weiner, David/H-8579-2014 FU NIAID NIH HHS [N01-AI-05397, N01-AI-25458] NR 68 TC 60 Z9 62 U1 0 U2 5 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL PY 2005 VL 21 IS 7 BP 629 EP 643 DI 10.1089/aid.2005.21.629 PG 15 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 955JX UT WOS:000231223300006 PM 16060834 ER PT J AU Wattendorf, DJ Muenke, M AF Wattendorf, DJ Muenke, M TI Diagnosis and management of fragile X syndrome SO AMERICAN FAMILY PHYSICIAN LA English DT Article ID PREMUTATION AB To complement the 2005 Annual Clinical Focus on medical genomics, AFP will be publishing a series of short reviews on genetic syndromes. This series was designed to increase awareness of these diseases so that family physicians can recognize and diagnose children with these disorders and understand the kind of care they might require in the future. The first review in this series discusses fragile X. syndrome. Copyright (c) 2005 American Academy of Family Physicians. C1 NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Muenke, M (reprint author), NHGRI, Med Genet Branch, NIH, 35 COnvent Dr,MSC3717,Bldg 35,Room 1B-203, Bethesda, MD 20892 USA. EM mmuenke@nhgri.nih.gov NR 7 TC 7 Z9 9 U1 0 U2 2 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD JUL 1 PY 2005 VL 72 IS 1 BP 111 EP 113 PG 3 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 944YN UT WOS:000230467300013 PM 16035691 ER PT J AU Marroquin, OC Kip, KE Mulukutla, SR Ridker, PM Pepine, CJ Tjandrawan, T Kelsey, SF Mankad, S Rogers, WJ Merz, CNB Sopko, G Sharaf, BL Reis, SE AF Marroquin, OC Kip, KE Mulukutla, SR Ridker, PM Pepine, CJ Tjandrawan, T Kelsey, SF Mankad, S Rogers, WJ Merz, CNB Sopko, G Sharaf, BL Reis, SE TI Inflammation, endothelial cell activation, and coronary microvascular dysfunction in women with chest pain and no obstructive coronary artery disease SO AMERICAN HEART JOURNAL LA English DT Article ID C-REACTIVE PROTEIN; CARDIAC SYNDROME-X; FLOW RESERVE; YOUNG MEN; ATHEROSCLEROSIS; ANGIOGRAMS; WISE AB Background Coronary artery microvascular dysfunction is prevalent in women with chest pain in the absence of obstructive coronary artery disease. (CAD) and is manifested by attenuated coronary flow reserve (CFR). Markers of inflammation and endothelial cell activation have been found to be elevated in patients with chest pain but without CAD. The relationship between inflammation, endothelial activation, and CFR is not known. Methods Ninety-four women with chest pain in the absence of obstructive angiographic CAD underwent catheterization-based assessment of CFR and measurement of levels of inflammatory markers'(n = 78) and endothelial cell activation in the NHLBI WISE study. Results Coronary flow reserve did not correlate with levels of C-reactive protein (high-sensitivity C-reactive protein) (r(s) = -0.07, P =.53), interleukin (IL)-6 (r(s) = -0.12, P =.31), IL-18 (r(s) = 0.14, P =.23), tumor necrosis factor alpha = -0.09, P =.43), transforming growth factor beta 1 (r(s) = 0.02, P=.84), and soluble intracellular adhesion molecule-1 (r(s) = 0.04, P =.68). Median levels of markers of inflammation and endothelial cell activation did not differ between the 57 women with abnormal CFR (<2.5) and the 37 women with normal coronary microvascular function (high-sensitivity C-reactive protein 0.32 vs 0.25 mg/dL, P =.80; IL-6 2.89 vs 2.39 pg/mL, P =.63; IL-18 218 vs 227 pg/mL, P =.59; tumor necrosis factor alpha 2.7 vs 2.4 pg/mL, P =.43; transforming growth factor beta 1 9928 vs 12 436 pg/mL, P =.76; soluble intracellular adhesion molecule-1 286 vs 287 pg/mL, P =.95). Multivariable models demonstrated no evidence of associations between markers of inflammation and of endothelial cell activation and CFR. Conclusions Coronary microvascular dysfunction is not associated with, markers of inflammation and endothelial cell activation in women with chest pain in the absence of obstructive CAD. These results suggest that inflammation and endothelial cell activation may not. play a pathophysiological role in coronary microvascular dysfunction. C1 Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15213 USA. W Penn Allegheny Hlth Syst, MCP Hahnemann Sch Med, Div Cardiol, Pittsburgh, PA USA. Brigham & Womens Hosp, Div Cardiol, Ctr Cardiovasc Dis Prevent, Boston, MA 02115 USA. Univ Florida, Div Cardiol, Gainesville, FL USA. Univ Alabama, Div Cardiol, Birmingham, AL USA. Cedars Sinai Med Ctr, Div Cardiol, Los Angeles, CA 90048 USA. NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. Rhode Isl Hosp, Div Cardiol, Providence, RI USA. RP Marroquin, OC (reprint author), Univ Pittsburgh, Med Ctr, Cardiovasc Inst, 200 Lothrop St, Pittsburgh, PA 15213 USA. EM marroquinoc@upmc.edu RI Reis, Steven/J-3957-2014; Marroquin, Oscar/F-2214-2015 OI Marroquin, Oscar/0000-0002-0909-0319 NR 21 TC 14 Z9 15 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUL PY 2005 VL 150 IS 1 BP 109 EP 114 DI 10.1016/j.ahj.2004.08.003 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 969FS UT WOS:000232219900016 PM 16084156 ER PT J AU Spiegel, AM Alving, BM AF Spiegel, AM Alving, BM TI Executive summary of the strategic plan for national institutes of health obesity research SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Symposium on SCience-Based Solutions to Obesity CY OCT 02, 2004 CL Anaheim, CA SP Coca-Cola Co Family Brands, ConAgra Foods, Hlth Foods Amer, McNeil Nutr, Nestle Nutr Inst, Nutr & Hlth Partnership, Peanut Inst, Slim Fast Foods Co, Wyeth Nutr, Harvard Med Sch, Div Nutr, Harvard Clin Nutr Res Ctr, Harvard Sch Public Hlth, Dept Nutr, Harvard Ctr Hlth Living, Amer Dietet Asssoc Fdn, ADA Weight Management Practice Grp DE obesity; research; National Institutes of Health; strategic plan; nutrition; diet; physical activity; behavior; environment; medical research; interdisciplinary research; translation; health disparities AB The Strategic Plan for National Institutes of Health (NIH) Obesity Research is intended to serve as a guide for coordinating obesity research activities across the NIH and for enhancing the development of new efforts based on identification of areas of greatest scientific opportunity and challenge. Developed by the NIH Obesity Research Task Force with critical input from external scientists and the public, the Strategic Plan reflects a dynamic planning process and presents a multidimensional research agenda, with an interrelated set of goals and strategies for achieving the goals. The major scientific themes around which the Strategic Plan is framed include the following: preventing and treating obesity through lifestyle modification; preventing and treating obesity through pharmacologic, surgical, or other medical approaches; breaking the link between obesity and its associated health conditions; and cross-cutting topics, including health disparities, technology, fostering of interdisciplinary research teams, investigator training, translational research, and education/outreach efforts. Through the efforts described in the Strategic Plan for NIH Obesity Research, the NIH will strive to facilitate and accelerate progress in obesity research to improve public health. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Spiegel, AM (reprint author), NIDDKD, NIH, 31 Ctr Dr,Bldg 31,Room 9A52, Bethesda, MD 20892 USA. EM spiegela@extra.niddk.nih.gov NR 0 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 2005 VL 82 IS 1 SU S BP 211S EP 214S PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 946JX UT WOS:000230569400002 PM 16002822 ER PT J AU Gray, KA Klebanoff, MA Brock, JW Zhou, HB Darden, R Needham, L Longnecker, MP AF Gray, KA Klebanoff, MA Brock, JW Zhou, HB Darden, R Needham, L Longnecker, MP TI In utero exposure to background levels of polychlorinated biphenyls and cognitive functioning among school-age children SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE child development; cohort studies; polychlorinated biphenyls ID HUMAN-MILK; ENVIRONMENTAL EXPOSURES; POSTNATAL EXPOSURE; DUTCH CHILDREN; YOUNG-CHILDREN; PCB CONGENERS; RAT; DEFICITS; MIXTURE; DIOXIN AB Polychlorinated biphenyls (PCBs) are ubiquitous environmental contaminants. In utero exposure to background levels of PCBs has been associated with intellectual impairment among children in most, but not all, studies. The authors evaluated prenatal PCB exposure in relation to cognitive test (intelligence quotient (IQ)) scores on the Wechsler Intelligence Scale for Children at age 7 years. Pregnant women were recruited from 12 US study centers from 1959 to 1965, and their children were followed until age 7 years (the Collaborative Perinatal Project). Third trimester serum was analyzed for PCBs in 1997-1999 for 732 women selected at random and for an additional 162 women whose children had either a low or a high IQ score. The PCB-IQ association was examined in multivariate models. Among those in the lowest exposure category (<1.25 mu g of PCB/liter of serum), the fully adjusted mean IQ score was 93.6 (standard error: 1.8); among those in the highest category (>= 5 mu g of PCB/liter), the mean IQ was 97.6 (standard error: 1.2); and overall the increase in IQ per unit increase in PCB level (mu g/liter) was 0.22 (95% confidence interval: -0.28, 0.71). In these data, in utero exposure to background levels of PCBs was not associated with lower IQ at age 7 years. C1 NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Chem Exposures & Mol Biol Branch, Off Program Dev, Div Extramural Res & Training,NIH,Dept Hlth & Hum, Res Triangle Pk, NC 27709 USA. NICHHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. Warren Wilson Coll, Dept Chem, Asheville, NC USA. Univ N Carolina, Sch Publ Hlth, Dept Biostat, Chapel Hill, NC USA. Westat Corp, Durham, NC USA. RP Longnecker, MP (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, MD A3-05, Res Triangle Pk, NC 27709 USA. EM longnecker@niehs.nih.gov OI Longnecker, Matthew/0000-0001-6073-5322 NR 46 TC 56 Z9 57 U1 1 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 1 PY 2005 VL 162 IS 1 BP 17 EP 26 DI 10.1093/aje/kwi158 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 939QU UT WOS:000230088300003 PM 15961582 ER PT J AU McDermott, MM Liu, K Criqu, MH Ruth, K Goff, D Saad, MF Wu, CL Homma, S Sharrett, AR AF McDermott, MM Liu, K Criqu, MH Ruth, K Goff, D Saad, MF Wu, CL Homma, S Sharrett, AR TI Ankle-brachial index and subclinical cardiac and carotid disease - The Multi-Ethnic Study of Atherosclerosis SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE arterial occlusive diseases; arteriosclerosis; carotid artery diseases; coronary disease; heart diseases ID PERIPHERAL ARTERIAL-DISEASE; INTIMA-MEDIA THICKNESS; CORONARY-HEART-DISEASE; CARDIOVASCULAR HEALTH; YOUNG-ADULTS; ARM INDEX; PREVALENCE; PRESSURE; CALCIFICATION; ASSOCIATION AB The authors studied associations between ankle-brachial index (ABI) and subclinical atherosclerosis in the Multi-Ethnic Study of Atherosclerosis. Participants included 3,458 women (average age = 62.6 years) and 3,112 men (average age = 62.8 years) who were free of clinically evident cardiovascular disease. Measurements included ABI, carotid artery intima-media thickness, and coronary artery calcium assessed with computed tomography. Five ABI categories were defined: <0.90 (definite peripheral arterial disease (PAD)), 0.90-0.99 (borderline ABI), 1.00-1.09 (low-normal ABI), 1.10-1.29 (normal ABI), and >1.30 (high ABI). Compared with that in men with normal ABI, significantly higher internal carotid artery intima-media thickness was observed in men with definite PAD (1.58 vs. 1.09; p < 0.001), borderline ABI (1.33 vs. 1.09; p < 0.001), and low-normal ABI (1.18 vs. 1.09; p < 0.001) after adjustment for confounders. Fully adjusted odds ratios for a coronary artery calcium score greater than 20 decreased across progressively higher ABI categories in both women (2.85 (definite PAD), 1.27 (borderline ABI), 1.11 (low-normal ABI), 1.00 (normal ABI; referent), and 0.78 (high ABI); p for trend = 0.0002) and men (3.26 (definite PAD), 1.72 (borderline ABI), 1.14 (low-normal ABI), 1.00 (normal ABI; referent), and 1.43 (high ABI); p for trend = 0.0002). These findings indicate excess coronary and carotid atherosclerosis at ABI values below 1.10 (men) and 1.00 (women) and may imply increased risk of cardiovascular events in persons with borderline and low-normal ABI. C1 Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27103 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. NHLBI, Epidemiol & Biometry Program, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Columbia Univ, Sch Med & Publ Hlth, Dept Med, New York, NY USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. RP McDermott, MM (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 675 N St Clair St,Suite 18-200, Chicago, IL 60611 USA. EM mdm608@northwestern.edu NR 37 TC 188 Z9 198 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUL 1 PY 2005 VL 162 IS 1 BP 33 EP 41 DI 10.1093/aje/kwi167 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 939QU UT WOS:000230088300005 PM 15961584 ER PT J AU Rutten, LJF Wanke, K Augustson, E AF Rutten, LJF Wanke, K Augustson, E TI Systems and individual factors associated with smoking status: Evidence from HINTS SO AMERICAN JOURNAL OF HEALTH BEHAVIOR LA English DT Article DE cigarette smoking; sustained quitting; health systems factors; depressive symptoms ID PSYCHIATRIC-DISORDERS; CIGARETTE-SMOKING; NATIONAL-HEALTH; UNITED-STATES; ALCOHOL-USE; TOBACCO USE; DRUG-USE; DEPRESSION; PREVALENCE; INTERVENTION AB Objectives: To examine the association of health care access/use, trust of physician advice, and depressive symptoms with the ability to sustain smoking cessation. Methods: Data from a nationally representative sample were used to compare current smokers (n=1246), sustained quitters (n=1502), and never smokers (n=3277). Results: Sustained quitters reported fewer depressive symptoms (OR=0.92) and were more likely to have health insurance (OR=1.75) and a usual source of care (OR=1.40) that they had seen within the last year (OR=2.16) and that they were more likely to trust (OR=1.40). Conclusions: Identification of these factors may inform providers' efforts to target and assist in smoking cessation. C1 Sci Applicat Int Corp, Mclean, VA 22102 USA. RP Augustson, E (reprint author), NCI, 6130 Execut Blvd,EPN-RM 4039, Rockville, MD 20852 USA. EM augustse@mail.nih.gov NR 33 TC 13 Z9 13 U1 0 U2 1 PU PNG PUBLICATIONS PI OAK RIDGE PA 2205-K OAK RIDGE RD, #115, OAK RIDGE, NC 27310 USA SN 1945-7359 J9 AM J HEALTH BEHAV JI Am. J. Health Behav. PD JUL-AUG PY 2005 VL 29 IS 4 BP 302 EP 310 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 941TE UT WOS:000230236300002 ER PT J AU Li, SL Tiab, L Jiao, XD Munier, FL Zografos, L Frueh, BE Sergeev, Y Smith, J Rubin, B Meallet, MA Forster, RK Hejtmancik, JF Schorderet, DF AF Li, SL Tiab, L Jiao, XD Munier, FL Zografos, L Frueh, BE Sergeev, Y Smith, J Rubin, B Meallet, MA Forster, RK Hejtmancik, JF Schorderet, DF TI Mutations in PIP5K3 are associated with Francois-Neetens Mouchetee fleck corneal dystrophy SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID GENETIC-LINKAGE; PROTEIN-KINASE; PIKFYVE; OPTIMIZATION AB Francois- Neetens fleck corneal dystrophy ( CFD) is a rare, autosomal dominant corneal dystrophy characterized by numerous small white flecks scattered in all layers of the stroma. Linkage analysis localized CFD to a 24- cM ( 18-Mb) interval of chromosome 2q35 flanked by D2S2289 and D2S126 and containing PIP5K3. PIP5K3 is a member of the phosphoinositide 3- kinase family and regulates the sorting and traffic of peripheral endosomes that contain lysosomally directed fluid phase cargo, by controlling the morphogenesis and function of multivesicular bodies. Sequencing analysis disclosed missense, frameshift, and/ or protein- truncating mutations in 8 of 10 families with CFD that were studied, including 2256delA, 2274delCT, 2709C -> T ( R851X), 3120C -> T ( Q988X), IVS19- 1G -> C, 3246G -> T ( E1030X), 3270C -> T ( R1038X), and 3466A -> G ( K1103R). The histological and clinical characteristics of patients with CFD are consistent with biochemical studies of PIP5K3 that indicate a role in endosomal sorting. C1 Inst Rech Ophtalmol, CH-1950 Sion, Switzerland. NEI, Ophthalm Genet & Clin Serv Branch, Bethesda, MD 20892 USA. NEI, Off Clin Director, Bethesda, MD 20892 USA. Jules Gonin Eye Hosp, Lausanne, Switzerland. Inselspital Bern, Dept Ophthalmol, CH-3010 Bern, Switzerland. LA Cty & USC Med Ctr, Doheny Eye Inst, Los Angeles, CA USA. Univ Miami, Sch Med, Bascom Palmer Eye Inst, Dept Ophthalmol, Miami, FL USA. RP Schorderet, DF (reprint author), Inst Rech Ophtalmol, Ave Grand Champ Sec 64, CH-1950 Sion, Switzerland. EM daniel.schorderet@iro.vsnet.ch NR 26 TC 63 Z9 65 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 2005 VL 77 IS 1 BP 54 EP 63 DI 10.1086/431346 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA 935PP UT WOS:000229794500005 PM 15902656 ER PT J AU Carlson, CS Aldred, SF Lee, PK Tracy, RP Schwartz, SM Rieder, M Liu, KA Williams, OD Iribarren, C Lewis, EC Fornage, M Boerwinkle, E Gross, M Jaquish, C Nickerson, DA Myers, RM Siscovick, DS Reiner, AP AF Carlson, CS Aldred, SF Lee, PK Tracy, RP Schwartz, SM Rieder, M Liu, KA Williams, OD Iribarren, C Lewis, EC Fornage, M Boerwinkle, E Gross, M Jaquish, C Nickerson, DA Myers, RM Siscovick, DS Reiner, AP TI Polymorphisms within the C-reactive protein (CRP) promoter region are associated with plasma CRP levels SO AMERICAN JOURNAL OF HUMAN GENETICS LA English DT Article ID CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; HAPLOTYPE RECONSTRUCTION; GENE-EXPRESSION; RISK-FACTORS; INFLAMMATION; MARKERS; POPULATION; PREDICTION; RECRUITMENT AB Elevated plasma levels of C- reactive protein ( CRP), an inflammation- sensitive marker, have emerged as an important predictor of future cardiovascular disease and metabolic abnormalities in apparently healthy men and women. Here, we performed a systematic survey of common nucleotide variation across the genomic region encompassing the CRP gene locus. Of the common single- nucleotide polymorphisms ( SNPs) identified, several in the CRP promoter region are strongly associated with CRP levels in a large cohort study of cardiovascular risk in European American and African American young adults. We also demonstrate the functional importance of these SNPs in vitro. C1 Univ Washington, Ctr Hlth Sci, Dept Genome Sci, Seattle, WA 98195 USA. Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA. Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Univ Vermont, Burlington, VT USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Alabama, Div Prevent Med, Birmingham, AL USA. Kaiser Permanente, Div Res, Oakland, CA USA. Univ Texas, Houston, TX USA. Univ Minnesota, Minneapolis, MN USA. NHLBI, Bethesda, MD 20892 USA. RP Carlson, CS (reprint author), Univ Washington, Ctr Hlth Sci, Dept Genome Sci, Room K-322,1705 NE Pacific St, Seattle, WA 98195 USA. EM csc47@u.washington.edu FU NHLBI NIH HHS [N01-HC-05187, HL66642, HL66682, HL71017, N01 HC045134, N01-HC-48047, N01-HC-48048, N01-HC-48049, N01-HC-48050, N01-HC-95095, N01HC05187, N01HC48047, N01HC48048, N01HC48049, N01HC48050, N01HC95095, R01 HL071017, U01 HL066642, U01 HL066682] NR 37 TC 216 Z9 222 U1 3 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0002-9297 J9 AM J HUM GENET JI Am. J. Hum. Genet. PD JUL PY 2005 VL 77 IS 1 BP 64 EP 77 DI 10.1086/431366 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 935PP UT WOS:000229794500006 PM 15897982 ER PT J AU Park, RM Schulte, PA Bowman, JD Walker, JT Bondy, SC Yost, MG Touchstone, JA Dosemeci, M AF Park, RM Schulte, PA Bowman, JD Walker, JT Bondy, SC Yost, MG Touchstone, JA Dosemeci, M TI Potential occupational risks for neurodegenerative diseases SO AMERICAN JOURNAL OF INDUSTRIAL MEDICINE LA English DT Article DE Alzheimer's disease; hairdresser; motor neuron disease; magnetic field; Parkinson's disease; pesticide; welding ID AMYOTROPHIC-LATERAL-SCLEROSIS; PROPORTIONATE MORTALITY RATIO; ELECTRIC UTILITY WORKERS; MAGNETIC-FIELD EXPOSURE; MOTOR-NEURON DISEASE; PARKINSONS-DISEASE; ALZHEIMERS-DISEASE; ELECTROMAGNETIC-FIELDS; SOLVENT EXPOSURE; DEMENTIA AB Background Associations between occupations and neurodegenerative diseases (NDD) may be discernable in death certificate data. Methods Hypotheses generated from 1982 to 1991 study were tested in data from 22 states for the years 1992-1998. Specific occupations and exposures to pesticides, solvents, oxidative stressors, magnetic fields, and welding fumes were evaluated. Results About one third (26187) of the occupations hypothesized with neurodegenerative associations had statistically significant elevated mortality odds ratios (MOR)for the same outcome. Occupations with the largest MORs were (a) for presenile dementia (PSD)dentists, graders/sorters (non-agricultural), and clergy; (b) for Alzheimer's disease (AD)-bank tellers, clergy, aircraft mechanics, and hairdressers; (c) for Parkinson's disease (PD)-biological scientists, clergy, religious workers, and post-secondary teachers; and (d) for motor neuron disease (MND)-veterinarians, hairdressers, and graders and sorters (non-agricultural). Teachers had significantly, elevated MORs for all four diseases, and hairdressers for three of the four. Non -horticultural farmers below age 65 had elevated PD (MOR = 2.23, 95% CI = 1.47-3.26), PSD (MOR = 2.22, 95% CI = 1.10-4.05), and AD (MOR = 1.76, 95% CI = 1.04-2.81). Sixty hertz magnetic fields exhibited significant exposure-response for AD and, below age 65, for PD (MOR = 1.87, 95% CI=1.14-2.98) and MND (MOR=1.63, 95% CI=1.10-2.39). Welding had elevated PD mortality below age 65 (MOR = 1.77, 95% CI = 1.08-2.75). Conclusions Support was observed for hypothesized excess neurodegenerative disease associated with a variety, of occupations, 60 Hz magnetic fields and welding. Published 2005 Wiley-Liss, Inc. C1 NIOSH, Ctr Dis Control & Prevent, Educ & Informat Div, Cincinnati, OH 45226 USA. NIOSH, Div Appl Res & Technol, Cincinnati, OH 45226 USA. NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA. Univ Calif Irvine, Dept Community & Environm Med, Irvine, CA USA. Univ Washington, Dept Environm Hlth, Seattle, WA 98195 USA. NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Rockville, MD USA. RP Park, RM (reprint author), NIOSH, Ctr Dis Control & Prevent, Educ & Informat Div, MS C-15,4676 Columbia Pkwy, Cincinnati, OH 45226 USA. EM rhp9@cdc.gov NR 94 TC 108 Z9 112 U1 1 U2 20 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0271-3586 J9 AM J IND MED JI Am. J. Ind. Med. PD JUL PY 2005 VL 48 IS 1 BP 63 EP 77 DI 10.1002/ajim.20178 PG 15 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 941NS UT WOS:000230222100009 PM 15940722 ER PT J AU Liu, YM Berthier-Schaad, Y Fink, NE Fallin, MD Tracy, RP Klag, MJ Smith, MW Coresh, J AF Liu, YM Berthier-Schaad, Y Fink, NE Fallin, MD Tracy, RP Klag, MJ Smith, MW Coresh, J TI beta-fibrinogen haplotypes and the risk for cardiovascular disease in a dialysis cohort SO AMERICAN JOURNAL OF KIDNEY DISEASES LA English DT Article DE beta-fibrinogen (FGB) gene; cardiovascular disease (CVD); cohort studies; end-stage renal disease (ESRD); haplotypes; inflammation ID ISCHEMIC-HEART-DISEASE; GENE-ENVIRONMENT INTERACTION; ACUTE MYOCARDIAL-INFARCTION; CORONARY-ARTERY DISEASE; ACUTE-PHASE REACTION; PLASMA-FIBRINOGEN; CAROTID ATHEROSCLEROSIS; HEMODIALYSIS-PATIENTS; PROMOTER REGION; RENAL-DISEASE AB Background. Elevated plasma fibrinogen levels are common in dialysis patients and may be related to an elevated risk for cardiovascular disease (CVD). We tested the hypothesis that genetic variation in the P-fibrinogen (FGB) gene, shown to explain 1% to 5% of fibrinogen level variation in the general population, has an important role in elevated fibrinogen levels and excess CVD risk in dialysis patients. Methods: Plasma fibrinogen was measured in 735 dialysis patients a median of 3 months from the start of dialysis therapy by using an automated clot-rate assay. Seven polymorphisms of the FGB gene were determined. Haplotype analysis was conducted using the Phase program to estimate haplotypes, with stratification for race. CVD events were ascertained from medical records. Results: During a median follow-up of 2.1 years, 279 CVD events occurred. Genotype frequencies were in Hardy-Weinberg equilibrium. Four common haplotypes identified were not associated with fibrinogen levels or CVD risk in the entire cohort or after stratification by race. The -455A allele, known to increase gene expression in vitro, was marginally associated with fibrinogen levels only in patients without diabetes (regression coefficient [P], 20 mg/dL [for +1 copy of the A allele; P = 0.06]), adjusted for age, sex, race, smoking, baseline dialysis modality, comorbidity, and history of diabetes and CVD. Post hoc analysis showed that -249C -> T (defining haplotype 3) was associated with greater fibrinogen levels and CVD risk among patients without diabetes and current smokers. Conclusion: The FGB gene likely does not have an important role in determining the variation in elevated plasma fibrinogen levels or excess CVD risk in dialysis patients. (c) 2005 by the National Kidney Foundation, Inc. C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. Natl Canc Inst, Lab Genom Divers, Frederick, MD USA. Natl Canc Inst, Sci Applicat Int Corp, Basic Res Program, Frederick, MD USA. Univ Vermont, Burlington, VT USA. RP Liu, YM (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Dept Publ Hlth Sci, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM yoliu@wfubmc.edu RI Smith, Michael/B-5341-2012 FU AHRQ HHS [R01-HS-08365]; NCI NIH HHS [N01-CO-12400]; NHLBI NIH HHS [R01-HL-62985, HL 46696, HL 58329]; NIDDK NIH HHS [K24-DK-02856, R01-DK-59616] NR 46 TC 6 Z9 6 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0272-6386 J9 AM J KIDNEY DIS JI Am. J. Kidney Dis. PD JUL PY 2005 VL 46 IS 1 BP 78 EP 85 DI 10.1053/j.ajkd.2005.03.008 PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 947CY UT WOS:000230622000010 PM 15983960 ER PT J AU Mills, JL Druschel, CM Pangilinan, F Pass, K Cox, C Seltzer, RR Conley, MR Brody, LC AF Mills, JL Druschel, CM Pangilinan, F Pass, K Cox, C Seltzer, RR Conley, MR Brody, LC TI Folate-related genes and omphalocele SO AMERICAN JOURNAL OF MEDICAL GENETICS PART A LA English DT Article DE omphalocele; ventral wall defects; folate; folic acid; multivitamins; vitamins; birth defects; MTHFR; MTHFD1; reduced folate carrier; transcobalamin II ID NEURAL-TUBE DEFECTS; SPINA-BIFIDA; RISK-FACTOR; 5,10-METHYLENETETRAHYDROFOLATE REDUCTASE; POLYMORPHISM; POPULATION; VITAMIN; CARRIER; PREVENTION; VARIANTS AB Women who take folic acid in the periconceptional period greatly reduce their chances of having a child with a neural tube defect (NTD). Using multivitamins may also reduce the risk of having a child with an omphalocele. In this study, we tested single nucleotide polymorphisms in folate-related enzyme genes for association with omphalocele. Polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methylenetetrahydrofolate dehydrogenase (MTHFD1), the reduced folate carrier (SLC19A1), and transcobalamin 11 (TCN2) were examined in 25 children with euploid omphalocele and 59 matched controls. Omphalocele cases were significantly more likely to carry the T allele of MTHFR 677C -> T, a known risk factor for NTDs (odds ratio 3.50, 95% confidence interval 1.07-11.47, P = 0.035). The MTHFD1 R653Q, SLC19A1 R27H, and TCN2 P259R polymorphisms showed no significant association with omphalocele. In this small study, the thermolabile variant of MTHFR, 677C T, was associated with an increased risk for omphalocele. This variant causes reduced enzyme activity, thus suggesting a mechanism by which multivitamins with folic acid might prevent omphalocele. Additional investigation is required. Published 2005 Wiley-Liss, Inc. C1 NICHD, NIH, Pediat Epidemiol Sect, Div Epidemiol Stat & Prevent Res,DHHS, Bethesda, MD 20892 USA. New York State Dept Hlth, Congenital Malformat Registry, Albany, NY USA. NHGRI, Genome Technol Branch, NIH, DHHS, Bethesda, MD 20892 USA. New York State Dept Hlth, Wadsworth Ctr, Albany, NY USA. RP Mills, JL (reprint author), NICHD, NIH, Pediat Epidemiol Sect, Div Epidemiol Stat & Prevent Res,DHHS, 6100 Bldg Room 7B03, Bethesda, MD 20892 USA. EM jamesmills@nih.gov NR 20 TC 9 Z9 9 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4825 J9 AM J MED GENET A JI Am. J. Med. Genet. A PD JUL 1 PY 2005 VL 136A IS 1 BP 8 EP 11 DI 10.1002/ajmg.a.30772 PG 4 WC Genetics & Heredity SC Genetics & Heredity GA 941KH UT WOS:000230213200002 PM 15937947 ER PT J AU Khaliq, AA Dimassi, H Huang, CY Narine, L Smego, RA AF Khaliq, AA Dimassi, H Huang, CY Narine, L Smego, RA TI Disciplinary action against physicians: Who is likely to get disciplined? SO AMERICAN JOURNAL OF MEDICINE LA English DT Article DE physician; discipline; disciplinary action; medical board; medical specialty ID MEDICAL DISCIPLINE; OREGON-BOARD; MALPRACTICE; STATE; EXPERIENCE; EXAMINERS AB PURPOSE: We sought to determine the characteristics of disciplined physicians at-large and the risk of disciplinary action over time and to report the type and frequency of complaints and the nature of disciplinary actions against allopathic physicians in Oklahoma. METHODS: Descriptive statistics, Kaplan-Meier analysis, and Cox proportional hazards modeling of publicly available data on physicians licensed by the Oklahoma Board of Medical Licensure and Supervision. RESULTS: Among 14 314 currently or previously licensed physicians, 396 (2.8%) had been disciplined. Using univariate proportional hazards analysis, men (P < 0.04), non-whites (P < 0.001), non-board-certified physicians (P < 0.001), and those in family medicine (P < 0.001), psychiatry (P < 0.001), general practice (P < 0.001), obstetrics-gynecology (P < 0.03) and emergency medicine (P < 0.001) were found to be at greater risk of being disciplined than other medical specialty groups. Foreign medical graduates had a higher risk of disciplinary action compared to US medical graduates (P < 0.001), although this finding was not confirmed by multivariate analysis. Kaplan-Meier analysis revealed that the proportion of physicians disciplined increased with each successive 10-year interval since first licensure. Complaints against physicians originated most often from the general public (66%), other physicians (5%), and staff (4%), and the complaints most frequently involved issues related to quality of care (25%), medication/prescription violations (19%), incompetence (18%), and negligence (17%). CONCLUSION: To improve physician behavior and reduce the need for disciplinary action, medical schools and residency training programs must continue to emphasize both patient care and medical professionalism as critical core competencies. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Dept Hlth Adv & Policy, Oklahoma City, OK 73190 USA. Amer Univ Beirut, Sch Nursing, Beirut, Lebanon. NIAID, Biostat Res Branch, Off Clin Res, NIH, Bethesda, MD USA. Univ N Carolina, Dept Hlth Behav & Adm, Charlotte, NC 28223 USA. NIAID, TB Res Sect, NIH, Bethesda, MD USA. RP Khaliq, AA (reprint author), Univ Oklahoma, Hlth Sci Ctr, Coll Publ Hlth, Dept Hlth Adv & Policy, POB 26901, Oklahoma City, OK 73190 USA. EM amir-khaliq@ouhsc.edu NR 16 TC 44 Z9 44 U1 0 U2 5 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD JUL PY 2005 VL 118 IS 7 BP 773 EP 777 DI 10.1016/j.amjmed.2005.01.051 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 945AL UT WOS:000230472600016 PM 15989912 ER PT J AU Varner, MW Leindecker, S Spong, CY Moawad, AH Hauth, JC Landon, MB Leveno, KJ Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M Peaceman, A O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM Gabbe, SG AF Varner, MW Leindecker, S Spong, CY Moawad, AH Hauth, JC Landon, MB Leveno, KJ Caritis, SN Harper, M Wapner, RJ Sorokin, Y Miodovnik, M Carpenter, M Peaceman, A O'Sullivan, MJ Sibai, BM Langer, O Thorp, JM Ramin, SM Mercer, BM Gabbe, SG CA Nat Institute Child Health Human TI The Maternal-Fetal Medicine Unit cesarean registry: Trial of labor with a twin gestation SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article; Proceedings Paper CT 51st Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 24-27, 2004 CL Houston, TX SP Soc Gynecol Invest DE trial of labor; twins; previous cesarean delivery ID VAGINAL BIRTH; DELIVERY; SECTION; WOMEN AB Objective: The purpose of this study was to identify the success rates and risks in women with a twin pregnancy who attempt a trial of labor after cesarean delivery. Study design: Cases were identified in the National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network's Cesarean Registry with a woman with a twin pregnancy who had had at least I previous cesarean delivery. Results: During the study period (1999-2002), 412 women fulfilled the study criteria, and 226 women had elective repeat cesarean delivery. Of the 186 women (45.1% of total) who attempted a trial of labor, 120 women were delivered successfully (success rate, 64.5%), and 66 women (35.5%) had a failed trial of labor. Thirty of the failed trials of labor involved a vaginal delivery for twin A and cesarean delivery for twin B. Women who attempted a trial of labor with twins had no increased risk of transfusion, endometritis, intensive care unit admissions, or uterine rupture when compared with elective repeat cesarean delivery. Fetal and neonatal complications were uncommon in either group at : 34 weeks of gestation. Conclusion: A trial of labor with twins after previous cesarean delivery does not appear to increase maternal morbidity. Perinatal morbidity is uncommon at : 34 weeks of gestation. (c) 2005 Mosby, Inc. All rights reserved. C1 Univ Utah, Sch Med, Dept Obstet & Gynecol, Salt Lake City, UT 84132 USA. George Washington Univ, Ctr Biostat, Washington, DC USA. NICHHD, Bethesda, MD 20892 USA. Univ Chicago, Chicago, IL 60637 USA. Univ Alabama Birmingham, Birmingham, AL USA. Ohio State Univ, Columbus, OH 43210 USA. SW Texas State Univ, Dallas, TX USA. Univ Pittsburgh, Pittsburgh, PA USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Thomas Jefferson Univ, Philadelphia, PA 19107 USA. Wayne State Univ, Detroit, MI USA. Univ Cincinnati, Cincinnati, OH USA. Columbia Univ, New York, NY USA. Brown Univ, Providence, RI 02912 USA. Northwestern Univ, Chicago, IL 60611 USA. Univ Miami, Miami, FL 33152 USA. Univ Tennessee, Memphis, TN 38163 USA. Univ Texas San Antonio, San Antonio, TX 78285 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Texas San Antonio, Houston, TX USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. Vanderbilt Univ, Nashville, TN USA. RP Varner, MW (reprint author), Univ Utah, Sch Med, Dept Obstet & Gynecol, 30 N 1900 E,Room 308, Salt Lake City, UT 84132 USA. EM mvarner@hsc.utah.edu RI Varner, Michael/K-9890-2013; OI caritis, steve/0000-0002-2169-0712; Varner, Michael/0000-0001-9455-3973; Peaceman, Alan/0000-0002-4515-4850 FU NICHD NIH HHS [HD 27883, HD 21414, HD 27869, HD 27889, HD 27905, HD 27915, HD 27917, HD 34116, HD 40485, HD19897, HD21410, HD27860, HD27861, HD34122, HD34136, HD34208, HD34210, HD36801, HD40500, HD40512, HD40544, HD40545, HD40560] NR 13 TC 23 Z9 23 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 EI 1097-6868 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUL PY 2005 VL 193 IS 1 BP 135 EP 140 DI 10.1016/j.ajog.2005.03.023 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 948BR UT WOS:000230691500023 PM 16021071 ER PT J AU Cui, CY Smith, JA Schlessinger, D Chan, CC AF Cui, CY Smith, JA Schlessinger, D Chan, CC TI X-linked anhidrotic ectodermal dysplasia disruption yields a mouse model for ocular surface disease and resultant blindness SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID HAIR FOLLICLE DEVELOPMENT; ECTODYSPLASIN-A RECEPTOR; FACTOR-KAPPA-B; TABBY SYNDROME; MUTATION; GENE; IMMUNODEFICIENCY; HOMOLOG; MICE; PATTERNS AB zX-linked anhidrotic/hypohidrotic ectodermal dysplasia (EDA) is caused by mutations in the (EDA) gene, which is required for the morphogenesis of ecto-derm-derived tissues. Although EDA function in skin appendage development has been studied in EDA mutant "Tabby" mice, we have recently identified characteristic abnormalities in the ocular surface, an ectoderm-derived tissue. Histology of eyes of Tabby males revealed that 1) as previously reported, mice lacked meibomian glands; 2) > 80% developed corneal lesions such as neovascularization, keratitis, ulceration, and keratinization identifiable from 9 weeks of age; and 3) > 80% showed ocular surface inflammation (blepharitis and conjunctivitis) when housed in a standard environment. Strikingly, both corneal defects and inflammation were prevented in Tabby mice bearing a transgene for the Eda-A1 isoform, but meibomian glands were restored little if at all. These findings suggest that intact ocular surface health is EDA dependent and that Tabby corneal abnormalities are not solely dependent on meibomian gland lipid secretion. Alternatively, susceptibility, to inflammation and other phenotypes could result from failure of the usual EDA receptor to activate nuclear factor-KB transcription factors. This can be further tested in Tabby and Tabby-EDA transgenic mice, which provide unique models of severe ocular surface disease. C1 NEI, Immunopathol Sect, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIA, Genet Lab, NIH, Baltimore, MD 21224 USA. RP Chan, CC (reprint author), NEI, Immunopathol Sect, Immunol Lab, NIH, Bldg 10,Room 10N103, Bethesda, MD 20892 USA. EM chanc@nei.nih.gov NR 29 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD JUL PY 2005 VL 167 IS 1 BP 89 EP 95 DI 10.1016/S0002-9440(10)62956-2 PG 7 WC Pathology SC Pathology GA 938XM UT WOS:000230036700010 PM 15972955 ER PT J AU Stapleton, CM Jaradat, M Dixon, D Kang, HS Kim, SC Liao, G Carey, MA Cristiano, J Moorman, MP Jetten, AM AF Stapleton, CM Jaradat, M Dixon, D Kang, HS Kim, SC Liao, G Carey, MA Cristiano, J Moorman, MP Jetten, AM TI Enhanced susceptibility of staggerer (ROR alpha(sg/sg)) mice to lipopolysaccharide-induced lung inflammation SO AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY LA English DT Article DE retinoid-related orphan receptor alpha; innate immune response; nuclear receptor ID RECEPTOR ROR-ALPHA; NF-KAPPA-B; AIRWAY INFLAMMATION; NUCLEAR RECEPTORS; PULMONARY INFLAMMATION; LYMPHOCYTE DEVELOPMENT; ALVEOLAR MACROPHAGES; HORMONE RECEPTORS; DEFICIENT MICE; RETINOIC ACID AB Stapleton, Cliona M., Maisa Jaradat, Darlene Dixon, Hong Soon Kang, Seong-Chul Kim, Grace Liao, Michelle A. Carey, Joey Cristiano, Michael P. Moorman, and Anton M. Jetten. Enhanced susceptibility of staggerer (ROR alpha(sg/sg)) mice to lipopolysaccharide-induced lung inflammation. Am J Physiol Lung Cell Mol Physiol 289: L144-L152, 2005. First published March 18, 2005; doi:10.1152/ajplung.00348.2004.-The retinoid-related orphan receptor alpha (ROR alpha), a member of the ROR subfamily of nuclear receptors, has been implicated in the control of a number of physiological processes, including the regulation of several immune functions. To study the potential role of ROR alpha in the regulation of innate immune responses in vivo, we analyzed the induction of airway inflammation in response to lipopolysaccharide (LPS) challenge in wild-type and staggerer ( ROR alpha sg/sg) mice, a natural mutant strain lacking ROR alpha expression. Examination of hematoxylin and eosin-stained lung sections showed that ROR alpha(sg/sg) mice displayed a higher degree of LPS-induced inflammation than wild-type mice. Bronchoalveolar lavage (BAL) was performed at 3, 16, and 24 h after LPS exposure to monitor the increase in inflammatory cells and the level of several cytokines/chemokines. The increased susceptibility of ROR alpha(sg/sg) mice to LPS-induced airway inflammation correlated with a higher number of total cells and neutrophils in BAL fluids from LPS-treated ROR alpha(sg/sg) mice compared with those from LPS-treated wild-type mice. In addition, IL-1 beta, IL-6, and macrophage inflammatory protein-2 were appreciably more elevated in BAL fluids from LPS-treated ROR alpha(sg/sg) mice compared with those from LPS-treated wildtype mice. The enhanced susceptibility of ROR alpha(sg/sg) mice appeared not to be due to a repression of I kappa B alpha expression. Our observations indicate that ROR alpha(sg/sg) mice are more susceptible to LPS-induced airway inflammation and are in agreement with the hypothesis that ROR alpha functions as a negative regulator of LPS-induced inflammatory responses. C1 NIEHS, Lab Resp Biol, Cell Biol Sect,Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol & Cellular Biol Sect, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Mol Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Stapleton, CM (reprint author), NIEHS, Lab Resp Biol, Cell Biol Sect,Div Intramural Res, NIH, 111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM jetten@niehs.nih.gov OI Jetten, Anton/0000-0003-0954-4445 NR 51 TC 32 Z9 33 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1040-0605 J9 AM J PHYSIOL-LUNG C JI Am. J. Physiol.-Lung Cell. Mol. Physiol. PD JUL PY 2005 VL 289 IS 1 BP L144 EP L152 DI 10.1152/ajplung.00348.2004 PG 9 WC Physiology; Respiratory System SC Physiology; Respiratory System GA 935HV UT WOS:000229772200017 PM 15778248 ER PT J AU Dmitrieva, NI Burg, MB Ferraris, JD AF Dmitrieva, NI Burg, MB Ferraris, JD TI DNA damage and osmotic regulation in the kidney SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Review DE hypertonicity; renal medulla; apoptosis; cell cycle delay ID RENAL MEDULLARY CELLS; ENHANCER-BINDING PROTEIN; HEAT-SHOCK PROTEINS; STRAND BREAK REPAIR; REQUIRES P38 KINASE; HYPERTONIC STRESS; HIGH NACL; HISTONE H2AX; STIMULATES TRANSCRIPTION; TARGETED DISRUPTION AB Dmitrieva, Natalia I., Maurice B. Burg, and Joan D. Ferraris. DNA damage and osmotic regulation in the kidney. Am J Physiol Renal Physiol 289: F2 - F7, 2005; doi: 10.1152/ajprenal. 00041.2005. - Renal medullary cells normally are exposed to extraordinarily high interstitial NaCl concentration as part of the urinary concentrating mechanism, yet they survive and function. Acute elevation of NaCl to a moderate level causes transient cell cycle arrest in culture. Higher levels of NaCl, within the range found in the inner medulla, cause apoptosis. Recently, it was surprising to discover that even moderately high levels of NaCl cause DNA double- strand breaks. The DNA breaks persist in cultured cells that are proliferating rapidly after adaptation to high NaCl, and DNA breaks normally are present in the renal inner medulla in vivo. High NaCl inhibits repair of broken DNA both in culture and in vivo, but the DNA is rapidly repaired if the level of NaCl is reduced. The inhibition of DNA repair is associated with suppressed activity of some DNA damage- response proteins like Mre11, Chk1, and H2AX but not that of others, like GADD45, p53, ataxia telangiectasia- mutated kinase (ATM), and Ku86. In this review, we consider possible mechanisms by which the renal cells escape the known dangerous consequences of persistent DNA damage. Furthermore, we consider that the persistent DNA damage may be a sensor of hypertonicity that activates ATM kinase to provide a signal that contributes to protective osmotic regulation. C1 NHLBI, Lab Kidney & Electrolyte Metab, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Burg, MB (reprint author), NHLBI, Lab Kidney & Electrolyte Metab, Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. EM maurice_burg@nih.gov RI Dmitrieva, Natalia/A-2924-2013 OI Dmitrieva, Natalia/0000-0001-8074-6950 NR 77 TC 13 Z9 14 U1 1 U2 2 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL PY 2005 VL 289 IS 1 BP F2 EP F7 DI 10.1152/ajprenal.00041.2005 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 934XC UT WOS:000229741900001 PM 15951478 ER PT J AU Morris, RG Uchida, S Brooks, H Knepper, MA Chou, CL AF Morris, RG Uchida, S Brooks, H Knepper, MA Chou, CL TI Altered expression profile of transporters in the inner medullary collecting duct of aquaporin-1 knockout mice SO AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY LA English DT Article DE ClC-nK1; urea ID UREA TRANSPORTER; RAT-KIDNEY; ALPHA-ENAC; VASOPRESSIN; ABUNDANCE; OSMOREGULATION; LOCALIZATION; PERMEABILITY; INVOLVEMENT; PHLORETIN AB Aquaporin-1 is the major protein responsible for transport of water across the epithelia of the proximal tubule and thin descending limbs. Rapid water efflux across the thin descending limb is required for the normal function of the countercurrent multiplier mechanism. Therefore, urinary concentrating capacity is severely impaired in aquaporin-1 knockout (AQP1 -/-) mice. Here, we have investigated the long-term consequences of deletion of the AQP1 gene product by profiling abundance changes in transporters expressed in the inner medullas of AQP1 (-/-) mice vs. heterozygotes [AQP1 (+/-)], which have a normal concentrating capacity. Semiquantitative immunoblotting demonstrated marked suppression of two proteins strongly expressed in the inner medullary collecting duct (IMCD): UT-A1 (a urea transporter) and AQP4 (a basolateral water channel). Furthermore, the urea permeability of the IMCD was significantly reduced in AQP1 (-/-)mice. In contrast, there was increased expression of three proteins normally expressed at higher levels in the cortical collecting duct (CCD) than in IMCD: AQP3 (another basolateral water channel) and the epithelial sodium channel subunits beta-ENaC and gamma-ENaC. Changes in expression of these proteins were confirmed by immunocytochemistry. Messenger RNA profiling (real-time RT-PCR) revealed changes in UT-A1, beta-ENaC, gamma-ENaC, and AQP3 transcript abundance that paralleled the changes in protein abundance. Thus, from the perspective of transport proteins, the IMCDs of AQP1 (-/-) mice have a significantly altered phenotype. To address whether these changes are specific to AQP1 (-/-) mice, we profiled IMCD transporter expression in a second knockout model manifesting a concentrating defect, that of ClC-nK1, a chloride channel in the ascending thin limb important for urinary concentration. As in the AQP1 knockout mice, ClC-nK1 (-/-) mice showed decreased expression of UT-A1 and increased expression of beta-ENaC and gamma-ENaC vs. WT controls. In conclusion, the expression profile of IMCD transporters is markedly altered in AQP1 -/- mice and this manifestation is related to the associated concentrating defect. C1 NHLBI, Lab Kidney & Electrolyte Metab, NIH, Bethesda, MD 20892 USA. Tokyo Med & Dent Univ, Grad Sch, Dept Nephrol, Bunkyo Ku, Tokyo, Japan. Univ Arizona, Dept Physiol, Tucson, AZ USA. RP Chou, CL (reprint author), NHLBI, Lab Kidney & Electrolyte Metab, NIH, Bldg 10,Rm 6N260,10 Ctr Dr MSC 1603, Bethesda, MD 20892 USA. EM chouj@nhlbi.nih.gov RI Uchida, Shinichi/D-1111-2013 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 26 TC 11 Z9 11 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1931-857X J9 AM J PHYSIOL-RENAL JI Am. J. Physiol.-Renal Physiol. PD JUL PY 2005 VL 289 IS 1 BP F194 EP F199 DI 10.1152/ajprenal.00121.2004 PG 6 WC Physiology; Urology & Nephrology SC Physiology; Urology & Nephrology GA 934XC UT WOS:000229741900021 PM 15713911 ER PT J AU Dishman, RK Motl, RW Sallis, JF Dunn, AL Birnbaum, AS Welk, GJ Bedimo-Rung, AL Voorhees, CC Jobe, JB AF Dishman, RK Motl, RW Sallis, JF Dunn, AL Birnbaum, AS Welk, GJ Bedimo-Rung, AL Voorhees, CC Jobe, JB TI Self-management strategies mediate self-efficacy and physical activity SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article ID SOCIAL-COGNITIVE DETERMINANTS; WHITE ADOLESCENT GIRLS; ACTIVITY QUESTIONNAIRE; ACTIVITY PATTERNS; OLDER CHILDREN; FIT INDEXES; EXERCISE; BEHAVIOR; INVARIANCE; VALIDITY AB Background: Self-efficacy theory proposes that girls who have confidence in their capability to be physically active will perceive fewer barriers to physical activity or be less influenced by them, be more likely to pursue perceived benefits of being physically active, and be more likely to enjoy physical activity. Self-efficacy is theorized also to influence physical activity through self-management strategies (e.g., thoughts, goals, plans, and acts) that support physical activity, but this idea has not been empirically tested. Methods: Confirmatory factor analysis was used to test the factorial validity of a measure of self-management strategies for physical activity. Next, the construct validity of the measure was tested by examining whether self-management strategies mediated the relationship between self-efficacy and self-reported physical activity, independently of several social-cognitive variables (i.e., perceived barriers, Outcome expectancy value, and enjoyment), among cross-sectional samples of 6th grade (n =309) and 8th grade (n =296) girls tested between February 14 and March 17, 2002. Data were analyzed in 2004. Results: Consistent with theory, self-efficacy had direct effects on the social-cognitive variables. The primary novel finding is that self-management strategies mediated the association of self-efficacy with physical activity in both samples. Conclusions: The measure of self-management strategies for physical activity yields valid scores among adolescent girls and warrants experimental study as a mediator of the influence of efficacy beliefs on physical activity. (c) 2005 American journal of Preventive Medicine. C1 Univ Georgia, Dept Kinesiol, Urbana, IL USA. Univ Illinois, Dept Kinesiol, Urbana, IL 61801 USA. San Diego State Univ, Dept Psychol, San Diego, CA 92182 USA. Cooper Inst, Behav Sci Res Grp, Golden, CO USA. Cornell Univ, Dept Publ Hlth, New York, NY USA. Iowa State Univ, Dept Hlth & Human Performance, Ames, IA USA. Louisiana State Univ, Hlth Sci Ctr, Dept Publ Hlth & Prevent Med, New Orleans, LA USA. Univ Maryland, Dept Kinesiol, College Pk, MD 20742 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. RP Dishman, RK (reprint author), Univ Georgia, Dept Exercise Sci, Ramsey Student Ctr, 300 River Rd, Athens, GA 30602 USA. EM rdishman@uga.edu FU NHLBI NIH HHS [U01 HL066853, U01 HL066853-01, U01 HL066855, U01 HL066855-01, U01 HL066857, U01 HL066857-01, U01HL66853, U01HL66855, U01HL66857, U01 HL066858, U01 HL066845, U01 HL066845-01, U01 HL066852, U01 HL066852-01, U01 HL066856, U01 HL066856-01, U01 HL066858-01, U01HL66845, U01HL66852, U01HL66856, U01HL66858] NR 59 TC 112 Z9 115 U1 2 U2 25 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD JUL PY 2005 VL 29 IS 1 BP 10 EP 18 DI 10.1016/j.amepre.2005.03.012 PG 9 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 939AE UT WOS:000230043700002 PM 15958246 ER PT J AU Miller, KE Laszlo, K Laudenslager, M Lindell, S Woodward, R Suomi, S AF Miller, K. E. Laszlo, K. Laudenslager, M. Lindell, S. Woodward, R. Suomi, S. TI Behavioral and physiological measures of temperament in captive tufted capuchins (Cebus apella) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD NIH, LCE NICHD, NIH Anim Ctr, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 43 BP 74 EP 74 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800044 ER PT J AU Howell, S Bales, K Evans, TA Jaffe, B Westergaard, G Higley, J AF Howell, S. Bales, K. Evans, T. A. Jaffe, B. Westergaard, G. Higley, J. TI The association between the neuropeptides oxytocin (OT) and vasopression (AVP) and the behavior of free-ranging female rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Alpha Genesis Inc, Yemasee, SC 29945 USA. Univ Calif Davis, Davis, CA USA. NIAAA, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 44 BP 75 EP 75 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800045 ER PT J AU Tiefenbacher, S Goldstein, MA Higley, JD Suomi, SJ Laudenslager, ML AF Tiefenbacher, S. Goldstein, M. A. Higley, J. D. Suomi, S. J. Laudenslager, M. L. TI Voluntary alcohol consumption in adult Macaca radiata: A pilot study SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Colorado, Hlth Sci Ctr, Dept Psychiat, Univ N Pavil, Denver, CO 80220 USA. NIAAA, LCTS, Sect Primate Models Psychopathol, Bethesda, MD USA. NICHHD, Comparat Ethol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 46 BP 76 EP 76 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800047 ER PT J AU Wu, JM Takahashi, DL Lawson, MS Pau, F Mattison, JA Ingram, DK Roth, GS Lane, MA Ottinger, MA Zelinski-Wooten, MB AF Wu, J. M. Takahashi, D. L. Lawson, M. S. Pau, F. Mattison, J. A. Ingram, D. K. Roth, G. S. Lane, M. A. Ottinger, M. A. Zelinski-Wooten, M. B. TI Predicting follicular response to controlled ovarian stimulation (COS) in rhesus monkeys SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20866 USA. Oregon Natl Primate Res Ctr, Beaverton, OR USA. NIA, Baltimore, MD 21224 USA. Merck & Co Inc, Rahway, NJ 07065 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 52 BP 80 EP 80 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800053 ER PT J AU Davis, E AF Davis, E. TI "More fun with a barrel full of monkeys" a non-human primate swing made from recycling plastic barrels SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIH ANIMAL Ctr, NIH, NICHD, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 53 BP 81 EP 81 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800054 ER PT J AU Barr, CS Lindell, SG Newman, TK Higley, S Suomi, SJ Goldman, D Higley, JD AF Barr, C. S. Lindell, S. G. Newman, T. K. Higley, S. Suomi, S. J. Goldman, D. Higley, J. D. TI Sequence variation in the 5 '-flanking region of the Macaca mulatta neuropeptide Y gene SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIH Anim Ctr, NIH, NIAAA, Lab Clin & Translat Studies, Poolesville, MD 20837 USA. NIAAA, NIH, Neurogenet Lab, Bethesda, MD 20892 USA. NICHD, NIH, Comparat Ethol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 67 BP 90 EP 91 PG 2 WC Zoology SC Zoology GA V44GS UT WOS:000202991800068 ER PT J AU Tiefenbacher, S Newman, TK Davenport, MD Meyer, JS Higley, JD Novak, MA AF Tiefenbacher, S. Newman, T. K. Davenport, M. D. Meyer, J. S. Higley, J. D. Novak, M. A. TI The role of two serotonin pathway gene polymorphisms in self-injurious behavior in singly housed Macaca mulatta SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Harvard Univ, Sch Med, New England Primate Res Ctr, Southborough, MA 01772 USA. NIAAA, NIH, Anim Ctr, Poolesville, MD USA. Univ Massachusetts, Dept Psychol, Amherst, MA 01003 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 68 BP 91 EP 91 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800069 ER PT J AU Dvoskin, RL Barr, CS Higley, SB Shannon, C Lindell, SG Goldman, D Higley, JD AF Dvoskin, R. L. Barr, C. S. Higley, S. B. Shannon, C. Lindell, S. G. Goldman, D. Higley, J. D. TI Functional variation of the Macaca mulatta CRH gene is associated with temperament and reproductive outcome SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NYU, Dept Anthropol, New York, NY 10003 USA. New York Consortium Evolutionary Primatol, New York, NY USA. NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 69 BP 92 EP 92 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800070 ER PT J AU Jaffe, BD Evans, TA Howell, S Westergaard, GC Higley, JD AF Jaffe, B. D. Evans, T. A. Howell, S. Westergaard, G. C. Higley, J. D. TI Left vs. right nipple preference in free-ranging infant rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Alpha Genesis Inc, Yemasee, SC 29945 USA. NIAAA, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 74 BP 95 EP 95 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800075 ER PT J AU Ruggiero, AM Roma, PG Silberberg, A Suomi, SJ AF Ruggiero, A. M. Roma, P. G. Silberberg, A. Suomi, S. J. TI Individual reward history, social comparison, and rejection of differentially valued goods in capuchin monkeys (Cebus apella) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, Poolesville, MD USA. American Univ, Dept Psychol, Washington, DC 20016 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 79 BP 98 EP 99 PG 2 WC Zoology SC Zoology GA V44GS UT WOS:000202991800080 ER PT J AU Chen, SA Schwandt, ML Lindell, SG Barr, CS Newman, TK Suomi, SJ Higley, JD AF Chen, S. A. Schwandt, M. L. Lindell, S. G. Barr, C. S. Newman, T. K. Suomi, S. J. Higley, J. D. TI Effects of acute intravenous ethanol administration on oral consumption of ethanol in rhesus macaques SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, NIH, LCTS, NIHAC, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 81 BP 100 EP 100 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800082 ER PT J AU Laszlo, K Miller, KE Suomi, SJ AF Laszlo, K. Miller, K. E. Suomi, S. J. TI Functional significance of urine washing in captive tufted capuchins (Cebus apella) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, Comparat Ethol Lab, Anim Ctr, Poolesville, MD 20837 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 114 BP 121 EP 122 PG 2 WC Zoology SC Zoology GA V44GS UT WOS:000202991800115 ER PT J AU Murray, L Weiss, A Gosling, SD AF Murray, L. Weiss, A. Gosling, S. D. TI Primate personality: Past, present and progress? SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Univ Coll Chester, Dept Psychol, Chester CH1 4BJ, Cheshire, England. NIA, Bethesda, MD 20892 USA. Univ Texas Austin, Austin, TX 78712 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 117 BP 123 EP 123 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800118 ER PT J AU Weiss, A King, JE Hopkins, WD AF Weiss, A. King, J. E. Hopkins, W. D. TI The generalizability of chimpanzee (Pan troglodytes) personality across two habitats: Zoological parks and Yerkes National Primate Research Center SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIA, Lab Personal & Cognit, NIH, Baltimore, MD 21224 USA. Univ Arizona, Dept Psychol, Tucson, AZ 85721 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 122 BP 126 EP 127 PG 2 WC Zoology SC Zoology GA V44GS UT WOS:000202991800123 ER PT J AU Suomi, SJ AF Suomi, S. J. TI Gene-environment interactions and personality differences in rhesus monkeys and other macaques SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHHD, Comparat Ethol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 123 BP 127 EP 127 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800124 ER PT J AU Novak, MS Sackett, GP Kenney, C AF Novak, M. S. Sackett, G. P. Kenney, C. TI Acute effects of psychosocial stressors on the mother and fetus in pigtailed macaques (Macaca nemestrina) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, Comparat Ethol Lab, NIH Anim Ctr, Poolesville, MD 20837 USA. Infant Primate Res Lab, Seattle, WA USA. Washington Natl Primate Res Ctr, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 143 BP 140 EP 141 PG 2 WC Zoology SC Zoology GA V44GS UT WOS:000202991800144 ER PT J AU Guillory, LC Schwandt, ML Newman, TK Suomi, SJ Higley, JD AF Guillory, L. C. Schwandt, M. L. Newman, T. K. Suomi, S. J. Higley, J. D. TI Early rearing condition affects adult csf serotonin metabolite and plasma cortisol concentrations in rhesus macaque (Macaca mulatta) mothers SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, LCTS, NIH, NIH Anim Ctr, Poolesville, MD 20837 USA. NICHD, Comparat Ethol Lab, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 161 BP 153 EP 154 PG 2 WC Zoology SC Zoology GA V44GS UT WOS:000202991800162 ER PT J AU Mckee, M Barr, CS Dvoskin, RL Higley, S Newman, TK Suomi, SJ Goldman, D Higley, JD AF McKee, M. Barr, C. S. Dvoskin, R. L. Higley, S. Newman, T. K. Suomi, S. J. Goldman, D. Higley, J. D. TI Association of a corticotropin-releasing hormone (CRH) gene haplotype with alcohol-induced stress axis activity in rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, LCTS, NIH, NIH Anim Ctr, Poolesville, MD 20837 USA. NIAAA, LNG, NIH, Bethesda, MD USA. NICHD, LCE, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 162 BP 154 EP 155 PG 2 WC Zoology SC Zoology GA V44GS UT WOS:000202991800163 ER PT J AU Gupte, M Barr, CS Duoskin, RL Newman, TK Higley, S Goldman, D Suomi, SJ Higley, JD AF Gupte, M. Barr, C. S. Duoskin, R. L. Newman, T. K. Higley, S. Goldman, D. Suomi, S. J. Higley, J. D. TI A polymorphism in the corticotropin-releasing hormone gene promoter is associated with increased hypothalamic-pituitary-adrenal axis activity following stress in rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, LNG, NIH, Rockville, MD 20852 USA. NIAAA, LCTS, NIH, NIH Anim Ctr, Rockville, MD USA. NICHD, LCE, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 163 BP 155 EP 155 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800164 ER PT J AU Davis, N Barr, CS Suomi, SJ Higley, JD Goldman, D Newman, TK AF Davis, N. Barr, C. S. Suomi, S. J. Higley, J. D. Goldman, D. Newman, T. K. TI Early infant experience, monoamine oxidase a (MAOA) genotype and their influence on aggression and ethanol consumption in male rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20852 USA. NICHHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 165 BP 156 EP 157 PG 2 WC Zoology SC Zoology GA V44GS UT WOS:000202991800166 ER PT J AU Wang, N Suomi, SJ Lindell, C AF Wang, N. Suomi, S. J. Lindell, C. TI Behavioral development in intensively-handled and non-intensively handled nursery-reared rhesus macaque (Macaca mulatta) neonates SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, Silver Spring, MD 20904 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 167 BP 158 EP 158 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800168 ER PT J AU Kenney, C Novak, MF Sackett, GP AF Kenney, C. Novak, M. F. Sackett, G. P. TI Maternal and fetal circadian rhythms during late gestation in pigtailed macaques (Macaca nemestrina) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHHD, Comparat Ethol Lab, NIH Anim Ctr, Poolesville, MD 20837 USA. Infant Primate Res Lab, Seattle, WA USA. Washington Natl Primate Res Ctr, Seattle, WA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 169 BP 159 EP 160 PG 2 WC Zoology SC Zoology GA V44GS UT WOS:000202991800170 ER PT J AU Schwandt, ML Ladd, K Higley, S Suomi, SJ Higley, JD AF Schwandt, M. L. Ladd, K. Higley, S. Suomi, S. J. Higley, J. D. TI Rearing condition and fluctuating asymmetry levels in infant rhesus macaques SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, NIH, Lab Clin & Translat Studies, Sect Comparat Primate Psychopathol, Poolesville, MD 20837 USA. NICHD, NIH, Comparat Ethol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 168 BP 159 EP 159 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800169 ER PT J AU Rakhovskaya, MV Becker, ML Bernhards, D Norcross, J Zehr, J Newman, J AF Rakhovskaya, M. V. Becker, M. L. Bernhards, D. Norcross, J. Zehr, J. Newman, J. TI Developmental changes in separation vocalizations of infant common marmosets SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, NIH, NIH Anim Ctr, Comparat Ethol Lab, Poolesville, MD 20837 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 170 BP 160 EP 160 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800171 ER PT J AU Chisholm, KL Schwandt, ML Becker, ML Suomi, SJ Higley, JD AF Chisholm, K. L. Schwandt, M. L. Becker, M. L. Suomi, S. J. Higley, J. D. TI Rearing condition differences in behavior when exposed to an unfamiliar intruder in rhesus macaques (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, NIH, Lab Clin & Translat Studies, Primate Unit,NIH Anim Ctr, Poolesville, MD 20837 USA. NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 184 BP 170 EP 170 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800185 ER PT J AU Jensen, JG Chisholm, KL Neamanll, TK Schwandt, ML Suomi, SJ Higley, JD AF Jensen, J. G. Chisholm, K. L. Neamanll, T. K. Schwandt, M. L. Suomi, S. J. Higley, J. D. TI An association between preadolescent rhesus macaques (Macaca mulatta) response to an acute stressor and alcohol consumption SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, NIH, Clin Studies Lab, Primate Unit,NIH Anim Ctr, Poolesville, MD 20837 USA. NICHD, NIH, Comparat Ethol Lab, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 189 BP 173 EP 174 PG 2 WC Zoology SC Zoology GA V44GS UT WOS:000202991800190 ER PT J AU Robbins, KLR Bennett, AJ Laudenslager, ML Suomi, SJ AF Robbins, K. L. Rasmussen Bennett, A. J. Laudenslager, M. L. Suomi, S. J. TI Developmental trajectories of free-ranging Cayo Santiago rhesus males: Evidence of association with a polymorphism in the serotonin transporter promoter region (SLC6A4) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIH, Comparat Ethol Lab, NIH Anim Ctr, Poolesville, MD 20837 USA. Wake Forest Univ, Sch Med, Dept Physiol Pharmacol, Winston Salem, NC 27109 USA. Univ Colorado Denver, Dept Psychiat, Denver, CO USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 206 BP 186 EP 186 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800207 ER PT J AU Newman, TK Barr, CS Suomi, SJ Goldman, D Higley, JD AF Newman, T. K. Barr, C. S. Suomi, S. J. Goldman, D. Higley, J. D. TI Age and monoamine oxidase a (MAOA) genotype effects on impulsive behavior in male rhesus monkeys (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20852 USA. NICHHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 208 BP 187 EP 188 PG 2 WC Zoology SC Zoology GA V44GS UT WOS:000202991800209 ER PT J AU McCormack, K Newrnan, TK Maestripieri, D Higley, JD Sanchez, MM AF McCormack, K. Newrnan, T. K. Maestripieri, D. Higley, J. D. Sanchez, M. M. TI Effects of serotonin transporter (5-HTT) gene variation and maternal maltreatment on behavior and hypothalamic pituitary adrenal (HPA) axis activity in rhesus monkeys (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA. Univ Chicago, Yerkes Natl Primate Res Ctr, Chicago, IL 60637 USA. Univ Chicago, Neurogenet Lab, NIAA, NIH, Chicago, IL 60637 USA. Univ Chicago, Inst Mind & Biol, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 209 BP 188 EP 188 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800210 ER PT J AU Bennett, AJ Szeliga, K Pierre, PJ Suomi, SJ Friedman, DP Grant, KA AF Bennett, A. J. Szeliga, K. Pierre, P. J. Suomi, S. J. Friedman, D. P. Grant, K. A. TI Preliminary data on long-term ethanol consumption patterns in early stressed monkeys (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Physiol & Pharmacol, Winston Salem, NC 27157 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Pediat, Winston Salem, NC 27157 USA. NICHD, Comparat Ethol Lab, NIH, Pooleville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 213 BP 191 EP 191 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800214 ER PT J AU O'Neill, P AF O'Neill, P. TI Early temperament ratings and lifespan social outcomes for two male rhesus monkeys (Macaca mulatta) SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Meeting Abstract C1 NICHD, Wagner Lab Comparat Ecol, Anim Ctr, NIH, Poolesville, MD 20837 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD JUL PY 2005 VL 66 SU 1 MA 225 BP 199 EP 199 PG 1 WC Zoology SC Zoology GA V44GS UT WOS:000202991800226 ER PT J AU Fisfalen, ME Schulze, TG DePaulo, JR DeGroot, LJ Badner, JA McMahon, FJ AF Fisfalen, ME Schulze, TG DePaulo, JR DeGroot, LJ Badner, JA McMahon, FJ TI Familial variation in episode frequency in bipolar affective disorder SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 57th Annual Meeting of the Society-of-Biological-Psychiatry CY MAY 16-18, 2002 CL PHILADELPHIA, PA SP Soc Biol Psychiat ID PSYCHOTIC SYMPTOMS; HYPOTHYROIDISM; ASSOCIATION; ILLNESS; MOOD; AGGREGATION; RELIABILITY; PEDIGREES; LINEALITY; VALIDITY AB Objective: Bipolar affective disorder is a familial illness characterized by recurrent episodes of mania and depression, but little is known about the familial nature of episode recurrence or its associated clinical features. The authors analyzed the recurrence frequency of affective episodes (episode frequency), along with associated clinical and demographic variables, in families with at least three members with a major affective disorder. Method: Members of 86 families ascertained through probands with bipolar affective disorder who had two or more first-degree relatives with a major affective disorder were interviewed by psychiatrists and assigned an all-sources diagnosis. Data for 407 subjects with a major affective disorder were analyzed. Episode frequency was estimated as the number of episodes of major depression, mania, and hypomania per year of illness. Results: Episode frequency was smoothly distributed over the range of 0.02-20.2 episodes/year. Episode frequency was significantly correlated among relatives (r = 0.56, p < 0.004). Earlier age at onset, bipolar II disorder, hallucinations or delusions, alcoholism, and suicidal behavior were all more prevalent in the highest than in the lowest quartiles of episode frequency. Female gender and recurrent major depression were more prevalent in the lowest quartile. Panic disorder, substance abuse, and thyroid disease were all unrelated to episode frequency. Subjects with DSM-IV rapid cycling did not differ from other affected subjects for most of the variables tested. Conclusions: Episode frequency is a highly familial trait in bipolar affective disorder, associated with several indicators of severity, and may be useful in defining clinical subtypes of bipolar affective disorder with greater genetic liability. DSM-IV rapid cycling was not supported by these data as the best predictor of familiality or severity. C1 Rosalin Franklin Univ Med & Sci, Mt Sinai Med Ctr, Dept Psychiat, Chicago, IL 60608 USA. Univ Chicago, Dept Psychiat, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Univ Heidelberg, Cent Inst Mental Hlth, Div Genet Epidemiol Psychiat, Mannheim, Germany. NIMH, Unit Genet Basis Mood & Anxiety Disorders, Bethesda, MD 20892 USA. RP Fisfalen, ME (reprint author), Rosalin Franklin Univ Med & Sci, Mt Sinai Med Ctr, Dept Psychiat, Calif 15th St, Chicago, IL 60608 USA. EM fism@sinai.org RI McMahon, Francis/A-7290-2009; Schulze, Thomas/H-2157-2013; OI McMahon, Francis/0000-0002-9469-305X FU Intramural NIH HHS NR 35 TC 47 Z9 48 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2005 VL 162 IS 7 BP 1266 EP 1272 DI 10.1176/appi.ajp.162.7.1266 PG 7 WC Psychiatry SC Psychiatry GA 941EB UT WOS:000230196500007 PM 15994708 ER PT J AU Kupka, RW Luckenbaugh, DA Post, RM Suppes, T Altshuler, LL Keck, PE Frye, MA Denicoff, KD Grunze, H Leverich, GS McElroy, SL Walden, J Nolen, WA AF Kupka, RW Luckenbaugh, DA Post, RM Suppes, T Altshuler, LL Keck, PE Frye, MA Denicoff, KD Grunze, H Leverich, GS McElroy, SL Walden, J Nolen, WA TI Comparison of rapid-cycling and non-rapid-cycling bipolar disorder based on prospective mood ratings in 539 outpatients SO AMERICAN JOURNAL OF PSYCHIATRY LA English DT Article; Proceedings Paper CT 5th International Conference on Bipolar Disorder CY JUN 12-14, 2003 CL Pittsburgh, PA ID FAMILY HISTORY; ILLNESS; VALIDITY; DEMOGRAPHICS AB Objective: To detect risk factors for rapid cycling in bipolar disorder, the authors compared characteristics of rapid-cycling and non-rapid-cycling patients both from a categorical and a dimensional perspective. Method: Outpatients with bipolar I disorder (N = 419), bipolar II disorder (N = 104), and bipolar disorder not otherwise specified (N = 16) were prospectively evaluated with daily mood ratings for 1 year. Subjects were classified as having rapid cycling (defined by the DSM-IV criterion of four or more manic or depressive episodes within 1 year) or not having rapid cycling, and the two groups' demographic and retrospective and prospective illness characteristics were compared. Associated factors were also evaluated in relationship to episode frequency. Results: Patients with rapid cycling (N = 206; 38.2%) significantly differed from those without rapid cycling (N = 333) with respect to the following independent variables: history of childhood physical and/or sexual abuse, bipolar I disorder subtype, number of lifetime manic or depressive episodes, history of rapid cycling, and history of drug abuse. The prevalence of these characteristics increased progressively with episode frequency. The proportion of women was greater than the proportion of men only among patients with eight or more episodes per year. The average time spent manic/hypomanic increased as a function of episode frequency, but the average time spent depressed was comparable in patients with one episode and in those with more than one episode. Brief episodes were as frequent as full-duration DSM-IV-defined episodes. Conclusions: A number of heterogeneous risk factors were progressively associated with increasing episode frequency. Depression predominated in all bipolar disorder patients, but patients with rapid cycling were more likely to be characterized by manic features. The findings overall suggest that rapid cycling is a dimensional course specifier arbitrarily defined on a continuum of episode frequency. C1 Altrecht Inst Mental Hlth Care, NL-3582 AC Utrecht, Netherlands. Univ Utrecht, Ctr Med, NL-3582 AC Utrecht, Netherlands. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NIMH, Biol Psychiat Branch, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Calif Los Angeles, Mood Disorders Res Program, Los Angeles, CA USA. Univ Cincinnati, Coll Med, Dept Psychiat, Psychopharmacol Res Program, Cincinnati, OH 45221 USA. Cincinnati Vet Affairs Med Ctr, Mental Hlth Care Line & Gen Clin Res Ctr, Cincinnati, OH USA. Univ Munich, Psychiat Klin, Munich, Germany. Univ Freiburg, Univ Klin Psychiat, Freiburg, Germany. Univ Groningen, Dept Psychiat, Groningen, Netherlands. RP Kupka, RW (reprint author), Altrecht Inst Mental Hlth Care, Tolsteegsingel 2A, NL-3582 AC Utrecht, Netherlands. EM r.kupka@planet.nl RI Nolen, Willem/E-9006-2014 NR 29 TC 107 Z9 109 U1 1 U2 3 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0002-953X J9 AM J PSYCHIAT JI Am. J. Psychiat. PD JUL PY 2005 VL 162 IS 7 BP 1273 EP 1280 DI 10.1176/appi.ajp.162.7.1273 PG 8 WC Psychiatry SC Psychiatry GA 941EB UT WOS:000230196500008 PM 15994709 ER PT J AU McGough, LJ Reynolds, SJ Quinn, TC Zenilman, JM AF McGough, LJ Reynolds, SJ Quinn, TC Zenilman, JM TI Which patients first? Setting priorities for antiretroviral therapy where resources are limited SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID UGANDA; AIDS; HIV AB The availability of limited funds from international agencies for the purchase of antiretroviral (ARV) treatment in developing countries presents challenges, especially in prioritizing who should receive therapy. Public input and the protection of human rights are crucial in making treatment programs equitable and accountable. By examining historical precedents of resource allocation, we aim to provoke and inform debate about current ARV programs. Through a critical review of the published literature, we evaluate 4 precedents for key lessons: the discovery of insulin for diabetes in 1922, the release of penicillin for civilian use in 1943, the development of chronic hemodialysis programs in 1961, and current allocation of liver transplants. We then describe current rationing mechanisms for ARVs. C1 Johns Hopkins Univ, Dept Infect Dis, Baltimore, MD USA. Johns Hopkins Univ, Dept Hist Med, Baltimore, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Zenilman, JM (reprint author), Johns Hopkins Bayview Med Ctr, Div Infect Dis, 4940 Eastern Ave,B-3 N, Baltimore, MD 21224 USA. EM jzenilma@jhmi.edu NR 38 TC 24 Z9 24 U1 0 U2 1 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 2005 VL 95 IS 7 BP 1173 EP 1180 DI 10.2105/AJPH.2004.052738 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 940EN UT WOS:000230126600027 PM 15983271 ER PT J AU Pace, C Talisuna, A Wendler, D Maiso, F Wabwire-Mangen, F Bakyaita, N Okiria, E Garrett-Mayer, ES Emanuel, E Grady, C AF Pace, C Talisuna, A Wendler, D Maiso, F Wabwire-Mangen, F Bakyaita, N Okiria, E Garrett-Mayer, ES Emanuel, E Grady, C TI Quality of parental consent in a Ugandan malaria study SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID INFORMED-CONSENT; TRIAL; VOLUNTARY; CONTEXT; AFRICA AB There is concern that illiteracy and limited education, lack of familiarity with research, and limited access to health care can jeopardize the ability of study participants, especially those in developing countries, to provide My informed and voluntary consent.(1-4) Despite this concern, few studies have been conducted to examine the quality of informed consent in the aforementioned settings.(5-10) In developing countries, where children are involved in vital research on diseases such as malaria and dysentery, even fewer studies have evaluated the quality of informed parental consent for pediatric trial participants unable to provide their own consent. This aspect of informed consent also is understudied in developed countries. At 4 separate sites in Uganda, we interviewed parents and guardians whose children were participating in a randomized study of antimalarial treatments. Immediately after parents consented to enroll their child in the antimalarial study, we interviewed those parents about their motivations for enrolling their child in the study, their experiences with the informed consent process, their comprehension of the trial, and the extent to which the enrollment decision was voluntary. C1 NIH, Dept Clin Bioeth, Sect Human Subjects, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Makerere Univ, Minist Hlth, Uganda Malaria Surveillance Project, Kampala, Uganda. Makerere Univ, Dept Women & Gender Studies, Kampala, Uganda. Johns Hopkins Univ, Sch Med, Dept Oncol, Div Biostat, Baltimore, MD USA. RP Grady, C (reprint author), NIH, Dept Clin Bioeth, Sect Human Subjects, Warren G Magnuson Clin Ctr, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM cgrady@cc.nih.gov NR 24 TC 22 Z9 22 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 800 I STREET, NW, WASHINGTON, DC 20001-3710 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD JUL PY 2005 VL 95 IS 7 BP 1184 EP 1189 DI 10.2105/AJPH.2004.053082 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 940EN UT WOS:000230126600029 PM 15933235 ER PT J AU Reid, L Meyrick, B Antony, VB Chang, LY Crapo, JD Reynolds, HY AF Reid, L Meyrick, B Antony, VB Chang, LY Crapo, JD Reynolds, HY TI The mysterious pulmonary brush cell - A cell in search of a function SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE airway epithelium; alveolar epithelium; microvilli; third pneumonocyte ID ELECTRON-MICROSCOPIC OBSERVATIONS; IMMOTILE CILIA SYNDROME; RAT LUNG; RESPIRATORY MUCOSA; BASAL BODIES; IDENTIFICATION; PREDOMINANCE; PATIENT; ABSENCE; GLANDS AB Brush cells, also termed tuft, caveolated, multivesicular, and fibrillovesicular cells, are part of theepithelial layer in the gastrointestinal and respiratory tracts. The cells are characterized by the presence of a tuft of blunt, squat microvilli (similar to 120-140/cell) on the cell surface. The microvilli contain filaments that stretch into the underlying cytoplasm. They have a distinctive pear shape with a wide base and a narrow microvillous apex. The function of the pulmonary brush cell is obscure. For this reason, a working group convened on August 23, 2004, in Bethesda, Maryland, to review the physiologic role of the brush (microvillous) cell in normal airways and alveoli and in respiratory diseases involving the alveolar region (e.g., emphysema and fibrosis) and airway disease characterized by either excessive or insufficient amounts of airway fluid (e.g., cystic fibrosis, chronic bronchitis, and exercise-induced asthma). The group formulated several suggestions for future investigation. For example, it would be useful to have a panel of specific markers for the brush cell and in this way separate these cells for culture and more direct examination of their function (e.g., microarray analysis and proteomics). Using quantitative analysis, it was suggested to examine the number and location of the cells in disease models. Understanding the function of these cells in alveoli and airways may provide clues to the pathogenesis of several disease states (e.g., cystic fibrosis and fibrosis) as well as a key for new therapeutic modalities. C1 NIDDK, Div Digest Dis & Nutr, Dept Hlth & Human Serv, Bethesda, MD USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Childrens Hosp, Boston, MA 02115 USA. Vanderbilt Univ, Ctr Lung Res, Dept Pathol, Nashville, TN 37232 USA. Univ Florida, Gainesville, FL USA. Natl Jewish Med & Res Ctr, Dept Environm & Occupat Hlth Sci, Denver, CO USA. Natl Jewish Med & Res Ctr, Dept Med, Denver, CO USA. RP Reynolds, HY (reprint author), NHLBI, Lung Biol & Dis Program, Div Lung Dis, Bldg 10, Bethesda, MD 20892 USA. EM reynoldh@mail.nih.gov NR 29 TC 20 Z9 22 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JUL 1 PY 2005 VL 172 IS 1 BP 136 EP 139 DI 10.1164/rccm.200502-203WS PG 4 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 939WD UT WOS:000230102400022 PM 15817800 ER PT J AU Maric, I Pittaluga, S Dale, JK Niemela, JE Delsol, G Diment, J Rosai, J Raffeld, M Puck, JM Straus, SE Jaffe, ES AF Maric, I Pittaluga, S Dale, JK Niemela, JE Delsol, G Diment, J Rosai, J Raffeld, M Puck, JM Straus, SE Jaffe, ES TI Histologic features of sinus histiocytosis with massive lymphadenopathy in patients with autoimmune lymphoproliferative syndrome SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article; Proceedings Paper CT 93rd Annual Meeting of the United-States-and-Canadian-Academy-of-Pathology CY MAR 06-12, 2004 CL Vancouver, CANADA SP US & Canadian Acad Pathol DE autoimmune lymphoproliferative syndrome; sinus histiocytosis with massive lymphadenopathy; Rosai-Dorfinar disease; autoimmune disease; histiocytoses; apoptosis; emperipolesis; Fas gene ID ROSAI-DORFMAN-DISEASE; FAS GENE-MUTATIONS; LYMPHOCYTE APOPTOSIS; DEFECTIVE LYMPHOCYTE; MALIGNANT-LYMPHOMA; CYTOKINE; ABNORMALITIES; ACTIVATION; DISORDER; ENTITY AB Autoimmune lymphoproliferative syndrome (ALPS) is an inherited disorder associated with defects in Fas-mediated apoptosis, characterized most often by childhood onset of lymphadenopathy, splenomegaly, hypergammaglobulinemia, and autoimmune phenomena. Children with sinus histiocytosis with massive lymphadenopathy (SHML) have a somewhat similar clinical phenotype in which prominent adenopathy also is associated with hypergammaglobulinemia, and autoimmune phenomena are reported in 10-15% of cases. We observed histopathological features of SHML in the lymph nodes of some of our ALPS patients, further suggesting an association between these two disorders. We, thus, reviewed the lymph nodes from 44 patients ALPS type la, all of whom were confirmed to have germline mutations in the TNFRSF6 gene encoding Fas (CD95/Apo-1). Eighteen of 44 (41%) patients had a histiocytic proliferation resembling SHML. The affected patients included 15 males and 3 females ranging in age from 11 months to 30 years at the time of the LN biopsy. The lymph nodes contained S-100+ histiocytes with characteristic nuclear features of SHML, and showed evidence of emperipolesis in both hematoxylin and eosin (H and E) and immuno-stained sections. The extent of the histiocytic proliferation was variable, being confluent in 2 cases, multifocal in 13, and only evident as isolated SHML-type histiocytes in 3. In lymph nodes without confluent SHML changes, increased numbers of CD3(+)CD4(-)CD8(-) (double negative) alpha beta T-cells, also negative for CD45RO, a feature of ALPS, could be identified in the paracortex. Furthermore, because SHML shares many clinical features with ALPS, we sought evidence of ALPS in sporadic SHML. We attempted to sequence TNFRSF6 DNA from archived tissue of 14 cases of Rosai-Dorfman disease. Full sequencing of the gene was successful in 4 of the cases; no mutations were identified. Nevertheless, our observations suggest that histologic features of SHML are part of the pathologic spectrum of ALPS type Ia. It remains to be determined if some cases of apparently sporadic SHML may be associated with heritable defects in Fas-mediated apoptosis. C1 NCI, Hematopathol Sect, Canc Res Ctr, Bethesda, MD 20892 USA. NIAID, Lab Clin Infect Dis, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Clin Pathol, Bethesda, MD USA. Hop Purpan, INSERM, Dept Oncogenese & Signalisat Cellules Hematopoiet, U563, Toulouse, France. NCI, Dept Pathol, Milan, Italy. NHGRI, Genet & Mol Biol Branch, Bethesda, MD 20892 USA. RP Jaffe, ES (reprint author), NIH, Pathol Lab, Bldg 10,Room 2N202,10 Ctr Dr,MSC-1500, Bethesda, MD 20892 USA. EM ejaffe@mail.nih.gov OI Niemela, Julie/0000-0003-4197-3792 NR 35 TC 57 Z9 60 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 2005 VL 29 IS 7 BP 903 EP 911 DI 10.1097/01.pas.0000157997.61177.08 PG 9 WC Pathology; Surgery SC Pathology; Surgery GA 939WF UT WOS:000230102600008 PM 15958855 ER PT J AU Fukuoka, J Franks, TJ Colby, TV Flaherty, KR Galvin, JFVR Hayden, D Gochuico, BR Kazerooni, EA Martinez, F Travis, WD AF Fukuoka, J Franks, TJ Colby, TV Flaherty, KR Galvin, JFVR Hayden, D Gochuico, BR Kazerooni, EA Martinez, F Travis, WD TI Peribronchiolar metaplasia: A common histologic lesion in diffuse lung disease and a rare cause of interstitial lung disease - Clinicopothologic features of 15 cases SO AMERICAN JOURNAL OF SURGICAL PATHOLOGY LA English DT Article DE peribronchiolar metaplasia; bronchiolar metaplasia; interstitial lung disease; small airway disease; pathology; bronchiolar fibrosis; bronchiolitis obliterans; high resolution computed tomography ID BRONCHIOLITIS; PNEUMONIA; FIBROSIS AB Peribronchiolar metaplasia (PBM) is a histologic lesion consisting of peribronchiolar metaplasia (PBM) of bronchiolar-type epithelium. Although widely recognized, PBM has received little attention in the pathologic literature and is not known to have clinical significance, We identified 15 cases in which PBM was the only major histologic finding in surgical lung biopsies from patients with interstitial lung disease (PBM-ILD), and we reviewed the clinical, imaging, and pathologic findings. The mean age was 57 years (range, 44-74 years) with 13 females and 2 males. One patient had been a welder with fume and asbestos exposure, another had pigeon exposure. Smoking history was available for 13 patients: three current smokers, one cocaine User, two former smokers, and seven never smokers. Three patients had collagen vascular disease. One had elevated serum antinuclear antibody titers. Pulmonary function data were available for 10 patients: one obstructive, five restrictive, two mixed obstructive and restrictive, and two normal. Computerized tomography in 7 patients showed mosaic attenuation in 3 patients and air trapping in I patient, no bronchiectasis, septal lines, or honeycombing were seen in any cases. All 11 patients with available follow-up are alive; 4 of them have experienced symptomatic improvement (follow-up, 0.6-6.9 years; mean, 2.4 years). PBM was found focally in other interstitial lung diseases, which were assessed for this lesion: 59% of usual interstitial pneumonia (17 of 29), 50% of nonspecific interstitial pneumonia (10 of 20), desquamative interstitial pneumonia (3 of 6), hypersensitivity pneumonitis (9 or 18), and 11% of respiratory bronchiolitis (2 of 18). In summary, PBM is a common histologic finding in various interstitial lung disorders, It is rarely the sole major lung biopsy finding in patients presenting with interstitial lung disease (PBM-ILD), patients are mostly older women, with mild symptoms and CT findings. Survival appears to be favorable. C1 NCI, Lab Populat Genet, Bethesda, MD 20892 USA. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. Armed Forces Inst Pathol, Dept Radiol, Washington, DC 20306 USA. Mayo Clin Scottsdale, Dept Lab Med, Scottsdale, AZ USA. Univ Michigan, Dept Pulm Med, Ann Arbor, MI 48109 USA. NHLBI, Bethesda, MD 20892 USA. Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. RP Travis, WD (reprint author), Mem Sloan Kettering Canc Ctr, Dept Pathol, 1275 York Ave, New York, NY 10021 USA. EM travisw@mskcc.org NR 18 TC 40 Z9 42 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0147-5185 J9 AM J SURG PATHOL JI Am. J. Surg. Pathol. PD JUL PY 2005 VL 29 IS 7 BP 948 EP 954 DI 10.1097/01.pas.0000168177.71405.ac PG 7 WC Pathology; Surgery SC Pathology; Surgery GA 939WF UT WOS:000230102600014 PM 15958861 ER PT J AU Meyers, CM Kirk, AD AF Meyers, CM Kirk, AD TI Workshop on late renal allograft dysfunction SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE alloantibody response; allograft dysfunction; kidney fibrosis; nephrotoxicity; polyoma virus nephropathy; protocol biopsy ID ANTIBODY-MEDIATED REJECTION; TRANSPLANTATION; NEPHROPATHY; RECIPIENTS; SURVIVAL; FAILURE; ORGAN; DNA AB Despite continued improvement in incidence of acute immune injury and short-term graft survival, late allograft dysfunction remains a significant problem in the renal transplant population. Recent reports suggest that rates of renal function decline are quite varied in the overall recipient population, and that individual rates for many recipients may not change substantially over time. Moreover, analyses also reveal distinct predictive factors for both early and late functional decline. Long-term outcome studies for renal transplantation, however, might be significantly limited by incomplete data sets for assessing clinical endpoints. In view of the heterogeneous factors that may cause progressive allograft injury, more routine biopsy sampling would allow a more complete characterization of induced injuries. Elucidating mechanisms of renal fibrosis in response to injury, in experimental systems and humans, is also an important goal in better understanding chronic allograft damage. Regulation of cell senescence genes and epithelial to mesenchymal transition, studied in other models of renal fibrosis, are likely relevant to studies of renal allograft dysfunction. Recent technical advances in analyzing biological samples may play a pivotal role in identifying and validating surrogate markers of allograft function for future interventional trials in transplantation. C1 NIDDKD, Div Kidney Urol & Hematol Dis, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. NIDDK, Transplantat Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. RP Meyers, CM (reprint author), NIDDKD, Div Kidney Urol & Hematol Dis, Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. EM cm420i@nih.gov RI Kirk, Allan/B-6905-2012 NR 26 TC 17 Z9 18 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD JUL PY 2005 VL 5 IS 7 BP 1600 EP 1605 DI 10.1111/j.1600-6143.2005.00926.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 933MV UT WOS:000229635100005 PM 15943617 ER PT J AU Kim, YJ Kumaraswami, V Choi, EW Mu, JB Follmann, DA Zimmerman, P Nutman, TB AF Kim, YJ Kumaraswami, V Choi, EW Mu, JB Follmann, DA Zimmerman, P Nutman, TB TI Genetic polymorphisms of eosinophil-derived neurotoxin and eosinophil cationic protein in tropical pulmonary eosinophilia SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID GAMMA-GLUTAMYL-TRANSPEPTIDASE; MAJOR BASIC-PROTEIN; CASTE POPULATIONS; INNATE IMMUNITY; BRUGIA-MALAYI; ALLELES; ASTHMA; ONCHOCERCIASIS; SUSCEPTIBILITY; RIBONUCLEASE AB Because eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP) are critical in the pathogenesis of tropical pulmonary eosinophilia (TPE), we analyzed genetic polymorphisms of both in 181 individuals from southern India with varying clinical manifestations of Witchereria bancrofti infection (including 26 with TPE). Using haplotype frequency analysis, we identified four known (of nine) and two novel haplotypes for EDN (1 2 7 8, 10, and 11). For ECP, five (of seven known) haplotypes (1-5) were identified. Although we found no significant association between frequencies of EDN and ECP polymorphisms and TPE development, we observed a unique pattern of EDN and ECP polymorphism distribution among this population. Genotype TT at locus 1088 of ECP in one TPE patient was not observed in any other clinical group. Although the EDN and ECP polymorphisms appear unlikely to be associated with the development of TPE, further analyses will be more definitive. C1 NIAID, Parasit Dis Lab, Helminth Immunol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA. TB Res Ctr, Madras, Tamil Nadu, India. Seoul Natl Univ, Coll Med, Dept Pediat, Seoul, South Korea. Case Western Reserve Univ, Univ Hosp Cleveland, Dept Med, Div Geog Med, Cleveland, OH USA. RP Kim, YJ (reprint author), NIAID, Parasit Dis Lab, Helminth Immunol Sect, NIH, 4 Ctr Dr,Bldg 1,Room B1-07, Bethesda, MD 20892 USA. EM yjkim@niaid.nih.gov; tnutman@niaid.nih.gov RI Choi, Eun Hwa/J-5691-2012 NR 49 TC 7 Z9 7 U1 0 U2 1 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUL PY 2005 VL 73 IS 1 BP 125 EP 130 PG 6 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 944TH UT WOS:000230451900026 PM 16014847 ER PT J AU John, CC Moormann, AM Pregibon, DC Sumba, PO Mchugh, MM Narum, DL Lanar, DE Schluchter, MD Kazura, JW AF John, CC Moormann, AM Pregibon, DC Sumba, PO Mchugh, MM Narum, DL Lanar, DE Schluchter, MD Kazura, JW TI Correlation of high levels of antibodies to multiple pre-erythrocytic Plasmodium falciparum antigens and protection from infection SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Article ID LIVER-STAGE ANTIGEN-1; MEROZOITE SURFACE PROTEIN-1; POLYMERASE-CHAIN-REACTION; CD4(+) T-CELL; CIRCUMSPOROZOITE PROTEIN; CLINICAL MALARIA; INHIBITORY ANTIBODIES; MONOCLONAL-ANTIBODIES; SPOROZOITE INVASION; SYNTHETIC PEPTIDES AB High levels of antibodies to multiple antigens may be more strongly associated with protection from infection than antibodies to a single antigen. Antibody-associated protection against Plasmodium falciparum infection was assessed in a cohort of 68 adults living in an area of holoendemic malaria in Kenya. Antibodies to the pre-erythrocytic antigens circumsporozoite protein (CSP), liver-stage antigen-1 (LSA-1), thrombospondin-related adhesive protein (TRAP), and blood-stage antigens apical membrane antigen-1 (AMA-1), erythrocyte binding antigen-175 (EBA-175), and merozoite surface protein 1 (MSP-1) were tested. Peptides were used for CSP (NANP repeat) and LSA-1 (central repeat), and recombinant antigens were used for TRAP (aa D-48-K-394), AMA-1 (ectodomain, (non-glycosylated), EBA-175 (non-glyconated), and MSP-1 (MSP-1(19)). Weekly microscopy testing for P. falciparum infection was performed over a 12-week period after drug-mediated clearance of P. falciparum parasitemia. Individuals with high levels of IgG antibodies (> 2 arbitrary units) to CSP, LSA-1, and TRAP had a 57% decrease in the risk of infection (95% confidence interval 20-77%, P = 0.016). This decreased risk remained significant after adjustment for age, prior parasitemia, bed net use, sickle cell trait, and village of residence. In contrast, protection against infection did not correlate with high levels of IgG antibodies to blood-stage antigens or IgM antibodies to pre-erythrocytic or blood-stage antigens. High levels of IgG antibodies to CSP, LSA-1, and TRAP may be useful immune correlates of protection against P. falciparum infection in malaria-endemic populations. C1 Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Rainbow Ctr Int Chil Hlth,Ctr Global Hlth & Dis, Div Pediat Infect Dis,Div Clin Epidemiol, Cleveland, OH 44106 USA. Kenya Govt Med Res Ctr, Kisumu, Kenya. NIH, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Washington, DC USA. RP John, CC (reprint author), Case Western Reserve Univ, Rainbow Babies & Childrens Hosp, Rainbow Ctr Int Chil Hlth,Ctr Global Hlth & Dis, Div Pediat Infect Dis,Div Clin Epidemiol, 11100 Euclid Ave,MS6008,RBC 487, Cleveland, OH 44106 USA. EM chandy.john@case.edu; ann.moormann@case.edu; pregibon@mit.edu; pos@case.edu; marilyan.mchugh@case.edu; dnarum@niaid.nih.gov; lanar@na.amedd.army.mil; mark.schluchter@case.edu RI John, Chandy/B-4164-2008; Lanar, David/B-3560-2011 FU NIAID NIH HHS [AI43906] NR 41 TC 61 Z9 61 U1 0 U2 3 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD JUL PY 2005 VL 73 IS 1 BP 222 EP 228 PG 7 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 944TH UT WOS:000230451900042 PM 16014863 ER PT J AU Floel, A Breitenstein, C Hummel, F Celnik, P Gingert, C Sawaki, L Knecht, S Cohen, LG AF Floel, A Breitenstein, C Hummel, F Celnik, P Gingert, C Sawaki, L Knecht, S Cohen, LG TI Dopaminergic influences on formation of a motor memory SO ANNALS OF NEUROLOGY LA English DT Article ID USE-DEPENDENT PLASTICITY; TRANSCRANIAL MAGNETIC STIMULATION; PREFRONTAL CORTEX; D-AMPHETAMINE; AGE; MODULATION; LEVODOPA; RECOVERY; EXCITABILITY; STROKE AB The ability of the central nervous system to form motor memories, a process contributing to motor learning and skill acquisition, decreases with age. Dopaminergic activity, one of the mechanisms implicated in memory formation, experiences a similar decline with aging. It is possible that restoring dopaminergic function in elderly adults could lead to improved formation of motor memories with training. We studied the influence of a single oral dose of levodopa (100mg) administered preceding training on the ability to encode an elementary motor memory in the primary motor cortex of elderly and young healthy volunteers in a randomized, double-blind, placebo-controlled design. Attention to the task and motor training kinematics were comparable across age groups and sessions. In young subjects, encoding a motor memory under placebo was more prominent than in older subjects, and the encoding process was accelerated by intake of levodopa. In the elderly group, diminished motor memory encoding under placebo was enhanced by intake of levodopa to levels present in younger subjects. Therefore, upregulation of dopaminergic activity accelerated memory formation in young subjects and restored the ability to form a motor memory in elderly subjects; possible mechanisms underlying the beneficial effects of dopaminergic agents on motor learning in neurorehabilitation. C1 NINDS, Human Cort Physiol Sect, NIH, Bethesda, MD 20817 USA. Univ Munster, Dept Neurol, D-4400 Munster, Germany. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. RP Cohen, LG (reprint author), NINDS, Human Cort Physiol Sect, NIH, 10 Ctr Dr, Bethesda, MD 20817 USA. EM cohenl@ninds.nih.gov RI Floel, Agnes/A-9426-2017; OI Knecht, Stefan/0000-0003-1056-9228 NR 53 TC 113 Z9 114 U1 1 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0364-5134 J9 ANN NEUROL JI Ann. Neurol. PD JUL PY 2005 VL 58 IS 1 BP 121 EP 130 DI 10.1002/ana.20536 PG 10 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 942NA UT WOS:000230287900013 PM 15984008 ER PT J AU Van Hoey, NM AF Van Hoey, NM TI Effect of cyclobenzaprine on tricyclic antidepressant assays SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE cyclobenzaprine; tricyclic antidepressant assays; interference; toxicology ID LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; AMITRIPTYLINE; INTERFERENCE; TOXICOLOGY; IMIPRAMINE; OVERDOSE; URINE AB OBJECTIVE: To evaluate cyclobenzaprine interference on tricyclic antidepressant assays. DATA SOURCES: Literature was identified through a MEDLINE search (1966-August 2004) using the search terms cyclobenzaprine, tricyclic antidepressant, toxicology, and assay. DATA SYNTHESIS: Cyclobenzaprine is structurally similar to tricyclic antidepressants and is often identified as a tricyclic antidepressant on toxicology assays. Older chromatographic assays demonstrate retention time differences of only seconds and nearly identical color stains between cyclobenzaprine and individual tricyclic antidepressants. In comparison, ultraviolet absorption ratios of 4.18 for amitriptyline and 1.85 for cyclobenzaprine are easily distinguished. Spectroscopy also consistently identifies cyclobenzaprine's unique mass-to-charge ratio peaks of 275 and 215 compared with those of amitriptyline, Available bioanalytic techniques are reviewed for their ability to correctly identify cyclobenzaprine and differentiate the drug from tricyclic antidepressants. CONCLUSIONS: When assays are positive for tricyclic antidepressants without a history of their use, an attempt should be made to identify confounders, such as cyclobenzaprine. Newer bioanalytic techniques, such as ultraviolet absorption and mass spectroscopy, accurately identify cyclobenzaprine in such instances. C1 Aspen Syst Corp, Natl Lib Med, Alexandria, VA 22314 USA. RP Van Hoey, NM (reprint author), Aspen Syst Corp, Natl Lib Med, 2109 Mill Rd,316, Alexandria, VA 22314 USA. EM nicole_vanhoey@comcast.net NR 19 TC 10 Z9 10 U1 0 U2 4 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD JUL-AUG PY 2005 VL 39 IS 7-8 BP 1314 EP 1317 DI 10.1345/aph.1E632 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 941QN UT WOS:000230229400024 PM 15956237 ER PT J AU Miller, FW AF Miller, FW TI Environmental factors and muscle weakness SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology CY JUN 08-11, 2005 CL Vienna, AUSTRIA C1 NIEHS, Environm Autoimmun Grp, Natl Inst Hlth, Bethesda, MD USA. OI Miller, Frederick/0000-0003-2831-9593 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2005 VL 64 SU 3 BP 36 EP 36 PG 1 WC Rheumatology SC Rheumatology GA 937FD UT WOS:000229909100111 ER PT J AU Goldbach-Mansky, R Canna, S Dailey, N Gelabert, A Rubin, B Kim, J Brewer, C Butman, J Turner, M Karp, B Hill, S Aksentijevich, I Haverkamp, M Holland, S Hoffman, S Pham, TH Hawkins, P Kastner, DL AF Goldbach-Mansky, R Canna, S Dailey, N Gelabert, A Rubin, B Kim, J Brewer, C Butman, J Turner, M Karp, B Hill, S Aksentijevich, I Haverkamp, M Holland, S Hoffman, S Pham, TH Hawkins, P Kastner, DL TI Unraveling the pathophysiology of neonatal onset mutisystem inflammatory disease (NOMID/CINCA) by blocking IL-1 with the IL-1 receptor antagonist ANAKINRA SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology CY JUN 08-11, 2005 CL Vienna, AUSTRIA C1 NIDDK, NIAMS, NIH, Bethesda, MD USA. NIDDK, DRD, NIH, Bethesda, MD USA. NIDDK, NCI, NIH, Bethesda, MD USA. NIDDK, NINDS, NIH, Bethesda, MD USA. NIDDK, NIAID, NIH, Bethesda, MD USA. NIDDK, NIAID, NIH, Bethesda, MD USA. Royal Free Hosp, Natl Amyloidosis Ctr, London NW3 2QG, England. RI Hawkins, Philip/C-5573-2008; Butman, John/A-2694-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2005 VL 64 SU 3 BP 72 EP 72 PG 1 WC Rheumatology SC Rheumatology GA 937FD UT WOS:000229909100221 ER PT J AU Canna, S Gelabert, A Aksentijevich, I Mellis, S Radin, A Papadopoulos, J Barham, B Wilson, M Hawkins, P Kastner, D Goldbach-Mansky, R AF Canna, S Gelabert, A Aksentijevich, I Mellis, S Radin, A Papadopoulos, J Barham, B Wilson, M Hawkins, P Kastner, D Goldbach-Mansky, R TI Treatment of 4 patients with cryopyrin-associated periodic syndromes with the long acting IL-1 inhibitor IL-1 trap SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology CY JUN 08-11, 2005 CL Vienna, AUSTRIA C1 NIAMS, NIH, Bethesda, MD USA. Regeneron Pharmaceut Inc, Div Rheumatol, Tarrytown, NY 10591 USA. Royal Free Hosp, Natl Amyloidosis Ctr, London NW3 2QG, England. RI Hawkins, Philip/C-5573-2008 NR 2 TC 2 Z9 2 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2005 VL 64 SU 3 BP 106 EP + PG 2 WC Rheumatology SC Rheumatology GA 937FD UT WOS:000229909100329 ER PT J AU Aksentijevich, I Balow, J Lin, H Jones, J Dailey, N Barham, B Canna, S Remmers, EF Goldbach-Mansky, R Kastner, DL AF Aksentijevich, I Balow, J Lin, H Jones, J Dailey, N Barham, B Canna, S Remmers, EF Goldbach-Mansky, R Kastner, DL TI Genetic susceptibility to the neonatal-onset multisystem inflammatory disease (NOMID/CINCA): Novel CIAS1 mutations and genomic strategies to resolve locus heterogeneity SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology CY JUN 08-11, 2005 CL Vienna, AUSTRIA C1 NIAMSD, Genet & Genom Branch, Bethesda, MD 20892 USA. Regeneron Pharmaceut, Dept Biostat, Tarrytown, NY USA. NIAMSD, Off Clin Director, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2005 VL 64 SU 3 BP 123 EP 123 PG 1 WC Rheumatology SC Rheumatology GA 937FD UT WOS:000229909100384 ER PT J AU Lee, J Lipsky, PE AF Lee, J Lipsky, PE TI Analysis of human fetal VH antibody repertoire: Evidence for developmental selection of autoreactive antibody specificity SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology CY JUN 08-11, 2005 CL Vienna, AUSTRIA C1 Ewha Womans Univ, Coll Med, Seoul, South Korea. NIAMS, NIH, Autoimmun Branch, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2005 VL 64 SU 3 BP 145 EP 145 PG 1 WC Rheumatology SC Rheumatology GA 937FD UT WOS:000229909100460 ER PT J AU Valencia, X Vogt, S Goldbach-Mansky, R Lipsky, P AF Valencia, X Vogt, S Goldbach-Mansky, R Lipsky, P TI CD4+CD25+T regulatory cell function in rheumatoid arthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology CY JUN 08-11, 2005 CL Vienna, AUSTRIA C1 NIAMS, Off Clin Director, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2005 VL 64 SU 3 BP 169 EP + PG 2 WC Rheumatology SC Rheumatology GA 937FD UT WOS:000229909100545 ER PT J AU Aletaha, D Ward, M AF Aletaha, D Ward, M TI Duration of disease and functional improvement in rheumatoid arthritis clinical trials: A pooled analysis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology CY JUN 08-11, 2005 CL Vienna, AUSTRIA C1 NIAMS, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2005 VL 64 SU 3 BP 208 EP 208 PG 1 WC Rheumatology SC Rheumatology GA 937FD UT WOS:000229909101018 ER PT J AU Aletaha, D Ward, M Machold, K Nell, VPK Stamm, T Smolen, JS AF Aletaha, D Ward, M Machold, K Nell, VPK Stamm, T Smolen, JS TI Remission and active disease in rheumatoid arthritis: Defining criteria for disease activity states SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology CY JUN 08-11, 2005 CL Vienna, AUSTRIA C1 Univ Vienna, Dept Rheumatol, Vienna, Austria. NIAMS, NIH, Bethesda, MD USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2005 VL 64 SU 3 BP 214 EP 214 PG 1 WC Rheumatology SC Rheumatology GA 937FD UT WOS:000229909101037 ER PT J AU Perez, P Urzua, U Munroe, D Aguilera, S Kwon, Y Molina, C Alliende, C Leyton, C Gonzalez, M AF Perez, P Urzua, U Munroe, D Aguilera, S Kwon, Y Molina, C Alliende, C Leyton, C Gonzalez, M TI Transcriptional profile of the salivary gland epithelium in Sjogren's syndrome patients SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT Annual European Congress of Rheumatology CY JUN 08-11, 2005 CL Vienna, AUSTRIA C1 Univ Chile, Program Cell & Mol Biol, ICBM, Fac Med, Santiago, Chile. SAIC Natl Canc Inst, Lab Mol Technol, Frederick, MD USA. SAIC Natl Canc Inst, Program Cell & Mol Biol, Frederick, MD USA. Univ Mayor, Oral Pathol Dept, Santiago, Chile. RI Urzua, Ulises/A-3982-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD JUL PY 2005 VL 64 SU 3 BP 306 EP 306 PG 1 WC Rheumatology SC Rheumatology GA 937FD UT WOS:000229909101353 ER PT J AU Kim, G Levine, RL AF Kim, G Levine, RL TI Molecular determinants of S-glutathionylation of carbonic anhydrase 3 SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID CARBONIC-ANHYDRASE-III; PHOSPHATASE-ACTIVITY; PROTEIN; THIOLATION; MUSCLE; ENZYME; CELLS; SULFHYDRYLS; EXPRESSION; MECHANISM AB Carbonic anhydrase 3 is easily S-glutathionylated in vivo and in vitro. The protein has two surface-exposed cysteine residues that can be modified. We found that Cys186 is more readily glutathionylated than Cys181. We studied a series of site-specific mutants to identify the residues that interact with Cys186 to make its thiol more reactive. We found that Lys211 is responsible for lowering the pK(a) of Cys186. We also found that two acidic residues, Asp188 and Glu212, interact with the thiol and actually decrease its reactivity. We speculate that conformational changes that alter the interaction with these three residues provide a mechanistic basis for modulation of the susceptibility of carbonic anhydrase 3 to glutathionylation. C1 NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP NIH, Bldg 50,Room 2351, Bethesda, MD 20892 USA. EM rlevine@nih.gov RI Levine, Rodney/D-9885-2011 FU NHLBI NIH HHS [Z01 HL000225-28] NR 34 TC 28 Z9 28 U1 1 U2 2 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUL-AUG PY 2005 VL 7 IS 7-8 BP 849 EP 854 DI 10.1089/ars.2005.7.849 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 942ZU UT WOS:000230322200003 PM 15998239 ER PT J AU Shackelford, RE Heinloth, AN Heard, SC Paules, RS AF Shackelford, RE Heinloth, AN Heard, SC Paules, RS TI Cellular and molecular targets of protein S-glutathiolation SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID CARBONIC-ANHYDRASE-III; ACTIVE-SITE CYSTEINE; KINASE-C-DELTA; GLYCERALDEHYDE-3-PHOSPHATE DEHYDROGENASE GENES; UBIQUITIN-CONJUGATING ENZYMES; SIGNAL-TRANSDUCTION PATHWAYS; HUMAN ENDOTHELIAL-CELLS; JUN DNA-BINDING; OXIDATIVE STRESS; REDOX REGULATION AB Oxidative stress and reactive oxygen species play a major role in both normal and pathophysiologic cellular processes. Although many cellular constituents can be damaged by oxidant exposure, cysteine thiol groups are among the most readily oxidized moieties found within cells. To avoid potentially irreversible cysteine thiol oxidation, cells have developed multiple antioxidant defenses to preserve these moieties. Among these defenses, protein S-glutathiolation has emerged as an important mechanism, both in the maintenance of thiol stability during oxidant exposure and as a rapid and efficient mechanism regulating protein activity and cellular metabolic pathways. Here we review the known molecular targets of S-glutathiolation, with emphasis on the varying molecular effects of S-glutathiolation on different proteins. C1 NIEHS, Growth Control & Canc Grp, Res Triangle Pk, NC 27709 USA. Louisiana State Univ, Dept Pathol, Shreveport, LA 71105 USA. RP NIEHS, Growth Control & Canc Grp, Mail Drop D2-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM paules@niehs.nih.gov NR 166 TC 41 Z9 44 U1 0 U2 0 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUL-AUG PY 2005 VL 7 IS 7-8 BP 940 EP 950 DI 10.1089/ars.2005.7.940 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 942ZU UT WOS:000230322200013 PM 15998249 ER PT J AU Ries, M Schiffmann, R AF Ries, M Schiffmann, R TI Fabry disease: Angiokeratoma, biomarker, and the effect of enzyme replacement therapy on kidney function SO ARCHIVES OF DERMATOLOGY LA English DT Letter C1 NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Ries, M (reprint author), NINDS, Dev & Metab Neurol Branch, NIH, 9000 Rockville Pike,Bldg 10,Room 3D03, Bethesda, MD 20892 USA. EM mr380t@nih.gov OI Ries, Markus/0000-0002-5054-5741 NR 7 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-987X J9 ARCH DERMATOL JI Arch. Dermatol. PD JUL PY 2005 VL 141 IS 7 BP 904 EP 905 DI 10.1001/archderm.141.7.904-b PG 2 WC Dermatology SC Dermatology GA 944PV UT WOS:000230442100019 PM 16027312 ER PT J AU Dickstein, DP Milham, MP Nugent, AC Drevets, WC Charney, DS Pine, DS Leibenluft, E AF Dickstein, DP Milham, MP Nugent, AC Drevets, WC Charney, DS Pine, DS Leibenluft, E TI Frontotemporal alterations in pediatric bipolar disorder - Results of a voxel-based morphometry study SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID WHITE-MATTER HYPERINTENSITIES; OBSESSIVE-COMPULSIVE DISORDER; TEMPORAL-LOBE STRUCTURES; PREFRONTAL CORTEX; MOOD DISORDERS; NEUROPSYCHOLOGICAL PERFORMANCE; NEUROANATOMICAL STRUCTURES; PSYCHIATRIC-DISORDERS; ALZHEIMERS-DISEASE; GLUCOSE-METABOLISM AB Context: While numerous magnetic resonance imaging (MRI) studies have evaluated adults with bipolar disorder (BPD), few have examined MRI changes in children with BPD. Objective: To determine volume alterations in children with BPD using voxel-based morphometry, an automated MRI analysis method with reduced susceptibility to various biases. A priori regions of interest included amygdala, accumbens, hippocampus, dorsolateral prefrontal cortex (DLPFC), and orbitofrontal cortex. Design: Ongoing study of the pathophysiology of pediatric BPD. Setting: Intramural National Institute of Mental Health; approved by the institutional review board. Patients: Pediatric subjects with BPD (n = 20) with at least I manic or hypomanic episode meeting strict DSM-IV criteria for duration and elevated, expansive mood. Controls (n = 20) and their first-degree relatives lacked psychiatric disorders. Groups were matched for age and sex and did not differ in IQ. Main Outcome Measures: With a 1.5-T MRI machine, we collected 1.2-mm axial sections (124 per subject) with an axial 3-dimensional spoiled gradient recalled echo in the steady state sequence. Image analysis was by optimized voxel-based morphometry. Results: Subjects with BPD had reduced gray matter volume in the left DLPFC. With a less conservative statistical threshold, additional gray matter reductions were found in the left accumbens and left amygdala. No difference was found in the hippocampus or orbitofrontal cortex. Conclusions: Our results are consistent with data implicating the prefrontal cortex in emotion regulation, a process that is perturbed in BPD. Reductions in amygdala and accumbens volumes are consistent with neuropsychological data on pediatric BPD. Further study is required to determine the relationship between these findings in children and adults with BPD. C1 NIMH, Pediat & Dev Neuropsychiat Branch, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. NYU, Sch Med, Dept Psychiat, New York, NY USA. CUNY Mt Sinai Sch Med, Dept Psychiat, New York, NY 10029 USA. RP Dickstein, DP (reprint author), NIMH, Pediat & Dev Neuropsychiat Branch, Mood & Anxiety Disorders Program, 10 Ctr Dr,MSC 1255,Bldg10,Room 4N208, Bethesda, MD 20892 USA. EM Dicksted@mail.nih.gov RI Dickstein, Daniel/L-3210-2016; OI Dickstein, Daniel/0000-0003-1647-5329; Nugent, Allison/0000-0003-2569-2480 NR 88 TC 163 Z9 167 U1 3 U2 9 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 2005 VL 62 IS 7 BP 734 EP 741 DI 10.1001/archpsyc.62.7.734 PG 8 WC Psychiatry SC Psychiatry GA 943KJ UT WOS:000230352100006 PM 15997014 ER PT J AU Taylor, CB Youngblood, ME Catellier, D Veith, RC Carney, RM Burg, MM Kaufmann, PG Shuster, J Mellman, T Blumenthal, JA Krishnan, R Jaffe, AS AF Taylor, CB Youngblood, ME Catellier, D Veith, RC Carney, RM Burg, MM Kaufmann, PG Shuster, J Mellman, T Blumenthal, JA Krishnan, R Jaffe, AS CA ENRICHD Investigators TI Effects of antidepressant medication of morbidity and mortality in depressed patients after myocardial infarction SO ARCHIVES OF GENERAL PSYCHIATRY LA English DT Article ID CORONARY-HEART-DISEASE; SEROTONIN REUPTAKE INHIBITORS; NERVOUS-SYSTEM ACTIVITY; MAJOR DEPRESSION; RATE-VARIABILITY; SERTRALINE TREATMENT; PLATELET REACTIVITY; ENHANCING RECOVERY; RISK; PAROXETINE AB Background: Depression after myocardial infarction (MI) is associated with higher morbidity and mortality. Although antidepressants are effective in reducing depression, their use in patients with cardiovascular disease remains controversial. Objective: To undertake a secondary analysis to determine the effects of using antidepressants on morbidity and mortality in post-MI patients who participated in the Enhancing Recovery in Coronary Heart Disease study. Design: Observational secondary analysis. Setting: Eight academic sites. Patients: The Enhancing Recovery in Coronary Heart Disease clinical trial randomized 2481 depressed and/or socially isolated patients from October 1, 1996, to October 31, 1999. Depression was diagnosed using a structured clinical interview. This analysis was conducted on the 1834 patients enrolled with depression (849 women and 985 men). Intervention: Use of antidepressant medication. Main Outcome Measures: Event-free survival was defined as the absence of death or recurrent MI. All-cause mortality was also examined. To relate exposure to antidepressants to subsequent morbidity and mortality, the data were analyzed using a time-dependent covariate model. Results. During a mean follow-up of 29 months, 457 fatal and nonfatal cardiovascular events occurred. The risk of death or recurrent MI was significantly lower in patients taking selective serotonin reuptake inhibitors (adjusted hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.38-0.84), as were the risk of all-cause mortality (adjusted HR, 0.59; 95% CI, 0.37-0.96) and recurrent MI (adjusted HR, 0.53; 95% Cl, 0.32-0.90), compared with patients who did not use selective serotonin reuptake inhibitors. For patients taking non-selective serotonin reuptake inhibitor antidepressants, the comparable HRs (95% CIS) were 0.72 (0.44-1.18), 0.64 (0.34-1.22), and 0.73 (0.38-1.38) for risk of death or recurrent MI, all-cause mortality, or recurrent MI, respectively, compared with nonusers. Conclusions: Use of selective serotonin reuptake inhibitors in depressed patients who experience an acute MI might reduce subsequent cardiovascular morbidity and mortality. A controlled trial is needed to examine this important issue. C1 Stanford Univ, Med Ctr, Dept Psychiat & Behav Sci, Stanford, CA 94305 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Washington Univ, Dept Psychiat & Behav Sci, St Louis, MO 63110 USA. Yale Univ, Dept Psychiat, New Haven, CT 06520 USA. NHLBI, Bethesda, MD 20892 USA. Univ Alabama, Dept Psychiat, Birmingham, AL USA. Dartmouth Coll Sch Med, Dept Psychiat, Hanover, NH USA. Duke Univ, Dept Psychiat, Durham, NC 27706 USA. Mayo Clin & Mayo Fdn, Dept Cardiol & Internal Med, Rochester, MN 55905 USA. RP Taylor, CB (reprint author), Stanford Univ, Med Ctr, Dept Psychiat & Behav Sci, 401 Quarry Rd, Stanford, CA 94305 USA. EM btaylor@stanford.edu FU NHLBI NIH HHS [N01-HC-55143, N01-HC-55140, N01-HC-55141, N01-HC-55142, N01-HC-55144, N01-HC-55145, N01-HC-55146, N01-HC-55147, N01-HC-55148] NR 35 TC 306 Z9 316 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-990X J9 ARCH GEN PSYCHIAT JI Arch. Gen. Psychiatry PD JUL PY 2005 VL 62 IS 7 BP 792 EP 798 DI 10.1001/archpsyc.62.7.792 PG 7 WC Psychiatry SC Psychiatry GA 943KJ UT WOS:000230352100014 PM 15997021 ER PT J AU Geroldi, C Frisoni, GB Paolisso, G Bandinelli, S Lamponi, M Abbatecola, AM Zanetti, O Guralnik, JM Ferrucci, L AF Geroldi, C Frisoni, GB Paolisso, G Bandinelli, S Lamponi, M Abbatecola, AM Zanetti, O Guralnik, JM Ferrucci, L TI Insulin resistance in cognitive impairment - The InCHIANTI study SO ARCHIVES OF NEUROLOGY LA English DT Article ID ALZHEIMERS-DISEASE; DIABETES-MELLITUS; APOLIPOPROTEIN-E; LEWY BODIES; DEMENTIA; RISK; ROTTERDAM; GLUCOSE; OLDER; ATHEROSCLEROSIS AB Objective: To test the association between cognitive impairment, with and without subcortical features, and insulin resistance in an elderly community-dwelling population. Design: Cross-sectional wave of an epidemiologic longitudinal study (InCHIANTI). Participants: A total of 523 people, aged 70 to 90 years without diabetes mellitus or hyperglycemia, from the InCHIANTI cohort were included in the study. A total of 119 individuals had cognitive impairment (MiniMental State Examination [MMSE] score < 25), 21 of whom had both cognitive impairment and subcortical features (CI/SF+ group). Control groups contained 23 individuals with a history of stroke and 381 individuals with no cognitive impairment (no CI group, MMSE score >= 25). Indicators of insulin resistance were the fasting plasma insulin level, insulin resistance index (Homeostasis Model Assessment of Insulin Resistance [HOMA-IR]), and insulin sensitivity index (Quantitative Insulin Sensitivity Check Index [QUICKI]). C1 IRCCS San Govanni Dio FBF, Lab Epidemiol & Neuroimaging, I-25125 Brescia, Italy. IRCCS San Govanni Dio FBF, Alzheimers Unit, I-25125 Brescia, Italy. Second Univ Naples, Dept Geriatr Med & Metab Dis, Naples, Italy. Italian Natl Res Ctr Aging Geriatr Dept, Lab Clin Epidemiol, Florence, Italy. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD USA. NIA, Clin Res Branch, Longitudinal Studies Sect, Baltimore, MD USA. RP Frisoni, GB (reprint author), IRCCS San Govanni Dio FBF, Lab Epidemiol & Neuroimaging, Via Pilastroni 4, I-25125 Brescia, Italy. EM gfrisoni@oh-fbf.it RI Geroldi, Cristina/K-1524-2016; Frisoni, Giovanni B/K-1360-2016; Zanetti, Orazio/K-9967-2016; OI Geroldi, Cristina/0000-0001-7861-1678; Frisoni, Giovanni B/0000-0002-6419-1753; Zanetti, Orazio/0000-0002-5408-0048; Paolisso, Giuseppe/0000-0002-2137-455X NR 30 TC 60 Z9 65 U1 3 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUL PY 2005 VL 62 IS 7 BP 1067 EP 1072 DI 10.1001/archneur.62.7.1067 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 945NG UT WOS:000230508600008 PM 16009759 ER PT J AU Lim, WK Fujimoto, C Ursea, R Mahesh, SP Silver, P Chan, CC Gery, I Nussenblatt, RB AF Lim, WK Fujimoto, C Ursea, R Mahesh, SP Silver, P Chan, CC Gery, I Nussenblatt, RB TI Suppression of immune-mediated ocular inflammation in mice by interleukin 1 receptor antagonist administration SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE UVEORETINITIS; RHEUMATOID-ARTHRITIS; BINDING PROTEIN; UVEITIS; CYTOKINES; DISEASE; MODEL; IL-1; MULTICENTER; INDUCTION AB Objective: To evaluate the effects of an interleukin I receptor antagonist (IL-1RA) on the development of immune-mediated ocular inflammation in mice. Methods: Recombinant, human, nonglycosylated IL-1RA (anakinra [kineret]) was tested for its inhibitory effects in 2 systems: (1) experimental autoimmune uveitis induced by interphotoreceptor retinoid-binding protein in B10A mice using routine procedures and evaluated by clinical and histological examination, and (2) ocular inflammation in mice induced by transfer of hen egg lysozyme-specific T cells to hen egg lysozymetransgenic mice. Treatment with IL-1RA included daily subcutaneous injections of the drug, at 300 and 500 mg/ kg, or phosphate-buffered saline as control. Results: Mean SE experimental autoimmune uveitis scores of histological ocular changes of the mice at day 14 postimmunization with interphotoreceptor retinoid-binding protein were 1.5 +/- 0.3 in control mice; 1.0 +/- 0.4 in 300-mg/kg anakinra-treated mice; and 0.5 +/- 0.2 in 500mg/kg anakinra-treated mice (P =.004). There was a corresponding decrease in the cellular immune response and cytokine production of immune cells in treated mice. Suppression of ocular inflammation by anakinra in the transfer system was also observed (P=.04). Conclusion: Human IL-1RA suppresses immune-mediated ocular inflammation in mice, affecting both the afferent and efferent components of the pathogenic immune response. Clinical Relevance: Systemic administration of IL-1RA may have clinical application in the management of patients with uveitis. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. Singapore Natl Eye Ctr, Singapore, Singapore. Singapore Eye Res Inst, Singapore, Singapore. RP Nussenblatt, RB (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N112, Bethesda, MD 20892 USA. EM drbob@nei.nih.gov NR 28 TC 32 Z9 35 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 2005 VL 123 IS 7 BP 957 EP 963 DI 10.1001/archopht.123.7.957 PG 7 WC Ophthalmology SC Ophthalmology GA 943KR UT WOS:000230352900010 PM 16009838 ER PT J AU Hyman, L Gwiazda, J Hussein, M Norton, TT Wang, Y Marsh-Tootle, W Everett, D AF Hyman, L Gwiazda, J Hussein, M Norton, TT Wang, Y Marsh-Tootle, W Everett, D CA COMET Study Grp TI Relationship of age, sex, and ethnicity with myopia progression and axial elongation in the correction of myopia evaluation trial SO ARCHIVES OF OPHTHALMOLOGY LA English DT Article ID SINGAPORE CHINESE CHILDREN; RANDOMIZED CLINICAL-TRIAL; BLUE MOUNTAINS EYE; HONG-KONG; REFRACTIVE ERROR; RISK-FACTORS; VISUAL IMPAIRMENT; SCHOOL-CHILDREN; UNITED-STATES; PREVALENCE AB Objective: To identify the baseline factors independently related to 3-year myopia progression and axial elongation in COMET. Methods: A total of 469 children were enrolled, randomly assigned to progressive addition lenses with a + 2.00 diopter (D) addition or to single vision lenses and observed for 3 years. Eligible children were 6 to 11 years old, with spherical equivalent myopia of -1.25 to -4.50 D, bilaterally. The primary and secondary outcomes, myopia progression by cycloplegic autorefraction and axial elongation by A-scan ultrasonography, were measured annually. Multiple linear regression was used to adjust for covariates, including treatment. Results: Younger baseline age (6-7 vs I I years, 8 vs I I years, and 9 vs 11 years, P <.001; 10 vs I I years, P = ' 04) female sex (P =.01), and each ethnic group compared with African Americans (Asian, P=.02; Hispanic, P=.002; mixed, P=.002; white, P=.001) were independently associated with faster 3-year progression. Children aged 6 to 7 years had the fastest progression of all age groups, progressing by a mean ( +/- SD) of 1.31 D +/- 0.13 more than children aged I I years. Females progressed 0.16 D more than the males. Children of mixed, Hispanic, Asian, and white ethnicity progressed more than African American children by 0.49 D +/- 0.16, 0.33 D +/- 0.11, 0.32 D +/- 0. 13, 0.27 D +/- 0.08, respectively. Age and ethnicity, but not sex, were independently associated with axial elongation. Among these myopic children, a 0.5 mm increase in axial length was associated with I D of myopia progression. Conclusions: Younger baseline age was the strongest factor independently associated with faster myopic progression and greater axial elongation at 3 years. African American children had less myopic progression and axial elongation than the other ethnic groups. C1 SUNY Stony Brook, Hlth Sci Ctr, Dept Prevent Med, Sch Med, Stony Brook, NY 11794 USA. New England Coll Optometry, Boston, MA USA. SW Med Sch, Dallas, TX USA. Univ Alabama, Sch Optometry, Birmingham, AL USA. NEI, Bethesda, MD 20892 USA. Univ Houston, Coll Optometry, Houston, TX USA. Penn Coll Optometry, Philadelphia, PA 19141 USA. RP Hyman, L (reprint author), SUNY Stony Brook, Hlth Sci Ctr, Dept Prevent Med, Sch Med, L3 086, Stony Brook, NY 11794 USA. EM lhyman@notes.cc.sunysb.edu FU NEI NIH HHS [EY 11752, EY 11740, EY 11754, EY 11756, EY 11805]; PHS HHS [WY 11755] NR 41 TC 48 Z9 52 U1 2 U2 10 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 2005 VL 123 IS 7 BP 977 EP 987 DI 10.1001/archopht.123.7.977 PG 11 WC Ophthalmology SC Ophthalmology GA 943KR UT WOS:000230352900013 PM 16009841 ER PT J AU Nussenblatt, R AF Nussenblatt, R TI Treating intraocular inflammatory disease in the 21st century SO ARCHIVES OF OPHTHALMOLOGY LA English DT Editorial Material C1 NEI, NIH, Bethesda, MD 20892 USA. RP Nussenblatt, R (reprint author), NEI, NIH, Bldg 10,Room 10S219,9000 Rockville Pike,MSC 1858, Bethesda, MD 20892 USA. EM DrBob@nei.nih.gov NR 2 TC 11 Z9 11 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 2005 VL 123 IS 7 BP 1000 EP 1001 DI 10.1001/archopht.123.7.1000 PG 2 WC Ophthalmology SC Ophthalmology GA 943KR UT WOS:000230352900016 PM 16009844 ER PT J AU Kass, MA Gordon, MO Kymes, SM AF Kass, MA Gordon, MO Kymes, SM TI Incorporating the results of the ocular hypertension treatment study into clinical practice SO ARCHIVES OF OPHTHALMOLOGY LA English DT Letter ID OPEN-ANGLE GLAUCOMA; INTRAOCULAR-PRESSURE; ONSET; PREVENTS C1 Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, St Louis, MO 63110 USA. NEI, Bethesda, MD 20892 USA. NIH, Natl Ctr Minor Hlth & Hlth Disparities, Bethesda, MD 20892 USA. Merck Res Labs, Whitehouse Stn, NJ USA. RP Gordon, MO (reprint author), Washington Univ, Sch Med, Dept Ophthalmol & Visual Sci, 660 S Euclid Ave,Campus Box 8230, St Louis, MO 63110 USA. EM mae@vrcc.wustl.edu FU NEI NIH HHS [EY 09307, EY 09341] NR 5 TC 5 Z9 5 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9950 J9 ARCH OPHTHALMOL-CHIC JI Arch. Ophthalmol. PD JUL PY 2005 VL 123 IS 7 BP 1021 EP 1022 DI 10.1001/archopht.123.7.1021-b PG 2 WC Ophthalmology SC Ophthalmology GA 943KR UT WOS:000230352900031 PM 16009857 ER PT J AU Ravassipour, DB Powell, CM Phillips, CL Hart, PS Hart, TC Boyd, C Wright, JT AF Ravassipour, DB Powell, CM Phillips, CL Hart, PS Hart, TC Boyd, C Wright, JT TI Variation in dental and skeletal open bite malocclusion in humans with amelogenesis imperfecta SO ARCHIVES OF ORAL BIOLOGY LA English DT Article DE face height; mandible; cephalometric; hereditary; enamel; Annelogenesis imperfecta ID ANTERIOR OPEN-BITE; NONSENSE MUTATION; ENAMEL DEFECTS; GENE AMELX; AIH1; IDENTIFICATION; NOMENCLATURE; PHENOTYPE; DEFORMITY; FAMILIES AB The amelogenesis imperfectas (Al) are a diverse group of genetic disorders primarily affecting the quality and or quantity of enamel, however, affected individuals often have an open bite malocclusion. Three main Al types are recognized based on the perceived developmental mechanisms involved and the enamel phenotype. The purpose of this investigation was to evaluate the association of the Al enamel defect with craniofacial features characteristic of an open bite malocclusion. The sample consisted of 54 Al affected and 34 unaffected family members from 18 different kindreds. Lateral cephalograms were digitized and measurements evaluated for vertical plane alterations using Z-scores. Forty two percent of Al affected individuals and 12% of unaffected family members had dental or skeletal open bite malocclusions. Skeletal open bite malocclusion was variably expressed in Al affected individuals. The enamel phenotype severity did not necessarily correspond with the presence or severity of open bite malocclussion. Open bite malocclusion occurred in individuals with Al caused by mutations in the AMELX and ENAM genes even though these genes are considered to be predominantly or exclusively expressed in teeth. Affected Al individuals with cephalometric values meeting our criteria of skeletal open bite malocclusion were observed in all three major Al types. The pathophysiological relationship between Al associated enamel defects and open bite malocclusion remains unknown. (c) Published by Elsevier Ltd. C1 Univ N Carolina, Dept Pediat Dent, Sch Dent, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Orthodont, Sch Dent, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Pediat, Sch Dent, Chapel Hill, NC 27599 USA. NHGRI, NIH, Bethesda, MD 20892 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. RP Wright, JT (reprint author), Univ N Carolina, Dept Pediat Dent, Sch Dent, Brauer Hall CB 7450, Chapel Hill, NC 27599 USA. EM tim-wright@dentistry.unc.edu RI Wright, John/B-5390-2013 FU NIDCR NIH HHS [DE12879] NR 48 TC 24 Z9 25 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0003-9969 J9 ARCH ORAL BIOL JI Arch. Oral Biol. PD JUL PY 2005 VL 50 IS 7 BP 611 EP 623 DI 10.1016/j.archoralbio.2004.12.003 PG 13 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 935YG UT WOS:000229818700002 PM 15892947 ER PT J AU Alter, BP Joenje, H Oostra, AB Pals, G AF Alter, BP Joenje, H Oostra, AB Pals, G TI Fanconi anemia - Adult head and neck cancer and hematopoietic mosaicism SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Article; Proceedings Paper CT 6th International Conference on Head and Neck Cancer CY AUG 09, 2004 CL Washington, DC SP Amer Head & Neck Soc ID SQUAMOUS-CELL CARCINOMA; HUMAN-PAPILLOMAVIRUS; RADIOSENSITIVITY; CHEMOTHERAPY; RADIOTHERAPY; REGISTRY; TUMORS AB Fanconi anemia (FA) is an autosomal recessive DNA repair disorder with a very high risk of cancer. (1,2)While most of the homozygotes are identified clinically because of characteristic birth defects and early-onset aplastic anemia, (3)a subset of patients, often with milder physical and hematologic phenotypes, remain undiagnosed. They are at very high risk of neoplasms, including acute myeloid leukemias and solid tumors. (4)All types of solid tumors (combined) develop at a rate that is 48 times greater than that experienced by the general population, and the cancer hazard rate is 2% per year by the age of 24 years, with a cumulative incidence in a competing risk model of 29% by the age of 45 years.(5) C1 Natl Canc Inst, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Clin Genet Branch, Rockville, MD 20852 USA. Vrije Univ Amsterdam, Med Ctr, Dept Clin Genet & Human Genet, NL-1081 HV Amsterdam, Netherlands. RP Alter, BP (reprint author), Natl Canc Inst, Dept Hlth & Human Serv, Div Canc Epidemiol & Genet, Clin Genet Branch, 6120 Execut Blvd,Execut Plaza S,Room 7020, Rockville, MD 20852 USA. EM alterb@mail.nih.gov NR 25 TC 33 Z9 33 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUL PY 2005 VL 131 IS 7 BP 635 EP 639 DI 10.1001/archotol.131.7.635 PG 5 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 944EO UT WOS:000230409300018 PM 16027289 ER PT J AU Van Waes, C AF Van Waes, C TI Head and neck squamous cell carcinoma in patients with Fanconi anemia SO ARCHIVES OF OTOLARYNGOLOGY-HEAD & NECK SURGERY LA English DT Editorial Material ID UBIQUITIN LIGASE; CANCER; PATHWAY C1 Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, Bethesda, MD 20892 USA. RP Van Waes, C (reprint author), Natl Inst Deafness & Other Commun Disorders, Head & Neck Surg Branch, Bldg 10,CRC Room 4-2732,10 Ctr Dr,MSC-1462, Bethesda, MD 20892 USA. EM vanwaesc@nidcd.nih.gov FU Intramural NIH HHS; NIDCD NIH HHS [Z01-DC-00016] NR 17 TC 5 Z9 5 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0886-4470 J9 ARCH OTOLARYNGOL JI Arch. Otolaryngol. Head Neck Surg. PD JUL PY 2005 VL 131 IS 7 BP 640 EP 641 DI 10.1001/archotol.131.7.640 PG 2 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 944EO UT WOS:000230409300019 PM 16027290 ER PT J AU Schmidt, M Affenito, SG Striegel-Moore, R Khoury, PR Barton, B Crawford, P Kronsberg, S Schreiber, G Obarzanek, F Daniels, S AF Schmidt, M Affenito, SG Striegel-Moore, R Khoury, PR Barton, B Crawford, P Kronsberg, S Schreiber, G Obarzanek, F Daniels, S TI Fast-food intake and diet quality in black and white girls - The national heart, lung, and blood institute growth and health study SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID NUTRIENT INTAKE; RESTAURANT USE; NHLBI GROWTH; CONSUMPTION; CHILDREN; ADOLESCENTS; CHOICES; WOMEN AB Objective: To examine trends in fast-food consumption and its relationship to calorie, fat, and sodium intake in black and white adolescent girls. Design: A longitudinal multicenter cohort study of the development of obesity and cardiovascular risk factors in black and white female adolescents. Data collection occurred annually using a validated 3-day food record and a food-patterns questionnaire. Subjects and Settings: A biracial and socioeconomically diverse group of 2379 black and white girls recruited from 3 centers. Main Outcome Measure: Three-day food records and a food-patterns questionnaire were examined for intake of fast food and its association with nutrient intake. We compared patterns of exposure to fast food and its impact on intake of calories, fat, and sodium. Results: East-food intake was positively associated with intake of energy, and sodium as well as total fat and saturated fat as a percentage of calories. Last-food intake increased with increasing age in both races. With increasingconsumption of fast food, energy, intake increased with an adjusted mean of 1837 kcal for the low fast-food frequency group vs 1966 kcal for the highest fast-food frequency group (P <.05). Total fat in the low fast-food frequency group was 34.3% as opposed to 35.8% in the highest fast-food frequency group (P <.05). Saturated fat went from 12.5% to 13% and sodium increased from 3085 mg to 3236 mg in the lowest vs the highest fast-food frequency group (P <.001). C1 Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. St Joseph Coll, Hartford, CT USA. Wesleyan Univ, Middletown, CT USA. Maryland Med Res Inst, Baltimore, MD USA. Univ Calif Berkeley, Berkeley, CA 94720 USA. Westat Corp, Rockville, MD USA. NHLBI, Bethesda, MD 20892 USA. RP Schmidt, M (reprint author), Cincinnati Childrens Hosp, Med Ctr, 3333 Burnet Ave MLC 7002, Cincinnati, OH 45229 USA. EM marcia.schmidt@cchmc.org OI Barton, Bruce/0000-0001-7878-8895 FU NHLBI NIH HHS [HC55023-26, U01-HL48941] NR 19 TC 109 Z9 112 U1 0 U2 8 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JUL PY 2005 VL 159 IS 7 BP 626 EP 631 DI 10.1001/archpedi.159.7.626 PG 6 WC Pediatrics SC Pediatrics GA 941QP UT WOS:000230229600005 PM 15996994 ER PT J AU Pise-Masison, CA Jeong, SJ Brady, JN AF Pise-Masison, CA Jeong, SJ Brady, JN TI Human T cell leukemia virus type 1: the role of Tax in leukemogenesis SO ARCHIVUM IMMUNOLOGIAE ET THERAPIAE EXPERIMENTALIS LA English DT Review DE T cell; leukemia; Tax protein ID NF-KAPPA-B; PROTEASOME INHIBITOR PS-341; ELEMENT-BINDING-PROTEIN; READING FRAME-I; TRIOXIDE INDUCES APOPTOSIS; PRIMARY HUMAN-LYMPHOCYTES; TUMOR-SUPPRESSOR PROTEIN; SERUM RESPONSE FACTOR; IMMEDIATE-EARLY GENES; P53 CORE DOMAIN AB Human T cell leukemia virus type I (HTLV-1) is a complex human retrovirus which is the causative agent of adult T cell leukemia (ATL). ATL occurs in about 4% of carriers and develops after a long latent period. Although the precise mechanism of HTLV-1 oncogenesis remains unclear, the pathogenesis has been linked to the pleiotropic activity of the viral transcriptional activator protein Tax. Tax has been shown to regulate viral and cellular gene expression and to functionally interfere with proteins involved in cell-cycle progression and DNA repair. This review will focus on the role of Tax in p53 inhibition. C1 NCI, Cellular Oncol Lab, Virus Tumor Biol Sect, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. RP Pise-Masison, CA (reprint author), NCI, Cellular Oncol Lab, Virus Tumor Biol Sect, Ctr Canc Res,NIH, Bldg 41 Room B303,9000 Rockville Pike, Bethesda, MD 20892 USA. EM masisonc@mail.nih.gov NR 180 TC 16 Z9 16 U1 0 U2 0 PU INST IMMUNOLOGY & EXPERIMENTAL THERAPY PI WROCLAW PA POLISH ACADEMY OF SCIENCES CZERSKA 12, 53-114 WROCLAW, POLAND SN 0004-069X J9 ARCH IMMUNOL THER EX JI Arch. Immunol. Ther. Exp. PD JUL-AUG PY 2005 VL 53 IS 4 BP 283 EP 296 PG 14 WC Immunology SC Immunology GA 954VB UT WOS:000231182100001 PM 16088313 ER PT J AU Hansen, A Reiter, K Ziprian, T Jacobi, A Hoffmann, A Gosemann, M Scholze, J Lipsky, PE Dorner, T AF Hansen, A Reiter, K Ziprian, T Jacobi, A Hoffmann, A Gosemann, M Scholze, J Lipsky, PE Dorner, T TI Dysregulation of chemokine receptor expression and function by B cells of patients with primary Sjogren's syndrome SO ARTHRITIS AND RHEUMATISM LA English DT Article ID SALIVARY-GLANDS; AUTOANTIBODY PRODUCTION; DEPRESSED PERCENTAGE; LYMPHOID FOLLICLES; TARGET ORGAN; FACTOR-I; DIFFERENTIATION; RESPONSIVENESS; MEMORY; BLOOD AB Objective. To assess whether abnormal chemokine receptor expression and/or abnormal responsiveness to the cognate ligands might underlie some of the disturbances in B cell homeostasis characteristic of primary Sjogren's syndrome (SS). Methods. Chemokine receptor expression by CD27- naive and CD27+ -memory B cells from patients with primary SS and healthy control subjects was analyzed using flow cytometry, single-cell reverse transcriptase-polymerase chain reaction (RT-PCR), and migration assays. Results. In contrast to healthy subjects, significantly higher expression of both surface CXCR4 and CXCR4 messenger RNA (mRNA) was seen in peripheral blood B cells from patients with primary SS. These differences were most prominent in CD27- naive B cells (P <= 0.0006). In addition, significantly higher frequencies of CD27- naive B cells from patients with primary SS expressed mRNA for the inhibitory regulator of G protein signaling 13 (P = 0.001). Expression of CXCR5 by peripheral CD27+ memory B cells was moderately diminished in patients with primary SS compared with healthy controls (P = 0.038). No significant differences were noted in the expression of CXCR3, CCR6, CCR7, and CCR9 between B cells from healthy controls and those from patients with primary SS. Transmigration assays of blood B cells from patients with primary SS and healthy controls showed comparable responses of CD27- naive B cells but significantly diminished responses of activated primary SS CD27+ memory B cells to the ligands of CXCR4 and CXCR5, CXCL12 (P = 0.032), and CXCL13 (B lymphocyte chemoattractant; B cell-attracting chemokine 1; P = 0.018), respectively, when compared with those from healthy controls. Finally, compared with controls, peripheral reduction but glandular accumulation of CXCR4+,CXCR5+,CD27+ memory B cells was identified in patients with primary SS. Conclusion. In primary SS, overexpression of CXCR4 by circulating blood B cells does not translate into enhanced migratory response to the cognate ligand, CXCL12. This migratory response may be modulated by intracellular regulators. Retention of CXCR4+,CXCR5+, CD27+ memory B cells in the inflamed glands seems to contribute to diminished peripheral CD27+ memory B cells in primary SS. C1 Univ Hosp Charite, Dept Med, Outpatient Dept, D-10098 Berlin, Germany. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Hansen, A (reprint author), Univ Hosp Charite, Dept Med, Outpatient Dept, Schumannstr 20-21, D-10098 Berlin, Germany. EM arne.hansen@charite.de NR 42 TC 35 Z9 36 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD JUL PY 2005 VL 52 IS 7 BP 2109 EP 2119 DI 10.1002/art.21129 PG 11 WC Rheumatology SC Rheumatology GA 946YB UT WOS:000230608100023 PM 15986367 ER PT J AU Galperin, MY Gomelsky, M AF Galperin, MY Gomelsky, M TI Bacterial signal transduction modules: From genomics to biology SO ASM NEWS LA English DT Article ID DOMAINS AB Comparative genomic analysis is used in research in order to account for all components within microbial signal transduction systems and to compare how various microorganisms organize those systems.This helps us to understand how microbial cells react to their environments. This knowledge is important for our ability to manipulate microbes in medical, biotechological, and agricultural applications. One of the major findings of comparative genomics is that microbial signaling systems are far more diverse than expected. For example, of 30 sensor histidine kinases encoded by Escherichia coli and 36 encoded by Bacillus subtilis, only 3 are shared by both organisms: the citrate sensor CitA/CitS, the decarboxylate sensor DcuS, and the chemotaxis protein CheA. C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Wyoming, Dept Biol Mol, Laramie, WY 82071 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov; gomelsky@uwyo.edu RI gomelsky, mark/F-6209-2010; Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 11 TC 13 Z9 13 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0044-7897 J9 ASM NEWS JI ASM News PD JUL PY 2005 VL 71 IS 7 BP 326 EP 333 PG 8 WC Microbiology SC Microbiology GA 004FA UT WOS:000234736200016 ER PT J AU Ben-Kasus, T Ben-Zvi, Z Marquez, VE Kelley, JA Agbaria, R AF Ben-Kasus, T Ben-Zvi, Z Marquez, VE Kelley, JA Agbaria, R TI Metabolic activation of zebularine, a novel DNA methylation inhibitor, in human bladder carcinoma cells SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE zebularine; 2(1H)-Pyrimidinone riboside; T24 bladder carcinoma; phosphorylation; DNA and RNA incorporation; DNA methyltransferase ID CYTIDINE DEAMINASE; CANCER-CELLS; RIBOSIDE ZEBULARINE; THYMIDINE KINASE; METHYLTRANSFERASE; MECHANISMS; CYTOSINE; ANALOGS; 1-BETA-D-ARABINOFURANOSYLCYTOSINE; PHOSPHORYLATION AB Zebularine (2(1H)-pyrimidinone riboside, Zeb), a synthetic analogue of cytidine that is a potent inhibitor of cytidine deaminase, has been recently identified as a general inhibitor of DNA methylation. This inhibition of DNA methyltransferase (DNMT) is hypothesized to be mechanism-based and result from formation of a covalent complex between the enzyme and zebularine-substituted DNA. Metabolic activation of Zeb thus requires that it be phosphorylated and incorporated into DNA. We have quantitatively assessed the phosphorylation and DNA incorporation of Zeb in T24 cells using 2-[C-14]-Zeb in conjunction with gradient anion-exchange HPLC and selected enzymatic and spectroscopic analyses. The corresponding 5'-mono-, di- and triphosphates of Zeb were readily formed in a dose- and time-dependent manner. Two additional Zeb-containing metabolites were tentatively identified as diphosphocholine (Zeb-DP-Chol) and diphosphoethanolamine adducts. Intracellular concentrations of Zeb-TP and Zeb-DP-Chol were similar and greatly exceeded those of other metabolites. DNA incorporation occurred but was surpassed by that of RNA by at least seven-fold. Equivalent levels and similar intracellular metabolic patterns were also observed in the Molt-4 (human T-lymphoblasts) and MC38 (murine colon carcinoma) cell lines. For male BALB/c nul nit mice implanted s.c. with the EJ6 variant of T24 bladder carcinoma and treated i.p. with 500 mg/kg 2-[C-14] -Zeb, the in vivo phosphorylation pattern of Zeb in tumor tissue examined 24 h after drug administration was similar to that observed in vitro. The complex metabolism of Zeb and its limited DNA incorporation suggest that these are the reasons why it is less potent than either 5-azacytidine or 5-aza-2'-deoxycytidine and requires higher doses for equivalent inhibition of DNMT. (c) 2005 Elsevier Inc. All rights reserved. C1 NCI, Med Chem Lab, Ctr Canc Res, NIH, Frederick, MD 21702 USA. Ben Gurion Univ Negev, Fac Hlth Sci, Dept Clin Pharmacol, IL-84105 Beer Sheva, Israel. RP Kelley, JA (reprint author), NCI, Med Chem Lab, Ctr Canc Res, NIH, Bldg 376,Room 106,376 Boyles St, Frederick, MD 21702 USA. EM kelleyj@dc37a.nci.nih.gov NR 48 TC 50 Z9 53 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 1 PY 2005 VL 70 IS 1 BP 121 EP 133 DI 10.1016/j.bcp.2005.04.010 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 938DG UT WOS:000229979500013 PM 15885659 ER PT J AU Liu, J He, YY Chignell, CF Clark, J Myers, P Saavedra, JE Waalkes, MP AF Liu, J He, YY Chignell, CF Clark, J Myers, P Saavedra, JE Waalkes, MP TI Limited protective role of V-PYRRO/NO against cholestasis produced by alpha-naphthylisothiocyanate in mice SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE V-PYRRO/NO; ANIT hepatotoxicity; cholestasis; inflammation; gene expression ID NITRIC-OXIDE DONOR; INDUCED LIVER-INJURY; INDUCED HEPATOTOXICITY; HEPATOCYTE APOPTOSIS; RAT HEPATOCYTES; TOXICITY; EXPRESSION; ISCHEMIA; PRODRUG; CELLS AB O-2-vinyl 1-(pyrrolidin-1-yl)diazen-1-ium-1,2-diolate (V-PYRRO/NO) is a liver-selective nitric oxide donor that has been shown to protect against hepatotoxic effects of endotoxin, acetaminophen and cadmium. This study examined the effects of V-PYRRO/NO on alpha-naphthylisothiocyanate (ANIT)-induced hepatotoxicity in mice. Mice were given V-PYRRO/NO via osmotic pumps (5.4 mg/ml; 0.5 mu l/h) starting 24 h before receiving a hepatotoxic dose of ANIT (150 mg/kg in olive oil, i.g.), and continuing for additional 48 h (3-day pumps). V-PYRRO/NO administration partially ameliorated ANIT-induced hepatotoxicity, as evidenced by reduced serum alanine aminotransferase and alkaline phosphatase, markers of liver cell death, and by improved liver pathology. However, V-PYRRO/NO had no effect on ANIT-induced cholestasis, as ANIT-increased serum bilirubin levels and gamma-glutamyl transpeptidase activity were not ameliorated. Microarray and real time RT-PCR analysis revealed that ANIT intoxication altered expression of various genes, including genes encoding metabolic enzymes, transporter proteins, acute phase proteins, inflammation- and, apoptosis-related genes, as well as other genes related to liver injury. V-PYRRO/NO treatment attenuated ANIT-induced elevations in certain inflammation- and apoptosis-related genes, but had no effect on ANIT-induced disturbance on the expression of genes related to metabolism, transport, and acute phase proteins. Thus, the liver-selective NO donor, V-PYRRO/NO, was partially protective against ANIT-induced liver injury, without affecting ANIT-induced cholestasis and cholestasis-related gene expression. Published by Elsevier Inc. C1 NIEHS, Inorgan Carcinogenesis Sect, Lab Comparat Carcinogenesis, NCI, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. NIEHS, Comparat Med Branch, Res Triangle Pk, NC 27709 USA. SAIC Frederick, Frederick, MD USA. RP Liu, J (reprint author), NIEHS, Inorgan Carcinogenesis Sect, Lab Comparat Carcinogenesis, NCI, Mail Drop F0-09,111 Alexander Dr, Res Triangle Pk, NC 27709 USA. EM liu6@nichs.nih.gov FU NCI NIH HHS [N01-CO-12400] NR 25 TC 9 Z9 9 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD JUL 1 PY 2005 VL 70 IS 1 BP 144 EP 151 DI 10.1016/j.bcp.2005.03.034 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 938DG UT WOS:000229979500015 PM 15913567 ER PT J AU Vuu, K Xie, JW McDonald, MA Bernardo, M Hunter, F Zhang, YT Li, K Bednarski, M Guccione, S AF Vuu, K Xie, JW McDonald, MA Bernardo, M Hunter, F Zhang, YT Li, K Bednarski, M Guccione, S TI Gadolinium-rhodamine nanoparticles for cell labeling and tracking via magnetic resonance and optical imaging SO BIOCONJUGATE CHEMISTRY LA English DT Article ID PARAMAGNETIC POLYMERIZED LIPOSOMES; MESENCHYMAL STEM-CELLS AB A novel dual-labeled nanoparticle for use in labeling and tracking cells in vivo is described. We report the construction and characterization of these gadolinium-rhodamine nanoparticles. These particles are constructed from lipid monomers with diacetylene bonds that are sonicated and photolyzed to form polymerized nanoparticles. Cells are efficiently labeled with these nanoparticles. We have inoculated labeled tumor cells subcutaneouosly into the flanks of C3H mice and have been able to image these labeled tumor cells via MRI and optical imaging. Furthermore, the labeled tumor cells can be visualized via fluorescent microscopy after tissue biopsy. Our results suggest that these nanoparticles could be used to track cells in vivo. This basic platform can be modified with different fluorophores and targeting agents for studying metastisic cell, stem cell, and immune cell trafficking among other applications. C1 Lucas Ctr MR Spect & Imaging, Dept Radiol, Stanford, CA 94305 USA. Howard Hughes Med Inst, Natl Inst Hlth, Res Scholars Program, Chevy Chase, MD 20815 USA. NIH, Mol Imaging Lab, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. Natl Inst Biomed Imaging & Bioengn, NIH, Bethesda, MD 20892 USA. RP Guccione, S (reprint author), Lucas Ctr MR Spect & Imaging, Dept Radiol, Room P284,1201 Welch Rd,MC 5488, Stanford, CA 94305 USA. EM Samira.guccione@stanford.edu NR 9 TC 103 Z9 107 U1 2 U2 16 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1043-1802 J9 BIOCONJUGATE CHEM JI Bioconjugate Chem. PD JUL-AUG PY 2005 VL 16 IS 4 BP 995 EP 999 DI 10.1021/bc050085z PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Multidisciplinary; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 948JU UT WOS:000230712900029 PM 16029042 ER PT J AU Ogurtsov, AY AF Ogurtsov, AY TI The properties of sequences involved in insertion and deletion mutagenesis in rodents SO BIOFIZIKA LA Russian DT Article DE insertion and deletion mutagenesis; intron ID DNA; NUCLEOTIDE; DIVERGENCE; SAMPLES; INDELS; LOCI AB We analyzed nucleotide sequences that were inserted to or deleted from genomic DNA during the divergence from common ancestor. The median length of these sequences is 3 nucleotides; they are enriched with palindromes and often repeat in adjacent DNA. C1 Russian Acad Sci, Inst Theoret & Expt Biophys, Pushchino 142290, Moscow, Russia. NIH, NCBI, Bethesda, MD 20892 USA. RP Ogurtsov, AY (reprint author), Russian Acad Sci, Inst Theoret & Expt Biophys, Pushchino 142290, Moscow, Russia. NR 12 TC 0 Z9 0 U1 0 U2 0 PU MEZHDUNARODNAYA KNIGA PI MOSCOW PA 39 DIMITROVA UL., 113095 MOSCOW, RUSSIA SN 0006-3029 J9 BIOFIZIKA+ JI Biofizika PD JUL-AUG PY 2005 VL 50 IS 4 BP 648 EP 651 PG 4 WC Biophysics SC Biophysics GA 969GB UT WOS:000232221000009 PM 16212055 ER PT J AU Ordonez, AE Bobb, A Greenstein, D Baker, N Sporn, A Lenane, M Malaspina, D Rapaport, J Gogtay, N AF Ordonez, AE Bobb, A Greenstein, D Baker, N Sporn, A Lenane, M Malaspina, D Rapaport, J Gogtay, N TI Lack of evidence for elevated obstetric complications in childhood onset schizophrenia SO BIOLOGICAL PSYCHIATRY LA English DT Article DE childhood-onset schizophrenia; obstetric complications ID INDIVIDUAL PATIENT DATA; RISK-FACTORS; FETAL HYPOXIA; PREGNANCY; ASSOCIATION; DISORDER; METAANALYSIS; HISTORY; AGE; INFLUENZA AB Background Pre-, peri-, and postnatal obstetric complications (OC) are reported to be more firequent in adult patients with schizopbrenia and have been linked to both greater severity and to "earlier" age of onset (before either age 18 or 22) in studies of adult patients. We hypothesized that by extrapolation, patients with childhood-onsel schizopbrenia (COS), with very early onset and very severe illness, would have bad more numerous or more salient OC compared with their healthy siblings. Methods: We compared The obstetric records of 60 COS children and 48 healthy siblings using the Columbia Obstetrics Complication Scale, a comprehensive measurement scale consisting of 37 variables having included a separate scale for fetal hypoxia. Results: Patients with COS did not have a higher incidence of OC than the healthy sibling control group with the exception of increased incidence of maternal vomiting. Conclusions: Obstetric complications, with The possible exception of maternal vomiting, are unlikely to play a major role in the etiopatbogenesis of childhood-onset schizophrenia. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. Columbia Univ, Dept Psychiat, New York, NY USA. RP Gogtay, N (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 3N202,10 Ctr Dr, Bethesda, MD 20892 USA. EM gogtayn@intra.nimh.nih.gov RI Gogtay, Nitin/A-3035-2008 NR 52 TC 10 Z9 10 U1 2 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD JUL 1 PY 2005 VL 58 IS 1 BP 10 EP 15 DI 10.1016/j.biopsych.2005.02.009 PG 6 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 942CI UT WOS:000230260100002 PM 15992518 ER PT J AU Gorak, E Geller, N Srinivasan, R Espinoza-Delgado, I Donohue, T Barrett, AJ Suffredini, A Childs, R AF Gorak, E Geller, N Srinivasan, R Espinoza-Delgado, I Donohue, T Barrett, AJ Suffredini, A Childs, R TI Engraftment syndrome after nonmyeloablative allogeneic hematopoietic stem cell transplantation: Incidence and effects on survival SO BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION LA English DT Article DE nonmyeloablative allogeneic hematopoietic stem cell transplantation; survival; engraftment syndrome; neutrophil recovery ID BONE-MARROW TRANSPLANTATION; VERSUS-HOST-DISEASE; GENE POLYMORPHISMS ASSOCIATE; BREAST-CANCER PATIENTS; AMPHOTERICIN-B; PULMONARY TOXICITY; TRANSFUSIONS; NEUTROPHILS; REGRESSION; MORTALITY AB Engraftment syndrome (ES) encompasses a constellation of symptoms that occur during neutrophil recovery after both autologous and allogeneic hematopoietic stem cell transplantation (HCT). Although it is well characterized after conventional myeloablative procedures, limited data exist on this complication after nonmyeloablative allogeneic HCT. The clinical manifestations, incidence, and risk factors associated with ES were investigated in a consecutive series of patients undergoing cyclophosphamide/fludarabine-based nomnyeloablative allogeneic HCT from a related HLA-compatible donor. Fifteen (10%) of 149 patients (median age, 53 years; range, 27-66 years) developed ES; the onset of symptoms occurred at a median of 10 days (range, 3-14 days), and they consisted of fever (100%), cough (53%), diffuse pulmonary infiltrates (100%), rash (13%), and room air hypoxia (87%). ES was more likely to develop in patients who received empiric amphotericin formulations after transplant conditioning (Fisher exact test; P =.007). In a multivariate analysis, older patient age, female sex, and treatment with amphotericin were predictors for the development of ES. Intravenous methylprednisolone led to the rapid resolution of ES; however, transplant-related mortality was significantly higher (cumulative incidence, 49% versus 16%; P =.0005), and median survival was significantly shorter (168 versus 418 days; P =.005) in patients with ES compared with non-ES patients. In conclusion, ES occurs commonly after cyclophosphamide/fludarabine-based nomnyeloablative transplantation and responds rapidly to corticosteroid treatment, but it is associated with a higher risk of nonrelapse mortality and with shorter overall survival. (c) 2005 American Society for Blood and Marrow Transplantation. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. NIH, Walter Reed Army Med Ctr, Bethesda, MD USA. NHLBI, Off Biostat, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Childs, R (reprint author), NHLBI, Hematol Branch, NIH, 10-7C103,10 Ctr Dr,MSC 1652, Bethesda, MD 20892 USA. EM childsr@nhlbi.nih.gov NR 42 TC 36 Z9 36 U1 0 U2 0 PU CARDEN JENNINGS PUBL CO LTD PI CHARLOTTESVILLE PA BLAKE CTR, STE 200, 1224 W MAIN ST, CHARLOTTESVILLE, VA 22903 USA SN 1083-8791 J9 BIOL BLOOD MARROW TR JI Biol. Blood Marrow Transplant. PD JUL PY 2005 VL 11 IS 7 BP 542 EP 550 DI 10.1016/j.bbmt.2005.04.009 PG 9 WC Hematology; Immunology; Transplantation SC Hematology; Immunology; Transplantation GA 944KD UT WOS:000230425500007 PM 15983554 ER PT J AU Ali, MA Bates, RB Crane, ZD Dicus, CW Gramme, MR Hamel, E Marcischak, J Martinez, DS McClure, KJ Nakkiew, P Pettit, GR Stessman, CC Sufi, BA Yarick, GV AF Ali, MA Bates, RB Crane, ZD Dicus, CW Gramme, MR Hamel, E Marcischak, J Martinez, DS McClure, KJ Nakkiew, P Pettit, GR Stessman, CC Sufi, BA Yarick, GV TI Dolastatin 11 conformations, analogues and pharmacophore SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID CYCLIC DEPSIPEPTIDE; LYNGBYA-MAJUSCULA; DERIVATIVES; ACTIN AB Twenty analogues of the natural antitumor agent dolastatin 11, including majusculamide C, were synthesized and tested for cytotoxicity against human cancer cells and stimulation of actin polymerization. Only analogues containing the 30-membered ring were active. Molecular modeling and NMR evidence showed the low-energy conformations. The amide bonds are all trans except for the one between the Tyr and Val units, which is cis. Since an analogue restricted to negative 2-3-4-5 angles stimulated actin polymerization but was inactive in cells, the binding conformation (most likely the lowest-energy conformation in water) has a negative 2-3-4-5 angle, whereas a conformation with a positive 2-3-4-5 angle (most likely the lowest energy conformation in chloroform) goes through cell walls. The highly active R alcohol from borohydride reduction of dolastatin I I is a candidate for conversion to prodrugs. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. NCI, Frederick, MD 21702 USA. Arizona State Univ, Dept Chem & Biochem, Tempe, AZ 85287 USA. Arizona State Univ, Canc Res Inst, Tempe, AZ 85287 USA. RP Bates, RB (reprint author), Univ Arizona, Dept Chem, Tucson, AZ 85721 USA. EM batesr@u.arizona.edu FU NCI NIH HHS [R01 CA78750] NR 10 TC 6 Z9 7 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUL 1 PY 2005 VL 13 IS 13 BP 4138 EP 4152 DI 10.1016/j.bmc.2005.04.040 PG 15 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 935VQ UT WOS:000229811900001 PM 15878670 ER PT J AU Shi, ZD Liu, HP Zhang, MC Worthy, KM Bindu, L Yang, DJ Fisher, RJ Burke, TR AF Shi, ZD Liu, HP Zhang, MC Worthy, KM Bindu, L Yang, DJ Fisher, RJ Burke, TR TI Synthesis of a C-terminally biotinylated macrocyclic peptide mimetic exhibiting high Grb2 SH2 domain-binding affinity SO BIOORGANIC & MEDICINAL CHEMISTRY LA English DT Article ID PHOSPHATE-CONTAINING LIGANDS; STRUCTURE-BASED DESIGN; HUMAN BREAST-CANCER; SIGNAL-TRANSDUCTION; OLEFIN METATHESIS; CELL MOTILITY; POTENT; INHIBITORS; SRC; SPECIFICITY AB Although considerable effort has been devoted to developing Grb2 SH2 domain-binding antagonists, important questions related to ligand specificity, and identification of intracellular targets remain unanswered. In order to begin addressing these issues, the design, synthesis, and evaluation of a novel biotinylated macrocycle are reported that bears biotin functionality at a C-terminal rather than the traditional N-terminal position. With a Grb2 SH2 domain-binding K-eq value of 3.4 nM, the title macrocycle (5) is among the most potent biotinylated SH2 domain-binding ligands yet disclosed. This should be a useful tool for elucidating physiological targets of certain Grb2 SH2 domain-binding antagonists. (c) 2005 Elsevier Ltd. All rights reserved. C1 NCI, CCR, Med Chem Lab, NIH, Frederick, MD 21702 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. SAIC Frederick, Prot Chem Lab, Frederick, MD 21702 USA. RP Burke, TR (reprint author), NCI, CCR, Med Chem Lab, NIH, Frederick, MD 21702 USA. EM tburke@helix.nih.gov RI Fisher, Robert/B-1431-2009; Burke, Terrence/N-2601-2014 NR 30 TC 11 Z9 11 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0968-0896 J9 BIOORGAN MED CHEM JI Bioorg. Med. Chem. PD JUL 1 PY 2005 VL 13 IS 13 BP 4200 EP 4208 DI 10.1016/j.bmc.2005.04.028 PG 9 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 935VQ UT WOS:000229811900008 PM 15893931 ER PT J AU Pedersen, MG Bertram, R Sherman, A AF Pedersen, MG Bertram, R Sherman, A TI Intra- and inter-islet synchronization of metabolically driven insulin secretion SO BIOPHYSICAL JOURNAL LA English DT Article ID PANCREATIC BETA-CELLS; HEPATIC GLUCOSE-PRODUCTION; PULSATILE INSULIN; ELECTRICAL-ACTIVITY; IN-VIVO; GLYCOLYTIC OSCILLATIONS; ULTRADIAN OSCILLATIONS; OXYGEN-CONSUMPTION; MATHEMATICAL-MODEL; CYTOPLASMIC CA2+ AB Insulin secretion from pancreatic beta-cells is pulsatile with a period of 5-10 min and is believed to be responsible for plasma insulin oscillations with similar frequency. To observe an overall oscillatory insulin pro. le it is necessary that the insulin secretion from individual beta-cells is synchronized within islets, and that the population of islets is also synchronized. We have recently developed a model in which pulsatile insulin secretion is produced as a result of calcium-driven electrical oscillations in combination with oscillations in glycolysis. We use this model to investigate possible mechanisms for intra-islet and inter-islet synchronization. We show that electrical coupling is sufficient to synchronize both electrical bursting activity and metabolic oscillations. We also demonstrate that islets can synchronize by mutually entraining each other by their effects on a simple model "liver,'' which responds to the level of insulin secretion by adjusting the blood glucose concentration in an appropriate way. Since all islets are exposed to the blood, the distributed islet-liver system can synchronize the individual islet insulin oscillations. Thus, we demonstrate how intra-islet and inter-islet synchronization of insulin oscillations may be achieved. C1 NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. Tech Univ Denmark, Dept Math, Kgs Lyngby, Denmark. Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. Florida State Univ, Inst Mol Biophys, Tallahassee, FL 32306 USA. RP Sherman, A (reprint author), NIDDKD, Lab Biol Modeling, NIH, Bethesda, MD 20892 USA. EM asherman@nih.gov RI Pedersen, Morten/F-4134-2012 OI Pedersen, Morten/0000-0002-2639-2394 NR 61 TC 65 Z9 66 U1 0 U2 5 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 2005 VL 89 IS 1 BP 107 EP 119 DI 10.1529/biophysj.104.055681 PG 13 WC Biophysics SC Biophysics GA 939ZX UT WOS:000230114500016 PM 15834002 ER PT J AU Zheng, WJ Brooks, BR AF Zheng, WJ Brooks, BR TI Probing the local dynamics of nucleotide-binding pocket coupled to the global dynamics: Myosin versus kinesin SO BIOPHYSICAL JOURNAL LA English DT Article ID ELASTIC-NETWORK MODEL; MOTOR DOMAIN; CONFORMATIONAL-CHANGE; PROTEINS; MOTIONS; MECHANISM; RELEASE; FAMILY; ATPASE AB Based on the elastic network model, we develop a new analysis for protein complexes, which probes the local dynamics of a subsystem that is elastically coupled to a fluctuating environment. This method is applied to a comparative dynamical analysis of the nucleotide-binding pocket of two motor proteins-myosins and kinesins. In myosins, the observed structural changes in the nucleotide-pocket from the transition state to the rigorlike state are dominated by the lowest normal mode that involves significant movements in both switch I and switch II; in kinesins, the measured conformational changes in the nucleotide-pocket are also dominated by the lowest mode, which, however, only involves large movement in switch I. We then compute the global structural changes induced by the nucleotide-pocket deformations as described by the dominant pocket-mode, which yield encouraging results: in myosins, multiple hinge motions involving the opening/ closing of the cleft between the upper and lower 50-kDa subdomains and the swinging movement of the converter are induced, which are dominated by precisely the same global mode that has been recently identified by us as important to the dynamical correlations among the nucleotide-pocket, the actin-binding site, and the converter; in kinesins, the induced global conformational changes are well described by a highly collective global mode which hints for a dynamical pathway spanning from the nucleotide-pocket to the neck-linker via the H6 helix. C1 NHLBI, Lab Computat Biol, NIH, Bethesda, MD 20892 USA. RP Zheng, WJ (reprint author), NHLBI, Lab Computat Biol, NIH, Bldg 10, Bethesda, MD 20892 USA. EM zhengwj@helix.nih.gov OI Zheng, Wenjun/0000-0002-6236-9765 NR 29 TC 68 Z9 69 U1 0 U2 6 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 2005 VL 89 IS 1 BP 167 EP 178 DI 10.1529/biophysj.105.063305 PG 12 WC Biophysics SC Biophysics GA 939ZX UT WOS:000230114500021 PM 15879477 ER PT J AU Tekle, E Oubrahim, H Dzekunov, SM Kolb, JF Schoenbach, KH Chock, PB AF Tekle, E Oubrahim, H Dzekunov, SM Kolb, JF Schoenbach, KH Chock, PB TI Selective field effects on intracellular vacuoles and vesicle membranes with nanosecond electric pulses SO BIOPHYSICAL JOURNAL LA English DT Article ID ELECTROPORATIVE DEFORMATION; UNILAMELLAR VESICLES; BIOLOGICAL CELLS; MAMMALIAN-CELLS; LIPID VESICLES; ELECTROPERMEABILIZATION; ELECTROCHEMOTHERAPY; TRANSLOCATION; TRANSFECTION; CONDUCTANCE AB Electric pulses across intact vesicles and cells can lead to transient increase in permeability of their membranes. We studied the integrity of these membranes in response to external electric pulses of high amplitude and submicrosecond duration with a primary aim of achieving selective permeabilization. These effects were examined in two separate model systems comprising of 1), a mixed population of 1,2-di-oleoyl-sn-glycero-3-phosphocholine phospholipid vesicles and in 2), single COS-7 cells, in which large endosomal membrane vacuoles were induced by stimulated endocytosis. It has been shown that large and rapidly varying external electric fields, with pulses shorter than the charging time of the outer-cell membrane, could substantially increase intracellular fields to achieve selective manipulations of intracellular organelles. The underlying principle of this earlier work is further developed and applied to the systems studied here. Under appropriate conditions, we show preferential permeabilization of one vesicle population in a mixed preparation of vesicles of similar size distribution. It is further shown that large endocytosed vacuoles in COS-7 cells can be selectively permeabilized with little effect on the integrity of outer cell membrane. C1 NHLBI, Biochem Lab, NIH, Bethesda, MD 20892 USA. MaxCyte Inc, Gaithersburg, MD USA. Old Dominion Univ, Phys Elect Res Inst, Ctr Bioelect, Norfolk, VA USA. RP Tekle, E (reprint author), NHLBI, Biochem Lab, NIH, Bldg 50,Rm 2127,50 South Dr,MSC-8012, Bethesda, MD 20892 USA. EM ephrem@helix.nih.gov RI Kolb, Juergen/A-5515-2016 OI Kolb, Juergen/0000-0002-0434-5001 NR 46 TC 71 Z9 76 U1 0 U2 6 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 2005 VL 89 IS 1 BP 274 EP 284 DI 10.1529/biophysj.104.054494 PG 11 WC Biophysics SC Biophysics GA 939ZX UT WOS:000230114500030 PM 15821165 ER PT J AU Dam, J Velikovsky, CA Mariuzza, RA Urbanke, C Schuck, P AF Dam, J Velikovsky, CA Mariuzza, RA Urbanke, C Schuck, P TI Sedimentation velocity analysis of heterogeneous protein-protein interactions: Lamm equation modeling and sedimentation coefficient distributions c(s) SO BIOPHYSICAL JOURNAL LA English DT Article ID SIZE-DISTRIBUTION ANALYSIS; SELF-ASSOCIATING SOLUTES; ANALYTICAL ULTRACENTRIFUGATION; NUMERICAL-SOLUTIONS; BOUNDARY ANALYSIS; SYSTEMS; ELECTROPHORESIS; BINDING; EQUILIBRIUM; COMPLEXES AB We describe algorithms for solving the Lamm equations for the reaction-diffusion-sedimentation process in analytical ultracentrifugation, and examine the potential and limitations for fitting experimental data. The theoretical limiting case of a small, uniformly distributed ligand rapidly reacting with a larger protein in a "constant bath'' of the ligand is recapitulated, which predicts the reaction boundary to sediment with a single sedimentation and diffusion coefficient. As a consequence, it is possible to express the sedimentation profiles of reacting systems as c(s) distribution of noninteracting Lamm equation solutions, deconvoluting the effects of diffusion. For rapid reactions, the results are quantitatively consistent with the "constant bath'' approximation, showing c(s) peaks at concentration-dependent positions. For slower reactions, the deconvolution of diffusion is still partially successful, with c(s) resolving peaks that reflect the populations of sedimenting species. The transition between c(s) peaks describing reaction boundaries of moderately strong interactions (K(D)similar to 10(-6) M) or resolving sedimenting species was found to occur in a narrow range of dissociation rate constant between 10(-3) and 10(-4) s(-1). The integration of the c(s) peaks can lead to isotherms of species populations or s-value of the reaction boundary, respectively, which can be used for the determination of the equilibrium binding constant. C1 NIH, Prot Biophys Resource, Div Bioengn & Phys Sci, ORS,OD, Bethesda, MD 20892 USA. Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, WM Keck Lab Struct Biol, Rockville, MD USA. Hannover Med Sch, Hannover, Germany. RP Schuck, P (reprint author), NIH, Prot Biophys Resource, Div Bioengn & Phys Sci, ORS,OD, Bldg 13,Rm 3N17,13 South Dr, Bethesda, MD 20892 USA. EM pschuck@helix.nih.gov OI Dam, Julie/0000-0001-6871-2678; Schuck, Peter/0000-0002-8859-6966 FU NIGMS NIH HHS [GM52801, R01 GM052801] NR 56 TC 105 Z9 107 U1 0 U2 12 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 2005 VL 89 IS 1 BP 619 EP 634 DI 10.1529/biophysj.105.059568 PG 16 WC Biophysics SC Biophysics GA 939ZX UT WOS:000230114500062 PM 15863475 ER PT J AU Dam, J Schuck, P AF Dam, J Schuck, P TI Sedimentation velocity analysis of heterogeneous protein-protein interactions: Sedimentation coefficient distributions c(s) and asymptotic boundary profiles from Gilbert-Jenkins theory SO BIOPHYSICAL JOURNAL LA English DT Article ID CHEMICALLY REACTING SYSTEMS; SIZE-DISTRIBUTION ANALYSIS; ANALYTICAL ULTRACENTRIFUGATION; SELF-ASSOCIATION; WEIGHT AVERAGE; LAMM EQUATION; ELECTROPHORESIS; EQUILIBRIUM; PATTERNS; BEHAVIOR AB Interacting proteins in rapid association equilibrium exhibit coupled migration under the influence of an external force. In sedimentation, two-component systems can exhibit bimodal boundaries, consisting of the undisturbed sedimentation of a fraction of the population of one component, and the coupled sedimentation of a mixture of both free and complex species in the reaction boundary. For the theoretical limit of diffusion-free sedimentation after infinite time, the shapes of the reaction boundaries and the sedimentation velocity gradients have been predicted by Gilbert and Jenkins. We compare these asymptotic gradients with sedimentation coefficient distributions, c(s), extracted from experimental sedimentation profiles by direct modeling with superpositions of Lamm equation solutions. The overall shapes are qualitatively consistent and the amplitudes and weight-average s-values of the different boundary components are quantitatively in good agreement. We propose that the concentration dependence of the area and weight-average s-value of the c(s) peaks can be modeled by isotherms based on Gilbert-Jenkins theory, providing a robust approach to exploit the bimodal structure of the reaction boundary for the analysis of experimental data. This can significantly improve the estimates for the determination of binding constants and hydrodynamic parameters of the complexes. C1 NIH, Prot Biophys Resource, Div Bioengn & Phys Sci, ORS,OD, Bethesda, MD 20892 USA. Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, WM Keck Lab Struct Biol, Rockville, MD USA. RP Schuck, P (reprint author), NIH, Prot Biophys Resource, Div Bioengn & Phys Sci, ORS,OD, Bldg 13,Rm 3N17,13 South Dr, Bethesda, MD 20892 USA. EM pschuck@helix.nih.gov OI Dam, Julie/0000-0001-6871-2678; Schuck, Peter/0000-0002-8859-6966 NR 59 TC 76 Z9 77 U1 1 U2 7 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JUL PY 2005 VL 89 IS 1 BP 651 EP 666 DI 10.1529/biophysj.105.059584 PG 16 WC Biophysics SC Biophysics GA 939ZX UT WOS:000230114500064 PM 15863474 ER PT J AU Howard, FB AF Howard, FB TI The stabilizing contribution of thymine in duplexes of (dA)(24) with (dU)(24), (dT)(24), (dU(12)-dT(12)), (dU-dT)(12), (dU(2)-dT(2))(6),or (dU(3)dT(3))(4): Nearest neighbor and next-nearest neighbor effects SO BIOPOLYMERS LA English DT Article DE thymine methyl group effect on stability; thymine sequence effect; nearest neighbor; dispersion interactions; polarizability; (dA)(24); (dU)(24); (dT)(24); (dU(12)-dT(12)); (dU-dT)(12); (dU(2)-dT(2))(6); (dU(3)-dT(3))(4); dependence of stability on cation concentration; thermodynamic cation release; CD ID POLY-RIBOTHYMIDYLIC ACID; HELIX-COIL TRANSITIONS; SYNTHETIC POLYNUCLEOTIDES; POLYADENYLIC ACID; NUCLEIC-ACIDS; COMPLEXES; EQUILIBRIA; DNA; ASSOCIATION; STACKING AB Ultraviolet melting curves are used to determine the effect of the pyrimidine 5-methyl group on the stability of duplexes of (dA)24 with (dU)(24), (dT)(24), (dU(12)-dT(12)) (dU-dT)(12), (dU(2)-dT(2))(6), and (dU(3)-dT(3))(4). Substitution of a T for a U results in all increase in stability, which is attributed to an increase in strength of dipole-induced dipole and dispersion (van der Waals) interactions. Significant additional enhancement occurs when two T residues are adjacent. A further increase in the number of adjacent T's has a relatively slight effect on T-m. The sequence effect appears to be largely attributable to all increment in dispersion forces. The CD spectra of the duplexes are all closely similar except in the region between 260 and 290 nm. A band near 272 nm associated with the presence of U ill the spectrum of (dA)(24).(dU)(24) decreases in intensity when T's are incorporated it? the pyrimidine strand. The band is completely replaced in the spectrum of (dA)(24).(dT)(24) with a new maximum at 282 nm and a minimum at 268 nm, both of lower magnitude. The emergence of the two new bands is correlated with the presence of adjacent T's once more, and only two adjacent T's appear necessary for a major part of the change to occur. The degree of cation release oil thermal dissociation of the oligomer dimers ranges from Delta i = 0.14 to 0.16, about the same or slightly less than values reported for polynucleotide duplexes and less than predicted from theoretical calculations. (c) 2005 Wiley Periodicals, Inc. C1 NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. RP Howard, FB (reprint author), NIDDK, Chem Phys Lab, Bethesda, MD 20892 USA. EM FrankH@intra.niddk.nih.gov NR 34 TC 15 Z9 15 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3525 J9 BIOPOLYMERS JI Biopolymers PD JUL PY 2005 VL 78 IS 4 BP 221 EP 229 DI 10.1002/bip.20289 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 942CL UT WOS:000230260400007 PM 15880386 ER PT J AU Gunn, LH Dunson, DB AF Gunn, LH Dunson, DB TI A transformation approach for incorporating monotone or unimodal constraints SO BIOSTATISTICS LA English DT Article DE changepoint; Gibbs sampler; hormone measurements; menstrual cycle; nested data; order-restricted inference; progesterone; shape constraint ID NONPARAMETRIC BAYESIAN BIOASSAY; ISOTONIC REGRESSION; MENSTRUAL CYCLES; MODELS; RESTRICTIONS; CONCEPTION; WOMEN; SHAPE AB Samples of curves are collected in many applications, including studies of reproductive hormone levels in the menstrual cycle. Many approaches have been proposed for correlated functional data of this type, including smoothing spline methods and other flexible parametric modeling strategies. In many cases, the underlying biological processes involved restrict the curve to follow a particular shape. For example, progesterone levels in healthy women increase during the menstrual cycle to a peak achieved at random location with decreases thereafter. Reproductive epidemiologists are interested in studying the distribution of the peak and the trajectory for women in different groups. Motivated by this application, we propose a simple approach for restricting each woman's mean trajectory to follow an umbrella shape. An unconstrained hierarchical Bayesian model is used to characterize the data, and draws from the posterior distribution obtained using a Gibbs sampler are then mapped to the constrained space. Inferences are based on the resulting quasi-posterior distribution for the peak and individual woman trajectories. The methods are applied to a study comparing progesterone trajectories for conception and nonconception cycles. C1 Georgia So Univ, Jiann Hsu Sch Publ Hlth, Statesboro, GA 30460 USA. Natl Inst Environm Hlth Sci, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Gunn, LH (reprint author), Georgia So Univ, Jiann Hsu Sch Publ Hlth, POB 8076, Statesboro, GA 30460 USA. EM Igunn@georgiasouthern.edu NR 17 TC 10 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JUL PY 2005 VL 6 IS 3 BP 434 EP 449 DI 10.1093/biostatistics/kci020 PG 16 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 948KV UT WOS:000230715600006 PM 15831579 ER PT J AU Gail, MH Pfeiffer, RA AF Gail, MH Pfeiffer, RA TI Response to Rockhill's letter to the editor SO BIOSTATISTICS LA English DT Letter ID RISKS C1 NCI, Dept Canc & Epidemiol & Genet, Biostat Branch, Bethesda, MD 20892 USA. RP Gail, MH (reprint author), NCI, Dept Canc & Epidemiol & Genet, Biostat Branch, Execut Plaza S, Bethesda, MD 20892 USA. EM gailm@mail.nih.gov RI Pfeiffer, Ruth /F-4748-2011 NR 2 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JUL PY 2005 VL 6 IS 3 BP 503 EP 504 DI 10.1093/biostatistics/kxi035 PG 2 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 948KV UT WOS:000230715600012 ER PT J AU Mazan-Mamczarz, K Kawai, T Martindale, JL Gorospe, M AF Mazan-Mamczarz, K Kawai, T Martindale, JL Gorospe, M TI En masse analysis of nascent translation using microarrays SO BIOTECHNIQUES LA English DT Article ID BINDING PROTEIN HUR; EXPRESSION AB We report a robust method for studying en masse changes in translation using cDNA arrays. The relative distribution of messenger RNAs (mRNAs) along polysome gradients was monitored by performing cDNA array analysis of each gradient fraction and quantifying the mRNA translational status by regression analysis. Using this strategy to study human carcinoma cells exposed to short-wavelength ultraviolet light (UVC), we identified a subset of 17 translationally induced mRNAs and a subset of 69 translationally repressed mRNAs following UVC irradiation. We describe an effective approach for globally investigating changes in protein biosynthesis. C1 NIA, LCMB, IRP, NIH, Baltimore, MD 21224 USA. RP Gorospe, M (reprint author), NIA, LCMB, IRP, NIH, Box 12,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM myriam-gorospe@nih.gov FU NIA NIH HHS [Z01 AG000511-08] NR 8 TC 10 Z9 10 U1 0 U2 0 PU EATON PUBLISHING CO PI WESTBOROUGH PA ONE RESEARCH DRIVE, SUITE 400A, PO BOX 1070, WESTBOROUGH, MA 01581-6070 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD JUL PY 2005 VL 39 IS 1 BP 61 EP + DI 10.2144/05391ST01 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 946PI UT WOS:000230584100013 PM 16060370 ER PT J AU Shiloach, J Fass, R AF Shiloach, J Fass, R TI Growing E-coli to high cell density - A historical perspective on method development SO BIOTECHNOLOGY ADVANCES LA English DT Review DE E. coli; growth strategies; acetate excretion; high density ID BENCH-SCALE FERMENTOR; FED-BATCH CULTURES; RECOMBINANT PROTEIN-PRODUCTION; ACETIC-ACID; ACETATE ACCUMULATION; CONCENTRATED CULTURE; ENHANCED PRODUCTION; DIALYSIS REACTOR; DEFINED MEDIUM; GROWTH-RATE AB E. coli is the major bacterial platform for expressing simple heterologous proteins. Growing E coli to high densities has been the subject of numerous studies since the early 1970s, exploring the limits of bacterial culture density in order to achieve maximum productivity. Research strategies were focused on improving the cultivation techniques, manipulating the bacteria's physiology or both. As a result, batch, fed batch and dialysis fermentation techniques had been developed. These growth strategies, together with optimization of media composition and the application of molecular biology methods, made it possible to grow E. coli to cell densities of up to 190 g/l (dry weight), while avoiding media precipitation and preventing acetate accumulation. Additional research on the effects of heterologous protein biosynthesis on signal transduction, proteolysis and post transcription events in E. coli may improve its productivity. Published by Elsevier Inc. C1 NIDDK, Biotechnol Unit, NIH, Bethesda, MD 20892 USA. IIBR, Dept Biotechnol, IL-74100 Ness Ziona, Israel. RP Shiloach, J (reprint author), NIDDK, Biotechnol Unit, NIH, Bldg 14A,Rm 173, Bethesda, MD 20892 USA. EM yossi@nih.gov NR 64 TC 196 Z9 212 U1 12 U2 114 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0734-9750 J9 BIOTECHNOL ADV JI Biotechnol. Adv. PD JUL PY 2005 VL 23 IS 5 BP 345 EP 357 DI 10.1016/j.biotechadv.2005.04.004 PG 13 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 938PL UT WOS:000230015200002 PM 15899573 ER PT J AU Heindel, JJ Levin, E AF Heindel, JJ Levin, E TI Developmental origins and environmental influences - Introduction SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Editorial Material C1 NIEHS, Div Extramural Res & Training, NIH, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Dept Psychiat & Behav Sci, Durham, NC 27710 USA. RP Heindel, JJ (reprint author), NIEHS, Div Extramural Res & Training, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM jerrold.heindel@nih.hhs.gov NR 3 TC 11 Z9 11 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JUL PY 2005 VL 73 IS 7 BP 469 EP 469 DI 10.1002/bdra.20141 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 949IX UT WOS:000230779700001 PM 15959884 ER PT J AU Newbold, RR Padilla-Banks, E Snyder, RJ Jefferson, WN AF Newbold, RR Padilla-Banks, E Snyder, RJ Jefferson, WN TI Developmental exposure to estrogenic compounds and obesity SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article ID DIETHYLSTILBESTROL C1 NIEHS, Dev Endocrinol Sect, Mol Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Newbold, RR (reprint author), NIEHS, Dev Endocrinol Sect, Mol Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM newbold1@niehs.nih.gov NR 6 TC 72 Z9 74 U1 3 U2 16 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JUL PY 2005 VL 73 IS 7 BP 478 EP 480 DI 10.1002/bdra.20147 PG 3 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 949IX UT WOS:000230779700006 PM 15959888 ER PT J AU Lucas, ML Seidel, NE Porada, CD Quigley, JG Anderson, SM Malech, HL Abkowitz, JL Zanjani, ED Bodine, DM AF Lucas, ML Seidel, NE Porada, CD Quigley, JG Anderson, SM Malech, HL Abkowitz, JL Zanjani, ED Bodine, DM TI Improved transduction of human sheep repopulating cells by retrovirus vectors pseudotyped with feline leukemia virus type C or RD114 envelopes SO BLOOD LA English DT Article ID HEMATOPOIETIC STEM-CELLS; SEVERE COMBINED IMMUNODEFICIENCY; IN-VIVO SELECTION; ADENOSINE-DEAMINASE DEFICIENCY; AMPHOTROPIC MURINE RETROVIRUS; CHRONIC GRANULOMATOUS-DISEASE; BLOOD CD34(+) CELLS; GENE-THERAPY; GIBBON APE; PERIPHERAL-BLOOD AB Gene therapy for hematopoietic diseases has been hampered by the low frequency of transduction of human hematopoietic stem cells (HSCs) with retroviral vectors pseudotyped with amphotropic envelopes. We hypothesized that transduction could be increased by the use of retroviral vectors pseudotyped with envelopes that recognize more abundant cellular receptors. The levels of mRNA encoding the receptors of the feline retroviruses, RD114 and feline leukemia virus type C (FeLV-C), were significantly higher than the level of gibbon ape leukemia virus (GaLV) receptor mRNA in cells enriched for human HSCs (Lin(-) CD34(+) CD38(-)). We cotransduced human peripheral blood CD34+ cells with equivalent numbers of FeLV-C and GALV or RD114 and GALV-pseudotyped retroviruses for injection into fetal sheep. Analysis of DNA from peripheral blood and bone marrow from recipient sheep demonstrated that FeLV-C- or RD1114-pseudotyped vectors were present at significantly higher levels than GALV-pseudotyped vectors. Analysis of individual myeloid colonies demonstrated that retrovirus vectors with FeLV-C and RD114 pseudotypes were present at 1.5 to 1.6 copies per cell and were preferentially integrated near known genes We conclude that the more efficient transduction of human HSCs with either FeLV-Cor RD114-pseudotyped retroviral particles may improve gene transfer in human clinical trials. C1 NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD 20892 USA. Univ Nevada, Reno, NV 89557 USA. NIAID, NIH, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. RP Bodine, DM (reprint author), NHGRI, Genet & Mol Biol Branch, NIH, 49 Convent Dr,MSC 4442,Bldg 49,Rm 3A04, Bethesda, MD 20892 USA. EM tedyaz@nhgri.nih.gov OI quigley, john/0000-0003-3116-4545 FU NHLBI NIH HHS [HL49042, HL31823, HL46598, HL66058, HL52955]; NICHD NIH HHS [HD43038] NR 71 TC 18 Z9 18 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2005 VL 106 IS 1 BP 51 EP 58 DI 10.1182/blood-2004-11-4491 PG 8 WC Hematology SC Hematology GA 940PN UT WOS:000230156500016 PM 15774617 ER PT J AU Kurokawa, M Ghosh, SK Ramos, JC Mian, AM Toomey, NL Cabral, L Whitby, D Barber, GN Dittmer, DP Harrington, WJ AF Kurokawa, M Ghosh, SK Ramos, JC Mian, AM Toomey, NL Cabral, L Whitby, D Barber, GN Dittmer, DP Harrington, WJ TI Azidothymidine inhibits NF-kappa B and induces Epstein-Barr virus gene expression in Burkitt lymphoma SO BLOOD LA English DT Article ID SARCOMA-ASSOCIATED HERPESVIRUS; PRIMARY EFFUSION LYMPHOMA; LATENT MEMBRANE-PROTEIN-1; CELLS; GANCICLOVIR; INDUCTION; APOPTOSIS; SUSCEPTIBILITY; TRANSCRIPTION; CHEMOTHERAPY AB The antiviral compound azidothymidine (AZT), alone or in combination with other agents, induces apoptosis in early-passage, Epstein-Barr virus-positive Burkitt lymphoma (EBV+ BL) lines and has clinical activity in EBV+ BL. We report here a mechanism of AZT's antitumor activity. The nuclei of these cells contain activated nuclear factor-kappa B (NF-kappa B) sub-units p50, c-Rel, RelB, and p52, but not p65. Treatment of primary EBV+ BL lines with AZT inhibited NF-kappa B within 1 to 2 hours. This was followed by up-regulation of EBV gene expression including viral thymidine kinase (vTK) and apoptosis. Subclones of EBV+ BL cells that demonstrated activated p65 were resistant to AZT. In EBV+ BLs, AZT but not ganciclovir (GCV) was highly phosphorylated to its monophosphate form (AZT-MID). Phosphorylation, as well as apoptosis, was markedly enhanced in the presence of hydroxyurea. AZT inhibits NF-kappa B and up-regulates EBV gene expression in primary EBV+ BLs. AZT with hydroxyurea may represent an inexpensive, targeted regimen for endemic BL. C1 Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Dept Med, Miami, FL 33136 USA. Univ Miami, Sch Med, Dept Microbiol & Immunol, Miami, FL 33136 USA. Miyazaki Univ, Coll Med, Dept Dermatol, Miyazaki, Japan. NCI, Viral Epidemiol Sect, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21701 USA. Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA. RP Harrington, WJ (reprint author), Univ Miami, Sch Med, Sylvester Comprehens Canc Ctr, Dept Med, Room 3400,1475 NW 12th Ave D8-4, Miami, FL 33136 USA. EM wharring@med.miami.edu FU NCI NIH HHS [1UO1-CA-70058, 1R01-CA-82274, R21-CA-97951] NR 25 TC 38 Z9 41 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2005 VL 106 IS 1 BP 235 EP 240 DI 10.1182/blood-2004-09-3748 PG 6 WC Hematology SC Hematology GA 940PN UT WOS:000230156500040 PM 15790788 ER PT J AU Lin, YW Slape, C Zhang, ZH Aplan, PD AF Lin, YW Slape, C Zhang, ZH Aplan, PD TI NUP98-HOXD13 transgenic mice develop a highly penetrant, severe myelodysplastic syndrome that progresses to acute leukemia SO BLOOD LA English DT Article ID ACUTE MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; ACUTE MYELOGENOUS LEUKEMIA; FUSION GENE; HEMATOPOIETIC COMPARTMENT; CHROMOSOME-TRANSLOCATION; BETHESDA PROPOSALS; NUCLEOPORIN NUP98; DE-NOVO; CLASSIFICATION AB The myelodysplastic syndromes (MDSs) are a group of clonal hematopoietic stem-cell disorders characterized by ineffective hematopoiesis and dysplasia. A wide spectrum of genetic aberrations has been associated with MDS, including chromosomal translocations involving the NUP98 gene. Using a NUP98-HOXD13 fusion gene, we have developed a mouse model that faithfully recapitulates all of the key features of MDS, including peripheral blood cytopenias, bone marrow dysplasia, and apoptosis, and transformation to acute leukemia. The MDS that develops in NUP98-HOXD13 transgenic mice is uniformly fatal. Within 14 months, all of the mice died of either leukemic transformation or severe anemia and leucopenia as a result of progressive MDS. The NUP98-HOXD13 fusion gene inhibits megakaryo cytic differentiation and increases apoptosis in the bone marrow, suggesting a mechanism leading to ineffective hematopoiesis in the presence of a hypercellular bone marrow. These mice provide an accurate preclinical model that can be used for the evaluation of MDS therapy and biology. C1 USN, Med Ctr, Genet Branch, NCI,NIH, Bethesda, MD 20889 USA. RP Aplan, PD (reprint author), USN, Med Ctr, Genet Branch, NCI,NIH, Bldg 8 Rm 5101,8901 Rockville Pike, Bethesda, MD 20889 USA. EM aplanp@mail.nih.gov RI Slape, Christopher/H-8586-2016; Aplan, Peter/K-9064-2016 OI Slape, Christopher/0000-0002-8407-3092; NR 45 TC 95 Z9 99 U1 0 U2 4 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2005 VL 106 IS 1 BP 287 EP 295 DI 10.1182/blood-2004-12-4794 PG 9 WC Hematology SC Hematology GA 940PN UT WOS:000230156500046 PM 15755899 ER PT J AU Bergsagel, PL Kuehl, WM Zhan, FH Sawyer, J Barlogie, B Shaughnessy, J AF Bergsagel, PL Kuehl, WM Zhan, FH Sawyer, J Barlogie, B Shaughnessy, J TI Cyclin D dysregulation: an early and unifying pathogenic event in multiple myeloma SO BLOOD LA English DT Article ID IN-SITU HYBRIDIZATION; CELL-LINES; UNDETERMINED SIGNIFICANCE; MONOCLONAL GAMMOPATHY; PLASMA-CELLS; B-CELLS; GENE; EXPRESSION; TRANSLOCATIONS; OVEREXPRESSION AB Two oncogenic pathways have been hypothesized for multiple myeloma (MM) and premalignant monoclonal gammopathy of undetermined significance (MGUS) tumors: a nonhyperdiplold pathway associated with a high prevalence of IgH-translocations and a hyperdiplold pathway associated with multiple trisomies of 8 chromosomes. Cyclin D1, D2, or D3 expression appears to be increased and/or dysregulated in virtually all MM tumors despite their low proliferative capacity. Translocations can directly dysregulate CCND1 (11q13) or CCND3 (6p21), or MAF (16q23) or MAFB (20q11) transcription factors that target CCND2. Biallelic dysregulation of CCND1 occurs in nearly 40 % of tumors, most of which are hyperdiploid. Other tumors express increased CCND2, either with or without a t(4;14) translocation. Using gene expression profiling to identify 5 recurrent translocations, specific trisomies, and expression of cyclin D genes, MM tumors can be divided into 8 TC (translocation/cyclin D) groups (11q13, 6p21, 4p16, maf, D1, D1 + D2, D2, and none) that appear to be defined by early, and perhaps initiating, oncogenic events. However, despite subsequent progression events, these groups have differing gene expression profiles and also significant differences in the prevalence of bone disease, frequency at relapse, and progression to extramedullary tumor. C1 Mayo Clin, Ctr Comprehens Canc, Scottsdale, AZ USA. Div Hematol Oncol, Scottsdale, AZ USA. NCI, Genet Branch, Bethesda, MD 20892 USA. Donna D & Donald M Lambert Lab Myeloma Genet, Little Rock, AR USA. Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. RP Kuehl, WM (reprint author), 8901 Rockville Pike,Bldg 8,Rm 5101, Bethesda, MD 20889 USA. EM bergsagel.p@mayo.edu; wmk@helix.nih.gov; jshaughnessy@uams.edu RI Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU NCI NIH HHS [CA100707, CA55819, CA97513] NR 36 TC 352 Z9 369 U1 2 U2 9 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 1 PY 2005 VL 106 IS 1 BP 296 EP 303 DI 10.1182/blood-2005-01-0034 PG 8 WC Hematology SC Hematology GA 940PN UT WOS:000230156500047 PM 15755896 ER PT J AU Reimers, M Weinstein, JN AF Reimers, M Weinstein, JN TI Quality assessment of microarrays: Visualization of spatial artifacts and quantitation of regional biases SO BMC BIOINFORMATICS LA English DT Article ID NORMALIZATION AB Background: Quality-control is an important issue in the analysis of gene expression microarrays. One type of problem is regional bias, in which one region of a chip shows artifactually high or low intensities (or ratios in a two-channel array) relative to the majority of the chip. Current practice in quality assessment for microarrays does not address regional biases. Results: We present methods implemented in R for visualizing regional biases and other spatial artifacts on spotted microarrays and Affymetrix chips. We also propose a statistical index to quantify regional bias and investigate its typical distribution on spotted and Affymetrix arrays. We demonstrate that notable regional biases occur on both Affymetrix and spotted arrays and that they can make a significant difference in the case of spotted microarray results. Although strong biases are also seen at the level of individual probes on Affymetrix chips, the gene expression measures are less affected, especially when the RMA method is used to summarize intensities for the probe sets. A web application program for visualization and quantitation of regional bias is provided at http://www.discover.nci.nih.gov/affytools. Conclusion: Researchers should visualize and measure the regional biases and should estimate their impact on gene expression measurements obtained. Here, we (i) introduce pictorial visualizations of the spatial biases; (ii) present for Affymetrix chips a useful resolution of the biases into two components, one related to background, the other to intensity scale factor; (iii) introduce a single parameter to reflect the global bias present across an array. We also examine the pattern distribution of such biases and conclude that algorithms based on smoothing are unlikely to compensate adequately for them. C1 NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. RP Reimers, M (reprint author), NCI, Genom & Bioinformat Grp, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. EM reimersm@mail.nih.gov; weinstein@dtpax2.ncifcrf.gov NR 13 TC 36 Z9 40 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD JUL 1 PY 2005 VL 6 AR 166 DI 10.1186/1471-2105-6-166 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 954SJ UT WOS:000231174800001 PM 15992406 ER PT J AU Mendez, I Sanchez-Pernaute, R Cooper, O Vinuela, A Ferrari, D Bjorklund, L Dagher, A Isacson, O AF Mendez, I Sanchez-Pernaute, R Cooper, O Vinuela, A Ferrari, D Bjorklund, L Dagher, A Isacson, O TI Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease SO BRAIN LA English DT Article DE transplantation; dopamine neuron; Parkinson's disease ID SENSORIMOTOR BEHAVIORAL RECOVERY; WEAVER MUTANT MICE; NEUROTROPHIC FACTOR; GRAFT-SURVIVAL; VENTRAL MESENCEPHALON; NEURAL TRANSPLANTATION; CALBINDIN D-28K; BASAL GANGLIA; RAT-BRAIN; NEURONS AB We report the first post-mortem analysis of two patients with Parkinson's disease who received fetal midbrain transplants as a cell suspension in the striatum, and in one case also in the substantia nigra. These patients had a favourable clinical evolution and positive F-18-fluorodopa PET scans and did not develop motor complications. The surviving transplanted dopamine neurons were positively identified with phenotypic markers of normal control human substantia nigra (n = 3), such as tyrosine hydroxylase, G-protein-coupled inward rectifying current potassium channel type 2 (Girk2) and calbindin. The grafts restored the cell type that provides specific dopaminergic innervation to the most affected striatal regions in the parkinsonian brain. Such transplants were able to densely reinnervate the host putamen with new dopamine fibres. The patients received only 6 months of standard immune suppression, yet by post-mortem analysis 3-4 years after surgery the transplants appeared only mildly immunogenic to the host brain, by analysis of microglial CD45 and CD68 markers. This study demonstrates that, using these methods, dopamine neuronal replacement cell therapy can be beneficial for patients with advanced disease, and that changing technical approaches could have a favourable impact on efficacy and adverse events following neural transplantation. C1 Harvard Univ, Sch Med, Neurogenerat Lab, McLean Hosp, Belmont, MA 02478 USA. McLean Hosp, NINDS Udall Parkinsons Dis Res Ctr Excellence, Belmont, MA 02478 USA. Dalhousie Univ, Halifax, NS, Canada. Queen Elizabeth II Hlth Sci Ctr, Div Neurosurg & Neurosci, Halifax, NS, Canada. McGill Univ, Montreal, PQ, Canada. Montreal Neurol Inst, McConnel Brain Imaging Ctr, Montreal, PQ, Canada. McLean Hosp, NINDS Udall Parkinsons Dis Res ctr Exellence, Belmont, MA 02178 USA. RP Isacson, O (reprint author), Harvard Univ, Sch Med, Neurogenerat Lab, McLean Hosp, MRC 130,115 Mill St, Belmont, MA 02478 USA. EM isacson@hms.harvard.edu FU NINDS NIH HHS [P50 NS 39793, P50 NS039793, P50 NS039793-06A10005] NR 67 TC 256 Z9 261 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-8950 J9 BRAIN JI Brain PD JUL PY 2005 VL 128 BP 1498 EP 1510 DI 10.1093/brain/awh510 PN 7 PG 13 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 941HB UT WOS:000230204800005 PM 15872020 ER PT J AU Loftis, JM Hauser, P Rifai, MA AF Loftis, JM Hauser, P Rifai, MA TI The association between viral clearance and depression in patients with hepatitis C receiving interferon-alpha and ribavirin SO BRAIN BEHAVIOR AND IMMUNITY LA English DT Letter ID VIRUS-INFECTION C1 Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. Oregon Hlth Sci Univ, Dept Psychiat, Portland, OR 97201 USA. Oregon Hlth Sci Univ, Dept Behav Neurosci, Portland, OR 97201 USA. Portland VA Med Ctr, JENS Lab, Portland, OR USA. NIMH, Off Clin Director, Bethesda, MD 20892 USA. RP Loftis, JM (reprint author), Portland VA Med Ctr, Behav Hlth & Clin Neurosci Div, Portland, OR USA. EM peter.hauser2@med.va.gov NR 9 TC 4 Z9 4 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 0889-1591 J9 BRAIN BEHAV IMMUN JI Brain Behav. Immun. PD JUL PY 2005 VL 19 IS 4 BP 271 EP 272 DI 10.1016/j.bbi.2005.03.007 PG 2 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 938JH UT WOS:000229995300001 PM 15944066 ER PT J AU Heidbreder, CA Gardner, EL Xi, ZX Thanos, PK Mugnaini, M Hagan, JJ Ashby, CR AF Heidbreder, CA Gardner, EL Xi, ZX Thanos, PK Mugnaini, M Hagan, JJ Ashby, CR TI The role of central dopamine D-3 receptors in drug addiction: a review of pharmacological evidence SO BRAIN RESEARCH REVIEWS LA English DT Review DE addiction; brain stimulation reward; conditioned place preference; dopamine D-3 receptors; SB-2770111-A; self-administration ID COCAINE-SEEKING BEHAVIOR; CONDITIONED PLACE PREFERENCE; NUCLEUS-ACCUMBENS CORE; STRESS-INDUCED RELAPSE; DISCRIMINATIVE STIMULUS PROPERTIES; CORTICOTROPIN-RELEASING-FACTOR; FREELY MOVING RATS; H-3 QUINPIROLE BINDING; POSTSESSION INTRAAMYGDALA NAFADOTRIDE; INTRACRANIAL SELF-STIMULATION AB The cfYNA for the doparnine D-3 receptor was isolated and characterized in 1990. Subsequent studies have indicated that D3 receptors, as well as D-3 receptor mRNA, are primarily localized in limbic regions in mammals. This finding led to the postulate that D3 receptors may be involved in drug dependence and addiction. However, this hypothesis has been difficult to test due to the lack of compounds with high selectivity for central D-3 receptors. The interpretation of results from studies using mixed D-2/D-3 agonists and/or antagonists is problematic because these agents have low selectivity for D-3 over D-2 receptors and it is likely that their actions are primarily related to D-2 receptor antagonism and possibly interaction with other neurotransmitter receptors. Currently, with the synthesis and characterization of new highly selective D-3 receptor antagonists such as SB-277011-A this difficulty has been surmounted. The purpose of the present article is to review, for the first time, the effects of various putative D-3 receptor selective compounds in animal models of drug dependence and addiction. The results obtained with highly selective D-3 receptor antagonists such as SB-277011-A, SB-414796, and NGB-2904 indicate that central D-3 receptors may play an important role in drug-induced reward, drug-taking, and cue-, drug-, and stress-induced reinstatement of drug-seeking behavior. Provided these results can be extrapolated to human drug addicts, they suggest that selective DA D-3 receptor antagonists may prove effective as potential pharmacotherapeutic agents to manage drug dependence and addiction. (c) 2005 Elsevier B.V. All rights reserved. C1 St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. GlaxoSmithKline Pharmaceut, Ctr Excellence Drug Discovery Psychiat, I-37135 Verona, Italy. Natl Inst Drug Abuse, Intramural Res Program, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Brookhaven Natl Lab, Dept Med, Upton, NY 11973 USA. RP Ashby, CR (reprint author), St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, 8000 Utopia Pkwy, Jamaica, NY 11439 USA. EM crashby@ix.netcom.com FU Intramural NIH HHS [Z99 DA999999] NR 315 TC 191 Z9 195 U1 2 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0173 J9 BRAIN RES REV JI Brain Res. Rev. PD JUL PY 2005 VL 49 IS 1 BP 77 EP 105 DI 10.1016/j.brainresrev.2004.12.033 PG 29 WC Neurosciences SC Neurosciences & Neurology GA 945XX UT WOS:000230537400005 PM 15960988 ER PT J AU Sen, HN Ursea, R Nussenblatt, RB Buggage, RR AF Sen, HN Ursea, R Nussenblatt, RB Buggage, RR TI Subconjunctival corticosteroid injection for the treatment of non-necrotising anterior scleritis SO BRITISH JOURNAL OF OPHTHALMOLOGY LA English DT Article ID EPISCLERITIS C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Sen, HN (reprint author), NEI, Immunol Lab, NIH, Bldg 10,Room 10N112, Bethesda, MD 20892 USA. EM nidamd@yahoo.com NR 8 TC 8 Z9 8 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0007-1161 J9 BRIT J OPHTHALMOL JI Br. J. Ophthalmol. PD JUL PY 2005 VL 89 IS 7 BP 917 EP 918 DI 10.1136/bjo.2004.052738 PG 2 WC Ophthalmology SC Ophthalmology GA 936UM UT WOS:000229880900031 PM 15965178 ER PT J AU Xiong, KM Hu, XQ Stewart, RR Weight, FF Li, CY AF Xiong, KM Hu, XQ Stewart, RR Weight, FF Li, CY TI The mechanism by which ethanol inhibits rat P2X(4) receptors is altered by mutation of histidine 241 SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE P2X; P2X(4) receptor; histidine; mutation; ethanol; competitive inhibition; noncompetitive inhibition; suramin; PPADS ID FAST SYNAPTIC TRANSMISSION; SINGLE-CHANNEL PROPERTIES; ATP-ACTIVATED CURRENT; DORSAL-HORN NEURONS; SPINAL-CORD; EXTRACELLULAR HISTIDINES; MEDIATED ENHANCEMENT; HIPPOCAMPAL-NEURONS; MAMMALIAN NEURONS; GLUTAMATE RELEASE AB 1 We investigated ethanol inhibition of the rat P2X(4) receptor and the contribution of the three histidine residues in the extracellular loop of this receptor to ethanol inhibition of receptor function, using site-directed mutagenesis and electrophysiological characterization of recombinant receptors. 2 In the wild-type receptor, 50, 200 and 500mM ethanol increasingly shifted the ATP concentration response curve to the right in a parallel manner, increasing the EC50 value without affecting E-max. However, 750 or 900mM ethanol did not produce a further increase in the EC50 value of the ATP concentration-response curve, suggesting that this inhibition is not competitive. 3 The P2X(4) receptor mutations H140A and H286A did not significantly alter ethanol inhibition of ATP-activated current. By contrast, the mutation H241A changed the mechanism by which ethanol inhibits receptor function; viz., ethanol inhibition was not associated with an increased EC50 value of the ATP concentration-response curve, instead, ethanol decreased the maximal response to ATP without affecting the EC50 value of the ATP concentration-response curve. 4 Ethanol inhibition of the H241A mutant was voltage independent between -60 and +20mV and ethanol did not alter the reversal potential of ATP-activated current. In addition, ethanol decreased the desensitization rate of the H241A-mediated current. 5 The purinoceptor antagonists, suramin and pyridoxal-phosphate-6-azophenyl-20,40-disulphonic acid ( PPADS), did not alter the magnitude of ethanol inhibition of ATP-activated current in the H241A mutant. 6 The results suggest that ethanol inhibits the wild-type rat P2X(4) receptor by an allosteric action to increase the EC50 value of the ATP concentration-response curve, the P2X(4) receptor mutation H241A alters the mechanism by which ethanol inhibits P2X(4) receptor function, and ethanol and PPADS or suramin appear to inhibit H241A-mutated receptors at independent sites. C1 NIAAA, Lab Mol & Cellular Neurobiol, NIH, Bethesda, MD 20892 USA. RP Li, CY (reprint author), AstraZeneca CNS Discovery, 1800 Concord Pike,A133,POB 15437, Wilmington, DE 19850 USA. EM chaoying.li@astrazeneca.com NR 44 TC 16 Z9 16 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD JUL PY 2005 VL 145 IS 5 BP 576 EP 586 DI 10.1038/sj.bjp.0706192 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 946QV UT WOS:000230588200004 PM 15765101 ER PT J AU Di Mascio, M Percus, JK Percus, OE Markowitz, M Ho, DD Perelson, AS AF Di Mascio, M Percus, JK Percus, OE Markowitz, M Ho, DD Perelson, AS TI Duration of an intermittent episode of viremia SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article ID ANTIRETROVIRAL THERAPY AB HIV-1 infected patients after being treated with potent combinations of antiretroviral drugs for 2-6 months typically reach a state in which virus can no longer be detected within their blood. These patients with undetectable virus occasionally have viral load measurements that are above the limit of detection of current assays. Such measurements are called blips. Here we examine the possibility that such blips represent infrequent measurements taken during a period of time in which there is a transient elevation of virus in the patient's blood, i.e., a so-called transient episode of viremia. By analyzing time series of blips from a large number of patients, we conclude that transient episodes of viremia exist and that on average they extend for a period of about 3 weeks. Published by Elsevier Ltd on behalf of Society for Mathematical Biology. C1 Los Alamos Natl Lab, Div Theoret, Los Alamos, NM 87545 USA. NIAID, NIH, Bethesda, MD 20892 USA. NYU, Courant Inst Math Sci, New York, NY 10012 USA. Rockefeller Univ, Aaron Diamond AIDS Res Ctr, New York, NY 10016 USA. RP Perelson, AS (reprint author), Los Alamos Natl Lab, Div Theoret, MS K710, Los Alamos, NM 87545 USA. EM asp@lanl.gov FU NCRR NIH HHS [RR06555, RR00102]; NIAID NIH HHS [AI40387, AI41534, AI47033, AI28433] NR 6 TC 13 Z9 13 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD JUL PY 2005 VL 67 IS 4 BP 885 EP 900 DI 10.1016/j.bulm.2004.11.003 PG 16 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 932BI UT WOS:000229528800012 PM 15893558 ER PT J AU Khan, MJ Partridge, EE Wang, SS Schiffman, M AF Khan, MJ Partridge, EE Wang, SS Schiffman, M CA Lesion Triage Sudy ALTS Grp TI Socioeconomic status and the risk of cervical intraepithelial neoplasia Grade 3 among oncogenic human papillomavirus DNA-positive women with equivocal or mildly abnormal cytology SO CANCER LA English DT Article DE cervical intraepithelial neoplasia; socioeconomic status; human papillomavirus; human papillomavirus; triage; cofactors ID MULTICENTRIC CASE-CONTROL; SQUAMOUS-CELL CARCINOMA; ASCUS-LSIL TRIAGE; CHLAMYDIA-TRACHOMATIS; UNDETERMINED SIGNIFICANCE; CANCER STATISTICS; RANDOMIZED-TRIAL; POOLED ANALYSIS; DETERMINANTS; INFECTION AB BACKGROUND. Low socioeconomic status (SES) is a reported risk factor for cervical carcinoma, but few studies have taken into account adequately the possibly confounding effects of oncogenic human papillomavirus (HPV) infection as well as access to screening and subsequent treatment. METHODS. Women (n = 5060 women) with a mean age of 27.5 years and with equivocal or mild cytologic cervical abnormalities were enrolled in the Atypical Squamous Cells of Undetermined Significance/Low- Grade Squamous Intraepithelial Lesion (ASCUS-LSIL) Triage Study (ALTS), a clinical trial that evaluated management strategies. The women were seen every 6 months for 2 years. The enrollment questionnaire assessed three indicators of SES: race/ethnicity, education, and source of payment for medical care. Multivariate logistic regression models were used to identify predictors of oncogenic HPV DNA positivity at enrollment and to assess associations between the SES indicators and risk of cervical intraepithelial neoplasia grade 3 (precancer) and carcinoma (>= CIN3) identified throughout the study (n = 506 women) among oncogenic HPV-positive women (n = 3133 women). RESULTS. SES indicators were not associated significantly with oncogenic HPV infection after adjustment for age at enrollment, recent and lifetime number of sexual partners, study center, and smoking history. Among women with oncogenic HPV, the risk of >= CIN3 increased with decreasing education (less than high school education: odds ratio [OR], 2.4; 95% confidence interval [95%CI], 1.5-3.7 vs. completed college). Black women (OR, 0.5; 95%CI, 0.4-0.7) and white/Hispanic women (OR, 0.4; 95%CI, 0.2-0.8) were at decreased risk for >= CIN3 compared with white/non-Hispanic women. The source of payment for medical care was not associated with risk. CONCLUSIONS. Factors associated with lower SES, such as low education, may serve as a surrogate for unknown factors that influence progression to ! CIN3 among women with oncogenic HPV infection. In this controlled setting with equalized follow-up and treatment, the decreased risk of CIN3 associated with black and white/Hispanic race/ethnicity could be further examined. Ongoing efforts should emphasize methods for equalizing screening and follow-up among women of varying SES, regardless of race or ethnicity. Published 2005 by the American Cancer Society. C1 Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35233 USA. Howard Hughes Med Inst, Res Scholars Program, HHMI, NIH, Chevy Chase, MD USA. NCI, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, NIH, Rockville, MD USA. RP Partridge, EE (reprint author), Univ Alabama, Dept Obstet & Gynecol, 618 S 20th St, Birmingham, AL 35233 USA. EM eep3840@uab.edu FU NCI NIH HHS [CN-55158, CN-55105, CN-55153, CN-55154, CN-55155, CN-55156, CN-55157, CN-55159] NR 41 TC 34 Z9 35 U1 1 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUL 1 PY 2005 VL 104 IS 1 BP 61 EP 70 DI 10.1002/cncr.21129 PG 10 WC Oncology SC Oncology GA 936KB UT WOS:000229852800008 PM 15889450 ER PT J AU Dignani, MC Rex, JH Chan, KW Dow, G DeMagalhaes-Silverman, M Maddox, AM Walsh, T Anaissie, E AF Dignani, MC Rex, JH Chan, KW Dow, G DeMagalhaes-Silverman, M Maddox, AM Walsh, T Anaissie, E TI Immunomodulation with interferon-gamma and colony-stimulating factors for refractory fungal infections in patients with leukemia SO CANCER LA English DT Article DE leukemia; candidiasis; interferon-gamma; fungal infections ID CHRONIC GRANULOMATOUS-DISEASE; ANTIFUNGAL CHEMOTHERAPY; SYSTEMIC INFECTION; THERAPY AB BACKGROUND. Invasive fungal infections (IFI) in immunocompromised patients are associated with significant morbidity and mortality, despite appropriate antifungal treatment and recovery from neutropenia. The outcome of these infections depends significantly on the overall state of immunosuppression, including mainly the phagocytic system (neutrophils and macrophages). Interferon-gamma (IFN-gamma), granulocyte-colony-stimulating factor (G-CSF) and granulocyte-macrophage-colony-stimulating factor (GM-CSF) are cytokines that enhance the activity of neutrophils and macrophages. METHODS. The authors reported 4 patients with leukemia and refractory invasive candidiasis or trichosporonosis despite 1-13 months of appropriate antifungal treatment. RESULTS. Cytokines were administered for 1.5-5 months without significant toxicity. For each patient, initiation of interferon-gamma plus a colony-stimulating factor resulted in a clinical response. The contribution of cytokines to control the fungal infection in these 4 patients was suggested by the strong inflammatory reaction observed in the 2 patients who had an immediate response (within 7 days of initiation of cytokine therapy) and by the good outcome in the 2 other patients in whom antifungal agents were discontinued at the start of cytokine therapy. CONCLUSIONS. These data suggested a potential role for immunomodulation in patients with leukemia with refractory invasive fungal infections. Published 2005 by the American Cancer Society. C1 Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Myeloma Inst Res & Therapy, Div Support Care, Little Rock, AR 72205 USA. Univ Texas, Sch Med, Ctr Infect Dis, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pediat, Houston, TX 77030 USA. Moncton Hosp, Dept Infect Dis, Moncton, NB, Canada. Univ Iowa, Sch Med, Div Hematol & Oncol, Dept Internal Med, Iowa City, IA 52242 USA. Univ Arkansas Med Sci, Dept Internal Med, Div Hematol & Oncol, Little Rock, AR 72205 USA. NCI, Immunocompromised Host Sect, NIH, Bethesda, MD 20892 USA. RP Anaissie, E (reprint author), Univ Arkansas Med Sci, Arkansas Canc Res Ctr, Myeloma Inst Res & Therapy, Div Support Care, 4301 W Markham,Mail Slot 776, Little Rock, AR 72205 USA. EM anaissieeliasj@uams.edu OI Dignani, Maria Cecilia/0000-0002-7446-6183 NR 15 TC 29 Z9 32 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0008-543X J9 CANCER JI Cancer PD JUL 1 PY 2005 VL 104 IS 1 BP 199 EP 204 DI 10.1002/cncr.21142 PG 6 WC Oncology SC Oncology GA 936KB UT WOS:000229852800024 PM 15929126 ER PT J AU Burger, H van Tol, H Brok, M Wiemer, EAC de Bruijn, EA Guetens, G de Boeck, G Sparreboom, A Verweij, J Nooter, K AF Burger, H van Tol, H Brok, M Wiemer, EAC de Bruijn, EA Guetens, G de Boeck, G Sparreboom, A Verweij, J Nooter, K TI Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps SO CANCER BIOLOGY & THERAPY LA English DT Article DE Gleevec; oral bioavailability; drug resistance; ABC transporters; Caco-2 cells; tyrosine kinase inhibitor; pharmacokinetic resistance; gastrointestinal absorption ID CANCER RESISTANCE PROTEIN; GASTROINTESTINAL STROMAL TUMORS; CHRONIC MYELOID-LEUKEMIA; BREAST-CANCER; TYROSINE KINASE; IN-VITRO; P-GLYCOPROTEIN; CELL-LINE; BIOAVAILABILITY; INHIBITOR AB Imatinib mesylate is a selective tyrosine kinase inhibitor that is successfully used in the treatment of Philadelphia- positive chronic and acute leukaemia's, and gastrointestinal stromal tumors. We investigated whether the intended chronic oral administration of imatinib might lead to the induction of the intestinal ABC transport proteins ABCB1, ABCC1 (MRP1), ABCC2 (MRP2) and ABCG2. Using Caco2 cells as an in vitro model for intestinal drug transport, we found that continuous exposure (up to 100 days) with imatinib (10 mu M) specifically upregulates the expression of ABCG2 (maximal similar to 17-fold) and ABCB1 (maximal similar to 5-fold). The induction of gene expression appeared to be biphasic in time, with a significant increase in ABCG2 and ABCB1 at day 3 and day 25, respectively, and was not mediated through activation of the human orphan nuclear receptor SXR/ NRI12. Importantly, chronic imatinib exposure of Caco2 cells resulted in a similar to 50% decrease in intracellular accumulation of imatinib, probably by enhanced ABCG2- and ABCB1-mediated efflux, as a result of upregulated expression of these drug pumps. Both ABCG2 and ABCB1 are normally expressed in the gastrointestinal tract and it might be anticipated that drug-induced upregulation of these intestinal pumps could reduce the oral bioavailability of imatinib, representing a novel mechanism of acquired pharmacokinetic drug resistance in cancer patients that are chronically treated with imatinib. C1 Erasmus MC, Dept Med Oncol, Josephine Nefkens Inst, NL-3000 DR Rotterdam, Netherlands. Katholieke Univ Leuven, Expt Oncol Lab, Louvain, Belgium. Univ Antwerp, Dept Chem, B-2020 Antwerp, Belgium. Univ Antwerp, Dept Oncol, B-2020 Antwerp, Belgium. NCI, Med Oncol Clin Res Unit, Bethesda, MD 20892 USA. RP Nooter, K (reprint author), Erasmus MC, Dept Med Oncol, Josephine Nefkens Inst, Room Be422,POB 1738, NL-3000 DR Rotterdam, Netherlands. EM k.nooter@erasmusmc.nl RI Sparreboom, Alex/B-3247-2008; OI Wiemer, Erik/0000-0002-0673-7236 NR 30 TC 123 Z9 130 U1 0 U2 6 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD JUL PY 2005 VL 4 IS 7 BP 747 EP 752 PG 6 WC Oncology SC Oncology GA 022GG UT WOS:000236042800016 PM 15970668 ER PT J AU Schmitz, KH Holtzman, J Courneya, KS Masse, LC Duval, S Kane, R AF Schmitz, KH Holtzman, J Courneya, KS Masse, LC Duval, S Kane, R TI Controlled physical activity trials in cancer survivors: A systematic review and meta-analysis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Review ID RANDOMIZED CONTROLLED-TRIAL; QUALITY-OF-LIFE; GROUP REHABILITATION PROGRAM; CELL CYTOTOXIC ACTIVITY; HIGH-DOSE CHEMOTHERAPY; BREAST-CANCER; AEROBIC EXERCISE; RESISTANCE EXERCISE; FATIGUE MANAGEMENT; MODERATE EXERCISE AB Background: Approximately 9.8 million cancer survivors are alive in the United States today. Enthusiasm for prescribing physical activity for cancer survivors depends on evidence regarding whether physical activity during or after completion of treatment results in improved outcomes such as cardiorespiratory fitness, fatigue, symptoms, quality of life, mental health, or change in body size. Methods: A systematic qualitative and quantitative review of the English language scientific literature identified controlled trials of physical activity interventions in cancer survivors during and after treatment. Data from 32 studies were abstracted, weighted mean effect sizes (WMES) were calculated from the 22 high-quality studies, and a systematic level of evidence criteria was applied to evaluate 25 outcomes. Results: There was qualitative and quantitative evidence of a small to moderate effect of physical activity interventions Introduction on cardiorespiratory fitness (WMES = 0.51 and 0.65 during and after treatment respectively, P < 0.01), physiologic outcomes and symptoms during treatment (WMES = 0.28, P < 0.01 and 0.39, P < 0.01, respectively), and vigor posttreatment (WMES = 0.83, P = 0.04). Physical activity was well tolerated in cancer survivors during and after treatment, but the available literature does not allow conclusions to be drawn regarding adverse events from participation. Conclusions: Physical activity improves cardiorespiratory fitness during and after cancer treatment, symptoms and physiologic effects during treatment, and vigor posttreatment. Additional physical activity intervention studies are needed to more firmly establish the range and magnitude of positive effects of physical activity among cancer survivors. C1 Univ Penn, Div Clin Epidemiol, Philadelphia, PA 19072 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Minnesota, Div Hlth Serv Res & Policy, Minneapolis, MN USA. Univ Minnesota, Clin Outcomes Res Ctr, Minneapolis, MN USA. Univ Alberta, Fac Phys Educ, Edmonton, AB, Canada. NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. RP Schmitz, KH (reprint author), Univ Penn, Div Clin Epidemiol, 423 Guardian Dr,9th Floor Blockley Dr, Philadelphia, PA 19072 USA. EM kschmitz@cceb.upenn.edu RI Schmitz, Kathryn/B-7154-2011 NR 63 TC 352 Z9 356 U1 5 U2 32 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2005 VL 14 IS 7 BP 1588 EP 1595 DI 10.1158/1055-9965.EPI-04-0703 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 945TS UT WOS:000230525700002 PM 16030088 ER PT J AU Butler, LM Duguay, Y Millikan, RC Sinha, R Gagne, JF Sandler, RS Guillemette, C AF Butler, LM Duguay, Y Millikan, RC Sinha, R Gagne, JF Sandler, RS Guillemette, C TI Joint effects between UDP-glucuronosyltransferase 1A7 genotype and dietary carcinogen exposure on risk of colon cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HETEROCYCLIC AMINE CONTENT; UGT1 GENE-COMPLEX; N-HYDROXY-PHIP; LIVER-MICROSOMES; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; FUNCTIONAL POLYMORPHISMS; AFRICAN-AMERICANS; VARYING DEGREES; TOTAL-ENERGY; RAT-LIVER AB The UDP-glucuronosyltransferase 1A7 (UGTIA7) gene is polymorphic and encodes an enzyme involved in the detoxification of heterocyclic amines MCA) and polycyclic aromatic hydrocarbons (PAH). Consumption of pan-fried and well-done meat are surrogates for HCA and PAH exposure and are possibly associated with colon cancer. We have evaluated whether UGT1A7 allelic variations are associated with colon cancer and whether UGT1A7 genotype modified associations among meat intake, exposure to HCAs and PAHs, and colon cancer in a population-based case-control study of African Americans (197 cases and 202 controls) and whites (203 cases and 210 controls). As part of a 150-item food frequency questionnaire, meat intake was assessed by cooking method and doneness and used to estimate individual HCA and PAH exposure. LIGT1A7 alleles (UGT1A7*1, UGT1A7*2, UGT1A7*3, and UGT1A7*4) were measured and genotypes were categorized into predicted activity groups (high: *1/*l, *1/*2, *2/*2; intermediate: *1/*3, *1/*4, *2/*3; low: *3/*3,*3/*4,*4/*4). There was no association with UGT1A7 low versus high/intermediate genotype [odds ratio (OR), 1.1; 95% confidence interval (95% CI), 0.7-1.81, regardless of race. Greater than additive joint effects were observed for UGT1A7 low genotype and HCA-related factors. For example, equal to or greater than the median daily intake of the HCA, 2-amino3,4,8-trimethylimidazo[4,5-flquinoxaline (DiMelQx) and having UGT1A7 low genotype was positively associated with colon cancer (OR, 2.4; 95% CI, 1.2-4.8), compared with less than the median daily intake and UGT1A7 high/intermediate genotypes. These data suggest that the associations among cooked meat-derived compound exposure, and colon cancer are modified by the UGT1A7 genotype. C1 Univ Calif Davis, Dept Publ Hlth Sci, Div Epidemiol, Davis, CA 95616 USA. CHU Laval, Pharmacogenom Lab, Oncol & Mol Endocrinol Res Ctr, Laval, PQ, Canada. Univ Laval, Fac Pharm, Quebec City, PQ G1K 7P4, Canada. Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. NCI, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Guillemette, C (reprint author), CHUQ Res Ctr, Canada Res Chair Pharmacogenom, Pharmacogenom Lab, 2705 Blvd Laurier, Quebec City, PQ G1V 4G2, Canada. EM Chantal.Guillemette@crchul.ulaval.ca RI Guillemette, Chantal/J-6463-2012; Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Guillemette, Chantal/0000-0002-1113-1212 FU NCI NIH HHS [P30-CA16086, R01-CA 66635]; NIDDK NIH HHS [P30 DK 34987]; NIEHS NIH HHS [P30-ES10126] NR 58 TC 37 Z9 39 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2005 VL 14 IS 7 BP 1626 EP 1632 DI 10.1158/1055-9965.EPI-04-0682 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 945TS UT WOS:000230525700007 PM 16030093 ER PT J AU Fenton, JI Hord, NG Lavigne, JA Perkins, SN Hursting, SD AF Fenton, JI Hord, NG Lavigne, JA Perkins, SN Hursting, SD TI Leptin, insulin-like growth factor-1, and insulin-like growth factor-2 are Mitogens in Apc(Min/+) but not Apc(+/+) colonic epithelial cell lines SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID COLORECTAL-CANCER; GASTROINTESTINAL-TRACT; SIGNALING PATHWAYS; P38 MAPK; IGF-II; EXPRESSION; RECEPTOR; INFLAMMATION; ACTIVATION; CHOLESTEROL AB The obese state is associated with elevated circulating levels of insulin, insulin-like growth factors (IGF), and leptin. Research is contradictory regarding the role of these elevated growth factors in colon cancer risk. We hypothesized that colonic epithelial cells that were Apc deficient (Apcm(Min/+)) but not those expressing wild-type Apc (Ape(+/+)) would experience a hyperproliferative and antiapoptotic phenotype when exposed to these growth factors. This hypothesis was addressed using two nontumorigenic murine colonic epithelial cell lines with distinct Apc genotypes: Apc(+/+) YAMC cells and Apc(Min/+) IMCE cells. Cells were treated for 48 hours with various concentrations of leptin (0.001-50 ng/mL), IGF-1 (0.1-200 ng/mL), or IGF-2 (0.1-600 ng/mL). In YAMC cells, leptin caused a significant decrease in cell proliferation (P < 0.01) compared with controls due to induction of caspase activity and apoptosis. In contrast, in the IMCE cells, leptin induced a 75% increase in cell proliferation compared with controls (P < 0.0001). IGF-1 and IGF-2 also induced 50% greater proliferation in the IMCE cells (P < 0.001) compared with controls. Cotreatment of IMCE cells with leptin and either IGF-1 or IGF-2 induced greater proliferation than either growth factor alone (P < 0.0001). IMCE cell proliferation caused by leptin only treatment was associated with activation of p42/44 mitogen-activated protein kinase (MAPK), P38 MAPK, and nuclear factor-kappa B nuclear translocation but not with MAPK kinase or Janus-activated kinase/ signal transducers and activators of transcription activation. These data provide the first evidence that leptin may interact with IGFs to promote survival and expansion of colonic epithelial cells that were Apc deficient (Apc(Min/+)) but not those expressing wild-type Apc (Apc(+/+)). C1 NCI, Canc Prevent Fellowship Program, Div Canc Prevent, Bethesda, MD 20892 USA. NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. Michigan State Univ, Dept Food Sci & Human Nutr, E Lansing, MI 48824 USA. RP Fenton, JI (reprint author), NCI, Canc Prevent Fellowship Program, Div Canc Prevent, 6130 Execut Blvd,MSC 7361, Bethesda, MD 20892 USA. EM imigjeni@msu.edu OI Fenton, Jenifer/0000-0002-8875-3239 NR 34 TC 61 Z9 61 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2005 VL 14 IS 7 BP 1646 EP 1652 DI 10.1158/1055-9965.EPI-04-0916 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 945TS UT WOS:000230525700010 PM 16030096 ER PT J AU Schairer, C Hill, D Sturgeon, SR Fears, T Mies, C Ziegler, RG Hoover, RN Sherman, ME AF Schairer, C Hill, D Sturgeon, SR Fears, T Mies, C Ziegler, RG Hoover, RN Sherman, ME TI Serum concentrations of estrogens, sex hormone binding globulin, and androgens and risk of breast hyperplasia in postmenopausal women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DISEASE; CANCER; BENIGN; ESTRADIOL; RECEPTOR; PLASMA; PROLIFERATION; SULFATE; LESIONS AB Objective: We sought to determine whether serum concentrations of estrogens, androgens, and sex hormone binding globulin in postmenopausal women were related to the presence of mammary hyperplasia, an established breast cancer risk factor. Methods: Study participants provided serum before breast biopsy or mastectomy in three hospitals in Grand Rapids, Michigan, between 1977 and 1987. A total of 179 subjects with breast hyperplasia were compared with 152 subjects with nonproliferative breast changes that are not associated with increased breast cancer risk. Results: The odds ratios (OR) associated with the three upper quartiles of estradiol in comparison with the lowest quartile were 2.2 [95% confidence interval (95% CI) 1.1-4.6], 2.5 (95% CI, 1.1-5.3), and 4.1 (95% Cl, 2.0-8.5; P-trend = 0.007). The corresponding ORs for bioavailable estradiol, estrone,and estrone sulfate were of generally similar magnitude (P-trend = 0.003 for bioavailable estradiol, 0.0004 for estrone, and 0.0009 for estrone sulfate). Relative to women concurrently in the lowest tertile for serum estradiol, estrone, and estrone sulfate, women concurrently in the highest tertile for all three hormones had an OR of 5.8 (93% CI, 2.2-15.2). Serum concentrations of sex hormone binding globulin, testosterone, dehydroepiandrosterone, androstenedione, and androstenediol were not associated with risk of hyperplasia. Conclusions: Serum concentrations of estrogens, but not of androgens or sex hormone binding globulin, were strongly and significantly associated with risk of breast hyperplasia in postmenopausal women, suggesting that estrogens are important early in the pathologic process towards breast cancer. C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ New Mexico, Albuquerque, NM 87131 USA. Univ Massachusetts, Amherst, MA 01003 USA. Univ Penn, Dept Pathol, Philadelphia, PA 19104 USA. RP Schairer, C (reprint author), NCI, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS,Room 8020 MSC 7234, Rockville, MD 20852 USA. EM schairec@exchange.nih.gov NR 23 TC 6 Z9 6 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2005 VL 14 IS 7 BP 1660 EP 1665 DI 10.1158/1055-9965.EPI-05-0017 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 945TS UT WOS:000230525700012 PM 16030098 ER PT J AU Kim, J Sun, PY Lam, YW Troncoso, P Sabichi, AL Babaian, RJ Pisters, LL Pettaway, CA Wood, CG Lippman, SM McDonnell, TJ Lieberman, R Logothetis, C Ho, SM AF Kim, J Sun, PY Lam, YW Troncoso, P Sabichi, AL Babaian, RJ Pisters, LL Pettaway, CA Wood, CG Lippman, SM McDonnell, TJ Lieberman, R Logothetis, C Ho, SM TI Changes in serum proteomic patterns by presurgical alpha-tocopherol and L-selenomethionine supplementation in prostate cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID SELENIUM SUPPLEMENTATION; PREVENTION; CARCINOMA; TRIAL AB Background: Evidence of the chemopreventive effects of the dietary antioxidants alpha-tocopherol (vitamin E) and L-selenomethionine (selenium) comes from secondary analysis of two phase III clinical trials that found treatment with these antioxidants reduced the incidence of prostate cancer. To determine the effects of selenium and vitamin E in blood and prostate tissue, we undertook a preoperative feasibility study complementary to the currently ongoing Selenium and Vitamin E Cancer Prevention Trial. Methods: Forty-eight patients with clinically localized prostate cancer enrolled on this 2 x 2 factorial design study were randomized to take selenium, vitamin E, both, or placebo for 3 to 6 weeks before prostatectomy. Sera were collected from patients before and after dietary supplementation. Thirty-nine patients were evaluable, and 29 age-matched disease-free men served as controls. Mass profiling of lipophilic serum proteins of lower molecular weight (2-13.5 kDa) wasconducted, and mass spectra data were analyzed using custom-designed software. Results: Weighted voting analyses showed a change in sera classification from cancerous to healthy for some patients with prostate cancer after dietary intervention. ANOVA analysis showed significantly different treatment effects on prediction strength changes among the four groups at a 95% confidence level. Eliminating an outlying value and performing post hoc analysis using Fisher's least significant difference method showed that effects in the group treated with the combination were significantly different from those of the other groups. Conclusion: In sera from patients with prostate cancer, selenium and vitamin E combined induced statistically significant proteomic pattern changes associated with prostate cancer-free status. C1 Univ Massachusetts, Sch Med, Dept Surg, Div Urol, Worcester, MA 01605 USA. Univ Texas, MD Anderson Canc Ctr, Dept Genitourinary Med Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Clin Canc Prevent, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Urol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Pathol, Houston, TX 77030 USA. NCI, Prostate & Urol Canc Res Grp, Div Canc Prevent, Bethesda, MD 20892 USA. RP Ho, SM (reprint author), Univ Massachusetts, Sch Med, Dept Surg, Div Urol, Lazare Res Bldg,Room 504,364 Plantat St, Worcester, MA 01605 USA. EM shuk-mei.ho@umassmed.edu FU NCI NIH HHS [CA88084, CA88761] NR 18 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 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2005 VL 14 IS 7 BP 1697 EP 1702 DI 10.1158/1055-9965.EPI-04-0679 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 945TS UT WOS:000230525700018 PM 16030104 ER PT J AU Ritchey, JD Huang, WY Chokkalingam, AP Gao, YT Deng, J Levine, P Stanczyk, FZ Hsing, AW AF Ritchey, JD Huang, WY Chokkalingam, AP Gao, YT Deng, J Levine, P Stanczyk, FZ Hsing, AW TI Genetic variants of DNA repair genes and prostate cancer: A population-based study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; INSULIN-RESISTANCE; EXCISION-REPAIR; RISK; POLYMORPHISMS; XRCC1; SUSCEPTIBILITY; IDENTIFICATION; MECHANISMS; HUMANS AB As part of a population-based case-control study in Shanghai, China, we investigated whether variants in several DNA repair genes, either alone or in conjunction with other risk factors, are associated with prostate cancer risk. Genomic DNA from 162 patients newly diagnosed with prostate cancer and 251 healthy men randomly selected from the population were typed for five nonsynonymous DNA repair markers. We found that the XRCC1-Arg399GIn AA and the MGMT-Leu84Phe CT+TT genotypes were associated with an increased risk of prostate cancer [odds ratio (OR), 2.18; 95% confidence interval (0), 0.99-4.81 and OR, 1.99; 95% CI, 1.19-3.34, respectively]. In contrast, XRCC3-Thr241Met, XPD-Lys751GIn, and MGMT-Ile143Val markers showed no significant associations with risk, although due to the much lower frequency of their variant alleles in this population we cannot rule out small to modest effects. There was a significant interaction between the MGMT-84 marker and insulin resistance (P-interaction = 0.046). Relative to men with the MGMT-84 CC genotype and a low insulin resistance (< 0.097), those having the CT-TT genotype and a greater insulin resistance had a 5.4-fold risk (OR, 5.39; 95% CI, 2.46-11.82). In addition, for the XRCC3-241 marker, relative to men with the CC genotype and a low intake of preserved foods (< 12.7 g/d), those harboring the CT+TT genotype and having a higher intake of preserved foods (> 12.7 g/d), which contain nitrosamines and nitrosamine precursors, had a significantly increased risk of prostate cancer risk (OR, 2.62; 95% CI, 1.13-6.06). In contrast, men with the CT+TT genotype and a low intake of preserved foods had a 69% reduction in risk (OR, 0.31; 95% CI, 0.10-0.96; P-interaction = 0.005). These results suggest that genetic variants in the DNA repair pathways may be involved in prostate cancer etiology and that other risk factors, including preserved foods and insulin resistance, may modulate prostate cancer risk in combination with genetic susceptibility in these repair pathways. Replication in larger studies is necessary to preclude chance findings, particularly those among subgroups, and clarify the mechanisms involved. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. George Washington Univ, Sch Publ Hlth & Hlth Serv, Washington, DC USA. Celera Diagnost LLC, Alameda, CA USA. Shanghai Canc Inst, Shanghai, Peoples R China. Univ So Calif, Keck Sch Med, Dept Obstet & Gynecol, Los Angeles, CA USA. RP Hsing, AW (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, EPS MSC 7234,6120 Execut Blvd, Bethesda, MD 20892 USA. EM hsinga@mail.nih.gov NR 37 TC 51 Z9 53 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2005 VL 14 IS 7 BP 1703 EP 1709 DI 10.1158/1055-9965.EPI-04-0809 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 945TS UT WOS:000230525700019 PM 16030105 ER PT J AU Lacey, JV Brinton, LA Lubin, JH Sherman, ME Schatzkin, A Schairer, C AF Lacey, JV Brinton, LA Lubin, JH Sherman, ME Schatzkin, A Schairer, C TI Endometrial carcinoma risks among menopausal estrogen plus progestin and unopposed estrogen users in a cohort of postmenopausal women SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Epidemiology CY SEP, 2003 CL Chicago, IL SP Amer Coll Epidemiol ID HORMONE-REPLACEMENT THERAPY; CANCER UNITED-STATES; BREAST-CANCER; CIGARETTE-SMOKING; OVARIAN-CANCER; RANDOMIZED-TRIALS; HYPERPLASIA; APOPTOSIS; PROLIFERATION; DISCREPANCY AB Background: Because unopposed estrogen substantially increases endometrial carcinoma risk, estrogen plus progestin is one menopausal hormone therapy formulation for women who have not had a hysterectomy. However, endometrial carcinoma risks among estrogen plus progestin users and among former unopposed estrogen users are not firmly established. Methods: We evaluated endometrial carcinoma risks associated with estrogen plus progestin and unopposed estrogen therapies in 30,379 postmenopausal Breast Cancer Detection Demonstration Project follow-up study participants. We ascertained hormone therapy use and other risk factors during telephone interviews and mailed questionnaires between 1979 and 1998. We identified 541 endometrial carcinomas via self-report, medical records, the National Death Index, and state cancer registries. Poisson regression generated time-dependent rate ratios (RR) and 95% confidence intervals (95% CI). Results: Endometrial carcinoma was significantly associated with estrogen plus progestin only use (n = 68 cancers; RR, 2.6; 95% CI, 1.9-3.5), including both sequential (progestin < 15 days per cycle; n = 32 cancers; RR, 3.0; 95% CI, 2.0-4.6) and continuous (progestin at least 15 days per cycle; n = 15 cancers; RR, 2.3; 95% CI, 1.3-4.0) regimens. The RR increased by 0.38 (95% Cl, 0.20-0.64) per year of estrogen plus progestin use, and RRs increased with increasing duration of use for both regimens. The strong association with unopposed estrogen use declined after cessation but remained significantly elevated 10 years after last use (RR, 1.5; 95% Cl, 1.0-2.1). Conclusions: Both estrogen plus progestin regimens significantly increased endometrial carcinoma risk in this study. Risks among unopposed estrogen users remained elevated long after last use. The prospect that all estrogen plus progestin regimens increase endometrial carcinoma risk deserves continued research. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Lacey, JV (reprint author), 6120 Execut Blvd,MSC 7234, Rockville, MD USA. EM jimlacey@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU Intramural NIH HHS NR 64 TC 49 Z9 53 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2005 VL 14 IS 7 BP 1724 EP 1731 DI 10.1158/1055-9965.EPI-05-0111 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 945TS UT WOS:000230525700022 PM 16030108 ER PT J AU McGlynn, KA Graubard, BI Nam, JM Stanczyk, FZ Longnecker, MP Klebanoff, MA AF McGlynn, KA Graubard, BI Nam, JM Stanczyk, FZ Longnecker, MP Klebanoff, MA TI Maternal hormone levels and risk of cryptorchism among populations at high and low risk of testicular germ cell tumors SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER RISK; ALPHA-FETOPROTEIN; UMBILICAL-CORD; UNDESCENDED TESTIS; UNITED-STATES; DYSGENESIS SYNDROME; SUBSEQUENT RISK; MULTIPLE BIRTHS; EARLY-PREGNANCY; SERUM AB Cryptorchism is one of the few well-described risk factors for testicular cancer. It has been suggested that both conditions are related to increased in utero estrogen exposure. The evidence supporting the "estrogen hypothesis" has been inconsistent, however. An alternative hypothesis suggests that higher in utero androgen exposure may protect against the development of cryptorchism and testicular cancer. In order to examine both hypotheses, we studied maternal hormone levels in two populations at diverse risks of testicular cancer; Black Americans (low-risk) and White Americans (high-risk). The study population of 200 mothers of cryptorchid sons and 200 mothers of non-cryptorchid sons was nested within the Collaborative Perinatal Project, a cohort study of pregnant women and their children. Third trimester serum levels of estradiol (total, free, bioavailable), estriol, testosterone (total, free, bioavailable), sex hormone-binding globulin, alpha-fetoprotein, and the ratios of estradiols to testosterones were compared between the case and control mothers. The results found no significant differences in the levels of testosterone (total, free, bioavailable), alpha-fetoprotein, sex hormone-binding globulin, or in the ratios of estrogens to androgens. Total estradiol, however, was significantly lower in the cases versus the controls (P = 0.03) among all mothers and, separately, among White mothers (P = 0.05). Similarly, estriol was significantly lower among all cases (P = 0.05) and among White cases (P = 0.05). These results do not support either the estrogen or the androgen hypothesis. Rather, lower estrogens in case mothers may indicate that a placental defect increases the risk of cryptorchism and, possibly, testicular cancer. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. NICHHD, NIH, Dept Hlth & Human Serv, Rockville, MD USA. Univ So Calif, Reprod Endocrine Res Lab, Keck Sch Med, Los Angeles, CA USA. NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP McGlynn, KA (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS-7060, Rockville, MD 20852 USA. EM mcglynnk@mail.nih.gov OI Longnecker, Matthew/0000-0001-6073-5322 NR 37 TC 20 Z9 20 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2005 VL 14 IS 7 BP 1732 EP 1737 DI 10.1158/1055-9965.EPI-05-0128 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 945TS UT WOS:000230525700023 PM 16030109 ER PT J AU Huang, WY Olshan, HF Schwartz, SM Berndt, SI Chen, C Llaca, V Chanock, SJ Fraumeni, JF Hayes, RB AF Huang, WY Olshan, HF Schwartz, SM Berndt, SI Chen, C Llaca, V Chanock, SJ Fraumeni, JF Hayes, RB TI Selected genetic polymorphisms in MGMT, XRCC1, XPD, and XRCC3 and risk of head and neck cancer: A pooled analysis SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID DNA-REPAIR METHYLTRANSFERASE; HOMOLOGY-DIRECTED REPAIR; SQUAMOUS-CELL CARCINOMA; DOUBLE-STRAND BREAKS; ADDUCTS; DAMAGE; SMOKING; ETHANOL; TOBACCO; ALKYLTRANSFERASE AB Tobacco and alcohol consumption are the major risk factors for head and neck cancer, likely due to DNA-damaging processes. Genetic variations in DNA repair genes may affect an individual's susceptibility to head and neck cancer. Pooling data and DNA specimens from three case-control studies in western Washington State, North Carolina, and Puerto Rico, totaling 555 cases (430 whites) and 792 controls (695 whites), we studied the risk of head and neck cancer in relation to common nonsynonymous single-nucleotide polymorphisms in four DNA repair genes: MGMT (Leu(84)Phe and Ile(143)Val), XRCC1 (Arg(399)Gln), XPD (Lys(751)Gln), and XRCC3 (Thr(241)Met). All single-nucleotide polymorphisms were assayed in a single laboratory. Among whites, carriage of the MGMT Phe84 [odds ratio (OR), 0.71; 95% confidence interval (95% CI), 0.51-0.98] or Val(143) (OR, 0.66; 95% CI, 0.47-0.92) allele was associated with a decreased risk of head and neck cancer; the haplotype distribution for MGMT differed significantly between cases and controls (covariate-adjusted global permutation test, P = 0.012). The XRCC1 GlnGln(399) genotype was also associated with decreased risk among whites (OR, 0.56; 95% Cl, 0.32-0.94), whereas XPD751 and XRCC3(241) were not associated with risk. Alcohol-related risks tended to vary with DNA repair genotypes, especially for MGMT variants, whereas no effect modification was noted with tobacco use. Consistent findings from three case-control studies suggest that selected DNA repair enzymes may play a role in head and neck carcinogenesis. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Pediat Oncol Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Natl Canc Inst Frederick, Ctr Adv Technol, Gaithersburg, MD USA. RP Huang, WY (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, EPS 8113,MSC 7240, Bethesda, MD 20892 USA. EM huangw@mail.nih.gov NR 50 TC 71 Z9 73 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2005 VL 14 IS 7 BP 1747 EP 1753 DI 10.1158/1055-9965.EPI-05-0162 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 945TS UT WOS:000230525700026 PM 16030112 ER PT J AU Moore, LE Huang, WY Chatterjee, N Gunter, M Chanock, S Yeager, M Welch, B Pinsky, P Weissfeld, J Hayes, RB AF Moore, LE Huang, WY Chatterjee, N Gunter, M Chanock, S Yeager, M Welch, B Pinsky, P Weissfeld, J Hayes, RB TI GSTM1, GSTT1, and GSTP1 polymorphisms and risk of advanced colorectal adenoma SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID S-TRANSFERASE GSTT1; CARCINOMA SEQUENCE; GENOTYPE; CANCER; SUSCEPTIBILITY; PHENOTYPE AB Cigarette smoking is a risk factor for colon adenoma. The glutathione S-transferase enzymes are involved in the detoxification of carcinogenic compounds including those found in tobacco smoke, and thus, may be important modifiers of individual risk of developing this disease. We examined the prevalence of GSTM1 and GSTT1 gene deletions, and two GSTP1 polymorphisms in 772 cases with advanced colorectal adenomas (> 1 cm, villous elements or high-grade dysplasia) of the distal colon (descending or sigmoid colon or rectum) and 777 sigmoidoscopy negative controls enrolled in the screening arm of the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial. Epidemiologic data on smoking was collected by self-administered questionnaire and DNA was extracted from whole blood or buffy coat. For GSTM1 and GSTT1, we used a newly developed TaqMan-based assay capable of discriminating heterozygous (+/-) individuals from those with two active alleles (+/+) and homozygous deletions (-/-). For GSTP1, the I105V and the A114V substitutions were identified using end point 5' nuclease assays (TaqMan). Adjusted odds ratios (OR) and 95% confidence intervals (95% CI) were determined using unconditional logistic regression, controlling for age, race, and gender. Advanced adenoma risk was increased in current/former smokers (OR, 1.4; 95% CI, 1.21.8). Risks were decreased in subjects with >= 1 inactive GSTM1 alleles (OR, 0.6; 95% CI, 0.4-0.9); and the association was independent of smoking status (P interaction = 0.59). Having >= 1 inactive GSTT1 allele was associated with increased risk among smokers (OR, 1.4; 95% CI, 1.1-1.9; P-trend = 0.02) but not among never smokers (OR, 0.9; 95% CI, 0.6-1.3) and a significant interaction between smoking and genotype was observed (P interaction = 0.05). In summary, this is the first study to report associations between colorectal adenomas and GSTM1 wild-type and GSTT1 null allele among smokers. These findings only became apparent using a newly developed assay able to distinguish heterozygous from wild-type individuals. Our data provide evidence that phenotypic differences between these two groups exist. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Natl Canc Inst, Ctr Adv Technol, Gaithersburg, MD USA. NCI, Frederick Canc Res & Dev Ctr, Intramural Res Support Program, Sci Appl Int Corp, Frederick, MD 21701 USA. Univ Pittsburgh, Ctr Canc, Pittsburgh, PA USA. RP Moore, LE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7034, Bethesda, MD 20892 USA. EM moorele@mail.nih.gov NR 29 TC 46 Z9 47 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUL PY 2005 VL 14 IS 7 BP 1823 EP 1827 DI 10.1158/1055-9965.EPI-05-0037 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 945TS UT WOS:000230525700037 PM 16030123 ER PT J AU Lu, ZX Ye, M Yan, GR Li, Q Tang, M Lee, LM Sun, LQ Cao, Y AF Lu, ZX Ye, M Yan, GR Li, Q Tang, M Lee, LM Sun, LQ Cao, Y TI Effect of EBV LMP1 targeted DNAzymes on cell proliferation and apoptosis SO CANCER GENE THERAPY LA English DT Article DE latent membrane protein; DNAzymes; EBV-associated carcinoma; targeted suppression ID EPSTEIN-BARR-VIRUS; MEMBRANE-PROTEIN 1; TRANSCRIPTION FACTOR EGR-1; SOLID TUMOR-GROWTH; NF-KAPPA-B; NASOPHARYNGEAL CARCINOMA; MESSENGER-RNA; DNA ENZYME; EXPRESSION; OLIGODEOXYNUCLEOTIDES AB The latent membrane protein (LMP1) encoded by Epstein - Barr virus (EBV) has been suggested to be one of the major oncogenic factors in EBV-mediated carcinogenesis. RNA-cleaving DNA enzymes are catalytic nucleic acids that bind and cleave a target RNA in a highly sequence-specific manner. In this study, we explore the potential of using DNAzymes as a therapeutic approach to EBV-associated carcinomas by targeting the LMP1 gene. In all, 13 different phosphorothioate-modified "10-23'' deoxyribozymes ( DNAzymes) were designed and synthesized against the LMP1 mRNA and transfected into B95-8 cells, which constitutively express the LMP1. Fluorescence microscopy was used to examine the cellular uptake and distribution in B95-8 cells. As demonstrated in Western blots, three out of 13 deoxyribozymes significantly downregulated the expression of LMP1 in B95-8 cells. These DNAzymes were shown to markedly inhibit B95-8 cell growth compared with a disabled DNAzyme and untreated controls, as determined by an alamarBlue Assay. It was further demonstrated that these DNAzymes arrested the B95-8 cells in G0/G1 using flow cytometry. Interestingly, the active DNAzymes could also downregulate the expression of Bcl-2 gene in treated cells, suggesting a close association between the LMP1 and Bcl-2 genes and their involvement in apoptosis. This was further confirmed with the result that the DNAzymes could induce the release of cytochrome c from mitochondria, which is the hallmark of the apoptosis. The present results suggest that the LMP1 may present a potential target for DNAzymes towards the EBV-associated carcinoma through cell proliferation and apoptosis pathways. C1 Univ New S Wales, Fac Med, St Vincents Clin Sch, Sydney, NSW, Australia. Cent S Univ, Canc Res Inst, Xiangya Sch Med, Changsha 410083, Peoples R China. NCI, Lab Mol Technol SAIC Frederick, Frederick, MD 21701 USA. RP Sun, LQ (reprint author), Univ New S Wales, Fac Med, St Vincents Clin Sch, Sydney, NSW, Australia. EM lun-quan.sun@unsw.edu.au; ycao98@publics.cs.hn.cn RI Cao, Ya/C-6801-2008 NR 31 TC 40 Z9 44 U1 1 U2 9 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0929-1903 J9 CANCER GENE THER JI Cancer Gene Ther. PD JUL PY 2005 VL 12 IS 7 BP 647 EP 654 DI 10.1038/sj.cgt.7700833 PG 8 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 936GP UT WOS:000229843800007 PM 15803142 ER PT J AU Savage, SA Stewart, BJ Liao, JS Helman, LJ Chanock, SJ AF Savage, SA Stewart, BJ Liao, JS Helman, LJ Chanock, SJ TI Telomere stability genes are not mutated in osteosarcoma cell lines SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID LENGTH; CANCER; TRF2; MECHANISM; PROTEINS; CONTAIN; TUMORS; RAP1 AB Osteosarcoma (OS), the most common primary bone tumor in adolescents and young adults, is characterized by a high degree of chromosomal abnormalities. Because telomeres are important for maintaining chromosomal integrity, it is plausible that germ-line or somatic mutations in the genes responsible for stabilizing the telomere complex could contribute to OS. We performed bi-directional sequence analysis in five OS cell lines and targeted all exons and proximal promoter regions in eight genes important in telomere stability: telomerase, the RNA component of telomerase (TERC), telomeric repeat binding factor 1, telomeric repeat binding factor 2, TERF1 interacting nuclear factor 2, human Rap1, protection of telomeres 1 and tankyrase. In this pilot study, we did not identify either somatic mutations or novel germ-line mutations in the five cell lines studied. However, we did confirm common genetic polymorphisms; an analysis of heterozygous sites suggests that loss of heterozygosity in OS is not present across these eight genes. (c) 2005 Elsevier Inc. All rights reserved. C1 NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Canc Res,NIH,Adv Technol Ctr, Bethesda, MD 20892 USA. NCI, Mol Oncol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, NIH, Bethesda, MD 20892 USA. RP Savage, SA (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Canc Res,NIH,Adv Technol Ctr, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM savagesh@mail.nih.gov RI Savage, Sharon/B-9747-2015 OI Savage, Sharon/0000-0001-6006-0740 NR 31 TC 5 Z9 5 U1 1 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0165-4608 J9 CANCER GENET CYTOGEN JI Cancer Genet. Cytogenet. PD JUL 1 PY 2005 VL 160 IS 1 BP 79 EP 81 DI 10.1016/j.cancergencyto.2004.12.004 PG 3 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 941NI UT WOS:000230221100013 PM 15949576 ER PT J AU Krishnan, K Khanna, C Helman, LJ AF Krishnan, K Khanna, C Helman, LJ TI The biology of metastases in pediatric sarcomas SO CANCER JOURNAL LA English DT Article DE metastasis; sarcoma; models ID COLORECTAL-CANCER; MATRIX METALLOPROTEINASES; TUMOR ANGIOGENESIS; CELL-ADHESION; PROGNOSTIC-FACTORS; TISSUE INHIBITOR; UP-REGULATION; SOLID TUMORS; TGF-BETA; OSTEOSARCOMA AB In the treatment of pediatric solid tumors, the presence or development of metastatic disease carries a universally poor prognosis. In fact, most cancer deaths result from metastases rather than primary tumor growth. Although the poor outcome associated with metastatic disease has been known for some time, an understanding of the processes that allow a cancer to disseminate is only now beginning to be understood. In order for a cancer to spread beyond its local site, a complex series of events must be undertaken that must allow the cancer not only to travel into and through the circulation but also prevent elimination of these cells by the host, as well as promote growth at the metastatic site. This review presents a current model of these processes. Some of the key molecular factors influencing their development are outlined in the context of this model. We present recent advances in our understanding of metastases, especially as they relate to experimental therapies and possible molecular targets of future therapies. Finally, we discuss progress being made in our ability to study metastases and expectations for the future. C1 NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Krishnan, K (reprint author), NCI, Pediat Oncol Branch, Bldg 10 CRC 1-3816,10 Ctr Dr, Bethesda, MD 20892 USA. EM krishhka@mail.nih.gov NR 68 TC 22 Z9 23 U1 0 U2 1 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PINE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. PD JUL-AUG PY 2005 VL 11 IS 4 BP 306 EP 313 DI 10.1097/00130404-200507000-00006 PG 8 WC Oncology SC Oncology GA 966ME UT WOS:000232023300006 PM 16197720 ER PT J AU Modiano, JF Breen, M Burnett, RC Parker, HG Inusah, S Thomas, R Avery, PR Lindblad-Toh, K Ostrander, EA Cutter, GC Avery, AC AF Modiano, JF Breen, M Burnett, RC Parker, HG Inusah, S Thomas, R Avery, PR Lindblad-Toh, K Ostrander, EA Cutter, GC Avery, AC TI Distinct B-cell and T-cell lymphoproliferative disease prevalence among dog breeds indicates heritable risk SO CANCER RESEARCH LA English DT Article ID NON-HODGKINS-LYMPHOMAS; CANINE MALIGNANT-LYMPHOMA; LINKAGE DISEQUILIBRIUM; CLASSIFICATION; EXPRESSION; LEUKEMIAS; THERAPY; BIOPSY; GENES; IL-15 AB Immunophenotypes in lymphoproliferative diseases (LPD) are prognostically significant, yet causative factors for these conditions, and specifically those associated with heritable risk, remain elusive. The full spectrum of LPD seen in humans occurs in dogs, but the incidence and lifetime risk of naturally occurring LPD differs among dog breeds. Taking advantage of the limited genetic heterogeneity that exists within dog breeds, we tested the hypothesis that the prevalence of LPD immunophenotypes would differ among different breeds. The sample population included 1,263 dogs representing 87 breeds. Immunopthenotype was determined by the presence of clonal rearrangements of immunoglobulin heavy chain or T-cell receptor gamma chain. The probability of observing the number of B-cell or T-cell tumors in a particular breed or breed group was compared with three reference populations. Significance was computed using x(2) test, and logistic regression was used to confirm binomial predictions. The data show that, among 87 breeds tested, 15 showed significant differences from the prevalence of LPD immunophenotypes seen across the dog population as a whole. More significantly, elevated risk for T-cell LPD seems to have arisen ancestrally and is retained in related breed groups, whereas increased risk for B-cell disease may stem from different risk factors, or combinations of risk factors, arising during the process of breed derivation and selection. The data show that domestic dogs provide a unique and valuable resource to define factors that mediate risk as well as genes involved in the initiation of B-cell and T-cell LPD. C1 Univ Colorado, Hlth Sci Ctr, Dept Immunol, AMC Canc Ctr, Denver, CO 80214 USA. Univ Colorado, Ctr Canc, Denver, CO 80214 USA. Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. N Carolina State Univ, Coll Vet Med, Dept Mol Biomed Sci, Raleigh, NC 27695 USA. NHGRI, Canc Genet Branch, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Biostat, Birmingham, AL 35294 USA. Harvard Univ, Broad Inst, Cambridge, MA 02138 USA. MIT, Cambridge, MA 02139 USA. Fred Hutchinson Canc Res Ctr, Div Human Biol, Seattle, WA 98104 USA. Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98104 USA. RP Modiano, JF (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Immunol, AMC Canc Ctr, 1600 Pierce St,2-Diamond Res Bldg, Denver, CO 80214 USA. EM modianoj@amc.org; Matthew_Breen@ncsu.edu RI Parker, Heidi/C-6954-2008; OI Modiano, Jaime/0000-0001-6398-7648; Ostrander, Elaine/0000-0001-6075-9738 FU NCI NIH HHS [K05 CA90754] NR 48 TC 77 Z9 78 U1 2 U2 22 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2005 VL 65 IS 13 BP 5654 EP 5661 DI 10.1158/0008-5472.CAN-04-4613 PG 8 WC Oncology SC Oncology GA 940SR UT WOS:000230165000024 PM 15994938 ER PT J AU Dong, DZ Ko, BC Baumeister, P Swenson, S Costa, F Markland, F Stiles, C Patterson, JB Bates, SE Lee, AS AF Dong, DZ Ko, BC Baumeister, P Swenson, S Costa, F Markland, F Stiles, C Patterson, JB Bates, SE Lee, AS TI Vascular targeting and antiangiogenesis agents induce drug resistance effector GRP78 within the tumor microenvironment SO CANCER RESEARCH LA English DT Article ID ENDOPLASMIC-RETICULUM STRESS; UNFOLDED PROTEIN RESPONSE; HUMAN CANCER-CELLS; GENE-EXPRESSION; CHAPERONE GRP78; DEATH PROGRAM; GLUCOSE; ACTIVATION; APOPTOSIS; GROWTH AB Therapeutic targeting of the tumor vasculature that destroys preexisting blood vessels of the tumor and antiangiogenesis therapy capitalize on the requirement of tumor cells on an intact vascular supply for oxygen and nutrients for growth, expansion and metastasis to the distal organs. Whereas these classes of agents show promise in delaying tumor progression, they also create glucose and oxygen deprivation conditions within the tumor that could trigger unintended prosurvival responses. The glucose-regulated protein GRP78, a major endoplasmic reticulum chaperone, is inducible by severe glucose depletion, anoxia, and acidosis. Here we report that in a xenograft model of human breast cancer, treatment with the vascular targeting agent, combretastatin A4P, or the antiangiogenic agent, contortrostatin, promotes transcriptional activation of the Grp78 promoter and elevation of GRP78 protein in surviving tumor cells. We further show that GRP78 is overexpressed in a panel of human breast cancer cells that has developed resistance to a variety of drug treatment regimens. Suppression of GRP78 through the use of lentiviral vector expressing small interfering RNA sensitizes human breast cancer cells to etoposide-mediated cell death. Our studies imply that antivascular and antiangiogenesis therapy that results in severe glucose and oxygen deprivation will induce GRP78 expression that could lead to drug resistance. C1 Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Biochem & Mol Biol, Los Angeles, CA 90089 USA. NCI, Canc Therapeut Branch, Canc Res Ctr, Bethesda, MD 20892 USA. MannKind Corp, Valencia, CA USA. RP Lee, AS (reprint author), Univ So Calif, Keck Sch Med, Kenneth Norris Jr Comprehens Canc Ctr, Dept Biochem & Mol Biol, Room 5308,1441 Eastlake Ave,MC-9176, Los Angeles, CA 90089 USA. EM amylee@hsc.usc.edu FU NCI NIH HHS [CA27607, CA59318] NR 50 TC 108 Z9 118 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2005 VL 65 IS 13 BP 5785 EP 5791 DI 10.1158/0008-5472.CAN-05-0754 PG 7 WC Oncology SC Oncology GA 940SR UT WOS:000230165000040 PM 15994954 ER PT J AU Du, BH Altorki, NK Kopelovich, L Subbaramaiah, K Dannenberg, AJ AF Du, BH Altorki, NK Kopelovich, L Subbaramaiah, K Dannenberg, AJ TI Tobacco smoke stimulates the transcription of amphiregulin in human oral epithelial cells: Evidence of a cyclic AMP-responsive element binding protein-dependent mechanism SO CANCER RESEARCH LA English DT Article ID GROWTH-FACTOR RECEPTOR; ARYL-HYDROCARBON RECEPTOR; FACTOR-ALPHA; LUNG-CANCER; CIGARETTE-SMOKE; LINE; CYCLOOXYGENASE-2; PROLIFERATION; PREVENTION; LIGANDS AB Activation of epidermal growth factor receptor (EGFR)mediated signaling has been implicated in the pathogenesis of tobacco smoke-induced cancers. Recently, elevated levels of amphiregulin, a ligand of the EGFR, were found in the oral mucosa of smokers. The main objective of this study was to elucidate the mechanism by which tobacco smoke induces amphiregulin. Treatment of a nontumorigenic human oral epithelial cell line (MSK-Leuk1) with a saline extract of tobacco smoke stimulated amphiregulin (AR) transcription resulting in increased amounts of amphiregulin mRNA and protein. Tobacco smoke stimulated the cyclic AMP (cAMF) -> protein kinase A (PKA) pathway leading to increased cAMP-responsive element binding protein-dependent activation of AR transcription. These inductive effects of tobacco smoke were dependent on the aryl hydrocarbon receptor (AhR). In fact, alpha-naphthoflavone, an AhR antagonist, blocked tobacco smoke-mediated induction of binding of cAMP-responsive element binding protein to the AR promoter and thereby suppressed the induction of amphiregulin. Notably, treatment of MSK-Leuk1 cells with tobacco smoke or exogenous amphiregulin stimulated DNA synthesis. An inhibitor of EGFR tyrosine kinase or a neutralizing antibody to amphiregulin abrogated the increase in DNA synthesis mediated by tobacco smoke. Taken together, these findings suggest that tobacco smoke stimulated a signaling pathway comprised of AhR -> cAMP -> PKA resulting in enhanced AR transcription and increased DNA synthesis. The ability of tobacco smoke to induce amphiregulin and thereby enhance DNA synthesis is likely to contribute to the procarcinogenic effects of tobacco smoke. C1 Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Cardiothorac Surg, New York, NY 10021 USA. NCI, Div Canc Prevent, Bethesda, MD 20892 USA. RP Dannenberg, AJ (reprint author), New York Presbyterian Cornell, Room F-206,525 E 68th St, New York, NY 10021 USA. EM ajdannen@med.cornell.edu FU NCI NIH HHS [1 R01 CA82578, N01-CN-35107, P01 CA106451] NR 37 TC 37 Z9 39 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2005 VL 65 IS 13 BP 5982 EP 5988 DI 10.1158/0008-5472.CAN-05-0628 PG 7 WC Oncology SC Oncology GA 940SR UT WOS:000230165000064 PM 15994978 ER PT J AU Tsurutani, J Castillo, SS Brognard, J Granville, CA Zhang, CY Gills, JJ Sayyah, J Dennis, PA AF Tsurutani, J Castillo, SS Brognard, J Granville, CA Zhang, CY Gills, JJ Sayyah, J Dennis, PA TI Tobacco components stimulate Akt-dependent proliferation and NF kappa B-dependent survival in lung cancer cells SO CARCINOGENESIS LA English DT Article ID NICOTINIC ACETYLCHOLINE-RECEPTORS; KINASE ACTIVATION; CIGARETTE-SMOKING; INDUCED APOPTOSIS; EPITHELIAL-CELLS; GROWTH-FACTOR; NECK-CANCER; EXPRESSION; CARCINOMA; PATHWAY AB Retrospective studies have shown that patients with tobacco-related cancers who continue to smoke after their diagnoses have lower response rates and shorter median survival compared with patients who stop smoking. To provide insight into the biologic basis for these clinical observations, we tested whether two tobacco components, nicotine or the tobacco-specific carcinogen, 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK), could activate the Akt pathway and increase lung cancer cell proliferation and survival. Nicotine or NNK, rapidly and potently, activated Akt in non-small cell lung cancer (NSCLC) or small cell lung cancer (SCLC) cells. Nicotinic activation of Akt increased phosphorylation of multiple downstream substrates of Akt in a time-dependent manner, including GSK-3, FKHR, tuberin, mTOR and S6K1. Since nicotine or NNK bind to cell surface nicotinic acetylcholine receptors (nAchR), we used RT-PCR to assess expression of nine alpha and three beta nAchR subunits in five NSCLC cell lines and two types of primary lung epithelial cells. NSCLC cells express multiple nAchR subunits in a cell line-specific manner. Agonists of alpha 3/alpha 4 or alpha 7 subunits activated Akt in a time-dependent manner, suggesting that tobacco components utilize these subunits to activate Akt. Cellular outcomes after nicotine or NNK administration were also assessed. Nicotine or NNK increased proliferation of NSCLC cells in an Akt-dependent manner that was closely linked with changes in cyclin D1 expression. Despite similar induction of proliferation, only nicotine decreased apoptosis caused by serum deprivation and/or chemotherapy. Protection conferred by nicotine was NF kappa B-dependent. Collectively, these results identify tobacco component-induced, Akt-dependent proliferation and NF kappa B-dependent survival as cellular processes that could underlie the detrimental effects of smoking in cancer patients. C1 NCI, Canc Therapeut Branch, Ctr Canc Res, Bethesda, MD 20889 USA. RP Dennis, PA (reprint author), Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM pdennis@nih.gov NR 50 TC 184 Z9 193 U1 0 U2 12 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUL PY 2005 VL 26 IS 7 BP 1182 EP 1195 DI 10.1093/carcin/bgi072 PG 14 WC Oncology SC Oncology GA 947MA UT WOS:000230648600003 PM 15790591 ER PT J AU Nowotny, M Gaidamakov, SA Crouch, RJ Yang, W AF Nowotny, M Gaidamakov, SA Crouch, RJ Yang, W TI Crystal structures of RNase H bound to an RNA/DNA hybrid: Substrate specificity and metal-dependent catalysis SO CELL LA English DT Article ID HIV-1 REVERSE-TRANSCRIPTASE; COLI RIBONUCLEASE HI; SINGLE ACTIVE-SITE; ESCHERICHIA-COLI; 3-DIMENSIONAL STRUCTURE; SYNAPTIC COMPLEX; POLYPURINE TRACT; SLICER ACTIVITY; DNA; TRANSPOSITION AB RNase H belongs to a nucleotidyl-transferase superfamily, which includes transposase, retroviral integrase, Holliday junction resolvase, and RISC nuclease Argonaute. We report the crystal structures of RNase H complexed with an RNA/DNA hybrid and a mechanism for substrate recognition and two-metal-ion-dependent catalysis. RNase H specifically recognizes the A form RNA strand and the B form DNA strand. Structure comparisons lead us to predict the catalytic residues of Argonaute and conclude that two-metal-ion catalysis is a general feature of the superfamily. In nucleases, the two metal ions are asymmetrically coordinated and have distinct roles in activating the nucleophile and stabilizing the transition state. In transposases, they are symmetrically coordinated and exchange roles to alternately activate a water and a 3'-OH for successive strand cleavage and transfer by a ping-pong mechanism. C1 NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. RP Yang, W (reprint author), NIDDKD, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. EM wei.yang@nih.gov RI Yang, Wei/D-4926-2011 OI Yang, Wei/0000-0002-3591-2195 NR 46 TC 327 Z9 335 U1 9 U2 29 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 0092-8674 J9 CELL JI Cell PD JUL 1 PY 2005 VL 121 IS 7 BP 1005 EP 1016 DI 10.1016/j.cell.2005.04.024 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 944RZ UT WOS:000230448000008 PM 15989951 ER PT J AU To, KKW Koshiji, M Hammer, S Huang, LE AF To, KKW Koshiji, M Hammer, S Huang, LE TI Genetic instability - The dark side of the hypoxic response SO CELL CYCLE LA English DT Article DE cell proliferation; hypoxia; HIF-1 alpha; Myc; mismatch repair; oxygen homeostasis; p21(cip1) ID DNA MISMATCH REPAIR; INDUCIBLE FACTOR-I; HIF-1-ALPHA; HIF-1; BINDING; ADAPTATION; EXPRESSION; P300/CBP; PROTEIN; TARGET AB Under low oxygen tension, the activated transcription factor HIF-1 alpha upregulates an array of hypoxia-inducible genes via heterodimerization with ARNT and binding to the hypoxia-responsive element in the promoter. Alternatively, HIF-1 alpha regulates hypoxia-responsive genes by functionally antagonizing the oncoprotein Myc via protein-protein interactions. This so-called HIF-1 alpha-Myc mechanism apparently not only accounts for the gene upregulation, but also for the gene downregulation during hypoxia, depending upon the activating and repressive nature of Myc in gene expression. Indeed, our recent study demonstrated that both mismatch repair genes, MSH2 and MSH6, are inhibited by this mechanism in a p53-dependent manner. In particular, the constitutively bound transcription factor Sp1 serves as a molecular switch by recruiting HIF-1 alpha in hypoxia to displace the transcription activator Myc from the promoter. Therefore, our findings shed light on the mechanisms underlying hypoxia-induced genetic instability, an "adverse" effect of the hypoxic response, and yet a germane process to tumor survival and progression. C1 NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. RP Huang, LE (reprint author), NCI, Human Carcinogenesis Lab, NIH, Bldg 37,Room 3044B,37 Convent Dr, Bethesda, MD 20892 USA. EM huange@mail.nih.gov RI To, Kenneth /M-4500-2013 OI To, Kenneth /0000-0003-2755-0283 NR 23 TC 25 Z9 25 U1 0 U2 4 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUL PY 2005 VL 4 IS 7 BP 881 EP 882 DI 10.4161/cc.4.7.1839 PG 2 WC Cell Biology SC Cell Biology GA 952EX UT WOS:000230986600009 PM 15970707 ER PT J AU Basu, MK Koonin, EV AF Basu, MK Koonin, EV TI Evolution of eukaryotic cysteine sulfinic acid reductase, sulfiredoxin (Srx), from bacterial chromosome partitioning protein ParB SO CELL CYCLE LA English DT Article DE oxidative stress; peroxiredoxins; sulfiredoxin; chromosome partitioning; horizontal gene transfer ID UNIT-COPY MINIPLASMIDS; BACILLUS-SUBTILIS; ESCHERICHIA-COLI; ACTIVE-SITE; SEGREGATION PROTEIN; DAUGHTER CELLS; DNA-BINDING; PEROXIREDOXINS; SEQUENCE; SPO0J AB Sufiredoxin (Srx) is a sulfinic acid reductase, a recently identified eukaryotic enzyme, which is involved in the reduction of the hyperoxidized sulfinic acid form of the catalytic cysteine of 2-Cys peroxiredoxins (Prx). This reaction contributes to the oxidative stress response and H2O2 mediated signaling. We show that Srx has significant sequence and structural similarity to a functionally unrelated protein, ParB, a DNA-binding protein with a helix-turn-helix (HTH) domain which is involved in chromosome partitioning in bacteria. Sequence comparison and phylogenetic analysis of the Srx and ParB protein families suggest that Srx evolved via truncation of ParB, which removed the entire C-terminal half of the protein, including the HTH domain, and a substitution of cysteine for a glutamic acid in a highly conserved structural motif of ParB. The latter substitution apparently created the sulfinic acid reductase catalytic site. Evolution of a redox enzyme from a DNA-binding protein, with retention of highly significant sequence similarity, is unusual, even when compared to functional switches accompanying recruitment of other prokaryotic proteins for new functions in eukaryotes. C1 Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Koonin, EV (reprint author), Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM koonin@ncbi.nlm.nih.gov NR 38 TC 14 Z9 15 U1 1 U2 2 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUL PY 2005 VL 4 IS 7 BP 947 EP 952 DI 10.4161/cc.4.7.1786 PG 6 WC Cell Biology SC Cell Biology GA 952EX UT WOS:000230986600021 PM 15917647 ER PT J AU Chua, KF Mostoslavsky, R Lombard, DB Pang, WW Saito, S Franco, S Kaushal, D Cheng, HL Fischer, MR Stokes, N Murphy, MM Appella, E Alt, FW AF Chua, KF Mostoslavsky, R Lombard, DB Pang, WW Saito, S Franco, S Kaushal, D Cheng, HL Fischer, MR Stokes, N Murphy, MM Appella, E Alt, FW TI Mammalian SIRT1 limits replicative life span in response to chronic genotoxic stress SO CELL METABOLISM LA English DT Article ID ARF TUMOR-SUPPRESSOR; DOUBLE-STRAND BREAKS; CELLULAR SENESCENCE; TRANSCRIPTION FACTORS; PREMATURE SENESCENCE; CALORIE RESTRICTION; ONCOGENIC RAS; GENE-PRODUCT; G(1) CONTROL; INK4A LOCUS AB The Saccharomyces cerevisiae chromatin silencing factor Sir2 suppresses genomic instability and extends replicative life span. In contrast, we find that mouse embryonic fibroblasts (MEFs) deficient for SIRT1, a mammalian Sir2 homolog, have dramatically increased resistance to replicative senescence. Extended replicative life span of SIRT1-deficient MEFs correlates with enhanced proliferative capacity under conditions of chronic, sublethal oxidative stress. In this context, SIRT1-deficient cells fail to normally upregulate either the p19(ARF) senescence regulator or its downstream target p53. However, upon acute DNA damage or oncogene expression, SIRT1-deficient cells show normal p19(ARF) induction and cell cycle arrest. Together, our findings demonstrate an unexpected SIRT1 function in promoting replicative senescence in response to chronic cellular stress and implicate p19(ARF) as a downstream effector in this pathway. C1 Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst,CBR Inst Biomed Res, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. RP Alt, FW (reprint author), Harvard Univ, Sch Med, Childrens Hosp, Howard Hughes Med Inst,CBR Inst Biomed Res, Boston, MA 02115 USA. EM alt@enders.tch.harvard.edu NR 64 TC 172 Z9 188 U1 0 U2 9 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1550-4131 J9 CELL METAB JI Cell Metab. PD JUL PY 2005 VL 2 IS 1 BP 67 EP 76 DI 10.1016/j.cmet.2005.06.007 PG 10 WC Cell Biology; Endocrinology & Metabolism SC Cell Biology; Endocrinology & Metabolism GA 949EJ UT WOS:000230767400010 PM 16054100 ER PT J AU Brik, A Alexandratos, J Lin, YC Elder, JH Olson, AJ Wlodawer, A Goodsell, DS Wong, CH AF Brik, A Alexandratos, J Lin, YC Elder, JH Olson, AJ Wlodawer, A Goodsell, DS Wong, CH TI 1,2,3-triazole as a peptide surrogate in the rapid synthesis of HIV-1 protease inhibitors SO CHEMBIOCHEM LA English DT Article DE click chemistry; inhibitors; peptidomimetics; triazole ID TERMINAL ALKYNES; AZIDES AB Substitute for another bond. Docking simulations of two potent inhibitors that bear the 1,2,3-triazole moiety produced two conformations of approximately equal energy. Further analysis of the protease by X-ray crystallography solved the ambiguity of the binding mode and revealed that the triazole ring is an effective amide surrogate and retains all the hydrogen bonds in the active site (see figure). C1 Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA. NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA. RP Wong, CH (reprint author), Scripps Res Inst, Dept Chem, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM wlodawer@ncifcrf.gov; goodsell@scripps.edu; wong@scripps.edu RI Brik, Ashraf/F-1583-2012 NR 13 TC 183 Z9 185 U1 5 U2 28 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1439-4227 J9 CHEMBIOCHEM JI Chembiochem PD JUL PY 2005 VL 6 IS 7 BP 1167 EP + DI 10.1002/cbic.200500101 PG 4 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 943UW UT WOS:000230381200003 PM 15934050 ER PT J AU Mixides, G Shende, V Teeter, LD Awe, R Musser, JM Graviss, EA AF Mixides, G Shende, V Teeter, LD Awe, R Musser, JM Graviss, EA TI Number of negative acid-fast smears needed to adequately assess infectivity of patients with pulmonary tuberculosis SO CHEST LA English DT Article DE infectivity; sputum smear; transmission; tuberculin; tuberculosis ID MULTIDRUG-RESISTANT TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; FIBEROPTIC BRONCHOSCOPY; SPUTUM SPECIMENS; UNITED-STATES; FAST BACILLI; TRANSMISSION; DIAGNOSIS; HIV; CONTACTS AB Study objectives: To investigate the relationship between the number of negative acid-fast bacilli (AFB) smear results and infectivity of pulmonary tuberculosis (TB). Design: Retrospective analysis. Methods and subjects: We examined 122 index cases in Harris County, TX, reported in 199S and 1999. All cases had only negative AFB smear results during the infectious period and were categorized in two groups: group A consisted of cases with only one or two sputum specimens collected and processed, and group B consisted of cases with at least three sputum specimens or at least one bronchoscopic specimen. Tuberculin skin test (TST) results of contacts were ascertained from the results of contact investigations performed by the City of Houston Department of Health and Human Services, Tuberculosis Control Division. Univariate and multivariate analyses were done to explore index case and contact attributes associated with tuberculosis (TB) transmission using positive TST results of contacts as a measure of recent transmission. Results: We found male gender and younger age of index cases along with Hispanic ethnicity of contacts to be independently associated with positive TST results, while younger contacts were less likely to be TST positive. Smear category of the index case (group A vs group B) was not independently associated with transmission. We also found that the first two sputum specimens in cases where three or more were performed yielded 90% of all positive culture results for Mycobacterium tuberculosis (MTB). Conclusions: We conclude that two sputum specimens negative for AFB stain are adequate for both assessing infectivity and for isolating MTB from patients with pulmonary TB. C1 Baylor Coll Med, Dept Pathol, Houston, TX 77030 USA. Baylor Coll Med, Dept Internal Med, Pulm & Crit Care Med Sect, Houston, TX 77030 USA. NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT USA. RP Graviss, EA (reprint author), Baylor Coll Med, Dept Pathol, 1 Baylor Plaza, Houston, TX 77030 USA. EM egraviss@bcm.tmc.edu FU NIAID NIH HHS [N01 AO 02738]; NIDA NIH HHS [DA 09238] NR 43 TC 8 Z9 8 U1 1 U2 1 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD JUL PY 2005 VL 128 IS 1 BP 108 EP 115 DI 10.1378/chest.128.1.108 PG 8 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 945VN UT WOS:000230530500021 PM 16002923 ER PT J AU Yazici, Y Erkan, D Harrison, MJ Nikolov, NP Paget, SA AF Yazici, Y Erkan, D Harrison, MJ Nikolov, NP Paget, SA TI Methotrexate use in rheumatoid arthritis is associated with few clinically significant liver function test abnormalities SO CLINICAL AND EXPERIMENTAL RHEUMATOLOGY LA English DT Article DE methotrexate; rheumatoid arthritis; liver function test; hepatic toxicity; monitoring guidelines ID LOW-DOSE METHOTREXATE; DOUBLE-BLIND; EFFICACY; GUIDELINES; TOXICITY; THERAPY; PLACEBO; UPDATE; TRIAL AB Objective. To determine the frequency of liver function tests (LFT) abnormalities associated with methotrexate (MTX) use in the treatment of rheumatoid arthritis (RA). Methods. A retrospective chart review for demographic information, RA-specific history, medication history, complications of therapy, results of all available blood tests (specifically aspartate amino-transferase (AST), alanine amino-transferase (ALT),complete blood count (CBC), albumin, creatinine), and liver biopsy reports was conducted for RA patients, who were currently using or have used MTX in the past. Results. A total of 2 791 LFTs were performed among 182 RA patients with 94 abnormal results. 152 patients (83.5%) with 2007 LFT evaluations demonstrated no abnormal results, compared with 30 patients (16.5%) who had at least one abnormal LFT in 784 tests. Twenty-two of the 30 patients with at least one LFT abnormality (73.3%) continued treatment despite the elevation without further evaluation or change in therapy, and subsequent LFT assessments were within normal limits. 128 patients (70.3%) remained on MTX at the time of our study The most common reason for discontinuation was inadequate response. Conclusions. MTX appears to be associated with very few clinically significant hepatic side effects. In view of these data, consideration as to revision of the current MTX monitoring guidelines in the direction of less frequent monitoring, especially in patients with no risk factors for liver disease, may be considered. C1 Cornell Univ, Weill Med Coll, Hosp Special Surg, Ithaca, NY 14853 USA. NYU, Hosp Joint Dis, New York, NY USA. NIAMS, IRP, OCD, DHHS,NIH, Bethesda, MD USA. RP Yazici, Y (reprint author), 515 E 72nd St 29E, New York, NY 10021 USA. EM yaziciy@yahoo.com NR 18 TC 15 Z9 15 U1 0 U2 2 PU CLINICAL & EXPER RHEUMATOLOGY PI PISA PA VIA SANTA MARIA 31, 56126 PISA, ITALY SN 0392-856X J9 CLIN EXP RHEUMATOL JI Clin. Exp. Rheumatol. PD JUL-AUG PY 2005 VL 23 IS 4 BP 517 EP 520 PG 4 WC Rheumatology SC Rheumatology GA 951GO UT WOS:000230917700014 PM 16095122 ER PT J AU Titus, MA Schell, MJ Lih, FB Tomer, KB Mohler, JL AF Titus, MA Schell, MJ Lih, FB Tomer, KB Mohler, JL TI Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ANDROGEN DEPRIVATION THERAPY; RECEPTOR GENE; ENDOCRINE-THERAPY; AMPLIFICATION; BICALUTAMIDE; PROGRESSION; METABOLISM; EXPRESSION; METASTASES; PROTEIN AB Purpose: Prostate cancer eventually recurs during androgen deprivation therapy despite castrate levels of serum androgens. Expression of androgen receptor and androgen receptor-regulated proteins suggests androgen receptor activation in recurrent prostate cancer. Many groups have pursued mechanisms of ligand-independent androgen receptor activation but we found high levels of testicular androgens in recurrent prostate cancer tissue using RIA. Experimental Designs: Prostate specimens from 36 men were procured preserving blood flow to prevent ischemia and cyropreserved immediately. Recurrent prostate cancer specimens from 18 men whose cancer recurred locally during androgen deprivation therapy and androgen-stimulated benign prostate specimens from 18 men receiving no hormonal treatments were studied. Tissue levels of testosterone and dihydrotestosterone were measured in each specimen using liquid chromatography/electrospray tandem mass spectrometry.Testosterone and dihydrotestosterone levels were compared with clinical variables and treatment received. Results: Testosterone levels were similar in recurrent prostate cancer (3.75 pmol/g tissue) and androgen-stimulated benign prostate (2.75 pmol/g tissue, Wilcoxon two-sided, P = 0.30). Dihydrotestosterone levels decreased 91 % in recurrent prostate cancer (1.25 pmol/g tissue) compared with androgen-stimulated benign prostate (13.7 pmol/g tissue; Wilcoxon two-sided, P < 0.0001) although dihydrotestosterone levels in most specimens of recurrent prostate cancer were sufficient for androgen receptor activation. Testosterone or dihydrotestosterone levels were not related to metastatic status, antiandrogen treatment, or survival (Wilcoxon rank sum, all P > 0.2). Conclusions: Recurrent prostate cancer may develop the capacity to biosynthesize testicular androgens from adrenal androgens or cholesterol. This surprising finding suggests intracrine production of dihydrotestosterone and should be exploited for novel treatment of recurrent prostate cancer. C1 Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Surg, Chapel Hill, NC 27599 USA. Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Biostat, Chapel Hill, NC 27599 USA. Natl Inst Environm Hlth Sci, Struct Biol Lab, Res Triangle Pk, NC USA. Roswell Pk Canc Inst, Dept Urol Oncol, Buffalo, NY 14263 USA. SUNY Buffalo, Sch Med & Biotechnol, Dept Urol, Buffalo, NY 14260 USA. RP Titus, MA (reprint author), Univ N Carolina, Sch Med, Lineberger Comprehens Canc Ctr, Dept Pathol & Lab Med, Chapel Hill, NC 27599 USA. EM matitus@med.unc.edu RI Tomer, Kenneth/E-8018-2013 FU NCI NIH HHS [CA-77739] NR 31 TC 322 Z9 327 U1 0 U2 8 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 JUL 1 PY 2005 VL 11 IS 13 BP 4653 EP 4657 DI 10.1158/1078-0432.CCR-05-0525 PG 5 WC Oncology SC Oncology GA 944BQ UT WOS:000230400300005 PM 16000557 ER PT J AU Mielke, S Sparreboom, A Steinberg, SM Gelderblom, H Unger, C Behringer, D Mross, K AF Mielke, S Sparreboom, A Steinberg, SM Gelderblom, H Unger, C Behringer, D Mross, K TI Association of paclitaxel pharmacokinetics with the development of peripheral neuropathy in patients with advanced cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID METASTATIC BREAST-CANCER; HIGH-DOSE PACLITAXEL; ONE-HOUR PACLITAXEL; BODY-SURFACE AREA; PHASE-II TRIAL; CREMOPHOR EL; LUNG-CANCER; NONLINEAR PHARMACOKINETICS; COMBINATION CHEMOTHERAPY; RANDOMIZED-TRIAL AB Purpose:The shortening of infusion time from 3 to 1 hour decreases the systemic exposure (area under the curve, AUC) of total and unbound paclitaxel but increases the AUC of its vehicle Cremophor EL, whereas the time above total paclitaxel concentrations of 0.05 mu mol/L (T-> 0.05) remains almost constant. As both Cremophor EL and paclitaxel are neurotoxic, we evaluated their pharmacodynamic effects on the development of peripheral neuropathy as the most important nonhematologic toxicity. Experimental Design: Patients with advanced cancer of different origin were randomized to receive a maximum of 12 weekly-given 1- or 3-hour infusions of 100 mg/m(2) paclitaxel (Taxol). Twenty-four patients were assessable for both pharmacokinetics and peripheral neuropathy development evaluated by a clinical scoring system including sensory symptoms, strength, tendon reflexes, and vibratory sense. Results: Patients with peripheral neuropathy development (n = 14) received more weeks of therapy (P = 0.056) and showed significantly higher T-> 0.05 (P = 0.022) and overall systemic drug exposures (weeks of therapy x AUC) for total paclitaxel (P = 0.002) and unbound paclitaxel (P = 0.003) than those without peripheral neuropathy. In Kaplan-Meier analyses, T-> 0.05 >= 10.6 hours (P = 0.023), AUC of total paclitaxel >= 4.7 mu g/mL x hour (P = 0.047), and AUC of unbound paclitaxel >= 0.375 mu g/mL x hour (P = 0.095) were identified as being potential factors for peripheral neuropathy development. In a Cox regression analysis, only T-> 0.05 >= 10.6 hours remained as an independent risk factor (relative risk, 18.43; P = 0.036) after adjusting for prior vincamycin (relative risk, 11.28; P = 0.038). Conclusions: From the results obtained in this study, it is concluded that exposure to paclitaxel but not Cremophor EL is associated with peripheral neuropathy development. C1 Univ Freiburg, Med Ctr, Dept Hematol & Oncol, D-7800 Freiburg, Germany. Univ Freiburg, Tumor Biol Ctr, Freiburg, Germany. NCI, Ctr Canc Res, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Clin Pharmacol Res Core, Bethesda, MD 20892 USA. Dr Daniel Den Hoed Canc Ctr, Dept Med Oncol, Erasmus MC, NL-3008 AE Rotterdam, Netherlands. Leiden Univ, Med Ctr, Dept Med Oncol, Leiden, Netherlands. RP Mielke, S (reprint author), NHLBI, Stem Cell Allogen Transplant Sect, Hematol Branch, DIR,NIH, Bldg 10 CRC, Room 3-5288,10 Ctr Dr,MSC 1202, Bethesda, MD 20892 USA. EM mielkes@nhlbi.nih.gov RI Sparreboom, Alex/B-3247-2008 NR 39 TC 71 Z9 74 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2005 VL 11 IS 13 BP 4843 EP 4850 DI 10.1158/1078-0432.CCR-05-0298 PG 8 WC Oncology SC Oncology GA 944BQ UT WOS:000230400300030 PM 16000582 ER PT J AU Lynch, TJ Bogart, JA Curran, WJ DeCamp, MM Gandara, DR Goss, G Henschke, CI Jett Jr Johnson, BE Kelly, KL Le Chevalier, T Mulshine, JL Scagliotti, GV Schiller, JH Shaw, A Thatcher, N Vokes, EE Wood, DE Hart, C AF Lynch, TJ Bogart, JA Curran, WJ DeCamp, MM Gandara, DR Goss, G Henschke, CI Jett, JR Johnson, BE Kelly, KL Le Chevalier, T Mulshine, JL Scagliotti, GV Schiller, JH Shaw, A Thatcher, N Vokes, EE Wood, DE Hart, C TI Early stage lung cancer - New approaches to evaluation and treatment: Conference summary statement SO CLINICAL CANCER RESEARCH LA English DT Editorial Material C1 Massachusetts Gen Hosp, Div Hematol Oncol, Boston, MA 02114 USA. Massachusetts Gen Hosp, Dana Farber Partners Canc Care, Boston, MA 02114 USA. Beth Israel Deaconess Med Ctr, Thorac Surg Sect, Boston, MA 02215 USA. Dana Farber Canc Inst, Boston, MA 02215 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. SUNY Upstate Med Univ, Dept Radiat Oncol, Syracuse, NY USA. Thomas Jefferson Univ Hosp, Dept Radiat Oncol, Philadelphia, PA 19107 USA. Univ Calif Davis, Ctr Canc, Sacramento, CA USA. Ottawa Reg Canc Ctr, Ctr Canc Therapeut, Ottawa, ON K1Y 4K7, Canada. Cornell Univ, Weill Med Coll, Dept Radiol, New York, NY USA. Mayo Clin Rochester, Thorac Dis & Med Oncol, Rochester, MN USA. Univ Colorado, Hlth Sci Ctr, Div Med Oncol, Denver, CO 80262 USA. Inst Gustave Roussy, Dept Med, Villejuif, France. NCI, Canc Res Ctr, Cell & Biol Branch, Expt Intervent Sect, Bethesda, MD 20892 USA. Univ Turin, Dept Clin & Biol Sci, S Luigi Gonzaga Hosp, Turin, Italy. Univ Wisconsin, Sch Med, Madison, WI USA. Christie Hosp NHS Trust, Dept Med Oncol, Manchester M20 4BX, Lancs, England. Univ Chicago, Med Ctr, Hematol Oncol Sect, Chicago, IL 60637 USA. Univ Washington, Div Cardiothorac Surg, Seattle, WA USA. InforMed, Narberth, PA USA. RP Lynch, TJ (reprint author), Massachusetts Gen Hosp, Div Hematol Oncol, 100 Blossom St,Cox 210, Boston, MA 02114 USA. EM tlynch@partners.org NR 0 TC 5 Z9 5 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 JUL 1 PY 2005 VL 11 IS 13 SU S BP 4981S EP 4983S DI 10.1158/1078-0432.CCR-05-9015 PG 3 WC Oncology SC Oncology GA 945JB UT WOS:000230497700001 PM 16000599 ER PT J AU Mulshine, JL AF Mulshine, JL TI Clinical issues in the management of early lung cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT International Conference on Early Stage Lung Cancer CY OCT 01-02, 2004 CL Cambridge, MA ID SPIRAL COMPUTED-TOMOGRAPHY; SMALL PULMONARY NODULES; AIDED DIAGNOSIS; ACTION PROJECT; TUMOR SIZE; FOLLOW-UP; CT; CARCINOMA; SURVIVAL; SMOKERS AB Lung cancer is commonly diagnosed after metastatic spread, when therapies are rarely curative, providing an impetus for continued research directed at exploring approaches for cost-effective early lung cancer detection. Recently published pilot studies across three continents support a benefit of spiral computed tomography (CT) in detecting earlier stage non - small cell lung cancer. Improved resolution of early lung cancer is a result of significant changes in CT imaging hardware and software. The status and implications of these developments are reviewed. Many aspects of the management of screening for early lung cancer could be informed by optimizing the downstream clinical management of potential lung cancers identified by CT screening. The first and most critical issue is whether or not this improved detection rate is clearly associated with a reduction in lung cancer-related mortality. However, other related issues such as cost-benefit evaluations are also considered. If smaller, truly localized primary cancer can be routinely detected, then options for less morbid interventions would also be desirable. The rapid improvement in resolution and cost of spiral CT has provided a powerful impetus to reconsider the possibilities for achieving safe, economical, and meaningful early lung cancer detection. C1 NCI, Cell & Canc Biol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Mulshine, JL (reprint author), NCI, Cell & Canc Biol Branch, Ctr Canc Res, 9000 Rockville Pike,Bldg 10,Room 12N226, Bethesda, MD 20892 USA. EM mulshinej@bprb.nci.nih.gov NR 43 TC 8 Z9 8 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUL 1 PY 2005 VL 11 IS 13 SU S BP 4993S EP 4998S DI 10.1158/1078-0432.CCR-05-9011 PG 6 WC Oncology SC Oncology GA 945JB UT WOS:000230497700004 PM 16000602 ER PT J AU Trombino, S Neri, M Puntoni, R Angelini, C Loprevite, M Cesario, A Granone, P Imperatori, A Dominioni, L Ardizzoni, A Filiberti, R Russo, P AF Trombino, S Neri, M Puntoni, R Angelini, C Loprevite, M Cesario, A Granone, P Imperatori, A Dominioni, L Ardizzoni, A Filiberti, R Russo, P TI Mutations in K-ras codon 12 detected in plasma DNA are not an indicator of disease in patients with non-small cell lung cancer SO CLINICAL CHEMISTRY LA English DT Letter ID INFLAMMATORY-BOWEL-DISEASE; METHYLATION PATTERNS; PAIRED SERUM; TUMOR C1 Natl Canc Inst, Dept Integrated Med Oncol DOMI, Unit Translat Res B Lung Canc, I-146132 Genoa, Italy. Natl Canc Inst, Dept Integrated Med Oncol DOMI, Unit Epidemiol & Biostat, I-146132 Genoa, Italy. Natl Canc Inst, Dept Integrated Med Oncol DOMI, Unit Med Oncol A, I-146132 Genoa, Italy. Natl Canc Inst, Dept Integrated Med Oncol DOMI, Unit Mol Epidemiol, I-146132 Genoa, Italy. Univ Genoa, Dept Biol, I-16126 Genoa, Italy. Univ Sacred Heart, Gen Thorac Surg, I-00168 Rome, Italy. Insubria Univ, Unit Thorac Surg, Varese, Italy. Hosp Parma, Unit Med Oncol, Parma, Italy. IRCCS, Translat & Clin Resp Pathol Lab, Rome, Italy. RP Russo, P (reprint author), Natl Canc Inst, Dept Integrated Med Oncol DOMI, Unit Translat Res B Lung Canc, Largo Rosanna Benzi 10, I-146132 Genoa, Italy. EM patrizia.russo@istge.it RI CESARIO, Alfredo/O-4215-2015; Neri, Monica/J-6308-2012 OI CESARIO, Alfredo/0000-0003-4687-0709; Neri, Monica/0000-0003-4796-3675 NR 13 TC 18 Z9 21 U1 0 U2 5 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUL PY 2005 VL 51 IS 7 BP 1313 EP 1314 DI 10.1373/clinchem.2004.043976 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 939VS UT WOS:000230101200054 PM 15976131 ER PT J AU Musso, C Shawker, T Cochran, E Javor, ED Young, J Gorden, P AF Musso, C Shawker, T Cochran, E Javor, ED Young, J Gorden, P TI Clinical evidence that hyperinsulinaemia independent of gonadotropins stimulates ovarian growth SO CLINICAL ENDOCRINOLOGY LA English DT Article ID LEPTIN-REPLACEMENT THERAPY; INSULIN-RESISTANCE; SEVERE LIPODYSTROPHY; NORMAL GIRLS; LEPRECHAUNISM; SECRETION; METFORMIN; WOMEN; PUBERTY; HYPERANDROGENISM AB Objective Ovarian enlargement is a constant feature of syndromes of extreme insulin resistance. The objective of this study is to show the role of insulin on ovarian growth in the presence of low gonadotropin levels. Patients Seven young patients with syndromes of extreme insulin resistance (five with lipodystrophy, one with Type B syndrome and one with Rabson-Mendenhall syndrome) were studied. Measurements Baseline LH concentrations and luteinizing hormone releasing hormone (LHRH) tests were performed. Total testosterone, insulin and C-peptide values were measured. Pelvic ultrasounds were performed. Results Four patients were prepubertal (age range 7-10 years old) and had prepubertal gonadotropin levels, and 2 of the 4 who were tested did not respond to LHRH (NIH 10 and RM-PAL). Three patients were Tanner stage 4 (age range 13-17 years old) and had low gonadotropins that did not respond to LHRH stimulation test. All seven patients had marked hyperinsulinaemia and 6 of 7 had at least one enlarged ovary. Testosterone values were increased in 4 of 7 patients. Conclusion This represents the first example of the pathologic role of insulin to stimulate ovarian growth with low circulating gonadotropins. Thus, while ovarian growth and steroidogenesis are normally stimulated by gonadotropins at puberty, hyperinsulinaemia stimulates pathologic growth of the ovary and an androgenic steroid profile that is active at all ages. We suggest that these patients constitute a model to separate the effect of insulin from gonadotropin in stimulating ovarian growth and/or steroidogenesis. C1 NIDDK, CEB, NIH, Bethesda, MD 20892 USA. NIH, Dept Radiol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Gorden, P (reprint author), NIDDK, CEB, NIH, 9000 Rockville Pike,Bldg 10,Rm 6 W-5-940, Bethesda, MD 20892 USA. EM carlam@intra.niddk.nih.gov; PhillipG@intra.niddk.nih.gov NR 38 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0300-0664 J9 CLIN ENDOCRINOL JI Clin. Endocrinol. PD JUL PY 2005 VL 63 IS 1 BP 73 EP 78 DI 10.1111/j.1365-2265.2005.02302.x PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 937GO UT WOS:000229912800012 PM 15963065 ER PT J AU Peters, KF Apse, KA Blackford, A McHugh, B Michalic, D Biesecker, BB AF Peters, KF Apse, KA Blackford, A McHugh, B Michalic, D Biesecker, BB TI Living with Marfan syndrome: coping with stigma SO CLINICAL GENETICS LA English DT Article DE coping; discrimination; genetic counseling; group identity; Marfan syndrome; stigma; support group ID QUALITY-OF-LIFE; GENETIC DISCRIMINATION; PERCEPTIONS; INFORMATION; COMMUNITY AB Social stigmatization can disrupt the ability of individuals with genetic conditions to successfully adapt to their situation. We offer data on perceptions of stigma from a cross-sectional survey of 174 adults with Marfan syndrome by self-report. Fifty-six respondents (32%) reported feeling discriminated against or socially devalued because of having Marfan syndrome. Endorsement of discrimination was significantly correlated with having depressive symptoms, low self-esteem, the view Marfan syndrome has had significant negative consequences on one's life, striae, and perceptions of workplace discrimination. Nearly 30% of respondents reported withdrawing from social situations that they anticipated would lead to feeling stigmatized, and 25% reported electing to keep their condition secret in potentially stigmatizing situations. Over 50% of respondents reported educating others about Marfan syndrome as a means of coping with their feelings of stigma, and endorsement of education was correlated with viewing involvement in the National Marfan Foundation as important. Instances of workplace discrimination were perceived by 20% of respondents, and 23% reported that they remained in a dissatisfying job due to having Marfan syndrome. Genetics professionals should actively engage patients with Marfan syndrome in discussions about social stigmatization and encourage use of coping strategies aimed at enhancing quality of life. C1 Penn State Univ, Ctr Dev & Hlth Genet, University Pk, PA 16802 USA. Penn State Univ, Dept Biobehav Hlth, University Pk, PA 16802 USA. NHGRI, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Div Neurogenet, Boston, MA 02215 USA. Johns Hopkins Sch Med, Div Biostat, Dept Oncol, Baltimore, MD USA. Penn State Univ, Dept Stat, Ctr Stat Consulting, University Pk, PA 16802 USA. NHGRI, Social Behav Res Branch, NIH, Bethesda, MD 20892 USA. RP Peters, KF (reprint author), Penn State Univ, Ctr Dev & Hlth Genet, 101 Amy Gardner House, University Pk, PA 16802 USA. EM kfp1@psu.edu FU Intramural NIH HHS NR 37 TC 30 Z9 31 U1 1 U2 10 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JUL PY 2005 VL 68 IS 1 BP 6 EP 14 DI 10.1111/j.1399-0004.2005.00446.x PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 932YI UT WOS:000229590300002 PM 15952980 ER PT J AU Griffin, AE Cobb, BR Anderson, PD Claassen, DA Helip-Wooley, A Huizing, M Gahl, WA AF Griffin, AE Cobb, BR Anderson, PD Claassen, DA Helip-Wooley, A Huizing, M Gahl, WA TI Detection of hemizygosity in Hermansky-Pudlak syndrome by quantitative real-time PCR SO CLINICAL GENETICS LA English DT Article DE breakpoint; C10orf33; genomic insertion/deletion; hemizygosity; Hermansky-Pudlak syndrome; real-time quantitative PCR ID LYSOSOME-RELATED ORGANELLES; PULMONARY-FIBROSIS; GENE; MUTATIONS; HPS4; BIOGENESIS; PROTEINS; COMPLEX; BLOC-3; FORM AB Hermansky - Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, a bleeding diathesis and, in some patients, pulmonary fibrosis or granulomatous colitis. HPS is associated with biosynthesis defects of melanosomes, platelet-dense bodies, and lysosomes. There are seven genetic HPS subtypes; HPS-1 is the most common. We used a real-time quantitative PCR (qPCR) approach to investigate six HPS-1 patients, previously assigned as having homozygous mutations in the HPS1 gene. HPS1 gene copy numbers, calculated by use of a comparative Ct method, revealed that one patient was in fact hemizygous for her c.1189delC (S396delC) HPS1 mutation. The causative deletion/insertion was 13,966 bp in size, with defined breakpoints, and involved an adjacent gene (C10orf33). A mechanism of formation is proposed for the deletion/insertion, and both multiplex and qPCR indicated that the deletion/insertion was present in the patient, her brother, and her father. qPCR amplification is valuable for detecting deletions too small to be identified by fluorescence in situ hybridization. This demonstration of hemizygosity, performed using genomic DNA, can eliminate concerns about non-paternity and can verify the diagnosis of an autosomal recessive disorder when a DNA alteration appears to be homozygous by standard PCR and sequencing methods, and its pathogenicity is in doubt. C1 NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NIH, Off Rare Dis, Intramural Program, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, 10 Ctr Dr,MSC 1851,Bldg 10,Room 10C-103, Bethesda, MD 20892 USA. EM bgahl@helix.nih.gov NR 32 TC 4 Z9 6 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JUL PY 2005 VL 68 IS 1 BP 23 EP 30 DI 10.1111/j.1399-0004.2005.00461.x PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 932YI UT WOS:000229590300004 PM 15952982 ER PT J AU Hamed, SA Sutherland-Smith, AJ Gorospe, JRM Kendrick-Jones, J Hoffman, EP AF Hamed, SA Sutherland-Smith, AJ Gorospe, JRM Kendrick-Jones, J Hoffman, EP TI DNA sequence analysis for structure/function and mutation studies in Becker muscular dystrophy SO CLINICAL GENETICS LA English DT Article DE actin-binding domain; Becker muscular dystrophy; dystrophin; dystrophin point mutations; quantitative multiplex fluorescence polymerase chain reaction ID ACTIN-BINDING DOMAIN; TRANSGENIC MDX MICE; TERMINAL DOMAINS; POINT MUTATIONS; FULL-LENGTH; DMD GENE; F-ACTIN; DUCHENNE; PROTEIN; DEFICIENCY AB We systematically screened the whole coding region of 18 male muscular dystrophy patients whose clinical, histological and laboratory findings suggest Becker muscular dystrophy (present but abnormal dystrophin). No systematic mutation study of a cohort of patients with dystrophin of normal quality but abnormal quantity has been published. The complete coding sequence of the dystrophin gene (11 kb) of each patient was subjected to an automated sequence analysis by using muscle biopsy RNA; 535 bp of the gene promoter and 5'UTR were likewise sequenced. We identified seven disease-causing mutations (40%). Six were novel, including missense, nonsense, small deletion and splice site mutations. Sixty percent (11/18) of patients with decreased quantities of normal molecular weight dystrophin showed no mutation, but most of them had a family history highly suggestive of X-linked inheritance, suggesting transcription or translational deleterious affection, i.e. outside what was screened. Quantitative multiplex fluorescence polymerase chain studies of mutation-negative patients showed normal levels of dystrophin mRNA. In three patients, there was some reduction of the transcript suggesting a deleterious undetected gene change resulted in the reduction of RNA levels. Our data address important structure/function and genotype/phenotype correlations and it suggests that dystrophin protein studies must be interpreted with caution in deletion-negative male muscular dystrophy patients. C1 Childrens Natl Med Ctr, Res Ctr Genet Med, Washington, DC 20010 USA. George Washington Univ, Washington, DC 20052 USA. Med Res Council Lab Mol Biol, Struct Studies Div, Cambridge, England. NHGRI, NIH, Bethesda, MD 20892 USA. RP Hamed, SA (reprint author), Assiut Univ Hosp, Dept Neuropsychiat, Assiut, Egypt. EM hamed_sherifa@yahoo.com RI Sutherland-Smith, Andrew/F-1813-2011 NR 45 TC 17 Z9 20 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9163 J9 CLIN GENET JI Clin. Genet. PD JUL PY 2005 VL 68 IS 1 BP 69 EP 79 DI 10.1111/j.1399-0004.2005.00455.x PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 932YI UT WOS:000229590300011 PM 15952989 ER PT J AU Beigel, J AF Beigel, J TI The emerging utility of neopterin? SO CLINICAL IMMUNOLOGY LA English DT Editorial Material ID ACUTE-RESPIRATORY-SYNDROME; SERUM NEOPTERIN; MAJOR OUTBREAK; SYNDROME SARS; INFECTION; NECROSIS; SEPSIS; RNA C1 Warren G Magnuson Clin Ctr, Dept Crit Care Med, NIH, Bethesda, MD 20892 USA. RP Beigel, J (reprint author), Warren G Magnuson Clin Ctr, Dept Crit Care Med, NIH, Bldg 10,7D43 10 Ctr Dr,MSC 1662, Bethesda, MD 20892 USA. EM jbeigel@mail.nih.gov RI Beigel, John/A-7111-2009 NR 25 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 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PD JUL PY 2005 VL 116 IS 1 BP 1 EP 2 DI 10.1016/j.clim.2005.03.008 PG 2 WC Immunology SC Immunology GA 936AJ UT WOS:000229824400001 PM 15925825 ER PT J AU Khalsa, JH Kresina, T Sherman, K Vocci, F AF Khalsa, JH Kresina, T Sherman, K Vocci, F TI Medical management of HIV - Hepatitis C virus coinfection in injection drug users SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID LIVER-DISEASE; INFECTION; THERAPY AB Several million people inject drugs of abuse and, as a result, are coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV). The treatment of this coinfected drug-abusing population is fraught with many problems such that clinicians and other health care providers have to determine whether patients should be treated first for drug addiction, for HIV/AIDS, or for HCV infection or simultaneously treated. These proceedings present the incidence and prevalence of coinfections with HIV and HCV in high-risk populations and discuss the underlying pathophysiology of coinfections and the problems and strategies of managing the treatment of coinfections among people who also inject illicit drugs. In addition, the expert panel recommended further research to determine the best possible treatment regimens applicable to injection drug users coinfected with HIV and HCV. C1 NIDA, Med Consequences Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. Univ Cincinnati, Coll Med, Div Digest Dis, Cincinnati, OH USA. RP Khalsa, JH (reprint author), NIDA, Med Consequences Branch, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, 6001 Execut Blvd,Rm 5198,MSC 9593, Bethesda, MD 20892 USA. EM jk98p@nih.gov NR 39 TC 7 Z9 7 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2005 VL 41 SU 1 BP S1 EP S6 DI 10.1086/429488 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 932CB UT WOS:000229530700001 PM 16265605 ER PT J AU Kresina, TF Bruce, RD Cargill, VA Cheever, LW AF Kresina, TF Bruce, RD Cargill, VA Cheever, LW TI Integrating care for hepatitis C virus (HCV) and primary care for HIV for injection drug users coinfected with HIV and HCV SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; MAINTENANCE TREATMENT; URBAN-POOR; INFECTION; BUPRENORPHINE; PREVENTION; MANAGEMENT; DEPENDENCE; OPIATE AB Injection drug use accounts for most of the incident infections with hepatitis C virus (HCV) and for at least one-third of new human immunodeficiency virus (HIV) infections. Coinfection with HCV and HIV presents complex and challenging medical conditions. Ensuring access to and maintaining care for HIV and HCV for drug users presents special challenges to the health care team that require a nonjudgmental attitude, experience, and patience. Care for HCV infection, however, can be used as an instrument to engage drug-using persons in ongoing primary care relationships. Common elements to both care for HCV infection and primary care for HIV infection are testing for and counseling about HCV and HIV, substance abuse and mental health services, social support, and subspecialty referral. These elements, in particular treatment for substance abuse, can be focal points for model care systems that provide integrative care for both HCV and HIV infections. C1 NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. NIH, Off AIDS Res, Bethesda, MD 20892 USA. US Hlth Resources & Serv Adm, Dept Hlth & Human Serv, HIV AIDS Bur, Rockville, MD 20857 USA. Yale Univ, Sch Med, Yale AIDS Program, New Haven, CT USA. RP Kresina, TF (reprint author), NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Bethesda, MD 20892 USA. EM tk13v@nih.gov NR 30 TC 13 Z9 13 U1 2 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 1 PY 2005 VL 41 SU 1 BP S83 EP S88 DI 10.1086/429502 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 932CB UT WOS:000229530700015 PM 16265621 ER PT J AU Quezado, M Ronchetti, R Rapkiewicz, A Santi, M Blumenthal, DT Rushing, EJ AF Quezado, M Ronchetti, R Rapkiewicz, A Santi, M Blumenthal, DT Rushing, EJ TI Chromogenic in situ hybridization accurately identifies EGFR amplification in small cell glioblastoma multiforme, a common subtype of primary GBM SO CLINICAL NEUROPATHOLOGY LA English DT Article DE glioblastoma; small cell phenotype; CISH; EGFR ID GROWTH-FACTOR RECEPTOR; MOLECULAR-GENETIC-ANALYSIS; SECONDARY GLIOBLASTOMAS; BREAST-CANCER; EXPRESSION; GLIOMAS; MUTATIONS; PROTEIN; GRADE; PTEN AB Primary glioblastoma multiforme (GBM) commonly overexpresses the epidermal growth factor receptor (EGFR) gene and its ligand-independent mutant, EGFRvIII Amplification of the EGFR gene has been implicated in the pathogenesis of primary GBM, in particular the small cell phenotype, and this finding may contribute to its aggressive clinical behavior. Anti-EGFR clinical trials for GBM are being conducted, and it would be useful to identify a rapid technique to determine whether EGFR expression and the small cell phenotype are associated with a response to therapy. In the present study we examined 56 cases of GBM using chromogenic in situ hybridization (CISH). CISH analysis and morphology identified 22 small cell (SCGBM) and 22 non-small cell glioblastoma (NSCGBM), and 12 cases of a mixed phenotype. Fourteen cases of SCGBM (14/22) showed EGFR amplification, while only 5 NSCGBM (5/22) cases showed amplification. We have therefore used CISH as an efficient, economic and reliable means for routinely assessing EGFR amplification in GBM, including the small cell variant. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Childrens Hosp, Natl Med Ctr, Washington, DC 20010 USA. Univ Utah, Huntsman Canc Ctr, Salt Lake City, UT USA. Armed Forces Inst Pathol, Dept Neuropathol & Ophthalm Pathol, Washington, DC 20306 USA. RP Rushing, EJ (reprint author), Armed Forces Inst Pathol, Dept Neuropathol & Ophthalm Pathol, Washington, DC 20306 USA. EM rushinge@afip.osd.mil NR 36 TC 13 Z9 13 U1 0 U2 2 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0722-5091 J9 CLIN NEUROPATHOL JI Clin. Neuropathol. PD JUL-AUG PY 2005 VL 24 IS 4 BP 163 EP 169 PG 7 WC Clinical Neurology; Pathology SC Neurosciences & Neurology; Pathology GA 946GB UT WOS:000230559300002 PM 16033132 ER PT J AU Usui, K Ikeda, A Takayama, M Matsuhashi, M Satow, T Begum, T Kinoshita, M Miyamoto, S Hashimoto, N Nagamine, T Fukuyama, H Shibasaki, H AF Usui, K Ikeda, A Takayama, M Matsuhashi, M Satow, T Begum, T Kinoshita, M Miyamoto, S Hashimoto, N Nagamine, T Fukuyama, H Shibasaki, H TI Processing of Japanese morphogram and syllabogram in the left basal temporal area: Electrical cortical stimulation studies SO COGNITIVE BRAIN RESEARCH LA English DT Article DE left basal temporal area; kana (syllabogram) processing; kanji (morphogram) processing; electrical cortical stimulation ID WORD FORM AREA; LANGUAGE AREA; REGIONS; KANJI; COMPREHENSION; RECOGNITION; DYNAMICS; AGRAPHIA; CORTEX; FMRI AB Language functions in the left basal temporal area (LBTA) were investigated using electrical cortical stimulation during functional mapping in six Japanese patients with refractory epilepsy. This study provides the first direct evidence that kana (Japanese syllabogram) is processed in the LBTA. Electrical stimulation of some areas within LBTA induced disturbance in overt reading of kana words only in the first trials, with no errors in the subsequent trials. By contrast, stimulation of the same area caused obvious disturbance in kana non-word reading in all trials. Since a kana word carries both meaning and sound while a kana non-word carries only sounds of a letter string, the contrasting results of partial and complete disturbance imply a possibility that there are two distinct pathways for kana reading: one dealing with both phonological and semantic aspects of the words and the other dealing only with phonological aspect. Kanji words (Japanese morphogram) and objects/pictures were found to be processed in an area different from the area for the kana non-word processing. Furthermore, the present study also identified the common area for processing kanji reading and object/picture naming. There were no errors in matching pictures with kanji words, indicating that concepts of pictures and meanings of kanji words were not interfered by the electrical stimulation of that area. The new insight provides a clue for partial description of processing pathways for language-related visual information in LBTA. Three types of information (morphological, phonological, and semantic) are conveyed together at some stages and are separated into different routes at some other stages. (c) 2005 Elsevier B.V. All rights reserved. C1 Kyoto Univ, Grad Sch Med, Dept Neurol, Sakyo Ku, Kyoto 6068507, Japan. Kyoto Univ, Human Brain Res Ctr, Sch Med, Sakyo Ku, Kyoto 6068507, Japan. Kyoto Univ, Grad Sch Med, Dept Neurosurg, Sakyo Ku, Kyoto 6068507, Japan. NINDS, NIH, Bethesda, MD 20892 USA. RP Ikeda, A (reprint author), Kyoto Univ, Grad Sch Med, Dept Neurol, Sakyo Ku, Kyoto 6068507, Japan. EM akio@kuhp.kyoto-u.ac.jp OI Ikeda, Akio/0000-0002-0790-2598 NR 29 TC 21 Z9 21 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0926-6410 J9 COGNITIVE BRAIN RES JI Cognit. Brain Res. PD JUL PY 2005 VL 24 IS 2 BP 274 EP 283 DI 10.1016/j.cogbrainres.2005.02.001 PG 10 WC Computer Science, Artificial Intelligence; Neurosciences; Neuroimaging SC Computer Science; Neurosciences & Neurology GA 948XA UT WOS:000230747800010 ER PT J AU Smith, JM Rao, SS Stump, KC Benazzi, C Sarli, G Detolla, LJ AF Smith, JM Rao, SS Stump, KC Benazzi, C Sarli, G Detolla, LJ TI Mammary ductal carcinoma with comedo pattern in a rhesus macaque SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Article ID NONHUMAN-PRIMATES; MACACA-MULATTA; MONKEY; TUMORS; NEOPLASIA; GLAND AB A 23-year-old female rhesus macaque presented with a 2.5-cm diameter, firm, moveable, lobulated subcutaneous mass associated with a supranummary teat on the right side of the chest. This animal was a retired breeder, currently in an aging study. No exogenous hormone treatments were noted in the animal's history. Chest radiographs were within normal limits. Blood screens showed no noteworthy variations from normal. Needle aspirate cytology showed clusters of neoplastic cells. Grossly the mass was well circumscribed, firm, and homogeneously tan, with a glandular appearance. Differential diagnoses included sebaceous or mammary adenoma, carcinoma in situ, and lobular or ductular carcinoma. Histopathology was consistent with a mammary ductal carcinoma with comedo pattern. Subsequent needle aspirate cytology from an adjacent right axillary lymph node showed tumor cells with a few lymphoid cells, interpreted as lymphatic spread. Chest radiographs 2 and 6 weeks postbiopsy showed no evidence of pulmonary metastasis. After I year, there was no marked change on chest radiographs, but a small cluster of new nodules was palpable in the right axillary region. Histopathology of an excisional biopsy of the new nodules indicated tumor growth subjacent to regional lymph nodes. Further treatment was not performed and the animal remained clinically normal five years after the initial diagnosis. Spontaneous mammary neoplasia is a major concern in human medicine, yet it rarely has been reported to occur in nonhuman primates. This case is important in documenting an additional case of spontaneous mammary tumor development. C1 NIH, OD, ORS, DVR, Bethesda, MD 20892 USA. NIAID, NIH, VRC, Bethesda, MD 20892 USA. NCI, NIH, Lab Anim Sci Program, Bethesda, MD 20892 USA. Univ Bologna, Div Vet Pathol, Dept Vet Publ Hlth & Anim Pathol, I-60066 Ozzano Dell Emilia, Italy. Univ Maryland, Sch Med, Comparat Med Program & Vet Resources, Baltimore, MD 21201 USA. RP Smith, JM (reprint author), NIH, OD, ORS, DVR, 9000 Rockville Pike,Bldg 14F,Rm 101, Bethesda, MD 20892 USA. NR 17 TC 5 Z9 5 U1 0 U2 2 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD JUL PY 2005 VL 44 IS 4 BP 29 EP 33 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 949DK UT WOS:000230764900006 PM 16050665 ER PT J AU Silverman, J Garnett, NL Giszter, SF Heckman, CJ Kulpa-Eddy, JA Lemay, MA Perry, CK Pinter, M AF Silverman, J Garnett, NL Giszter, SF Heckman, CJ Kulpa-Eddy, JA Lemay, MA Perry, CK Pinter, M TI Decerebrate mammalian preparations: Unalleviated or fully alleviated pain? A review and opinion SO CONTEMPORARY TOPICS IN LABORATORY ANIMAL SCIENCE LA English DT Review ID MINIMUM ALVEOLAR CONCENTRATION; BISPECTRAL INDEX; SEVOFLURANE; ISOFLURANE AB In experimental decerebration of mammals, the cerebral cortex and thalamus are surgically or otherwise inactivated under traditional (pharmacologic) general anesthesia. Once the effects of the pharmacologic anesthesia have dissipated, the animal remains alive, but there is neither pain sensation nor consciousness. Because the Animal Welfare Act and its regulations recognize drugs as the only means to alleviate pain, it is unclear whether a decerebrate animal should be placed in U.S. Department of Agriculture (USDA) pain and distress category D (pain or distress alleviated by drugs) or E (unalleviated pain or distress). We present a rationale for including decerebrate animals in USDA category D. We also provide a general review of decerebration and suggestions for institutional animal care and use committees having to evaluate decerebration protocols. C1 Univ Massachusetts, Sch Med, Dept Anim Med, Worcester, MA 01655 USA. NIH, Off Lab Anim Welfare, Bethesda, MD 20892 USA. Drexel Univ, Coll Med, Dept Neurobiol & Anat, Philadelphia, PA 19129 USA. Northwestern Univ, Sch Med, Dept Physiol, Chicago, IL 60611 USA. Northwestern Univ, Sch Med, Dept Phys Med & Rehabil, Chicago, IL 60611 USA. USDA, Riverdale, MD 20737 USA. Drexel Univ, Hlth & Soc Programs, Coll Nursing & Hlth Profess, Philadelphia, PA 19102 USA. Emory Univ, Sch Med, Dept Physiol, Atlanta, GA 30322 USA. RP Silverman, J (reprint author), Univ Massachusetts, Sch Med, Dept Anim Med, Worcester, MA 01655 USA. RI Perry, Constance/E-1930-2014 FU NINDS NIH HHS [P50 NS024707-160011, P50 NS024707] NR 20 TC 11 Z9 11 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1060-0558 J9 CONTEMP TOP LAB ANIM JI Contemp. Top. Lab. Anim. Sci. PD JUL PY 2005 VL 44 IS 4 BP 34 EP 36 PG 3 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 949DK UT WOS:000230764900007 PM 16050666 ER PT J AU Anderson, LM AF Anderson, LM TI Cancer biology and hormesis: Comments on Calabrese (2005) SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review DE cultural cells; dose response; in vivo models ID HUMAN-BREAST-CANCER; CELLS; TAMOXIFEN; SURAMIN; TUMOR; CULTURE; URINARY; MODEL AB Large numbers of chemicals of a variety of types exhibit apparent hormetic effects on cultured human cancer cells, causing stimulation of cell growth or related changes at low doses, followed by inhibition at higher doses. Many of the studies listed are not fully convincing, due to lack of appropriate controls or sufficient number of doses. However, the proposed hormetic response seems firmly established in a subset of these experiments. Significance with regard to in vivo cancer growth has not been pursued and must be a priority for the future. For several examples where in vivo titers are known, such as, resveratrol, suramin, and tamoxifen, comparison of the dose and concentration ranges confirms that hormesis could be an issue in vivo. Further investigations are warranted, especially for therapeutic drugs, phytochemicals, and environmental toxicants. C1 NCI, Comparat Carcinogenesis Lab, Frederick, MD 21702 USA. RP Anderson, LM (reprint author), NCI, Comparat Carcinogenesis Lab, Bldg 538,Ft Detrick, Frederick, MD 21702 USA. EM Andersol@ncifcrf.gov NR 22 TC 3 Z9 4 U1 2 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8444 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PD JUL PY 2005 VL 35 IS 6 BP 583 EP 586 DI 10.1080/10408440500246777 PG 4 WC Toxicology SC Toxicology GA 992TY UT WOS:000233908100002 PM 16422393 ER PT J AU Foroughi, S Prussin, C AF Foroughi, S Prussin, C TI Clinical management of eosinophilic gastrointestinal disorders SO CURRENT ALLERGY AND ASTHMA REPORTS LA English DT Editorial Material ID BONE-MINERAL DENSITY; ELEMENTAL DIET; GASTROENTERITIS; ESOPHAGITIS; CHILDREN C1 NIAID, Lab Allerg Dis, NIH, Bethesda, MD 20892 USA. RP Foroughi, S (reprint author), NIAID, Lab Allerg Dis, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM cprussin@niaid.nih.gov OI Prussin, Calman/0000-0002-3917-3326 NR 9 TC 9 Z9 9 U1 0 U2 0 PU CURRENT SCIENCE INC PI PHILADELPHIA PA 400 MARKET STREET, STE 700, PHILADELPHIA, PA 19106 USA SN 1529-7322 J9 CURR ALLERGY ASTHM R JI Curr. Allergy Asthma Rep. PD JUL PY 2005 VL 5 IS 4 BP 259 EP 261 DI 10.1007/s11882-005-0062-4 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 949TC UT WOS:000230810000001 PM 15967064 ER PT J AU Cho, J Lee, C Kang, S Lee, J Lee, H Bok, J Woo, J Moon, Y Choi, Y AF Cho, J Lee, C Kang, S Lee, J Lee, H Bok, J Woo, J Moon, Y Choi, Y TI Molecular cloning of a phytase gene (phy M) from Pseudomonas syringae MOK1 SO CURRENT MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; ACID-PHOSPHATASE; EXPRESSION; OVEREXPRESSION; PURIFICATION; SEQUENCE; FUNGI; SP. AB A phytase gene (phy M) was cloned from Pseudomonas syringae MOK1 by two steps of degenerate PCR and inverse PCR. This gene consists of 1,287 nucleotides and encodes a polypeptide of 428 amino acids with a deduced molecular mass of 46,652 kDa. Based on its amino acid sequence, the Phy M shares the active site RHGXRXP and HD sequence motifs, typically characterized by histidine acid phosphatases familly. Each phy M gene fragment encoding mature Phy M with its own signal sequence (pEPSS) and without (pEPSM) was subcloned into the E. coli BL21 (DE3) expression vector, pET22b (+). The enzyme activity in crude extracts of clone pEPSM was 2.514 Umg(-1) of protein, and about 10-fold higher than that of clone pEPSS. C1 Natl Inst Environm Hlth Sci, Inositide Signaling Grp, DHSS, NIH, Res Triangle Pk, NC 27709 USA. Seoul Natl Univ, Coll Agr & Life Sci, Sch Agr Biotechnol, Seoul 151742, South Korea. NIMH, Bethesda, MD 20892 USA. Jinju Natl Univ, Jinju 660758, South Korea. RP Cho, J (reprint author), Natl Inst Environm Hlth Sci, Inositide Signaling Grp, DHSS, NIH, POB 12233, Res Triangle Pk, NC 27709 USA. EM cho3@niehs.nih.gov NR 26 TC 16 Z9 16 U1 1 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0343-8651 J9 CURR MICROBIOL JI Curr. Microbiol. PD JUL PY 2005 VL 51 IS 1 BP 11 EP 15 DI 10.1007/s00284-005-4482-0 PG 5 WC Microbiology SC Microbiology GA 949WE UT WOS:000230818800003 PM 15971093 ER PT J AU Doffinger, R Patel, S Kumararatne, DS AF Doffinger, R Patel, S Kumararatne, DS TI Human immunodeficiencies that predispose to intracellular bacterial infections SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review DE human immunodeficiency; intracellular bacterial infection ID ANHIDROTIC ECTODERMAL DYSPLASIA; ESSENTIAL MODULATOR MUTATION; INTERFERON-GAMMA; MYCOBACTERIAL INFECTION; CLINICAL-FEATURES; CALMETTE-GUERIN; ALPHA MUTATION; IMMUNITY; DEFICIENCY; TUBERCULOSIS AB Purpose of review Patients treated with anti-tumour necrosis factor agents have an increased risk of active tuberculosis. Mycobacteria are bacterial pathogens capable of surviving and multiplying within macrophages; these infections are characterised by granulomatous inflammation. This review addresses the effects of inherited and acquired immunodeficiencies on the susceptibility to the development of intracellular bacterial infections. Recent findings Primary and secondary immunodeficiencies that result in severely impaired T cell function or macrophage activation result in an increased risk of mycobacterial and Salmonella infection. Conversely, inherited or acquired antibody or complement deficiency does not lead to increased susceptibility to these pathogens. Inherited defects in the interleukin-1 2/interleukin-23-dependent interferon-gamma pathway due to mutations in genes encoding the p40 chain common to interleukin-1 2 and interleukin-23, the beta 1 chain shared by interleukin-1 2 and interleukin-23 receptors, interferon-gamma receptor chains 1 or 2, or signal transducer and activator of transcription, predispose to severe infections caused by poorly pathogenic mycobacteria and Salmonella species. Acquired defects of cytokine function causing increased susceptibility to these pathogens include anti-tumor necrosis factor therapy and the generation of interferon-gamma-neutralising autoantibodies. Defective nuclear factor kappa B activation caused by hypomorphic mutations of the nuclear factor kappa B essential modulator gene, which compromises the function of Toll receptors, interleukin-IL receptors, and tumor necrosis factor-alpha receptors, also increases susceptibility to severe mycobacterial infections. Patients with inherited defects in the phagocyte nicotine-adenine dinucleotide phosphate oxidase system are highly susceptible to Salmonella infections but only exhibit slightly increased susceptibility to mycobacteria. Summary Collectively, these observations highlight immune mechanisms that are essential for protection against intracellular bacteria, This information provides clinicians with a framework for investigating patients with potentially life-threatening intracellular bacterial infections. C1 Dept Clin Biochem & Immunol, Cambridge, 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 38 TC 30 Z9 30 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD JUL PY 2005 VL 17 IS 4 BP 440 EP 446 DI 10.1097/01.bor.0000166387.70475.dd PG 7 WC Rheumatology SC Rheumatology GA 938FP UT WOS:000229985600009 PM 15956841 ER PT J AU O'Hara, FP Beck, E Barr, LK Wong, LL Kessler, DS Riddle, RD AF O'Hara, FP Beck, E Barr, LK Wong, LL Kessler, DS Riddle, RD TI Zebrafish Lmx1b.1 and Lmx1b.2 are required for maintenance of the isthmic organizer SO DEVELOPMENT LA English DT Article DE isthmus; Lmx1b; mesencephalon; metencephalon; Pax; Wnt; zebrafish ID MIDBRAIN-HINDBRAIN BOUNDARY; CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; CEREBELLAR DEVELOPMENT; DEVELOPMENTAL DEFECTS; ENGRAILED EXPRESSION; INT-1 PROTOONCOGENE; VERTEBRATE LIMB; HOMEOBOX GENES; MOTOR-NEURONS AB The mesencephalic and metencephalic region (MMR) of the vertebrate central nervous system develops in response to signals produced by the isthmic organizer (IsO). We have previously reported that the LIM homeobox transcription factor Lmx1b is expressed within the chick IsO, where it is sufficient to maintain expression of the secreted factor wnt1. In this paper, we show that zebrafish express two Lmx1b orthologs, lmx1b.1 and lmx1b.2, in the rostral IsO, and demonstrate that these genes are necessary for key aspects of MMR development. Simultaneous knockdown of Lmxlb.1 and Lmxlb.2 using morpholino antisense oligos results in a loss of wnt1, wnt3a, wnt10b, pax8 and fgf8 expression at the IsO, leading ultimately to programmed cell death and the loss of the isthmic constriction and cerebellum. Single morpholino knockdown of either Lmx1b.1 or Lmx1b.2 has no discernible effect on MMR development. Maintenance of lmx1b.1 and lmx1b.2 expression at the isthmus requires the function of no isthmus/pax2.1, as well as Fgf signaling. Transient misexpression of Lmx1b.1 or Lmx1b.2 during early MMR development induces ectopic wnt1 and fgf8 expression in the MMR, as well as throughout much of the embryo. We propose that Lmxlb.1- and Lmxlb.2-mediated regulation of wnt1, wnt3a, wnt10b, pax8 and fgf8 maintains cell survival in the isthmocerebellar region. C1 NINDS, NIH, Bethesda, MD 20892 USA. RP Kessler, DS (reprint author), Univ Oklahoma, Hlth Sci Ctr, Dept Ophthalmol, Philadelphia, PA 19104 USA. EM kesslerd@mail.med.upenn.edu RI Wong, Lily/D-7737-2011 OI Wong, Lily/0000-0003-0569-3398 FU NINDS NIH HHS [NS041005, R01 NS041005] NR 64 TC 37 Z9 37 U1 1 U2 1 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUL PY 2005 VL 132 IS 14 BP 3163 EP 3173 DI 10.1242/dev.01898 PG 11 WC Developmental Biology SC Developmental Biology GA 954UL UT WOS:000231180400002 PM 15944182 ER PT J AU Chatterjee, B Chin, AJ Valdimarsson, G Finis, C Sonntag, JM Choi, BY Tao, L Balasubramanian, K Bell, C Krufka, A Kozlowski, DJ Johnson, RG Lo, CW AF Chatterjee, B Chin, AJ Valdimarsson, G Finis, C Sonntag, JM Choi, BY Tao, L Balasubramanian, K Bell, C Krufka, A Kozlowski, DJ Johnson, RG Lo, CW TI Developmental regulation and expression of the zebrafish connexin43 gene SO DEVELOPMENTAL DYNAMICS LA English DT Article DE gap junction; connexin; Cx43 Cx32.2; promoter; zebrafish; mouse; embryo ID GAP-JUNCTION PROTEIN; IMPLANTATION MOUSE EMBRYO; CARDIAC NEURAL CREST; CELL COMMUNICATION; LENS DEVELOPMENT; MESSENGER-RNAS; WILD-TYPE; V-SRC; PHOSPHORYLATION; TRANSCRIPTION AB We cloned and sequenced the zebrafish (Danio rerio) connexin43 (Cx43 alpha 1) gone. The predicted protein sequence shows a high degree of sequence conservation. Transcript analyses revealed multiple transcription start sites and a potential alternative transcript encoding a N-terminally truncated Cx43 alpha 1 protein. Maternal Cx43a1 transcripts were detected, with zygotic expression initiated before gastrulation. In situ hybridization revealed many Cx43 alpha 1 expression domains, including the notochord and brain, heart and vasculature, many resembling patterns seen in mammalian embryos. Of interest, a reporter construct under control of the mouse Cx43 alpha 1 promoter was observed to drive green fluorescent protein expression in zebrafish embryos in domains mimicking the native Cx43 alpha 1 expression pattern in fish and mice. Sequence comparison between the mouse and zebrafish Cx43 alpha 1 promoter sequences, showed the conservation of several transcription factor motifs, which otherwise shared little overall sequence homology. The conservation of protein sequence and developmental gene regulation would suggest that Cx43 alpha 1 gap junctions are likely to have conserved roles in vertebrate embryonic development. (c) 2005 Wiley-Liss, Inc. C1 NHLBI, Dev Biol Lab, NIH, Bethesda, MD 20814 USA. Univ Penn, Sch Med, Dept Pediat, Div Cardiol, Philadelphia, PA 19104 USA. Childrens Hosp Philadelphia, Div Cardiol, Philadelphia, PA 19104 USA. Univ Manitoba, Dept Zool, Winnipeg, MB R3T 2N2, Canada. Univ Manitoba, Dept Biochem & Mol Genet, Winnipeg, MB R3T 2N2, Canada. Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN USA. Med Coll Georgia, Dept Anat & Cellular Biol, Inst Mol Med & Genet, Augusta, GA 30912 USA. RP Lo, CW (reprint author), NHLBI, Dev Biol Lab, NIH, 50 S Dr MSC8019,Bldg 50,Room 4537, Bethesda, MD 20814 USA. EM loc@nhibi.nih.gov OI Chin, Alvin/0000-0002-0417-8653; Krufka, Alison/0000-0002-8921-6291 FU NHLBI NIH HHS [ZO-1 HL005701]; NIDCD NIH HHS [F32-DC0311, F32 DC000311] NR 93 TC 19 Z9 21 U1 0 U2 1 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 JUL PY 2005 VL 233 IS 3 BP 890 EP 906 DI 10.1002/dvdy.20426 PG 17 WC Anatomy & Morphology; Developmental Biology SC Anatomy & Morphology; Developmental Biology GA 936YS UT WOS:000229892100020 PM 15895415 ER PT J AU Chen, H Sullivan, G Quon, MJ AF Chen, H Sullivan, G Quon, MJ TI Assessing the predictive accuracy of QUICKI as a surrogate index for insulin sensitivity using a calibration model SO DIABETES LA English DT Article ID SIMPLE QUANTITATIVE METHODS; NORMAL GLUCOSE-METABOLISM; TYPE-2 DIABETIC-PATIENTS; FASTING PLASMA-GLUCOSE; CHECK INDEX; MINIMAL-MODEL; CLAMP TECHNIQUE; CARDIOVASCULAR-DISEASE; RECIPROCAL INDEX; TOLERANCE TEST AB The quantitative insulin-sensitivity check index (QUICKI) has an excellent linear correlation with the glucose clamp index of insulin sensitivity (SIClamp) that is better than that of many other surrogate indexes. However, correlation between a surrogate and reference standard may improve as variability between subjects in a cohort increases (i.e., with an increased range of values). Correlation may be excellent even when prediction of reference values by the surrogate is poor. Thus, it is important to evaluate the ability of QUICKI to accurately predict insulin sensitivity as determined by the reference glucose clamp method. In the present study, we used a calibration model to compare the ability of QUICKI and other simple surrogates to predict SIClamp. Predictive accuracy was evaluated by both root mean squared error of prediction as well as a more robust leave-one-out cross-validation-type root mean squared error of prediction (CVPE). Based on data from 116 glucose clamps obtained from nonobese, obese, type 2 diabetic, and hypertensive subjects, we found that QUICKI and log (homeostasis model assessment [HOMA]) were both excellent at predicting SIClamp (CVPE = 1.45 and 1.51, respectively) and significantly better than HOMA, 1/HOMA, and fasting insulin (CVPE = 3.17, P < 0.001; 1.67, P < 0.02; and 2.85, P < 0.001, respectively). QUICKI and log(HOMA) also had the narrowest distribution of residuals (measured SIClamp - predicted SIClamp). In a subset of subjects (n = 78) who also underwent a frequently sampled intravenous glucose tolerance test with minimal model analysis, QUICKI was significantly better than the minimal model index of insulin sensitivity (SIMM) at predicting SIClamp (CVPE = 1.54 vs. 1.98, P = 0.001). We conclude that QUICKI and log(HOMA) are among the most accurate surrogate indexes for determining insulin sensitivity in humans. C1 NIH, Natl Ctr Complementary & Alternat Med, Diabet Unit, Bethesda, MD 20892 USA. RP Quon, MJ (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Diabet Unit, Bldg 10,Room 6C-205,10 Ctr Dr MSC 1632, Bethesda, MD 20892 USA. EM quonm@nih.gov RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 44 TC 119 Z9 121 U1 0 U2 4 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2005 VL 54 IS 7 BP 1914 EP 1925 DI 10.2337/diabetes.54.7.1914 PG 12 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940SI UT WOS:000230164000003 PM 15983190 ER PT J AU Javor, ED Cochran, EK Musso, C Young, JR DePaoli, AM Gorden, P AF Javor, ED Cochran, EK Musso, C Young, JR DePaoli, AM Gorden, P TI Long-term efficacy of leptin replacement in patients with generalized lipodystrophy SO DIABETES LA English DT Article ID REVERSES INSULIN-RESISTANCE; RECOMBINANT LEPTIN; CONGENITAL LIPODYSTROPHY; DIABETES-MELLITUS; HEPATIC STEATOSIS; OB/OB MICE; THERAPY; OBESE; LIPOATROPHY; ADIPOSE AB Ectopic fat accumulation has been implicated as a contributing factor in the abnormal metabolic state of obesity. One human model of ectopic fat deposition is generalized lipodystrophy. Generalized lipodystrophy is a rare disorder characterized by a profound deficiency of adipose tissue with resultant loss of triglyceride storage capacity and reduced adipokines, including leptin. Subjects with generalized lipodystrophy and reduced leptin levels often have an increased appetite leading to hyperphagia. Excess fuel consumption, coupled with a lack of adipose tissue, contributes to the significant ectopic triglyceride accumulation in the muscle and liver seen in these subjects. This ectopic fat, along with the deficiency in leptin signaling and perhaps other adipokines, likely contributes to insulin resistance, diabetes, and hepatic steatosis. We report here the long-term effects of leptin replacement in a cohort of these subjects. Fifteen patients with generalized lipodystrophy were treated with twice-daily recombinant methionyl human leptin (r-metHuLeptin) for 12 months. We evaluated metabolic parameters at baseline and every 4 months. Antidiabetes medications were decreased or discontinued as necessary. Reductions were seen in serum fasting glucose (from 205 +/- 19 to 126 +/- 11 mg/dl; P < 0.001), HbA(1c) (from 9 +/- 0.4 to 7.1 +/- 0.5%; P < 0.001), triglycerides (from 1,380 +/- 500 to 516 +/- 236 mg/dl; P < 0.001), LDL (from 139 +/- 16 to 85 +/- 7 mg/dl; P < 0.01), and total cholesterol (from 284 +/- 40 to 167 +/- 21 mg/dl; P < 0.01). HDL was unchanged (from 31 +/- 3 to 29 +/- 2 mg/dl; P = 0.9). Liver volumes were significantly reduced (from 3,663 +/- 326 to 2,190 +/- 159 cm 3; P < 0.001), representing loss of steatosis. Decreases were seen in total body weight (from 61.8 +/- 3.6 to 57.4 +/- 3.4 kg; P = 0.02) and resting energy expenditure (from 1,929 +/- 86 to 1,611 +/- 101 kcal/24 h; P < 0.001). R-metHuLeptin led to significant and sustained improvements in glycemia, dyslipidemia, and hepatic steatosis. Leptin represents the first novel, effective, long-term treatment for severe forms of lipodystrophy. C1 NIDDKD, Clin Endocrinol Branch, NIH, Bethesda, MD USA. Amgen Inc, Thousand Oaks, CA USA. RP Javor, ED (reprint author), 10 Ctr Dr,CRC Room 6-5940, Bethesda, MD 20892 USA. EM edwardj@intra.niddk.nih.gov NR 37 TC 131 Z9 137 U1 1 U2 3 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 J9 DIABETES JI Diabetes PD JUL PY 2005 VL 54 IS 7 BP 1994 EP 2002 DI 10.2337/diabetes.54.7.1994 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 940SI UT WOS:000230164000012 PM 15983199 ER PT J AU Jones, HE Johnson, RE Jasinski, DR O'Grady, KE Chisholm, CA Choo, RE Crocetti, M Dudas, R Harrow, C Huestis, MA Jansson, LM Lantz, M Lester, BM Milio, L AF Jones, HE Johnson, RE Jasinski, DR O'Grady, KE Chisholm, CA Choo, RE Crocetti, M Dudas, R Harrow, C Huestis, MA Jansson, LM Lantz, M Lester, BM Milio, L TI Buprenorphine versus methadone in the treatment of pregnant opioid-dependent patients: effects on the neonatal abstinence syndrome SO DRUG AND ALCOHOL DEPENDENCE LA English DT Article DE opioids; women; buprenorphine; methadone; NAS; infants; prenatal ID COCAINE ABSTINENCE; BEHAVIORAL-APPROACH; BIRTH-WEIGHT; ADDICTION; MAINTENANCE; MANAGEMENT; WITHDRAWAL; HEROIN; OPIATE; WOMEN AB This study was designed to compare the neonatal abstinence syndrome (NAS) in neonates of methadone and buprenorphine maintained pregnant opioid-dependent women and to provide preliminary safety and efficacy data for a larger multi-center trial. This randomized, double-blind, double-dummy, flexible dosing, parallel-group controlled trial was conducted in a comprehensive drug-treatment facility that included residential and ambulatory care. Participants were opioid-dependent pregnant women and their neonates. Treatment involved daily administration of either sublingual buprenorphine or oral methadone using flexible dosing of 4-24 mg or 20- 100 mg, respectively. Primary a priori outcome measures were: (1) number of neonates treated for NAS; (2) amount of opioid agonist medication used to treat NAS; (3) length of neonatal hospitalization; and (4) peak NAS score. Two of 10 (20%) buprenorphine-exposed and 5 of 11 (45.5%) methadone-exposed neonates were treated for NAS (p =.23). Total amount of opioid-agonist medication administered to treat NAS in methadone-exposed neonates was three times greater than for buprenorphine-exposed neonates (93.1 versus 23.6; p =. 13). Length of hospitalization was shorter for buprenorphine-exposed than for methadone-exposed neonates (p =.021). Peak NAS total scores did not significantly differ between groups (p =.25). Results suggest that buprenorphine is not inferior to methadone on outcome measures assessing NAS and maternal and neonatal safety when administered starting in the second trimester of pregnancy. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21224 USA. Univ Maryland, Dept Psychol, College Pk, MD 20742 USA. Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Baltimore, MD 21224 USA. Natl Inst Drug Abuse, Div Intramural Res, Baltimore, MD 21224 USA. Brown Univ, Sch Med, Dept Pediat, Dept Psychiat & Human Behav, Providence, RI 02905 USA. RP Jones, HE (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Johns Hopkins Bayview Med Campus,D-3-E,4940 Easte, Baltimore, MD 21224 USA. EM hejones@jhmi.edu OI dudas, robert/0000-0001-6837-121X FU NCRR NIH HHS [M01RR-02719]; NIDA NIH HHS [DA R01 12220] NR 47 TC 157 Z9 161 U1 3 U2 23 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0376-8716 J9 DRUG ALCOHOL DEPEN JI Drug Alcohol Depend. PD JUL PY 2005 VL 79 IS 1 BP 1 EP 10 DI 10.1016/j.drugalcdep.2004.11.013 PG 10 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 940XV UT WOS:000230180100001 PM 15943939 ER PT J AU Kobayashi, K Yamanaka, Y Iwazaki, N Nakajo, I Hosokawa, M Negishi, M Chiba, K AF Kobayashi, K Yamanaka, Y Iwazaki, N Nakajo, I Hosokawa, M Negishi, M Chiba, K TI Identification of HMG-CoA reductase inhibitors as activators for human, mouse and rat constitutive androstane receptor SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID PREGNANE X-RECEPTOR; NUCLEAR RECEPTOR; SIGNALING PATHWAY; HUMAN HEPATOCYTES; GENE-EXPRESSION; CYP2B6 GENE; CAR; INDUCTION; LIVER; LIGANDS AB Constitutive active (or androstane) receptor (CAR, NR1I3), a member of the nuclear receptor family, is a major regulator for induction of cytochrome P450 2B (CYP2B) genes by phenobarbital. Phenobarbital-like inducer, 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene is a potent mouse CAR ligand that has been used to study CAR target genes in mice but does not activate human CAR (hCAR) or rat CAR (rCAR). Although 6-(4-chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde O-(3,4-dichlorobenzyl) oxime (CITCO) was reported to be an hCAR agonistic ligand, activation of hCAR by CITCO in cell-based reporter assay was weak. Therefore, we performed a screening of 50 drugs and chemicals using cell-based reporter assays to identify activators of hCAR. Among them, HMG-CoA reductase inhibitors (cerivastatin, simvastatin, fluvastatin, and atorvastatin) enhanced the hCAR-mediated transcriptional activation of phenobarbital-responsive enhancer module reporter gene by up to 3-fold. Similar activation by HMG-CoA reductase inhibitors was also observed with mouse and rat CARs. On the other hand, pravastatin did not activate hCAR at the concentrations tested (up to 30 mu M). The extent of activation by the HMG-CoA reductase inhibitors was stronger than that by CITCO. Cerivastatin, simvastatin, fluvastatin, and atorvastatin induced CYP2B6 mRNA in stable hCAR-expressed FLC7 cells but not in original FLC7 cells. Therefore, we concluded that CAR mediates the effects of HMG-CoA reductase inhibitors on the induction of CYP2B genes, although HMG-CoA reductase inhibitors also activate pregnane X receptor. HMG-CoA reductase inhibitors such as cerivastatin would be useful to study for elucidating molecular and cellular mechanisms of hCAR. C1 Chiba Univ, Grad Sch Pharmaceut Sci, Lab Pharmacol & Toxicol, Chuo Ku, Chiba 2608675, Japan. NIEHS, Pharmacogenet Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Kobayashi, K (reprint author), Chiba Univ, Grad Sch Pharmaceut Sci, Lab Pharmacol & Toxicol, Chuo Ku, Inohana 1-8-1, Chiba 2608675, Japan. EM kaoruk@p.chiba-u.ac.jp NR 26 TC 50 Z9 51 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUL PY 2005 VL 33 IS 7 BP 924 EP 929 DI 10.1124/dmd.104.002741 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 936GC UT WOS:000229842500010 PM 15802384 ER PT J AU Devan, BD Duffy, KB Bowker, JL Bharati, IS Nelson, CM Daffin, LW Spangler, EL Ingram, DK AF Devan, BD Duffy, KB Bowker, JL Bharati, IS Nelson, CM Daffin, LW Spangler, EL Ingram, DK TI Phosphodiesterase type 5 (PDE5) inhibition and cognitive enhancement SO DRUGS OF THE FUTURE LA English DT Review ID 14-UNIT T-MAZE; LONG-TERM DEPRESSION; OBJECT RECOGNITION MEMORY; DEPENDENT PROTEIN-KINASE; VIAGRA((R)) SILDENAFIL CITRATE; RECEPTOR ANTAGONIST MEMANTINE; HIPPOCAMPAL PYRAMIDAL CELLS; D-ASPARTATE RECEPTOR; MORRIS WATER MAZE; NITRO-L-ARGININE AB Drug development for the treatment of dementia and age-related cognitive decline has been slow to produce clinically viable alternatives to the two existing FDA approved drug treatments, AChE inhibitors and the noncompetitive NMDA receptor antagonist, memantine. Recent human and preclinical animal studies suggest that phosphodiesterase type 5 (PDE5) inhibitors, already in clinical use for the treatment of erectile dysfunction in men, may have central cognitive enhancing effects. Recent behavioral pharmacological studies with rodents demonstrate that PDE5 inhibitors improve memory consolidation in young animals using passive avoidance and object recognition tasks. In addition, we have shown that pretraining administration of the PDE5 inhibitor sildenafil citrate can attenuate a spatial learning impairment in the 14-unit T-maze. Research findings with aged animals show that pretraining administration of sildenafil can improve the long-term retention of spatial memory 1 week following maze acquisition. We propose that the available research findings provide preclinical support for a possible alternative use of PDE5 inhibitors as cognitive enhancing agents that improve different kinds of learning and memory and protect brain systems against neurodegeneration. C1 NIA, Behav Neurosci Sect, Lab Expt Gerontol, NIH,Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Devan, BD (reprint author), NIA, Behav Neurosci Sect, Lab Expt Gerontol, NIH,Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM DevanBr@grc.nia.nih.gov NR 124 TC 11 Z9 11 U1 0 U2 3 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0377-8282 J9 DRUG FUTURE JI Drug Future PD JUL PY 2005 VL 30 IS 7 BP 725 EP 736 DI 10.1358/dof.2005.030.07.929862 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 976MW UT WOS:000232738700007 ER PT J AU Yu, AM Fukamachi, K Krausz, KW Cheung, C Gonzalez, FJ AF Yu, AM Fukamachi, K Krausz, KW Cheung, C Gonzalez, FJ TI Potential role for human cytochrome P450 3A4 in estradiol homeostasis SO ENDOCRINOLOGY LA English DT Article ID HUMAN LIVER-MICROSOMES; MAMMARY-GLAND DEVELOPMENT; PREGNANE-X-RECEPTOR; BREAST-CANCER RISK; DRUG-METABOLISM; TRANSGENIC MICE; GROWTH-HORMONE; URINARY 6-BETA-HYDROXYCORTISOL; EPITHELIAL-CELLS; DEFICIENT MICE AB Previously, a human CYP3A4-transgenic (Tg-CYP3A4) mouse line was reported to exhibit enhanced metabolism of midazolam by cytochrome P450 3A4 (CYP3A4) expressed in small intestine. Here we show that expression of CYP3A4 and murine cyp3a and cyp2b was both age and sex dependent. CYP3A4 was expressed in the livers of male and female Tg-CYP3A4 mice at 2 and 4 wk of age. Since 6 wk, CYP3A4 was undetectable in male livers, whereas it was constitutively expressed in female livers at decreased levels (3- to 5-fold). Pregnenolone 16 alpha-carbonitrile markedly induced hepatic CYP3A4 expression, and the level was higher in females than males. Induction of intrinsic murine cyp3a and cyp2b was also sex dependent. Tg-CYP3A4 females were found to be deficient in lactation, leading to a markedly lower pup survival. The mammary glands of the Tg-CYP3A4 lactating mothers had underdeveloped alveoli with low milk content. Furthermore, beta-casein and whey acidic protein mRNAs were expressed at markedly lower levels in Tg-CYP3A4 pregnant and nursing mouse mammary glands compared with wild-type mice. This impaired lactation phenotype was associated with significantly reduced serum estradiol levels in Tg-CYP3A4 mice. A pharmacokinetic study revealed that the clearance of iv administrated [H-3] estradiol was markedly enhanced in Tg-CYP3A4 mice compared with wild-type mice. These results suggest that CYP3A4 may play an important role in estradiol homeostasis. This may be of concern for treatment of pregnant and lactating women because CYP3A4 gene expression and enzymatic activity can be potentially modified by CYP3A4 inhibitors or inducers in medications, supplements, beverages, and diet. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. SUNY Buffalo, Dept Pharmaceut Sci, Buffalo, NY 14221 USA. RP Gonzalez, FJ (reprint author), NCI, Lab Metab, NIH, Bldg 37,Room 3106, Bethesda, MD 20892 USA. EM fjgonz@helix.nih.gov NR 76 TC 50 Z9 52 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 JUL PY 2005 VL 146 IS 7 BP 2911 EP 2919 DI 10.1210/en.2004-1248 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 935HZ UT WOS:000229772700007 PM 15817670 ER PT J AU Smaniotto, S de Mello-Coelho, V Villa-Verde, DMS Pleau, JM Postel-Vinay, MC Dardenne, M Savino, W AF Smaniotto, S de Mello-Coelho, V Villa-Verde, DMS Pleau, JM Postel-Vinay, MC Dardenne, M Savino, W TI Growth hormone modulates thymocyte development in vivo through a combined action of laminin and CXC chemokine ligand 12 SO ENDOCRINOLOGY LA English DT Article ID CELL MIGRATION; THYMUS; MICE; FIBRONECTIN; ADHESION; LYMPHOPOIESIS; ENGRAFTMENT; CHEMOTAXIS; EXPRESSION; RECEPTORS AB Previous evidence indicates that GH modulates thymic cell migration. In this study we approached this issue in vivo, studying thymocyte migration in GH transgenic animals and in normal mice treated intrathymically with GH. Extracellular matrix and chemokines are involved in thymocyte migration. In this respect, thymocyte adhesion to laminin was higher in GH-treated animals than controls, and the numbers of migrating cells in laminin-coated Transwells was higher in GH-transgenic and GH-injected mice. Additionally, CXC chemokine ligand 12 (CXCL12)-driven migration was higher in GH-Tg and GH-treated animals compared with controls. Interestingly, although CXCR4 expression on thymocytes did not change in GH-Tg mice, the CXCL12 intrathymic contents were higher. We found that CXCL12, in conjunction with laminin, would additionally enhance the migration of thymocytes previously exposed to high concentrations of GH in vivo. Lastly, there was an augmentation of recent thymic emigrants in lymph nodes from GH-Tg and GH-injected animals. In conclusion, enhanced thymocyte migration in GH transgenic mice as well as GH-injected mice results at least partially from a combined action of laminin and CXCL12. Considering that GH is presently being used as an adjuvant therapeutic agent in immunodeficiencies, including AIDS, the concepts defined herein provide important background knowledge for future GH-based immune interventions. C1 Inst Oswaldo Cruz, Oswaldo Cruz Fdn, Dept Immunol,Fiocruz Assoc Lab Immunol, Lab Thymus Res,INSERM, BR-21045900 Rio De Janeiro, Brazil. Fed Univ Alagoas, Dept Morphol, BR-57072970 Maceio, Brazil. Hop Necker Enfants Malad, Unite Mixte Rech 8147, F-75743 Paris, France. Hop Necker Enfants Malad, INSERM, Unite 344, F-75743 Paris, France. NIA, NIH, Baltimore, MD 21224 USA. RP Savino, W (reprint author), Inst Oswaldo Cruz, Oswaldo Cruz Fdn, Dept Immunol,Fiocruz Assoc Lab Immunol, Lab Thymus Res,INSERM, Ave Brasil 4365, BR-21045900 Rio De Janeiro, Brazil. EM savino@fiocruz.br NR 34 TC 36 Z9 38 U1 1 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0013-7227 J9 ENDOCRINOLOGY JI Endocrinology PD JUL PY 2005 VL 146 IS 7 BP 3005 EP 3017 DI 10.1210/en.2004-0709 PG 13 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 935HZ UT WOS:000229772700016 PM 15802502 ER PT J AU Resnik, DB Portier, C AF Resnik, DB Portier, C TI Pesticide testing on human subjects: Weighing benefits and risks SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID CONFLICTS-OF-INTEREST; CLINICAL-TRIALS; LYMPHOMA; EXPOSURE; CONDUCT; ETHICS; HEALTH AB In the debate surrounding testing pesticides on human subjects, two distinct positions have emerged. The first position holds that pesticide experiments on human subjects should be allowed, but only under stringent scientific and ethical standards. The second position asserts that these experiments should never be allowed. In this article, we evaluate what we consider to be the strongest argument for the second position-namely, that the benefits of the experiments are not significant enough to justify the risks posed to healthy subjects. We challenge this argument by examining the benefits and risks of testing pesticides on human subjects. We argue that a study that intentionally exposes humans subjects to pesticides should be permitted if a) the knowledge gained from the study, is expected to promote human health; b) the knowledge cannot be reasonably obtained by, other means; c) the study is not expected to cause serious or irreversible harm to the subjects; and a) appropriate safeguards are in place to minimize harm to the subjects. C1 NIEHS, NIH, Off Sci Director, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Natl Toxicol Program, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Resnik, DB (reprint author), NIEHS, NIH, Off Sci Director, Dept Hlth & Human Serv, POB 12233,Mail Drop NH-6, Res Triangle Pk, NC 27709 USA. EM resnikd@niehs.nih.gov RI Portier, Christopher/A-3160-2010 OI Portier, Christopher/0000-0002-0954-0279 NR 41 TC 15 Z9 15 U1 0 U2 4 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 JUL PY 2005 VL 113 IS 7 BP 813 EP 817 DI 10.1289/ehp.7720 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 941YT UT WOS:000230250800026 PM 16002367 ER PT J AU Weis, BK Balshawl, D Barr, JR Brown, D Ellisman, M Liov, P Omenn, G Potter, JD Smith, MT Sohn, L Suk, WA Sumner, S Swenberg, J Walt, DR Watkins, S Thompson, C Wilson, SH AF Weis, BK Balshawl, D Barr, JR Brown, D Ellisman, M Liov, P Omenn, G Potter, JD Smith, MT Sohn, L Suk, WA Sumner, S Swenberg, J Walt, DR Watkins, S Thompson, C Wilson, SH TI Personalized exposure assessment: Promising approaches for human environmental health research SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE body burden; epidemiology; exposure; exposure assessment; exposure technology; geographic information systems; GIS; sensors ID S-TRANSFERASE M1; GEOGRAPHIC INFORMATION-SYSTEMS; AMBIENT AIR-POLLUTION; RISK-ASSESSMENT; LUNG-CANCER; DNA-DAMAGE; FLUORESCENT NANOSENSORS; GENETIC-VARIANTS; DISSOLVED-OXYGEN; PUBLIC-HEALTH AB New technologies and methods for assessing human exposure to chemicals, dietary and lifestyle factors, infectious agents, and other stressors provide an opportunity to extend the range of human health investigations and advance our understanding of the relationship between environmental exposure and disease. An ad hoc Committee on Environmental Exposure Technology Development was convened to identify new technologies and methods for deriving personalized exposure measurements for application to environmental health studies. The committee identified a "toolbox" of methods for measuring external (environmental) and internal (biologic) exposure and assessing human behaviors that influence the likelihood of exposure to environmental agents. The methods use environmental sensors, geographic information systems, biologic sensors, toxico-genomics, and body burden (biologic) measurements. We discuss each of the methods in relation to current use in human health research; specific gaps in the development, validation, and application of the methods are highlighted. We also present a conceptual framework for moving these technologies into use and acceptance by the scientific community. The framework focuses on understanding complex human diseases using an integrated approach to exposure assessment to define particular exposure-disease relationships and the interaction of genetic and environmental factors in disease occurrence. Improved methods for exposure assessment will result in better means of monitoring and targeting intervention and prevention programs. Key words: body burden, epidemiology, exposure, exposure assessment, exposure technology, geographic information systems, GIS, sensors. C1 NIEHS, DERT, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Univ Calif San Diego, Dept Neurosci, La Jolla, CA 92093 USA. Univ Med & Dent New Jersey, Environm & Occupat Hlth Sci Inst, Piscataway, NJ 08854 USA. Univ Michigan, Sch Med, Ann Arbor, MI USA. Univ Michigan, Sch Publ Hlth, Ann Arbor, MI 48109 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. Univ Calif Berkeley, Dept Mech Engn, Berkeley, CA 94720 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. Tufts Univ, Dept Chem, Medford, MA 02155 USA. Univ Pittsburgh, Dept Cell Biol & Physiol, Pittsburgh, PA USA. RP Weis, BK (reprint author), NIEHS, DERT, NIH, Dept Hlth & Human Serv, POB 12233,MD EC-27,111 TW Alexander Dr, Res Triangle Pk, NC 27709 USA. EM weis@niehs.nih.gov OI Potter, John/0000-0001-5439-1500; Omenn, Gilbert S./0000-0002-8976-6074 NR 121 TC 63 Z9 64 U1 6 U2 28 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 JUL PY 2005 VL 113 IS 7 BP 840 EP 848 DI 10.1289/ehp.7651 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 941YT UT WOS:000230250800029 PM 16002370 ER PT J AU Schisterman, EF Whitcomb, BW Louis, GMB Louis, TA AF Schisterman, EF Whitcomb, BW Louis, GMB Louis, TA TI Lipid adjustment in the analysis of environmental contaminants and human health risks SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE causal modeling; directed acyclic graphs; organochlorines; polychlorinated biphenyls; risk estimation; serum lipids ID PLASMA ORGANOCHLORINE LEVELS; BREAST-CANCER RISK; POLYCHLORINATED-BIPHENYLS; ADIPOSE-TISSUE; OCCUPATIONAL EXPOSURE; HUMAN-SERUM; BLOOD; EPIDEMIOLOGY; METABOLISM; WORKERS AB The literature on exposure to lipophilic agents such as polychlorinated biphenyls (PCBs) is conflicting, posing challenges for the interpretation of potential human health risks. Laboratory variation in quantifying PCBs may account for some of the conflicting study results. For example, for quantification purposes, blood is often used as a proxy for adipose tissue, which makes it necessary to model serum lipids when assessing health risks of PCBs. Using a simulation Study, we evaluated four statistical models (unadjusted, standardized, adjusted, and two-stage) for the analysis of PCB exposure, serum lipids, and health outcome risk (breast cancer). We applied eight candidate true causal scenarios, depicted by directed acyclic graphs, to illustrate the ramifications of mis-specification of underlying assumptions when interpreting results. Statistical models that deviated from underlying causal assumptions generated biased results. Lipid standardization, or the division of serum concentrations by serum lipids, was observed to be highly prone to bias. We conclude that investigators must consider biology, biologic medium (e.g., nonfasting blood samples), laboratory measurement, and other underlying modeling assumptions when devising a statistical plan for assessing health outcomes in relation to environmental exposures. C1 NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA. Johns Hopkins Univ, Dept Biostat, Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD 21205 USA. RP Schisterman, EF (reprint author), NICHHD, Epidemiol Branch, Div Epidemiol Stat & Prevent Res, NIH,Dept Hlth & Human Serv, 6100 Execut Blvd,Room 7B03, Rockville, MD 20852 USA. EM schistee@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X; Buck Louis, Germaine/0000-0002-1774-4490 NR 32 TC 195 Z9 199 U1 4 U2 16 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 JUL PY 2005 VL 113 IS 7 BP 853 EP 857 DI 10.1289/ehp.7640 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 941YT UT WOS:000230250800031 PM 16002372 ER PT J AU Kamel, F Engel, LS Gladen, BC Hoppin, JA Alavanja, MCR Sandler, DP AF Kamel, F Engel, LS Gladen, BC Hoppin, JA Alavanja, MCR Sandler, DP TI Neurologic symptoms in licensed private pesticide applicators in the Agricultural Health Study SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE fumigants; insecticides; neurologic symptoms; organochlorines; organophosphates; pesticide applicators; pesticides ID ORGANOPHOSPHATE PESTICIDES; FARM-WORKERS; EXPOSURE; NEUROTOXICITY; ASSOCIATION; FARMWORKERS; INHIBITION; SEQUELAE; COHORT AB Exposure to high levels of many pesticides has both acute and long-term neurologic consequences, but little is known about the neurotoxicity of chronic exposure to moderate levels of pesticides. We analyzed cross-sectional data from 18,782 white male licensed private pesticide applicators enrolled in the Agricultural Health Study in 1993-1997. Applicators provided information on lifetime pesticide use and 23 neurologic symptoms typically associated with pesticide intoxication. An indicator of more symptoms (>= 10 vs. < 10) during the year before enrollment was associated with cumulative lifetime days of insecticide use: odds ratios (95% confidence intervals) were 1.64 (1-36-1-97) for 1-50 days, 1.89 (1.58-2.25) for 51-500 days, and 2.50 (2.00-3-13) for > 500 days, compared with never users. A modest association for fumigants [> 50 days, 1.50 (1.24-1.81)] and weaker relationships for herbicides [> 500 days, 1.32 (0.99-1.75)] and fungicides [> 50 days, 1.23 (1.00-1.50)] were observed. Pesticide use within the year before enrollment was not associated with symptom count. Only associations with insecticides and fumigants persisted when all four pesticide groups were examined simultaneously. Among chemical classes of insecticides, associations were strongest for organophosphates and organochlorines. Associations with cumulative exposure persisted after excluding individuals who had a history of pesticide poisoning or had experienced an event involving high personal pesticide exposure. These results suggest that self-reported neurologic symptoms are associated with cumulative exposure to moderate levels of fumigants and organophosphate and organochlorine insecticides, regardless of recent exposure or history of poisoning. C1 NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, NIH, Dept Hlth & Human Serv, Rockville, MD USA. RP Kamel, F (reprint author), NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, 111 TW Alexander Dr,Room A360, Res Triangle Pk, NC 27709 USA. EM kamel@niehs.nih.gov OI Kamel, Freya/0000-0001-5052-6615; Sandler, Dale/0000-0002-6776-0018; Engel, Lawrence/0000-0001-9268-4830 NR 35 TC 56 Z9 59 U1 1 U2 7 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 JUL PY 2005 VL 113 IS 7 BP 877 EP 882 DI 10.1289/ehp.7645 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 941YT UT WOS:000230250800035 PM 16002376 ER PT J AU Goehl, TJ AF Goehl, TJ TI Note from the editors: Striving for a more reader-friendly journal SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Goehl, TJ (reprint author), NIEHS, NIH, Dept Hlth & Human Serv, POB 12233, Res Triangle Pk, NC 27709 USA. EM goehl@niehs.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUL PY 2005 VL 113 IS 7 BP A439 EP A439 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 941YT UT WOS:000230250800002 ER PT J AU Ranhotra, HS Teng, CT AF Ranhotra, HS Teng, CT TI Assessing the estrogenicity of environmental chemicals with a stably transfected lactoferrin gene promoter reporter in HeLa cells SO ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE stable transfection; HeLa cells; lactoferrin; xenoestrogens; estrogen receptors ID BREAST-CANCER CELLS; ENDOCRINE DISRUPTORS; RECEPTOR-BETA; ELEMENTS; ACTIVATION; LACTOTRANSFERRIN; TRANSCRIPTION; EXPRESSION; RESPONSES; UTERUS AB Lactoferrin is an important marker protein of the estrogens. In mice, lactoferrin expression is stimulated in the uterus by ligand-bound estrogen receptors (ERs). With this study we aimed to evaluate the effect of different environmental estrogenic chemicals on the mouse lactoferrin gene expression in a cell-based assay. We constructed a reporter that contains the firefly luciferase gene under hormone-inducible control of a 1.1 kbp fragment of the mouse lactoferrin gene promoter. In an attempt to study the promoter regulation in a chromatin context, we stably transfected the construct (pGL3-mLF-Luc) into HeLa cells, and a stable clone (HeLa-mLF-Luc) incorporating the construct was subsequently generated. Transient transfection of HeLa-mLF-Luc cells with ER alpha and ER beta expression plasmids showed that both 17 beta-estradiol (E2) and diethylstilbestrol (DES) at 10(-7) M Significantly increased luciferase expression via ER alpha and ER beta. Xenoestrogens such as bisphenol A, 4-octylphenol, 4-nonylphenol and the phytoestrogen genistein when used at increasing concentrations (10(-8) to 10(-5) M) revealed varying magnitudes of activation (1.96-8-fold). The environmental estrogens showed similar magnitudes of luciferase induction when acting through ER alpha and ER beta-mediated pathways. Also, in the absence of ERs, the xenoestrogens could not induce luciferase expression thereby reflecting receptor dependency. Taken together, the results indicate a significant responsiveness of the stably transfected mouse lactoferrin promoter to endogenous estrogen and environmental estrogenic compounds through ERs. This cell-based transcription assay system may be useful in understanding the susceptibility of estrogen target gene expression by these chemicals at the chromatin level. Published by Elsevier B.V. C1 NIEHS, Gene Regulat Sect, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA. RP Teng, CT (reprint author), NIEHS, Gene Regulat Sect, Lab Reprod & Dev Toxicol, Res Triangle Pk, NC 27709 USA. EM teng@niehs.nih.gov NR 27 TC 4 Z9 4 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1382-6689 J9 ENVIRON TOXICOL PHAR JI Environ. Toxicol. Pharmacol. PD JUL PY 2005 VL 20 IS 1 BP 42 EP 47 DI 10.1016/j.etap.2004.10.002 PG 6 WC Environmental Sciences; Pharmacology & Pharmacy; Toxicology SC Environmental Sciences & Ecology; Pharmacology & Pharmacy; Toxicology GA 930AL UT WOS:000229388000008 PM 21783566 ER PT J AU Engel, SAM Erichsen, HC Savitz, DA Thorp, J Chanock, SJ Olshan, AF AF Engel, SAM Erichsen, HC Savitz, DA Thorp, J Chanock, SJ Olshan, AF TI Risk of spontaneous preterm birth is associated with common proinflammatory cytokine polymorphisms SO EPIDEMIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; FACTOR-ALPHA GENE; PROMOTER REGION; AMNIOTIC-FLUID; HAPLOTYPE FREQUENCIES; HUMAN-PREGNANCY; DELIVERY; LABOR; DISEASE; INTERLEUKIN-10 AB Background: Preliminary data suggest that common genetic variation in immune. response genes can contribute to the risk for spontaneous preterm birth and possibly small -for-gestational age (SGA). Methods: We investigated the relationship of polymorphisms in 6 cytokine genes associated with inflammation-interleukin (IL)1 alpha, IL1 beta, IL2, IL6, tumor necrosis factor (TNF), and lymphotoxin a (LTA)-with spontaneous preterm and SGA birth in a nested casecontrol study drawn from a prospective pregnancy cohort. Women were recruited between 24 and 29 weeks' gestation at the Wake County and University of North Carolina, Chapel Hill obstetric clinics between February 1996 and June 2000. We inferred haplotypes using the EM algorithm and the Bayesian method, PHASE. We then compared haplotype frequency distributions and implemented semi-Bayesian hierarchical logistic regression analyses to obtain odds ratio (OR) estimates and 95% confidence intervals (Cls) for each polymorphism. Results: Two haplotypes spanning the TNF/LTA genes were associated with increased risk for spontaneous preterm birth in white subjects (for the AGG haplotype, OR = 1.5 [95% CI=0.8-2.6]; for the GAC haplotype, 1.6 [0.9-2.9]). Additionally, carriers of the GAG haplotype were found to have decreased risk of spontaneous preterm birth (0.6; 0.3-1.0). The TNF(-488)A and LTA(IVS1-82)C variants, constituents of the AGG and GAC haplotypes respectively, were also strongly associated with increased risk of spontaneous preterm birth. Conclusions: Our results suggest that common genetic variants in proinflammatory cytokine genes could influence the risk for spontaneous preterm birth. Selected TNF/LTA haplotypes were associated with spontaneous preterm birth in both African-American and white subjects. Our data do not support an inflammatory etiology for SGA. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. NCI, Sect Genom Variat, Pediat Oncol Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA. NCI, Core Genotyping Facil, Ctr Adv Technol, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Engel, SAM (reprint author), Mt Sinai Sch Med, Dept Community & Prevent Med, 1 Gustave L Levy Pl,Box 1172, New York, NY 10029 USA. EM Stephanie.Engel@mssm.edu FU NCRR NIH HHS [RR00046]; NICHD NIH HHS [HD28684, HD28684A]; NIEHS NIH HHS [P30ES10126]; PHS HHS [5 T32 A107001] NR 50 TC 101 Z9 101 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2005 VL 16 IS 4 BP 469 EP 477 DI 10.1097/01.ede.0000164539.09250.31 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 939JF UT WOS:000230068000007 PM 15951664 ER PT J AU Engel, SAM Olshan, AF Savitz, DA Thorp, J Erichsen, HC Chanock, SJ AF Engel, SAM Olshan, AF Savitz, DA Thorp, J Erichsen, HC Chanock, SJ TI Risk of small-for-gestational age is associated with common anti-inflammatory cytokine polymorphisms SO EPIDEMIOLOGY LA English DT Article ID NECROSIS-FACTOR-ALPHA; EXTRA-PLACENTAL MEMBRANES; PRETERM DELIVERY; LINKAGE DISEQUILIBRIUM; HAPLOTYPE FREQUENCIES; HUMAN-PREGNANCY; AMNIOTIC-FLUID; GENE; INTERLEUKIN-10; PROMOTER AB Background: Anti-inflammatory cytokines play a key role in pregnancy maintenance. Genetic variation in anti-inflammatory cytokines could influence a woman's risk of adverse reproductive outcomes. Methods: We investigated the relationship of polymorphisms in interleukin 4 (IL4), IL5, IL10, IL13, and transforming growth factor (TGF beta 1) with spontaneous preterm birth and small-for-gestational age (SGA) in a nested case-control study of a prospective pregnancy cohort. Women were recruited between 24 and 29 weeks' gestation at the Wake County and University of North Carolina, Chapel Hill obstetric clinics between February 1996 and June 2000. We inferred haplotypes using the EM algorithm and the Bayesian method, PHASE. Semi-Bayesian hierarchical logistic regression was used to obtain odds ratio (OR) estimates and 95% confidence intervals (CIs) for each polymorphism. Results: African-American mothers who carried the IL4 GCC haplotype had greater risk of spontaneous preterm birth (OR = 2.9; 95% CI = 1.2-7.4). In white mothers, carriers of the "low-produc-ing" IL4 CC and IL10 ATA haplotypes had markedly reduced risk of SGA (for the CC haplotype, 0.2 [0.0-1.2]; for the ATA haplotype, 0.5 [0.3-0.8]), whereas carriers of the "high-producing" IL4(-589)T variant had increased risk of SGA in both African-American and white mothers. Conclusions: Variants related to decreased anti-inflammatory cytokine production may lower risk of SGA. Furthermore, the same mechanism that protects against SGA might increase risk of spontaneous preterm birth. C1 Univ N Carolina, Sch Publ Hlth, Dept Epidemiol, Chapel Hill, NC USA. Univ N Carolina, Sch Med, Dept Obstet & Gynecol, Chapel Hill, NC USA. NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Core Genotyping Facil, Ctr Adv Technol, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Engel, SAM (reprint author), Mt Sinai Sch Med, Dept Community & Prevent Med, 1 Gustave L Levy Pl,Box 1172, New York, NY 10029 USA. EM Stephanie.Engel@mssm.edu FU NCRR NIH HHS [RR00046]; NICHD NIH HHS [HD28684, HD28684A]; NIEHS NIH HHS [P30ES10126]; PHS HHS [5 T32 A107001] NR 45 TC 32 Z9 33 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2005 VL 16 IS 4 BP 478 EP 486 DI 10.1097/01.ede.0000164535.36412.6b PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 939JF UT WOS:000230068000008 PM 15951665 ER PT J AU Sallmen, M Weinberg, CR Baird, DD Lindbohm, ML Wilcox, AJ AF Sallmen, M Weinberg, CR Baird, DD Lindbohm, ML Wilcox, AJ TI Has human fertility declined over time? Why we may never know SO EPIDEMIOLOGY LA English DT Article ID 1ST-PREGNANCY PLANNERS; WAITING TIME; PREGNANCY; FECUNDITY; SUBFECUNDITY; DETERMINANTS; QUALITY; GERMANY; DENMARK; SWEDEN AB Background: Reports of decreased semen quality over time have raised concerns about possible reductions in human fertility. Studies of couple fertility have produced conflicting results. We evaluate how changes in the availability and use of effective contraception and induced abortion might bias the direct study of time trends in couple fertility. Methods: We assess the potential for bias in the context of 2 common study designs: (1) a study of time-to-pregnancy that estimates fecundability (excluding unintended pregnancies) and (2) a study of infertility rates that categorizes couples as fertile or infertile (including couples with unintended pregnancies as fertile). Results: In time-to-pregnancy studies, bias alone could produce more than a 2-fold apparent increase in fecundability over recent decades. In studies of infertility rates, the bias works in the opposite direction: a 30% underestimation of infertility during earlier decades could produce an apparent decrease in fertility over time. Conclusions: Over the past 5 decades, changes in social factors that affect the rate and fate of unintended pregnancies could substantially bias time trends in fertility. These biases may explain the conflicting reports in the literature. Except in rare settings in which the factors affecting reproductive choices have not changed, it is probably impossible to identify biologic changes in fertility over recent decades. C1 Finnish Inst Occupat Hlth, Dept Epidemiol & Biostat, FI-00250 Helsinki, Finland. NIEHS, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC 27709 USA. RP Sallmen, M (reprint author), Finnish Inst Occupat Hlth, Dept Epidemiol & Biostat, Topeliuksenkatu 41 aA, FI-00250 Helsinki, Finland. EM Markku.Sallmen@ttl.fi OI Wilcox, Allen/0000-0002-3376-1311; Baird, Donna/0000-0002-5544-2653 NR 34 TC 45 Z9 46 U1 1 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2005 VL 16 IS 4 BP 494 EP 499 DI 10.1097/01.ede.0000165391.65690.e1 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 939JF UT WOS:000230068000010 PM 15951667 ER PT J AU Brinton, LA Westhoff, CL Scoccia, B Lamb, EJ Althuis, MD Mabie, JE Moghissi, KS AF Brinton, LA Westhoff, CL Scoccia, B Lamb, EJ Althuis, MD Mabie, JE Moghissi, KS TI Causes of infertility as predictors of subsequent cancer risk SO EPIDEMIOLOGY LA English DT Article ID POLYCYSTIC-OVARY-SYNDROME; HOSPITAL DISCHARGE DIAGNOSIS; OVULATION-STIMULATING DRUGS; RED HAIR COLOR; BREAST-CANCER; ENDOMETRIAL CARCINOMA; CUTANEOUS MELANOMA; FERTILITY DRUGS; UNITED-STATES; WOMEN AB Background: Although studies have found elevated risks of certain cancers linked to infertility, the underlying reasons remain unclear. Methods: In a retrospective cohort study of 12,193 U.S. women evaluated for infertility between 1965 and 1988, 581 cases of cancer were identified through 1999. We used standardized incidence ratios (SIRs) to compare cancer risk with the general population. Analyses within the cohort estimated rate ratios (RRs) associated with infertility after adjusting for other risk predictors. Results: Infertility patients demonstrated a higher cancer risk than the general population (SIR = 1.23; 95% confidence interval [CI] = 1.1-1.3), with nulligravid (primary infertility) patients at even higher risk (1.43; 1.3-1.6). Particularly elevated risks among primary infertility patients were observed for cancers of the uterus (1.93) and ovaries (2.73). Analyses within the cohort revealed increased RRs of colon, ovarian, and thyroid cancers, and of melanomas associated with endometriosis. Melanomas were linked with anovulatory problems, whereas uterine cancers predominated among patients with tubal disorders. When primary infertility patients with specific causes of infertility were compared with unaffected patients who had secondary infertility, endometriosis was linked with distinctive excesses of cancers of the colon (RR = 2.40; 95% CI = 0.7-8.4), ovaries (2.88; 1.2-7.1), and thyroid (4.65; 0.8-25.6) cancers, as well as melanomas (2.32; 0.8-6.7). Primary infertility due to anovulation particularly predisposed to uterine cancer (2.42; 1.0-5.8), and tubal disorders to ovarian cancer (1.61; 0.7-3.8). Primary infertility associated with male-factor problems was associated with unexpected increases in colon (2.85; 0.9-9.5) and uterine (3.15; 1.0-9.5) cancers. Conclusions: The effects of infertility may extend beyond gynecologic cancers. Thyroid cancers and melanomas deserve specific attention, particularly with respect to endometriosis. C1 NCI, Rockville, MD 20852 USA. Columbia Univ, New York, NY USA. Univ Illinois, Chicago, IL USA. Stanford Univ, Stanford, CA 94305 USA. Informat Management Serv Inc, Rockville, MD USA. Wayne State Univ, Detroit, MI USA. RP Brinton, LA (reprint author), NCI, 6120 Execut Blvd,Room 7068, Rockville, MD 20852 USA. EM brinton@nih.gov RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 FU NCI NIH HHS [N02-CP-40511] NR 40 TC 62 Z9 63 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2005 VL 16 IS 4 BP 500 EP 507 DI 10.1097/01.ede.0000164812.02181.d5 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 939JF UT WOS:000230068000011 PM 15951668 ER PT J AU Colt, JS Severson, RK Lubin, J Rothman, N Camann, D Davis, S Cerhan, JR Cozen, W Hartge, P AF Colt, JS Severson, RK Lubin, J Rothman, N Camann, D Davis, S Cerhan, JR Cozen, W Hartge, P TI Organochlorines in carpet dust and non-Hodgkin lymphoma SO EPIDEMIOLOGY LA English DT Article ID POLYCHLORINATED BIPHENYL CONGENERS; WESTERN WASHINGTON; ADIPOSE-TISSUE; UNITED-STATES; EXPOSURE; WORKERS; PESTICIDES; MORTALITY; CANCER; RISK AB Background: The incidence of non-Hodgkin lymphoma (NHL) has risen over the past several decades. Reasons for this increase are largely unexplained. Methods: In this population-based case-control study, we examined NHL risk and exposure to organochlorine compounds using concentrations in carpet dust as an exposure indicator. We identified NHL cases, uninfected with HIV, diagnosed between 1998 and 2000 among women and men ages 20-74 years in Iowa, Los Angeles County, and the Detroit and Seattle metropolitan areas. Controls were selected using random-digit-dialing or Medicare files. Organochlorine concentrations were measured in vacuum bag dust from 603 white cases and 443 white controls who had owned most of their carpets for at least 5 years. Results: NHL risk was elevated if any of the polychlorinated biphenyl (PCB) congeners (PCBs 105, 138, 153, 170, or 180) was detected (odds ratio = 1.5; 95% confidence interval = 1.2-2.0). Risk was elevated in the top tertile of PCB 180 (1.7; 1. 1-2.6) and in the top 2 tertiles of total PCBs (middle tertile, 1.6 [1.1-2.4]; top tertile 1.5 [1.0-2.2]). There was a positive trend in risk with increasing PCB 180 levels (P trend = 0.03). NHL risk was elevated if dichlorodiphenyldichloroethylene (DDE) was detected (1.3; 1.01.7), but only among men. A positive, but not monotonic, doseresponse relationship was observed for DDE (P trend = 0.02). Conclusions: Our findings suggest an increased risk of NHL associated with exposure to PCBs, with evidence of greater effects for PCB 180. There is also some evidence of an association with DDE. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Wayne State Univ, Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Dept Family Med, Detroit, MI USA. SW Res Inst, San Antonio, TX USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Washington, Seattle, WA 98195 USA. Mayo Clin, Coll Med, Rochester, MN USA. Univ So Calif, Los Angeles, CA USA. RP Colt, JS (reprint author), NCI, Occupat & Environm Epidemiol Branch, 6120 Execut Blvd,Room 8112, Rockville, MD 20852 USA. EM coltj@mail.nih.gov OI Cerhan, James/0000-0002-7482-178X FU NCI NIH HHS [N02-CP-19114, N01-CN-67008, N01-CN-67010, N01-PC-65064, N01-PC-67009, N02-CP-71105] NR 40 TC 64 Z9 65 U1 1 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2005 VL 16 IS 4 BP 516 EP 525 DI 10.1097/01.ede.0000164811.25760.f1 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 939JF UT WOS:000230068000014 PM 15951670 ER PT J AU Ward, MH Nuckols, JR Giglierano, J Bonner, MR Wolter, C Airola, M Mix, W Colt, JS Hartge, P AF Ward, MH Nuckols, JR Giglierano, J Bonner, MR Wolter, C Airola, M Mix, W Colt, JS Hartge, P TI Positional accuracy of two methods of geocoding SO EPIDEMIOLOGY LA English DT Article ID GEOGRAPHIC INFORMATION-SYSTEM; ENVIRONMENTAL EPIDEMIOLOGY; EXPOSURE; PATTERNS; GIS AB Background: Geocoding is often used in epidemiologic studies to map residences with geographic information systems (GIS). The accuracy of the method is usually not determined. Methods: We collected global positioning system (GPS) measurements at homes in a case-control study of non-Hodgkin lymphoma in Iowa. We geocoded the addresses by 2 methods: (1) in-house, using ArcView 3.2 software and the U.S. Census Bureau TIGER 2000 street database; and (2) automated geocoding by a commercial firm. We calculated the distance between the geocoded and GPS location (positional error) overall and separately for homes within towns and outside (rural). We evaluated the error in classifying homes with respect to their proximity to crop fields. Results: Overall, the majority of homes were geocoded with positional errors of less than 100 in by both methods (ArcView/TIGER 2000, median 62 m [interquartile range = 39-103]; commercial firm, median 61 in [interquartile range 35-137]). For town residences, the percent geocoded with errors of 100 in was 8 1 % for ArcView/ TIGER 2000 and 84% for the cominercial firm. For rural residences, a smaller percent of addresses were geocoded with this level of accuracy, especially by the commercial firm (ArcView/TIGER 2000, 56%; commercial firm, 28%). Geocoding errors affected our classification of homes according to their proximity to agricultural fields at 100 in, but not at greater distances (250-500 m). Conclusions: Our results indicate greater positional errors for rural addresses compared with town addresses. Using a commercial firm did not improve accuracy compared with our in-house method. The effect of geocoding errors on exposure classification will depend on the spatial variation of the exposure being studied. C1 NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. Iowa Geol Survey, Iowa City, IA USA. WESTAT Corp, Rockville, MD 20850 USA. RP Ward, MH (reprint author), NCI, Occupat & Environm Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, 6120 Execut Blvd,EPS 8104, Bethesda, MD 20892 USA. EM wardm@mail.nih.gov NR 23 TC 75 Z9 75 U1 4 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2005 VL 16 IS 4 BP 542 EP 547 DI 10.1097/01.ede.0000165364.54925.f3 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 939JF UT WOS:000230068000017 PM 15951673 ER PT J AU Palmer, JR Wise, LA Robboy, SJ Titus-Ernstoff, L Noller, KL Herbst, AL Troisi, R Hoover, RN AF Palmer, JR Wise, LA Robboy, SJ Titus-Ernstoff, L Noller, KL Herbst, AL Troisi, R Hoover, RN TI Hypospadias in sons of women exposed to diethylstilbestrol in utero SO EPIDEMIOLOGY LA English DT Article ID FOLLOW-UP; TUMORS; CRYPTORCHIDISM; DESCENDANTS; PREGNANCY; MOTHERS; ADENOCARCINOMA; ASSOCIATION; FERTILITY; INUTERO AB Background: Diethylstilbestrol (DES) is a synthetic estrogen that was widely prescribed to pregnant women before 1971. DES increases the risk of breast cancer in women who took the drug and the risk of reproductive tract abnormalities in their offspring. Dutch investigators have reported a 20-fold increase in risk of hypospadias among sons of women who were exposed to DES in utero. We assessed this relation in data from an ongoing study of DES-exposed persons. Methods: Several U.S. cohorts of women with documented exposure in utero to DES have been followed by mailed questionnaires since the 1970s. Comparison subjects are unexposed women of the same ages. In 1997, participants were asked about congenital abnormalities in their children. We calculated prevalence odds ratios for the risk of hypospadias in sons of exposed mothers relative to sons of unexposed mothers using generalized estimating equations to adjust for multiple sons per mother and controlling for maternal age at the son's birth. Results: We obtained data from 3916 exposed and 1746 unexposed women. These women reported a total of 13 liveborn sons with hypospadias (10 exposed, 3 unexposed). The prevalence odds ratio for risk of hypospadias among the exposed was 1.7 (95% confidence interval = 0.4-6.8). Conclusions: Our findings do not support a greatly increased risk of hypospadias among the sons of women exposed to DES in utero, as has been previously reported. C1 Boston Univ, Slone Epidemiol Ctr, Boston, MA 02215 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Dartmouth Hitchcock Med Ctr, Norris Cotton Canc Ctr, Lebanon, NH 03766 USA. Tufts Univ New England Med Ctr, Dept Obstet & Gynecol, Boston, MA 02111 USA. Univ Chicago, Dept Obstet & Gynecol, Chicago, IL 60637 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Palmer, JR (reprint author), Boston Univ, Slone Epidemiol Ctr, 1010 Commonwealth Ave, Boston, MA 02215 USA. EM jpalmer@slone.bu.edu OI Palmer, Julie/0000-0002-6534-335X; Wise, Lauren/0000-0003-2138-3752 FU NCI NIH HHS [N01-CP-21168, N01-CP-51017, N01-CP-01289] NR 25 TC 36 Z9 40 U1 1 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2005 VL 16 IS 4 BP 583 EP 586 DI 10.1097/01.ede.0000164789.59728.6d PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 939JF UT WOS:000230068000025 PM 15951681 ER PT J AU Wacholder, S AF Wacholder, S TI Population risk measures SO EPIDEMIOLOGY LA English DT Letter C1 NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Wacholder, S (reprint author), NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. EM Wacholder@NIH.gov NR 3 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2005 VL 16 IS 4 BP 594 EP 594 DI 10.1097/01.ede.0000165812.41597.08 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 939JF UT WOS:000230068000031 PM 15951687 ER PT J AU Binder, JR Bellgowan, PSF Hammeke, TA Possing, ET Frost, JA AF Binder, JR Bellgowan, PSF Hammeke, TA Possing, ET Frost, JA TI A comparison of two fMRI protocols for eliciting hippocampal activation SO EPILEPSIA LA English DT Article DE hippocampus; functional magnetic resonance imaging; memory; epilepsy ID MEDIAL TEMPORAL-LOBE; INTRACAROTID AMOBARBITAL TEST; POSITRON-EMISSION-TOMOGRAPHY; FUNCTIONAL MRI; EPISODIC MEMORY; PARAHIPPOCAMPAL CORTICES; NOVELTY DETECTION; QUANTITATIVE MRI; SEMANTIC SYSTEM; BRAIN ACTIVITY AB Purpose: Previous research suggests that the hippocampus is modulated both by stimulus novelty and by the extent to which relational processing (formation of associations) occurs during episodic encoding. The aim of this study was to compare hippocampal activation patterns measured by functional magnetic resonance imaging (fMRI) during encoding protocols emphasizing either novelty or relational processing. Methods: fMRI was performed on 32 healthy volunteers while they encoded complex visual scenes or unrecognizable scrambled versions of the same scenes. In the Novelty contrast, encoding of novel scenes was compared with encoding of a repeated pair of scenes. In the Relational Processing contrast, semantic encoding of novel scenes was compared with structural encoding of scrambled scenes. Results: Both protocols elicited bilateral hippocampal activation. Overall mean activation values were similar for the two protocols, but the Relational Processing protocol resulted in a larger volume of hippocampal activation. The pattern of activation along the longitudinal hippocampal axis differed for the two protocols. The Novelty contrast produced stronger activation in the posterior hippocampus, whereas the Relational Processing contrast produced stronger activation in the anterior hippocampus. Conclusions: Hippocampal activation is determined by both stimulus novelty and degree of relational processing during encoding. Given the importance of anterior hippocampal pathology in temporal lobe epilepsy, an approach emphasizing modulation of relational processing may be preferable for clinical fMRI of the medial temporal lobes. C1 Med Coll Wisconsin, Dept Neurol, Milwaukee, WI 53226 USA. NIH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Binder, JR (reprint author), Med Coll Wisconsin, Dept Neurol, 9200 W Wisconsin Ave, Milwaukee, WI 53226 USA. EM jbinder@mcw.edu OI Binder, Jeffrey/0000-0002-2233-5640 FU NCRR NIH HHS [M01 RR 00058]; NIMH NIH HHS [1F32 MH 11921-01A1, P01 MH 51358]; NINDS NIH HHS [R01 NS 35929, R01 NS 33576] NR 88 TC 44 Z9 44 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUL PY 2005 VL 46 IS 7 BP 1061 EP 1070 DI 10.1111/j.1528-1167.2005.62004.x PG 10 WC Clinical Neurology SC Neurosciences & Neurology GA 944LZ UT WOS:000230431800009 PM 16026558 ER PT J AU Magrath, I Shanta, V Advani, S Adde, M Arya, LS Banavali, S Bhargava, M Bhatia, K Gutierrez, M Liewehr, D Pai, S Sagar, TG Venzon, D AF Magrath, I Shanta, V Advani, S Adde, M Arya, LS Banavali, S Bhargava, M Bhatia, K Gutierrez, M Liewehr, D Pai, S Sagar, TG Venzon, D TI Treatment of acute lymphoblastic leukaemia in countries with limited resources; lessons from use of a single protocol in India over a twenty year peroid SO EUROPEAN JOURNAL OF CANCER LA English DT Article ID FOLLOW-UP; T-CELL; CHILDHOOD; CHILDREN; SURVIVAL; THERAPY; PHARMACOGENOMICS; REARRANGEMENTS; CHEMOTHERAPY; EXPERIENCE AB In the 1970s, survival rates after treatment for acute lymphoblastic leukaemia (ALL) in children and young adults (less than 25 years) in India were poor, even in specialised cancer centres. The introduction of a standard treatment protocol (MCP841) and improvements in supportive care in three major cancer centres in India led to an increase in the event-free survival rate (EFS) from less than 20% to 45-60% at 4 years. Results of treatment with protocol MCP841 between 1984 and 1990 have been published and are briefly reviewed here. In addition, previously unpublished data from 1048 patients treated between 1990 and 1997 are reported. Significant differences in both patient populations and treatment outcome were noted among the centres. In one centre, a sufficiently large number of patients were treated each year to perform an analysis of patient characteristics and outcome over time. Although steady improvement in outcome was observed, differences in the patient populations in the time periods examined were also noted. Remarkably, prognostic factors common to all three centres could not be defined. Total white blood cell count (WBC) was the only statistically significant risk factor identified in multivariate analyses in two of the centres. Age is strongly associated with outcome in Western series, but was not a risk factor for EFS in any of the centres. Comparison of patient characteristics with published series from Western nations indicated that patients from all three Indian centres had more extensive disease at presentation, as measured by WBC, lymphadenopathy and organomegaly. The proportions of ALLs with precursor T-cell immunophenotypes, particularly in Chennai, were also increased, even when differences in the age distribution were taken into consideration (in < 18-year olds, the range was 21.1-42.7%), and in molecular analyses performed on leukaemic cells from over 250 patients less than 21-years-old with precursor B-cell ALL, a lower frequency of TEL-AML1-positive ALL,cases than reported in Western series was observed. The worse outcome of treatment in Indian patients compared with recent Western series was probably due to the higher rate of toxic deaths in the Indian patients, and possibly also due to their more extensive disease - which is, at least partly, a consequence of delay in diagnosis. Differences in the spectrum of molecular subtypes may also have played a role. The higher toxic death rates observed are likely to have arisen from a combination of more extensive disease at diagnosis, co-morbidities (e.g., intercurrent infections), differences in the level of hygiene achievable in the average home, poor access to acute care, and more limited supportive care facilities in Indian hospitals. Toxic death was not associated with WBC at presentation, and hence would tend to obscure the importance of this, and, potentially, other risk factors, as prognostic indicators. Since the prevalence of individual risk factors varies in different populations and over time, their relative importance would also be expected to vary in different centres and in different time periods. This was, in fact, observed. These findings have important implications for the treatment of ALL in countries of low socioeconomic status; it cannot be assumed that risk factors defined in Western populations are equally appropriate for patient assignment to risk-adapted therapy groups in less affluent countries. They also demonstrate that heterogeneity in patient populations and resources can result in significant differences in outcome, even when the sae treatment protocol is used. This is often overlooked when comparing published patient series. Published by Elsevier Ltd. C1 Inst Pasteur, INCTR, B-1180 Brussels, Belgium. Inst Canc Res, WIA, Madras, Tamil Nadu, India. Tata Mem Hosp, Bombay 400012, Maharashtra, India. All India Inst Med Sci, Delhi, India. King Faisal Specialist Hosp & Res Ctr, Riyadh 11211, Saudi Arabia. NCI, Bethesda, MD 20892 USA. RP Magrath, I (reprint author), Inst Pasteur, INCTR, 642 Rue Engeland, B-1180 Brussels, Belgium. EM imagrath@inctr.be RI Venzon, David/B-3078-2008; OI Bhargava, Manorama/0000-0003-2135-7298 NR 36 TC 70 Z9 72 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0959-8049 J9 EUR J CANCER JI Eur. J. Cancer PD JUL PY 2005 VL 41 IS 11 BP 1570 EP 1583 DI 10.1016/j.ejca.2004.11.004 PG 14 WC Oncology SC Oncology GA 955AK UT WOS:000231196800020 PM 16026693 ER PT J AU Johnson, EO Kamilaris, TC Calogero, AE Gold, PW Chrousos, GP AF Johnson, EO Kamilaris, TC Calogero, AE Gold, PW Chrousos, GP TI Experimentally-induced hyperthyroidism is associated with activation of the rat hypothalamic-pituitary-adrenal axis SO EUROPEAN JOURNAL OF ENDOCRINOLOGY LA English DT Article ID ADRENOCORTICAL FUNCTION; ACTH-SECRETION; THYROID STORM; HORMONE; THYROTOXICOSIS; CORTICOSTERONE; STIMULATION; THYROXINE; RESPONSES AB Objective: Previous studies on the effects of altered thyroid function on the secretion and metabolism of adrenocortical hormones suggest a degree of adrenocortical hyperactivity in hyperthyroidism. We have previously shown that experimentally-induced hyperthyroidism is associated with significant alterations in pituitary-adrenal responsiveness to synthetic ovine corticotropin-releasing hormone (oCRH) that are contingent upon the duration of the altered thyroid function. The purpose of this study was to assess the time-dependent effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis by in vivo stimulation of the hypothalamic CRH neuron and adrenal cortex. Methods: The functional integrity of the HPA axis was examined in vivo in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given 50 mu g of thyroxine every day for 7 or 60 days. Responses to insulin-induced hypoglycemia and IL-1 alpha stimulation were used to assess the hypothalamic CRH neuron. Adrenocortical reserve was assessed in response to low-dose adrenocorticotropic hormone (ACTH), following suppression of the HPA axis with dexamethasone. Adrenal and thymus tissue weight, in addition to basal plasma ACTH corticosterone and thyroid indices were also determined. Results: Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days, cerebrospinal fluid (CSF) corticosterone levels were significantly increased. Basal plasma ACTH levels were similar to controls. Although plasma ACTH responses to hypoglycemic stress and IL-1 alpha administration in both short- and long-term hyperthyroidism were normal, corticosterone responses to the ACTH release during the administration of these stimuli were significantly increased. The adrenal reserve was significantly elevated in short-term hyperthyroidsim. Long-term hyperthyroidism, however, was associated with a significant reduction in adrenocortical reserve. A significant increase in adrenal weights and a decrease in thymus weights were observed in both short- and long-term hyperthyroidism. Conclusions: The available data confirms that hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally affected still remains unclear. Despite the sustained hyperactivity of the HPA axis, long-term experimentally-induced hyperthyroidism is associated with diminished adrenal functional reserve. The alterations in HPA function in states of disturbed thyroid function were found to be somewhat more pronounced as the duration of thyroid dysfunction increased. C1 Univ Ioannina, Sch Med, Dept Anat Histol Embryol, GR-45110 Ioannina, Greece. NIH, Neuroendocrinol Branch, Bethesda, MD 20892 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. Univ Athens, Sch Med, Dept Pediat, GR-11527 Athens, Greece. RP Johnson, EO (reprint author), Univ Ioannina, Sch Med, Dept Anat Histol Embryol, GR-45110 Ioannina, Greece. EM ejohnson@cc.cc.uoi.gr NR 26 TC 34 Z9 38 U1 0 U2 2 PU BIO SCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 0804-4643 J9 EUR J ENDOCRINOL JI Eur. J. Endocrinol. PD JUL PY 2005 VL 153 IS 1 BP 177 EP 185 DI 10.1530/eje.1.01923 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 947WG UT WOS:000230677400022 PM 15994759 ER PT J AU Mauch, P Ng, A Aleman, B Carde, P Constine, L Diehl, V Dinshaw, K Gospodarowicz, M Hancock, S Hodgson, D Hoppe, R Liang, R Loeffler, M Specht, L Travis, LB Wirth, A Yahalom, J AF Mauch, P Ng, A Aleman, B Carde, P Constine, L Diehl, V Dinshaw, K Gospodarowicz, M Hancock, S Hodgson, D Hoppe, R Liang, R Loeffler, M Specht, L Travis, LB Wirth, A Yahalom, J TI Report from the Rockefellar Foundation Sponsored International Workshop on reducing mortality and improving quality of life in long-term survivors of Hodgkin's disease: July 9-16, 2003, Bellagio, Italy SO EUROPEAN JOURNAL OF HAEMATOLOGY LA English DT Article; Proceedings Paper CT 6th International Symposium on Hodgkins Disease CY SEP 18-21, 2004 CL Cologne, GERMANY SP German Hodgkin Study Grp DE Hodgkin's disease; cancer survivors; complications ID ESTROGEN PLUS PROGESTIN; MEDIASTINAL RADIATION-THERAPY; HEALTHY POSTMENOPAUSAL WOMEN; BREAST-CANCER; PNEUMOCOCCAL VACCINE; ANTIBODY-RESPONSES; CARDIAC TOXICITY; CHEMOTHERAPY; RADIOTHERAPY; TRIAL AB A workshop, sponsored by the Rockefellar Foundation, was held between 9 to 16 July, 2003 to devise strategies to reduce mortality and improve quality of life of long-term survivors of Hodgkin's disease. Participants were selected for their clinical and research background on late effects after Hodgkin's disease therapy. Experts from both developed and developing nations were represented in the workshop, and efforts were made to ensure that the proposed strategies would be globally applicable whenever possible. The types of late complications, magnitude of the problem, contributing risk factors, methodology to assess the risk, and challenges faced by developing countries were presented. The main areas of late effects of Hodgkin's disease discussed were as follows: second malignancy, cardiac disease, infection, pulmonary dysfunction, endocrine abnormalities, and quality of life. This report summarizes the findings of the workshop, recommendations, and proposed research priorities in each of the above areas. C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Netherlands Canc Inst, Amsterdam, Netherlands. Inst Gustave Roussy, Villejuif, France. Univ Rochester, Rochester, NY USA. Univ Cologne, Cologne, Germany. Tata Mem Hosp, Bombay, Maharashtra, India. Univ Toronto, Princess Margaret Hosp, Toronto, ON, Canada. Stanford Univ, Palo Alto, CA 94304 USA. Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Univ Leipzig, D-7010 Leipzig, Germany. Univ Copenhagen, DK-1168 Copenhagen, Denmark. NIH, Rockville, MD USA. Peter MacCallum Canc Ctr, Melbourne, Vic, Australia. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. RP Mauch, P (reprint author), 75 Francis St,ASB1-L2, Boston, MA 02115 USA. EM pmauch@lroc.harvard.edu NR 47 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0902-4441 J9 EUR J HAEMATOL JI Eur. J. Haematol. PD JUL PY 2005 VL 75 SU 66 BP 68 EP 76 PG 9 WC Hematology SC Hematology GA 932YT UT WOS:000229591400012 ER PT J AU Xie, X Lemcke, T Gussio, R Zaharevitz, DW Leost, M Meijer, L Kunick, C AF Xie, X Lemcke, T Gussio, R Zaharevitz, DW Leost, M Meijer, L Kunick, C TI Epoxide-containing side chains enhance antiproliferative activity of paullones SO EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY LA English DT Article DE antiproliferative activity; cyclin-dependent kinases; epoxides; paullones; Stille coupling ID CYCLIN-DEPENDENT KINASES; ANTICANCER DRUG DISCOVERY; INHIBITORS; CANCER; TARGETS; SCREEN; AGENTS; HIV-1; ACID AB The introduction of side chains bearing epoxide motifs into the molecular scaffold of kenpaullone and 9-trifluoromethylpaullone led to improved antiproliferative activity of the novel derivatives for human tumor cell lines. The syntheses were accomplished applying Stille coupling for the introduction of unsaturated side chains into the 2-position of the paullones and subsequently employing a hydrogen peroxide/nitrile mixture for the epoxidation of C,C-double bonds. (c) 2005 Elsevier SAS. All rights reserved. C1 Tech Univ Carolo Wilhelmina Braunschweig, Inst Pharmazeut Chem, D-38106 Braunschweig, Germany. Univ Hamburg, Inst Pharm, D-20146 Hamburg, Germany. NCI, Rockville, MD 20893 USA. CNRS, Biol Stn, F-29682 Roscoff, France. RP Kunick, C (reprint author), Tech Univ Carolo Wilhelmina Braunschweig, Inst Pharmazeut Chem, Beethovenstr 55, D-38106 Braunschweig, Germany. EM c.kunick@tu-braunschweig.de NR 29 TC 25 Z9 26 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS PA 23 RUE LINOIS, 75724 PARIS, FRANCE SN 0223-5234 J9 EUR J MED CHEM JI Eur. J. Med. Chem. PD JUL PY 2005 VL 40 IS 7 BP 655 EP 661 DI 10.1016/j.ejmech.2005.02.004 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 938OO UT WOS:000230012900005 PM 15935900 ER PT J AU Toba, Y Pakiam, JG Wray, S AF Toba, Y Pakiam, JG Wray, S TI Voltage-gated calcium channels in developing GnRH-1 neuronal system in the mouse SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE axon outgrowth; LHRH neurons; nasal explants; neuronal migration; nifedipine; olfactory system; omega-conotoxin GVIA ID HORMONE NEURONS; NEURITE OUTGROWTH; LHRH NEURONS; CAENORHABDITIS-ELEGANS; OLFACTORY PLACODE; CORTICAL-NEURONS; EXPLANT CULTURES; PROGENITOR CELLS; GROWTH CONES; IN-VITRO AB Migration of gonadotropin-releasing hormone-1 (GnRH-1) neurons from the nasal placode into the central nervous system occurs in all vertebrates. This study characterizes the expression of L- and N-type voltage-gated calcium channels (VGCCs) in migrating GnRH-1 neurons in mice. Class C (L-type) and class B (N-type) VGCGs were detected in GnRH-1 cells and cells in the olfactory and vomeronasal epithelium during prenatal development. This expression pattern was mimicked in a nasal explant model known to retain many characteristics of GnRH-1 development in vivo. Using this in vitro system, perturbation studies were performed to elucidate the role of VGCCs in GnRH-1 neuronal development. This report shows that olfactory axon outgrowth and GnRH-1 neuronal migration are attenuated when nasal explants are grown in calcium-free media, and that this effect is temporally restricted to an early developmental period. Blockade of either the L- or the N-type channel did not alter GnRH-1 cell number or overall olfactory axon outgrowth. However, blockade of N-type channels altered the distribution of GnRH-1 neurons in the periphery of the nasal explants. In these explants, more GnRH-1 neurons were located proximal to, and fewer GnRH-1 neurons distal to, the main tissue mass, suggesting a general decrease in the rate of GnRH-1 neuronal migration. These results indicate that extracellular calcium is required for initiating GnRH-1 neuronal migration and that these events are partially dependent on N-type VGCC signals. C1 NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Wray, S (reprint author), NINDS, Cellular & Dev Neurobiol Sect, NIH, Bethesda, MD 20892 USA. EM swray@codon.nih.gov OI wray, susan/0000-0001-7670-3915 NR 55 TC 20 Z9 20 U1 0 U2 0 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 JUL PY 2005 VL 22 IS 1 BP 79 EP 92 DI 10.1111/j.1460-9568.2005.04194.x PG 14 WC Neurosciences SC Neurosciences & Neurology GA 946MW UT WOS:000230577400009 PM 16029198 ER PT J AU Kleeberger, SR AF Kleeberger, SR TI Genetic aspects of pulmonary responses to inhaled pollutants SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article; Proceedings Paper CT Workshop on Experimental Assessment of the Toxicological Effects of Inhaled Complex Mixtures on the Respiratory Systems CY APR 23-25, 2005 CL Barcelona, SPAIN SP Univ Barcelona, Fac Med, Univ Valencia, Fac Med, European Soc Pathol, Catalunya Canc AECC DE air pollution; susceptibility factors; genetic factors; quantitative analysis; mapping technologies; human and mouse genomes ID OZONE-INDUCED INFLAMMATION; INDUCED LUNG INFLAMMATION; AIR-POLLUTION; MEXICO-CITY; ASTHMATIC-CHILDREN; LINKAGE ANALYSIS; RECEPTOR 4; SUSCEPTIBILITY; EXPOSURE; MICE AB Air pollution continues to be a major public health concern in industrialized cities throughout the world. Recent population and epidemiological studies that have associated ozone and particulate exposures with morbidity and mortality outcomes underscore the important detrimental effects of these pollutants on the lung. Inter-individual variation in human responses to air pollutants suggests that some subpopulations are at increased risk to the detrimental effects of pollutant exposure, and it has become clear that genetic background is an important susceptibility factor. Environmental exposures to inhaled pollutants and genetic factors associated with disease risk likely interact in a complex fashion that varies from one population to another. The relationships between the genetic background and disease risk and severity is often evaluated through traditional family-based linkage studies and positional cloning techniques. Case-control studies based on association of disease or disease subphenotypes with candidate genes may have certain advantages over family pedigree studies, and have become useful for understanding complex disease phenotypes. This is based in part on continued development of quantitative analysis and development of mapping technologies. Linkage analyses with genetically standardized animal models are useful to identify genetic determinants of host responses to environmental stimuli. For example, linkage analyses using inbred mice have identified chromosomal segments (quantitative trait loci, QTL) that contain genes that control susceptibility to the lung inflammatory and immune dysfunction responses to ozone, nitrogen dioxide, zinc oxide, and sulfate-associated particles. Candidate genes within the pollutant susceptibility QTLs have been tested for proof-of-concept using gene-targeting and overexpression models. Importantly, significant homology exists between the human and mouse genomes. Therefore, comparative mapping between the human and mouse genomes should yield candid ate susceptibility genes that may be tested by association studies in humans. The combined human studies and mouse modeling will provide important insight to understanding genetic factors that contribute to differential susceptibility to pollutants in human populations. (c) 2005 Elsevier GmbH. All rights reserved. C1 Natl Inst Environm Hlth Sci, Lab Resp Biol, Res Triangle Pk, NC 27709 USA. RP Kleeberger, SR (reprint author), Natl Inst Environm Hlth Sci, Lab Resp Biol, 111 TW Alexander Dr,Bldg 101,Rm D240, Res Triangle Pk, NC 27709 USA. EM kleeber1@niehs.nih.gov NR 49 TC 20 Z9 22 U1 0 U2 2 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD JUL PY 2005 VL 57 SU 1 BP 147 EP 153 DI 10.1016/j.etp.2005.05.017 PG 7 WC Pathology; Toxicology SC Pathology; Toxicology GA 954KL UT WOS:000231153900011 PM 16092722 ER PT J AU Rothemund, Y Schaefer, M Grusser, SM Flor, H AF Rothemund, Y Schaefer, M Grusser, SM Flor, H TI Localization of the human female breast in primary somatosensory cortex SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article DE EEG; trunk representation; electrical stimulation; somatosensory evoked potential (SEP); source localization ID POSTCENTRAL PARIETAL CORTEX; LARGE-ARRAY BIOMAGNETOMETER; ELECTRICAL-STIMULATION; EVOKED-POTENTIALS; CEREBRAL-CORTEX; BODY-SURFACE; MEG; REPRESENTATION; HOMUNCULUS; FIELDS AB Rationale: Despite an extensive body of research on the topography of the primary somatosensory cortex (S1) little is known about the representation of the trunk. Aim: The aim of this study was to determine the representation of the breast in S1 in human females. Results: The representation of the human breast in primary somatosensory cortex was determined in ten healthy female subjects. Non-painful electrical stimulation of the mammilla (Th4 dermatome), groin (L1 dermatome) and the first digit of both sides of the body activated cutaneous receptors and thus elicited somatosensory evoked potentials. The representation of these body parts in primary somatosensory cortex (S1) was determined using neuroelectric source imaging. Equivalent current dipole localizations were overlaid with individual structural magnetic resonance images to account for individual cortical differences. The breast representation was localized between the representation of the groin and the first digit. In the medial-lateral direction the representation of the breast was approximately 15 mm lateral of the longitudinal fissure in the contralateral hemisphere. Source localizations were stable across subjects. However, one subject showed ipsilateral representation of the breast, which might be related to bilateral receptive fields of the ventral body midline representation. This study confirms the Penfield and Rasmussen (1950) invasive data by use of noninvasive source imaging. C1 Univ Heidelberg, Cent Inst Mental Hlth, Dept Clin & Cognit Neurosci, D-68159 Mannheim, Germany. NINDS, Human Cortical Physiol Sect, NIH, Bethesda, MD 20892 USA. Inst Med Psychol, Ctr Humanities & Hlth Sci, D-10117 Berlin, Germany. RP Rothemund, Y (reprint author), Univ Hosp Charite Psychosomat Med, Luisenstr 13A, D-10117 Berlin, Germany. EM yvonne.rothemund@charite.de OI Flor, Herta/0000-0003-4809-5398 NR 29 TC 5 Z9 5 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0014-4819 J9 EXP BRAIN RES JI Exp. Brain Res. PD JUL PY 2005 VL 164 IS 3 BP 357 EP 364 DI 10.1007/s00221-005-2257-2 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 947EB UT WOS:000230625100009 PM 15791462 ER PT J AU Dey, N Howell, BW De, PK Durden, DL AF Dey, N Howell, BW De, PK Durden, DL TI CSK negatively regulates nerve growth factor induced neural differentiation and augments AKT kinase activity SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE PC12 cells; CSK; SRC; FYN; YES; NGF; RAS; RAC; AKT; ERK; neurite outgrowth; integrin; migration ID SIGNAL-TRANSDUCTION PATHWAYS; MEDIATES NEURITE OUTGROWTH; PC12 CELL-DIFFERENTIATION; PROTEIN-TYROSINE KINASES; SRC-FAMILY; C-SRC; NEURONAL DIFFERENTIATION; BRAIN-DEVELOPMENT; TRK RECEPTORS; ACTIVATION AB Src family kinases are involved in transducing growth factor signals for cellular differentiation and proliferation in a variety of cell types. The activity of all Src family kinases (SFKs) is controlled by phosphorylation at their C-terminal 527-tyrosine residue by C-tenninal SRC kinase, CSK. There is a paucity of information regarding the role of CSK and/or specific Sre family kinases in neuronal differentiation. Pretreatment of PC12 cells with the Src family kinase inhibitor, PP1, blocked NGF-induced activation of SFKs and obliterated neurite outgrowth. To confirm a role for CSK and specific isoforms of SFKs in neuronal differentiation, we overexpressed active and catalytically dead CSK in the rat pheochromocytoma cell line, PC12. CSK overexpression caused a profound inhibition of NGF-induced activation of FYN, YES, RAS, and ERK and inhibited neurite outgrowth, NGF-stimulated integrin-directed migration and blocked the NGF-induced conversion of GDP-RAC to its GTP-bound active state. CSK overexpression markedly augmented the activation state of AKT following NGF stimulation. In contrast, kinase-dead CSK augmented the activation of FYN, RAS, and ERK and increased neurite outgrowth. These data suggest a distinct requirement for CSK in the regulation of NGF/TrkA activation of RAS, RAC, ERK, and AKT via the differential control of SFKs in the orchestration of neuronal differentiation. (c) 2005 Elsevier Inc. All rights reserved. C1 Emory Univ, Sch Med, Dept Pediat, Sect Pediat Hematol Oncol,AFLAC Canc Ctr, Atlanta, GA 30022 USA. Emory Univ, Sch Med, Blood Disorders Serv, Atlanta, GA 30022 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Durden, DL (reprint author), Emory Univ, Sch Med, Dept Pediat, Sect Pediat Hematol Oncol,AFLAC Canc Ctr, Atlanta, GA 30022 USA. EM Don_Durden@oz.ped.emory.edu OI Howell, Brian/0000-0002-0204-0773 FU NCI NIH HHS [CA94233] NR 46 TC 26 Z9 26 U1 0 U2 1 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD JUL 1 PY 2005 VL 307 IS 1 BP 1 EP 14 DI 10.1016/j.yexcr.2005.02.029 PG 14 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 934QJ UT WOS:000229723000001 PM 15890337 ER PT J AU Hayden, RE Luong, QT Hills, RK Wheatley, K Khanim, KL Steeg, PS Drayson, MT Bunce, CM AF Hayden, RE Luong, QT Hills, RK Wheatley, K Khanim, KL Steeg, PS Drayson, MT Bunce, CM TI NM23-H1 acts as a potent survival factor against primary AML cells and normal blast cells SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 30-AUG 02, 2005 CL Univ Glasgow, Glasgow, SCOTLAND HO Univ Glasgow C1 Univ Birmingham, Sch Biosci, Birmingham, W Midlands, England. Univ Calif Los Angeles, Dept Med, Dept Haematol & Oncol, Los Angeles, CA 90024 USA. Univ Birmingham, Birmingham Clin Trials Unit, Birmingham, W Midlands, England. Univ Birmingham, Div Immun & Infect, Birmingham, W Midlands, England. NCI, Womens Canc Sect, Bethesda, MD 20892 USA. RI Luong, Quang/C-3253-2015 NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2005 VL 33 IS 7 SU 1 MA 12 BP 40 EP 40 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 951DB UT WOS:000230908100009 ER PT J AU Cokic, VP Economou, AP Wahl, LM Milenkovic, P Schechter, AN AF Cokic, VP Economou, AP Wahl, LM Milenkovic, P Schechter, AN TI G protein-coupled receptors in hydroxyurea activation of nitric oxide/CGMP pathways and gamma-globin induction SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 30-AUG 02, 2005 CL Univ Glasgow, Glasgow, SCOTLAND HO Univ Glasgow C1 Inst Med Res, Belgrade, Serbia Monteneg. Univ Geneva, Fac Med, Geneva, Switzerland. NIDCR, NIH, Bethesda, MD USA. NIDDK, NIH, Bethesda, MD USA. 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2005 VL 33 IS 7 SU 1 MA 161 BP 80 EP 80 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 951DB UT WOS:000230908100151 ER PT J AU Cokic, VP Beleslin-Cokic, BB Noguchi, CT Schechter, AN AF Cokic, VP Beleslin-Cokic, BB Noguchi, CT Schechter, AN TI Hydroxyurea induces eNOS activity and protein levels in endothelial cells SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 30-AUG 02, 2005 CL Univ Glasgow, Glasgow, SCOTLAND HO Univ Glasgow C1 Inst Med Res, Lab Expt Hematol, Belgrade, Serbia Monteneg. Univ Clin Ctr, Sch Med, Inst Endocrinol Diabet & Metab, Belgrade, Serbia Monteneg. NIDDK, Mol Med Branch, NIH, Bethesda, MD USA. 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2005 VL 33 IS 7 SU 1 MA 190 BP 87 EP 88 PG 2 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 951DB UT WOS:000230908100180 ER PT J AU Chen, TC Smith, AL Ellison, FM Young, NS AF Chen, TC Smith, AL Ellison, FM Young, NS TI C-Kit expression and signaling in the regulation of hematopoietic stem cell proliferation and senescence SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 30-AUG 02, 2005 CL Univ Glasgow, Glasgow, SCOTLAND HO Univ Glasgow C1 NHLBI, Bethesda, MD 20892 USA. 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2005 VL 33 IS 7 SU 1 MA 214 BP 93 EP 93 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 951DB UT WOS:000230908100203 ER PT J AU Chen, L Shi, Y Chin, K Rodgers, GP AF Chen, L Shi, Y Chin, K Rodgers, GP TI Evidence of interconversion within hematopoietic lineage committed cells SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract CT 34th Annual Meeting of the International-Society-for-Experimental-Hematology CY JUL 30-AUG 02, 2005 CL Univ Glasgow, Glasgow, SCOTLAND HO Univ Glasgow C1 NIDDK, Mol & Clin Hematol Branch, NIH, Bethesda, MD USA. 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 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUL PY 2005 VL 33 IS 7 SU 1 MA 217 BP 94 EP 94 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 951DB UT WOS:000230908100206 ER PT J AU Saito-Nakano, Y Loftus, BJ Hall, N Nozaki, T AF Saito-Nakano, Y Loftus, BJ Hall, N Nozaki, T TI The diversity of rab GTPases in Entamoeba histolytica SO EXPERIMENTAL PARASITOLOGY LA English DT Article; Proceedings Paper CT 2nd EMBO Workshop on Pathogenesis and Amoebiasis CY NOV 16-20, 2004 CL Ein Gedi, ISRAEL DE Entamoeba histolytica; membrane traffic; phylogeny; Rab GTPase ID GTP-BINDING PROTEINS; MEMBRANE; ENDOSOMES; PATHWAY; FAMILY; GENE AB Rab proteins are ubiquitous small GTP-binding proteins that form a highly conserved family and regulate vesicular trafficking. Recent completion of the genome of the enteric protozoan parasite Entamoeba histolytica enabled us to identify an extremely large number (> 90) of putative Rab genes. Multiple alignment and phylogenic analysis of amebic, human, and yeast Rab showed that only 22 amebic Rab proteins including EhRab1, EhRab2, EhRab5, EhRab7, EhRab8, EhRab11, and EhRab21 showed significant similarity to Rab from other organisms. The 69 remaining amebic Rab proteins showed only moderate similarity (< 40% identity) to Rab proteins from other organisms. Approximately one-third of Rab proteins including Rab7, Rab11, and RabC form 15 subfamilies, which contain up to nine isoforms. Approximately 70% of amebic Rab genes contain single or multiple introns, and this proportion is significantly higher than that of common genes in this organism. Twenty-five Rabs possess an atypical carboxyl terminus such as CXXX, XCXX, XXCX, XXXC, and no cysteine. We propose annotation of amebic Rab genes and discuss biological significance of this extraordinary diversity of EhRab proteins in this organism. (c) 2005 Elsevier Inc. All rights reserved. C1 Gunma Univ, Grad Sch Med, Dept Parasitol, Maebashi, Gumma 3718511, Japan. NIAID, Dept Parasitol, Shinjuku Ku, Tokyo 1628640, Japan. Inst Genom Res, Rockville, MD 20850 USA. Japan Sci & Technol Agcy, Precursory Res Embryon Sci & Technol, Tachikawa, Tokyo 1900012, Japan. RP Nozaki, T (reprint author), Gunma Univ, Grad Sch Med, Dept Parasitol, 3-39-22 Showa Machi, Maebashi, Gumma 3718511, Japan. EM nozaki@med.gunma-u.ac.jp OI Hall, Neil/0000-0003-2808-0009 NR 28 TC 66 Z9 70 U1 1 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4894 J9 EXP PARASITOL JI Exp. Parasitol. PD JUL PY 2005 VL 110 IS 3 BP 244 EP 252 DI 10.1016/j.exppara.2005.02.021 PG 9 WC Parasitology SC Parasitology GA 939JA UT WOS:000230067400015 PM 15955319 ER PT J AU Rathore, D McCutchan, TF Sullivan, M Kumar, S AF Rathore, D McCutchan, TF Sullivan, M Kumar, S TI Antimalarial drugs: current status and new developments SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE antimalarial; artemisinin; artesunate; atovaquone; chloroquine; lumefantrine; malaria; mefloquine; Plasmodium; protease inhibitors; pyrimethamine; sulfadoxine; triclosan ID PLASMODIUM-FALCIPARUM MALARIA; NONIMMUNE COLOMBIAN SOLDIERS; PLACEBO-CONTROLLED TRIAL; UNCOMPLICATED FALCIPARUM; DOUBLE-BLIND; SULFADOXINE-PYRIMETHAMINE; AFRICAN CHILDREN; IN-VITRO; PEPTIDE DEFORMYLASE; PROTEIN FARNESYLTRANSFERASE AB Malaria continues to be a major threat in the developing world, with > 1 million clinical episodes and 3000 deaths every day. in the last century, malaria claimed between 150 and 300 million lives, accounting for 2 - 5% of all deaths. Currently similar to 40% of the world population resides in areas of active malaria transmission. The disease symptoms are most severe in young children and pregnant women. A total of 90% of the disease-associated mortality occurs in Subsaharan Africa, despite the fact that malaria is indigenous to most tropical regions. A licensed vaccine for malaria has not become a reality and antimalarial drugs are the only available method of treatment. Although chloroquine, the first synthetically developed antimalarial, proved to be an almost magical cure for > 30 years, the emergence and spread of chloroquine-resistant parasites has made it virtually ineffective in most parts of the world. Currently, artemisinin, a plant-derived antimalarial, is the only available drug that is globally effective against the parasite. Although several new drugs have been introduced in the past 30 years, widespread or isolated cases of resistance indicate that their window of effectiveness will be limited. Thus, there is an urgent need to develop new therapeutics and regimens for malaria control. This article presents an overview of the currently available antimalarial chemotherapy options and the efforts being undertaken to develop new drugs based on both the recent technological advances and modifications to the old remedies, and on combination therapies. C1 Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20850 USA. Virginia Polytech Inst & State Univ, Virginia Bioinformat Inst, Blacksburg, VA 24061 USA. NIAID, Lab Malaria & Vector Res, Rockville, MD 20850 USA. RP Kumar, S (reprint author), Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Rockville Pike, Rockville, MD 20850 USA. EM KumarS@cber.fda.gov NR 111 TC 40 Z9 42 U1 1 U2 12 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3784 J9 EXPERT OPIN INV DRUG JI Expert Opin. Investig. Drugs PD JUL PY 2005 VL 14 IS 7 BP 871 EP 883 DI 10.1517/13543784.14.7.871 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 950DH UT WOS:000230837300011 PM 16022576 ER PT J AU Berman, J AF Berman, J TI Miltefosine to treat leishmaniasis SO EXPERT OPINION ON PHARMACOTHERAPY LA English DT Review DE clinical trials; cutaneous leishmaniasis; miltefosine; oral therapy; preclinical evaluation; visceral leishmaniasis ID INDIAN VISCERAL LEISHMANIASIS; CUTANEOUS LEISHMANIASIS; ORAL MILTEFOSINE; ETHER LYSOPHOSPHOLIPIDS; DONOVANI PROMASTIGOTES; TRYPANOSOMA-CRUZI; AMINOSIDINE; INFECTION; EFFICACY; ANALOGS AB Leishmaniasis exists in both visceral and cutaneous forms, and miltefosine is the first oral agent with demonstrable efficacy against both types of this disease. At a dose of similar to 2.5 mg/kg/day for 28 days, miltefosine is > 90% curative for visceral disease in India and cutaneous disease in Colombia. Miltefosine is a lecithin analogue and its mechanism may be to inhibit phosphatidylcholine biosynthesis in the causative parasites. The clinical half-life of miltefosine is similar to 7 days. Whether or not miltefosine can be used for widespread out-patient treatment of individuals and whole populations depends on whether its efficacy and tolerability can be maintained in further treatment trials. C1 NIH, Natl Ctr Complementary & Alternat Med, Off Clin & Regulatory Affairs, Bethesda, MD 20892 USA. RP Berman, J (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Off Clin & Regulatory Affairs, 6707 Democracy Blvd,Suite 401, Bethesda, MD 20892 USA. EM Bermajo@mail.nih.gov NR 22 TC 36 Z9 38 U1 0 U2 6 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1465-6566 J9 EXPERT OPIN PHARMACO JI Expert Opin. Pharmacother. PD JUL PY 2005 VL 6 IS 8 BP 1381 EP 1388 DI 10.1517/14656566.6.8.1381 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 952GG UT WOS:000230991400009 PM 16013987 ER PT J AU Zelenka, PS Smith, J AF Zelenka, PS Smith, J TI Therapeutic potential of CDK5 inhibitors to promote corneal epithelial wound healing SO EXPERT OPINION ON THERAPEUTIC PATENTS LA English DT Review DE cornea; cyclin-dependent kinase; diabetic keratopathy; epithelium; infectious keratitis; neurotrophic keratopathy; wound healing ID CYCLIN-DEPENDENT KINASE-5; TYROSINE-HYDROXYLASE; CELL-ADHESION; SUBSTANCE-P; EXPRESSION; DIFFERENTIATION; MIGRATION; ACTIVATOR; DEFECTS; GROWTH AB Cyclin-dependent kinase 5 (CDK5) is generally considered to be a neuron-specific enzyme, and CDK5 inhibitors have most often been claimed for pharmacologic use in neurodegenerative diseases. However, recent findings indicate that CDK5 also has important functions in some non-neuronal cells, where it regulates such processes as differentiation, senescence, adhesion and migration. In particular, CDK5 activity has been shown to increase adhesion and decrease migration of corneal epithelial cells, both in vitro and in transgenic mouse models. Conversely, inhibition of CDK5 activity significantly enhances closure of corneal epithelial defects, suggesting a novel therapeutic use for CDK5 inhibitors. This review evaluates the therapeutic potential of currently available CDK5 inhibitors for this application and considers the types of corneal epithelial defects that may benefit from such treatment. C1 NEI, NIH, Bethesda, MD 20892 USA. RP Zelenka, PS (reprint author), NIH Bldg 7,Room 102,7 Mem Dr,MSC 0704, Bethesda, MD 20892 USA. EM zelenkap@nei.nih.gov; smithj@nei.nih.gov NR 96 TC 5 Z9 5 U1 0 U2 1 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1354-3776 J9 EXPERT OPIN THER PAT JI Expert Opin. Ther. Patents PD JUL PY 2005 VL 15 IS 7 BP 875 EP 887 DI 10.1517/13543776.15.7.875 PG 13 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 950EJ UT WOS:000230840100008 ER PT J AU Liu, F Boross, P Tozser, J Louis, JM Harrison, RW Weber, IT AF Liu, F Boross, P Tozser, J Louis, JM Harrison, RW Weber, IT TI Analysis of HIV-1 protease mutants to understand mechanisms of resistance SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 Georgia State Univ, Dept Biol, Atlanta, GA USA. Debrecen Univ, Fac Med, Dept Biochem & Mol Biol, Debrecen, Hungary. NIDDKD, Phys Chem Lab, NIH, Bethesda, MD 20892 USA. Georgia State Univ, Dept Comp Sci, Atlanta, GA 30303 USA. EM fliu@student.gsu.edu RI Tozser, Jozsef/A-7840-2008 OI Tozser, Jozsef/0000-0003-0274-0056 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 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 12 EP 12 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826100038 ER PT J AU Morozov, V Wawrousek, EF AF Morozov, V Wawrousek, EF TI Arrested apoptosis in lens fiber cells: a possible role of alpha-crystallin SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 NEI, Mol & Dev Biol Lab, NIH, Bethesda, MD 20892 USA. EM morozovv@nei.nih.gov 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 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 40 EP 40 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826100135 ER PT J AU Meshorer, E Toiber, D Bryk, B Dori, A Soreq, H AF Meshorer, E Toiber, D Bryk, B Dori, A Soreq, H TI SC35 promotes prolonged stress-induced 3 ' alternative splicing of acetylcholinesterase SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 Hebrew Univ Jerusalem, Jerusalem, Israel. NCI, NIH, Bethesda, MD 20892 USA. EM meshoree@mail.nih.gov 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 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 50 EP 50 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826100170 ER PT J AU Koonin, EV Jordan, IK Kondrashov, FA Adzhubei, IA Wolf, YI Kondrashov, AS Sunyaev Sr AF Koonin, EV Jordan, IK Kondrashov, FA Adzhubei, IA Wolf, YI Kondrashov, AS Sunyaev, SR TI Universal and lineage-specific trends in protein evolution SO FEBS JOURNAL LA English DT Meeting Abstract CT 30th Congress of the Federation-of-European-Biochemical-Societies (FEBS)/9th IUBMB Conference CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Federat European Biochem Soc, Int Union Biochem & Mol Biol C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. Univ Calif Davis, Sect Evolut & Ecol, Davis, CA 95616 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Med,Div Genet, Boston, MA 02115 USA. EM koonin@ncbi.nlm.nih.gov RI Kondrashov, Fyodor Alexeevich/H-6331-2015 OI Kondrashov, Fyodor Alexeevich/0000-0001-8243-4694 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 79 EP 79 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826100266 ER PT J AU Moroz, OV Harkiolaki, M Galperin, MY Murzin, AG Makarova, KS Koonin, EV Gonzales-Pacanowska, D Wilson, KS AF Moroz, OV Harkiolaki, M Galperin, MY Murzin, AG Makarova, KS Koonin, EV Gonzales-Pacanowska, D Wilson, KS TI Structural analysis of dimeric dUTPases from Campylobacter jejuni and Leishmania major SO FEBS JOURNAL LA English DT Meeting Abstract CT 30th Congress of the Federation-of-European-Biochemical-Societies (FEBS)/9th IUBMB Conference CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Federat European Biochem Soc, Int Union Biochem & Mol Biol C1 Univ York, York Struct Biol Lab, York YO10 5DD, N Yorkshire, England. Canc Res UK Cell Signaling Grp, Oxford, England. Weatherall Inst Mol Med, Oxford, England. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. MRC, Ctr Prot Engn, Cambridge, England. Inst Parasitol & Biomed Lopez Neyra, Granada, Spain. EM olga@ysbl.york.ac.uk NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 94 EP 94 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826100318 ER PT J AU Koonin, EV Wolf, YI Carmel, L AF Koonin, EV Wolf, YI Carmel, L TI Correlations between quantitative measures of genome evolution, expression and function SO FEBS JOURNAL LA English DT Meeting Abstract CT 30th Congress of the Federation-of-European-Biochemical-Societies (FEBS)/9th IUBMB Conference CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Federat European Biochem Soc, Int Union Biochem & Mol Biol C1 NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. EM koonin@ncbi.nlm.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 103 EP 103 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826100348 ER PT J AU Karginov, VA Nestorovich, EM Moayeri, M Leppla, SH Fahmi, NE Vaisman, II Hecht, SM Bezrukov, SM AF Karginov, VA Nestorovich, EM Moayeri, M Leppla, SH Fahmi, NE Vaisman, II Hecht, SM Bezrukov, SM TI Blocking anthrax at the PA channel SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 Innovat Biol Inc, Manassas, VA USA. NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD USA. NIAID, Bacterial Toxins & Therapeut Sect, NIH, Bethesda, MD 20892 USA. Pinnacle Pharmaceut Inc, Charlottesville, VA USA. George Mason Univ, Sch Computat Sci, Manassas, VA USA. EM vak@innovbio.com RI Vaisman, Iosif/K-5268-2012 OI Vaisman, Iosif/0000-0001-6858-1516 NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 192 EP 192 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826101181 ER PT J AU Gottesman, MM Paterson, JK Chen, KG Annereau, JP Szakacs, G AF Gottesman, MM Paterson, JK Chen, KG Annereau, JP Szakacs, G TI New ABC transporters associated with multidrug resistance in cancer SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 NCI, Canc Res Ctr, Cell Biol Lab, Bethesda, MD 20892 USA. EM mgottesman@nih.gov RI Szakacs, Gergely/A-2580-2009; Chen, Kevin/D-6769-2011 OI Szakacs, Gergely/0000-0002-9311-7827; Chen, Kevin/0000-0003-2983-6330 NR 0 TC 1 Z9 1 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 206 EP 206 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826101228 ER PT J AU Kopp, S Pleban, K Bates, SE Ecker, GF Chiba, P AF Kopp, S Pleban, K Bates, SE Ecker, GF Chiba, P TI Feature based drug/protein interaction in multispecific proteins - Lessons learnt from multidrug efflux pumps ABCB1 and ABCG2 SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 Med Univ Vienna, Inst Med Chem, Ctr Physiol & Pathophysiol, Funct Biol Lab, Vienna, Austria. Univ Vienna, Dept Pharmaceut Med Chem, Pharmacoinformat Lab, Vienna, Austria. NCI, Canc Therapeut Branch, Bethesda, MD 20892 USA. EM stephan.kopp@meduniwien.ac.at NR 0 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 210 EP 210 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826101241 ER PT J AU Hwang, BH Gu, ZH Gilpin, NW Badia-Elder, NE Stewart, RB Hansson, A Heilig, M AF Hwang, BH Gu, ZH Gilpin, NW Badia-Elder, NE Stewart, RB Hansson, A Heilig, M TI Up-regulation of NPYY2 receptors in the hippocampal CA3 region of alcohol-preferring (P) rats relative to alcohol-non-preferring (NP) rats: a potential role of hippocampal Y2 receptors in mediating alcohol intake SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 Indiana Univ, Indianapolis, IN 46204 USA. IUPUI, Psychol, Indianapolis, IN USA. NIAAA, Lab Clin & Translat Studies, Rockville, MD 20852 USA. EM bhwang@iupui.edu 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 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 221 EP 221 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826101279 ER PT J AU Baghy, K Nagy, P Iozzo, RV Thorgeirsson, SS Kovalszky, I AF Baghy, K Nagy, P Iozzo, RV Thorgeirsson, SS Kovalszky, I TI Establishment of double transgenic mice for investigating the relationship of decorin and TGF-beta 1 SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 Semmelweis Univ, Inst Pathol & Expt Canc Res 1, Budapest, Hungary. Thomas Jefferson Univ, Dept Pathol Anat & Cell Biol, Philadelphia, PA 19107 USA. NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM cory_@ludens.elte.hu 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 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 265 EP 266 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826101427 ER PT J AU Sellers, JR AF Sellers, JR TI Regulation and mechanics of myosin V SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. EM sellersj@nhlbi.nih.gov 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 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 333 EP 333 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826101657 ER PT J AU Toth, J Kovacs, M Wang, F Nyitray, L Sellers, JR AF Toth, J Kovacs, M Wang, F Nyitray, L Sellers, JR TI Drosophila myosin V: solution kinetics and motile properties SO FEBS JOURNAL LA English DT Meeting Abstract CT 30th Congress of the Federation-of-European-Biochemical-Societies (FEBS)/9th IUBMB Conference CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Federat European Biochem Soc, Int Union Biochem & Mol Biol C1 NHLBI, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. EOTVOS Lorand Univ, Biokemiai Tanszek, Budapest, Hungary. EM tothj@mail.nih.gov RI Kovacs, Mihaly/A-6841-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 336 EP 336 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826101668 ER PT J AU Tie, Y Boross, P Wang, YF Gaddis, L Ghosh, AK Louis, JM Harrison, RW Weber, IT AF Tie, Y Boross, P Wang, YF Gaddis, L Ghosh, AK Louis, JM Harrison, RW Weber, IT TI High resolution crystal structures of HIV-1 protease mutants with potent new inhibitors SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 Georgia State Univ, Dept Chem, Atlanta, GA 30303 USA. Univ Debrecen, Dept Biochem & Mol Biol, Debrecen, Hungary. Georgia State Univ, Dept Biol, Atlanta, GA USA. Univ Illinois, Dept Chem, Chicago, IL 60680 USA. NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. Georgia State Univ, Dept Comp Sci, Atlanta, GA 30303 USA. EM ytie@student.gsu.edu 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 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 394 EP 394 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826102165 ER PT J AU Huang, FL Huang, KP AF Huang, FL Huang, KP TI Thionylation of PKC by reactive sulfur species: disulfide S-monoxide and disulfide S-dioxide SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 NICHD, Endocrinol & Reprod Res Branch, NIH, Bethesda, MD USA. EM huangk@mail.nih.gov 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 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 415 EP 415 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826102236 ER PT J AU Chen, HC Wang, G Backlund, PS Boykins, RA AF Chen, HC Wang, G Backlund, PS Boykins, RA TI Phosphorylation and O-glycosylation sites identification in peptides by Ba-hydroxide catalyzed beta-elimination/propanethiol addition and mass spectrometric analyses SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 NICHD, Endo Repro Res Br, NIH, Bethesda, MD USA. NICHD, Lab Cell & Mol Biophys, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Bethesda, MD USA. EM chenha@mail.nih.gov 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 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 526 EP 526 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826102610 ER PT J AU Choi, WS Kim, YM Her, E Lee, HY Han, JW Lee, HW Hiragun, T Beaven, MA AF Choi, WS Kim, YM Her, E Lee, HY Han, JW Lee, HW Hiragun, T Beaven, MA TI Src family kinases regulates the activation of phospholipase D2 and degranulation in RBL 2H3 cells SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 Konkuk Univ, Immunol Lab, Coll Med, Chungju, South Korea. Duksung Womens Univ, Dept Gen Educ, Seoul, South Korea. Konyang Univ, Coll Med, Nonsan, South Korea. Sungkyunkwan Univ, Coll Pharm, Suwon 440746, South Korea. NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. EM wahnchoi@kku.ac.kr 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 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 543 EP 543 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826102667 ER PT J AU Sidorova, NY Muradymov, S Rau, DC AF Sidorova, NY Muradymov, S Rau, DC TI A novel self-cleavage assay for measuring DNA binding of restriction endonucleases SO FEBS JOURNAL LA English DT Meeting Abstract CT IUBMB 50th Anniversary Symposium CY JUL 02-07, 2005 CL Budapest, HUNGARY SP Int Union Biochem Molecular Biol C1 NICHD, LPSB, NIH, Bethesda, MD USA. EM sidorova@mail.nih.gov 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 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 SU 1 BP 565 EP 565 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 005MG UT WOS:000234826102742 ER PT J AU LaRonde-LeBlanc, N Guszczynski, T Copeland, T Wlodawer, A AF LaRonde-LeBlanc, N Guszczynski, T Copeland, T Wlodawer, A TI Structure and activity of the atypical serine kinase Rio1 SO FEBS JOURNAL LA English DT Article DE autophosphorylation; nucleotide complex; protein kinase; ribosome biogenesis; Rio1 ID DEPENDENT PROTEIN-KINASE; PRE-RIBOSOMAL-RNA; CRYSTAL-STRUCTURE; SACCHAROMYCES-CEREVISIAE; CATALYTIC SUBUNIT; PEPTIDE INHIBITOR; FULGIDUS RIO2; SUPERFAMILY; REFINEMENT; GENOME AB Rio1 is the founding member of the RIO family of atypical serine kinases that are universally present in all organisms from archaea to mammals. Activity of Rio1 was shown to be absolutely essential in Saccharomyces cerevisiae for the processing of 18S ribosomal RNA, as well as for proper cell cycle progression and chromosome maintenance. We determined high-resolution crystal structures of Archaeoglobus fulgidus Rio1 in the presence and absence of bound nucleotides. Crystallization of Rio1 in the presence of ATP or ADP and manganese ions demonstrated major conformational changes in the active site, compared with the uncomplexed protein. Comparisons of the structure of Rio1 with the previously determined structure of the Rio2 kinase defined the minimal RIO domain and the distinct features of the RIO subfamilies. We report here that Ser108 represents the sole autophosphorylation site of A. fulgidus Rio1 and have therefore established its putative peptide substrate. In addition, we show that a mutant enzyme that cannot be autophosphorylated can still phosphorylate an inactive form of Rio1, as well as a number of typical kinase substrates. C1 Natl Canc Inst, MCL, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. Natl Canc Inst, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. RP Wlodawer, A (reprint author), Natl Canc Inst, MCL, Prot Struct Sect, Macromol Crystallog Lab, Bldg 536,Rm 5, Frederick, MD 21702 USA. EM wlodawer@ncifcrf.gov RI LaRonde-LeBlanc, Nicole/C-3399-2009 OI LaRonde-LeBlanc, Nicole/0000-0002-2778-8358 NR 30 TC 36 Z9 41 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2005 VL 272 IS 14 BP 3698 EP 3713 DI 10.1111/j.1742-4658.2005.04796.x PG 16 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 942PA UT WOS:000230293100019 PM 16008568 ER PT J AU Sung, H Han, KC Kim, JC Oh, KW Yoo, HS Hong, JT Chung, YB Lee, CK Lee, KS Song, S AF Sung, H Han, KC Kim, JC Oh, KW Yoo, HS Hong, JT Chung, YB Lee, CK Lee, KS Song, S TI A set of epitope-tagging integration vectors for functional analysis in Saccharomyces cerevisiae SO FEMS YEAST RESEARCH LA English DT Article DE Saccharomyces cerevisiae; epitope tagging; integration vector ID SUBCELLULAR-LOCALIZATION; FLUORESCENT PROTEIN; SHUTTLE VECTORS; SEPTIN FUNCTION; BUDDING YEAST; CYTOKINESIS; EXPRESSION; MODULES; PRODUCT; CDC5 AB Functional analysis of genes from Saccharomyces cereuisiae has been the major goal after determination of genome sequences. Even though several tools for molecular-genetic analyses have been developed, only a limited number of reliable genetic tools are available to support functional assay at protein level. Epitope tagging is a powerful tool for detecting, purifying, and functional studying of proteins. But systematic tagging systems developed with integration vectors are not available. Here, we have constructed a set of integration vectors allowing a translational fusion of interested proteins to the four different epitope tags (HA, Myc, Flag, and GFP). To confirm function and expression of C-terminal-tagged proteins, we used Cdc11, a component of the septin filament that encircles the mother bud neck and consists of five major proteins: Cdc3, Cdc10, Cdc11, Cdc12, and Sep7. The tagged version of Cdc11 expressed under its endogenous promoter was found to be physiologically functional, as evidenced by localization at the neck and suppression of the growth defect associated with the temperature-sensitive mutation of cdc11-6. The expressed proteins were efficiently detected with antibodies against Cdc11 or the epitopes. When immunoprecipitated with anti-Myc antibody, each septin protein tagged with Myc was effectively copurified with other septin components, indicating formation of a stable septin complex. Because the modules of the tags were located under the same array of eighteen restriction sites on integration vectors containing four different markers (HIS3, TRP1, LEU2, or URA3), this tagging system provides efficient multiple tagging and stable expression of a gene of interest. (c) 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 Chungbuk Natl Univ, Coll Pharm, Cheongju, Chungbuk, South Korea. Chungbuk Natl Univ, NRL, Biotechnol Res Inst, Cheongju, Chungbuk, South Korea. NCI, Met Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Song, S (reprint author), Chungbuk Natl Univ, Coll Pharm, 48 Gaeshindong, Cheongju, Chungbuk, South Korea. EM songs@chungbuk.ac.kr NR 24 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-1356 J9 FEMS YEAST RES JI FEMS Yeast Res. PD JUL PY 2005 VL 5 IS 10 BP 943 EP 950 DI 10.1016/j.femsyr.2005.03.008 PG 8 WC Biotechnology & Applied Microbiology; Microbiology; Mycology SC Biotechnology & Applied Microbiology; Microbiology; Mycology GA 948AQ UT WOS:000230688800007 PM 15996627 ER PT J AU Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL AF Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL TI Glycemic load, glycemic index, and carbohydrate intake in relation to risk of cholecystectomy in women SO GASTROENTEROLOGY LA English DT Article ID CORONARY-HEART-DISEASE; GALLBLADDER-DISEASE; GALLSTONE DISEASE; CHOLESTEROL; INSULIN; DIET; PREVALENCE; LIPEMIA; FOODS; FAT AB Background & Aims: High-carbohydrate diets with a high glycemic response may exacerbate the metabolic consequences of the insulin-resistance syndrome. The effect on the incidence of gallstone disease is not clear. Methods: We examined the associations between high-carbohydrate diets with a high glycemic response and the risk of cholecystectomy in a cohort of women who were aged from 35 to 61 years in JL984 and had no history of gallstone disease. As part of the Nurses' Health Study, the women reported on questionnaires mailed to them every 2 years both their carbohydrate intake and whether they had undergone cholecystectomy. Result : During 16 years of follow-up, we ascertained 5771 new cases of cholecystectomy. After adjusting for age and other known or suspected risk factors in a multivariate model, the relative risk for the highest compared with the lowest quintile of dietary carbohydrate was 1.35 (95% CI: 1.17-1.55, P for trend < .0001). The relative risks for the highest compared with the lowest quintile were 1.50 for glycemic load (95% CI: 1.32-1.71, P for trend < .0001) and 1.32 for glycemic index (95% CI: 1.20-1.45, P for trend < .0001). Independent positive associations were also seen for intakes of starch and sucrose. Conclusions: Our findings suggest that a higher intake of carbohydrate, dietary glycemic load, and glycemic index may enhance risk of cholecystectomy in women. C1 Univ Kentucky, Ctr Med, Div Digest Dis & Nutr, Lexington, KY 40536 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Boston, MA USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. RP Tsai, CJ (reprint author), Univ Kentucky, Ctr Med, Div Digest Dis & Nutr, 800 Rose St, Lexington, KY 40536 USA. EM hpcjt@channing.harvard.edu FU NCI NIH HHS [CA55075]; NIDDK NIH HHS [DK46200] NR 40 TC 42 Z9 43 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD JUL PY 2005 VL 129 IS 1 BP 105 EP 112 DI 10.1053/j.gastro.2005.05.016 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 944JI UT WOS:000230423100015 PM 16012940 ER PT J AU Megumi, Y Miyauchi, Y Sakurai, H Nobeyama, H Lorick, K Nakamura, E Chiba, T Tanaka, K Weissman, AM Kirisako, T Ogawa, O Iwai, K AF Megumi, Y Miyauchi, Y Sakurai, H Nobeyama, H Lorick, K Nakamura, E Chiba, T Tanaka, K Weissman, AM Kirisako, T Ogawa, O Iwai, K TI Multiple roles of Rbx1 in the VBC-Cul2 ubiquitin ligase complex SO GENES TO CELLS LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; HIF-ALPHA; NEDD8; SCF; FAMILY; UBIQUITYLATION; DEGRADATION; PATHWAY; IDENTIFICATION; HYDROXYLATION AB The importance of the ubiquitin system largely depends on ubiquitin ligases, E3s, as they determine the specificity of the system. Rbx1/ROC1/Hrt1, a RING finger protein, functions as an important component of the cullin-containing SCF and VBC-Cul2 ligases. Modification of cullins by NEDD8 (NEDDylation), has been shown to be essential for the E3 activity of both SCF and VBC-Cul2, and it was suggested that Rbx1 acts as the E3 for cullin NEDDylation. RING finger is composed of eight cysteine and histidine residues that bind to zinc ions. Rbx1 is a highly evolutionarily conserved protein; however, the eighth coordination residue in its RING finger is aspartate (D97) rather than cysteine. Substitution of D97 with each of the other 19 amino acids demonstrates that aspartate is superior to cysteine in cullin NEDDylation. Interestingly, however, different D97 mutants demonstrate different activities towards 6 cullins tested. Importantly, we were able to discriminate between the NEDDylating activity of Rbx1 and its involvement in the ubiquitylation reaction within the context of VBC-Cul2. Moreover, while Rbx1 is not involved in governing the stability of SCF, Rbx1 mutants destabilize VBC-Cul2. Taken together, these results indicate that various mechanisms regulate both the activities and the stability of cullin-based ligases. C1 Osaka City Univ, Grad Sch Med, Dept Mol Cell Biol, Abeno Ku, Osaka 5458585, Japan. Kyoto Univ, Grad Sch Med, Dept Urol, Sakyo Ku, Kyoto 6068501, Japan. NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. Tokyo Metropolitan Inst Med Sci, Dept Mol Oncol, Tokyo 1138613, Japan. Japan Sci & Technol Corp, CREST, Kawaguchi, Saitama 3320012, Japan. RP Iwai, K (reprint author), Osaka City Univ, Grad Sch Med, Dept Mol Cell Biol, Abeno Ku, 1-4-3 Asahi Machi, Osaka 5458585, Japan. EM kiwai@med.osaka-cu.ac.jp NR 31 TC 16 Z9 16 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1356-9597 J9 GENES CELLS JI Genes Cells PD JUL PY 2005 VL 10 IS 7 BP 679 EP 691 DI 10.1111/j.1365-2443.2005.00869.x PG 13 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 937GS UT WOS:000229913200005 PM 15966899 ER PT J AU Hughes, AL Packer, B Welch, R Bergen, AW Chanock, SJ Yeager, M AF Hughes, AL Packer, B Welch, R Bergen, AW Chanock, SJ Yeager, M TI Effects of natural selection on interpopulation divergence at polymorphic sites in human protein-coding loci SO GENETICS LA English DT Article ID SINGLE-NUCLEOTIDE POLYMORPHISMS; MOLECULAR EVOLUTION; GENETIC-VARIATION; CANDIDATE GENES; HUMAN GENOME; DISEASE; POPULATION; MUTATIONS; SNPS; DIVERSITY AB To develop new strategies for searching for genetic associations with complex human diseases, we analyzed 2784 single-nucleotide polymorphisms (SNPs) in 396 protein-coding genes involved in biological processes relevant to cancer and other complex diseases, with respect to gene diversity within samples of individuals representing the three major historic human populations (African, European, and Asian) and with respect to interpopulation genetic distance. Reduced levels of both intrapopulation gene diversity and interpopulation genetic distance were seen in the case of SNPs located within the 5'-UTR and at nonsynonymous SNPs, causing radical changes to protein structure. Reduction of gene diversity at SNP loci in these categories was evidence of purifying selection acting at these sites, which in turn causes a reduction in interpopulation divergence. By contrast, a small number of SNP sites in these categories revealed unusually high genetic distances between the two most diverged populations (African and Asian); these loci may have historically been subject to divergent selection pressures. C1 Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA. NCI, FCRDC, SAIC, Intramural Res Support Program, Frederick, MD 21702 USA. NCI, Core Genotyping Facil, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Hughes, AL (reprint author), Univ S Carolina, Dept Biol Sci, Coker Life Sci Bldg,700 Sumter St, Columbia, SC 29208 USA. EM austin@biol.sc.edu OI Bergen, Andrew/0000-0002-1237-7644 FU NCI NIH HHS [N01-CO-12400, N01CO12400]; NIGMS NIH HHS [GM43940, R01 GM043940] NR 45 TC 16 Z9 18 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUL PY 2005 VL 170 IS 3 BP 1181 EP 1187 DI 10.1053/genetics.104.037077 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 953RH UT WOS:000231097700017 PM 15911586 ER PT J AU Cooper, GM Stone, EA Asimenos, G Green, ED Batzoglou, S Sidow, A AF Cooper, GM Stone, EA Asimenos, G Green, ED Batzoglou, S Sidow, A CA NISC Comparative Sequencing Progra TI Distribution and intensity of constraint in mammalian genomic sequence SO GENOME RESEARCH LA English DT Article ID TRANSPOSABLE ELEMENTS; REGULATORY SEQUENCES; CONSERVED SEQUENCES; NONCODING SEQUENCES; MAXIMUM-LIKELIHOOD; MULTIPLE ALIGNMENT; PLACENTAL MAMMALS; REGIONS; MOUSE; GENE AB Comparisons of orthologous genomic DNA sequences call be used to characterize regions that have been subject to purifying selection and are enriched for functional elements. We here present the results of such ail analysis on ail alignment of sequences from 29 mammalian species. The alignment captures -3.9 neutral Substitutions per site and spans similar to 1.9 Mbp of the human genome. We identify constrained elements from 3 bp to over 1 kbp in length, covering similar to 5.5% of the human locus. Our estimate for the total amount of nonexonic constraint experienced by this locus is roughly twice that for exonic constraint. Constrained elements tend to Cluster, and we identify large constrained regions that correspond well with known functional elements. While constraint density inversely correlates with mobile element density, we also show the presence of unambiguously constrained elements overlapping mammalian ancestral repeats. In addition, we describe a number of elements in this region that have undergone intense purifying selection throughout mammalian evolution, and we show that these important elements are more numerous than previously thought. These results were obtained with Genomic Evolutionary Rate Profiling (GERP), a statistically rigorous and biologically transparent framework for constrained element identification. CERP identifies regions at high resolution that exhibit nucleotide substitution deficits, and measures these deficits as "rejected substitutions." Rejected substitutions reflect the intensity of past Purifying selection and are used to rank and characterize constrained elements. We anticipate that GERP and the types of analyses it facilitates will provide further insights and improved annotation for the human genome as mammalian genome sequence data become richer. C1 Stanford Univ, Dept Genet, Stanford, CA 94305 USA. Stanford Univ, Dept Stat, Stanford, CA 94305 USA. Stanford Univ, Dept Pathol, Stanford, CA 94305 USA. Stanford Univ, Dept Comp Sci, Stanford, CA 94305 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. NHGRI, NISC, NIH, Bethesda, MD 20892 USA. RP Sidow, A (reprint author), Stanford Univ, Dept Genet, Stanford, CA 94305 USA. EM arend@stanford.edu RI Cooper, Gregory/D-6914-2011; Stone, Eric/Q-7840-2016 OI Cooper, Gregory/0000-0001-5509-9923; NR 63 TC 491 Z9 501 U1 2 U2 19 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1088-9051 J9 GENOME RES JI Genome Res. PD JUL PY 2005 VL 15 IS 7 BP 901 EP 913 DI 10.1101/gr.3577405 PG 13 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA 944JQ UT WOS:000230424000001 PM 15965027 ER PT J AU Wright, JD Li, JD Gerhard, DS Zhang, ZY Huettner, PC Powell, MA Gibb, RK Herzog, TJ Mutch, DG Trinkaus, KM Rader, JS AF Wright, JD Li, JD Gerhard, DS Zhang, ZY Huettner, PC Powell, MA Gibb, RK Herzog, TJ Mutch, DG Trinkaus, KM Rader, JS TI Human papillomavirus type and tobacco use as predictors of survival in early stage cervical carcinoma SO GYNECOLOGIC ONCOLOGY LA English DT Article DE human papillomavirus; tobacco use; cervical carcinoma ID CIGARETTE-SMOKE CONDENSATE; HUMAN ENDOCERVICAL CELLS; PROGNOSTIC-SIGNIFICANCE; UTERINE CERVIX; LUNG-CANCER; DNA-DAMAGE; NEOPLASIA; CARCINOGENESIS; EXPRESSION; NICOTINE AB Objective. Molecular and environmental co-factors are known risk factors for cervical cancer. The aim of this study was to define the prognostic significance of HPV 18 and its phylogenetically related viruses and smoking on survival in patients with early stage cervical cancer. Methods. HPV typing was performed on stage IB-IIB cervical tumors. Subjects positive for HPV 18 or 45 were compared to the remainder of the cohort and to women with tumors containing HPV 16, 31, or 52. Tobacco use was ascertained by patient questionnaire. Results. Tumors of 255 women were evaluated. The presence of HPV 18 or 45 was associated with decreased survival. In a multivariable Cox proportional hazards analysis comparing patients with HPV IS or 45 containing tumors to the rest of the cohort, the hazard ratio for death from cervical cancer was 2.08 (95% CI, 1.07-4.04). The hazard ratio for death from cervical cancer was 2.41 (95% CI, 1.17-4.96) when the HPV 18 and 45 group was compared to women with HPV 16 or its related viruses, 31 and 52. Smoking was associated with a decreased survival for women with HPV 18 or 45, even after adjusting for other known prognostic factors (P = 0.031). Conclusions. In addition to pathologic indicators, molecular and environmental co-factors are important determinates of outcome in early stage cervical cancer. The presence of HPV 18 or 45 is associated with a decreased survival. The adverse effect of HPV 18 and 45 on survival is compounded by tobacco use. (c) 2005 Elsevier Inc. All rights reserved. C1 Washington Univ, Sch Med, Div Gynecol Oncol, Dept Obstet & Gynecol, St Louis, MO 63110 USA. Natl Canc Inst, Off Canc Genom, St Louis, MO 63130 USA. Washington Univ, Sch Med, Dept Pathol & Immunol, St Louis, MO 63130 USA. Washington Univ, Sch Med, Div Biostat, St Louis, MO 63130 USA. RP Wright, JD (reprint author), Washington Univ, Sch Med, Div Gynecol Oncol, Dept Obstet & Gynecol, 4911 Barnes Hosp Plaza,Box 8064, St Louis, MO 63110 USA. EM wrightj@msnotes.wustl.edu NR 51 TC 12 Z9 12 U1 2 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0090-8258 J9 GYNECOL ONCOL JI Gynecol. Oncol. PD JUL PY 2005 VL 98 IS 1 BP 84 EP 91 DI 10.1016/j.ygyno.2005.03.038 PG 8 WC Oncology; Obstetrics & Gynecology SC Oncology; Obstetrics & Gynecology GA 942LP UT WOS:000230284200014 PM 15894364 ER PT J AU Berntorp, E Astermark, J Donfield, SM Nelson, GW Oldenburg, J Shapiro, AD Dimichele, DM Ewenstein, BM Gomperts, ED Winkler, CA AF Berntorp, E Astermark, J Donfield, SM Nelson, GW Oldenburg, J Shapiro, AD Dimichele, DM Ewenstein, BM Gomperts, ED Winkler, CA CA Hemophilia Inhibitor Genetics Stud TI Haemophilia Inhibitor Genetics Study - evaluation of a model for studies of complex diseases using linkage and association methods SO HAEMOPHILIA LA English DT Letter ID SINGLE NUCLEOTIDE POLYMORPHISMS; HUMAN GENOME; DISEQUILIBRIUM; SEQUENCE; TRAITS; GENES C1 Univ Hosp, Dept Coagulat Disorders, Malmo, Sweden. Rho Inc, Chapel Hill, NC USA. NCI, Sci Applicat Int Corp Frederick, Frederick, MD 21701 USA. Inst Transfus Med & Immune Hematol, Frankfurt, Germany. Indiana Hemophilia & Thrombosis Ctr, Indianapolis, IN USA. Cornell Univ, Weill Med Coll, New York, NY USA. Baxter Biosci, Westlake Village, CA USA. RP Berntorp, E (reprint author), Univ Hosp, Dept Coagulat Disorders, Malmo, Sweden. EM erik.berntorp@medforsk.mas.lu.se FU NCI NIH HHS [N01-CO-12400] NR 23 TC 12 Z9 13 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD JUL PY 2005 VL 11 IS 4 BP 427 EP 429 DI 10.1111/j.1365-2516.2005.01119.x PG 3 WC Hematology SC Hematology GA 944MH UT WOS:000230432600024 PM 16011603 ER PT J AU Hampson, LA Emanuel, EJ AF Hampson, LA Emanuel, EJ TI The prognosis for changes in end-of-life care after the Schiavo case SO HEALTH AFFAIRS LA English DT Article ID ADVANCE DIRECTIVES; PREFERENCES; DECISIONS; PATIENT AB Americans have reached consensus that (1) people have a right to refuse life-sustaining medical interventions, and (2) interventions that can be terminated include artificial nutrition and hydration. The one unresolved issue is how to decide for mentally incompetent patients. Only about 20 percent of Americans have completed living wills, and data show that family members are poor at predicting patients' wishes for life-sustaining care. But despite court cases and national consensus that these are private and not legislative matters, the Schiavo case is unlikely to change practices except to increase the number of Americans who complete living wills. C1 NIH, Dept Clin Bioeth, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NR 21 TC 9 Z9 9 U1 2 U2 3 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL-AUG PY 2005 VL 24 IS 4 BP 972 EP 975 DI 10.1377/hlthaff.24.4.972 PG 4 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 947CV UT WOS:000230621600009 PM 16012137 ER PT J AU Nahin, RL Pontzer, CH Chesney, MA AF Nahin, RL Pontzer, CH Chesney, MA TI Racing toward the integration of complementary and alternative medicine: A marathon or a sprint? SO HEALTH AFFAIRS LA English DT Article AB Health care opinion leaders concur that integration of complementary and alternative medicine (CAM) into the U.S. health care system must be based on strong supporting evidence of safety and efficacy. As others have pointed out, integration is under way, despite the lack of reliable, rigorous science supporting the use of most CAM treatments. We contend that optimal integration of CAM is a long-term endeavor-a marathon rather than a sprint. The evidence base does not now support its wholesale assimilation; market forces, although compelling, should not be the primary consideration in integration. C1 NIH, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Nahin, RL (reprint author), NIH, Natl Ctr Complementary & Alternat Med, Bldg 10, Bethesda, MD 20892 USA. EM nahinr@mail.nih.gov NR 15 TC 6 Z9 6 U1 3 U2 4 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUL-AUG PY 2005 VL 24 IS 4 BP 991 EP 993 DI 10.1377/hlthaff.24.4.991 PG 3 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 947CV UT WOS:000230621600012 PM 16012139 ER PT J AU Gilbert, ES AF Gilbert, ES TI The biological effects of ionizing radiation (BEIR VII) report's models for estimating cancer risks SO HEALTH PHYSICS LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUL PY 2005 VL 89 IS 1 SU S BP S33 EP S33 PG 1 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 938FS UT WOS:000229985900084 ER PT J AU Simon, SL Ibrahim, SA VanMiddlesworth, L Filipy, RE Bouville, A AF Simon, SL Ibrahim, SA VanMiddlesworth, L Filipy, RE Bouville, A TI Ra-226 and the thyroid gland: Maybe we know less than we thought SO HEALTH PHYSICS LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. Colorado State Univ, Ft Collins, CO 80523 USA. Univ Tennessee, Sch Med, Knoxville, TN 37996 USA. Washington State Univ, US transuranium & Uranium Registries, Pullman, WA 99164 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUL PY 2005 VL 89 IS 1 SU S BP S22 EP S22 PG 1 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 938FS UT WOS:000229985900056 ER PT J AU Thierry-Chef, I Simon, SL Miller, DL AF Thierry-Chef, I Simon, SL Miller, DL TI Doses received by pediatric patients from interventional fluoroscopy procedures SO HEALTH PHYSICS LA English DT Meeting Abstract C1 NCI, Radiat Epidemiol Branch, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD JUL PY 2005 VL 89 IS 1 SU S BP S55 EP S56 PG 2 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 938FS UT WOS:000229985900151 ER PT J AU McCaul, KD Peters, E Nelson, W Stefanek, M AF McCaul, KD Peters, E Nelson, W Stefanek, M TI Linking decision-making research and cancer prevention and control: Important themes SO HEALTH PSYCHOLOGY LA English DT Article DE decision-making themes; decision preferences; cancer research ID RISK; PERCEPTIONS AB This article describes 6 themes underlying the multiple presentations from the Basic and Applied Decision Making in Cancer Control meeting, held February 19-20, 2004. The following themes have important implications for research and practice linking basic decision-making research to cancer prevention and control: (a) Traditional decision-making theories fail to capture real-world decision making, (b) decision makers are often unable to predict future preferences, (c) preferences are often constructed on the spot and thus are influenced by situational cues, (d) decision makers often rely on feelings rather than beliefs when making a decision, (e) the perspective of the decision maker is critical in determining preferences, and (f) informed decision making may-or may not-yield the best decisions. C1 N Dakota State Univ, Dept Psychol, Fargo, ND 58105 USA. Decis Res, Eugene, OR USA. Natl Canc Inst, Div Canc Control & Populat Sci, Basic & Biobehav Res Branch, Bethesda, MD USA. RP McCaul, KD (reprint author), N Dakota State Univ, Dept Psychol, Fargo, ND 58105 USA. EM kevin.mccaul@ndsu.edu NR 29 TC 10 Z9 10 U1 2 U2 6 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JUL PY 2005 VL 24 IS 4 SU S BP S106 EP S110 DI 10.1037/0278-6133.24.4.SI06 PG 5 WC Psychology, Clinical; Psychology SC Psychology GA 954ZW UT WOS:000231195300016 PM 16045412 ER PT J AU Nelson, W Stefanek, M Peters, E McCaul, KD AF Nelson, W Stefanek, M Peters, E McCaul, KD TI Basic and applied decision making in cancer control SO HEALTH PSYCHOLOGY LA English DT Article DE cancer; decision making; judgment and decision making ID CHOICE; COGNITION; RISK AB Decision making is fundamental to all aspects of cancer care-prevention, detection, treatment, survivorship, and end of life-yet researchers and clinicians have limited knowledge of the ways in which patients and their health care providers make critical health decisions. Recognizing how important it is to understand how patients and their providers make potentially life-altering decisions, the National Cancer Institute developed a decision making in cancer control initiative. The goal of this initiative is to enhance understanding of human decision-making processes so that individuals can make more informed and satisfying choices regarding their health. This article describes the multidisciplinary meeting that provided the scientific foundation for this initiative. C1 NCI, Bethesda, MD 20892 USA. N Dakota State Univ, Dept Psychol, Fargo, ND 58105 USA. RP Nelson, W (reprint author), NCI, 6130 Execut Blvd, Bethesda, MD 20892 USA. EM nelsonw@mail.nih.gov NR 47 TC 13 Z9 13 U1 2 U2 4 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 0278-6133 J9 HEALTH PSYCHOL JI Health Psychol. PD JUL PY 2005 VL 24 IS 4 SU S BP S3 EP S8 DI 10.1037/0278-6133.24.4.S3 PG 6 WC Psychology, Clinical; Psychology SC Psychology GA 954ZW UT WOS:000231195300001 PM 16045416 ER PT J AU MacDonald, S Yates, J Lance, R Giganti, N Chepurko, D AF MacDonald, S Yates, J Lance, R Giganti, N Chepurko, D TI Are you asking the right admission questions when assessing dyspnea? SO HEART & LUNG LA English DT Article ID OBSTRUCTIVE PULMONARY-DISEASE; CARE; SCALES AB BACKGROUND: Dyspnea is an important admission parameter to detect undiagnosed cardiopulmonary conditions. The typical admission question, "Are you short of breath?" can give insufficient or misleading data. OBJECTIVES: A group of clinical research nurses sought to improve dyspnea assessments by using a more accurate measure that would not unduly lengthen the admission process itself. The methodology used to achieve this outcome was research utilization. METHODS: On admission, 103 patients were given the standard question "Are you short of breath?" followed by 4 Visual Analog Scales of Dyspnea (VASD). These response measures assess the degree of dyspnea in relationship to variable exertion activities on a scale of 0 to 10. All responses to VASD were analyzed using descriptive statistics. RESULTS: The results showed that 30% of patients who responded "No" to the shortness of breath query scored 5 or more for dyspnea on the VASD. All scores of 5 or more were reported to the primary care provider for further workup. CONCLUSION: The results from this project gave impetus to designing a more formal research study that could validate VASD use in clinical admission assessments. C1 NIH, Nursing & Patient Care Serv, Ctr Clin, Bethesda, MD 20892 USA. RP MacDonald, S (reprint author), 12017 Winding Creek Way, Germantown, MD 20874 USA. NR 33 TC 3 Z9 3 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0147-9563 J9 HEART LUNG JI Heart Lung PD JUL-AUG PY 2005 VL 34 IS 4 BP 260 EP 269 DI 10.1016/j.hrtlng.2004.12.002 PG 10 WC Cardiac & Cardiovascular Systems; Nursing; Respiratory System SC Cardiovascular System & Cardiology; Nursing; Respiratory System GA 947GQ UT WOS:000230631800006 PM 16027647 ER PT J AU Feld, JJ Dinh, H Arenovich, T Marcus, VA Wanless, IR Heathcote, EJ AF Feld, JJ Dinh, H Arenovich, T Marcus, VA Wanless, IR Heathcote, EJ TI Autoimmune hepatitis: Effect of symptoms and cirrhosis on natural history and outcome SO HEPATOLOGY LA English DT Article ID CHRONIC ACTIVE HEPATITIS; LIVER-DISEASE; CORTICOSTEROID-THERAPY; EARLY PROGNOSIS; REMISSION; AZATHIOPRINE; MAINTENANCE; PATTERNS; FIBROSIS AB Although the natural history of autoimmune hepatitis (AIH) has been characterized, little is known about patients who present asymptornatically. Consequently, whether they require immunosuppressive therapy with its associated complications is unclear. To compare the natural history of asymptomatic AIH with symptomatic AIH, a large cohort of patients from a single center was examined. All patients with a clinical diagnosis of AIH were reassessed using the revised criteria of the International Autoimmune Hepatitis Group. Liver histology, response to therapy, and survival were assessed. Patients asymptomatic at presentation (n = 31) had lower serum aminotransferase, bilirubin, and immunoglobulin G (IgG) values at baseline. Half of the asymptomatic patients received no therapy, and their survival was no different from that of the total cohort. Ten-year survival was 80.0% (62.5%-97.5%) in the asymptomatic group and 83.8% (75.1%-92.6%) in the symptomatic patients (P = NS). Survival to liver-related endpoints at 10 years was similar in both groups: 89.5% (75.7%100%) asymptomatic and 83.8% (75.1%-92.6%) symptomatic patients (P = NS). Patients with cirrhosis at baseline had poorer 10-year survival (61.9% [CI 44.9%-78.9%]) than those without cirrhosis at presentation (94.0% (CI 87.4%-100%]) (P =.003) regardless of whether they presented with symptoms or whether they received immunosuppressive therapy. In conclusion, patients with AIH who are asymptomatic at presentation have a good prognosis and may not require immunosuppressive therapy. Cirrhosis on initial liver biopsy portends a poor prognosis in all patients with AIH. C1 Univ Toronto, Univ Hlth Network, Dept Med, Toronto, ON, Canada. Univ Toronto, Univ Hlth Network, Dept Pathol, Toronto, ON, Canada. Montreal Gen Hosp, Dept Pathol, Montreal, PQ H3G 1A4, Canada. RP Feld, JJ (reprint author), NIDDK, Liver Dis Branch, NIH, 10 Ctr Dr,Room 9B16,MSC 1800, Bethesda, MD 20892 USA. EM feldj@niddk.nih.gov NR 25 TC 130 Z9 141 U1 1 U2 7 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUL PY 2005 VL 42 IS 1 BP 53 EP 62 DI 10.1002/hep.20732 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 941BI UT WOS:000230189200009 PM 15954109 ER PT J AU Chan, CC Tuo, J Bojanowski, CM Csaky, KG Green, WR AF Chan, CC Tuo, J Bojanowski, CM Csaky, KG Green, WR TI Detection of CX3CR1 single nucleotide polymorphism and expression on archived eyes with age-related macular degeneration SO HISTOLOGY AND HISTOPATHOLOGY LA English DT Article DE age-related macular degeneration; single nuclear polymorphism; CX3CR1; chemokine; macrophage ID APOLIPOPROTEIN-E GENE; CHOROIDAL NEOVASCULARIZATION; BRUCHS MEMBRANE; CHEMOKINE RECEPTORS; RISK-FACTORS; FRACTALKINE; ASSOCIATION; DISEASE; CX(3)CR1; SUSCEPTIBILITY AB There is a significant genetic component in age-related macular degeneration (AMD). CX3CR1, which encodes the fractalkine (chemokine, CX3CL1) receptor, has two single nucleotide polymorphisms (SNPs): V2491 and T280M. These SNPs are correlated with other aged-related diseases such as atherosclerosis. We have reported an association of CX3CR1 SNP and AMD. In this study we examined CX3CR1 SNP frequencies and protein expression on archived sections of AMD and normal eyes. We microdissected non-retinal, peripheral retinal and macular cells from archived slides of eyes of AMD patients and normal subjects. CX3CR1 SNP typing was conducted by PCR and restriction fragment length polymorphism analysis. CX3CR1 transcripts from retinal cells were also measured using RT-PCR. CX3CR1 protein expression was evaluated using avidin-biotin complex immunohistochemistry. We successfully extracted DNA from 32/40 AMD cases and 2/2 normal eyes. Among the 32 AMD cases, IS had neovascular AMD and 14 had non-neovascular AMD. The M280 allele was detected in 19/64 (32 cases x2) with a frequency of 29.7%, which was significantly higher as compared to the frequency in the normal population (11.2%). We detected CX3CR1 expression in the various retinal cells. CX3CR1 transcript and protein levels were diminished in the macular lesions. This study successfully analyzed CX3CR1 SNP and transcript expression in microdissected cells from archived paraffin fixed slides. Our data suggest that the M280 allele, a SNP resulting in aberrant CX3CR1 and CX3CL1 interaction, as well as lowered expression of macular CX3CR1, may contribute to the development of AMD. C1 NEI, NIH, Bethesda, MD 20895 USA. Johns Hopkins Univ, Sch Med, Wilmer Eye Inst, Baltimore, MD 21205 USA. RP Chan, CC (reprint author), NEI, NIH, Bldg 10,Rm 10N103,10 Ctr Dr, Bethesda, MD 20895 USA. EM chanc@nei.nih.gov FU Intramural NIH HHS [Z01 EY000222-22, Z01 EY000418-04] NR 61 TC 46 Z9 49 U1 0 U2 3 PU F HERNANDEZ PI MURCIA PA PLAZA FUENSANTA 2-7 C, 30008 MURCIA, SPAIN SN 0213-3911 J9 HISTOL HISTOPATHOL JI Histol. Histopath. PD JUL PY 2005 VL 20 IS 3 BP 857 EP 863 PG 7 WC Cell Biology; Pathology SC Cell Biology; Pathology GA 942MS UT WOS:000230287100023 PM 15944936 ER PT J AU Goodman, MT Hernandez, BY Hewitt, S Lynch, CF Cote, TR Frierson, HF Moskaluk, CA Killeen, JL Cozen, W Key, CR Clegg, L Reichman, M Hankey, BF Edwards, B AF Goodman, MT Hernandez, BY Hewitt, S Lynch, CF Cote, TR Frierson, HF Moskaluk, CA Killeen, JL Cozen, W Key, CR Clegg, L Reichman, M Hankey, BF Edwards, B TI Tissues from population-based cancer registries: A novel approach to increasing research potential SO HUMAN PATHOLOGY LA English DT Article DE cancer registry; neoplasm; SEER program; tissue bank; tissue microarray ID IN-SITU HYBRIDIZATION; GENE-EXPRESSION; PROSTATE-CANCER; BREAST-CANCER; MICROARRAY TECHNOLOGY; HUMAN-PAPILLOMAVIRUS; MOLECULAR PATHOLOGY; CERVICAL-CANCER; DNA; AMPLIFICATION AB Population-based cancer registries, such as those included in the Surveillance, Epidemiology, and End-Results (SEER) Program, offer tremendous research potential beyond traditional surveillance activities. We describe the expansion of SEER registries to gather formalin-fixed, paraffin-embedded tissue from cancer patients on a population basis. Population-based tissue banks have the advantage of providing an unbiased sampling frame for evaluating the public health impact of genes or protein targets that may be used for therapeutic or diagnostic purposes in defined communities. Such repositories provide a unique resource for testing new molecular classification schemes for cancer, validating new biologic markers of malignancy, prognosis and progression, assessing therapeutic targets, and measuring allele frequencies of cancer-associated genetic polymorphisms or germline mutations in representative samples. The assembly of tissue microarrays will allow for the use of rapid, large-scale protein-expression profiling of tumor samples while limiting depletion of this valuable resource. Access to biologic specimens through SEER registries will provide researchers with demographic, clinical, and risk factor information on cancer patients with assured data quality and completeness. Clinical outcome data, such as disease-free survival, can be correlated with previously validated prognostic markers. Furthermore, the anonymity of the study subject can be protected through rigorous standards of confidentiality. SEER-based tissue resources represent a step forward in true, population-based tissue repositories of tumors from US patients and may serve as a foundation for molecular epidemiology studies of cancer in this country. (C) 2005 Published by Elsevier Inc. C1 Univ Hawaii, Canc Res Ctr Hawaii, Etiol Program, Hawaii Tumor Registry, Honolulu, HI 96813 USA. NCI, Tissue Array Res Program, NIH, Bethesda, MD 20852 USA. Univ Iowa, State Hlth Registry Iowa, Coll Publ Hlth, Iowa City, IA 52242 USA. NCI, Surveillance Res Program, Div Canc Control & Populat Sci, NIH, Rockville, MD 20852 USA. Kapiolani Med Ctr Women & Children, Dept Pathol, Honolulu, HI 96826 USA. Univ Virginia, Med Ctr, Dept Pathol, Charlottesville, VA 22908 USA. Univ So Calif, Los Angeles Canc Surveillance Syst, Los Angeles, CA 90033 USA. Univ New Mexico, New Mexico Tumor Registry, Canc Res & Treatment Ctr, Albuquerque, NM 87131 USA. RP Goodman, MT (reprint author), Univ Hawaii, Canc Res Ctr Hawaii, Etiol Program, Hawaii Tumor Registry, Honolulu, HI 96813 USA. EM mare@crch.hawaii.edu OI Hewitt, Stephen/0000-0001-8283-1788 FU NCI NIH HHS [N01 CN 25403, N01 CN 67001, N01 PC 35137] NR 39 TC 29 Z9 30 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0046-8177 J9 HUM PATHOL JI Hum. Pathol. PD JUL PY 2005 VL 36 IS 7 BP 812 EP 820 DI 10.1016/j.humpath.2005.03.010 PG 9 WC Pathology SC Pathology GA 956NE UT WOS:000231305800017 PM 16084952 ER PT J AU Jackson, LW Schisterman, EF Dey-Rao, R Browne, R Armstrong, D AF Jackson, LW Schisterman, EF Dey-Rao, R Browne, R Armstrong, D TI Oxidative stress and endometriosis SO HUMAN REPRODUCTION LA English DT Article DE endometriosis; infertility; oxidative stress; thiobarbituric acid-reactive substances ID LOW-DENSITY-LIPOPROTEIN; LIPID-PEROXIDATION; ANTIOXIDANT STATUS; ACID PEROXIDATION; ENZYME-ACTIVITIES; PERITONEAL-FLUID; LUTEAL PHASES; FREE-RADICALS; WOMEN; INFERTILITY AB BACKGROUND: Little is known about the aetiology of endometriosis; however, in the presence of oxidative stress, reactive oxygen species might increase growth and adhesion of endometrial cells in the peritoneal cavity, leading to endometriosis and infertility. Within a study investigating persistent organic compounds and endometriosis, the authors evaluated the association between oxidative stress and endometriosis. METHODS: Women aged 18-40 years who were undergoing laparoscopy were contacted to participate in the study (n = 100); 84 were eligible and agreed to be interviewed; 78 provided blood specimens. Four markers of oxidative stress and antioxidant status were measured in serum for 61 women. Multiple imputation of missing data was used to generate values for the missing oxidative stress data. RESULTS: Thirty-two women had visually confirmed endometriosis at laparoscopy while 52 did not, including 22 undergoing tubal ligation and 30 with idiopathic infertility. There was a weak association between thiobarbituric acid-reactive substances (nmol/ml) and endometriosis, after adjusting for age, body mass index, current smoking, hormone use in the past 12 months, gravidity, serum vitamin E, serum estradiol, and total serum lipids (beta = 1.18; 95% CI-0.04, 2.39). CONCLUSIONS: These results suggest that oxidative stress might play a role in the development and progression of endometriosis, which should be evaluated in larger studies. C1 NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. Zeptometrix Corp, Buffalo, NY 14202 USA. SUNY Buffalo, Dept Biotech & Clin Lab Sci, Buffalo, NY 14214 USA. Oxidat Stress Associates Inc, Gainesville, FL 32601 USA. RP Jackson, LW (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. EM jacksole@mail.nih.gov OI Schisterman, Enrique/0000-0003-3757-641X FU NIEHS NIH HHS [1R01ES09044-01] NR 46 TC 89 Z9 96 U1 1 U2 6 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUL PY 2005 VL 20 IS 7 BP 2014 EP 2020 DI 10.1093/humrep/dei001 PG 7 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 943NA UT WOS:000230359600040 PM 15817589 ER PT J AU Alvero, R Segars, J AF Alvero, R Segars, J TI Reply: The presence of blood in the transfer catheter negatively influences outcome at embryo transfer SO HUMAN REPRODUCTION LA English DT Letter ID IN-VITRO FERTILIZATION; DIFFICULT; IMPACT C1 Univ Colorado, Ctr Hlth Sci, Aurora, CO USA. NICHHD, Unit Reprod Endocrinol, Reprod Biol & Med Branch, NIH,DHHS, Bethesda, MD 20892 USA. RP Alvero, R (reprint author), Univ Colorado, Ctr Hlth Sci, Aurora, CO USA. EM ruben.alvero@uchsc.edu NR 7 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0268-1161 J9 HUM REPROD JI Hum. Reprod. PD JUL PY 2005 VL 20 IS 7 BP 2030 EP 2031 DI 10.1093/humrep/de813 PG 2 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 943NA UT WOS:000230359600044 ER PT J AU Alderman, MH Arnett, DK Bakris, GL Black, HR Boerwinkle, E Califf, RM Cushman, WC Cutler, J Davis, BR Devereux, RB Ferdinand, K Fleg, JL Fournier, A Furberg, CD Giles, TD Gottdiener, JS Grimm, RH Hyman, DJ Jamerson, KA Kostis, JB Krauss, RM Leenen, FHH Levey, AS Levy, D MacMahon, S Oparil, S Probstfield, JL Psaty, BM Roccella, E Salive, M Schwartz, WB Svetkey, L Throckmorton, D Turner, ST Velletri, P Wright, J AF Alderman, MH Arnett, DK Bakris, GL Black, HR Boerwinkle, E Califf, RM Cushman, WC Cutler, J Davis, BR Devereux, RB Ferdinand, K Fleg, JL Fournier, A Furberg, CD Giles, TD Gottdiener, JS Grimm, RH Hyman, DJ Jamerson, KA Kostis, JB Krauss, RM Leenen, FHH Levey, AS Levy, D MacMahon, S Oparil, S Probstfield, JL Psaty, BM Roccella, E Salive, M Schwartz, WB Svetkey, L Throckmorton, D Turner, ST Velletri, P Wright, J CA Natl Heart Lung Blood Inst Working TI Major clinical trials of hypertension - What should be done next? SO HYPERTENSION LA English DT Article DE clinical trials; drug therapy ID CHRONIC HEART-FAILURE; BLOOD-PRESSURE CONTROL; EVIDENCE-BASED PROOF; CARDIOVASCULAR-DISEASE; KIDNEY-DISEASE; RANDOMIZED-TRIAL; ANGIOTENSIN-II; UNITED-STATES; PREVENTION; RISK AB The National Heart, Lung, and Blood Institute assembled an ad hoc working group to evaluate opportunities for new major clinical trials in the field of hypertension. The mandate of this working group was to consider the possible designs of major randomized clinical trials focused on clinical outcomes that might merit significant investment by the National Institutes of Health. The group concluded that the ideal pragmatic clinical trial would have a factorial design and include a population at elevated risk of cardiovascular disease events. Subjects would be randomized to a target of systolic blood pressure <130 versus 130 to 150 mm Hg for adequate separation of means. Initial treatment with thiazide diuretic would be followed by randomization to angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blocker, calcium channel blocker, or aldosterone antagonist. A third drug could be added according to a protocol. DNA, proteins, and metabolites would be collected in a sample adequate to assess differential impact of treatment on outcome as a function of genotype, proteomic, and metabolomic expression. Subclinical markers and images would also be measured in a sample of patients to develop evidence of ability to predict ultimate effect on clinical outcomes. This ideal trial would take place within a network, funded for at least a decade, aimed at connecting primary care providers with hypertension specialists. Within the network, substudies or independent studies would be coordinated to develop a continuously improving base of knowledge about the effective delivery of hypertension care. C1 Duke Clin Res Inst, Durham, NC 27715 USA. NHLBI, Framingham Heart Study, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Rush Med Univ, Chicago, IL USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Texas, Hlth Sci Ctr, Houston, TX USA. Univ Tennessee, Hlth Sci Ctr, Knoxville, TN 37996 USA. Univ Texas, Sch Publ Hlth, Austin, TX 78712 USA. New York Presbyterian Hosp, New York, NY USA. Xavier Univ, Coll Pharm, New Orleans, LA 70125 USA. Univ Hosp, Dept Nephrol, Amiens, France. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Louisiana State Univ, Sch Med, Baton Rouge, LA 70803 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Michigan, Med Ctr, Ann Arbor, MI 48109 USA. Robert Wood Johnson Med Sch, Piscataway, NJ USA. Childrens Hosp Oakland, Res Inst, Oakland, CA 94609 USA. Univ Ottawa, Inst Heart, Ottawa, ON K1N 6N5, Canada. Tufts Univ, Sch Med, Medford, MA 02155 USA. Univ Sydney, Sydney, NSW 2006, Australia. Univ Alabama Birmingham, Vasc Biol & Hypertens Program, Birmingham, AL USA. Univ Washington, Sch Med, Clin Trials Serv Unit, Seattle, WA 98195 USA. NHLBI, OPEC, Bethesda, MD 20892 USA. Ctr Medicare & Medicaid Serv, Div Med & Surg Serv, Baltimore, MD USA. Tufts Univ New England Med Ctr, Div Nephrol, Boston, MA 02111 USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Cardiorenal Drugs, Rockville, MD 20857 USA. Mayo Clin Rochester, Rochester, MN USA. Case Western Reserve Univ, Cleveland, OH 44106 USA. RP Califf, RM (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM Calif001@mc.duke.edu NR 31 TC 16 Z9 18 U1 2 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X EI 1524-4563 J9 HYPERTENSION JI Hypertension PD JUL PY 2005 VL 46 IS 1 BP 1 EP 6 DI 10.1161/01.HYP.0000168924.37091.58 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 938OM UT WOS:000230012700001 ER PT J AU Kramer, H Jacobs, DR Bild, D Post, W Saad, MF Detrano, R Tracy, R Cooper, R Liu, K AF Kramer, H Jacobs, DR Bild, D Post, W Saad, MF Detrano, R Tracy, R Cooper, R Liu, K TI Urine albumin excretion and subclinical cardiovascular disease - The multi-ethnic study of atherosclerosis SO HYPERTENSION LA English DT Article; Proceedings Paper CT Annual Clinical Meeting of the National-Kidney-Foundation CY APR 28-MAY 02, 2004 CL Chicago, IL SP Natl Kidney Fdn DE cardiovascular diseases; urine ID LEFT-VENTRICULAR HYPERTROPHY; BEAM COMPUTED-TOMOGRAPHY; CORONARY-ARTERY DISEASE; INTIMA-MEDIA THICKNESS; ALBUMIN/CREATININE RATIO; HYPERTENSIVE PATIENTS; CREATININE RATIO; RISK DEVELOPMENT; CAROTID-ARTERY; BLOOD-PRESSURE AB We examined the association between urine albumin excretion ( UAE) and common and internal carotid artery intima-media thickness ( IMT), end-diastolic left ventricular ( LV) mass, and coronary artery calcification ( CAC) scores using data from the Multi-Ethnic Study of Atherosclerosis ( MESA), a population-based study of 6814 adults aged 45 to 85 years without clinical cardiovascular disease ( CVD). The mean age of the MESA participants was 62.7 years, 47% were male, and 15% had diabetes mellitus ( DM). Sex-specific spot urine albumin/creatinine ratios were used to define 4 UAE categories: normal, high normal, microalbuminuria, and macroalbuminuria. CAC scores were log-transformed after adding 1 to all scores. Mean values of subclinical CVD measures were computed by level of UAE after adjustment for blood pressure, DM, and other covariates. After adjustment for all covariates, geometric mean CAC scores were higher among participants with high normal UAE ( 8.8; P = 0.07), microalbuminuria ( 9.9; P = 0.002), and macroalbuminuria ( 13.1; P = 0.02) compared with normal UAE ( 7.4), but only microalbuminuria reached statistical significance. Mean LV mass ( g/m(2.7)) was significantly higher in participants with high normal UAE ( 37.0; P = 0.001), microalbuminuria ( 38.3; P = 0.0001), and macroalbuminuria ( 42.3; P = 0.0001) compared with normal UAE ( 36.0) after adjustment for all covariates. No significant difference in mean carotid IMT was found after adjustment for all covariates. Similar results were noted in MESA participants with and without DM. In conclusion, higher UAE, including levels below microalbuminuria, may reflect the presence of subclinical CVD among adults without established CVD. C1 Loyola Univ, Loyola Med Ctr, Dept Prevent Med, Div Nephrol, Maywood, IL 60153 USA. Loyola Univ, Dept Med, Div Nephrol, Maywood, IL 60153 USA. Univ Minnesota, Div Epidemiol, Minneapolis, MN 55455 USA. Univ Oslo, Dept Nutr, N-0316 Oslo, Norway. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Harbor UCLA Med Ctr, Los Angeles Biomed Res Inst, Div Cardiol, Torrance, CA 90509 USA. Univ Vermont, Coll Med, Dept Pathol, Lab Clin Biochem Res, Burlington, VT 05405 USA. Univ Vermont, Coll Med, Dept Biochem, Lab Clin Biochem Res, Burlington, VT 05405 USA. Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. RP Kramer, H (reprint author), Loyola Univ, Loyola Med Ctr, Dept Prevent Med, Div Nephrol, 2160 1st Ave, Maywood, IL 60153 USA. EM hkramer@lumc.edu OI Kramer, Holly/0000-0002-6374-837X FU NHLBI NIH HHS [N01-HC-95162, N01-HC-95159, N01-HC-95160, N01-HC-95161, N01-HC-95163, N01-HC-95164, N01-HC-95165, N01-HC-95166] NR 26 TC 86 Z9 88 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2005 VL 46 IS 1 BP 38 EP 43 DI 10.1161/01.HYP.0000171189.48911.18 PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 938OM UT WOS:000230012700011 PM 15956113 ER PT J AU Contreras, G Greene, T Agodoa, LY Cheek, D Junco, G Dowie, D Lash, J Lipkowitz, M Miller, ER Ojo, A Sika, M Wilkening, B Toto, RD AF Contreras, G Greene, T Agodoa, LY Cheek, D Junco, G Dowie, D Lash, J Lipkowitz, M Miller, ER Ojo, A Sika, M Wilkening, B Toto, RD CA AASK Study Grp Investigators TI Blood pressure control, drug therapy, and kidney disease SO HYPERTENSION LA English DT Article DE angiotensin converting enzyme; calcium channel blockers; hypertension; renal disease ID CALCIUM-CHANNEL BLOCKERS; CONVERTING ENZYME-INHIBITION; STAGE RENAL-DISEASE; DIABETIC NEPHROPATHY; TYPE-2 DIABETES/; CONTROLLED TRIAL; PROGRESSION; RAT; IRBESARTAN; RAMIPRIL AB The African American Study of Kidney Disease and Hypertension examined the effect on renal function decline of 2 blood pressure ( BP) goals ( low mean arterial pressure [ MAP] <= 92 versus usual MAP 102 to 107 mm Hg) and 3 antihypertensives ( ramipril versus amlodipine versus metoprolol). We previously reported that in all drug groups combined the BP intervention had similar effects on the primary outcome of glomerular filtration rate ( GFR) slope or the main secondary clinical composite outcome of end-stage renal disease ( ESRD), death, or GFR decline by 50% or 25 mL/min per 1.73 m(2). This report examines the effect of the BP intervention separately in the 3 drug groups. The BP effect was similar among the drug groups for either GFR slope or the main clinical composite. However, the BP effect differed significantly among the drug groups for the composite of ESRD or death ( P = 0.035) and ESRD alone ( P = 0.021). Higher event rates for amlodipine patients assigned to the usual BP goal ( 0.087 per patient-year for ESRD or death and 0.064 per patient-year for ESRD) were seen compared with the remaining groups of the factorial design ( range, 0.041 to 0.050 for ESRD or death; and range, 0.027 to 0.036 for ESRD). The low BP goal was associated with reduced risk of ESRD or death ( risk reduction 51%; 95% confidence interval, 13% to 73%) and ESRD ( 54%; 8% to 77%) for amlodipine patients, but not for patients assigned to the other drug groups. These secondary analyses suggest a benefit of the low BP goal among patients assigned to amlodipine, but they must be interpreted cautiously. C1 Univ Miami, Div Nephrol & Hypertens, Miami, FL 33136 USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. NIH, Washington, DC USA. Med Univ S Carolina, Charleston, SC 29425 USA. Columbia Univ Coll Phys & Surg, Harlem Hosp Ctr, New York, NY 10032 USA. Rush Univ, Med Ctr, Chicago, IL 60612 USA. Mt Sinai Hosp, New York, NY 10029 USA. Johns Hopkins Univ, Baltimore, MD USA. Univ Michigan, Ann Arbor, MI 48109 USA. Vanderbilt Univ, Nashville, TN USA. Emory Univ, Atlanta, GA 30322 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. RP Contreras, G (reprint author), Univ Miami, Div Nephrol & Hypertens, 1600 NW 10th Ave,RMSB,Rm 7168, Miami, FL 33136 USA. EM gcontrer@med.miami.edu FU NIDDK NIH HHS [5K24DK0281802] NR 23 TC 18 Z9 20 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUL PY 2005 VL 46 IS 1 BP 44 EP 50 DI 10.1161/01.HYP.0000166746.04472.60 PG 7 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 938OM UT WOS:000230012700012 PM 15897360 ER PT J AU Goertzen, AL Jones, DW Seidel, J Li, K Green, MV AF Goertzen, AL Jones, DW Seidel, J Li, K Green, MV TI First results from the high-resolution mouseSPECT annular scintillation camera SO IEEE TRANSACTIONS ON MEDICAL IMAGING LA English DT Article DE micro SPECT; mouse imaging; pinhole SPECT ID PINHOLE SPECT; MICE AB High-resolution single-photon emission computed tomography (SPECT) imaging in small animals tends to use long imaging times and large injected doses due to the poor sensitivity of single pinhole gamma cameras. To increase sensitivity while maintaining spatial resolution, we designed and constructed a multi-pinhole collimator array to replace the parallel hole collimators of a Ceraspect human SPECT brain scanner. The Ceraspect scanner is composed of an annular NaI(Tl) crystal within which the eight pinhole collimators (1-mm-diameter holes) rotate while projecting nonoverlapping images of the object onto the stationary annular crystal. In this manner, only one-eighth of a collimator rotation is required to acquire a full circle orbit tomographic data set. The imaging field of view (FOV) has a diameter of 25.6 mm in the transverse direction, which is sufficient to encompass a mouse in the transverse direction. The axial FOV is 25.6 mm at the center of the FOV and 13.9 mm at the edge of the transverse FOV. Data are currently acquired in step-and-shoot mode; however, the system is capable of list mode acquisition with the collimator continuously rotating. Images are reconstructed using a cone-beam ordered subsets expectation maximization method. The reconstructed spatial resolution of the system is 1.7 mm and the sensitivity at the center of the FOV is 13.8 cps/microCi. A whole-body bone scan of a mouse injected with [Tc-99 m]MDP clearly revealed skeletal structures such as the ribs and vertebral bodies. These preliminary results suggest that this approach is a good tradeoff between resolution and sensitivity and, with further refinement, may permit dynamic imaging in living animals. C1 Montreal Neurol Hosp & Inst, McConnell Brain Imaging Ctr, Montreal, PQ H3A 2B4, Canada. NIH, Imaging Phys Lab, Ctr Clin, Bethesda, MD 20892 USA. NIMH, NIMH SPECT Lab, Clin Brain Disorders Branch, IRP,NIH, Bethesda, MD 20892 USA. RP Goertzen, AL (reprint author), Montreal Neurol Hosp & Inst, McConnell Brain Imaging Ctr, 3801 Univ St, Montreal, PQ H3A 2B4, Canada. EM goertzen@bic.mni.mcgill.ca RI Goertzen, Andrew/E-7877-2011; OI Goertzen, Andrew/0000-0002-4043-0799 NR 12 TC 29 Z9 31 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0278-0062 J9 IEEE T MED IMAGING JI IEEE Trans. Med. Imaging PD JUL PY 2005 VL 24 IS 7 BP 863 EP 867 DI 10.1109/TMI.2005.843782 PG 5 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Computer Science; Engineering; Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA 941ML UT WOS:000230218800005 PM 16011315 ER PT J AU Bolland, S AF Bolland, S TI A newly discovered Fc receptor that explains IgG-isotype disparities in effector responses SO IMMUNITY LA English DT Editorial Material ID GAMMA-RIII CD16; PROTECTION; ARTHRITIS; MICE AB The known IgG FcRs primarily mediate inflammation by interacting with IgG1, even though IgG2 isotypes tend to be more pathogenic. Nimmerjahn et al. (2005) have just identified a novel Fc gamma R that binds IgG2 but not IgG1, potentially explaining differences in biological activity that are seen with various IgG isotypes (Nimmerjahn et al., 2005). C1 NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. RP Bolland, S (reprint author), NIAID, Immunogenet Lab, NIH, 12441 Parklawn Dr 217, Rockville, MD 20852 USA. NR 7 TC 7 Z9 8 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2005 VL 23 IS 1 BP 2 EP 4 DI 10.1016/j.immuni.2005.07.002 PG 3 WC Immunology SC Immunology GA 952SC UT WOS:000231024800002 PM 16039573 ER PT J AU Sarafova, SD Erman, B Yu, Q Van Laethem, F Guinter, T Sharrow, SO Feigenbaum, L Wildt, KF Ellmeier, W Singer, A AF Sarafova, SD Erman, B Yu, Q Van Laethem, F Guinter, T Sharrow, SO Feigenbaum, L Wildt, KF Ellmeier, W Singer, A TI Modulation of coreceptor transcription during positive selection dictates lineage fate independently of TCR/coreceptor specificity SO IMMUNITY LA English DT Article ID RESTRICTED T-CELLS; GENE-EXPRESSION; CD8 LINEAGE; TRANSGENIC MICE; DEVELOPING THYMOCYTES; STOCHASTIC MECHANISM; CD4-DEFICIENT MICE; INSTRUCTIVE MODEL; ANTIGEN RECEPTOR; REGULATES CD4 AB For developing T cells, coreceptor choice is matched to T cell antigen receptor (TCR) MHC specificity during positive selection in the thymus, but the mechanism remains uncertain. Here, we document that TCR-mediated positive selection signals inactivate the immature CD8(III) enhancer in double positive (DP) thymocytes, explaining in part the cessation of CD8 coreceptor transcription that occurs during positive selection. More importantly, by placing CD4 protein expression under the control of CD8 transcriptional regulatory elements, we demonstrate that cessation of CD4 coreceptor transcription during positive selection results in precisely the same lineage fate as cessation of CD8 coreceptor transcription. That is, MHC-II-signaled DP thymocytes differentiated into CD8-lineage cytotoxic T cells, despite the MHC-II specificity and CD4 dependence of their TCRs. This study demonstrates that termination of coreceptor transcription during positive selection promotes CD8-lineage fate, regardless of TCR specificity or coreceptor protein identity. C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NCI, Lab Immune Cell Biol, Bethesda, MD 20892 USA. Sabanci Univ, Fac Engn & Nat Sci, Biol Sci & Bioengn Program, TR-34956 Istanbul, Turkey. NCI, Frederick Canc Res & Dev Ctr, Ft Detrick, MD 21702 USA. Univ Vienna, Inst Immunol, VIRCC, A-1235 Vienna, Austria. RP Singer, A (reprint author), NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. EM singera@nih.gov OI Ellmeier, Wilfried/0000-0001-8192-8481 FU Austrian Science Fund FWF [Y 163] NR 47 TC 44 Z9 44 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2005 VL 23 IS 1 BP 75 EP 87 DI 10.1016/j.immuni.2005.05.011 PG 13 WC Immunology SC Immunology GA 952SC UT WOS:000231024800010 PM 16039581 ER PT J AU Guo, LY Hu-Li, J Paul, WE AF Guo, LY Hu-Li, J Paul, WE TI Probabilistic regulation in TH2 cells accounts for monoallelic expression of IL-4 and IL-13 SO IMMUNITY LA English DT Article ID LOCUS-CONTROL REGION; ASYNCHRONOUS REPLICATION; COORDINATE REGULATOR; ALLELIC EXCLUSION; GENE; RESPONSES; INTERLEUKIN-13; ACCESSIBILITY; DELETION; CLUSTER AB II4 and II13, closely linked genes, are expressed monoallelically in TH2 cells. Four different approaches (RNA FISH, cultures from II13T-II4/II13-G4 mice, cultures from heterozygous II13-II4 double knockout mice, and a highly selected set of BABL/c*CAST/Ei clones displaying strong II4 allelic bias) were utilized to study monoallelic expression of II4 and coexpression of II4 and II13 on the same chromosome. There was a random probability for expression of one or two II4 and one or two II13 alleles; coexpression of cis and trans II4 and II13 alleles was equally probable. Histone H3 acetylation of CNS1, located in the II13-II4 intergenic region, was permissive for expression of IL-4 and IL-13 but did not determine the degree of their expression. Thus, monoallelism at the II4 locus is a complex process; expression is linked to opening CNS1 but probability of expression is controlled at other sites. Based on these probabilities, individual cells randomly express II4 and II13 alleles. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Guo, LY (reprint author), NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. EM lguo@niaid.nih.gov NR 34 TC 55 Z9 55 U1 0 U2 1 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUL PY 2005 VL 23 IS 1 BP 89 EP 99 DI 10.1016/j.immuni.2005.05.008 PG 11 WC Immunology SC Immunology GA 952SC UT WOS:000231024800011 PM 16039582 ER PT J AU Berrigan, D Lavigne, JA Perkins, SN Nagy, TR Barrett, JC Hursting, SD AF Berrigan, D Lavigne, JA Perkins, SN Nagy, TR Barrett, JC Hursting, SD TI Phenotypic effects of calorie restriction and insulin-like growth factor-1 treatment on body composition and bone mineral density of C57BL/6 mice: Implications for cancer prevention SO IN VIVO LA English DT Article DE bone mineral density; calorie restriction; insulin-like growth factor-1; mice; cancer prevention ID X-RAY ABSORPTIOMETRY; DIETARY RESTRICTION; SPONTANEOUS TUMORIGENESIS; P53-DEFICIENT MICE; BINDING-PROTEINS; DBA/2 MICE; IGF-I; ENERGY; RATS; WEIGHT AB Background: Calorie restriction (CR) inhibits carcinogenesis and delays aging. Some anti-carcinogenic effects of CR are mediated by decreased circulating insulin-like growth factor-1 (IGF-1); however, IGF-1 also plays an important role in regulating growth and bone density. Materials and Methods: We quantified tradeoffs involving the CR/IGF-1 axis in C57BL/6 mice by examining body composition and bone characteristics in ad libitum fed, 20, 30 or 40% CR mice that received placebo or recombinant murine IGF-1 delivered with a time-release pellet. After 26 days, carcasses were scanned with a PIXImus II dual-energy X-ray absorptiometer. Results: CR reduced body weight and percent body fat and had non-linear effects on bone density. IGF-1 restored bone density to control levels or greater in the CR mice. Conclusion: Cancer prevention efforts based on CR and down-regulation of the IGF-1 pathway will require consideration of deleterious effects on bone. C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. Novartis Inst Biomed Res Inc, Cambridge, MA 02139 USA. RP Berrigan, D (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, Execut Plaza N MSC 7344,Room 4009A, Bethesda, MD 20892 USA. EM berrigad@mail.nih.gov FU NIDDK NIH HHS [P30-DK56336] NR 38 TC 27 Z9 27 U1 0 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDRITIOU-KALAMOU RD KAPANDRITI, PO BOX 22, ATHENS 19014, GREECE SN 0258-851X J9 IN VIVO JI In Vivo PD JUL-AUG PY 2005 VL 19 IS 4 BP 667 EP 673 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 939UE UT WOS:000230097100004 PM 15999532 ER PT J AU Clifton, DR Dooley, CA Grieshaber, SS Carabeo, RA Fields, KA Hackstadt, T AF Clifton, DR Dooley, CA Grieshaber, SS Carabeo, RA Fields, KA Hackstadt, T TI Tyrosine phosphorylation of the chlamydial effector protein Tarp is species specific and not required for recruitment of actin SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; HOST-CELLS; HELA-CELLS; INCLUSION MEMBRANE; GENOME SEQUENCE; C-TRACHOMATIS; INFECTION; PNEUMONIAE; ENTRY; TIR AB Chlamydiae are obligate intracellular pathogens that efficiently induce their endocytosis by susceptible eukaryotic host cells. Recently, a Chlamydia trachomatis type III secreted effector protein, Tarp, was found to be translocated and tyrosine phosphorylated at the site of entry and associated with the recruitment of actin that coincides with endocytosis. C trachomatis Tarp possesses up to six direct repeats of approximately 50 amino acids each. The majority of the tyrosine residues are found within this repeat region. Here we have ectopically expressed distinct domains of Tarp in HeLa 229 cells and demonstrated that tyrosine phosphorylation occurs primarily within the repeat region, while recruitment of actin is mediated by the C-terminal domain of the protein. A comparison of other sequenced chlamydial genomes revealed that each contains an ortholog of Tarp, although Chlamydia muridarum, Chlamydophila caviae, and Chlamydophila pneumoniae Tarp lack the large repeat region. Immunofluorescence and immunoblotting using an antiphosphotyrosine antibody show no evidence of phosphotyrosine at the site of entry of C. muridarum, C. caviae, and C. pneumoniae, although each species similarly recruits actin. Ectopic expression of full-length C trachomatis and C caviae Tarp confirmed that both recruit actin but only C. trachomatis Tarp is tyrosine phosphorylated. The data indicate that the C-terminal domain of Tarp is essential for actin recruitment and that tyrosine phosphorylation may not be an absolute requirement for actin recruitment. The results further suggest the potential for additional, unknown signal transduction pathways associated specifically with C. trachomatis. C1 NIAID, Host Parasite Interact Sect, Lab Intracellular Parasites, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. RP Hackstadt, T (reprint author), NIAID, Host Parasite Interact Sect, Lab Intracellular Parasites, Rocky Mt Labs,NIH, Hamilton, MT 59840 USA. EM ted_hackstadt@nih.gov FU NIAID NIH HHS [K22 AI052252, K22 AI052252-02, R01 AI065545, R01 AI065545-02] NR 40 TC 65 Z9 67 U1 0 U2 3 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 JUL PY 2005 VL 73 IS 7 BP 3860 EP 3868 DI 10.1128/IAI.73.7.3860-3868.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 940NL UT WOS:000230151100005 PM 15972471 ER PT J AU Murray, HW Flanders, KC Donaldson, DD Sypek, JP Gotwals, PJ Liu, JG Ma, XJ AF Murray, HW Flanders, KC Donaldson, DD Sypek, JP Gotwals, PJ Liu, JG Ma, XJ TI Antagonizing deactivating cytokines to enhance host defense and chemotherapy in experimental visceral leishmaniasis SO INFECTION AND IMMUNITY LA English DT Article ID GROWTH-FACTOR-BETA; CELL-ASSOCIATED CYTOKINES; TGF-BETA; IMMUNE-RESPONSE; MAJOR INFECTION; IN-VIVO; INTERLEUKIN-10 RECEPTOR; DONOVANI INFECTION; GAMMA-INTERFERON; DEFICIENT MICE AB In experimental visceral leishmaniasis, inhibition of interleukin 10 (IL-10) signaling enhances Th1-cell-associated responses, promoting gamma interferon (IFN-gamma) secretion, granuloma assembly, macrophage activation with substantial liver parasite killing, and synergy with pentavalent antimony (Sb) chemotherapy. To determine if inhibiting other suppressive cytokines has similar therapeutic potential, Leishmania donovani-infected BALB/c mice were injected with anti-IL-4 monoclonal antibody or receptor fusion antagonists of IL-13 or transforming growth factor beta (TGF-beta). Targeting IL-13 or TGF-beta enabled inhibition of L. donovani replication but little parasite killing; anti-IL-4 had no effect. None of the three antagonists promoted IFN-gamma production, granuloma maturation, or Sb efficacy. Excess IL-13 and TGF-beta exacerbated liver infection; however, effects were transient. Among IL-10, IL-4, IL-13, and TGF-beta, cytokines capable of disabling Th1-cell mechanisms (including those which support chemotherapy), IL-10 appears to be the appropriate target for therapeutic inhibition in visceral L. donovani infection. C1 Cornell Univ, Weill Med Coll, Dept Med, New York, NY 10021 USA. Cornell Univ, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. NCI, Lab Cell Regulat & Carcinogenesis, Bethesda, MD 20892 USA. Wyeth Ayerst Res, Cambridge, MA 02140 USA. Biogen Idec, Cambridge, MA 02142 USA. RP Murray, HW (reprint author), Cornell Univ, Weill Med Coll, Dept Med, Box 136,1300 York Ave, New York, NY 10021 USA. EM hwmurray@med.cornell.edu FU NIAID NIH HHS [R01 AI045899, AI45899, AI 16369] NR 63 TC 41 Z9 41 U1 0 U2 2 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 JUL PY 2005 VL 73 IS 7 BP 3903 EP 3911 DI 10.1128/IAI.73.7.3903-3911.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 940NL UT WOS:000230151100010 PM 15972476 ER PT J AU Giersing, B Miura, K Shimp, R Wang, J Zhou, H Orcutt, A Stowers, A Saul, A Miller, LH Long, C Singh, S AF Giersing, B Miura, K Shimp, R Wang, J Zhou, H Orcutt, A Stowers, A Saul, A Miller, LH Long, C Singh, S TI Posttranslational modification of recombinant Plasmodium falciparum apical membrane antigen 1: Impact on functional immune responses to a malaria vaccine candidate SO INFECTION AND IMMUNITY LA English DT Article ID PICHIA-PASTORIS; O-GLYCOSYLATION; EXPRESSION; PROTEINS; INVASION; AMA-1; ANTIBODIES; MONKEYS; MICE; IMMUNOGENICITY AB Recombinant apical membrane antigen 1 (AMA1) is a leading vaccine candidate for Plasmodium falciparum malaria, as antibodies against recombinant P. falciparum AMA1 (PfAMA1) interrupt merozoite invasion into erythrocytes. In order to investigate the role of posttranslational modification in modulating the functional immune response to recombinant AMA1, two separate alleles of PfAMA1 (FVO and 3D7), in which native N-glycosylation sites have been mutated, were produced using Escherichia coli and a Pichia pastoris expression system. Recombinant Pichia pastoris AMA1-FVO (PpAMA1-FVO) and PpAMA1-3D7 are O-linked glycosylated, and 45 % of PpAMA1-3D7 is nicked, though all four recombinant molecules react with conformation-specific monoclonal antibodies. To address the immunological effect of O-linked glycosylation, we compared the immunogenicity of E. coli AMA1-FVO (EcAMA1-FVO) and PpAMA1-FVO antigens, since both molecules are intact. The effect of antigen nicking was then investigated by comparing the immunogenicity of EcAMA1-3D7 and PpAMA1-3D7. Our data demonstrate that there is no significant difference in the rabbit antibody titer elicited towards EcAMA1-FVO and PpAMA1-FVO or to EcAMA1-3D7 and PpAMA1-3D7. Furthermore, we have demonstrated that recombinant AMA1 (FVO or 3D7), whether expressed and refolded from E. coli or produced from the Pichia expression system, is equivalent and mimics the functionality of the native protein in in vitro growth inhibition assay experiments. We conclude that in the case of recombinant AMA1, the E. coli and P. pastoris-derived antigens are immunologically and functionally equivalent and are unaffected by the posttranslational modification resulting from expression in these two systems. C1 NIAID, Malaria Vaccine Dev Branch, Rockville, MD 20852 USA. RP Singh, S (reprint author), Twinbrook 1,Room 1210A,5640 Fisher Lane, Rockville, MD 20852 USA. EM ssingh@niaid.nih.gov RI Saul, Allan/I-6968-2013 OI Saul, Allan/0000-0003-0665-4091 NR 47 TC 23 Z9 23 U1 0 U2 3 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 JUL PY 2005 VL 73 IS 7 BP 3963 EP 3970 DI 10.1128/IAI.73.7.3963-3970.2005 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 940NL UT WOS:000230151100017 PM 15972483 ER PT J AU Mitre, E Norwood, S Nutman, TB AF Mitre, E Norwood, S Nutman, TB TI Saturation of immunoglobulin E (IgE) binding sites by polyclonal IgE does not explain the protective effect of helminth infections against atopy SO INFECTION AND IMMUNITY LA English DT Article ID FC-EPSILON-RI; HUMAN BASOPHILS; SERUM IGE; HISTAMINE-RELEASE; ALLERGIC REACTIVITY; HYGIENE HYPOTHESIS; EXPRESSION; RECEPTORS; PARASITES; CHILDREN AB One hypothesis for the decreased rates of atopy observed among helminth-infected individuals is that parasite-induced polyclonal immunoglobulin E (IgE) outcompetes allergen-specific IgE for Fc epsilon RI binding on basophils and mast cells. In experiments with fresh blood drawn from filaria-infected patients, we found no association between ratios of polyclonal to Brugia malayi antigen (BmAg)-specific IgE (range, 14:1 to 388:1) and basophil responses to BmAg as measured by histamine release. Using serum samples from a filaria-infected patient who also had dust mite (Dermatophagoides pteronyssinus) -specific IgE antibodies from time points with various ratios of polyclonal to D.pteronyssinus-specific IgE (16:1 to 86:1), we demonstrated that increased ratios of polyclonal to D. pteronyssinus-specific IgE did not attenuate basophil sensitization as measured by D. pteronyssinus-specific histamine release. Suppression of histamine release was likely not observed in either of these sets of experiments because polyclonal to antigen-specific IgE ratios were not sufficiently high, as concurrent passive sensitization of basophil experiments required ratios of polyclonal to antigen-specific IgE of greater than 500:1 to suppress basophil histamine release. Further, the intensity of IgE staining in basophil populations from 20 patients with active filaria infections correlated strongly with total serum IgE levels (rho = 0.698; P = 0.0024) with no plateau in intensity of IgE staining, even though some patients had total IgE levels of greater than 10,000 ng/ml. Our data therefore suggest that in helminth infections (and in filarial infections in particular), the ratios of polyclonal to allergen -specific IgE rarely reach those levels necessary to inhibit allergen-specific IgE-Fc epsilon RI binding and to suppress allergen-induced degranulation of mast cells and basophils. C1 NIAID, Helminth Immunol Sect, LPD, NIH, Bethesda, MD 20892 USA. RP Mitre, E (reprint author), NIAID, Helminth Immunol Sect, LPD, NIH, 4 Ctr Lane,Room 4-126, Bethesda, MD 20892 USA. EM emitre@niaid.nih.gov NR 31 TC 33 Z9 37 U1 1 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2005 VL 73 IS 7 BP 4106 EP 4111 DI 10.1128/IAI.73.7.4106-4111.2005 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 940NL UT WOS:000230151100033 PM 15972499 ER PT J AU Pantelic, M Kim, YJ Bolland, S Chen, I Shively, J Chen, T AF Pantelic, M Kim, YJ Bolland, S Chen, I Shively, J Chen, T TI Neisseria gonorrhoeae kills carcinoembryonic antigen-related cellular adhesion molecule 1 (CD66a)-expressing human B cells and inhibits antibody production SO INFECTION AND IMMUNITY LA English DT Article ID GONOCOCCAL OPACITY PROTEINS; FC-GAMMA-RIIB; TYROSINE PHOSPHATASES SHP-1; BILIARY GLYCOPROTEIN CD66A; VIRUSES DISRUPT FUNCTIONS; EPITHELIAL-CELLS; MEASLES-VIRUS; HUMAN-LYMPHOCYTES; PHASE VARIATION; PATHOGENIC NEISSERIAE AB Neisseria gonorrhoeae cells (gonococci [GC]), the etiological agents for gonorrhea, can cause repeated infections. During and after gonococcal infection, local and systemic antigonococcal antibody levels are low. These clinical data indicate the possibility that GC may suppress immune responses during infection. Carcinoembryonic antigen-related cellular adhesion molecule 1 (CEACAM1 or CD66a), a receptor for GC opacity (Opa) proteins, was shown to mediate inhibitory signals. In the present study, human B cells were activated by interleukin-2 to express CEACAM1 and then stimulated to secrete antibodies and simultaneously coincubated with Opa(-) and Opal GC of strain MS11. Our results show that this OpaI GC has the ability to inhibit antibody production. The interaction of GC and CEACAM1 with human peripheral B cells also results in induction of cell death. The same findings were observed in DT40 B cells. This CEACAM1-promoted cell death pathway does not involve the inhibitory signals or the tyrosine phosphatases SHP-1 and SHP-2 but depends on Bruton's tyrosine kinase in DT40 cells. Our results suggest that Neisseria gonorrhoeae possesses the ability to suppress antibody production by killing CEACAM1-expressing B cells. C1 Indiana Univ, Sch Med, Div Infect Dis, Dept Microbiol & Immunol,Walther Oncol Ctr, Indianapolis, IN 46202 USA. NIAID, Immunogenet Lab, NIH, Rockville, MD 20852 USA. City Hope Natl Med Ctr, Beckman Res Inst, Div Immunol, Duarte, CA 91010 USA. Publ Hlth Res Inst, Newark, NJ USA. RP Chen, T (reprint author), Indiana Univ, Sch Med, Div Infect Dis, Dept Microbiol & Immunol,Walther Oncol Ctr, MS415E,635 Barnhill Dr, Indianapolis, IN 46202 USA. EM tiechen@iupui.edu OI Chen, Ines/0000-0002-1405-9703 FU FIC NIH HHS [R03 TW006270, R03TW006270]; NIAID NIH HHS [R01 AI047736]; PHS HHS [R01A1 47736] NR 67 TC 51 Z9 55 U1 0 U2 2 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 JUL PY 2005 VL 73 IS 7 BP 4171 EP 4179 DI 10.1128/IA.73.7.4171-4179.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 940NL UT WOS:000230151100041 PM 15972507 ER PT J AU Peng, DX Choudhury, BP Petralia, RS Carlson, RW Gu, XX AF Peng, DX Choudhury, BP Petralia, RS Carlson, RW Gu, XX TI Roles of 3-deoxy-D-manno-2-octulosonic acid transferase from Moraxella catarrhalis in lipooligosaccharide biosynthesis and virulence SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE PROTEIN; BRANHAMELLA-CATARRHALIS; LIPID-A; ESCHERICHIA-COLI; NEISSERIA-MENINGITIDIS; PSEUDOMONAS-AERUGINOSA; HAEMOPHILUS-INFLUENZAE; EPITHELIAL-CELLS; SEROTYPE-A; BACTERICIDAL ACTIVITY AB Lipooligosaccharide (LOS), a major outer membrane component of Moraxella catarrhalis, is a possible virulence factor in the pathogenesis of human infections caused by the organism. However, information about the roles of the oligosaccharide chain from LOS in bacterial infection remains limited. Here, a kdtA gene encoding 3-deoxy-D-manno-2-octulosonic acid (Kdo) transferase, which is responsible for adding Kdo residues to the lipid A portion of the LOS, was identified by transposon mutagenesis and construction of an isogenic kdtA mutant in strain O35E. The resulting O35EkdtA mutant produced only lipid A without any core oligosaccharide, and it was viable. Physicochemical and biological analysis revealed that the mutant was susceptible to hydrophobic reagents and a hydrophilic glycopeptide and was sensitive to bactericidal activity of normal human serum. Importantly, the mutant showed decreased toxicity by the Limulus amebocyte lysate assay, reduced adherence to human epithelial cells, and enhanced clearance in lungs and nasopharynx in a mouse aerosol challenge model. These data suggest that the oligosaccharide moiety of the LOS is important for the biological activity of the LOS and the virulence capability of the bacteria in vitro and in vivo. This study may bring new insights into novel vaccines or therapeutic interventions against M. catarrhalis infections. C1 Natl Inst Deafness & Other Commun Disorders, Vaccine Res Sect, Rockville, MD 20850 USA. Natl Inst Deafness & Other Commun Disorders, Sect Neurotransmitter Receptor Biol, Rockville, MD 20850 USA. Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. RP Gu, XX (reprint author), 5 Res Court,Room 2A31, Rockville, MD 20850 USA. EM guxx@nidcd.nih.gov NR 51 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2005 VL 73 IS 7 BP 4222 EP 4230 DI 10.1128/IAI.73.7.4222-4230.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 940NL UT WOS:000230151100047 PM 15972513 ER PT J AU Moayeri, M Webster, JI Wiggins, JF Leppla, SH Sternberg, EM AF Moayeri, M Webster, JI Wiggins, JF Leppla, SH Sternberg, EM TI Endocrine perturbation increases susceptibility of mice to anthrax lethal toxin SO INFECTION AND IMMUNITY LA English DT Article ID PITUITARY-ADRENAL AXIS; GLUCOCORTICOID-RECEPTOR; BACILLUS-ANTHRACIS; PROTECTIVE ANTIGEN; GENE-EXPRESSION; MACROPHAGE SENSITIVITY; PLASMA-CORTICOSTERONE; HORMONE RECEPTORS; KINASE-KINASE; LEWIS RATS AB Bacillus anthracis lethal toxin (LT) causes vascular collapse and high lethality in BALB/cJ mice, intermediate lethality in C57BL/6j mice, and no lethality in DBA/2J mice. We found that adrenalectomized (ADX) mice of all three strains had increased susceptibility to LT. The increased susceptibility of ADX-DBA/2J mice was not accompanied by changes in their macrophage sensitivity or cytokine response to LT. DBA/2J mice showed no change in serum corticosteroid levels in response to LT injection, while BALB/cJ mice showed a fivefold increase in serum corticosterone. However, LT inhibited dexamethasone (DEX)-induced glucocorticoid receptor gene activation to similar extents in all three strains. DEX treatment did not rescue ADX mice from LT-mediated mortality. Surprisingly, oral DEX treatment also sensitized adrenally intact DBA/2J mice to LT lethality at all doses tested and also exacerbated LT-mediated pathogenesis and mortality in BALB/cJ mice. Aldosterone did not protect ADX mice from toxin challenge. These results indicate that susceptibility to anthrax LT in mice depends on a fine but easily perturbed balance of endocrine functions. Thus, the potentially detrimental consequences of steroid therapy for anthrax must be considered in treatment protocols for this disease. C1 NIAID, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. NIMH, Sect Neuroendocrine Immunol & Behav, NIH, Bethesda, MD 20892 USA. RP Moayeri, M (reprint author), NIAID, Microbial Pathogenesis Sect, NIH, Bldg 30,Room 303, Bethesda, MD 20892 USA. EM mmoayeri@niaid.nih.gov RI Webster Marketon, Jeanette/H-5613-2011 OI Webster Marketon, Jeanette/0000-0002-3627-1094 NR 59 TC 29 Z9 30 U1 0 U2 0 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 JUL PY 2005 VL 73 IS 7 BP 4238 EP 4244 DI 10.1128/IAI.73.7.4238-4244.2005 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 940NL UT WOS:000230151100049 PM 15972515 ER PT J AU Kurup, VP Raju, R Manickam, P AF Kurup, VP Raju, R Manickam, P TI Profile of gene expression in a murine model of allergic bronchopulmonary aspergillosis SO INFECTION AND IMMUNITY LA English DT Article ID ADAM33 GENE; ASTHMA; MICE; HYPERRESPONSIVENESS; ASSOCIATION; EOSINOPHILS; FUMIGATUS; ARGINASE AB Allergic brunchopulmonary aspergillosis (ABPA) results from the interactions of the Aspergillus allergens and immune system of the patients. We studied the gene expression profile in a mouse model of ABPA. Of the 12,000 genes studied, 1,300 genes showed enhanced expression and represent chemokine, cytokine, growth factor, signal transduction, and transmembrane receptor genes as well as genes related to arginine metabolism. C1 Vet Adm Med Ctr, Res Serv, Milwaukee, WI 53295 USA. Med Coll Wisconsin, Div Allergy Immunol, Milwaukee, WI USA. NIH, Neuromuscular Dis Sect, Bethesda, MD 20892 USA. Capital Genomix Inc, Rockville, MD USA. RP Kurup, VP (reprint author), Vet Adm Med Ctr, Res Serv, 151-I,5000 W Natl Ave, Milwaukee, WI 53295 USA. EM vkurup@mcw.edu RI Raju, Raghavan/E-9219-2011 NR 17 TC 5 Z9 7 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2005 VL 73 IS 7 BP 4381 EP 4384 DI 10.1128/IAI.73.7.4381-4384.2005 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 940NL UT WOS:000230151100067 PM 15972533 ER PT J AU Kumar, S Barillas-Mury, C AF Kumar, S Barillas-Mury, C TI Ookinete-induced midgut peroxidases detonate the time bomb in anopheline mosquitoes SO INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY LA English DT Article; Proceedings Paper CT Keystone Conference on Genetic Manipulation of Insects CY FEB, 2004 CL Taos, NM DE Anopheles stephensi; midgut; invasion; peroxidase; nitration; nitric oxide synthase ID NITRIC-OXIDE; EOSINOPHIL PEROXIDASE; TYROSINE NITRATION; DIFFERENTIAL EXPRESSION; NITROTYROSINE FORMATION; STAPHYLOCOCCUS-AUREUS; MALARIA INFECTION; DEPENDENT MANNER; RESPONSIVE GENES; IMMUNE-RESPONSE AB Previous analysis of the temporal-spatial relationship between ookinete migration and the cellular localization of genes mediating midgut immune defense responses suggested that, in order to survive, parasites must complete invasion before toxic chemicals ("a bomb") are generated by the invaded cell. Recent studies indicate that ookinete invasion induces tyrosine nitration as a two-step reaction, in which NOS induction is followed by a localized increase in peroxidase activity. Peroxidases utilize nitrite and hydrogen peroxide as substrates, and detonate the time bomb by generating reactive nitrogen intermediates, such as nitrogen dioxide, which mediate nitration. There is evidence that peroxidases also mediate antimicrobial responses to bacteria, fungi and parasites in a broad range of biological systems including humans and plants. Defense reactions that generate toxic chemicals are also potentially harmful to the host mounting the response and often results in apoptosis. The two-step nitration pathway is probably an ancient response, as it has also been described in vertebrate leukocytes and probably evolved as a mechanism to circumscribe the toxic products generated during defense responses involving protein nitration. Published by Elsevier Ltd. C1 NIH, Lab Malaria & Vector res, Rockville, MD 20852 USA. RP Barillas-Mury, C (reprint author), NIH, Lab Malaria & Vector res, 12735 Twinbrook Pkwy, Rockville, MD 20852 USA. EM cbarillas@niaid.nih.gov FU NIAID NIH HHS [R01AI45573] NR 45 TC 33 Z9 33 U1 0 U2 4 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 JUL PY 2005 VL 35 IS 7 BP 721 EP 727 DI 10.1016/j.ibmb.2005.02.014 PG 7 WC Biochemistry & Molecular Biology; Entomology SC Biochemistry & Molecular Biology; Entomology GA 930WE UT WOS:000229447000008 PM 15894189 ER PT J AU Caballero-Hernandez, D Weberb, RJ Hicks, ME Tamez-Guerra, R Rodriguez-Padilla, C Tamez-Guerra, P Rice, KC Ananthan, S Gomez-Flores, R AF Caballero-Hernandez, D Weberb, RJ Hicks, ME Tamez-Guerra, R Rodriguez-Padilla, C Tamez-Guerra, P Rice, KC Ananthan, S Gomez-Flores, R TI Potentiation of rat lymphocyte proliferation by novel non-peptidic synthetic opioids SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE SNC 80; naltrindole derivatives; naltrexone derivatives; non-peptide opioids; delta-opioid agonist; mu-opioid agonists; lymphoproliferation ID NITRIC-OXIDE PRODUCTION; CD4(+) T-CELLS; IN-VITRO; MACROPHAGE FUNCTIONS; IMMUNE FUNCTION; NATURAL-KILLER; RECEPTOR EXPRESSION; PERIPHERAL-BLOOD; CONCANAVALIN-A; MU AB Opioids represent a major source of relief for acute and chronic, moderate to severe nonmalignant pain. However, opioid abuse may cause immunosuppression leading to infections and cancer development. Recently we reported results on novel non-peptidic delta- and mu-selective opioids that induced immunopotentiation in vitro and ex vivo. In the present study, we investigated the effects of the delta agonist SNC 80, and mu agonists, naltrindole and naltrexone derivatives for their capacity to alter lymphoproliferation in vitro. They were observed to stimulate lymphoproliferation at concentrations ranging from 10(-10) to 10(-5) M. SNC 80 significantly (p<0.05) stimulated (43-311%) proliferation of resident and concanavalin A (Con A)-treated lymphocytes; the naltrindole derivatives 9332 and 9333 caused significant (p<0.05) 26-47% and 13-43%, respectively, stimulation of Con A-treated lymphoproliferation; whereas the naltrexone derivatives 9334 and 9336 significantly (p<0.05) stimulated 9-40% and 15-69%, respectively, proliferation of resident and Con A-treated lymphocytes. These novel opioid ligands could serve as immunotherapeutic agents by increasing the pool of lymphocytes with potential use in the treatment of infectious diseases including AIDS. This study provides evidence of the relationship structure/function of opioids on lymphoproliferation, and supports further evaluation of opioids with immunomodulatory potential in preclinical and clinical studies. (C) 2005 Elsevier B.V. All rights reserved. C1 Univ Autonoma Nuevo Leon, Fac Ciencias Biol, Dept Microbiol & Inmunol, San Nicolas De Los Garza, NL, Mexico. UIC Coll Med, Dept Biomed & Therapeut Sci, Peoria, IL USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. So Res Inst, Dept Organ Chem, Birmingham, AL 35255 USA. RP Gomez-Flores, R (reprint author), Loma Panoram 321-1,Colonia Loma Larga, Monterrey 64710, Nuevo Leon, Mexico. EM rgomez60@hotmail.com OI Caballero-Hernandez, Diana/0000-0002-5446-1238 NR 38 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD JUL PY 2005 VL 5 IS 7-8 BP 1271 EP 1278 DI 10.1016/j.intimp.2005.03.009 PG 8 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 934NA UT WOS:000229714300016 PM 15914331 ER PT J AU Duan, HM Duan, HP Zhang, ZY Tong, TJ AF Duan, HM Duan, HP Zhang, ZY Tong, TJ TI Irreversible cellular senescence induced by prolonged exposure to H2O2 involves DNA-damage-and-repair genes and telornere shortening SO INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY LA English DT Article DE cellular senescence; oxidative stress; hydrogen peroxide; DNA damage; DNA repair; telomere; human fibroblast ID HUMAN-DIPLOID FIBROBLASTS; SINGLE-STRAND BREAKS; OXIDATIVE STRESS; REPLICATIVE SENESCENCE; HYDROGEN-PEROXIDE; HUMAN-CELLS; IN-VITRO; TELOMERES; P16(INK4A); EXPRESSION AB H2O2 has been the most commonly used inducer for stress-induced premature senescence (SIPS), which shares features of replicative senescence. However, there is still uncertainty whether SIPS and replicative senescence differ or utilize different pathways. 'Young' human diploid fibroblasts (HDFs), treated with prolonged low doses of hydrogen peroxide, led to irreversible cellular senescence. Cells exhibited senescent-morphological features, irreversible G1 cell cycle arrest and irreversible senescence-associated P-galactosidase positivity. The appearance of these cellular senescence markers was accompanied by significant increases of p21, gadd45 expression and p53 binding activity, as well as a significant decline in DNA repair capability and accelerated telomere shortening. Our results suggest that multiple pathways might be involved in oxidative SIPS, including genes related to DNA-damage-and-repair and telomere shortening, and that SIPS shares the same mechanisms with replicative senescence in vivo. Our findings indicate that several aging theories can be merged together by a common mechanism of oxidative damage, and that the level of oxidative DNA-damage-and-repair capacity may be exploited as reliable markers of cell senescence. (c) 2005 Elsevier Ltd. All rights reserved. C1 Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100083, Peoples R China. Natl Inst Deafness & Other Commun Disorders, Tumor Biol Sect, Head & Neck Surg Branch, NIH, Bethesda, MD 20892 USA. Shiji Peoples Hosp Guangzhou Panyu, Dept Internal Med, Guangzhou 511450, Peoples R China. RP Tong, TJ (reprint author), Peking Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, Beijing 100083, Peoples R China. EM ttj@bjmu.edu.cn NR 49 TC 74 Z9 80 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1357-2725 J9 INT J BIOCHEM CELL B JI Int. J. Biochem. Cell Biol. PD JUL PY 2005 VL 37 IS 7 BP 1407 EP 1420 DI 10.1016/j.biocel.2005.01.010 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 926ZG UT WOS:000229161600009 PM 15833273 ER PT J AU Asai-Sato, M Nagashima, Y Miyagi, E Sato, K Ohta, I Vonderhaar, BK Hirahara, F AF Asai-Sato, M Nagashima, Y Miyagi, E Sato, K Ohta, I Vonderhaar, BK Hirahara, F TI Prolactin inhibits apoptosis of ovarian carcinoma cells induced by serum starvation or cisplatin treatment SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE ovarian carcinoma; prolactin; prolactin receptors; apoptosis; cisplatin ID EPITHELIAL-CELLS; BREAST-CANCER; RECEPTOR; GROWTH; EXPRESSION; ESTROGEN; ADENOCARCINOMA; PROSTATE; CULTURE; RISK AB Prolactin, a peptide hormone essential for the development and function of reproductive organs, is involved in development of breast, prostate and colorectal cancers. However, the role of prolactin on the carcinogenesis of ovarian carcinomas is unclear. In this study, we show that mRNA of prolactin receptor is expressed in 5 out of 9 ovarian carcinoma cell lines, 15 out of 17 cases of surgical samples and all of normal ovarian surface epithelium, while prolactin transcript is detected only in I ovarian carcinoma cell line and in I of the surgical samples. For the prolactin receptor-positive ovarian carcinoma cells, exogenous prolactin did not affect the proliferation but markedly inhibited apoptosis. Therefore, actual cell growth was enhanced by prolactin in a dose-dependent manner. The blocking of prolactin receptor by antibody severely impaired the antiapoptotic and growth-promoting effects of prolactin. Interestingly, the cisplatin-induced cell death of the prolactin receptor-positive cells was significantly inhibited by pretreatment with prolactin. These findings indicate a responsiveness of ovarian carcinomas to prolactin and suggest that the prolactin/prolactin receptor system may be a new therapeutic target of ovarian carcinomas. © 2005 Wiley-Liss. Inc. C1 Yokohama City Univ, Grad Sch Med, Dept Obstet Gynecol & Mol Reprod Sci, Kanazawa Ku, Yokohama, Kanagawa 2360004, Japan. Yokohama City Univ, Grad Sch Med, Dept Mol Pathol, Yokohama, Kanagawa 2360004, Japan. Natl Def Med Coll, Dept Internal Med 3, Saitama, Japan. NCI, Canc Res Ctr, Lab Mammary Biol & Tumorigenesis, Bethesda, MD 20892 USA. RP Hirahara, F (reprint author), Yokohama City Univ, Grad Sch Med, Dept Obstet Gynecol & Mol Reprod Sci, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 2360004, Japan. EM hrafu@med.yokohama-cu.ac.jp NR 29 TC 19 Z9 20 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 2005 VL 115 IS 4 BP 539 EP 544 DI 10.1002/ijc.20810 PG 6 WC Oncology SC Oncology GA 925WA UT WOS:000229082800005 PM 15700312 ER PT J AU Sakoda, LC Graubard, BI Evans, AA London, WT Lin, WY Shen, FM McGlynn, KA AF Sakoda, LC Graubard, BI Evans, AA London, WT Lin, WY Shen, FM McGlynn, KA TI Toenail selenium and risk of hepatocellular carcinoma mortality in Haimen City, China SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE neoplasm; liver; selenium; epidemiology ID GLUTATHIONE-PEROXIDASE ACTIVITY; PRIMARY LIVER-CANCER; PLASMA SELENIUM; SUPEROXIDE-DISMUTASE; MENSTRUAL-CYCLE; SERUM SELENIUM; TRACE-ELEMENTS; S-TRANSFERASE; RAT LIVER; HEPATITIS AB Selenium (Se) is an essential trace mineral with known anticarcinogenic properties in humans. However, few studies have examined the association between Se nutrient status and risk of liver cancer. We conducted a nested case-control study comparing the Se content in toenail clippings of 166 individuals (154 men, 12 women) with hepatocellular carcinoma (HCC) to 394 healthy controls (360 men, 34 women) in Haimen City, China, where HCC is a leading cause of mortality,, Toenail Se concentration was measured by inductively coupled plasma-optical emission spectroscopy. Median toenail Se was lower for HCC cases than controls (p = 0.03). Adjusted odds ratios and 95% confidence intervals for HCC mortality by increasing quartile of toenail Se were 1.00 (reference), 0.58 (0.32-1.03), 0.83 (0.48-1.42) and 0.50 (0.28-0.90), with a marginally significant trend in risk observed (p for trend 0.06). This inverse association appeared stronger among those who did not consume alcohol and among women. Future studies are needed to examine the interrelationship between Se, viral hepatitis infection and HCC in (order to better understand the etiologic mechanisms involved and evaluate the true chemopreventive potential of Se compounds for liver diseases. (c) Published 2005 Wiley-Liss, Inc. C1 NCI, NIH, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, Rockville, MD 20852 USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Haimen Ctr Dis Control, Haimen City, Peoples R China. Fudan Univ, Sch Publ Hlth, Dept Epidemiol, Shanghai, Peoples R China. RP Sakoda, LC (reprint author), NCI, NIH, Div Canc Epidemiol & Genet, Dept Hlth & Human Serv, 6120 Execut Blvd,EPS 7067, Rockville, MD 20852 USA. EM sakodal@mail.nih.gov RI Evans, Alison/I-4970-2013 FU NCI NIH HHS [CA-06927, CA-40737] NR 42 TC 22 Z9 23 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 2005 VL 115 IS 4 BP 618 EP 624 DI 10.1002/ijc.20937 PG 7 WC Oncology SC Oncology GA 925WA UT WOS:000229082800016 PM 15704105 ER PT J AU Tanaka, H Horikawa, L Barrett, JC Oshimura, M AF Tanaka, H Horikawa, L Barrett, JC Oshimura, M TI Evidence for inactivation of distinct telomerase repressor genes in different types of human cancers SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE cellular senescence; telomerase repressor gene; chromosome transfer; somatic cell hybrids ID TUMOR-SUPPRESSOR GENE; CELLULAR SENESCENCE; CATALYTIC SUBUNIT; GROWTH-ARREST; CHROMOSOME 3; CELLS; HTERT; LINE; TRANSCRIPTION; RASSF1A AB Telomerase activation, a critical event in human carcinogenesis, may result from defects in telomerase-repressing mechanisms. Data from microcell-mediated chromosome transfer (MMICT) suggests the presence of telomerase repressor genes that become inactivated during carcinogenic processes. The transfer of a normal human chromosome 3 represses telomerase activity of both human renal cell carcinoma (RCC) and breast carcinoma (BC) cells. For a genetic complementation analysis of telomerase repression, 2 RCC cell lines (KC12 and RCC23) and a BC cell line (21NT) were used to make somatic cell hybrids. All of the self-hybrids (KC12xKC12 and 21NTx21NT) and hybrids from 2 RCC cell lines (KC12xRCC23) expressed the telomerase activity similarly to their parental cells, excluding the possibility of a ploidy-associated change in telomerase activity and suggesting the same genetic effect shared by the 2 RCC cell lines. In contrast, the fusion of BC and RCC cells (21NTxKC12 and 21NTxRCC23) produced a significant number of telomerase-negative hybrids, suggesting that the RCC and BC cells have different defects in the telomerase repression, which are functionally corrected through genetic complementation in the hybrids. This notion was supported by the mapping of the RCC telomerase repressor gene to a 5.7-Mb region on 3p21, which is different from the candidate region for the BC telomerase repressor gene on the same chromosomal band. These findings provide direct evidence for inactivation of distinct telomerase repressor genes in different types of human cancers and may have implications in the tissue-specific regulation of telomerase during human development and carcinogenesis. © 2005 Wiley-Liss, Inc. C1 Tottori Univ, Fac Med, Sch Life Sci, Dept Mol & Cell Genet, Tottori 680, Japan. NCI, NIH, Ctr Canc Res, Canc & Aging Sect,Lab Biosyst & Canc, Bethesda, MD 20892 USA. Tottori Univ, Grad Sch Med Sci, Dept Biomed Sci Regenerat Med & Biofunct, Tottori 680, Japan. RP Tanaka, H (reprint author), Indiana Univ, Sch Med, Dept Med & Mol Genet, 975 W Walnut St,IB-241, Indianapolis, IN 46202 USA. EM hirtanak@iupui.edu NR 29 TC 2 Z9 3 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 2005 VL 115 IS 4 BP 653 EP 657 DI 10.1002/ijc.90879 PG 5 WC Oncology SC Oncology GA 925WA UT WOS:000229082800021 PM 15688423 ER PT J AU Khan, MJ Herrero, R Schiffman, M AF Khan, MJ Herrero, R Schiffman, M TI Re: Munoz et al., "Against which human papillomavirus types shall we vaccinate and screen? The international perspective." - Int J Cancer 2004; 111 : 278-85 SO INTERNATIONAL JOURNAL OF CANCER LA English DT Letter ID HPV TYPES; NEOPLASIA; DNA C1 NCI, NIH, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Howard Hughes Med Inst, Chevy Chase, MD USA. Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. RP Khan, MJ (reprint author), NCI, NIH, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS Room 7057, Rockville, MD 20852 USA. EM khanmi@mail.nih.gov NR 9 TC 0 Z9 2 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUL 1 PY 2005 VL 115 IS 4 BP 670 EP 670 DI 10.1002/ijc.20947 PG 1 WC Oncology SC Oncology GA 925WA UT WOS:000229082800024 PM 15704103 ER PT J AU Terra, SG McGorray, SP Wu, R McNamara, DM Cavallari, LH Walker, JR Wallace, MR Johnson, BD Merz, CNB Sopko, G Pepine, CJ Johnson, JA AF Terra, SG McGorray, SP Wu, R McNamara, DM Cavallari, LH Walker, JR Wallace, MR Johnson, BD Merz, CNB Sopko, G Pepine, CJ Johnson, JA TI Association between beta-adrenergic receptor polymorphisms and their G- protein-coupled receptors with body mass index and obesity in women: a report from the NHLBI-sponsored WISE study SO INTERNATIONAL JOURNAL OF OBESITY LA English DT Article DE beta-adrenergic receptor; body mass index; pharmacogenetics ID BETA(3)-ADRENERGIC RECEPTOR; TRP64ARG POLYMORPHISM; GLN27GLU POLYMORPHISM; GENE; SUBUNIT; WEIGHT; BETA(1)-ADRENOCEPTOR; METAANALYSIS; POPULATION; LIPOLYSIS AB OBJECTIVES: The beta-adrenergic receptor (beta AR) genes are candidate genes for obesity because of their roles in energy homeostasis and promotion of lipolysis in human adipose tissue. Objective is to determine the association between obesity and polymorphisms in genes of the beta(1)AR (ADRB1), beta(2)AR (ADRB2), beta(3)AR (ADRB3), Gs protein alpha (GNAS1), to which all three beta-receptors couple and the G protein beta 3 subunit (GNB3), to which beta(3)ARs couple. DESIGN: A case-control genetic association study. SUBJECTS: A total of 643 black or white women enrolled in Women's Ischemia Syndrome Evaluation ( WISE) study. MEASUREMENTS: Genotypes were determined by PCR with single primer extension. Associations between genotype and body mass index (BMI), waist-to-hip ratio (WHR), waist circumference, and obesity were made. RESULTS: Polymorphisms in the three bAR genes, GNAS1, and GNB3 were not associated with BMI, WHR, waist circumference, or obesity. Linear and logistic regression analyses found no contribution of either genotype or haplotype with anthropometric measurements or obesity. CONCLUSIONS: Our study suggests that among American women with suspected coronary heart disease, polymorphisms in the bARs and their G-protein-coupled receptors do not contribute to increased BMI, WHR, waist circumference, or obesity. Given that 50% of all women die from coronary heart disease, and a higher percentage have heart disease during their lifetime, our results are likely generalizable to many American women. C1 Univ Florida, Coll Pharm, Dept Pharm Practice, Gainesville, FL 32610 USA. Univ Florida, Dept Stat, Gainesville, FL 32610 USA. Univ Pittsburgh, Med Ctr, Cardiovasc Inst, Pittsburgh, PA USA. Univ Illinois, Dept Pharm Practice, Chicago, IL USA. Orchid Biosci Inc, Princeton, NJ USA. Univ Florida, Coll Med, Dept Mol Genet & Microbiol, Gainesville, FL 32610 USA. Univ Florida, Coll Med, Dept Pediat, Gainesville, FL 32610 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Cedars Sinai Med Ctr, Dept Med, Div Cardiol, Cedars Sinai Res Inst, Los Angeles, CA 90048 USA. NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. Univ Florida, Dept Med, Div Cardiol, Gainesville, FL 32610 USA. RP Johnson, JA (reprint author), Univ Florida, Coll Pharm, Dept Pharm Practice, POB 100486, Gainesville, FL 32610 USA. EM johnson@cop.ufl.edu FU NCRR NIH HHS [M01-RR00425]; NHLBI NIH HHS [N01-HV68161, N01-HV68162, N01-HV68163, N01-HV68164, R03HL65729, U01-HL64924-01] NR 38 TC 22 Z9 24 U1 0 U2 3 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 JUL PY 2005 VL 29 IS 7 BP 746 EP 754 DI 10.1038/sj.ijo.0802978 PG 9 WC Endocrinology & Metabolism; Nutrition & Dietetics SC Endocrinology & Metabolism; Nutrition & Dietetics GA 934WZ UT WOS:000229741600003 PM 15917856 ER PT J AU Jo, WS Jeong, MH Jin, YH Jang, JY Nam, BH Son, SH Choi, SS Yoo, YH Kang, CD Lee, JD Jeong, SJ AF Jo, WS Jeong, MH Jin, YH Jang, JY Nam, BH Son, SH Choi, SS Yoo, YH Kang, CD Lee, JD Jeong, SJ TI Loss of mitochondrial membrane potential and caspase activation enhance apoptosis in irradiated K562 cells treated with herbimycin A SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article DE mitochondria; caspase; apoptosis; irradiation; K562; herbimycin A ID PROTEIN-TYROSINE KINASE; PH(1)-POSITIVE LEUKEMIA-CELLS; MITOTIC CATASTROPHE; DNA-DAMAGE; CYTOCHROME-C; IN-VIVO; DEATH; CHECKPOINT; RADIOSENSITIVITY; INHIBITION AB Purpose: We previously reported that herbimycin A (HMA) alters the mode of cell death of K562 cells induced by radiation and enhanced their radiosensitivity. In the present study, we explored the apoptosis-inducing activity of HMA and the fundamental mechanism via which it regulates radiation-induced cell death. Materials and methods: Chronic myelogenous leukemia (CML) cell line K562 was used. For X-irradiation and drug treatment, cells were plated at approximately 2610 5 cells/ml. Exponentially growing cells were treated with 10 Gy of X-ray using a 6-MeV X-ray machine at a dose rate of 200-300 cGy/min. The cells were treated with 0.25 mu M HMA immediately after irradiation and HMA remained for the entire culture period. The modes of cell death were discriminated by morphological changes, analysis of cell cycle, analysis of the mitochondrial events, and the expression of apoptosis-related proteins. Results: Our data demonstrates that radiation induced a significant time-dependent increase of cell death and failed to sustain a prolonged G2 arrest in K562 cells. Radiation-induced cell death caused the accumulation of cyclinB1 and weak nuclear fragmentation, suggesting a mitotic catastrophe. This mitotic catastrophe was dependent upon the mitochondrial permeability transition pore (PTP) opening and was independent of caspase-3. In contrast, K562 cells treated with radiation and HMA had an accelerated cell death and induced a p53-independent apoptosis. This apoptotic pathway was dependent upon an initial hyperpolarization of the mitochondrial inner membrane, following the release of cytochrome c and subsequent caspase-3 activation. Conclusions: Two mechanisms of radiation-induced cell death in K562 cells, mitotic catastrophe and apoptosis, are regulated through distinct pathways, mitochondria and caspase-independent and -dependent, respectively. The findings of this study may provide new insights into improving the efficiency of radiotherapy in CML patients. C1 NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Dong A Univ, Coll Med, BK21 Program, Res Supporting Ctr Med Sci, Pusan, South Korea. Pusan Natl Univ, Coll Med, Dept Biochem, Pusan, South Korea. Pusan Natl Univ, Dept Microbiol, Pusan, South Korea. RP Jeong, SJ (reprint author), NCI, Virus Tumor Biol Sect, Cellular Oncol Lab, Ctr Canc Res,NIH, 41 Medlars Dr,Bldg 41,Room B302, Bethesda, MD 20892 USA. EM jeongs@mail.nih.gov NR 44 TC 10 Z9 11 U1 0 U2 1 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 JUL PY 2005 VL 81 IS 7 BP 531 EP 543 DI 10.1080/09553000500303773 PG 13 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 986IM UT WOS:000233443300007 PM 16263657 ER PT J AU Brooks, JP Danforth, DN Albert, P Sciuto, LC Smith, SL Camphausen, KA Poggi, MM AF Brooks, JP Danforth, DN Albert, P Sciuto, LC Smith, SL Camphausen, KA Poggi, MM TI Early ipsilateral breast tumor recurrences after breast conservation affect survival: An analysis of the National Cancer Institute randomized trial SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article; Proceedings Paper CT 46th Annual Meeting of the American-Society-for-Therapeutic-Radiology-and-Oncology CY OCT 03-07, 2004 CL Atlanta, GA SP Amer Soc Therapeut Radiol & Oncol DE breast carcinoma; conservation; local recurrence; prognostic factors; survival ID 25-YEAR FOLLOW-UP; LOCAL RECURRENCE; CONSERVING THERAPY; DISTANT METASTASES; PROGNOSTIC FACTORS; MASTECTOMY; CARCINOMA; RADIOTHERAPY; IRRADIATION; LUMPECTOMY AB Purpose: To evaluate the effect of an ipsilateral breast tumor recurrence (IBTR) after breast-conservation therapy (BCT) on survival. Methods and Materials: One hundred twenty-one women were randomized to BCT. Patients with an IBTR were analyzed to determine survival. Analysis was performed with Kaplan-Meier estimates, log-rank tests, and time-dependent covariate Cox models. Results: At a median follow-up of 18.4 years, 27 patients had an IBTR. The median survival time after IBTR was 13.1 years. The 5-year survival rate was 91.8% (95% confidence interval [CI], 81.5-100%). The 10-year survival rate was 54.3% (95% CI, 35.8-82.6%). According to a Cox model with time-dependent covariates, the hazard ratio or relative risk of dying for those with an IBTR at < 5.3 years after BCT relative to patients without an IBTR after BCT is 1.47 (95% CI, 1.02-2.12%; p = 0.04). The hazard ratio for those who relapse after 5.3 years is 0.59 (95% CI, 0.22-1.61%; p = 0.31). Age at randomization, original tumor size, and the presence of positive regional nodes at initial presentation were not found to be associated with decreased survival. Conclusions: There seems to be a significant association of early IBTR after BCT with decreased survival. Local control should be maximized. C1 USN, Natl Naval Med Ctr, Div Radiat Oncol, Bethesda, MD 20889 USA. NCI, Radiat Oncol Branch, Bethesda, MD 20892 USA. NCI, Surg Branch, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Bethesda, MD 20892 USA. RP Poggi, MM (reprint author), USN, Natl Naval Med Ctr, Div Radiat Oncol, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM MMPoggi@Bethesda.med.navy.mil NR 19 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD JUL 1 PY 2005 VL 62 IS 3 BP 785 EP 789 DI 10.1016/j.ijrobp.2004.12.001 PG 5 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 935FY UT WOS:000229766300026 PM 15936560 ER PT J AU Riazuddin, SA Zulfiqar, F Zhang, QJ Sergeev, YV Qazi, ZA Husnain, T Caruso, R Riazuddin, S Sieving, PA Hejtmancik, JF AF Riazuddin, SA Zulfiqar, F Zhang, QJ Sergeev, YV Qazi, ZA Husnain, T Caruso, R Riazuddin, S Sieving, PA Hejtmancik, JF TI Autosomal recessive retinitis pigmentosa is associated with mutations in RP1 in three consanguineous Pakistani families SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID NONSENSE MUTATION; LINKAGE ANALYSIS; GENE; PROTEIN; DYSTROPHIES AB Purpose. To localize and identify the gene and mutations causing autosomal recessive retinitis pigmentosa in three consanguineous Pakistani families. Methods. Blood samples were collected and DNA was extracted. A genome-wide scan was performed by using 382 polymorphic microsatellite markers on genomic DNA from affected and unaffected family members, and lod scores were calculated. Results. A genome-wide scan of 25 families gave an hlod=4.53 with D8S260. Retinitis pigmentosa in all three families mapped to a 14.21-cM (21.19-Mb) region on chromosome 8 at q11, flanked by D8S532 and D8S260. This region harbors RP1, which is known to cause autosomal dominant retinitis pigmentosa. Sequencing of the coding exons of RP1 showed mutations in all three families: two single-base deletions, c.4703delA and c.5400delA, resulting in a frame shift, and a 4-bp insertion, c.1606insTGAA, all causing premature termination of the protein. All affected individuals in these families are homozygous for the mutations. Parents and siblings heterozygous for the mutant allele did not show any signs or symptoms of RP. Conclusions. These results provide strong evidence that mutations in RP1 can result in recessive as well as dominant retinitis pigmentosa. The findings suggest that truncation of RP1 before the BIF motif or within the terminal portion results in a simple loss of RP1 function, producing a recessive inheritance pattern. In contrast, disruption of RP1 within or immediately after the BIF domain may result in a protein with a deleterious effect and hence a dominant inheritance pattern. C1 NEI, OGVFB, NIH, Bethesda, MD 20892 USA. Univ Punjab, Ctr Excellence Mol Biol, Lahore, Pakistan. RP Hejtmancik, JF (reprint author), NEI, OGVFB, NIH, Bldg 10,Room 10B10,10 Ctr Dr,MSC 1860, Bethesda, MD 20892 USA. EM f3h@helix.nih.gov RI Husnain, Tayyab/G-3805-2015; SHEIKH, RIAZUDDIN/L-2406-2015 NR 24 TC 26 Z9 26 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 JUL PY 2005 VL 46 IS 7 BP 2264 EP 2270 DI 10.1167/iovs.04-1280 PG 7 WC Ophthalmology SC Ophthalmology GA 939ZK UT WOS:000230112800006 PM 15980210 ER PT J AU Brzezinski, JA Brown, NL Tanikawa, A Bush, RA Sieving, PA Vitaterna, MH Takahashi, JS Glaser, T AF Brzezinski, JA Brown, NL Tanikawa, A Bush, RA Sieving, PA Vitaterna, MH Takahashi, JS Glaser, T TI Loss of circadian photoentrainment and abnormal retinal electrophysiology in Math5 mutant mice SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SCOTOPIC THRESHOLD RESPONSE; DARK-ADAPTED ELECTRORETINOGRAM; CONE BIPOLAR CELLS; TRAIT LOCI QTL; GANGLION-CELL; MOUSE RETINA; RAT RETINA; PHARMACOLOGICAL ANALYSIS; INTERGENICULATE LEAFLET; PHOTIC ENTRAINMENT AB Purpose. To determine how the absence of retinal ganglion cells (RGCs) in Math5 (Atoh7) mutant mice affects circadian behavior and retinal function. Methods. The wheel-running behavior of wild-type and Math5 mutant mice was measured under various light-dark cycle conditions. To evaluate retinal input to the suprachiasmatic nuclei (SCN) anatomically, the retinohypothalamic tracts were labeled in vivo. To assess changes in retinal function, corneal flash electroretinograms (ERGs) from mutant and wild-type mice were compared under dark- and light-adapted conditions. Alterations in retinal neuron populations were evaluated quantitatively and with cell-type-specific markers. Results. The Math5-null mice did not entrain to light and exhibited free-running circadian behavior with a mean period (23.6 +/- 0.15 hours) that was indistinguishable from that of wild-type mice (23.4 +/- 0.19 hours). The SCN showed no anterograde labeling with a horseradish peroxidase-conjugated cholera toxin B (CT-HRP) tracer. ERGs recorded from mutant mice had diminished scotopic a- and b-wave and photopic b-wave amplitudes. The scotopic b-wave was more severely affected than the a- wave. The oscillatory potentials (OPs) and scotopic threshold response (STR) were also reduced. Consistent with these ERG findings, a pan-specific reduction in the number of bipolar cells and a smaller relative decrease in the number of rods in mutant mice were observed. Conclusions. Math5-null mice are clock-blind and have no RGC projections to the SCN. RGCs are thus essential for photoentrainment in mice, but are not necessary for the development or intrinsic function of the SCN clock. RGCs are not required to generate any of the major ERG waveforms in mice, including the STR, which is produced by ganglion cells in some other species. The diminished amplitude of b-wave, OPs, and STR components in Math5 mutants is most likely caused by the decreased abundance of retinal interneurons. C1 Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Univ Cincinnati, Sch Med, Dept Pediat, Childrens Hosp Res Fdn,Div Dev Biol, Cincinnati, OH USA. Univ Cincinnati, Sch Med, Dept Pediat, Childrens Hosp Res Fdn,Div Ophthalmol, Cincinnati, OH USA. Natl Inst Deafness & Other Commun Disorders, Sect Translat Res Retinal & Macular Degenerat, Bethesda, MD USA. NEI, Bethesda, MD 20892 USA. Northwestern Univ, Ctr Funct Genom, Evanston, IL USA. Northwestern Univ, Howard Hughes Med Inst, Dept Neurobiol & Physiol, Evanston, IL USA. RP Glaser, T (reprint author), Univ Michigan, Dept Internal Med, 1150 W Med Ctr Dr,4520 MSRB I Box 0651, Ann Arbor, MI 48109 USA. EM tglaser@umich.edu RI Takahashi, Joseph/E-8482-2012 OI Takahashi, Joseph/0000-0003-0384-8878 FU Howard Hughes Medical Institute; NEI NIH HHS [R01 EY013612, EY11729, EY13612, R01 EY013612-04, R01 EY014259, T32 EY013934, T32 EY13934]; NIGMS NIH HHS [T32 GM007544, T32 GM07544] NR 99 TC 37 Z9 37 U1 0 U2 2 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 JUL PY 2005 VL 46 IS 7 BP 2540 EP 2551 DI 10.1167/iovs.04-1123 PG 12 WC Ophthalmology SC Ophthalmology GA 939ZK UT WOS:000230112800042 PM 15980246 ER PT J AU Li, CM Chung, BH Presley, JB Malek, G Zhang, XM Dashti, N Li, L Chen, JG Bradley, K Kruth, HS Curcio, CA AF Li, CM Chung, BH Presley, JB Malek, G Zhang, XM Dashti, N Li, L Chen, JG Bradley, K Kruth, HS Curcio, CA TI Lipoprotein-like particles and cholesteryl esters in human Bruch's membrane: Initial characterization SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID TRIGLYCERIDE TRANSFER PROTEIN; PIGMENT EPITHELIAL-CELLS; LOW-DENSITY-LIPOPROTEIN; AGE-RELATED MACULOPATHY; MACULAR DEGENERATION; APOLIPOPROTEIN-B; ATHEROSCLEROTIC LESIONS; INTERPRETIVE HISTORY; LIPID-ACCUMULATION; HUMAN RETINA AB Purpose. To isolate and characterize cholesteryl ester-containing, lipoprotein-like particles (LLPs) from normal aged human Bruch's membrane (BrM)/choroid(Ch). Methods. From BrM/Ch of 20 eyes of 10 donors aged >60 years, LLPs were released by high-salt buffer, fractionated by density gradient ultracentrifugation, and characterized by determining cholesterol, triglyceride, and phospholipid concentration (by enzymatic colorimetry and fluorometry); cholesteryl ester composition (by electrospray ionization mass spectrometry, ESI/MS); and particle morphology (by negative stain electron microscopy). Apolipoprotein (apo) gene expression was determined with RT-PCR, Western blot analysis, and immunofluorescence of retinal-choroidal cryosections. In paraformaldehyde-preserved eyes (20 eyes of 20 donors), cholesteryl ester composition of BrM/Ch, cornea, and sclera was determined by ESI/MS. Results. A pooled fraction of LLP released from BrM/Ch (concentrated total LLP, density [d]<1.24 g/mL fraction) was fractionated into two peaks. A large Peak 1 (with plasma LDL-HDL density range), containing predominantly phospholipid and unesterified cholesterol, was morphologically heterogeneous. A small Peak 2 (with plasma VLDL density range), enriched with esterified cholesterol, contained similar to 100 nm diameter round electron-lucent particles. Both peaks contained apoB and apoA-I, RPE and retina contained apoA-I mRNA transcripts, and BrM and drusen contained apoA-I immunoreactivity. Peaks 1 and 2, native RPE, and fresh BrM/Ch were cholesteryl linoleate enriched and contained little cholesteryl docosahexaenoate. Preserved BrM/Ch was cholesteryl oleate-enriched, unlike sclera and cornea. Conclusions. BrM/Ch LLP do not resemble plasma lipoproteins in density profile, cholesterol distribution, or morphology. Peak 2 contains EC-rich LLP resembling BrM particles in situ. BrM/Ch cholesteryl esters respond to long-term storage differently than esters of plasma lipoprotein origin accumulated in other ocular tissues. Evidence of intraocular apoB and apoA-I expression supports an emerging hypothesis that the RPE assembles and secretes a large, possibly novel, lipoprotein particle. C1 Univ Alabama Birmingham, Sch Med, Dept Ophthalmol, Birmingham, AL USA. Univ Alabama Birmingham, Sch Med, Dept Med, Div Geriatr Gerontol,Atherosclerosis Res Unit, Birmingham, AL USA. NHLBI, Sect Expt Atherosclerosis, NIH, Bethesda, MD 20892 USA. RP Univ Alabama Birmingham, Sch Med, Callahan Eye Fdn Hosp, Dept Ophthalmol, 700 S 18th St,Room H020, Birmingham, AL 35294 USA. EM curcio@uab.edu FU NCI NIH HHS [P30 CA13148-32]; NEI NIH HHS [EY06109]; NHLBI NIH HHS [R01 HL60936, P01HL34343] NR 63 TC 68 Z9 70 U1 0 U2 2 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI ROCKVILLE PA 12300 TWINBROOK PARKWAY, ROCKVILLE, MD 20852-1606 USA SN 0146-0404 EI 1552-5783 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD JUL PY 2005 VL 46 IS 7 BP 2576 EP 2586 DI 10.1167/iovs.05-0034 PG 11 WC Ophthalmology SC Ophthalmology GA 939ZK UT WOS:000230112800047 PM 15980251 ER PT J AU Biggar, RJ Engels, EA Ly, S Kahn, A Schymura, MJ Sackoff, J Virgo, P Pfeiffer, RM AF Biggar, RJ Engels, EA Ly, S Kahn, A Schymura, MJ Sackoff, J Virgo, P Pfeiffer, RM TI Survival after cancer diagnosis in persons with AIDS SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV; prognosis; mortality; United States; highly active antiretroviral therapy ID IMMUNODEFICIENCY-VIRUS-INFECTION; LUNG-CANCER; MORTALITY; HIV-1; ERA AB The survival of persons with AIDS (PWA) has recently improved because of better antiretroviral therapies. Similarly, the prognosis of cancer has also improved. To determine if survival in PWA with cancer has also improved, we compared cancer survival in adults with and without AIDS using data from New York City from 1980 through 2000. Analyses were made for AIDS-related cancers (Kaposi sarcoma, non-Hodgkin lymphoma [NHL], and cervical cancer) and for 8 non-AIDS-related cancers (lung, larynx, colorectum, anus, Hodgkin lymphoma, breast, prostate, and testis). Death hazard ratios compared survival in PWA with cancer with that in cancer patients without AIDS, adjusted for age, sex, race, and calendar-time of cancer occurrence. The 24-month survival rate of PWA with cancer (9015 AIDS cancers and 929 non-AIDS-related cancers of 8 types) improved significantly for most cancer types. By 1996 through 2000, the 24-month survival rate in PWA was 58% for Kaposi sarcoma, 41% for peripheral NHL, 29% for central nervous system NHL, and 64% for cervical cancer. For non-AIDS-related cancers, survival of PWA was lowest for lung cancer (10%) but was > 50% for most other cancer types. In 1996 through 2000, significant differences in survival between cancer patients with and without AIDS still remained for Hodgkin lymphoma and lung, larynx, and prostate cancers. We conclude that recent improvements in AIDS and cancer care have greatly narrowed the gap in survival between cancer patients with and without AIDS. Clinicians should be encouraged by the improving prognosis and be diligent about detecting and treating cancer in PWA. C1 NCI, Viral Epidemiol Branch, DCEG, NIH,DHHS, Rockville, MD 20852 USA. New York City Dept Hlth & Mental Hyg, Program Epidemiol, New York, NY USA. New York State Dept Hlth, New York State Canc Registry, Albany, NY USA. Comp Sci Corp, Rockville, MD USA. NCI, Biostat Branch, DCEG, NIH,DHHS, Rockville, MD 20852 USA. RP Biggar, RJ (reprint author), NCI, Viral Epidemiol Branch, DCEG, NIH,DHHS, 6120 Execut Blvd,Room 8014, Rockville, MD 20852 USA. EM biggarb@mail.gov RI Pfeiffer, Ruth /F-4748-2011 NR 19 TC 84 Z9 85 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 JUL 1 PY 2005 VL 39 IS 3 BP 293 EP 299 DI 10.1097/01.qai.0000164033.02947.e3 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 940YQ UT WOS:000230182200005 PM 15980688 ER PT J AU Gerber, JG Rosenkranz, SL Fichtenbaum, CJ Vega, JM Yang, A Alston, BL Brobst, SW Segal, Y Aberg, JA AF Gerber, JG Rosenkranz, SL Fichtenbaum, CJ Vega, JM Yang, A Alston, BL Brobst, SW Segal, Y Aberg, JA CA AIDS Clin Trials Grp A5108 Team TI Effect of efavirenz on the pharmacokinetics of simvastatin, atorvastatin, and pravastatin - Results of AIDS clinical trials group 5108 study SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV infection; hydroxymethylglutaryl coenzyme A reductase inhibitors; statins; nonnucleoside reverse transcriptase inhibitors; drug interactions ID COMBINATION ANTIRETROVIRAL THERAPY; ORGANIC ANION TRANSPORTER; A REDUCTASE INHIBITORS; BIOTRANSFORMATION PRODUCTS; LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; DRUG-INTERACTIONS; HUMAN PLASMA; HUMAN SERUM; RHABDOMYOLYSIS AB Efavirenz (EFV) is associated with hyperlipidemia when used in combination with other antiretroviral drugs. EFV is a mixed inducer/inhibitor of cytochrome P450 (CYP) 3A4 isozyme and may interact with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors that are primarily metabolized via CYP3A4. To assess the drug-drug interaction of EFV used in combination with simvastatin (SIM), atorvastatin (ATR), or pravastatin (PRA), an open-label trial was conducted in 52 healthy adult HIV-seronegative subjects across AIDS Clinical Trials Group sites in the United States. Subjects received 40 mg of SIM, 10 mg of ATR, or 40 mg of PRA daily on days 0 through 3 and days 15 through 18. EFV was administered daily at a dose of 600 mg on days 4 through 18. SIM, ATR, and PRA concentrations were determined before and after EFV and EFV concentrations were determined before and after statins. EFV reduced SIM acid exposure (area under the curve at 0 to 24 hours [AUC(0) (24h)]) by 58% (Wilcoxon signed rank test, P = 0.003) and active HMG-CoA reductase inhibitory activity by 60% (P < 0.001). EFV reduced ATR exposure by 43% (P < 0.001) and the total active ATR exposure by 34% (P = 0.005). EFV administration resulted in a 40% decrease in PRA exposure (P = 0.005). SIM, ATR, and PRA had no effect on non-steady-state EFV concentrations. In conclusion, EFV, when administered with SIM, ATR, or PRA, can result in significant induction of statin metabolism. The reduced inhibition of HMG-CoA reductase activity during coadministration of EFV may result in diminished antilipid efficacy at usual doses of SIM, ATR, and PR-A. C1 Univ Colorado, Hlth Sci Ctr, Denver, CO 80262 USA. Harvard Univ, Sch Publ Hlth, Stat Data & Anal Ctr, Boston, MA 02115 USA. Univ Cincinnati, Coll Med, Cincinnati, OH USA. Merck & Co Inc, W Point, PA USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. Social & Sci Syst Inc, Silver Spring, MD USA. Washington Univ, St Louis, MO USA. RP Gerber, JG (reprint author), Univ Colorado, Hlth Sci Ctr, 4200 E 9th Ave,Box C237, Denver, CO 80262 USA. EM John.gerber@UCHSC.edu FU NCRR NIH HHS [5-M01-RR00070, 5-M01-RR00051, 5-M01-RR00052, 5-M01-RR0044]; NIAID NIH HHS [AI-25897, AI-25903, AI-27658, AI-27664, AI-27666, AI-27668, AI-38855, AI-38858] NR 29 TC 94 Z9 99 U1 1 U2 7 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 JUL 1 PY 2005 VL 39 IS 3 BP 307 EP 312 DI 10.1097/01.qai.0000167156.44980.33 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 940YQ UT WOS:000230182200007 PM 15980690 ER PT J AU Cohn, JA Hashemi, FB Camarca, M Kong, F Xu, JH Beckner, SK Kovacs, AA Reichelderfer, PS Spear, GT AF Cohn, JA Hashemi, FB Camarca, M Kong, F Xu, JH Beckner, SK Kovacs, AA Reichelderfer, PS Spear, GT TI HIV-inducing factor in cervicovaginal secretions is associated with bacterial vaginosis in HIV-1-infected women SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1; bacterial vaginosis; vaginitis; cervicovaginal lavage; sexually transmitted diseases; MRP-8 protein ID IMMUNODEFICIENCY-VIRUS TYPE-1; FEMALE GENITAL-TRACT; VAGINAL FLORA; EXPRESSION; INFECTION; DISTURBANCES; QUANTITATION; REPLICATION; ACQUISITION; RNA AB Objective: Certain cervicovaginal lavage (CVL) fluid samples obtained from HIV-1-infected and uninfected women stimulate in vitro HIV-1 replication. This activity, HIV-inducing factor (HIF), changes when: CVL fluid is heated. We sought to confirm a previous observation that HIF was associated with bacterial vaginosis (BV). Methods: HIF was measured in unheated and heated CVL fluid obtained from HIV-1-infected women and compared with the presence of BV by Nugent scores, other genital tract conditions, and cervicovaginal HIV-1 shedding. Results: Among the 295 women studied. 54% of CVL samples had HIF activity and 21% showed heat-stable HIF activity. In adjusted logistic regression, heat-stable HIF was associated with BV (odds ratio [OR] = 51.7, 95% confidence interval [CI]: 5.0 530.7) and with intermediate flora (OR = 43.3, 95% CI: 3.6, 521.1); heat-labile HIF was not associated with BV Neither heat-stable nor heat-labile HIF was associated with other cervicovaginal conditions nor, after controlling for plasma viral load, with genital tract HIV-1 shedding. Conclusion: We confirmed the association of HIF with BV and attribute it to the heat-stable component. Heat-stable activity is also associated, although less strongly, with intermediate vaginal flora. We propose that heat-stable HIF is a result of products of BV-associated bacteria. C1 Wayne State Univ, Div Infect Dis, Dept Med, Sch Med, Detroit, MI USA. Rush Presbyterian St Lukes Med Ctr, Dept Immunol & Microbiol, Chicago, IL 60612 USA. Westat Corp, Clin Trials Div, Rockville, MD USA. Univ So Calif, Maternal Child & Adolescent HIV Management & Res, Sch Med, Los Angeles, CA USA. NICHHD, Populat Res Ctr, NIH, Bethesda, MD 20892 USA. RP Cohn, JA (reprint author), 4201 St Antoine 7D, Detroit, MI 48201 USA. EM jcohn@med.wayne.edu OI Bonakdarhashemi, Farhad/0000-0001-5533-3871 FU NIAID NIH HHS [R01 AI052065-01, N01-AI-15123, R01 AI052065]; NICHD NIH HHS [P01 HD040539, P01 HD40539]; PHS HHS [282-98-0015] NR 29 TC 22 Z9 27 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 JUL 1 PY 2005 VL 39 IS 3 BP 340 EP 346 DI 10.1097/01.qai.0000146599.47925.e0 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 940YQ UT WOS:000230182200013 PM 15980696 ER PT J AU Nansel, TR Doyle, F Frederick, MM Zhang, J AF Nansel, TR Doyle, F Frederick, MM Zhang, J TI Quality of life in women undergoing medical treatment for early pregnancy failure SO JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING LA English DT Article DE depression; early pregnancy failure; first trimester loss; miscarriage; misoprostol; quality of life; spontaneous abortion; stress; treatment acceptability ID DEPRESSION-HAPPINESS SCALE; EARLY MISCARRIAGE; MANAGEMENT; ANXIETY; GRIEF; EXPERIENCE; SYMPTOMS; DISORDER; ABORTION; TRIAL AB Objectives: To examine predictors of quality of life, depression, and stress in women undergoing medical management of early pregnancy failure with misoprostal and to assess the relationship of quality of life, depression, and stress to treatment acceptability. Design: Descriptive observational study of women undergoing medical management of early pregnancy failure with misoprostol conducted as part of a multicenter pilot study testing the efficacy of saline-moistened versus dry application of vaginal misoprostol. Data were collected prior to treatment through 15 days posttreatment. Setting: Four university-based hospitals. Participants: Women (n = 80) <= 11 weeks pregnant diagnosed with anembryonic gestation or fetal demise. Intervention: Vaginal misoprostol for medical evacuation. Main Outcome Measures: Quality of life (physical role functioning, emotional role functioning, social functioning, vitality, and bodily pain), depression, stress, and treatment acceptability. Results: Women who received medical evacuation demonstrated poorer quality of life than same-age published population norms, scoring 0.25 to 0.78 of a standard deviation below the population mean for four of the five subscales. Conclusions: Nurses should assist patients to minimize and manage physical symptoms during treatment for early pregnancy failure. Women with higher external demands and lower social/tangible support may need greater assistance. C1 NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Miami, Sch Med, Dept Obstet & Gynecol, Miami, FL 33101 USA. Clin Trials & Surveys Corp, Baltimore, MD USA. RP Nansel, TR (reprint author), NICHHD, Div Epidemiol Stat & Prevent Res, Dept Hlth & Human Serv, 6100 Execut Blvd,Rm 7B13,MSC 7510, Bethesda, MD 20892 USA. EM nanselt@mail.nih.gov OI Nansel, Tonja/0000-0002-8298-7595 FU NICHD NIH HHS [N01-HD-1-3323, N01-HD-1-3321, N01-HD-1-3322, N01-HD-1-3324, N01-HD-1-3325] NR 35 TC 8 Z9 10 U1 0 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0884-2175 J9 JOGNN-J OBST GYN NEO JI JOGNN PD JUL-AUG PY 2005 VL 34 IS 4 BP 473 EP 481 DI 10.1177/0884217505278319 PG 9 WC Nursing; Obstetrics & Gynecology SC Nursing; Obstetrics & Gynecology GA 946UK UT WOS:000230598600008 PM 16020415 ER PT J AU Arbes, SJ Sever, M Mehta, J Collette, N Thomas, B Zeldin, DC AF Arbes, SJ Sever, M Mehta, J Collette, N Thomas, B Zeldin, DC TI Exposure to indoor allergens in day-care facilities: Results from 2 North Carolina counties SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE alternaria species; Alt a 1; Bla g 1; Can f 1; cat allergen; child day-care centers; cockroach allergen; day care; Der f 1; Der p 1; dog allergen; dust mite allergen; Fel d 1; indoor allergens; mouse allergen; Mus m 1 ID HOUSE-DUST MITE; INNER-CITY CHILDREN; DER-P-I; FEL D 1; MULTIPLE COMPARISONS; COCKROACH ALLERGENS; DOMESTIC ALLERGENS; EPIDEMIOLOGIC DATA; ATOPIC CHILDREN; NATIONAL-SURVEY AB Background: With 63% of US children under 5 years of age in regular child care, day-care facilities could be an important source of exposure to indoor allergens. Objective: This study examined levels of 7 indoor allergens in 89 day-care facilities in 2 North Carolina counties. Methods: At each facility, a questionnaire was administered, observations were made, and vacuumed dust samples were collected from carpeted and noncarpeted areas of one room. Allergen concentrations were measured with antibody-based ELISAs. Results: Each allergen was detected in a majority of facilities (52% to 100%). Geometric mean concentrations were 5.19 mu g/g for Alternaria alternata, 2.06 mu g/g for Can f 1, 1.43 mu g/g for Fel d 1, 0.21 U/g for Bla g 1, 0.20 mu g/g for Der p 1, 0.10 mu g/g for Der f 1, and 0.01 mu g/g for Mus m 1. Concentrations for 5 of the 7 allergens were not statistically different from concentrations found in southern US homes sampled in the National Survey of Lead and Allergens in Housing. In rooms with carpet and hard-surfaced flooring, levels of A alternata, Can f 1, Der f 1, Der p 1, and Fel d 1 were statistically higher on carpet. Conclusions: In this survey of day-care facilities in North Carolina, detectable levels of indoor allergens were commonly found. For many young children and day-care staff, day-care facilities might be a source of clinically relevant exposures to indoor allergens. C1 NIEHS, NIH, Div Intramural Res, Res Triangle Pk, NC 27709 USA. RP Zeldin, DC (reprint author), NIEHS, NIH, Div Intramural Res, POB 12233,MD D2-01, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov OI Sever, Michelle/0000-0002-2435-1214 NR 31 TC 43 Z9 43 U1 0 U2 2 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 JUL PY 2005 VL 116 IS 1 BP 133 EP 139 DI 10.1016/j.jaci.2005.04.022 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 017IC UT WOS:000235686300021 PM 15990786 ER PT J AU Wunschmann, S Gustchina, A Chapman, MD Pomes, A AF Wunschmann, S Gustchina, A Chapman, MD Pomes, A TI Cockroach allergen Bla g 2: An unusual aspartic proteinase SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT 60th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 18-23, 2004 CL San Francisco, CA SP Amer Acad Allergy, Asthma & Immunol DE asthma; allergy; allergens; cock-roach; aspartic proteinase ID PREGNANCY-ASSOCIATED GLYCOPROTEINS; HOUSE-DUST MITE; ACTIVE-SITE; CATHEPSIN-D; P-I; PROTEASE; IDENTIFICATION; CLONING; PEPSIN; CD23 AB Background: Enzymatic activity of mite, fungal, and bee venom allergens is thought to potentiate their allergenicity. Bla g 2 is a potent cockroach allergen, but despite sharing sequence homology with aspartic proteinases, it contains critical amino acid substitutions that impair proteolytic activity. The biologic function of Bla g 2 remains unclear. Objective: We sought to investigate the effects of specific amino acid substitutions on enzymatic activity, and the peptide-binding capability of Bla g 2. Methods: Site-directed mutagenesis was used to produce a recombinant Bla g 2 mutant (Mut) with corrected canonical triads and a flap region. Another mutant (MutF(-)) was expressed after additional mutations in the flap region of Mut. Bla g 2 wild-type (Wt), Mut, and MutF(-) were assayed for aspartic proteinase activity, and Bla g 2 Wt was tested for pepstatin binding. Results: Recombinant Bla g 2 Wit and Mut did not show enzymatic activity in a milk-clotting and hemoglobin assay. By using a modified hemoglobin assay, residual activity inhibited by pepstatin was detected for MutF(-) and Wt at 20 mu g/mL, whereas pepsin was active at a 1000-fold lower concentration. Most of Bla g 2 binding to pepstatin-agarose was nonspecific. Conclusion: Residual proteolytic activity was found for Bla g 2 at concentrations of approximately 4 mM. This weak activity suggests that proteolysis is not the primary function of this allergen and that it is unlikely to contribute to the allergenicity of Bla g 2. Bla g 2 has a cleft that might specifically bind ligands other than pepstatin. C1 INDOOR Biotechnol Inc, Charlottesville, VA 22903 USA. NCI, Frederick, MD 21701 USA. RP Wunschmann, S (reprint author), INDOOR Biotechnol Inc, 1216 Harris St, Charlottesville, VA 22903 USA. EM sabina@inbio.com OI Pomes, Anna/0000-0002-8729-1829 NR 33 TC 44 Z9 46 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2005 VL 116 IS 1 BP 140 EP 145 DI 10.1016/j.jaci.2005.04.024 PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 017IC UT WOS:000235686300022 PM 15990787 ER PT J AU Saini, P Prasad, T Gaur, NA Shukla, S Jha, S Komath, SS Khan, LA Haq, QMR Prasad, R AF Saini, P Prasad, T Gaur, NA Shukla, S Jha, S Komath, SS Khan, LA Haq, QMR Prasad, R TI Alanine scanning of transmembrane helix 11 of Cdr1p ABC antifungal efflux pump of Candida albicans: identification of amino acid residues critical for drug efflux SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE transmembrane segment 11; azoles; synergy; multidrug resistance; rhodamine 6G ID HUMAN P-GLYCOPROTEIN; MULTIDRUG TRANSPORTER CDR1P; PROTEIN SECONDARY STRUCTURE; NUCLEOTIDE-BINDING DOMAIN; SACCHAROMYCES-CEREVISIAE; TOPOLOGY PREDICTION; RESISTANCE; YEAST; FLUCONAZOLE; CYCLOSPORINE AB Objectives: To investigate the role of transmembrane segment 11 (TMS11) of Candida albicans drug resistance protein (Cdr1p) in drug extrusion. Methods: We replaced each of the 21 putative residues of TMS11 with alanine by site-directed mutagenesis. The Saccharomyces cerevisiae AD1-8u(-) strain was used to overexpress the green fluorescent protein tagged wild-type and mutant variants of TMS11 of Cdr1p. The cells expressing mutant variants were functionally characterized. Results: Out of 21 residues of TMS11, substitution of seven residues, i.e. A1346G, A1347G, T1351A, T1355A, L1358A, F1360A and G1362A, affected differentially the substrate specificity of Cdr1p, while 14 mutants had no significant effect on Cdr1p function. TMS11 projection in an alpha-helical configuration revealed with few exceptions (A1346 and F1360), a distinct segregation of mutation-sensitive residues (A1347, T1351, T1355, L1358 and G1362) towards the more hydrophilic face. Interestingly, mutation-insensitive residues seem to cluster towards the hydrophobic side of the helix. Competition of rhodamine 6G efflux, in the presence of excess of various substrates in the cells expressing native Cdr1p, revealed for the first time the overlapping binding site between azoles (such as ketoconazole, miconazole and itraconazole) and rhodamine 6G. The ability of these azoles to compete with rhodamine 6G was completely lost in mutants F1360A and G1362A, while it was selectively lost in other variants of Cdr1p. We further confirmed that fungicidal synergism of calcineurin inhibitor FK520 with azoles is mediated by Cdr1p; wherein in addition to conserved T1351, substitution of T1355, L1358 and G1362 of TMS11 also resulted in abrogation of synergism. Conclusions: Our study for the first time provides an insight into the possible role of TMS11 of Cdr1p in drug efflux. C1 Jawaharlal Nehru Univ, Sch Life Sci, Biochim Membranes Lab, New Delhi 110067, India. NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Virginia, Sch Med, Charlottesville, VA 22908 USA. Jamia Millia Islamia, Dept Biosci, New Delhi 110025, India. RP Prasad, R (reprint author), Jawaharlal Nehru Univ, Sch Life Sci, Biochim Membranes Lab, New Delhi 110067, India. EM rp47@hotmail.com RI Jha, Sudhakar /B-2308-2009; OI Gaur, Naseem/0000-0002-1224-8789 NR 38 TC 28 Z9 30 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD JUL PY 2005 VL 56 IS 1 BP 77 EP 86 DI 10.1093/jac/dki183 PG 10 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 948OE UT WOS:000230724800007 PM 15937063 ER PT J AU Katsiaras, A Newman, AB Kriska, A Brach, J Krishnaswami, S Feingold, E Kritchevsky, SB Li, RL Harris, TB Schwartz, A Goodpaster, BH AF Katsiaras, A Newman, AB Kriska, A Brach, J Krishnaswami, S Feingold, E Kritchevsky, SB Li, RL Harris, TB Schwartz, A Goodpaster, BH TI Skeletal muscle fatigue, strength, and quality in the elderly: the Health ABC Study SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE muscle quality; isokinetic dynamometry; aging ID ADDUCTOR POLLICIS MUSCLE; DIFFERENT FIBER TYPES; ELBOW FLEXOR MUSCLES; GENDER-DIFFERENCES; CONTRACTILE PROPERTIES; COMPUTED-TOMOGRAPHY; ISOMETRIC-EXERCISE; BODY-COMPOSITION; OLDER-ADULTS; AGE AB We examined the muscle fatigue characteristics in older men and women and determined whether these were related to the size, strength, or quality of muscle. A total of 1,512 men and women aged 70 - 79 yr from the Health, Aging, and Body Composition Study participated in this study. Muscle cross-sectional area and attenuation were determined with computed tomography. Skeletal muscle fatigue and strength ( peak torque) of the knee extensors and flexors were measured using isokinetic dynamometry. Men were more fatigue resistant than women for both knee extension ( fatigue index: 70.4 +/- 15.3 vs. 66.9 +/- 14.3%; P < 0.05) and knee flexion (67.9 +/- 16.4 vs. 64.9 +/- 17.6%; P < 0.05). Peak torque and muscle quality (specific torque) were higher in men than women for knee extension (99.6 +/- 28.2 vs. 63.0 +/- 16.8 N center dot m and 1.62 +/- 0.43 vs. 1.51 +/- 0.39 N center dot m/cm(2); both P < 0.05) and for knee flexion (74.0 +/- 26.4 vs. 49.6 +/- 15.9 N center dot m and 2.47 +/- 1.29 vs. 2.22 +/- 0.78 N center dot m/cm(2); both P < 0.05). Total work and power output was greater in men compared with women for both the quadriceps ( 1,353 +/- 451 vs. 832 +/- 264 J and 87.7 +/- 33.5 vs. 53.3 +/- 19.2 W; both P < 0.05) and the hamstrings ( 741 +/- 244 vs. 510 +/- 141 J and 35.4 +/- 16.0 vs. 23.7 +/- 10.2 W; both P < 0.05). In both genders, the quadriceps was able to perform more work with greater power compared with the hamstrings. Those who were stronger actually had greater fatigue after adjusting for age, race, physical activity, and total body fat. In conclusion, older men were more fatigue resistant than women, although in both men and women greater fatigue was not related to muscle weakness. C1 Univ Pittsburgh, Dept Med, Div Endocrinol & Metab, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Epidemiol, Pittsburgh, PA USA. Univ Pittsburgh, Sch Hlth & Rehabil Sci, Dept Phys Therapy, Pittsburgh, PA USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA USA. Wake Forest Univ, Bowman Gray Sch Med, Sect Geriatr, Winston Salem, NC USA. Univ Tennessee, Ctr Hlth Sci, Dept Prevent Med, Memphis, TN 38163 USA. NIA, Lab Epidemiol Biometry & Demog, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Epidemiol & Biostat, San Francisco, CA 94143 USA. RP Katsiaras, A (reprint author), Univ Maryland, Sch Med, Baltimore VA Maryland Hlth Care Syst, GRECC BT-GR-18,10 N Greene St, Baltimore, MD 21201 USA. EM akatsiar@grecc.umaryland.edu RI Brach, Jennifer/A-6912-2009; Newman, Anne/C-6408-2013; OI Newman, Anne/0000-0002-0106-1150; Kriska, Andrea/0000-0002-3522-0869; Feingold, Eleanor/0000-0003-2898-6484 FU NIA NIH HHS [N01-AG-6-2101, N01-AG-6-2103, N01-AG-6-2106] NR 62 TC 51 Z9 55 U1 0 U2 12 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 JUL PY 2005 VL 99 IS 1 BP 210 EP 216 DI 10.1152/japplphysiol.01276.2004 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 943WM UT WOS:000230385800029 PM 15718402 ER PT J AU Lucia, A Gomez-Gallego, F Barroso, I Rabadan, M Bandres, F San Juan, AF Chicharro, JL Ekelund, U Brage, S Earnest, CP Wareham, NJ Franks, PW AF Lucia, A Gomez-Gallego, F Barroso, I Rabadan, M Bandres, F San Juan, AF Chicharro, JL Ekelund, U Brage, S Earnest, CP Wareham, NJ Franks, PW TI PPARGC1A genotype (Gly482Ser) predicts exceptional endurance capacity in European men SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE single nucleotide polymorphism; maximal oxygen uptake; metabolism; genetics; diabetes ID RECEPTOR-GAMMA COACTIVATOR-1; HUMAN SKELETAL-MUSCLE; MESSENGER-RNA EXPRESSION; CARDIORESPIRATORY FITNESS; DIABETES-MELLITUS; EPITROCHLEARIS MUSCLE; RAT EPITROCHLEARIS; INSULIN-RESISTANCE; GENE-EXPRESSION; FIBER TYPE AB Animal and human data indicate a role for the peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PPARGC1A) gene product in the development of maximal oxygen uptake ((V) over dot O-2 max), a determinant of endurance capacity, diabetes, and early death. We tested the hypothesis that the frequency of the minor Ser482 allele at the PPARGC1A locus is lower in World-class Spanish male endurance athletes ( cases) [ n = 104; mean (SD) age: 26.8 (3.8) yr] than in unfit United Kingdom (UK) Caucasian male controls [ n = 100; mean ( SD) age: 49.3 (8.1) yr]. In cases and controls, the Gly482Ser genotype met Hardy-Weinberg expectations ( P > 0.05 in both groups tested separately). Cases had significantly higher (V) over dot O-2 max [73.4 ( 5.7) vs. 29.4 ml center dot kg(-1) center dot min(-1) ( 3.8); P < 0.0001] and were leaner [ body mass index: 20.6 ( 1.5) vs. 27.6 kg/m(2) ( 3.9); P < 0.0001] than controls. In unadjusted chi(2) analyses, the frequency of the minor Ser482 allele was significantly lower in cases than in controls (29.1 vs. 40.0%; P = 0.01). To assess the possibility that genetic stratification could confound these observations, we also compared Gly482Ser genotype frequencies in Spanish ( n = 164) and UK Caucasian men ( n = 381) who were unselected for their level of fitness. In these analyses, Ser482 allele frequencies were very similar (36.9% in Spanish vs. 37.5% in UK Caucasians, P = 0.83), suggesting that confounding by genetic stratification is unlikely to explain the association between Gly482Ser genotype and endurance capacity. In summary, our data indicate a role for the Gly482Ser genotype in determining aerobic fitness. This finding has relevance from the perspective of physical performance, but it may also be informative for the targeted prevention of diseases associated with low fitness such as Type 2 diabetes. C1 NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. European Univ Madrid, Madrid, Spain. Univ Complutense, Dept Toxicol, E-28040 Madrid, Spain. Wellcome Trust Sanger Inst, Metab Dis Grp, Cambridge, England. Higher Sports Council, Dept Sports Med, Madrid, Spain. Univ Complutense, Sch Nursing, E-28040 Madrid, Spain. Med Res Ctr, Epidemiol Unit, Cambridge, England. Cooper Inst Ctr Human Performance & Nutr Res, Dallas, TX USA. RP Franks, PW (reprint author), NIDDK, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM pfranks@niddk.nih.gov RI Ekelund, Ulf/A-1046-2008; Brage, Soren/C-6415-2013; Gomez-Gallego, Felix/H-6925-2013; Lucia, Alejandro/M-2759-2014 OI Franks, Paul/0000-0002-0520-7604; BANDRES MOYA, FERNANDO/0000-0002-4675-8226; Brage, Soren/0000-0002-1265-7355; Lucia, Alejandro/0000-0002-3025-2060 FU Wellcome Trust NR 38 TC 61 Z9 71 U1 0 U2 3 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 JUL PY 2005 VL 99 IS 1 BP 344 EP 348 DI 10.1152/japplphysiol.00037.2005 PG 5 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 943WM UT WOS:000230385800046 PM 15705733 ER PT J AU Chatterjee, I Becker, P Grundmeier, M Bischoff, M Somerville, GA Peters, G Sinha, B Harraghy, N Proctor, RA Herrmann, M AF Chatterjee, I Becker, P Grundmeier, M Bischoff, M Somerville, GA Peters, G Sinha, B Harraghy, N Proctor, RA Herrmann, M TI Staphylococcus aureus ClpC is required for stress resistance, aconitase activity, growth recovery, and death SO JOURNAL OF BACTERIOLOGY LA English DT Article ID SIGMA-FACTOR SIGMA(B); BACILLUS-SUBTILIS; LISTERIA-MONOCYTOGENES; STATIONARY-PHASE; GENE-EXPRESSION; BIOFILM FORMATION; HIGH-TEMPERATURE; HEAT-SHOCK; VIRULENCE; COMPETENCE AB The ability of Staphylococcus aureus to adapt to various conditions of stress is the result of a complex regulatory response. Previously, it has been demonstrated that Clp homologues are important for a variety of stress conditions, and our laboratory has shown that a clpC homologue was highly expressed in the S. aureus strain DSM20231 during biofilm formation relative to expression in planktonic cells. Persistence and longterm survival are a hallmark of biofilm-associated staphylococcal infections, as cure frequently fails even in the presence of bactericidal antimicrobials. To determine the role of clpC in this context, we performed metabolic, gene expression, and long-term growth and survival analyses of DSM20231 as well as an isogenic clpC allelic-replacement mutant, a sigB mutant, and a clpC sigB double mutant. As expected, the clpC mutant showed increased sensitivity to oxidative and heat stresses. Unanticipated, however, was the reduced expression of the tricarboxylic acid (TCA) cycle gene citB (encoding aconitase), resulting in the loss of aconitase activity and preventing the catabolization of acetate during the stationary phase. clpC inactivation abolished post-stationary-phase recovery but also resulted in significantly enhanced stationary-phase survival compared to that of the wild-type strain. These data demonstrate the critical role of the ClpC ATPase in regulating the TCA cycle and implicate ClpC as being important for recovery from the stationary phase and also for entering the death phase. Understanding the stationary- and post-stationary-phase recovery in S. aureus may have important clinical implications, as little is known about the mechanisms of long-term persistence of chronic S. aureus infections associated with formation of biofilms. C1 Univ Saarland, Inst Med Microbiol & Hyg, Inst Infect Dis Med, D-6650 Homburg, Germany. Univ Hosp Munster, Inst Med Microbiol, Munster, Germany. Univ Zurich, Inst Med Microbiol, Zurich, Switzerland. NIAID, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, NIH, Hamilton, MT 59840 USA. Univ Wisconsin, Sch Med, Dept Med & Med Microbiol & Immunol, Madison, WI USA. RP Kirrberger Str,Bldg 43, D-66421 Homburg, Germany. EM mathias.herrmann@uniklinik-saarland.de RI Somerville, Greg/B-1326-2013; Herrmann, Mathias/B-6475-2013; Bischoff, Markus/D-2130-2014 OI Somerville, Greg/0000-0002-0991-8737; Bischoff, Markus/0000-0001-6734-2732 FU NIAID NIH HHS [AI42072, R01 AI042072] NR 50 TC 53 Z9 55 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2005 VL 187 IS 13 BP 4488 EP 4496 DI 10.1128/JB.187.13.4488-4496.2005 PG 9 WC Microbiology SC Microbiology GA 939AS UT WOS:000230045100022 PM 15968059 ER PT J AU Munavar, H Zhou, YN Gottesman, S AF Munavar, H Zhou, YN Gottesman, S TI Analysis of the Escherichia coli Alp phenotype: Heat shock induction in ssrA mutants SO JOURNAL OF BACTERIOLOGY LA English DT Article ID CAPSULAR POLYSACCHARIDE SYNTHESIS; CELL-DIVISION INHIBITOR; CLPYQ HSLUV PROTEASE; TRANSCRIPTIONAL REGULATION; DEPENDENT DEGRADATION; TRANS-TRANSLATION; DNA-REPLICATION; TAGGING SYSTEM; LON; PROTEINS AB The major phenotypes of lon mutations, UV sensitivity and overproduction of capsule, are due to the stabilization of two substrates, SulA and RcsA. Inactivation of transfer mRNA (tmRNA) (encoded by ssrA), coupled with a multicopy kanamycin resistance determinant, suppressed both Ion phenotypes and restored the rapid degradation of SulA. This novel protease activity was named Alp but was never identified further. We report here the identification, mapping, and characterization of a chromosomal mutation, faa (for function affecting Alp), that leads to full suppression of a Delta lon ssrA::cat host and thus bypasses the requirement for multicopy Kan(r);faa and ssrA mutants are additive in their ability to suppress lon mutants. The faa mutation was mapped to the C terminus of dnaJ(G232); dnaJ null mutants have similar effects. The identification of a Ion suppressor in dnaJ suggested the possible involvement of heat shock. We find that ssrA mutants alone significantly induce the heat shock response. The suppression of UV sensitivity, both in the original Alp strain and in faa mutants, is reversed by mutations in clpY, encoding a subunit of the heat shock-induced ClpYQ protease that is known to degrade SulA. However, capsule synthesis is not restored by clpY mutants, probably because less RcsA accumulates in the Alp strain and because the RcsA that does accumulate is inactive. Both ssrA effects are partially relieved by ssrA derivatives encoding protease-resistant tags, implicating ribosome stalling as the primary defect. Thus, ssrA and faa each suppress two Ion mutant phenotypes but by somewhat different mechanisms, with heat shock induction playing a major role. C1 NCI, Mol Biol Lab, Bethesda, MD 20892 USA. Madurai Kamaraj Univ, Dept Mol Biol, Sch Biol Sci, Ctr Excellence Genom Sci, Madurai 625021, Tamil Nadu, India. RP NCI, Mol Biol Lab, Bldg 37,Rm 5132, Bethesda, MD 20892 USA. EM susang@helix.nih.gov NR 44 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2005 VL 187 IS 14 BP 4739 EP 4751 DI 10.1128/JB.187.14.4739-4751.2005 PG 13 WC Microbiology SC Microbiology GA 943JU UT WOS:000230350500006 PM 15995188 ER PT J AU Roy, SK Shuman, JD Platanias, LC Shapiro, PS Reddy, SPM Johnson, PF Kalvakolanu, DV AF Roy, SK Shuman, JD Platanias, LC Shapiro, PS Reddy, SPM Johnson, PF Kalvakolanu, DV TI A role for mixed lineage kinases in regulating transcription factor CCAAT/enhancer-binding protein-beta-dependent gene expression in response to interferon-gamma SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID C/EBP-BETA; MAPK PATHWAYS; DNA-BINDING; IFN-GAMMA; PHOSPHORYLATION; ACTIVATION; NF-IL6; DOMAIN; ALPHA; CELLS AB Transcription factor CCAAT/enhancer-binding protein-beta(C/EBP-beta) regulates a variety of cellular functions in response to exogenous stimuli. We have reported earlier that C/EBP-beta induces gene transcription through a novel interferon (IFN)- response element called gamma-IFN-activated transcriptional element. We show here that IFN-gamma-induced, C/EBP-beta/gamma-IFN-activated transcriptional element-dependent gene expression is regulated by mixed lineage kinases (MLKs), members of the mitogen-activated protein kinase kinase kinase family. MLK3 appears to activate C/EBP-beta in response to IFN-gamma by a mechanism involving decreased phosphorylation of a specific phosphoacceptor residue, Ser(64), within the transactivation domain. Decreased phosphorylation of Ser64 was independent of IFN-gamma-stimulated ERK1/2 activation and did not require the ERK phosphorylation site Thr(189) located in regulatory domain 2 of C/EBP-beta. Together these studies provide the first evidence that MLK3 is involved in IFN-gamma signaling and identify a novel mechanism of transcriptional activation by IFN-gamma. C1 Univ Maryland, Sch Med, Greenebaum Canc Ctr, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Mol & Cellular Biol Program, Baltimore, MD 21201 USA. Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. NCI, Lab Prot Dynam & Signaling, NIH, Frederick, MD 21702 USA. Northwestern Univ, Sch Med, Robert Lurie Canc Ctr, Chicago, IL 60611 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD 21205 USA. RP Kalvakolanu, DV (reprint author), Univ Maryland, Sch Med, Greenebaum Canc Ctr, Dept Microbiol & Immunol, 665 W Baltimore St,9th Floor, Baltimore, MD 21201 USA. EM dkalvako@umaryland.edu RI Johnson, Peter/A-1940-2012; OI Johnson, Peter/0000-0002-4145-4725; Shuman, Jon/0000-0001-8412-9087 FU NCI NIH HHS [CA73381, CA105005, CA77816, CA78282]; NHLBI NIH HHS [HL58122, HL66109] NR 49 TC 17 Z9 17 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 1 PY 2005 VL 280 IS 26 BP 24462 EP 24471 DI 10.1074/jbc.M413661200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 939ZT UT WOS:000230114000022 PM 15878863 ER PT J AU Han, SJ Hamdan, FF Kim, SK Jacobson, KA Brichta, L Bloodworth, LM Li, JH Wess, J AF Han, SJ Hamdan, FF Kim, SK Jacobson, KA Brichta, L Bloodworth, LM Li, JH Wess, J TI Pronounced conformational changes following agonist activation of the M-3 muscarinic acetylcholine receptor SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PROTEIN-COUPLED RECEPTORS; DISULFIDE CROSS-LINKING; BETA(2) ADRENERGIC-RECEPTOR; LIGHT-DEPENDENT CHANGES; CYTOPLASMIC END; CONSTITUTIVE ACTIVATION; SULFHYDRYL REACTIVITY; PALMITOYLATION SITES; RHODOPSIN STRUCTURE; ALPHA-HELICES AB The conformational changes that convert G protein-coupled receptors (GPCRs) activated by diffusible ligands from their resting into their active states are not well understood at present. To address this issue, we used the M-3 muscarinic acetylcholine receptor, a prototypical class A GPCR, as a model system, employing a recently developed disulfide cross-linking strategy that allows the formation of disulfide bonds using Cys-substituted mutant M-3 muscarinic receptors present in their native membrane environment. In the present study, we generated and analyzed 30 double Cys mutant M-3 receptors, all of which contained one Cys substitution within the C-terminal portion of transmembrane domain (TM) VII (Val-541 to Ser-546) and another one within the C-terminal segment of TM I (Val-88 to Phe-92). Following their transient expression in COS-7 cells, all mutant receptors were initially characterized in radioligand binding and second messenger assays (carbachol-induced stimulation of phosphatidylinositol hydrolysis). This analysis showed that all 30 double Cys mutant M-3 receptors were able to bind muscarinic ligands with high affinity and retained the ability to stimulate G proteins with high efficacy. In situ disulfide cross-linking experiments revealed that the muscarinic agonist, carbachol, promoted the formation of cross-links between specific Cys pairs. The observed pattern of disulfide cross-links, together with receptor modeling studies, strongly suggested that M-3 receptor activation induces a major rotational movement of the C-terminal portion of TM VII and increases the proximity of the cytoplasmic ends of TM I and VII. These findings should be of relevance for other family A GPCRs. C1 NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NIDDK, Mol Recognit Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDK, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Rm B1A-05,8 Ctr Dr,MSC 0810, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009; Li, Jianhua/B-7671-2011; Han, Sung-Jun/B-9547-2012 OI Jacobson, Kenneth/0000-0001-8104-1493; Li, Jianhua/0000-0002-5744-3182; NR 57 TC 29 Z9 29 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 1 PY 2005 VL 280 IS 26 BP 24870 EP 24879 DI 10.1074/jbc.M500379200 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 939ZT UT WOS:000230114000070 PM 15870064 ER PT J AU Gurung, B Yu, L Xia, D Yu, CA AF Gurung, B Yu, L Xia, D Yu, CA TI The iron-sulfur cluster of the Rieske iron-sulfur protein functions as a proton-exiting gate in the cytochrome bc(1) complex SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ELECTRON-TRANSFER; DOMAIN MOVEMENT; BOVINE HEART; BC1 COMPLEX; RHODOBACTER-SPHAEROIDES; SACCHAROMYCES-CEREVISIAE; YEAST MITOCHONDRIA; QUINONE REDUCTION; TETHER REGION; B(6)F COMPLEX AB The destruction of the Rieske iron-sulfur cluster ([2Fe-2S]) in the bc(1) complex by hematoporphyrin-promoted photoinactivation resulted in the complex becoming proton-permeable (Miki, T., Yu, L., and Yu, C.-A. ( 1991) Biochemistry 30, 230-238). To study further the role of this [2Fe-2S] cluster in proton translocation of the bc(1) complex, Rhodobacter sphaeroides mutants expressing His-tagged cytochrome bc(1) complexes with mutations at the histidine ligands of the [2Fe-2S] cluster were generated and characterized. These mutants lacked the [2Fe-2S] cluster and possessed no bc(1) activity. When the mutant complex was co-inlaid in phospholipid vesicles with intact bovine mitochondrial bc(1) complex or cytochrome c oxidase, the proton ejection, normally observed in intact reductase or oxidase vesicles during the oxidation of their corresponding substrates, disappeared. This indicated the creation of a proton-leaking channel in the mutant complex, whose [2Fe-2S] cluster was lacking. Insertion of the bc(1) complex lacking the head domain of the Rieske iron-sulfur protein, removed by thermolysin digestion, into PL vesicles together with mitochondrial bc(1) complex also rendered the vesicles proton-permeable. Addition of the excess purified head domain of the Rieske iron-sulfur protein partially restored the proton-pumping activity. These results indicated that elimination of the [2Fe-2S] cluster in mutant bc(1) complexes opened up an otherwise closed proton channel within the bc(1) complex. It was speculated that in the normal catalytic cycle of the bc(1) complex, the [2Fe-2S] cluster may function as a proton-exiting gate. C1 Oklahoma State Univ, Dept Biochem & Mol Biol, Stillwater, OK 74078 USA. NCI, Lab Cell Biol Ctr, NIH, Bethesda, MD 20892 USA. RP Oklahoma State Univ, Dept Biochem & Mol Biol, 255 NRC, Stillwater, OK 74078 USA. EM cayuq@okstate.edu FU NIGMS NIH HHS [GM30721] NR 53 TC 15 Z9 18 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 1 PY 2005 VL 280 IS 26 BP 24895 EP 24902 DI 10.1074/jbc.M503319200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 939ZT UT WOS:000230114000073 PM 15878858 ER PT J AU Gudderra, NP Ribeiro, JMC Andersen, JF AF Gudderra, NP Ribeiro, JMC Andersen, JF TI Structural determinants of factor IX(a) binding in nitrophorin 2, a lipocalin inhibitor of the intrinsic coagulation pathway SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID BUG RHODNIUS-PROLIXUS; SURFACE-PLASMON RESONANCE; OXIDE TRANSPORT PROTEIN; BLOOD-FEEDING INSECT; NITRIC-OXIDE; CRYSTAL-STRUCTURE; BLOODSUCKING BUG; HIGH-AFFINITY; HEME PROTEIN; GLA DOMAIN AB Nitrophorin 2 (NP2) is a salivary lipocalin from Rhodnius prolixus that binds with coagulation factors IX (fIX) and IXa (fIXa). Binding of NP2 with fIXa results in potent inhibition of the intrinsic factor Xase complex. A panel of site-directed surface mutants of NP2 was generated to locate determinants of high affinity fIX( a) binding. The locations of the mutations were based on comparisons with the related, but less potent, inhibitor nitrophorin 3 (NP3). Three point mutants (K21A, K92A, and V94A) were found that clearly reduced the inhibitory potency as measured by the activity of a reconstituted factor Xase system. Binding of NP2 with fIXa and fIX as measured by surface plasmon resonance and isothermal titration calorimetry was reduced in a similar manner. Of the three mutants, two (K92A and V94A) were located on the loop connecting beta-strands E and F of the lipocalin beta-barrel. The largest changes were seen with the K92A mutation, which lies at the apex of the loop, with a smaller effect being seen with mutation of Val(94). Combination of four E-F loop mutations (K92A, A93K, V94A, E97A) in a single mutant reduced the inhibitory potency and binding to levels similar to those seen with NP3 without affecting heme or histamine binding. C1 NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. RP Andersen, JF (reprint author), NIAID, Lab Malaria & Vector Res, NIH, Twinbrook 3 Bldg,12735 Twinbrook Pkwy, Bethesda, MD 20892 USA. EM jandersen@niaid.nih.gov OI Ribeiro, Jose/0000-0002-9107-0818 NR 29 TC 23 Z9 23 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 1 PY 2005 VL 280 IS 26 BP 25022 EP 25028 DI 10.1074/jbc.M504386200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 939ZT UT WOS:000230114000086 PM 15866866 ER PT J AU Kim, HP Korn, LL Gamero, AM Leonard, WJ AF Kim, HP Korn, LL Gamero, AM Leonard, WJ TI Calcium-dependent activation of interleukin-21 gene expression in T cells SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLONY-STIMULATING FACTOR; TRANSCRIPTION FACTOR NFAT; IL-2 MESSENGER-RNA; COMMON GAMMA-CHAIN; FACTOR-ALPHA GENE; CYCLOSPORINE-A; NUCLEAR FACTOR; B-CELLS; LYMPHOCYTES-T; RECEPTOR AB Interleukin (IL)-21 is a gamma(c)-dependent cytokine produced by activated T cells with important actions for T, B, and NK cells. The IL-21 gene is adjacent to the IL-2 gene, and like IL-2, IL-21 is strongly induced at the transcriptional level after T cell activation. Interestingly, however, in contrast to the IL-2 gene, a calcium ionophore alone was sufficient to induce IL-21 gene expression in preactivated T cells. Two DNase I hypersensitivity sites were found in the IL-21 gene, corresponding to nucleotide sequences that are conserved in humans and mice. One site is located at the IL-21 promoter region and conferred T cell receptor-mediated IL-21 gene transcription. TCR-induced IL-21 gene expression was inhibited by cyclosporin A and FK506. Correspondingly, the IL-21 5'-regulatory region contains three NFAT binding sites, and induction of IL-21 promoter activity was impaired when these sites were mutated or following treatment with cyclosporin A. Thus, our studies reveal that in contrast to IL-2, a calcium signal alone is sufficient to mediate induction of the IL-21 in preactivated T lymphocytes and that this induction appears to result from specific NFAT binding. C1 NHLBI, Lab Mol Immunol, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Lab, NIH, Frederick, MD 21702 USA. RP Leonard, WJ (reprint author), NHLBI, Lab Mol Immunol, NIH, Bldg 10,Rm 7N252, Bethesda, MD 20892 USA. EM wjl@helix.nih.gov NR 43 TC 48 Z9 48 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUL 1 PY 2005 VL 280 IS 26 BP 25291 EP 25297 DI 10.1074/jbc.M501459200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 939ZT UT WOS:000230114000116 PM 15879595 ER PT J AU Sun, JZ Feng, HQ Lin, GX Zeng, WY Hu, JS AF Sun, JZ Feng, HQ Lin, GX Zeng, WY Hu, JS TI NMR assignments of the winged-helix domain of human Werner syndrome protein SO JOURNAL OF BIOMOLECULAR NMR LA English DT Article C1 Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. NCI, Biochem Lab, NIH, Bethesda, MD 20892 USA. RP Hu, JS (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. EM jh336@umail.umd.edu NR 2 TC 3 Z9 3 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0925-2738 J9 J BIOMOL NMR JI J. Biomol. NMR PD JUL PY 2005 VL 32 IS 3 BP 261 EP 261 DI 10.1007/s10858-005-7960-6 PG 1 WC Biochemistry & Molecular Biology; Spectroscopy SC Biochemistry & Molecular Biology; Spectroscopy GA 960NV UT WOS:000231601300017 PM 16132834 ER PT J AU Koblinski, JE Wu, M Demeler, B Jacob, K Kleinman, HK AF Koblinski, JE Wu, M Demeler, B Jacob, K Kleinman, HK TI Matrix cell adhesion activation by non-adhesion proteins SO JOURNAL OF CELL SCIENCE LA English DT Article DE cell adhesion; fibronectin; osteonectin; collagen ID PLASMA FIBRONECTIN; ADSORPTION; INTEGRINS; FRAGMENTS; BINDING AB Cell adhesion to the extracellular matrix is important in many biological processes. Various ligands and cell surface receptors have been defined. In vitro cell adhesion to matrix proteins and to other 'adhesion' proteins is generally measured on plastic culture substrates. We have found that the presence of low levels of adhesion proteins, e.g. fibronectin, together with high concentrations of nonadhesion proteins, e.g. osteonectin, can promote cell attachment on plastic culture dishes. This promotion of adhesion occurs even when the concentrations of fibronectin, collagen and other adhesive proteins are too low to support cell attachment alone. Other non-adhesive proteins that have similar activity in 'triggering' the attachment of cells to low levels of adhesion molecules include bovine serum albumin (BSA) and cytochrome C. The non-adhesive protein must be added to the plate first, or together with the low amount of the adhesion protein, to iactivate' cell attachment. Adding the adhesion protein fibronectin to the plate first, followed by osteonectin, resulted in no 'activation' of attachment. The non-adhesive protein did not bind to the adhesive protein nor did it alter the level of adhesive protein binding to the substrate. The non-adhesive protein did, however, expose integrin-binding sites of the adhesive protein fibronectin. These data confirm and extend previous data by others demonstrating the role of non-adhesive proteins in regulating the conformation and cell adhesive activity of matrix adhesion proteins on plastic surfaces. Such findings might explain contradictions in the literature about the activity of 'adhesive proteins'. C1 Natl Inst Dent & Craniofacial Res, Cell Biol Sect, Craniofacial Dev Biol & Regenerat Branch, NIH,DHHS, Bethesda, MD 20892 USA. Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78229 USA. SWITCH Biotech AG, D-82061 Neuried, Germany. RP Kleinman, HK (reprint author), Natl Inst Dent & Craniofacial Res, Cell Biol Sect, Craniofacial Dev Biol & Regenerat Branch, NIH,DHHS, Bethesda, MD 20892 USA. EM hkeinman@mail.nih.gov OI Wu, Michael C./0000-0002-3357-6570 FU NCI NIH HHS [CA-91572] NR 25 TC 25 Z9 25 U1 1 U2 8 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 JUL 1 PY 2005 VL 118 IS 13 BP 2965 EP 2974 DI 10.1242/jcs.02411 PG 10 WC Cell Biology SC Cell Biology GA 952WK UT WOS:000231036200019 PM 15976454 ER PT J AU Han, F Adams, CS Tao, ZL Williams, CJ Zaka, R Tuan, RS Norton, PA Hickok, NJ AF Han, F Adams, CS Tao, ZL Williams, CJ Zaka, R Tuan, RS Norton, PA Hickok, NJ TI Transforming growth factor-beta 1 (TGF-beta 1) regulates ATDC5 chondrogenic differentiation and fibronectin isoform expression SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE fibronectin; TGF-beta 1; collagen type II; collagen type I; alcian blue; alternative splicing ID GROWTH-FACTOR-BETA; MESENCHYMAL PROGENITOR CELLS; TUBULAR EPITHELIAL-CELLS; SPLICED EDA SEGMENT; PRE-MESSENGER-RNA; IN-VITRO; TGF-BETA; RAT FIBRONECTIN; CARTILAGE; EIIIA AB Regulated splicing of fibronectin (FN) occurs during the mesenchymal to chondrocyte transition and ultimately results in the relative enrichment of an extra domain B (EDB) exon-containing FN isoform with the suggestion that FN isoforms may play a functional role in chondrogenesis. Promotion of chondrogenesis can also be achieved by treatment with transforming growth factor-beta (TGF-beta), which also regulates FN isoform expression. We have examined the effects of TGF-beta treatment on the assumption of the chondrogenic phenotype in the teratoma-derived cell line ATDC5 and tested whether these effects on chondrogenesis are paralleled by appropriate changes in FN isoform expression. ATDC5 cells were maintained in a pre-chondrogenic state and, in this state, treated with 10 ng/ml TGF-beta. The cells started to elaborate a matrix rich in sulfated proteoglycans, such that within the first 12 days of culture, TGF-beta 1 treatment appeared to slightly accelerate early acquisition of an Alcian blue-stained matrix, and caused a close- and time-dependent decrease in collagen type I expression; changes in collagen type II expression were variable. At later times, cells treated with TGF-beta became indistinguishable from those of the controls. Interestingly, TGF-beta treatment caused a significant close- and time-dependent decrease in the proportion of FN containing the extra domain A (EDA) and the EDB exons. These data suggest that TGF-beta induces the early stages of chondrogenic maturation in this pre-chondrogenic line and that TGF-P treatment increases expression of FN isoforms that lack the EDA and EDB exons. Published 2005 Wiley-Liss, Inc.dagger C1 Thomas Jefferson Univ, Dept Orthopaed Surg, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Med, Div Rheumatol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Dept Biochem & Mol Pharmacol, Philadelphia, PA 19107 USA. Thomas Jefferson Univ, Jefferson Ctr Biomed Res, Philadelphia, PA 19107 USA. NIAMS, Cartilage Biol & Orthopaed Branch, NIH, Bethesda, MD USA. RP Hickok, NJ (reprint author), Thomas Jefferson Univ, Dept Orthopaed Surg, 1015 Walnut St,Suite 501, Philadelphia, PA 19107 USA. EM Noreen.Hickok@jefferson.edu OI Norton, Pamela/0000-0003-1327-9250; Adams, Christopher/0000-0003-2100-4417 FU NIAMS NIH HHS [AR44360, AR39740, AR46821, AR45181]; NIDCR NIH HHS [DE-10875, DE-13310, DE-05748] NR 49 TC 26 Z9 26 U1 1 U2 4 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 JUL 1 PY 2005 VL 95 IS 4 BP 750 EP 762 DI 10.1002/jcb.20427 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 936EZ UT WOS:000229839600010 PM 15832361 ER PT J AU Wong, HK Wilson, DM AF Wong, HK Wilson, DM TI XRCC1 and DNA polymerase beta interaction contributes to cellular alkylating-agent resistance and single-strand break repair SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Article DE XRCC1; POL beta; DNA binding; EM9; functional complementation; base excision; single-strand break repair ID BASE EXCISION-REPAIR; SISTER-CHROMATID EXCHANGE; LIGASE-III ACTIVITY; POLY(ADP-RIBOSE) POLYMERASE; PROTEIN XRCC1; BRCT DOMAIN; EM9 MUTANT; CHO CELLS; DAMAGE; REQUIREMENT AB X-ray cross complementing 1 (XRCC1) protein has been suggested to bind to DNA single-strand breaks (SSBs) and organize protein interactions that facilitate efficient DNA repair. Using four site-specifically modified human XRCC1 mutant expression systems and functional complementation assays in Chinese hamster ovary (CHO) XRCC1 deficient EM9 cells, we evaluated the cellular contributions of XRCC1 s proposed N-terminal domain (NTD) DNAbinding and DNA polymerase beta (POL beta) interaction activities. Results within demonstrate that the interaction with POL beta is biologically important for alkylating agent resistance and SSB repair, whereas the proposed DNA binding function is not critical to these phenotypes. Our data favor a model where the interaction of XRCC1 with POL beta contributes to efficient DNA repair in vivo, whereas its interactions with target DNA is biologically less relevant. Published 2005 Wiley-Liss, Inc.dagger C1 NIA, Lab Mol Gerontol, Baltimore, MD 21224 USA. RP Wilson, DM (reprint author), NIA, Lab Mol Gerontol, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM wilsonda@grc.nia.nih.gov NR 49 TC 34 Z9 34 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0730-2312 J9 J CELL BIOCHEM JI J. Cell. Biochem. PD JUL 1 PY 2005 VL 95 IS 4 BP 794 EP 804 DI 10.1002/jcb.20448 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 936EZ UT WOS:000229839600014 PM 15838887 ER PT J AU Zhou, J Ando, H Macova, M Dou, JT Saavedra, JM AF Zhou, J Ando, H Macova, M Dou, JT Saavedra, JM TI Angiotensin II AT(1) receptor blockade abolishes brain microvascular inflammation and heat shock protein responses in hypertensive rats SO JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM LA English DT Article DE brain ischemia; brain microvessels; heat shock proteins; inflammation; receptor antagonists ID FACTOR-KAPPA-B; MICROVESSEL ENDOTHELIAL-CELLS; SMOOTH-MUSCLE-CELLS; ADHESION MOLECULE-1; OXIDATIVE STRESS; BLOOD-PRESSURE; EXPRESSION; STROKE; ACTIVATION; KIDNEY AB Endothelial dysfunction and inflammation enhance vulnerability to hypertensive brain damage. To explore the participation of Angiotensin II (Ang II) in the mechanism of vulnerability to cerebral ischemia during hypertension, we examined the expression of inflammatory factors and the heat shock protein (HSP) response in cerebral microvessels from spontaneously hypertensive rats and their normotensive controls, Wistar Kyoto rats. We treated animals with vehicle or the Ang II AT, receptor antagonist candesartan, 0.3 mg/kg/day, via subcutaneously implanted osmotic minipumps for 4 weeks. Spontaneously hypertensive rats expressed higher Angiotensin II AT, receptor protein and mRNA than normotensive controls. Candesartan decreased the macrophage infiltration and reversed the enhanced tumor necrosis factor-alpha and interleukin-1 beta rnRNA and nuclear factor-kappa B in microvessels in hypertensive rats. The transcription of many HSP family genes, including HSP60, HSP70 and HSP90, and heat shock factor-1 was higher in hypertensive rats and was downregulated by AT(1) receptor blockade. Our results suggest a proinflammatory action of Ang II through AT, receptor stimulation in cerebral microvessels during hypertension, and very potent antiinflammatory effects of the Ang II AT(1) receptor antagonist. These compounds might be considered as potential therapeutic agents against ischemic and inflammatory diseases of the brain. C1 NIMH, Pharmacol Sect, Dept Hlth & Human Serv, Div Intramural Res Programs,NIH, Bethesda, MD 20892 USA. RP Zhou, J (reprint author), NIMH, Pharmacol Sect, Dept Hlth & Human Serv, Div Intramural Res Programs,NIH, 10 Ctr Dr,MSC 1514,Bldg 10,Room 2D57, Bethesda, MD 20892 USA. EM ZhouJ@intra.nimh.nih.gov NR 34 TC 77 Z9 80 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-678X J9 J CEREBR BLOOD F MET JI J. Cereb. Blood Flow Metab. PD JUL PY 2005 VL 25 IS 7 BP 878 EP 886 DI 10.1038/sj.jcbfm.9600082 PG 9 WC Endocrinology & Metabolism; Hematology; Neurosciences SC Endocrinology & Metabolism; Hematology; Neurosciences & Neurology GA 940CW UT WOS:000230122300010 PM 15729290 ER PT J AU Fortuny, LAI Garolera, M Romo, DH Feldman, E Barillas, HF Keefe, R Lemaitre, MJ Martin, AO Mirsky, A Monguio, I Morote, G Parchment, SA Parchment, LJ Da Pena, E Politis, DG Sedo, MA Taussik, I Valdivia, F De Valdivia, LE Maestre, KV AF Fortuny, LAI Garolera, M Romo, DH Feldman, E Barillas, HF Keefe, R Lemaitre, MJ Martin, AO Mirsky, A Monguio, I Morote, G Parchment, SA Parchment, LJ Da Pena, E Politis, DG Sedo, MA Taussik, I Valdivia, F De Valdivia, LE Maestre, KV TI Research with Spanish-speaking populations in the United States: Lost in the translation - A commentary and a plea SO JOURNAL OF CLINICAL AND EXPERIMENTAL NEUROPSYCHOLOGY LA English DT Article ID PSYCHOMETRIC THEORY; SCALE TRANSLATIONS; WHITE RESEARCHERS; LANGUAGE; EQUIVALENCE; ISSUES; MODEL; ITEM AB Verbal material used to assess the cognitive abilities of Spanish-speakers in the the United States is frequently of linguistically unacceptable quality. The use of these materials in research settings is thought to pose a serious threat to test validity and hence to the validity of claimed results or conclusions. The authors explain how and why incorrect language finds its way into cognitive tests used in research and other settings and suggest solutions to this serious problem. C1 Univ Autonoma Barcelona, E-08193 Barcelona, Spain. Bilingual Clin Neuropsychol, Tucson, AZ USA. Duke Univ, Med Ctr, Durham, NC USA. Univ N Carolina, Sch Med, Chapel Hill, NC USA. No Illinois Univ, De Kalb, IL 60115 USA. NIMH, NIH, Bethesda, MD 20892 USA. St Gregory Coll Preparatory Sch, Tucson, AZ USA. Univ Arizona, Tucson, AZ USA. Univ Calif San Diego, San Diego, CA 92103 USA. MultiLingual Testing, Natick, MA USA. Univ Buenos Aires, Buenos Aires, DF, Argentina. Neurol Associates Tucson, Tucson, AZ USA. Pima Community Coll, Tucson, AZ USA. Univ Barcelona, Barcelona, Spain. RP Fortuny, LAI (reprint author), 6601 E Grant Rd,Suite 115, Tucson, AZ 85715 USA. EM tibet@lartiola.com NR 31 TC 11 Z9 12 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1380-3395 J9 J CLIN EXP NEUROPSYC JI J. Clin. Exp. Neuropsychol. PD JUL PY 2005 VL 27 IS 5 BP 555 EP 564 DI 10.1080/13803390490918282 PG 10 WC Psychology, Clinical; Clinical Neurology; Psychology SC Psychology; Neurosciences & Neurology GA 936WB UT WOS:000229885000003 ER PT J AU Putnam, K Chrousos, GP Nieman, LK Rubinow, DR AF Putnam, K Chrousos, GP Nieman, LK Rubinow, DR TI Sex-related differences in stimulated hypothalamic-pituitary-adrenal axis during induced gonadal suppression SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CORTICOTROPIN-RELEASING HORMONE; RESTRAINT-INDUCED ACTIVATION; MENSTRUAL-CYCLE PHASE; PARAVENTRICULAR NUCLEUS; PSYCHOSOCIAL STRESS; CORTISOL RESPONSE; MALE-RAT; GENDER; ACTH; PLASMA AB Context: Sex-related differences in the stress response are well described in the animal literature but in humans are inconsistent and appear to reflect both the method used to stimulate the hypothalamic-pituitary-adrenal (HPA) axis and the age of the subjects. Sex-related differences in reproductive steroid levels further confound efforts to define the specific role of the sex of the individual in stress axis responsivity. Objective: The aim of this study was to address this role independent of differences in reproductive steroid levels. We compared HPA axis response to pharmacological (CRH) and physiological ( exercise) stressors in two groups of young to middle-aged ( 18 - 45 yr) men ( n = 10 and 8) and women ( n = 12 and 13) undergoing gonadal suppression with leuprolide acetate ( monthly im injection of 7.5 mg in men and 3.75 mg in women). Design: Exercise and CRH stimulation tests were performed during induced hypogonadal conditions. Setting: The study was conducted at a National Institutes of Health Clinical Center Outpatient Clinic. Patient or Other Participants: Male and female normal volunteers participated in the study. Main Outcome Measures: The main outcome measures were stimulated ACTH and cortisol levels. Results: Both CRH ( 1 mu g/kg) stimulation and graded treadmill exercise stimulation occurred in the month after the second leuprolide injection to ensure gonadal suppression. Despite the absence of sex differences in estradiol or testosterone at the time of testing, men showed increased stimulated ACTH ( repeated-measures ANOVA for CRH, P < 0.005) and cortisol ( repeated-measures ANOVA for exercise, P < 0.05) compared with women. Among the summary measures, area under the curve (AUC) for cortisol was significantly greater in men than women after exercise. Although the AUC for ACTH was not significantly different across sexes, the initial AUC ( 0 - 30 min) was significantly greater in men for both procedures. No significant sex differences were found in a measure of adrenal responsivity, the cortisol to ACTH ratio, for either procedure. Cortisol-binding globulin levels did not differ between men and women and were not correlated with stimulated HPA axis measures. These data confirm earlier reports of sex differences in stimulated HPA axis activity and demonstrate that these differences exist even under induced hypogonadal conditions (i.e. in the absence of characteristic differences in reproductive steroids). C1 NIMH, Off Special Populat, Rockville, MD 20857 USA. NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. NIMH, Geriatr Psychiat Branch, Bethesda, MD 20892 USA. NIMH, Behav Endocrinol Branch, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Mil & Emergency Med, Bethesda, MD 20814 USA. NIH, Clin Ctr Nursing Dept, Bethesda, MD 20892 USA. Cornell Univ, Weill Med Coll, New York, NY 10021 USA. NICHHD, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. Cornell Univ, Dept Psychiat, New York, NY 10021 USA. RP NIMH, Off Special Populat, Rockville, MD 20857 USA. EM rubinowd@mail.nih.gov NR 52 TC 5 Z9 5 U1 1 U2 5 PU ENDOCRINE SOC PI WASHINGTON PA 2055 L ST NW, SUITE 600, WASHINGTON, DC 20036 USA SN 0021-972X EI 1945-7197 J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2005 VL 90 IS 7 BP 4224 EP 4231 DI 10.1210/jc.2004-2525 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 943FT UT WOS:000230339100066 ER PT J AU Mitchell, MD Chang, MC Chaiworapongsa, T Lan, HY Helliwell, RJA Romero, R Sato, TA AF Mitchell, MD Chang, MC Chaiworapongsa, T Lan, HY Helliwell, RJA Romero, R Sato, TA TI Identification of 9 alpha,11 beta-prostaglandin F-2 in human amniotic fluid and characterization of its production by human gestational tissues SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ACTIVATED RECEPTOR-GAMMA; 15-DEOXY-DELTA(12,14)-PROSTAGLANDIN J(2); PROSTAGLANDIN D-2; FETAL MEMBRANES; PRETERM LABOR; PPAR LIGAND; PARTURITION; INFECTION; APOPTOSIS; TERM AB Context: 9 alpha, 11 beta-Prostaglandin F-2 (9 alpha, 11 beta-PGF(2)) can contract uterine smooth muscle with a potency equal to PGF(2 alpha). Its presence in the human uterus and production by human gestational tissues is unknown. Objective: These studies were performed to determine whether the PGD(2)-derived 9 alpha,11 beta-PGF(2) is both present in human amniotic fluid and synthesized by human gestational tissues and if so, whether labor-related substances could regulate its production. Results: Detectable concentrations of 9 alpha, 11 beta-PGF(2) were found in amniotic fluid samples and appeared to increase in late gestation. All gestational tissues studied synthesized 9 alpha, 11 beta-PGF(2), with the placenta having the highest basal production rate, followed by the amnion and then the choriodecidua. IL-1 beta and TNF alpha caused concentration-dependent increases in 9 alpha, 11 beta-PGF(2) production in human amnion and choriodecidual explants. Moreover, treatment of choriodecidual and placental explants with lipopolysaccharide resulted in a significant increase in 9 alpha, 11 beta-PGF(2) production rates, reaching a maximum of 13-fold in the choriodecidua. Studies examining the effects of the addition of exogenous PGD(2) strongly indicated that the choriodecidua has significant ability to convert PGD(2) to 9 alpha, 11 beta-PGF(2), whereas the amnion has little. Conclusions: These results demonstrate for the first time that 9 alpha, 11 beta-PGF(2) is present in human amniotic fluid and that it is produced by human gestational tissues and up-regulated by bacterial cell wall components and proinflammatory cytokines. We suggest that this prostaglandin may play a part in the mechanisms of human labor at term and preterm. C1 Univ Auckland, Liggins Inst, Auckland 1020, New Zealand. Univ Auckland, Natl Res Ctr Growth & Dev, Auckland 1020, New Zealand. NICHHD, Perinatal Res Branch, Detroit, MI 48201 USA. RP Mitchell, MD (reprint author), Univ Auckland, Liggins Inst, Auckland 1020, New Zealand. EM m.mitchell@auckland.ac.nz RI Mitchell, Murray/A-8639-2010 OI Mitchell, Murray/0000-0002-6167-7176 NR 31 TC 18 Z9 18 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUL PY 2005 VL 90 IS 7 BP 4244 EP 4248 DI 10.1210/jc.2004-2496 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 943FT UT WOS:000230339100069 PM 15840748 ER PT J AU Karne, RJ Chen, H Sullivan, G Quon, MJ AF Karne, RJ Chen, H Sullivan, G Quon, MJ TI Letter re: Limited accuracy of surrogates of insulin resistance during puberty in obese and lean children at risk for altered glucoregulation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Letter ID SENSITIVITY CHECK INDEX; SECRETION; QUICKI C1 Natl Ctr Complementary & Alternat Med, Diabet Unit, NIH, Bethesda, MD 20892 USA. RP Quon, MJ (reprint author), Natl Ctr Complementary & Alternat Med, Diabet Unit, NIH, 10 Ctr Dr,Bldg 10,Room 6C-205, Bethesda, MD 20892 USA. EM quonm@nih.gov RI Quon, Michael/B-1970-2008 NR 14 TC 2 Z9 2 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 JUL PY 2005 VL 90 IS 7 BP 4418 EP 4419 DI 10.1210/jc.2005-0528 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 943FT UT WOS:000230339100098 PM 16002414 ER PT J AU Brant, LJ Sheng, SL Morrell, CH Zonderman, AB AF Brant, LJ Sheng, SL Morrell, CH Zonderman, AB TI Data from a longitudinal study provided measurements of cognition to screen for Alzheimer's disease SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE Alzheimer's disease; classification; disease screening; longitudinal data; random-effects models; visual memory performance ID RANDOM-EFFECTS MODELS; MEMORY LOSS; IMPAIRMENT; DEMENTIA; HEALTH; PREDICTORS; DIAGNOSIS; ONSET AB Background: This article presents a computerized method to help predict individuals at risk for developing Alzheimer's disease (AD). This would be a valuable tool for clinicians in developing treatment plans for potential AD patients. Using the initial level and rates of change in visual memory performance, such a method could predict potential AD patients in a fast and inexpensive manner. A longitudinal case-control study of 52 female and 145 male participants was performed in a gerontology research center using premorbid tests of visual memory and neurologic examinations to identify individuals with and without dementia and AD. Methods: The classification method for each individual starts on the second examination and proceeds to compute that person's risk of AD one examination at a time based on all the follow-up information of the remaining individuals. Results: By performing a crossvalidation study, the optimal combination of sensitivity and specificity derived from a receiver operating characteristic (ROC) curve showed 65% of the Alzheimer cases and 75% of the noncases were correctly classified for females, while 65 and 60% of cases and noncases, respectively, were correctly classified for males. Conclusion: Longitudinal measurements of cognition can be useful in detecting the presence of AD. (c) 2005 Elsevier Inc. All rights reserved. C1 NIA, Ctr Gerontol Res, Baltimore, MD 21224 USA. Loyola Coll, Dept Math Sci, Baltimore, MD 21205 USA. RP Brant, LJ (reprint author), NIA, Ctr Gerontol Res, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM larry_brant@nih.gov OI Zonderman, Alan B/0000-0002-6523-4778 NR 32 TC 6 Z9 6 U1 0 U2 2 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 JUL PY 2005 VL 58 IS 7 BP 701 EP 707 DI 10.1016/j.jclinepi.2005.01.003 PG 7 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 938YB UT WOS:000230038200009 PM 15939221 ER PT J AU Grady, C AF Grady, C TI Payment of clinical research subjects SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID PAYING RESEARCH SUBJECTS; HEALTHY-VOLUNTEERS; RANDOMIZED-TRIAL; MONETARY INCENTIVES; UNDUE INDUCEMENT; PARTICIPATION; WILLINGNESS; MOTIVATIONS; 5-DOLLAR; CONSENT AB Offering payment to clinical research subjects, in an effort to enhance recruitment by providing an incentive to take part or enabling subjects to participate without financial sacrifice, is a common yet uneven and contentious practice in the US. Concern exists regarding the potential for payment to unduly influence participation and thus obscure risks, impair judgment, or encourage misrepresentation. Heightening these concerns is the participation not only of adults but also of children in pediatric research trials. Thorough assessment of risks, careful eligibility screening, and attention to a participant's freedom to refuse all serve to reduce the possibility of compensation adversely affecting the individual and/or the study. Institutional review boards currently evaluate payment proposals with minimal guidance from federal regulations. Here, reasons for providing payment, payment models, ethical concerns, and areas for further research are examined. C1 NIH, Dept Clin Bioeth, Ctr Clin, Bethesda, MD 20892 USA. RP Grady, C (reprint author), NIH, Dept Clin Bioeth, Ctr Clin, Bldg 10,Room 1C118, Bethesda, MD 20892 USA. EM cgrady@nih.gov NR 49 TC 90 Z9 91 U1 7 U2 15 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 JUL PY 2005 VL 115 IS 7 BP 1681 EP 1687 DI 10.1172/JCI25694 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942OX UT WOS:000230292800004 PM 16007244 ER PT J AU Zarember, KA Malech, HL AF Zarember, KA Malech, HL TI HIF-1 alpha: a master regulator of innate host defenses? SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID TRANSCRIPTION FACTOR; NEUTROPHIL SURVIVAL; ACTIVATION; EPSILON; PATHWAY; HIF-1 AB in the days following infection, when the human body develops and refines antibodies and prepares to mount an adaptive immune response, the bulwark of innate host defense against microbial infection is the polymorphonuclear leukocyte (PMN). PMNs seek out, identify, engulf, and sterilize invading microbes using both O-2-dependent and O-2-independent antimicrobial systems. A decrease in PMN numbers or function caused by immunosuppression or disease increases the risk of infection. In this issue of the JCI, Peyssonnaux et al. identify a novel and essential role for hypoxia-inducible factor-1 alpha in regulating several important PMN functions relevant to host defense, including transcription of cationic antimicrobial polypeptides and induction of NO synthase (see the related article beginning on page 1806). C1 NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. RP Malech, HL (reprint author), NIAID, Host Def Lab, NIH, 10 Ctr Dr,MSC 1456, Bethesda, MD 20892 USA. EM HMALECH@niaid.nih.gov OI Malech, Harry/0000-0001-5874-5775 NR 21 TC 56 Z9 60 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2005 VL 115 IS 7 BP 1702 EP 1704 DI 10.1172/JCI25740 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942OX UT WOS:000230292800007 PM 16007247 ER PT J AU Kim, T Loh, YP AF Kim, T Loh, YP TI Chromogranin A: a surprising link between granule biogenesis and hypertension SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Editorial Material ID INHIBITORY PEPTIDE CATESTATIN; CATECHOLAMINE RELEASE; ON/OFF SWITCH; CALCIUM; STORAGE AB Chromogranin A (CHGA) and its derived peptides, which are stored and released from dense-core secretory granules of neuroendocrine cells, have been implicated as playing multiple roles in the endocrine, cardiovascular, and nervous systems. In this issue of the JCI, Mahapatra et al. present in vivo evidence for 2 important functions of CHGA: the regulation of catecholamine-containing dense-core chromaffin granule biogenesis in the adrenal gland and the control of blood pressure (see the related article beginning on page 1942). Obliteration of CHGA expression in a KO mouse model led to decreased size and number of chromaffin granules as well as hypertension in these animals. Transgenic expression of human Chga and exogenous injection of human catestatin, a CHGA-derived nicotinic cholinergic antagonist, restored normal blood pressure in these mice. These results suggest a coupled relationship between CHGA-mediated chromaffin granule biogenesis, necessary for catecholamine storage, and catestatin-induced inhibition of cholinergic-stimulated catecholamine release, which regulates autonomic control of blood pressure. C1 NICHHD, Cellular Neurobiol Sect, NIH, Bethesda, MD 20892 USA. RP Loh, YP (reprint author), NICHHD, Cellular Neurobiol Sect, NIH, 49 Convent Dr,Mail Code 4480, Bethesda, MD 20892 USA. EM lohp@mail.nih.gov NR 19 TC 25 Z9 26 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2005 VL 115 IS 7 BP 1711 EP 1713 DI 10.1172/JCI25706 PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942OX UT WOS:000230292800010 PM 16007250 ER PT J AU Kobayashi, T Soegiarto, DW Yang, YZ Lanske, B Schipani, E McMahon, AP Kronenberg, HM AF Kobayashi, T Soegiarto, DW Yang, YZ Lanske, B Schipani, E McMahon, AP Kronenberg, HM TI Indian hedgehog stimulates periarticular chondrocyte differentiation to regulate growth plate length independently of PTHrP SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HORMONE-RELATED PEPTIDE; ENDOCHONDRAL BONE-DEVELOPMENT; PARATHYROID-HORMONE; EXPRESSION; PROLIFERATION; RECEPTOR; PROGRESSION; PRECURSORS; PROTEIN; GENE AB In the developing growth plate, periarticular chondrocytes proliferate, differentiate into columnar chondrocytes, and then further differentiate into postmitotic hypertrophic chondrocytes. Parathyroid hormone-related (PTH-related) protein (PTHrP), regulated by Indian hedgehog (Ihh), prevents premature hypertrophic differentiation, thereby maintaining the length of columns. Ihh regulates cartilage development through PTHrP-independent pathways as well. Here we show that Ihh stimulates differentiation of periarticular to columnar chondrocytes (periarticular chondrocyte differentiation) and thereby regulates the length of columns independently of PTHrP. Mosaic ablation of the PTH/PTHrP receptor in the growth plate caused upregulation of Ihh action, PTHrP upregulation, acceleration of periarticular chondrocyte differentiation, and elongation of the columnar region. Decreasing Ihh action in these mice reduced elongation of columns, whereas decreasing PTHrP showed only a modest effect on column length. Overexpression of Ihh caused PTHrP upregulation, elongation of columns, and acceleration of periarticular chondrocyte differentiation. PTHrP heterozygosity in this model had a minimal effect on the elongation of columns. Moreover, the elongation of columns and stimulation of periarticular chondrocyte differentiation in these models were still observed when PTHrP signaling was maintained so that it remained constant. These results demonstrate that Ihh acts on periarticular chondrocytes to stimulate their differentiation, thereby regulating the columnar cell mass independently of PTHrP. C1 Massachusetts Gen Hosp, Endocrine Unit, Boston, MA 02114 USA. Max Planck Inst Biochem, D-82152 Martinsried, Germany. NHGRI, Dev Genet Sect, Genet Dis Res Branch, Bethesda, MD 20892 USA. Forsyth Inst, Dept Oral & Dev Biol, Boston, MA USA. Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. RP Kronenberg, HM (reprint author), Massachusetts Gen Hosp, Endocrine Unit, 50 Blossom St, Boston, MA 02114 USA. EM kronenberg.henry@mgh.harvard.edu FU NIDDK NIH HHS [DK56246, P01 DK056246] NR 26 TC 127 Z9 139 U1 0 U2 4 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 JUL PY 2005 VL 115 IS 7 BP 1734 EP 1742 DI 10.1172/JCI24397 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942OX UT WOS:000230292800013 PM 15951842 ER PT J AU Sereti, I Imamichi, H Natarajan, V Imamichi, T Ramchandani, MS Badralmaa, Y Berg, SC Metcalf, JA Hahn, BK Shen, JM Powers, A Davey, RT Kovacs, JA Shevach, EM Lane, HC AF Sereti, I Imamichi, H Natarajan, V Imamichi, T Ramchandani, MS Badralmaa, Y Berg, SC Metcalf, JA Hahn, BK Shen, JM Powers, A Davey, RT Kovacs, JA Shevach, EM Lane, HC TI In vivo expansion of CD4(+)CD45RO-CD25(+) T cells expressing foxP3 in IL-2-treated HIV-infected patients SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TRANSCRIPTION FACTOR FOXP3; PERIPHERAL-BLOOD; INTERMITTENT INTERLEUKIN-2; SUBCUTANEOUS INTERLEUKIN-2; ANTIRETROVIRAL THERAPY; DRIVEN PROLIFERATION; SUPPRESSOR FUNCTION; REGULATORY CELLS; CONTROLLED-TRIAL AB Administration of IL-2 to HIV-infected patients leads to expansion of a unique subset of CD4(+)CD45RO(-)CD25(+) cells. In this study, the origin, clonality, and function of these cells were investigated. Analysis of TCR excision circles revealed that the CD4(+)CD45RO-CD25(+) cells were the product of peripheral expansion but remained polyclonal as determined by TCR repertoire analysis. Phenotypically, these cells were distinct from naturally occurring Tregs; they exhibited intermediate features, between those of memory and naive cells, and had lower susceptibility to apoptosis than CD45RO(-)CD25(-) or memory T cells. Studies of intracellular cytokine production and proliferation revealed that cytokine-expanded naive CD25(+) cells had low IL-2 production and required costimulation for proliferation. Despite elevated expression of forkhead transcription factor P3 (foxP3), they exerted only weak suppression compared with CD45RO(+)CD25(+)high cells (Tregs). In summary, in vivo IL-2 administration to HIV-infected patients leads to peripheral expansion of a population of long-lived CD4(+)CD45RO(-)CD25(+) cells that express high levels of foxP3 but exert weak suppressive function. These CD4(+)CD25(+) cytokine-expanded naive cells, distinct from antigen-triggered cells and Tregs, play a role in the maintenance of a state of low turnover and sustained expansion of the CD4(+) T cell pool. C1 NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Frederick, MD USA. NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Sereti, I (reprint author), NIAID, Clin & Mol Retrovirol Sect, Immunoregulat Lab, NIH, Bldg 10,Room 11B-04,10 Ctr Dr,Mail Stop Code 1876, Bethesda, MD 20892 USA. EM isereti@niaid.nih.gov FU NCI NIH HHS [N01CO12400, N01-CO-12400] NR 46 TC 104 Z9 107 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2005 VL 115 IS 7 BP 1839 EP 1847 DI 10.1172/JCI124307 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942OX UT WOS:000230292800023 PM 15937547 ER PT J AU Meyer-Lindenberg, A Mervis, CB Sarpal, D Koch, P Steele, S Kohn, P Marenco, S Morris, CA Das, S Kippenhan, S Mattay, VS Weinberger, DR Berman, KF AF Meyer-Lindenberg, A Mervis, CB Sarpal, D Koch, P Steele, S Kohn, P Marenco, S Morris, CA Das, S Kippenhan, S Mattay, VS Weinberger, DR Berman, KF TI Functional, structural, and metabolic abnormalities of the hippocampal formation in Williams syndrome SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID TEMPORAL-LOBE EPILEPSY; LONG-TERM POTENTIATION; N-ACETYL ASPARTATE; MEMORY; BRAIN; HEMIZYGOSITY; REGION; MICE; SCHIZOPHRENIA; INVOLVEMENT AB Williams syndrome (WS), caused by microdeletion of some 21 genes on chromosome 7q11.23, is characterized by dysmorphic features, mental retardation or learning difficulties, elastin arteriopathy, and striking neurocognitive and social-behavioral abnormalities. Recent studies of murine knockouts of key genes in the microdeleted region, LIM kinase 1 (LIMK1) and cytoplasmatic linker protein 2 (CYLN2), demonstrated significant functional and metabolic abnormalities, but grossly normal structure, in the hippocampal formation (1417). Furthermore, deficits in spatial navigation and long-term memory, major cognitive domains dependent on hippocampal function, have been described in WS. We used multimodal neuroimaging to characterize hippocampal structure, function, and metabolic integrity in 12 participants with WS and 12 age-, sex-, and IQ-matched healthy controls. PET and functional MRI studies showed profound reduction in resting blood flow and absent differential response to visual stimuli in the anterior HF in WS. Spectroscopic measures of N-acetyl aspartate, considered a marker of synaptic activity, were reduced. Hippocampal size was preserved, but subtle alterations in shape were present. These data demonstrate abnormalities in HF in WS in agreement with murine models, implicate LIMK1 and CYLN2 in human hippocampal function, and suggest that hippocampal dysfunction may contribute to neurocognitive abnormalities in WS. C1 NIMH, Sect Integrat Neuroimaging, Bethesda, MD 20892 USA. NIMH, Neuroimaging Core Facil, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, Genes Cognit & Psychosis Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Louisville, Dept Psychol & Brain Sci, Neurodev Sci Lab, Louisville, KY 40292 USA. Univ Nevada, Sch Med, Dept Pediat, Las Vegas, NV 89154 USA. RP Meyer-Lindenberg, A (reprint author), 10-4C101,9000 Rockville Pike, Bethesda, MD 20892 USA. EM andreasml@nih.gov RI Marenco, Stefano/A-2409-2008; Sarpal, Deepak/O-5630-2014; OI Marenco, Stefano/0000-0002-2488-2365; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU NINDS NIH HHS [NS35102, R01 NS035102] NR 53 TC 82 Z9 85 U1 0 U2 3 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 JUL PY 2005 VL 115 IS 7 BP 1888 EP 1895 DI 10.1172/JCI24892 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942OX UT WOS:000230292800029 PM 15951840 ER PT J AU Kaufman, HL DeRaffele, G Mitcham, J Moroziewicz, D Cohen, SM Hurst-Wicker, KS Cheung, K Lee, DS Divito, J Voulo, M Donovan, J Dolan, K Manson, K Panicali, D Wang, E Horig, H Marincola, FM AF Kaufman, HL DeRaffele, G Mitcham, J Moroziewicz, D Cohen, SM Hurst-Wicker, KS Cheung, K Lee, DS Divito, J Voulo, M Donovan, J Dolan, K Manson, K Panicali, D Wang, E Horig, H Marincola, FM TI Targeting the local tumor microenvironment with vaccinia virus expressing B7.1 for the treatment of melanoma SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID T-CELL IMMUNITY; COSTIMULATORY MOLECULE B7; DENDRITIC CELLS; INTRATUMORAL VACCINATION; METASTATIC MELANOMA; ESTABLISHED TUMORS; MALIGNANT-MELANOMA; ANTITUMOR IMMUNITY; CLINICAL-TRIAL; ANTIGEN AB Immunotherapy for the treatment of metastatic melanoma remains a major clinical challenge. The melanoma microenvironment may lead to local T cell tolerance in part through downregulation of costimulatory molecules, such as B7.1 (CD80). We report the results from the first clinical trial, to our knowledge, using a recombinant vaccinia virus expressing B7.1 (rV-B7.1) for monthly intralesional. vaccination of accessible melanoma lesions. A standard 2-dose-escalation phase I clinical trial was conducted with 12 patients. The approach was wen tolerated with only low-grade fever, myalgias, and fatigue reported and 2 patients experiencing vitiligo. An objective partial response was observed in 1 patient and disease stabilization in 2 patients, 1 of whom is alive without disease 59 months following vaccination. All patients demonstrated an increase in postvaccination antibody and T cell responses against vaccinia virus. Systemic immunity was tested in HLA-A*0201 patients who demonstrated an increased frequency of gp100 and T cells specific to melanoma antigen recognized by T cells I (MART-1), also known as Melan-A, by ELISPOT assay following local rV-B7.1 vaccination. Local immunity was evaluated by quantitative real-time RT-PCR, which suggested that tumor regression was associated with increased expression of CD8 and IFN-gamma. The local delivery of vaccinia virus expressing 137.1 was well tolerated and represents an innovative strategy for altering the local tumor microenvironment in patients with melanoma. C1 Columbia Univ, Med Ctr, Dept Surg, New York, NY 10032 USA. Columbia Univ, Dept Med, New York, NY USA. Columbia Univ, Dept Bioinformat, New York, NY USA. Albert Einstein Coll Med, Dept Surg, New York, NY USA. Albert Einstein Coll Med, Dept Radiol, New York, NY USA. Albert Einstein Coll Med, Dept Pathol, New York, NY USA. Ther Biol Corp, Cambridge, MA USA. NIH, Dept Transfus Med, Immunogenet Sect, Bethesda, MD USA. RP Kaufman, HL (reprint author), Columbia Univ, Med Ctr, Dept Surg, 630 W 168th St,Phys & Surg Bldg 17-508, New York, NY 10032 USA. EM hlk2003@columbia.edu FU NCRR NIH HHS [M01 RR000645, RR00645]; PHS HHS [R01 93696] NR 68 TC 72 Z9 84 U1 0 U2 1 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JUL PY 2005 VL 115 IS 7 BP 1903 EP 1912 DI 10.1172/JCI24624 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 942OX UT WOS:000230292800031 PM 15937544 ER PT J AU Said-Salim, B Mathema, B Braughton, K Davis, S Sinsimer, D Eisner, W Likhoshvay, Y DeLeo, FR Kreiswirth, BN AF Said-Salim, B Mathema, B Braughton, K Davis, S Sinsimer, D Eisner, W Likhoshvay, Y DeLeo, FR Kreiswirth, BN TI Differential distribution and expression of Panton-Valentine leucocidin among community-acquired methicillin-resistant Staphylococcus aureus strains SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INFECTIONS; LEUKOCIDIN; EMERGENCE; PNEUMONIA; EVOLUTION; PATHOGEN; CHILDREN; CASSETTE; DISEASE; CLONES AB Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is an emerging threat worldwide. CA-MRSA strains differ from hospital-acquired MRSA strains in their antibiotic susceptibilities and genetic backgrounds. Using several genotyping methods, we clearly define CA-MRSA at the genetic level and demonstrate that the prototypic CA-MRSA strain, MW2, has spread as a homogeneous clonal strain family that is distinct from other CA-MRSA strains. The Panton-Valentine leucocidin (PVL)-encoding genes, lukF and lukS, are prevalent among CA-MRSA strains and have previously been associated with CA-MRSA infections. To better elucidate the role of PVL in the pathogenesis of CA-MRSA, we first analyzed the distribution and expression of PVL among different CA-MRSA strains. Our data demonstrate that PVL genes are differentially distributed among CA-MRSA strains and, when they are present, are always transcribed, albeit with strain-to-strain variability of transcript levels. To directly test whether PVL is critical for the pathogenesis of CA-MRSA, we evaluated the lysis of human polymorphonuclear leukocytes (PMNs) during phagocytic interaction with PVL-positive and PVL-negative CA-MRSA strains. Unexpectedly, there was no correlation between PVL expression and PMN lysis, suggesting that additional virulence factors underlie leukotoxicity and, thus, the pathogenesis of CA-MRSA. C1 Publ Hlth Res Inst, TB Ctr, Newark, NJ 07103 USA. NIH, Rocky Mt Labs, Lab Human Bacterial Pathogenesis, Hamilton, MT 59840 USA. NIAID, NIH, Hamilton, MT 59840 USA. Univ Med & Dent New Jersey, Dept Microbiol & Mol Genet, Newark, NJ 07103 USA. RP Kreiswirth, BN (reprint author), Publ Hlth Res Inst, TB Ctr, 225 Warren St, Newark, NJ 07103 USA. EM barry@phri.org OI DeLeo, Frank/0000-0003-3150-2516 NR 34 TC 80 Z9 90 U1 0 U2 6 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 JUL PY 2005 VL 43 IS 7 BP 3373 EP 3379 DI 10.1128/JCM.43.7.3373-3379.2005 PG 7 WC Microbiology SC Microbiology GA 947AR UT WOS:000230614900053 PM 16000462 ER PT J AU El Saleeby, CM Allison, KJ Knapp, KM Walsh, TJ Hayden, RT AF El Saleeby, CM Allison, KJ Knapp, KM Walsh, TJ Hayden, RT TI Discordant rise in galactomannan antigenemia in a patient with resolving aspergillosis, renal failure, and ongoing hemodialysis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID CELL TRANSPLANT RECIPIENTS; INVASIVE ASPERGILLOSIS; CIRCULATING GALACTOMANNAN; NEUTROPENIC PATIENTS; IN-VIVO; DIAGNOSIS AB We describe the case of a patient with improving invasive aspergillosis and paradoxically rising serum galactomannan levels in the presence of chronic renal failure and ongoing hemodialysis. Dialysate tested negative for galactomannan, demonstrating the inability of treatments such as hemodialysis to clear Aspergillus antigen from serum. In patients with renal failure and aspergillosis, rising serum galactomannan levels may not necessarily signify progressive infection. C1 St Jude Childrens Res Hosp, Dept Pathol, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Infect Dis, Memphis, TN 38105 USA. Univ Tennessee, Ctr Hlth Sci, Dept Pediat, Memphis, TN 38163 USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. RP Hayden, RT (reprint author), St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St,Mail Stop 250, Memphis, TN 38105 USA. EM randall.hayden@stjude.org FU NCI NIH HHS [P30 CA021765, P30 CA 21765] NR 14 TC 11 Z9 14 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 JUL PY 2005 VL 43 IS 7 BP 3560 EP 3563 DI 10.1128/JCM.43.7.3560-3563.2005 PG 4 WC Microbiology SC Microbiology GA 947AR UT WOS:000230614900098 PM 16000507 ER PT J AU Dye, BA Selwitz, RH AF Dye, BA Selwitz, RH TI The relationship between selected measures of periodontal status and demographic and behavioural risk factors SO JOURNAL OF CLINICAL PERIODONTOLOGY LA English DT Article DE dental public health; dental research; epidemiology; ordinal regression; periodontal disease; periodontal indices ID TREATMENT NEEDS CPITN; ATTACHMENT LOSS; UNITED-STATES; CIGARETTE-SMOKING; OLDER ADULTS; ORAL HEALTH; NHANES-III; DISEASE; PREVALENCE; SEVERITY AB Objective: To assess differences between selected periodontal measures by demographic and behavioural factors in a nationally representative sample of the United States. Methods: Data for 11,347 person's ages 20-79 years from the third National Health and Nutrition Examination Survey (NHANES III) were used. Indices and measures constructed from NHANES III data used for this study were: derived community periodontal index (dCPI), attachment loss extent index (ALEI), attachment loss (AL) scores, and a Periodontal Status Measure (PSM) developed for this study. Results: The influence of demographic and behavioural factors varied across the four indices examined in multivariate cumulative logistic models. Moreover, there was significant effect modification by cigarette smoking with age in the ALEI and AL models. The odds ratio (OR) of increasing periodontal disease status among 20-39 year olds as measured by AL or ALEI for current smokers compared with non-smokers were OR=6.2 (95% confidence interval (CI)=4.1, 8.7) and OR=5.6 (95% CI=3.7, 8.7), respectively. In a similar comparison, the OR for dCPI was 2.6 (95% CI=1.7, 3.8). Furthermore, Mexican American ethnicity was generally not significant in any models using dCPI, PSM, AL, or ALEI and prior dental visit was more likely to be significant only in the dCPI and PSM models. Discussion: Among the well-known demographic and behavioural influences on periodontal health status, some, such as race/ethnicity and prior dental visit status have different relationships with differing periodontal measures employed to assess periodontal status. Moreover, potential interactions among cofactors also are dependent upon the measure selected. Periodontal research findings may be influenced significantly by periodontal measure selection and its affect on measurement validity. This may have particular relevance to issues concerning disease surveillance and assessing reduction of disparities in oral health. Consequently, a renewed approach to developing appropriate measures for periodontal epidemiology is needed. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, NHANES Program, Hyattsville, MD 20782 USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. RP Dye, BA (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, NHANES Program, 3311 Toledo Rd,Rm 4416, Hyattsville, MD 20782 USA. EM bfd1@cdc.gov NR 50 TC 27 Z9 29 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0303-6979 J9 J CLIN PERIODONTOL JI J. Clin. Periodontol. PD JUL PY 2005 VL 32 IS 7 BP 798 EP 808 DI 10.1111/j.1600-051X.2005.00742.x PG 11 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 937WI UT WOS:000229956300018 PM 15966889 ER PT J AU Zivotofsky, AZ Goldberg, ME Powell, KD AF Zivotofsky, AZ Goldberg, ME Powell, KD TI Rhesus monkeys behave as if they perceive the Duncker illusion SO JOURNAL OF COGNITIVE NEUROSCIENCE LA English DT Article ID ILLUSORY STIMULUS MOTION; REMEMBERED TARGETS; PONZO ILLUSION; EYE-MOVEMENTS; SACCADES; PERCEPTION; PRIMATE; PURSUIT; NEURONS; CORTEX AB The visual system uses the pattern of motion on the retina to analyze the motion of objects in the world, and the motion of the observer him/herself. Distinguishing between retinal motion evoked by movement of the retina in space and retinal motion evoked by movement of objects in the environment is computationally difficult, and the human visual system frequently misinterprets the meaning of retinal motion. In this study, we demonstrate that the visual system of the Rhesus monkey also misinterprets retinal motion. We show that monkeys erroneously report the trajectories of pursuit targets or their own pursuit eye movements during an epoch of smooth pursuit across an orthogonally moving background. Furthermore, when they make saccades to the spatial location of stimuli that flashed early in an epoch of smooth pursuit or fixation, they make large errors that appear to take into account the erroneous smooth eye movement that they report in the first experiment, and not the eye movement that they actually make. C1 NEI, Bethesda, MD 20892 USA. Bar Ilan Univ, IL-52100 Ramat Gan, Israel. Columbia Univ, New York, NY 10027 USA. New York State Psychiat Inst & Hosp, New York, NY 10032 USA. Univ Illinois, Chicago, IL USA. RP Zivotofsky, AZ (reprint author), NEI, Bethesda, MD 20892 USA. EM zivotoa@mail.biu.ac.il FU NEI NIH HHS [R01 EY014978-01, P30 EY019007, R01 EY014978, R01 EY014978-02, R01 EY014978-03] NR 29 TC 12 Z9 12 U1 1 U2 1 PU M I T PRESS PI CAMBRIDGE PA FIVE CAMBRIDGE CENTER, CAMBRIDGE, MA 02142 USA SN 0898-929X J9 J COGNITIVE NEUROSCI JI J. Cogn. Neurosci. PD JUL PY 2005 VL 17 IS 7 BP 1011 EP 1017 DI 10.1162/0898929054475235 PG 7 WC Neurosciences; Psychology, Experimental SC Neurosciences & Neurology; Psychology GA 951MA UT WOS:000230933400003 PM 16102233 ER PT J AU Benson, JM Stagner, BB Martin, GK Friedman, M Durr, SE Gomez, A McDonald, J Fleming, LE Backer, LC Baden, DG Bourdelais, A Naar, J Lonsbury-Martin, BL AF Benson, JM Stagner, BB Martin, GK Friedman, M Durr, SE Gomez, A McDonald, J Fleming, LE Backer, LC Baden, DG Bourdelais, A Naar, J Lonsbury-Martin, BL TI Cochlear function in mice following inhalation of brevetoxin-3 SO JOURNAL OF COMPARATIVE PHYSIOLOGY A-NEUROETHOLOGY SENSORY NEURAL AND BEHAVIORAL PHYSIOLOGY LA English DT Article DE brevetoxin; CBA/CaJ mice; distortion-product otoacoustic emissions; cochlear function ID PRODUCT OTOACOUSTIC EMISSIONS; AMINOGLYCOSIDE OTOTOXICITY; NOISE EXPOSURE; RATS; ELIMINATION; PBTX-3; ADULT; MOUSE; YOUNG; CBA AB Brevetoxin-3 was shown previously to adversely affect central auditory function in goldfish. The present study evaluated the effects of exposure to this agent on cochlear function in mice using the 2f(1)-f(2) distortion-product otoacoustic emission (DPOAE). Towards this end, inbred CBA/CaJ mice were exposed to a relatively high concentration of brevetoxin-3 (similar to 400 mu g/m(3)) by nose-only inhalation for a 2-h period. Further, a subset of these mice received a second exposure a day later that lasted for an additional 4 h. Mice exposed only once for 2 h did not exhibit any notable cochlear effects. Similarly, mice exposed two times, for a cumulative dose of 6 h, exhibited essentially no change in DPOAE levels. C1 Univ Colorado, Hlth Sci Ctr, Dept Otolaryngol, Denver, CO 80202 USA. Lovelace Resp Res Inst, Albuquerque, NM USA. Univ Miami, NIEHS, Marine & Freshwater Biomed Res Ctr, Miami, FL 33152 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Univ N Carolina, Marine Sci Res Ctr, Wilmington, NC 28401 USA. Jerry L Pettis Mem Vet Adm Med Ctr, Res Serv 151, Loma Linda, CA 92357 USA. RP Martin, GK (reprint author), Univ Colorado, Hlth Sci Ctr, Dept Otolaryngol, 4200 E 9th Ave, Denver, CO 80202 USA. EM glen.martin2@med.va.gov FU NIDCD NIH HHS [DC03114, R01 DC000613, R01 DC003114, DC00613]; NIEHS NIH HHS [ES10594, P01 ES010594-05, P01 ES010594] NR 24 TC 2 Z9 2 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-7594 J9 J COMP PHYSIOL A JI J. Comp. Physiol. A -Neuroethol. Sens. Neural Behav. Physiol. PD JUL PY 2005 VL 191 IS 7 BP 619 EP 626 DI 10.1007/s00359-005-0613-0 PG 8 WC Behavioral Sciences; Neurosciences; Physiology; Zoology SC Behavioral Sciences; Neurosciences & Neurology; Physiology; Zoology GA 947EC UT WOS:000230625200004 PM 15902474 ER PT J AU Nilsson, O Mitchum, RD Schrier, L Ferns, SP Barnes, KM Troendle, JF Baron, J AF Nilsson, O Mitchum, RD Schrier, L Ferns, SP Barnes, KM Troendle, JF Baron, J TI Growth plate senescence is associated with loss of DNA methylation SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID DIPLOID CELL STRAINS; CATCH-UP GROWTH; CHONDROCYTE DIFFERENTIATION; REPLICATIVE SENESCENCE; ARTICULAR-CARTILAGE; HUMAN FIBROBLASTS; RESTING ZONE; MOUSE CELLS; LIFE-SPAN; CULTURE AB The overall body size of vertebrates is primarily determined by longitudinal bone growth at the growth plate. With age, the growth plate undergoes programmed senescence, causing longitudinal bone growth to slow and eventually cease. Indirect evidence suggests that growth plate senescence occurs because stem-like cells in the growth plate resting zone have a finite proliferative capacity that is gradually exhausted. Similar limits on replication have been observed when many types of animal cells are placed in cell culture, an effect known as the Hayflick phenomenon. However, we found that the number of population doublings of rabbit resting zone chondrocytes in culture did not depend on the age of the animal from which the cells were harvested, suggesting that the mechanisms limiting replicative capacity of growth plate chondrocytes in vivo are distinct from those in vitro. We also observed that the level of DNA methylation in resting zone chondrocytes decreased with age in vivo. This loss of methylation appeared to occur specifically with the slow proliferation of resting zone chondrocytes in vivo and was not observed with the rapid proliferation of proliferative zone chondrocytes in vivo (i.e. the level of DNA methylation did not change from the resting zone to the hypertrophic zone), with proliferation of chondrocytes in vitro, or with growth of the liver in vivo. Thus, the overall level of DNA methylation decreases during growth plate senescence. This finding is consistent with the hypothesis that the mechanism limiting replication of growth plate chondrocytes in vivo involves loss of DNA methylation and, thus, loss of DNA methylation might be a fundamental biological mechanism that limits longitudinal bone growth in mammals, thereby determining the overall adult size of the organism. C1 NICHD, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NICHD, Biometry & Math Stat Branch, NIH, Bethesda, MD 20892 USA. RP Nilsson, O (reprint author), NICHD, Dev Endocrinol Branch, NIH, Bldg CRC,Room 1-3330,10 Ctr Dr MSC 1103, Bethesda, MD 20892 USA. EM oia.nilsson@nih.gov NR 38 TC 24 Z9 26 U1 0 U2 3 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 JUL PY 2005 VL 186 IS 1 BP 241 EP 249 DI 10.1677/joe.1.06016 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 947UD UT WOS:000230671900023 PM 16002553 ER PT J AU Kim, EY Bin Hong, Y Lai, ZN Cho, YH Brady, RO Jung, SC AF Kim, EY Bin Hong, Y Lai, ZN Cho, YH Brady, RO Jung, SC TI Long-term expression of the human glucocerebrosidase gene in vivo after transplantation of bone-marrow-derived cells transformed with a lentivirus vector SO JOURNAL OF GENE MEDICINE LA English DT Article DE Gaucher disease; lentivirus; transplantation; glucocerebrosidase; hematopoietic stem cell ID HEMATOPOIETIC STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; GAUCHER-DISEASE; PROGENITOR CELLS; CD34(+) CELLS; NONDIVIDING CELLS; RETROVIRAL VECTOR; STROMAL CELLS; MOUSE MODEL; ADULT MICE AB Background Gaucher disease is a lysosomal storage disorder resulting from a deficiency of glucocerebrosidase (GC). Recently, lentivirus vectors have been developed for efficient gene transfer into hematopoietic stem cells (HSCs). A recombinant lentivirus vector was used to evaluate the transduction of the human GC gene into murine bone-marrow-derived HSCs and its expression in their progeny. Methods Murine HSCs were transduced with lentivirus vector (lenti-EF-GC; MOI = 10 - 100). We transplanted female wild-type C57BL/6J mice with genetically modified male HSCs via the tail vein. Results We show that intravenous transplantation of transduced HSCs has therapeutic potential. Enzyme activity was increased two- to threefold in various tissues, especially in the hematopoietic system. Numerous transplanted HSCs survived for 6 months and were shown by PCR to contain the provirus genes; the Y chromosome was identified by FISH analysis in the cells of female mouse recipients. Conclusions The recombinant lentiviral vector transduces HSCs that are capable of long-term gene expression in vivo. This approach is potentially useful for the treatment of patents with Gaucher disease and other lysosomal storage disorders. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Ewha Womans Univ, Coll Med, Dept Biochem, Seoul 158710, South Korea. Natl Inst Hlth, Dept Biomed Sci, Div Genet Dis, Seoul, South Korea. Hanyang Univ, Coll Med, Dept Med Genet, Seoul 133791, South Korea. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Jung, SC (reprint author), Ewha Womans Univ, Coll Med, Dept Biochem, Mok 6 Dong, Seoul 158710, South Korea. EM jungsc@ewha.ac.kr OI Jung, Sung-Chul/0000-0002-3174-8965 NR 57 TC 12 Z9 14 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD JUL PY 2005 VL 7 IS 7 BP 878 EP 887 DI 10.1002/jgm.732 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 948DI UT WOS:000230695800005 PM 15712335 ER PT J AU Soza, A Heller, T Ghany, M Lutchman, G Liang, TJ Germain, J Hsu, HH Park, Y Hoofnagle, JH AF Soza, A Heller, T Ghany, M Lutchman, G Liang, TJ Germain, J Hsu, HH Park, Y Hoofnagle, JH TI Pilot study of interferon gamma for chronic hepatitis C SO JOURNAL OF HEPATOLOGY LA English DT Article DE antiviral therapy; cytokines; interferon alfa; interferon gamma; viral kinetics; bone marrow suppression ID HUMAN ALPHA-INTERFERON; COMBINATION THERAPY; ANTIVIRAL ACTIVITY; CONTROLLED TRIAL; VIRUS; RIBAVIRIN AB Background/Aims: Currently, there are no effective therapies available for patients with chronic hepatitis C who have failed to respond to optimal interferon alfa-based regimens. The aims of this pilot study were to assess the antiviral activity and safety of interferon gamma in chronic hepatitis C. Methods: Patients with chronic hepatitis C, genotype 1, who had not responded to or who had relapsed after therapy with interferon alfa and ribavirin were enrolled in a trial of interferon gamma 1b given in doses of 100, 200 or 400 mu g subcutaneously three times weekly for 4 weeks. Frequent blood samples were obtained for HCV RNA levels. Results: Fourteen patients were enrolled. Geometric mean HCV RNA levels remained unchanged. Serum aminotransferase levels also did not change, while there were significant decreases in neutrophil counts (- 41 % from baseline) and hematocrit (-5%). Low grade fever and malaise were common with the first injection of interferon gamma, but no serious side effects were encountered. Conclusions: Although relatively well tolerated, interferon gamma in doses of 100-400 mu g thrice weekly had no effect on HCV RNA levels in patients with chronic hepatitis C who had failed to achieve a sustained response to interferon alfa-based therapies. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. C1 NIDDKD, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. NIH, Dept Transfus Med, Warren G Magnusen Clin Ctr, Bethesda, MD 20892 USA. InterMune Inc, Brisbane, CA USA. RP Hoofnagle, JH (reprint author), Bldg 31,Room 9A27,31 Ctr Dr, Bethesda, MD 20892 USA. EM hoofnaglej@extra.niddk.nih.gov RI Soza, Alejandro/C-2907-2009 NR 24 TC 24 Z9 28 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 JUL PY 2005 VL 43 IS 1 BP 67 EP 71 DI 10.1016/j.jhep.2005.02.023 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 942KW UT WOS:000230282300014 PM 15913831 ER PT J AU Schmidt-Kuntzel, A Eizirik, E O'Brien, SJ Menotti-Raymond, M AF Schmidt-Kuntzel, A Eizirik, E O'Brien, SJ Menotti-Raymond, M TI Tyrosinase and tyrosinase related protein 1 alleles specify domestic cat coat color phenotypes of the albino and brown loci SO JOURNAL OF HEREDITY LA English DT Article ID OCULOCUTANEOUS ALBINISM; HIMALAYAN MOUSE; MOLECULAR-BASIS; FELIS-CATUS; SIAMESE CAT; GENE; PIGMENTATION; TEMPERATURE; MUTATIONS; EXPRESSION AB The genes encoding enzymes of the tyrosinase family are strong candidates for coat color variation in mammals. To investigate their influence in domestic cat coat color, we determined the complete nucleotide coding sequence of the domestic cat genes tyrosinase (TYR)-a plausible candidate gene for the albino (C) locus, and tyrosinase related protein 1 (TYRP1)-a candidate gene for the brown (B) locus. Sequence variants between individuals exhibiting variation in pigmentation were submitted to association studies. In TYR, two nonsynonymous substitutions encoding TYR-G301R and TYR-G227W were associated with the siamese and burmese phenotypes of the albino locus, respectively. TYRP1 was mapped on chromosome D4 within 5 cM of a highly polymorphic microsatellite, previously found to be fixed in a cat breed selected for the chocolate (b) allele of the B locus, which reinforced TYRP1 as a candidate gene for the B locus in the domestic cat. Two DNA polymorphisms, one leading to a TYRP1-A3G substitution in the signal peptide and another to an in-frame insertion TYRP1-421ins17/18 caused by a donor splice site mutation in intron 6, were associated with the chocolate (b) allele. A premature UAG stop codon at position 100 of TYRP1 was associated with a second allele of the B locus, cinnamon (b(l)). The results provide very strong evidence that the specific nucleotide variants of feline TYR (chromosome D1) are causative of the siamese (c(s)) and burmese (c(b)) alleles of the albino locus, as well as nucleotide variants of TYRP1 (chromosome D4) as specifying the chocolate (b) and cinnamon (b(l)) alleles of the B locus. C1 NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. George Washington Univ, Dept Genet, Washington, DC USA. NCI, Lab Genom Divers, Frederick, MD 21701 USA. PUCRS, Fac Biociencias, BR-90619900 Porto Alegre, RS, Brazil. RP Schmidt-Kuntzel, A (reprint author), NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. EM aschmidt@ncifcrf.gov RI Eizirik, Eduardo/K-8034-2012 OI Eizirik, Eduardo/0000-0002-9658-0999 FU NCI NIH HHS [N02 CO 12400] NR 58 TC 55 Z9 56 U1 1 U2 16 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1503 J9 J HERED JI J. Hered. PD JUL PY 2005 VL 96 IS 4 BP 289 EP 301 DI 10.1093/jhered/esi066 PG 13 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 950HA UT WOS:000230847000001 PM 15858157 ER PT J AU Kutzler, MA Robinson, TM Chattergoon, MA Choo, DK Choo, AY Choe, PY Ramanathan, MP Parkinson, R Kudchodkar, S Tamura, Y Sidhu, M Roopchand, V Kim, JJ Pavlakis, GN Felber, BK Waldmann, TA Boyer, JD Weiner, DB AF Kutzler, MA Robinson, TM Chattergoon, MA Choo, DK Choo, AY Choe, PY Ramanathan, MP Parkinson, R Kudchodkar, S Tamura, Y Sidhu, M Roopchand, V Kim, JJ Pavlakis, GN Felber, BK Waldmann, TA Boyer, JD Weiner, DB TI Coimmunization with an optimized IL-15 plasmid results in enhanced function and longevity of CD8 T cells that are partially independent of CD4 T cell help SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNE-RESPONSE; DNA VACCINATION; ACUTE INFECTION; IN-VITRO; RHEUMATOID-ARTHRITIS; CARBOXYL-TERMINUS; CD8-T-CELL MEMORY; RHESUS MACAQUES; CD4-T-CELL HELP; GROWTH-FACTOR AB DNA vaccines are a promising technology for the induction of Ag-specific immune responses, and much recent attention has gone into improving their immune potency. In this study we test the feasibility of delivering a plasmid encoding IL-15 as a DNA vaccine adjuvant for the induction of improved Ag-specific CD8(+) T cellular immune responses. Because native IL-15 is poorly expressed, we used PCR-based strategies to develop an optimized construct that expresses 80-fold higher than the native IL-15 construct. Using a DNA vaccination model, we determined that immunization with optimized IL-15 in combination with HIV-1gag DNA constructs resulted in a significant enhancement of Ag-specific CD8(+) T cell proliferation and IFN-gamma secretion, and strong induction of long-lived CD8(+) T cell responses. In an influenza DNA vaccine model, communization with plasmid expressing influenza A PR8/34 hemagglutinin with the optimized IL-15 plasmid generated improved long term CD8(+) T cellular immunity and protected the mice against a lethal mucosal, challenge with influenza virus. Because we observed that IL-15 appeared to mostly adjuvant CD8(+) T cell function, we show that in the partial, but not total, absence of CD4(+) T cell help, plasmid-delivered IL-15 could restore CD8 secondary immune responses to an antigenic DNA plasmid, supporting the idea that the effects of IL-15 on CD8(+) T cell expansion require the presence of low levels of CD4 T cells. These data suggest a role for enhanced plasmid IL-15 as a candidate adjuvant for vaccine or immunotherapeutic studies. C1 Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. Emory Univ, Sch Med, Dept Microbiol & Immunol, Atlanta, GA 30322 USA. Harvard Univ, Sch Med, Program Biol & Biomed Sci, Boston, MA 02115 USA. Natl Inst Adv Ind Sci & Technol, Sapporo, Hokkaido, Japan. Wyeth Lederle, Vaccine Discovery, Pearl River, NY 10965 USA. Viral Genomix, Blue Bell, PA 19422 USA. Basic Res Labs, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. RP Weiner, DB (reprint author), Univ Penn, Sch Med, Dept Pathol & Lab Med, 422 Curie Blvd,Room 505 Stellar Chance Labs, Philadelphia, PA 19104 USA. EM dbweiner@mail.med.upenn.edu RI Weiner, David/H-8579-2014 FU NIAID NIH HHS [F32AI054142] NR 71 TC 139 Z9 146 U1 2 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2005 VL 175 IS 1 BP 112 EP 123 PG 12 WC Immunology SC Immunology GA 939CW UT WOS:000230050900015 PM 15972637 ER PT J AU Bagenstose, LM Agarwal, RK Silver, PB Harlan, DM Hoffmann, SC Kampen, RL Chan, CC Caspi, RR AF Bagenstose, LM Agarwal, RK Silver, PB Harlan, DM Hoffmann, SC Kampen, RL Chan, CC Caspi, RR TI Disruption of CD40/CD40-ligand interactions in a retinal autoimmunity model results in protection without tolerance SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; CD40-CD40 LIGAND INTERACTION; BINDING PROTEIN IRBP; T-CELL-ACTIVATION; CD40 LIGAND; INTERLEUKIN-12 PRODUCTION; MULTIPLE-SCLEROSIS; REGULATORY CELLS; BLOCKADE; UVEORETINITIS AB We examined the role of CD40/CD40L interactions on the development of experimental autoimmune uveoretinitis (EAU), a cell-mediated, Th1-driven autoimmune disease that serves as a model for autoimmune uveitis in humans. EAU-susceptible B10.RIII mice immunized with the retinal autoantigen interphotoreceptor retinoid binding protein in CFA and treated with anti-CD40L Ab (MR1) had reduced incidence and severity of disease. Real-time PCR analysis revealed that the innate and adaptive responses of protected mice were reduced, without an obvious shift toward a Th2 cytokine profile. In contrast to some other reports, no evidence was found for regulatory cells in adoptive transfer experiments. To determine whether CD40L blockade resulted in long-term tolerance, mice protected by treatment with MR1 Ab were rechallenged for uveitis after circulating MR1 Ab levels dropped below the detection limit of ELISA. MR1-treated mice developed severe EAU and strong cellular responses to interphotoreceptor retinoid binding protein, comparable to those of control mice. These responses were higher than in mice that had not received the primary immunization concurrently with anti-CD40L treatment. We conclude that 1) CD40/CD40L interaction is required for EAU and its disruption prevents disease development; 2) CD40L blockade inhibits the innate response to immunization and reduces priming, but does not result in immune deviation; and 3) protection is dependent on persistence of anti-CD40L Abs, and long-term tolerance is not induced. Furthermore, immunological memory develops under cover of CD40L blockade causing enhanced responses upon rechallenge. Taken together, our data suggest that ongoing CD40/CD40L blockade might be required to maintain a therapeutic effect against uveitis. C1 NEI, Immunol Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Islet & Autoimmun Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, Transplantat Branch, NIH, Bethesda, MD 20892 USA. RP Caspi, RR (reprint author), NEI, Immunol Lab, NIH, 10 Ctr Dr,Bldg 10,Room 10N222, Bethesda, MD 20892 USA. EM rcaspi@helix.nih.gov NR 53 TC 24 Z9 26 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2005 VL 175 IS 1 BP 124 EP 130 PG 7 WC Immunology SC Immunology GA 939CW UT WOS:000230050900016 PM 15972638 ER PT J AU Lundqvist, A Childs, R AF Lundqvist, A Childs, R TI Allogeneic hematopoietic cell transplantation as immunotherapy for solid tumors - Current status and future directions SO JOURNAL OF IMMUNOTHERAPY LA English DT Review DE allogeneic stem cell transplantation; nonmyeloablative transplantation; graft versus tumor; graft versus leukemia; renal cell carcinoma ID BONE-MARROW-TRANSPLANTATION; VERSUS-HOST-DISEASE; CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; CYTOTOXIC T-LYMPHOCYTES; ACTIVATED KILLER CELLS; PERIPHERAL-BLOOD; REDUCED-INTENSITY; DONOR LYMPHOCYTES; IMMUNE ESCAPE AB Although myeloablative conditioning can cytoreduce or debulk malignancies, the curative antitumor effects of allogeneic hematopoietic stem cell transplantation (HCT) are mostly mediated by transplanted donor immune cells. A heightened awareness and appreciation of the immune-mediated anticancer effects that occur after allogeneic transplantation has led to the increasing use of reduced-intensity stem cell transplantation (RIST) approaches to treat advanced malignancies. The graft-versus-leukemia effects that occur against hematologic cancers after RIST have recently attracted oncologists to explore the therapeutic potential of allogeneic HCT for treatment-refractory solid tumors. Delayed tumor regression after RIST in a subset of patients with metastatic renal cell, breast, ovarian, pancreatic, and colon carcinoma has recently been reported, confirming the existence of a graft-versus-tumor effect in solid tumors. Advanced disease states, rapidly growing tumors, and accrual of patients with extremely short survival are factors that have been identified to limit the efficacy of allogeneic immunotherapy. This review discusses results of allogeneic HCT for solid tumors and the development of newer transplant strategies to optimize the potential of the graft-versus-tumor effect. C1 NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. RP Childs, R (reprint author), NHLBI, Hematol Branch, NIH, Bldg 10-CRC,Room 3-5330, Bethesda, MD 20892 USA. EM childsr@nih.gov NR 76 TC 24 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JUL-AUG PY 2005 VL 28 IS 4 BP 281 EP 288 DI 10.1097/01.cji.0000165354.19171.8f PG 8 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 941MP UT WOS:000230219200001 PM 16000944 ER PT J AU Guimond, M Fry, TJ Mackall, CL AF Guimond, M Fry, TJ Mackall, CL TI Cytokine signals in T-cell homeostasis SO JOURNAL OF IMMUNOTHERAPY LA English DT Review DE T-cell homeostasis; IL7; IL15; homeostatic peripheral expansion; lymphopenia ID BONE-MARROW-TRANSPLANTATION; IN-VIVO; ADOPTIVE IMMUNOTHERAPY; IMMUNE RECONSTITUTION; DRIVEN PROLIFERATION; LYMPHOPENIC HOSTS; RECEPTOR SIGNALS; MHC COMPLEXES; MEMORY CELLS; NAIVE CD4 AB Thymic production of T cells declines rapidly with age, and therefore homeostatic cycling (HC) of mature lymphocytes plays an important role in maintaining stable numbers of mature T lymphocytes bearing sufficient repertoire diversity. Following lymphocyte depletion, HC changes in quality and magnitude, resulting in homeostatic peripheral expansion (HPE), a state of widespread T-cell cycling that serves to increase T-cell number and to maintain T-cell repertoire diversity to the greatest extent possible. Recent studies delineating the requirements for HC and HPE have shown that naive CD4(+) cells and naive CD8(+) cells require both IL7 and TCR engagement for survival, cycling, and homeostatic expansion, whereas CD8(+) memory cells are maintained and expanded by cytokine signals alone, independent of TCR engagement. While basal levels of IL15 are sufficient for HC and HPE of CD8(+) memory cells, supranormal levels of IL7 will also suffice. The requirements for memory CD4(+) cells remain unclear, but current models hypothesize that either IL7 or TCR triggering may be sufficient. Thus, the changes in immune physiology that are present in lymphopenic hosts can be largely accounted for by cytokine-driven signals, especially those rendered by IL7 or IL15. As the alterations in immune physiology present in lymphopenic hosts may be conducive to stronger antitumor immune responsiveness, careful delineation of the factors responsible may be expected to give rise to approaches to augment the effectiveness of current antitumor immunotherapies. C1 NCI, Pediat Oncol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. RP Mackall, CL (reprint author), Bldg 10-CRC,Rm 1W-3940,10 Ctr Dr,MSC 1104, Bethesda, MD 20892 USA. EM cm35c@nih.gov NR 60 TC 28 Z9 30 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JUL-AUG PY 2005 VL 28 IS 4 BP 289 EP 294 DI 10.1097/01.cji.0000165356.03924.e7 PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 941MP UT WOS:000230219200002 PM 16000945 ER PT J AU Garland, L Gitlitz, B Ebbinghaus, S Pan, H de Haan, H Puri, RK Von Hoff, D Figlin, R AF Garland, L Gitlitz, B Ebbinghaus, S Pan, H de Haan, H Puri, RK Von Hoff, D Figlin, R TI Phase I trial of intravenous IL-4 Pseudomonas exotoxin protein (NBI-3001) in patients with advanced solid tumors that express the IL-4 receptor SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE phase 1; immunotoxin; renal carcinoma; non-small cell lung carcinoma ID PERMUTED INTERLEUKIN 4-TOXIN; DIRECTED CYTOTOXIN THERAPY; TARGETED CYTOTOXIN; ANTITUMOR-ACTIVITY; CARCINOMA-CELLS; CANCER-CELLS; HUMAN HEAD; TOXIN; XENOGRAFT; TOLERABILITY AB NBI-3001 is a novel immunotoxin of attenuated Pseudomonas exotoxin fused to circularly permutated IL-4, which has shown some antitumor effects in glioblastoma multiforme with intratumoral administration. The authors evaluated the safety and tolerability of NBI-3001 administered intravenously in a dose-escalation design to patients with renal cell and non-small cell lung carcinoma whose tumors showed at least 10% IL-4 receptor expression. Cohorts of three to six patients were treated at dose levels of 0.008, 0.016, and 0.027 mg/m(2) daily X 5 days every 28 days. Neutralizing antibody (NAB)titers, plasma levels of NBI-3001, and patient tolerability were monitored sequentially 14 patients received a total of 36 cycles of NBI-3001 (range 1-6). No dose-limiting toxicities were noted at dose levels 0.008 and 0.016 mg/m(2). At 0.027 mg/m(2), two patients developed self-limiting, grade 3 or 4 transaminase elevation during cycle 1. NAB titers of more than 1: 100 were detected in five of the seven patients treated with at least two cycles; the median titer after cycle I and the median maximum titer in subsequent cycles were 1:50 and approximately 1:1,710, respectively. No objective tumor responses were noted. Eight of 12 evaluable patients with renal cell carcinoma had stable disease; four patients had disease progression. High NAB titers resulted in four patients being withdrawn from the study. The dose-limiting toxicity for intravenous NBI-3001 was transaminase elevation at 0.027 mg/m(2). NBI-3001 at 0.016 mg/m(2) was well tolerated. Low circulating levels of NBI-3001, coupled with rising NAB titers, may have contributed to the lack of response in tumors that express IL-4R. C1 Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. Neurocrine Biosci Inc, San Diego, CA USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol,NIH, Bethesda, MD 20014 USA. Univ Calif Los Angeles, Jonsson Comprehens Canc Ctr, Los Angeles, CA 90024 USA. RP Garland, L (reprint author), Univ Arizona, Arizona Canc Ctr, 1515 N Campbell Ave,Ste 1969E, Tucson, AZ 85724 USA. EM lgarland@azcc.arizona.edu NR 25 TC 31 Z9 33 U1 0 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JUL-AUG PY 2005 VL 28 IS 4 BP 376 EP 381 DI 10.1097/01.cji.0000162782.86008.mL PG 6 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 941MP UT WOS:000230219200013 PM 16000956 ER PT J AU Powell, DJ Parker, LL Rosenberg, SA AF Powell, DJ Parker, LL Rosenberg, SA TI Large-scale depletion of CD25(+) regulatory T cells from patient leukapheresis samples SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE human; CD25; regulatory T cells; clinical; depletion ID METASTATIC MELANOMA; IMMUNE-RESPONSES; AUTOIMMUNE-DISEASE; ANTIGEN-4 BLOCKADE; CANCER REGRESSION; CLINIMACS DEVICE; ACUTE INFECTION; PHASE-I; LYMPHOCYTES; FOXP3 AB The ability to selectively enrich or deplete T lymphocytes of specific phenotype and function holds significant promise for application in adoptive immunotherapy protocols. Although CD4(+) T cells can have an impact on CD8(+) T-cell effector function, memory, and maintenance, a subset of CD4(+) T cells, CD25(+) regulatory T cells (T-reg), can regulate peripheral self tolerance and possess the ability to suppress antitumor responses. The authors report the ability to selectively deplete CD25(+) T-reg cells from patient leukapheresis samples using a clinical-grade, large-scale immunomagnetic system. Using leukapheresis samples containing up to 1.3 x 10(10) white blood cells, efficient depletion of T-reg cells was measured by flow cytometric analysis of CD25 expression and FOXP3 expression on post-depletion products. Remnant CD25(+) cells could not be detected in CD25-depleted products after short-term culture in IL-2 or enriched following secondary immunomagnetic selection for CD25(+) cells, confirming that efficient depletion had occurred. In parallel to efficient enrichment of CD25(-) cells, immumomagnetic selection resulted in the recovery of T-reg cells, since CD25(+) lymphocytes removed during depletion were primarily composed of CD4(+) T cells that expressed high levels of FOXP3 and possessed suppressive activity against autologous TCR-stimulated CD4(+) CD25- T cells in vitro. These results show that selective separation of functional CD25(+) T-reg cells from large-scale samples can be performed in large scale under clinical-grade conditions with sufficient selection, recovery, viability, ability to expand, and function for potential use in adoptive immunotherapy. C1 NCI, Clin Res Ctr, Surg Branch, NIH, Bethesda, MD 20892 USA. RP Rosenberg, SA (reprint author), NCI, Clin Res Ctr, Surg Branch, NIH, Room 3W-3940,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM sar@nih.gov FU NCI NIH HHS [Z01 SC003811-31] NR 45 TC 33 Z9 33 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD JUL-AUG PY 2005 VL 28 IS 4 BP 403 EP 411 DI 10.1097/01.cji.0000170363.22585.5a PG 9 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 941MP UT WOS:000230219200017 PM 16000960 ER PT J AU Bhatti, S Vilenski, L Tight, R Smego, RA AF Bhatti, S Vilenski, L Tight, R Smego, RA TI Histoplasma endocarditis: clinical and mycologic features and outcomes SO JOURNAL OF INFECTION LA English DT Article; Proceedings Paper CT 41st Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 09-12, 2003 CL San Diego, CA SP Infect Dis Soc Amer DE infective endocarditis; Histoplasma capsulatum; Histoplasma endocarditis ID PROSTHETIC VALVE ENDOCARDITIS; AMPHOTERICIN B THERAPY; CAPSULATUM ENDOCARDITIS; VEGETATIVE ENDOCARDITIS; FUNGAL ENDOCARDITIS; FLUCONAZOLE; INFECTIONS; DIAGNOSIS; SURGERY; TISSUE AB Objectives. To define the salient clinical and microbiotogic characteristics and outcome of infective endocarditis caused by Histoplasma capsulatum. Methods. Case report and review of 43 literature cases. Results. Infection involved both native (36 cases) and prosthetic (7) heart valves, had a high rate of systemic embotization (58%), and a more delayed diagnosis than bacterial endocarditis. Cardiac involvement generally occurred on mitral and/or aortic valves, and almost always in the setting of disseminated disease. Antemortem diagnosis was best made by serology (serum antibody titers or urinary antigen) or culture of blood (positive in < 20% of cases), bone marrow, excised valves, and other non-blood specimens. Other diagnostic methods included histopathology and immunofluorescent staining of tissue samples. Untreated infection was uniformly fatal. Prolonged antifungal. therapy with amphotericin B, without surgical intervention, appeared more effective than for Candida endocarditis. Conclusions. Histoplasma endocarditis is an infrequent but important cause of left-sided, blood culture-negative endocarditis. Its true prevalence may be underestimated because of the relative difficulty in making a precise microbiologic diagnosis. Amphotericin B therapy appears more effective than for Candida endocarditis, white the rote for azole treatment and secondary prophylaxis remains uncertain. Indications for surgical valve replacement are similar to those for bacterial. endocarditis. (c) 2004 The British Infection Society. Published by Elsevier Ltd. All. rights reserved. C1 Univ N Dakota, Dept Med, Fargo, ND USA. Aga Khan Univ, Coll Med, Dept Med, Karachi, Pakistan. RP Smego, RA (reprint author), NIAID, TB Res Sect, Immunogenet Lab, NIH, Twinbrook 2,Room 236,MSC 8180,12441 Parklawn Dr, Rockville, MD 20852 USA. EM rsmego@niaid.nih.gov NR 44 TC 16 Z9 18 U1 0 U2 4 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 0163-4453 J9 J INFECTION JI J. Infect. PD JUL PY 2005 VL 51 IS 1 BP 2 EP 9 DI 10.1016/j.jinf.2004.10.002 PG 8 WC Infectious Diseases SC Infectious Diseases GA 947AC UT WOS:000230613400002 PM 15979483 ER PT J AU Flys, T Nissley, DV Claasen, CW Jones, D Shi, CJ Guay, LA Musoke, P Mmiro, F Strathern, JN Jackson, JB Eshleman, JR Eshleman, SH AF Flys, T Nissley, DV Claasen, CW Jones, D Shi, CJ Guay, LA Musoke, P Mmiro, F Strathern, JN Jackson, JB Eshleman, JR Eshleman, SH TI Sensitive drug-resistance assays reveal long-term persistence of HIV-1 variants with the K103N Nevirapine (NVP) resistance mutation in some women and infants after the administration of single-dose NVP: HIVNET 012 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID ANTIRETROVIRAL THERAPY; TRANSMISSION; INTRAPARTUM AB Background. The HIV Network for Prevention Trials (HIVNET) 012 trial showed that NVP resistance (NVPR) emerged in some women and children after the administration of single-dose nevirapine (SD-NVP). We tested whether K103N-containing human immunodeficiency virus (HIV)-1 variants persisted in women and infants 1 year or more after the administration of SD-NVP. Methods. We analyzed samples from 9 women and 5 infants in HIVNET 012 who had NVPR 6-8 weeks after the administration of SD-NVP. Samples were analyzed with the ViroSeq system and with 2 sensitive resistance assays, LigAmp and TyHRT. Results. ViroSeq detected the K103N mutation in 8 of 9 women and in 2 of 5 infants. LigAmp detected the K103N mutation at low levels in 8 of 9 women and in 4 of 5 infants. K103N was not detected by ViroSeq 12 24 months after the administration of SD-NVP but was detected by LigAmp in 3 of 9 women and in 1 of 5 infants. K103N was also detected in those samples by use of the TyHRT assay. Conclusions. K103N-containing variants persist in some women and infants for 1 year or more after the administration of SD-NVP. Sensitive resistance assays may provide new insight into the impact of antiretroviral drug exposure on HIV-1 evolution. C1 Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Sci Applicat Int Corp, Gene Regulat & Chromosome Biol Lab, Reverse Transcript & Mol Biol Sect, Basic Res Program, Frederick, MD USA. NCI, Frederick, MD 21701 USA. Makerere Univ, Dept Paediat, Kampala, Uganda. Makerere Univ, Dept Obstet & Gynaecol, Kampala, Uganda. RP Eshleman, SH (reprint author), Johns Hopkins Med Inst, Dept Pathol, Ross Bldg 646,720 Rutland Ave, Baltimore, MD 21205 USA. EM seshlem@jhmi.edu FU NCI NIH HHS [N01-CO-12400]; NIAID NIH HHS [U01-AI-38858, N01-AI-35173, N01-AI-45200, N0I-AI-35173-417, U01-AI-46745, U01-AI-48054]; NICHD NIH HHS [R01-HD042965-01] NR 16 TC 142 Z9 147 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 1 PY 2005 VL 192 IS 1 BP 24 EP 29 DI 10.1086/430742 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 935PX UT WOS:000229795300006 PM 15942890 ER PT J AU Grivel, JC Garcia, M Moss, WJ Margolis, LB AF Grivel, JC Garcia, M Moss, WJ Margolis, LB TI Inhibition of HIV-1 replication in human lymphoid tissues ex vivo by measles virus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID CXCR4-TROPIC HIV-1; INFECTION; SUPPRESSION; MIP-1-ALPHA; MIP-1-BETA; RANTES; AIDS; LOAD AB Human immunodeficiency virus (HIV) type 1 replication and disease progression are enhanced by various pathogens in coinfected individuals. However, acute infection with measles virus (MV) has been found to suppress HIV-1 replication in coinfected children. We investigated the mechanisms of this phenomenon using human lymphoid tissues coinfected ex vivo with HIV-1 and MV. MV inhibited both CXCR4-tropic (X4) and CCR5-tropic (R5) HIV-1, but the inhibitory effect was particularly profound for R5 virus, which transmits infection and dominates the early stages of HIV-1 disease. MV inhibits the replication of R5 HIV-1 in coinfected tissues by up-regulation of the CC chemokine RANTES, a well-known inhibitor of R5 HIV-1 infection, and this up-regulation is augmented in tissues coinfected with R5 HIV-1. Deciphering the molecular mechanisms by which MV and other pathogens alter local cytokine/chemokine networks and cause tissue microenvironments to become detrimental to HIV-1 may significantly contribute to the development of effective anti-HIV therapies. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Immunol, Baltimore, MD 21205 USA. NICHHD, Mol & Cellular Biophys Lab, Bethesda, MD 20892 USA. RP Margolis, LB (reprint author), NIH, Bldg 10,Rm 9D58,10 Ctr Dr, Bethesda, MD 20892 USA. EM margolis@helix.nih.gov NR 17 TC 26 Z9 26 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 1 PY 2005 VL 192 IS 1 BP 71 EP 78 DI 10.1086/430743 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 935PX UT WOS:000229795300012 PM 15942896 ER PT J AU Tsenova, L Ellison, E Harbacheuski, R Moreira, AL Kurepina, N Reed, MB Mathema, B Barry, CE Kaplan, G AF Tsenova, L Ellison, E Harbacheuski, R Moreira, AL Kurepina, N Reed, MB Mathema, B Barry, CE Kaplan, G TI Virulence of selected Mycobacterium tuberculosis clinical isolates in the rabbit model of meningitis is dependent on phenolic glycolipid produced by the bacilli SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Keystone Symposia on Tuberculosis - Integrating Host and Pathogen Biology CY JAN 25-30, 2003 CL Taos, NM ID CENTRAL-NERVOUS-SYSTEM; NECROSIS-FACTOR-ALPHA; PROTECTIVE IMMUNE-RESPONSE; AUTOIMMUNE ENCEPHALOMYELITIS; MONOCYTE ACTIVATION; NITRIC-OXIDE; STRAINS; PATHOGENESIS; COMPLEX; BIOSYNTHESIS AB Infection with Mycobacterium tuberculosis in humans results in active disease in similar to 10% of immune-competent individuals, with the most-severe clinical manifestations observed when the bacilli infect the central nervous system (CNS). Here, we use a rabbit model of tuberculous meningitis to evaluate the severity of disease caused by the M. tuberculosis clinical isolates CDC1551, a highly immunogenic strain, and HN878 or W4, 2 members of the W/Beijing family of strains. Compared with infection with CDC1551, CNS infection with HN878 or W4 resulted in higher bacillary loads in the cerebrospinal fluid and brain, increased dissemination of bacilli to other organs, persistent levels of tumor necrosis factor-a, higher leukocytosis, and more-severe clinical manifestations. This pathogenic process is associated with the production by HN878 of a polyketide synthase derived phenolic glycolipid (PGL), as demonstrated by reduced virulence in rabbits infected with an HN878 mutant disrupted in the pks1-15 gene, which is required for PGL synthesis. C1 Publ Hlth Res Inst, Lab Mycobacterial Immun & Pathogenesis, Newark, NJ 07103 USA. Publ Hlth Res Inst, TB Ctr, Newark, NJ 07103 USA. NYU Med Ctr, Dept Pathol, New York, NY 10016 USA. NIAID, TB Res Sect, NIH, Rockville, MD USA. RP Kaplan, G (reprint author), Publ Hlth Res Inst, Lab Mycobacterial Immun & Pathogenesis, 225 Warren St, Newark, NJ 07103 USA. EM kaplan@phri.org RI Barry, III, Clifton/H-3839-2012; OI waluyo, imam/0000-0002-1813-9487 FU Intramural NIH HHS [Z01 AI000734-12]; NIAID NIH HHS [AI 054338] NR 46 TC 146 Z9 156 U1 1 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 1 PY 2005 VL 192 IS 1 BP 98 EP 106 DI 10.1086/430614 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 935PX UT WOS:000229795300015 PM 15942899 ER PT J AU Tock, CL Turner, LR Batra, P Coelho, S Miller, SA Beer, J Radonovich, M Brady, JN Turner, ML Vogel, JC AF Tock, CL Turner, LR Batra, P Coelho, S Miller, SA Beer, J Radonovich, M Brady, JN Turner, ML Vogel, JC TI Transcriptonal profiling of the epidermal response to ultraviolet radiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. US FDA, CDRH, OST, Rockville, MD USA. Core Microarray Facil, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUL PY 2005 VL 125 IS 1 MA 933 BP A5 EP A5 PG 1 WC Dermatology SC Dermatology GA 943GR UT WOS:000230342000052 ER PT J AU Berch, DB AF Berch, DB TI Making sense of number sense: Implications for children with mathematical disabilities SO JOURNAL OF LEARNING DISABILITIES LA English DT Article ID ARITHMETICAL COGNITION; NUMERICAL INEQUALITY; INSTRUCTION; JUDGMENTS; STUDENTS; DEFICITS; DOMAIN; LINE AB Drawing on various approaches to the study of mathematics learning, Gersten, Jordan, and Flojo (in this issue) explore the implications of this research for identifying children at risk for developing mathematical disabilities. One of the key topics Gersten et al. consider in their review is that of "number sense." I expand on their preliminary effort by examining in detail the diverse set of components purported to be encompassed by this construct. My analysis reveals some major differences between the ways in which number sense is defined in the mathematical cognition literature and its definition in the literature in mathematics education. I also present recent empirical evidence and theoretical perspectives bearing on the importance of measuring the speed of making magnitude comparisons. Finally, I discuss how differing conceptions of number sense inform the issue of whether and to what extent it may be teachable. C1 NICHHD, Child Dev & Behav Branch, NIH, Math & Sci Cognit & Learning Program, Bethesda, MD 20892 USA. RP Berch, DB (reprint author), NICHHD, Child Dev & Behav Branch, NIH, Math & Sci Cognit & Learning Program, 6100 Execut Blvd,Room 4B05, Bethesda, MD 20892 USA. EM berchd2@mail.nih.gov NR 53 TC 116 Z9 120 U1 2 U2 25 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0022-2194 J9 J LEARN DISABIL-US JI J. Learn. Disabil. PD JUL-AUG PY 2005 VL 38 IS 4 BP 333 EP 339 DI 10.1177/00222194050380040901 PG 7 WC Education, Special; Rehabilitation SC Education & Educational Research; Rehabilitation GA 946KR UT WOS:000230571500008 PM 16122065 ER PT J AU Chen, X Oppenheim, JJ Howard, OMZ AF Chen, X Oppenheim, JJ Howard, OMZ TI BALB/c mice have more CD4(+)CD25(+) T regulatory cells and show greater susceptibility to suppression of their CD4(+)CD25(-) responder T cells than C57BL/6 mice SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE rodent; T lymphocytes; tolerance/suppression/anergy ID IMMUNOLOGICAL SELF-TOLERANCE; TOLEROGENIC DENDRITIC CELLS; AUTOIMMUNE-DISEASES; IMMUNE-RESPONSES; LEISHMANIA-MAJOR; IN-VITRO; RECEPTOR; ACTIVATION; INFECTION; STRAINS AB Increasing evidence indicates that CD4(+)CD25(+) T regulatory (Treg) cells control a wide spectrum of immune responses. The initial identification of CD4(+)CD25(+) Treg cell as a "professional suppressor" was based on observations made in BALB/c mice. This mouse strain is well known to preferentially develop T helper cell type 2 responses, to he more susceptible to intracellular parasite infection, to have a higher tumor incidence, and to be more resistant to the induction of autoimmune diseases, as compared with C57BL/6 (116) mice. We therefore decided to compare Treg cell function of B6 and BALB/c mice. We observed that the frequency of CD4(+)CD25(+) T cells in the thymus and peripheral lymphoid organs of BALB/c mice was higher than in B6 mice. CD4(+)CD25(+) Treg cells from both mouse strains shared similar phenotypic properties, including expression of characteristic immunological markers and hyporesponsiveness to T cell receptor cross-linking and in their capacity to suppress proliferation of BAILB/c CD4(+)CD25(-) T responder (Tres) cells. However, CD4(+)CD25(-) Tres cells from B6 mice were notably less susceptible to suppression by CD4(+)CD25(+) Treg cells from either mouse strain. Our data suggest that the number and the level of suppression of CD4(+)CD25(+) Treg cells for CD4(+)CD25(-) Tres cells may be dictated by genetic background. Our data also suggest that differences in the CD4(+)CD25(+) Treg cell number and the susceptibility of CD4(+)CD25(-) Tres cells may, at least in part, account for the differences in immune response between B6 and BALB/c strains of mice. C1 SAIC Frederick Inc, Basic Res Program, Ft Detrick, MD 21702 USA. NCI, Mol Immunoregulat Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Chen, X (reprint author), SAIC Frederick Inc, Basic Res Program, POB B,Bldg 560,Rm 31-19, Ft Detrick, MD 21702 USA. EM xinc@ncifcrf.gov RI Howard, O M Zack/B-6117-2012; Chen, Xin/I-6601-2015 OI Howard, O M Zack/0000-0002-0505-7052; Chen, Xin/0000-0002-2628-4027 FU PHS HHS [N01-C0-12400] NR 48 TC 67 Z9 71 U1 1 U2 4 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 JUL PY 2005 VL 78 IS 1 BP 114 EP 121 DI 10.1189/jlb.0604341 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 942OI UT WOS:000230291300015 PM 15845645 ER PT J AU Kim, MP Zhou, M Wahl, LM AF Kim, MP Zhou, M Wahl, LM TI Angiotensin II increases human monocyte matrix metalloproteinase-1 through the AT(2) receptor and prostaglandin E-2: implications for atherosclerotic plaque rupture SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE angiotensin II receptor subtype 2; inflammation; cytokines ID CHLAMYDIA-PNEUMONIAE; DIFFERENTIAL REGULATION; MYOCARDIAL-INFARCTION; CORONARY-ARTERIES; CYTOKINES; LESIONS; ACTIVATION; EXPRESSION; MIGRATION; ALPHA AB Angiotensin II (Ang II)-mediated hypertension increases the risk for acute coronary syndrome, a consequence of atherosclerotic plaque rupture, which may be caused by matrix metalloproteinases (MMPs). Here, we show that human primary monocytes stimulated with tumor necrosis factor alpha (TNF-alpha) and granulocyte macrophage-colony stimulating factor (GM-CSF) release Ang II, which is an integral component of the signal transduction pathway that leads to IVMP-1 production. An Ang II-mediated increase in MMP-1 synthesis occurred only in conjunction with cytokine stimulation. Moreover, Ang II mediated its effect through the Ang II type 2 (AT(2)) receptor, as demonstrated by enhancement of MMP-1 production by an AT2 agonist, CGP-42112A, and inhibition of MMP-1 production by PD1233319, an AT(2) antagonist. Additionally, exogenons Ang II caused a significant enhancement in MMP-1 production by cytokine-stimulated monocytes, and the most effective enhancement occurrred when Ang II was added 6 h after stimulation. Furtherinore, Ang II and the AT(2) agonist increased prostaglandin E-2 (PGE(2)), which in turn mediated the increase in MMP-1, as shown by the inhibition of MMP-1 by indomethacin or aspirin. In contrast, the AT(2) antagonist inhibited the PGE(2) production induced by TNF-alpha and GM-CSF. Ang II, through its interaction with the AT(2) receptor, has a central role in mediating the PGE(2)-dependent production of MMP-1 by monocytes stimulated with TNF-alpha and GM-CSF. These observations provide insight into the association between hypertension and acute coronary syndrome and a possible mechanism by which Ang-converting enzyme inhibitor and aspirin may reduce the risk for heart attacks. C1 NIH, Immunopathol Sect, Natl Inst Dent & Craniofacial Res, Bethesda, MD 20892 USA. Natl Inst Hlth Res Scholar, Howard Hughes Med Inst, Bethesda, MD USA. RP Wahl, LM (reprint author), NIH, Immunopathol Sect, Natl Inst Dent & Craniofacial Res, 30 Convent Dr,Bldg 30,Room 325, Bethesda, MD 20892 USA. EM lwahl@dir.nidcr.nih.gov NR 31 TC 46 Z9 49 U1 0 U2 2 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 JUL PY 2005 VL 78 IS 1 BP 195 EP 201 DI 10.1189/jlb.1204715 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 942OI UT WOS:000230291300023 PM 15817699 ER PT J AU Lu, YB Wahl, LM AF Lu, YB Wahl, LM TI Production of matrix metalloproteinase-9 by activated human monocytes involves a phosphatidylinositol-3 kinase/Akt/IKK alpha/NF-kappa B pathway SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE lipopolysaccharide; pleckstrin homology; PIP3 ID MATRIX METALLOPROTEINASES; DIFFERENTIAL REGULATION; SIGNALING PATHWAYS; KINASE-B; EXPRESSION; CELLS; AKT; UBIQUITINATION; MECHANISMS; SYSTEM AB Matrix metalloproteinase-9 (MMP-9) is considered to be an important component in the progression of inflammation. Monocytes/macrophages are prominent at inflammation sites, and activation of these cells by stimulants, such as hpopolysaccharide (LPS) or tumor necrosis factor alpha and granulocyte macrophage-colony stimulating factor, leads to the production of significant amounts of MMP-9. Here, we show that LPS stimulation of monocytes results in MMP-9 production through a phosphatidyhnositol-3 kinase (PI-3K)/ Akt/inhibitor Of kappa B (I kappa B) kinase-a (IKK alpha)/nuclear factor (NF)-kappa B pathway. This new role for Akt in signaling leading to MMP-9 production was demonstrated by inhibitor and immunoprecipitation studies. LY294002 or wortmannin, inhibitors of P1-3K, suppressed LPS-induced Akt activity and MMP-9 production. Evidence for the participation of Akt in monocyte MMP-9 synthesis was demonstrated by the inhibition of MMP-9 by SH-5, a specific inhibitor of Akt. The mechanism by which Akt regulates MMP-9 is through the activation of NF-kappa B, as shown by coinunnnoprecipitation of the phosphorylated form of IKK alpha and Akt as well as the SH-5 suppression of the dissociation Of I kappa B from NF-kappa B and the activation of NF-kappa B p65. The role of NF-kappa B in regulation of MMP-9 was demonstrated further by the inhibition of MMP-9 production by proteasome inhibitors, lactacystin and MG-132, which prevented the ubiquitination and dissociation of I kappa B from NF kappa-B. This is the first demonstration that Akt is involved in the signaling pathway leading to the production of monocyte MMP-9 and provides an additional approach in the regulation of this enzyme in human primary monocytes. C1 NIDCR, Immunopathol Sect, NIH, Bethesda, MD 20892 USA. RP Wahl, LM (reprint author), NIDCR, Immunopathol Sect, NIH, 30 Convent Dr,Bldg 30,Room 3A-300, Bethesda, MD 20892 USA. EM lwahl@dir.nider.nih.gov NR 28 TC 82 Z9 88 U1 0 U2 1 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 JUL PY 2005 VL 78 IS 1 BP 259 EP 265 DI 10.1189/jlb.0904498 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 942OI UT WOS:000230291300030 PM 15800029 ER PT J AU Bujold, E Romero, R Chaiworapongsa, T Kim, YM Kim, GJ Kim, MR Espinoza, J Goncalves, LF Edwin, S Mazor, M AF Bujold, E Romero, R Chaiworapongsa, T Kim, YM Kim, GJ Kim, MR Espinoza, J Goncalves, LF Edwin, S Mazor, M TI Evidence supporting that the excess of the sVEGFR-1 concentration in maternal plasma in preeclampsia has a uterine origin SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE preeclampsia; soluble vascular endothelial growth factor receptor-1(sVEGFR-1); placental growth factor (PlGF); uterine vein; angiogenesis ID ENDOTHELIAL GROWTH-FACTOR; HUMAN EXTRAVILLOUS TROPHOBLAST; RENIN-ANGIOTENSIN SYSTEM; NITRIC-OXIDE; PLACENTAL GROWTH; FETAL-GROWTH; GESTATIONAL HYPERTENSION; PERIPHERAL CIRCULATIONS; FLK-1/KDR ACTIVATION; SIGNAL-TRANSDUCTION AB Background. Preeclampsia has been considered an anti-angiogenic state. Two factors have been implicated in the genesis of this state: soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and placental growth factor (PlGF). Indeed, the concentrations of PlGF, an angiogenic factor, are lower in preeclampsia than in normal pregnancy, while the opposite is the case for the anti-angiogenic factor, sVEGFR-1. The source of the excess sVEGFR-1 has not yet been determined. Since the placenta could be a source of sVEGFR-1, we conducted a study to determine whether there is a gradient in the plasma concentration of sVEGFR-1 and PlGF between the uterine vein and the antecubital vein in both patients with preeclampsia and normal pregnant women. Methods. A cross-sectional study was performed to determine the plasma concentrations of sVEGFR-1 and PlGF in the uterine and antecubital vein of patients with preeclampsia (n = 9) and normal pregnant women at term (n = 9). Plasma samples were collected from antecubital and uterine veins at the time of cesarean section. The concentrations of sVEGFR-1 and PlGF were determined using specific enzyme-linked immunoassays. The differences of plasma concentrations of sVEGFR-1 and PlGF between uterine and antecubital veins in both groups were compared by paired t-tests. Results. Patients with preeclampsia had a significantly higher mean plasma concentration of sVEGFR-1 in the uterine vein than in the antecubital vein (uterine vein: mean 13,675 +/- 5,684 pg/ml vs. antecubital vein: mean 10,234 +/- 4,700 pg/ml; paired t-tests, p = 0.04). In contrast, among normal pregnant women at term, there was no significant difference in plasma concentrations of sVEGFR-1 between the uterine and antecubital veins (uterine vein: mean 1,918 +/- 665 pg/ml vs. antecubital vein: mean 1,750 +/- 475 pg/ml; paired t-tests, p = 0.1). The mean plasma concentration of sVEGFR-1, either in the antecubital or uterine vein, was significantly higher in preeclampsia than in normal pregnancy (unpaired t-tests; both p < 0.001). There was no significant difference in the mean plasma concentration of PlGF between the uterine and the antecubital veins in both the preeclamptic ( uterine vein, mean +/- SD: 129 +/- 106 pg/ml vs. antecubital vein, mean +/- SD: 82 +/- 43 pg/ml; paired t-tests, p = 0.2) and normal pregnancy groups ( uterine vein, mean +/- SD: 331 +/- 254 pg/ml vs. antecubital vein, mean +/- SD: 319 +/- 259 pg/ml; paired t-tests, p = 0.4). The mean plasma concentration of PlGF, either in the uterine or antecubital vein, was lower in preeclampsia than in normal pregnancy ( unpaired t-tests; p = 0.008 and 0.02 respectively). Conclusions. Plasma concentration of sVEGFR-1 was higher in the uterine vein than in the antecubital vein in women with preeclampsia. This provides evidence supporting the concept that the uterus is a potential source of the excess circulating sVEGFR-1 concentration in preeclamptic women. C1 Wayne State Univ, Hutzel Womens Hosp, Dept Obstet & Gynecol, Detroit, MI USA. NICHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD USA. Wayne State Univ, Hutzel Womens Hosp, Dept Pathol, Detroit, MI USA. Ben Gurion Univ Negev, Soroka Med Ctr, Dept Obstet & Gynecol, IL-84105 Beer Sheva, Israel. RP Romero, R (reprint author), Wayne State Univ, Hutzel Womens Hosp, NICHD, Perinatol Res Branch, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov NR 85 TC 56 Z9 57 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 JUL PY 2005 VL 18 IS 1 BP 9 EP 16 DI 10.1080/14767050500202493 PG 8 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 962FR UT WOS:000231716900002 PM 16105786 ER PT J AU Gomez, R Romero, R Nien, JK Medina, L Carstens, M Kim, YM Chaiworapongsa, T Espinoza, J Gonzalez, R AF Gomez, R Romero, R Nien, JK Medina, L Carstens, M Kim, YM Chaiworapongsa, T Espinoza, J Gonzalez, R TI Idiopathic vaginal bleeding during pregnancy as the only clinical manifestation of intrauterine infection SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE intraamniotic infection; chorioamnionitis; vaginal bleeding; preterm premature rupture of membranes; premature birth ID PRETERM PREMATURE RUPTURE; POLYMERASE-CHAIN-REACTION; TUMOR-NECROSIS-FACTOR; AMNIOTIC-FLUID; INTRAAMNIOTIC INFECTION; UREAPLASMA-UREALYTICUM; MICROBIAL INVASION; FETAL MEMBRANES; ABRUPTIO PLACENTAE; INTACT MEMBRANES AB Objective. To determine the frequency and clinical significance of microbial invasion of the amniotic cavity (MIAC) in patients with vaginal bleeding in the absence of placenta previa, preterm labor or preterm premature rupture of membranes (PROM). Study design. This retrospective cohort study included patients who presented with vaginal bleeding between 18 and 35 weeks, and underwent an amniocentesis shortly after admission for the assessment of the microbiologic status of the amniotic cavity and/or fetal lung maturity. Amniotic fluid was cultured for aerobic and anaerobic bacteria, as well as genital mycoplasmas. Patients presenting with preterm labor, preterm PROM, placenta previa, overt placental abruption, and an intrauterine device in situ were excluded, as well as those with local cervical bleeding. MIAC was defined as a positive amniotic fluid culture. Analysis was conducted with non-parametric statistics. Results. One hundred and fourteen patients met the entry criteria. MIAC was detected in 14% of cases (16/114). Patients with vaginal bleeding and a gestational age 528 weeks at the time of amniocentesis had a significantly higher frequency of MIAC than those with a gestational age 528 weeks [25% (13/52) vs. 4.8% (3/62), respectively; p < 0.01]. Ureaplasma urealyticum was the microorganism most frequently isolated from the amniotic fluid. Except for one case admitted at 33 weeks, all patients with MIAC had an early preterm delivery 432 weeks. Patients with vaginal bleeding and MIAC had a shorter procedure-to-delivery interval than those without MIAC [MIAC, median survival 19 days (95% CI 10-27 days) vs. no MIAC, median survival 50 days (95% CI 37-62 days); p < 0.0001]. Patients with vaginal bleeding and MIAC had a significantly lower gestational age at delivery and lower birth weight than those with vaginal bleeding and negative amniotic fluid cultures (for gestational age, median 25 weeks, range 21-33 weeks vs. median 37 weeks, range 19-42 weeks, respectively; p < 0.01, and for birth weight, median 750 grams, range 520-1820 grams vs. 2800 grams, range 520 4880 grams, respectively; p < 0.01), as well as a higher frequency of subsequent preterm PROM [81.3% (13/16) vs. 9.2% (9/98); p < 0.01]. Conclusions. MIAC was detected in 14% of patients with 'idiopathic' vaginal bleeding and was associated with subsequent preterm PROM and early preterm delivery. Vaginal bleeding may be the only clinical manifestation of MIAC, and it predisposes to adverse outcome. C1 Pontificia Univ Catolica Chile, Sotero del Rio Hosp, CEDIP, Puente Alto, Chile. NICHHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. NICHHD, Perinatol Res Branch, NIH, DHHS, Detroit, MI USA. Wayne State Univ, Sch Med, Dept Obstet & Gynecol, Detroit, MI 48201 USA. Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. RP Romero, R (reprint author), NICHD, Perinatol Res Branch, NIH, DHHS, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.nih.gov NR 54 TC 52 Z9 56 U1 0 U2 1 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 JUL PY 2005 VL 18 IS 1 BP 31 EP 37 DI 10.1080/14767050500217863 PG 7 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 962FR UT WOS:000231716900005 PM 16105789 ER PT J AU Grimm, D Tilly, K Bueschel, DM Fisher, MA Policastro, PF Gherardini, FC Schwan, TG Rosa, PA AF Grimm, D Tilly, K Bueschel, DM Fisher, MA Policastro, PF Gherardini, FC Schwan, TG Rosa, PA TI Defining plasmids required by Borrelia burgdorferi for colonization of tick vector Ixodes scapularis (Acari : Ixodidae) SO JOURNAL OF MEDICAL ENTOMOLOGY LA English DT Article DE Lyme disease; vector-borne; spirochete; lp25; lp28-1 ID LYME-DISEASE SPIROCHETE; OUTER-SURFACE PROTEIN; GENE-EXPRESSION; LINEAR PLASMIDS; EXPERIMENTAL-INFECTION; STRAIN B31; VLSE; SEQUENCE; GENOME; AGENT AB Maintenance in nature of Borrelia burgdorferi, the pathogenic bacterium that causes Lyme disease, requires transmission through an infectious cycle that includes a tick vector and a mammalian host. The genetic requirements for persistence in these disparate environments have not been well defined. B. burgdorferi has a complex genome composed of a chromosome and > 20 plasmids. Previous work has demonstrated that B. burgdorferi requires two plasmids, 1p25 and 1p28-1, in the mammalian host. To investigate the requirement for these same two plasmids during tick infection, we experimentally infected larval ticks with B. burgdorferi lacking either 1p25 or 1p28-1 and then assessed the spirochete load in ticks at different points of the infection. Whereas plasmid 1p28-1 was dispensable in ticks, plasmid 1p25 was essential for tick infection. Furthermore, we investigated the requirement in ticks for the 1p25 gene bbe22, which encodes a nicotinamidase that is necessary and sufficient for mammalian infection by B. burgdorferi clones lacking 1p25. This gene was also sufficient in ticks to restore survival of spirochetes lacking 1p25. This is the first study to investigate the requirement for specific plasmids by B. burgdorferi within the tick vector, and it begins to establish the genomic components required for persistence of this pathogen throughout its natural infectious cycle. C1 NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, Hamilton, MT 59804 USA. RP Rosa, PA (reprint author), NIAID, Lab Human Bacterial Pathogenesis, Rocky Mt Labs, NIH, 903 S 4th St, Hamilton, MT 59804 USA. EM prosa@niaid.nih.gov NR 52 TC 33 Z9 33 U1 2 U2 2 PU ENTOMOL SOC AMER PI LANHAM PA 9301 ANNAPOLIS RD, LANHAM, MD 20706 USA SN 0022-2585 J9 J MED ENTOMOL JI J. Med. Entomol. PD JUL PY 2005 VL 42 IS 4 BP 676 EP 684 DI 10.1603/0022-2585(2005)042[0676:DPRBBB]2.0.CO;2 PG 9 WC Entomology; Veterinary Sciences SC Entomology; Veterinary Sciences GA 944DR UT WOS:000230406400023 PM 16119559 ER PT J AU Baser, ME Kuramoto, L Woods, R Joe, H Friedman, JM Wallace, AJ Ramsden, RT Olschwang, S Bijlsma, E Kalamarides, M Papi, L Kato, R Carroll, J Lazaro, C Joncourt, F Parry, DM Rouleau, GA Evans, DGR AF Baser, ME Kuramoto, L Woods, R Joe, H Friedman, JM Wallace, AJ Ramsden, RT Olschwang, S Bijlsma, E Kalamarides, M Papi, L Kato, R Carroll, J Lazaro, C Joncourt, F Parry, DM Rouleau, GA Evans, DGR TI The location of constitutional neurofibromatosis 2 (NF2) splice site mutations is associated with the severity of NF2 SO JOURNAL OF MEDICAL GENETICS LA English DT Review ID FAMILIAL ADENOMATOUS POLYPOSIS; GERM-LINE MUTATIONS; GENOTYPE-PHENOTYPE CORRELATIONS; TYPE-2 NEUROFIBROMATOSIS; VESTIBULAR SCHWANNOMAS; TUMOR-SUPPRESSOR; APC GENE; MISSENSE MUTATIONS; SOMATIC MOSAICISM; DISEASE AB Neurofibromatosis 2 ( NF2) patients with constitutional splice site NF2 mutations have greater variability in disease severity than NF2 patients with other types of mutations; the cause of this variability is unknown. We evaluated genotype-phenotype correlations, with particular focus on the location of splice site mutations, using mutation and clinical information on 831 patients from 528 NF2 families with identified constitutional NF2 mutations. The clinical characteristics examined were age at onset of symptoms of NF2 and number of intracranial meningiomas, which are the primary indices of the severity of NF2. Two regression models were used to analyse genotype-phenotype correlations. People with splice site mutations in exons 1 - 5 had more severe disease than those with splice site mutations in exons 11 - 15. This result is compatible with studies showing that exons 2 and 3 are required for self-association of the amino terminal of the NF2 protein in vitro, and that deletions of exons 2 and 3 in transgenic and knockout mouse models of NF2 cause a high prevalence of Schwann cell derived tumours. C1 Univ British Columbia, Dept Stat, Vancouver, BC V6T 1W5, Canada. Univ British Columbia, Dept Med Genet, Vancouver, BC, Canada. St Marys Hosp, Univ Dept Med Genet, Manchester M13 0JH, Lancs, England. Manchester Royal Infirm, Dept Otolaryngol, Manchester M13 9WL, Lancs, England. Fdn Jean Dausset, CEPH, INSERM, U434, Paris, France. Leiden Univ, Med Ctr, Dept Clin Genet, Leiden, Netherlands. Univ Hosp Beaujon, Dept Neurosurg, Clichy, France. Univ Florence, Dept Clin Physiopathol, Florence, Italy. Higashisaitama Natl Hosp, Dept Pediat, Saitama, Japan. Inst Med & Vet Sci, Div Mol Pathol, Adelaide, SA 5000, Australia. Ctr Genet Med & Mol, IRO, Barcelona, Spain. Childrens Univ Hosp, Div Human Genet, Bern, Switzerland. NCI, Genet Epidemiol Branch, Bethesda, MD 20892 USA. McGill Univ, Dept Neurol, Montreal, PQ H3A 2T5, Canada. RP Baser, ME (reprint author), 10622 Kinnard Ave,203, Los Angeles, CA 90024 USA. EM michael.baser@verizon.net RI Olschwang, Sylviane/G-2716-2013; OI Papi, Laura/0000-0003-4552-9517; Evans, Gareth/0000-0002-8482-5784 NR 54 TC 38 Z9 42 U1 0 U2 1 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 JUL PY 2005 VL 42 IS 7 BP 540 EP 546 DI 10.1136/jmg.2004.029504 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 941SZ UT WOS:000230235800002 PM 15994874 ER PT J AU Ivanova, A Liao, SY Lerman, MI Ivanov, S Stanbridge, EJ AF Ivanova, A Liao, SY Lerman, MI Ivanov, S Stanbridge, EJ TI STRA13 expression and subcellular localisation in normal and tumour tissues: implications for use as a diagnostic and differentiation marker SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID TRANSMEMBRANE CARBONIC-ANHYDRASES; FACTOR DEC1 STRA13; CELL LUNG-CANCER; MN ANTIGEN; HYPOXIA; TRANSCRIPTION; PROTEIN; CARCINOMA; OVEREXPRESSION; SUPPRESSOR AB Background: STRA13 is a bHLH transcription factor that plays a crucial role in cell differentiation, proliferation, apoptosis, and response to hypoxia. Objective: To assess STRA13 involvement in carcinogenesis and evaluate its diagnostic value. Methods: A comprehensive analysis was undertaken of the endogenous protein expression in 389 normal and corresponding malignant specimens, using newly generated polyclonal antibodies. Results: STRA13 was commonly expressed in epithelial cells of normal and neoplastic tissues where it was confined mostly to the nucleus. Intense cytoplasmic STRA13 immunoreactivity was characteristic of myoepithelial and differentiated squamous epithelial cells of all organ sites and their neoplastic counterparts, suggesting application of STRA13 as a myoepithelial cell marker. A distinctive apical granular cytoplasmic staining pattern observed in the pancreas and large intestine was retained in corresponding metastatic carcinomas, providing for identification of the primary sites of these disseminating tumours. In less differentiated tumours there was a tendency to lose the cytoplasmic staining or to switch to nuclear STRA13 staining. Analysis of STRA13, HIF-1 alpha, and CAIX expression patterns in a large set of various tumours substantiated the association of STRA13 with HIF-1 alpha expression and hypoxia in vivo. Investigation of the molecular mechanisms of STRA13 nucleo-cytoplasmic shuttling suggested that STRA13 employs nuclear import/export that utilises the NLS/NES motifs situated within the N-terminus and in the middle of the protein. Conclusions: STRA13 may serve as a marker for myoepithelial cells, for the degree of tumour differentiation, and for identification of the primary site of certain metastatic tumours. In combination with CAIX and CAXII markers, it may lead to a more accurate classification of all renal carcinomas. C1 NCI, Immunobiol Lab, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. Univ Calif Irvine, Sch Med, Dept Microbiol & Mol Genet, Irvine, CA 92717 USA. RP Ivanova, A (reprint author), NCI, Immunobiol Lab, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM ivanova@mail.ncifcrf.gov OI Ivanov, Sergey/0000-0001-9770-7237 FU NCI NIH HHS [N01-CO-56000] NR 28 TC 13 Z9 15 U1 0 U2 2 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 JUL PY 2005 VL 42 IS 7 BP 565 EP 576 DI 10.1136/jmg.2004.029835 PG 12 WC Genetics & Heredity SC Genetics & Heredity GA 941SZ UT WOS:000230235800006 PM 15994878 ER PT J AU Goldin, LR McMaster, ML Ter-Minassian, M Saddlemire, S Harmsen, B Lalonde, G Tucker, MA AF Goldin, LR McMaster, ML Ter-Minassian, M Saddlemire, S Harmsen, B Lalonde, G Tucker, MA TI A genome screen of families at high risk for Hodgkin lymphoma: evidence for a susceptibility gene on chromosome 4 SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID LINKAGE ANALYSIS; COMPLEX TRAITS; LOD SCORES; DISEASE; RELATIVES; CANCER; HLA; DISSECTION; MUTATIONS; PROGRAM C1 NCI, Genet Epidemiol Branch, DCEG, NIH, Bethesda, MD 20892 USA. Westat Res Inc, Rockville, MD USA. RP Goldin, LR (reprint author), NCI, Genet Epidemiol Branch, DCEG, NIH, 6120 Execut Blvd,7236 MSC, Bethesda, MD 20892 USA. EM goldinl@mail.nih.gov RI Tucker, Margaret/B-4297-2015 FU NCI NIH HHS [N02-CP-01108]; NCRR NIH HHS [RR03655] NR 43 TC 33 Z9 34 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 JUL PY 2005 VL 42 IS 7 BP 595 EP 601 DI 10.1136/jmg.2004.027433 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 941SZ UT WOS:000230235800011 PM 15994882 ER PT J AU Tilkeridis, C Bei, T Garantziotis, S Stratakis, CA AF Tilkeridis, C Bei, T Garantziotis, S Stratakis, CA TI Association of a COL1A1 polymorphism with lumbar disc disease in young military recruits SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID INTERVERTEBRAL DISC; I COLLAGEN; DEGENERATION; DENSITY; MATRIX AB Background: Lumbar disc disease (LDD), one of the most common conditions for which patients seek medical care, has been associated with sequence changes of the COL genes. COL1A1, however, has not been studied in young patients with LDD; COL1A1 polymorphisms have been associated with bone mineral density (BMD) in several populations and with LDD in older adults. Objective: To study COL1A1 polymorphisms in young Greek army recruits with LDD. Subjects: These young soldiers were diagnosed with early LDD at the time of their presentation to a military training site. All patients had radiological confirmation of their disease; a control group was also studied. Methods: Sp1-binding site polymorphism of the COL1A1 gene was investigated by standard methods. Results: There was an increased frequency of the "ss'' genotype (33.3%) in LDD patients; none of the controls had this genotype. In addition, a significantly smaller number of controls was heterozygotes for this allele. Conclusions: A previously studied sequence change of the regulatory region of the COL1A1 gene, the same as has previously been associated with low BMD in many populations and LDD in older adults, showed a strong association with LDD in young male soldiers who were recently diagnosed with this disease. C1 Hellen Armed Forces, Ctr Recruitment Mil Personnel Hlth Serv, Arta, Greece. NICHHD, Sect Genet & Endocrinol, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHD, Sect Endocrinol & Genet, DEB, NIH,CRC, Bldg 10,Room I-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI Garantziotis, Stavros/A-6903-2009 OI Garantziotis, Stavros/0000-0003-4007-375X NR 9 TC 32 Z9 35 U1 1 U2 1 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 JUL PY 2005 VL 42 IS 7 AR e44 DI 10.1136/jmg.2005.033225 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 941SZ UT WOS:000230235800019 PM 15994869 ER PT J AU Fujitani, M Kawai, H Proia, RL Kashiwagi, A Yasuda, H Yamashita, T AF Fujitani, M Kawai, H Proia, RL Kashiwagi, A Yasuda, H Yamashita, T TI Binding of soluble myelin-associated glycoprotein to specific gangliosides induces the association of p75(NTR) to lipid rafts and signal transduction SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE gangliosides; lipid rafts; myelin associated glycoprotein; Nogo; p75 NTR ID P75 RECEPTOR; NEURITE OUTGROWTH; NOGO RECEPTOR; AXONAL REGENERATION; NERVE REGENERATION; RHO; INHIBITION; MAG; INTERACTS; PROTEIN AB Myelin-associated glycoprotein (MAG) is a potent inhibitor of neurite outgrowth from a variety of neurons. Here we show that gangliosides, GT1b and GD1a, as well as the Nogo receptor, are functional binding partners for soluble MAG-Fc. Postnatal cerebellar neurons from mice deficient in the GalNAcT gene are insensitive to MAG with regard to neurite outgrowth and lack in the activation of RhoA. MAG-Fc or the antibody to GT1b and GD1a elicits recruitment of p75(NTR.) to lipid rafts, specialized microdomain for signal transduction. Disruption of lipid rafts results in abolishment of inhibitory effects of MAG-Fc and the Nogo peptide. These findings establish gangliosides as functional binding partners for soluble MAG. Gangliosides may play a role in translocation of p75(NTR.) to lipid rafts for initiation of the signal transduction. C1 Chiba Univ, Grad Sch Med, Dept Neurobiol, Chuo Ku, Chiba 2608670, Japan. Shiga Univ Med Sci, Dept Neurol, Shiga, Japan. NIDDKD, Genet Dev & Dis Branch, NIH, Bethesda, MD 20892 USA. RP Yamashita, T (reprint author), Chiba Univ, Grad Sch Med, Dept Neurobiol, Chuo Ku, 1-8-1 Inohana, Chiba 2608670, Japan. EM t-yamashita@faculty.chiba-u.jp RI Proia, Richard/A-7908-2012 NR 31 TC 31 Z9 31 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2005 VL 94 IS 1 BP 15 EP 21 DI 10.1111/j.1471-4159.2005.03121.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 934JO UT WOS:000229705300002 PM 15953345 ER PT J AU Lu, L Dempsey, J Shaham, Y Hope, BT AF Lu, L Dempsey, J Shaham, Y Hope, BT TI Differential long-term neuroadaptations of glutamate receptors in the basolateral and central amygdala after withdrawal from cocaine self-administration in rats SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE AMPA receptors; cocaine self-administration; incubation; NMDA receptors; relapse; withdrawal ID VENTRAL TEGMENTAL AREA; MESOLIMBIC DOPAMINE SYSTEM; DRUG-SEEKING BEHAVIOR; KNOCK-OUT MICE; PSYCHOMOTOR STIMULANTS; NUCLEUS-ACCUMBENS; BRAIN-REGIONS; SENSITIZATION; ADDICTION; INCUBATION AB Humans and laboratory animals remain highly vulnerable to relapse to cocaine-seeking after prolonged periods of withdrawal from the drug. It has been hypothesized that this persistent cocaine relapse vulnerability involves drug-induced alterations in glutamatergic synapses within the mesolimbic dopamine reward system. Previous studies have shown that cocaine self-administration induces long-lasting neuroadaptations in glutamate neurons of the ventral tegmental area and nucleus accumbens. Here, we determined the effect of cocaine self-administration and subsequent withdrawal on glutamate receptor expression in the amygdala, a component of the mesolimbic dopamine system that is involved in cocaine seeking and craving induced by drug-associated cues. Rats were trained for 10 days to self-administer intravenous cocaine (6 h/day) or saline (a control condition) and were killed after one or 30 withdrawal days. Basolateral and central amygdala tissues were assayed for protein expression of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunits (GluR1 and GluR2) and the NMDA receptor subunits (NR1, NR2A and NR2B). In the basolateral amygdala, GluR1 but not GluR2 levels were increased on days 1 and 30, NR2A levels were increased on day 1, and NR2B levels were decreased on day 30 of withdrawal from cocaine. In the central amygdala, GluR2 but not GluR1 levels were increased on days 1 and 30, NR1 levels were increased on day 30 and NR2A or NR2B levels were not altered after withdrawal from cocaine. These results indicate that cocaine self-administration and subsequent withdrawal induces long-lasting and differential neuroadaptations in basolateral and central amygdala glutamate receptors. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, NIH DHHS, Baltimore, MD 21224 USA. RP Lu, L (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, NIH DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM llu@intra.nida.nih.gov RI Hope, Bruce/A-9223-2010; shaham, yavin/G-1306-2014 OI Hope, Bruce/0000-0001-5804-7061; NR 52 TC 43 Z9 47 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2005 VL 94 IS 1 BP 161 EP 168 DI 10.1111/j.1471-4159.2005.03178.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 934JO UT WOS:000229705300016 PM 15953359 ER PT J AU Lin, ZC Uhl, GR AF Lin, ZC Uhl, GR TI Proline mutations induce negative-dosage effects on uptake velocity of the dopamine transporter SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE dynamics; expression; molecular modeling; monoamine transport; mutagenesis ID COCAINE ANALOG RECOGNITION; NEUROTRANSMITTER TRANSPORTERS; NOREPINEPHRINE TRANSPORTERS; FORCE-FIELD; EXPRESSION; PROTEINS; DOMAINS; CLONING; OLIGOMERIZATION; RESIDUES AB Ala and Gly substitutions for Pro 101 (P101) located in transmembrane domain 2 of the dopamine transporter (DAT) abolished transport activity but did not disrupt plasma membrane expression. Due to the high conservation of P101 in all neurotransmitter transporters and the capability of Pro to add flexibility to helices, we hypothesized that P101 contributes to the dynamic feature of substrate translocation. To test this hypothesis, here we analysed transport activity for DAT mutants where this Pro was mutated into different amino acids, including Ser, Val, Leu and Phe. The transmembrane domain 2 helix of P101F, unlike the other mutants, was computationally predicted to have a Van der Waals energy threefold higher than the wild-type helix. P101F mutant expression was consistently disrupted in COS cells. Among all the other mutants that express normally, P101V, with a side-chain size close to that of Pro, restores the transport activity of P101A by sevenfold. Most importantly, P101V, P101L and P101S display negative-dosage effects on dopamine (DA) transport, i.e. the velocity-concentration curve for DA uptake does not show a plateau with increasing [DA] but rather peaks and then goes down. These data support the view that P101 of DAT plays an essential role in DA translocation. C1 NIDA, Mol Neurobiol Branch, IRP, NIH, Baltimore, MD 21224 USA. RP Lin, ZC (reprint author), NIDA, Mol Neurobiol Branch, IRP, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM zlin@intra.nida.nih.gov NR 42 TC 3 Z9 3 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2005 VL 94 IS 1 BP 276 EP 287 DI 10.1111/j.1471-4159.2005.03196.x PG 12 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 934JO UT WOS:000229705300027 PM 15953370 ER PT J AU Kishida, KT Pao, M Holland, SM Klann, E AF Kishida, KT Pao, M Holland, SM Klann, E TI NADPH oxidase is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1 SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE learning and memory; long-term potentiation; oxygen species; reactive; superoxide ID LONG-TERM POTENTIATION; CHRONIC GRANULOMATOUS-DISEASE; SMOOTH-MUSCLE-CELLS; NITRIC-OXIDE; PROTEIN-KINASE; SUPEROXIDE PRODUCTION; MAP KINASE; PHOSPHORYLATION; STIMULATION; CASCADE AB Previous studies have shown that N-methyl-D-aspartate (NMDA) receptor activation results in production of reactive oxygen species (ROS) and activation of extracellular signal-regulated kinase (ERK) in hippocampal area CA1. In addition, application of ROS to hippocampal slices has been shown to result in activation of ERK in area CA1. To determine whether these events were linked causally, we investigated whether ROS are required for NMDA receptor-dependent activation of ERK. In agreement with previous studies, we found that treatment of hippocampal slices with NMDA resulted in activation of ERK in area CA1. The NMDA receptor-dependent activation of ERK was either blocked or attenuated by a number of antioxidants, including the general antioxidant N-acetyl-L-cysteine (L-NAC), the superoxide-scavenging enzyme superoxide dismutase (SOD), the membrane-permeable SOD mimetic Mn(III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), the hydrogen peroxide-scavenging enzyme catalase, and the catalase mimetic ebselen. The NMDA receptor-dependent activation of ERK also was blocked by the NADPH oxidase inhibitor diphenylene iodonium (DPI) and was absent in mice that lacked p47(phox), one of the required protein components of NADPH oxidase. Taken together, our results suggest that ROS production, especially superoxide production via NADPH oxidase, is required for NMDA receptor-dependent activation of ERK in hippocampal area CA1. C1 Baylor Coll Med, Dept Physiol & Mol Biophys, Houston, TX 77030 USA. Baylor Coll Med, Dept Neurosci, Houston, TX 77030 USA. Childrens Natl Med Ctr, Dept Psychiat, Washington, DC 20010 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Baylor Coll Med, Dept Physiol & Mol Biophys, 1 Baylor Pl BCM 335, Houston, TX 77030 USA. EM eklann@bcm.tmc.edu FU NINDS NIH HHS [F31 NS047852]; PHS HHS [N5034007, N5047852] NR 42 TC 87 Z9 89 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-3042 EI 1471-4159 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2005 VL 94 IS 2 BP 299 EP 306 DI 10.1111/j.1471-4159.2005.03189.x PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 942NN UT WOS:000230289200002 PM 15998281 ER PT J AU Zimring, JC Kapp, LM Yamada, M Wess, J Kapp, JA AF Zimring, JC Kapp, LM Yamada, M Wess, J Kapp, JA TI Regulation of CD8(+) cytolytic T lymphocyte differentiation by a cholinergic pathway SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE acetylcholine; neuroimmunology; T cells; cytotoxic T lymphocyte ID MUSCARINIC ACETYLCHOLINE-RECEPTOR; FOS GENE-EXPRESSION; ACETYLTRANSFERASE MESSENGER-RNA; PHARMACOLOGICAL STIMULATION; MONONUCLEAR LEUKOCYTES; ARACHIDONIC-ACID; ANTIGEN RECEPTOR; CELL ACTIVATION; PROTEIN-KINASE; KNOCKOUT MICE AB In this report, we provide evidence that muscarinic receptors play a role in the generation of CD8(+) cytolytic T lymphocytes. Analysis of mice with targeted deletions of each of the known muscarinic receptors (M-1-M-5) showed that CD8(+) T cells from M-1 receptor-deficient mice had a defect in the ability to differentiate into cytolytic T lymphocytes. Additional pharmacological experiments support the role of muscarinic receptors in wild type mice and suggest that acetylcholine may be involved. Together, these findings suggest that the M-1 muscarinic receptor is involved in CTL development, thus providing novel insights into CD8(+) T cell biology and the potential role of cholinergic signaling in immune regulation. (C) 2005 Elsevier B.V. All rights reserved. C1 Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. Univ Alabama, Dept Ophthalmol, Birmingham, AL 35233 USA. NIDDK, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Zimring, JC (reprint author), Emory Univ, Sch Med, Dept Pathol, Woodruff Mem Res Bldg,Room 7301,101 Woodruff Circ, Atlanta, GA 30322 USA. EM jzimrin@emory.edu OI Zimring, James/0000-0002-1063-4010 FU NCI NIH HHS [CA-70372]; NEI NIH HHS [P30EY06360]; NIAID NIH HHS [AI060017-01] NR 48 TC 41 Z9 47 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD JUL PY 2005 VL 164 IS 1-2 BP 66 EP 75 DI 10.1016/j.jneuroim.2005.03.018 PG 10 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 944XM UT WOS:000230464400008 PM 15913791 ER PT J AU Foltynie, T Lewis, SGJ Goldberg, TE Blackwell, AD Kolachana, BS Weinberger, DR Robbins, TW Barker, RA AF Foltynie, T Lewis, SGJ Goldberg, TE Blackwell, AD Kolachana, BS Weinberger, DR Robbins, TW Barker, RA TI The BDNF Val(66)Met polymorphism has a gender specific influence on planning ability in Parkinson's disease SO JOURNAL OF NEUROLOGY LA English DT Article DE Parkinson's disease; BDNF; planning; cognition ID NEUROTROPHIC FACTOR GENE; FACTOR MESSENGER-RNA; VAL66MET POLYMORPHISM; WORKING-MEMORY; VENTRAL MESENCEPHALON; RECEPTOR EXPRESSION; COGNITIVE DEFICITS; PREFRONTAL CORTEX; D-3 RECEPTORS; PERFORMANCE AB Parkinson's disease (PD) patients show a range of cognitive deficits, which may relate to abnormalities in dopaminergic transmission in fronto-striatal circuitry. In this study, we have investigated the impact of brain-derived neurotrophic factor ( BDNF) val(66)met polymorphisms on performance of the Tower of London (TOL) test of planning by PD patients. This polymorphism significantly influences BDNF secretion in the CNS, and BDNF is known to influence dopaminergic neurons and cognitive processes. Patients with PD totalling 291 who had undergone detailed motor and cognitive assessments as part of a population- based study of PD were genotyped for the BDNF val66met polymorphism. The impact of this polymorphism on cognitive ability was determined using multivariate analysis to adjust for possible confounding variables. Patients with low rates of BDNF secretion (met alleles) performed significantly better at the TOL task than those with high rates of secretion (val alleles). Furthermore, subgroup analyses revealed that the effect is most apparent in women and among patients with prior dopaminergic exposure. We speculate that BDNF may interact with dopaminergic transmission and dopamine receptor stimulation in the frontostriatal circuitry, with subsequent consequences on cognition in Parkinson's disease. C1 Univ Cambridge, Cambridge Ctr Brain Repair, Cambridge CB2 2PY, England. NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. Addenbrookes Hosp, Dept Psychiat, Cambridge, England. Univ Cambridge, Dept Expt Psychol, Cambridge CB2 2PY, England. RP Foltynie, T (reprint author), Univ Cambridge, Cambridge Ctr Brain Repair, Forvie Site,Robinson Way, Cambridge CB2 2PY, England. EM tf210@medschl.cam.ac.uk FU Medical Research Council [G0001067]; Wellcome Trust NR 41 TC 60 Z9 62 U1 0 U2 7 PU DR DIETRICH STEINKOPFF VERLAG PI DARMSTADT PA PO BOX 10 04 62, D-64204 DARMSTADT, GERMANY SN 0340-5354 J9 J NEUROL JI J. Neurol. PD JUL PY 2005 VL 252 IS 7 BP 833 EP 838 DI 10.1007/s00415-005-0756-5 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 942YK UT WOS:000230318600013 PM 15772739 ER PT J AU Ravina, B Putt, M Siderowf, A Farrar, JT Gillespie, M Crawley, A Fernandez, HH Trieschmann, MM Reichwein, S Simuni, T AF Ravina, B Putt, M Siderowf, A Farrar, JT Gillespie, M Crawley, A Fernandez, HH Trieschmann, MM Reichwein, S Simuni, T TI Donepezil for dementia in Parkinson's disease: a randomised, double blind, placebo controlled, crossover study SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Article ID ALZHEIMERS-DISEASE; COGNITIVE IMPAIRMENT; CONTROLLED TRIAL; LEWY BODIES; ASSESSMENT SCALE; RATING-SCALE; RIVASTIGMINE; MULTICENTER; MORTALITY; EFFICACY AB Objective: To study the safety and efficacy of a cholinesterase inhibitor, donepezil hydrochloride, for the treatment of dementia in Parkinson's disease (PD). Methods: This was a randomised double blind, placebo controlled, crossover study in 22 subjects with PD and dementia. Participants were randomised to receive either donepezil followed by identical placebo, or placebo followed by donepezil. Donepezil was administered at 5-10 mg/day. Treatment periods were 10 weeks with a washout period of 6 weeks between the two periods. The primary outcome measure was the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAScog). Results: Donepezil was well tolerated and most adverse events were mild. There was no worsening of PD symptoms as measured by the total or motor sections of the Unified Parkinson's Disease Rating Scale. There was a 1.9 point trend toward better scores on the ADAScog on treatment compared with placebo that was not statistically significant. The secondary cognitive measures showed a statistically significant 2 point benefit on the Mini Mental Status Examination and no change on the Mattis Dementia Rating Scale (MDRS). The Clinical Global Impression of Change (CGI) showed a significant 0.37 point improvement on donepezil. No improvement was observed on the MDRS or the Brief Psychiatric Rating Scale. Carryover between treatment periods was observed but was not statistically significant. Conclusions: Donepezil was well tolerated and did not worsen PD. There may be a modest benefit on aspects of cognitive function. The possible clinical benefit measured by CGI was reflected in only one of the cognitive scales used in this study. C1 NINDS, Ctr Neurosci, Bethesda, MD 20892 USA. Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA. Univ Florida, Dept Neurol, Gainesville, FL USA. Brown Univ, Dept Neurol, Providence, RI 02912 USA. Northwestern Univ, Dept Neurol, Chicago, IL 60611 USA. RP Ravina, B (reprint author), NINDS, Ctr Neurosci, Rm 2225,601 Execut Blvd, Bethesda, MD 20892 USA. EM ravinab@ninds.nih.gov RI Farrar, John/A-1037-2007 OI Farrar, John/0000-0001-8656-5157 FU AHRQ HHS [K08-HS00004]; NIA NIH HHS [AG10124]; NICHD NIH HHS [P30-HD02679-14] NR 34 TC 131 Z9 135 U1 2 U2 7 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0022-3050 J9 J NEUROL NEUROSUR PS JI J. Neurol. Neurosurg. Psychiatry PD JUL PY 2005 VL 76 IS 7 BP 934 EP 939 DI 10.1136/jnnp.2004.050682 PG 6 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 940IL UT WOS:000230137200008 PM 15965198 ER PT J AU Blohm, G Missal, M Lefevre, P AF Blohm, G Missal, M Lefevre, P TI Direct evidence for a position input to the smooth pursuit system SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID EYE-MOVEMENT SYSTEM; ROSTRAL SUPERIOR COLLICULUS; SACCADE TARGET SELECTION; VISUAL-SEARCH TASK; CATCH-UP SACCADES; ECCENTRIC TARGETS; TRACKING; STIMULUS; RESPONSES; MONKEYS AB When objects move in our environment, the orientation of the visual axis in space requires the coordination of two types of eye movements: saccades and smooth pursuit. The principal input to the saccadic system is position error, whereas it is velocity error for the smooth pursuit system. Recently, it has been shown that catch-up saccades to moving targets are triggered and programmed by using velocity error in addition to position error. Here, we show that, when a visual target is flashed during ongoing smooth pursuit, it evokes a smooth eye movement toward the flash. The velocity of this evoked smooth movement is proportional to the position error of the flash; it is neither influenced by the velocity of the ongoing smooth pursuit eye movement nor by the occurrence of a saccade, but the effect is absent if the flash is ignored by the subject. Furthermore, the response started around 85 ms after the flash presentation and decayed with an average time constant of 276 ms. Thus this is the first direct evidence of a position input to the smooth pursuit system. This study shows further evidence for a coupling between saccadic and smooth pursuit systems. It also suggests that there is an interaction between position and velocity error signals in the control of more complex movements. C1 Catholic Univ Louvain, Neurophysiol Lab, Brussels, Belgium. Catholic Univ Louvain, Ctr Syst Engn & Appl Mech, Brussels, Belgium. York Univ, Ctr Vis Res, Toronto, ON M3J 2R7, Canada. NEI, NIH, Bethesda, MD 20892 USA. RP Lefevre, P (reprint author), Univ Catholique Louvain, CESAME, 4 Ave G Lemaitre, B-1348 Louvain, Belgium. EM lefevre@csam.ucl.ac.be NR 53 TC 31 Z9 33 U1 0 U2 4 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUL PY 2005 VL 94 IS 1 BP 712 EP 721 DI 10.1152/jn.00093.2005 PG 10 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 940HY UT WOS:000230135500063 PM 15728771 ER PT J AU Giovacchini, G Toczek, MT Bonwetsch, R Bagic, A Lang, LX Fraser, C Reeves-Tyer, P Herscovitch, P Eckelman, WC Carson, RE Theodore, WH AF Giovacchini, G Toczek, MT Bonwetsch, R Bagic, A Lang, LX Fraser, C Reeves-Tyer, P Herscovitch, P Eckelman, WC Carson, RE Theodore, WH TI 5-HT1A receptors are reduced in temporal lobe epilepsy after partial-volume correction SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE 5-HT1A receptors; temporal lobe epilepsy; partial-volume correction; PET; depression ID POSITRON-EMISSION-TOMOGRAPHY; METABOLIC ABNORMALITIES; BLOOD-FLOW; IN-VIVO; PET; BINDING; WAY-100635; DEPRESSION; SEROTONIN; MODEL AB Preclinical studies suggest that serotonin 1A receptors (5-HT1A) play a role in temporal lobe epilepsy (TLE). Previous PET studies reported decreased 5-HT1A binding ipsilateral to epileptic foci but did not correct for the partial-volume effect (PVE) due to structural atrophy. Methods: We used PET with F-18-trans-4-fluoro-N-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl-N-(2pyridyl)cyclohexanecarboxamide (F-18-FCWAY), a 5-HT1A receptor antagonist, to study 22 patients with TLE and 10 control subjects. In patients, F-18-FDG scans also were performed. An automated MR-based partial-volume correction (PVC) algorithm was applied. Psychiatric symptoms were assessed with the Beck Depression Inventory Scale. Results: Before PVC, significant (uncorrected P < 0.05) reductions of 18F-FCWAY binding potential (BP) were detected in both mesial and lateral temporal structures, mainly ipsilateral to the seizure focus, in the insula, and in the raphe. Group differences were maximal in ipsilateral mesial temporal regions (corrected P < 0.05). After PVC, differences in mesial, but not lateral, temporal structures and in the insula remained highly significant (corrected P < 0.05). Significant (uncorrected P < 0.05) BP reductions were also detected in TLE patients with normal MR images (n = 6), in mesial temporal structures. After PVC, asymmetries in BP remained significantly greater than for glucose metabolism in hippocampus and parahippocampus. There was a significant inverse relation between the Beck Depression score and the ipsilateral hippocampal BP, both before and after PVC. Conclusion: Our study shows that in TLE patients, reductions of 5-HT1A receptor binding in mesial temporal structures and insula are still significant after PVC. In contrast, partial-volume effects may be an important contributor to 5-HT1A receptor-binding reductions in lateral temporal lobe. Reduction of 5-HT1A receptors in the ipsilateral hippocampus may contribute to depressive symptoms in TLE patients. C1 NIH, Ctr Clin, PET Dept, Bethesda, MD 20892 USA. Univ Pisa, Sch Med, Postgrad Specialty Sch Nucl Med, I-56100 Pisa, Italy. NINDS, Clin Epilepsy Sect, NIH, Bethesda, MD USA. RP Theodore, WH (reprint author), NIH, Ctr Clin, PET Dept, Bldg 10,Room 5N-250,9000 Rockville Pke,MSC 1408, Bethesda, MD 20892 USA. EM theodorw@ninds.nih.gov RI Carson, Richard/H-3250-2011 OI Carson, Richard/0000-0002-9338-7966 FU NINDS NIH HHS [Z01 NS002236-30] NR 40 TC 85 Z9 87 U1 0 U2 4 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 JUL PY 2005 VL 46 IS 7 BP 1128 EP 1135 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 943DI UT WOS:000230331900010 PM 16000281 ER PT J AU Sato, N Hassan, R Axworthy, DB Wong, KJ Yu, S Theodore, LJ Lin, YK Park, L Brechbiel, MW Pastan, I Paik, CH Carrasquillo, JA AF Sato, N Hassan, R Axworthy, DB Wong, KJ Yu, S Theodore, LJ Lin, YK Park, L Brechbiel, MW Pastan, I Paik, CH Carrasquillo, JA TI Pretargeted radioimmunotherapy of mesothelin-expressing cancer using a tetravalent single-chain Fv-streptavidin fusion protein SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE radioimmunotherapy; Y-90-DOTA-biotin; biodistribution; pretargeting ID INTERNAL DOSE ASSESSMENT; ANTIBODY-STREPTAVIDIN; RECOMBINANT IMMUNOTOXIN; MONOCLONAL-ANTIBODIES; ANTITUMOR-ACTIVITY; COLON-CANCER; NUDE-MICE; THERAPY; XENOGRAFTS; MODEL AB Mesothelin is a glycoprotein that is overexpressed in several human tumors, including mesotheliomas and ovarian cancers, and has been identified as a potential target for therapy. We evaluated the biodistribution and tumor-targeting ability of an antimesothelin tetravalent single-chain Fv-streptavidin fusion protein (SS1scFvSA) in mice. Methods: SS1scFvSA was labeled with (125)l or In-111 for evaluation of internalization in vitro and for optimization of its biodistribution. The A431-K5 mesothelin transfected cell line was used as the target. We used a 3-step pretargeting approach consisting of injections of (i) SS1scFvSA, followed 20 h later by (ii) a synthetic clearing agent, and (iii) 4 h later, radiolabeled (In-111, Y-88/Y-90, or Lu-177) 1,4,7,10-tetraazacyclododecane-N,N',N",N"'-tetraacetic acid (DOTA)-biotin. To optimize the tumor uptake, the effect of the specific activity of In-111-DOTA-biotin was evaluated. Results: Approximately 60% of SS1sc FvSA internalized within 6 h. The optimal dose of SS1scFvSA for pretargeting was 600 mu g. Decreasing the specific activity of DOTA-biotin by administering 0.1-5 mu g of DOTA-biotin resulted in tumor uptake decreasing from 31.8 to 5.5 %ID/g (percentage injected dose per gram) at 2 h. Pretargeted therapy of A431-K5 tumor with Y-90 doses of 11.1-32.4 MBq resulted in a dose-dependent tumor response. With 32.4 MBq, 86% of mice survived tumor free for 110 d. All nontreated mice died, with a median survival of 16 d. Conclusion: SS1scFvSA localized in the mesothelin-expressing tumor, resulting in a high accumulation of radiolabeled DOTA-biotin. The specific activity of DOTA-biotin had a significant effect on its tumor uptake. Therapeutic tumor doses were obtained without dose-limiting toxicity. C1 Warren G Magnuson Clin Ctr, Dept Nucl Med, NIH, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. NeoRx Corp, Seattle, WA USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Carrasquillo, JA (reprint author), Warren G Magnuson Clin Ctr, Dept Nucl Med, NIH, 10 Ctr Dr,MSC-1180, Bethesda, MD 20892 USA. EM jcarrasquilio@cc.nih.gov RI Carrasquillo, Jorge/E-7120-2010; OI Carrasquillo, Jorge/0000-0002-8513-5734 NR 31 TC 28 Z9 29 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 JUL PY 2005 VL 46 IS 7 BP 1201 EP 1209 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 943DI UT WOS:000230331900019 PM 16000290 ER PT J AU Haggans, CJ Regan, KS Brown, LM Wang, CL Krebs-Smith, A Coates, PM Swanson, CA AF Haggans, CJ Regan, KS Brown, LM Wang, CL Krebs-Smith, A Coates, PM Swanson, CA TI Computer access to research on dietary supplements: A database of federally funded dietary supplement research SO JOURNAL OF NUTRITION LA English DT Article DE dietary supplements; federally funded nutrition research; database resources ID NATIONAL-HEALTH; NONVITAMIN AB Dietary supplement use is prevalent in the United States, but support for supplement research has been relatively modest and only recently emphasized at the NIH. The, Dietary Supplement Health and Education Act of 1994 led to the creation of the Office of Dietary Supplements (ODS) at the NIH to promote research on dietary supplements. In order to track federally funded dietary supplement research, the ODS developed a database known as Computer Access to Research on Dietary Supplements (CARDS). This article provides an overview of the development and potential uses of the CARDS database. In addition, we report that NIH-funded dietary supplement research steadily increased from fiscal year (FY) 1999 through 2002. The majority of NIH institutes or centers (ICs) funded research relevant to dietary supplements during this time, led by the National Cancer Institute and one of the newest NIH ICs, the National Center for Complementary and Alternative Medicine. CARDS data indicate that NIH-funded dietary supplement research from FY 1999 through 2002 involved primarily vitamins, minerals, botanicals and phytochemicals. Cancer and cardiovascular disease, two of the leading causes of morbidity and mortality in the United States, collectively accounted for almost 45% of the research related to dietary supplements. A variety of types of research studies were funded, with the majority consisting of human intervention studies. This information is useful to evaluate trends in federally funded dietary supplement research, identify research gaps, and help research scientists identify potential sources of NIH funding. C1 NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. RP Haggans, CJ (reprint author), NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. EM haggansc@od.nih.gov NR 7 TC 5 Z9 5 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JUL PY 2005 VL 135 IS 7 BP 1796 EP 1799 PG 4 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 943DE UT WOS:000230331500032 PM 15987867 ER PT J AU Curwin, BD Hein, MJ Sanderson, WT Nishioka, MG Reynolds, SJ Ward, EM Alavanja, MC AF Curwin, BD Hein, MJ Sanderson, WT Nishioka, MG Reynolds, SJ Ward, EM Alavanja, MC TI Pesticide contamination inside farm and nonfarm homes SO JOURNAL OF OCCUPATIONAL AND ENVIRONMENTAL HYGIENE LA English DT Article DE children; house dust; pesticide exposure; surface wipe ID AGRICULTURAL-WORKERS; LAWN APPLICATIONS; CHILDREN; EXPOSURE; DUST; 2,4-D AB Twenty-five farm (F) households and 25 nonfarm (NF) households in Iowa were enrolled in a stud), investigating agricultural pesticide contamination inside homes. Air, surface wipe, and dust samples were collected. Samples from 39 homes (20 F and 19 NF) were analyzed for atrazine, metolachlor, acetochlor, alachlor, and chlorpyrifos. Samples from I I homes (5 F and 6 NF) were analyzed for glyphosate and 2,4-Dichlorophenoxyac etic acid (2,4-D). Greater than 88% of the air and greater than 74% of the wipe samples were below the limit of detection (LOD). Among the air and wipe samples, chlorpyrifos was detected most frequently in homes. In the dust samples, all the pesticides were detected in greater than 50% of the samples except acetochlor and alachlor, which were detected in less than 30% of the samples. Pesticides in dust samples were detected more often in farm homes except 2,4-D, which was detected in 100% of the farm and nonfarm home samples. The average concentration in dust was higher in farm homes versus nonfarm homes for each pesticide. Further analysis of the data was limited to those pesticides with at least 50% of the dust samples above the LOD. All farms that sprayed a pesticide had higher levels of that pesticide in dust than both farms that did not spray that pesticide and nonfarms; however, am), atrazine and metolachlor were significantly higher. The adjusted geometric-mean pesticide concentration in dust for farms that sprayed a particular pesticide ranged from 94 to 1300 ng/g compared with 12 to 1000 ng/g for farms that did not spray a particular pesticide, and 2.4 to 320 ng/g for nonfarms. The distributions of the pesticides throughout the mrious rooms sampled suggest that the strictly agricultural herbicides atrazine and metolachlor are potentially being brought into the home on the farmer's shoes and clothing. These herbicides are not applied in or around the home but they appear to be getting into the home paraoccupationally. For agricultural pesticides, take-home exposure may be an important source of home contamination. C1 NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA. Univ Iowa, Dept Environm & Occupat Hlth, Iowa City, IA USA. Battelle Mem Inst, Columbus, OH 43201 USA. Colorado State Univ, Dept Environm & Radiol Hlth Sci, Ft Collins, CO 80523 USA. Amer Canc Soc, Dept Epidemiol & Surveillance Res, Atlanta, GA 30329 USA. Natl Canc Inst, Bethesda, MD USA. RP Curwin, BD (reprint author), NIOSH, Div Surveillance Hazard Evaluat & Field Studies, Cincinnati, OH 45226 USA. EM bcurwin@cdc.gov NR 25 TC 42 Z9 45 U1 0 U2 16 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1545-9624 J9 J OCCUP ENVIRON HYG JI J. Occup. Environ. Hyg. PD JUL PY 2005 VL 2 IS 7 BP 357 EP 367 DI 10.1080/15459620591001606 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 944ED UT WOS:000230408000005 PM 16020099 ER PT J AU Chen, XJ Levine, ID AF Chen, XJ Levine, ID TI Epinephrine-induced excitation and sensitization of rat C-fiber nociceptors SO JOURNAL OF PAIN LA English DT Article DE pain; hyperalgesia; inflammation ID PRIMARY AFFERENT NEURONS; SYMPATHETICALLY MAINTAINED PAIN; STREPTOZOTOCIN-DIABETIC RAT; ALTERED TEMPORAL PATTERN; PROTEIN-KINASE-A; NERVE INJURY; INFLAMMATORY PAIN; NEUROPATHIC PAIN; NORADRENALINE HYPERALGESIA; MECHANICAL HYPERALGESIA AB Although epinephrine (EPI) has been suggested to contribute to the pain and hyperalgesia associated with inflammation and nerve injury, there have been very few in vivo electrophysiologic studies of the effects of EPI on nociceptors. We found with the single-unit recording technique that the intradermal administration of EPI resulted in excitation of a group of C fibers and a decrease in the mechanical activation threshold in a non-overlapping group. Unexpectedly, the fibers that were neither excited nor demonstrated a decrease in threshold demonstrated as a group a significant increase in response to sustained suprathreshold mechanical stimuli, an effect not observed in the other 2 groups of C fibers. This identifies a novel response of C-fiber nociceptors to an inflammatory mediator and suggests it is present in a class of C fibers previously considered unresponsive to hyperalgesic inflammatory mediators. Perspective: Our study provides support for the suggestion that EPI, a neuroendocrine stress hormone as well as an inflammatory mediator, might contribute to pain syndromes, especially in the setting of chronic stress. (c) 2005 by the American Pain Society. C1 Univ Calif San Francisco, NIH Pain Ctr, Dept Anat, Div Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH Pain Ctr, Dept Med, Div Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, NIH Pain Ctr, Dept Oral & Maxillofacial Surg, Div Neurosci, San Francisco, CA 94143 USA. RP Levine, ID (reprint author), Univ Calif San Francisco, NIH Pain Ctr, Dept Anat, Div Neurosci, Box 0440,C-555, San Francisco, CA 94143 USA. EM levine@itsa.ucsf.edu FU NINDS NIH HHS [NS21647] NR 50 TC 10 Z9 10 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 1526-5900 J9 J PAIN JI J. Pain PD JUL PY 2005 VL 6 IS 7 BP 439 EP 446 DI 10.1016/j.jpain.2005.02.004 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 950PB UT WOS:000230868300005 PM 15993822 ER PT J AU Spector, LG Klebanoff, MA Feusner, JH Georgieff, MK Ross, JA AF Spector, LG Klebanoff, MA Feusner, JH Georgieff, MK Ross, JA TI Childhood cancer following neonatal oxygen supplementation SO JOURNAL OF PEDIATRICS LA English DT Article ID LOW-BIRTH-WEIGHT; RISK; HEPATOBLASTOMA; CHILDREN; EXPOSURE; LESSONS AB Objective To evaluate the relationship between neonatal oxygen supplementation (O-2) and childhood cancer in the Collaborative Perinatal Project (CPP). Study design The CPP consisted of 54,795 children born between 1959 and 1966 and followed to age 8 years. We used Cox proportional hazards modeling to examine the association between history of neonatal O-2 and cancer (n = 48). Results The hazard ratio (HR) for any O-2 was 1.77 (95% confidence interval [CI] = 0.94 to 3.35). The HR for continuous duration of O-2 was near 1 and not significant. However, the HRs were 0.69 (95% CI = 0.17 to 2.88) and 2.87 (95% CI = 1.46 to 5.66) when comparing 0 to 2 and 3 or more minutes of O-2, respectively, to no O-2. The latter association was weaker (HR = 2.00; 95% CI = 0.88 to 4.54) and not significant (P = .10) when analysis was restricted to cancers diagnosed after age 1 year (n = 41). Conclusions These findings are consistent with an association between O-2 for 3 minutes or longer and cancer in childhood, and should serve as a basis for further study. C1 Univ Minnesota, Dept Pediat, Dept Epidemiol Clin Res, Minneapolis, MN 55455 USA. NICHD, Div Epidemiol Stat & Prevent Res, Rockville, MD USA. Childrens Hosp & Res Ctr Oakland, Dept Hematol Oncol, Oakland, CA USA. RP Spector, LG (reprint author), Univ Minnesota, Dept Pediat, Dept Epidemiol Clin Res, 420 Delaware St SE,MMC 715, Minneapolis, MN 55455 USA. EM spector@epi.umn.edu OI Spector, Logan/0000-0003-2516-0222 NR 19 TC 65 Z9 68 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUL PY 2005 VL 147 IS 1 BP 27 EP 31 DI 10.1016/j.jpeds.2005.03.008 PG 5 WC Pediatrics SC Pediatrics GA 949GR UT WOS:000230773600009 PM 16027689 ER PT J AU Henklein, P Bruns, K Nimtz, M Wray, V Tessmer, U Schubert, U AF Henklein, P Bruns, K Nimtz, M Wray, V Tessmer, U Schubert, U TI Influenza A virus protein PB1-42: synthesis and characterization of the biologically active full length protein and related peptides SO JOURNAL OF PEPTIDE SCIENCE LA English DT Article DE influenza A virus protein PB1-F2; protein synthesis; piperidide-formation; chemical ligation; MALDI-TOF mass spectrometry; TOCSY nuclear magnetic resonance spectroscopy ID SECONDARY STRUCTURE PREDICTION; TOTAL CHEMICAL-SYNTHESIS; LEUKEMIA-VIRUS TYPE-1; INFLUENZA-A VIRUSES; C-TERMINAL DOMAIN; MITOCHONDRIAL PROTEIN; HIV-1 VPR; PHOSPHORYLATION; MEMBRANE; LIGATION AB Recently the discovery of a novel 87 amino acid influenza A virus (IAV) protein, named PB1-F2, has been reported that originates from an alternative reading frame in the PB1 polymerase gene and is encoded in most of the known human IAV isolates. Using optimized protocols, full length biologically active sPB1-F2 and a number of fragments have been synthesized by following either the standard elongation SPPS method or by native chemical ligation of unprotected N- and C-terminal peptide fragments at the histidine and cysteine residues located in position 41 and 42 of the native sequence, respectively. The ligation procedure afforded the most efficient synthesis of sPB1-F2 and facilitated the generation of various mutants of sPB1-F2 from pre-synthesized peptide fragments. During the synthesis of sPB1-F2, the formation of succinimide and subsequent conversion to the piperidine derivative at the aspartic acid residue in position 23 was observed. This reaction was forestalled by applying specific modifications to the SPPS protocol. The chain-elongation SPPS protocol is optimal for producing small peptides of sPB1-F2, their derivatives and precursors for a subsequent ligation protocol, while the full length protein, mutants and labelled derivatives are more conveniently and efficiently synthesized by SPPS protocols that include native chemical ligation. The molecular identity of sPB1-F2 was confirmed by peptide mapping, mass spectrometry, N-terminal sequencing, H-1 NMR spectroscopy and Western blot analysis. The latter analysis afforded direct evidence of the inherent tendency of sPB1-F2 to undergo oligomerization, a phenomenon observed both for full length sPB1-F2 and fragments thereof, as well as for its full length viral counterpart. Our synthesis protocols open the field for multiple biological and structural studies on sPB1-F2 that, similar to the molecule expressed in an IAV context, induces apoptosis and interacts with membranes in vitro and in vivo, as shown in previous studies. Copyright (c) 2005 European Peptide Society and John Wiley & Sons, Ltd. C1 Humboldt Univ, Inst Biochem, D-10117 Berlin, Germany. German Res Ctr Biotechnol, Dept Biol Struct, Braunschweig, Germany. Univ Hamburg, Heinrich Pette Inst Expt Virol & Immunol, D-2000 Hamburg, Germany. NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. Univ Erlangen Nurnberg, Inst Clin & Mol Virol, D-8520 Erlangen, Germany. RP Henklein, P (reprint author), Humboldt Univ, Inst Biochem, Monbijoustr 2, D-10117 Berlin, Germany. EM peter.henklein@charite.de FU NIDDK NIH HHS [R01 DK59537-01] NR 32 TC 20 Z9 25 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1075-2617 J9 J PEPT SCI JI J. Pept. Sci. PD JUL PY 2005 VL 11 IS 8 BP 481 EP 490 DI 10.1002/psc.641 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 958FP UT WOS:000231430400005 PM 15641124 ER PT J AU Stevenson, GW Folk, JE Rice, KC Negus, SS AF Stevenson, GW Folk, JE Rice, KC Negus, SS TI Interactions between delta and mu opioid Agonists in assays of schedule-controlled responding, thermal nociception, drug self-administration, and drug versus food choice in rhesus monkeys: Studies with SNC80 [(+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]-N ,N-diethylbenzamide] and heroin SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID TAIL-WITHDRAWAL PROCEDURE; RAPID ASSESSMENT; COCAINE; RECEPTORS; MORPHINE; ANTAGONISM; MODULATION; ANTINOCICEPTION; BUPRENORPHINE; QUADAZOCINE AB Interactions between delta and mu opioid agonists in rhesus monkeys vary as a function of the behavioral endpoint. The present study compared interactions between the delta agonist SNC80 [(+)-4-[(alpha R)-alpha-((2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl]- N,N-diethylbenzamide] and the mu agonist heroin in assays of schedule-controlled responding, thermal noc-iception, and drug self-administration. Both SNC80 (ED50 = 0.43 mg/kg) and heroin (ED50 = 0.088 mg/kg) produced a dose-dependent and complete suppression of response rates in the assay of schedule-controlled responding. Heroin also produced thermal antinociception (ED5 degrees C = 0.18 mg/kg) and maintained drug self-administration under both a fixed ratio schedule [dose-effect curve peak at 0.0032 mg/kg/injection (inj)] and under a food versus heroin concurrent-choice schedule dule (ED50 = 0.013 mg/ kg/ inj), whereas SNC80 did not produce thermal antinociception or maintain self-administration. Fixed ratio mixtures of SNC80 and heroin (1.6:1, 4.7:1, and 14:1 SNC80/heroin) produced additive effects in the assay of schedule-controlled responding and superadditive effects in the assay of thermal nociception. Also, SNC80 did not enhance the reinforcing effects of heroin, indicating that mixtures of SNC80 and heroin produced additive or infra-additive reinforcing effects. These results provide additional evidence to suggest that delta/mu interactions depend on the experimental endpoint and further suggest that delta agonists may selectively enhance the antinociceptive effects of mu agonists while either not affecting or decreasing the sedative and reinforcing effects of mu agonists. C1 Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, Belmont, MA 02478 USA. NIDDKD, Med Chem Lab, NIH, Bethesda, MD 20892 USA. RP Negus, SS (reprint author), Harvard Univ, McLean Hosp, Sch Med, Alcohol & Drug Abuse Res Ctr, 115 Mill St, Belmont, MA 02478 USA. EM negus@mclean.harvard.edu FU NIDA NIH HHS [P01-DA14528, T32-DA07252, R01-DA11460] NR 42 TC 30 Z9 31 U1 0 U2 2 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 2005 VL 314 IS 1 BP 221 EP 231 DI 10.1124/jpet.104.082685 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 936GF UT WOS:000229842800027 PM 15792997 ER PT J AU Collins, GT Witkin, JM Newman, AH Svensson, KA Grundt, P Cao, JJ Woods, JH AF Collins, GT Witkin, JM Newman, AH Svensson, KA Grundt, P Cao, JJ Woods, JH TI Dopamine agonist-induced yawning in rats: A dopamine D3 receptor-mediated behavior SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID WILD-TYPE MICE; HIGH-AFFINITY; LOCOMOTOR-ACTIVITY; D-3 RECEPTORS; INDUCED HYPOTHERMIA; BODY-TEMPERATURE; COCAINE-SEEKING; KNOCK-OUT; ANTAGONIST; APOMORPHINE AB A specific role for the dopamine D3 receptor in behavior has yet to be elucidated. We now report that dopamine D2/D3 agonists elicit dose-dependent yawning behavior in rats, resulting in an inverted U-shaped dose-response curve. A series of experiments was directed toward the hypothesis that the induction of yawning is a D3 receptor-mediated effect, whereas the inhibition of the yawning observed at higher doses is due to competing D2 receptor activity. We compared several dopaminergic agonists with a range of in vitro D3 selectivity, including PD-128,907 [(S)-(+)-(4aR, 10bR)-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-[1] benzopyrano-[4,3-b]-1,4-oxazin-9-ol HCl], PD-128,908 [(R)-(-)-(4aS, 10bS)-3,4,4a, 10b-tetrahydro-4-propyl-2H,5H-[1]benzopyrano-[4,3-b]-1,4-oxazin-9-ol HCl], quinelorane [(5aR-trans)-5,5a, 6,7,8, 9,9a, 10-octahydro-6-propylpyrido[2,3-g] quinazolin-2-amine dihydrochloride], pramipexole (N'-propyl-4,5,6,7-tetrahydrobenzothiazole-2,6-diamine), 7-OH-DPAT [(+/-)-7-hydroxy-2-dipropylaminotetralin HBr], quinpirole [trans-(-)-(4aR)-4,4a,5,6,7,8, 8a,9-octahydro-5-propyl-1H-pyrazolo[3,4-g] quinoline HCl], bromocriptine [(+)-2-bromo-12'- hydroxy-2'-(1-methylethyl)-5'-(2-methylpropyl) ergotaman-3',6'-18-trione methanesulfonate], and apomorphine [(R)-(-)-5,6,6a,7-tetrahydro-6-methyl-4H-dibenzo[de,g]quinoline-10,11-diol HCl] with respect to their ability to induce yawning in rats. A series of D2/D3 antagonists differing in selectivity for D3 over D2 receptors were evaluated for their ability to alter the effects of the dopamine agonists. The antagonists L-741,626 (3-[4-(4-chlorophenyl)-4-hydroxypiperidin-L-yl]methyl-1H-indole), haloperidol (4-[4-(4- chlorophenyl)-4- hydroxy. C1 Univ Michigan, Sch Med, Dept Pharmacol, Ann Arbor, MI 48109 USA. Lilly Res Labs, Psychiat Drug Grp, Indianapolis, IN USA. NIDA, Intramural Res Program, Med Chem Sect, NIH, Baltimore, MD 21224 USA. RP Woods, JH (reprint author), Univ Michigan, Sch Med, Dept Pharmacol, 1301 MSRB 3, Ann Arbor, MI 48109 USA. EM jhwoods@umich.edu RI Collins, Gregory/K-3125-2012 FU NIDA NIH HHS [P50 DA000254, K21 DA000254, R01 DA009161, P01 DA000254, DA 00254, DA 09161] NR 50 TC 89 Z9 90 U1 0 U2 5 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 JUL PY 2005 VL 314 IS 1 BP 310 EP 319 DI 10.1124/jpet.105.085472 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 936GF UT WOS:000229842800036 PM 15833897 ER PT J AU Xiao, JJ Huang, Y Dai, ZY Sadee, W Chen, JY Liu, SJ Marcucci, G Byrd, J Covey, JM Wright, J Grever, M Chan, KK AF Xiao, JJ Huang, Y Dai, ZY Sadee, W Chen, JY Liu, SJ Marcucci, G Byrd, J Covey, JM Wright, J Grever, M Chan, KK TI Chemoresistance to depsipeptide FK228 [(E)-(1S,4S,10S,21R)-7-[(Z)-ethylidene]-4,21-diisopropyl-2-oxa-12,13-dit hia-5,8,20,23-tetraazabicyclo[8,7,6]-tricos-16-ene-3,6,9,22-pentanone] is mediated by reversible MDR1 induction in human cancer cell lines SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID HISTONE DEACETYLASE INHIBITORS; RESISTANCE-ASSOCIATED PROTEIN; P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; MEMBRANE TRANSPORTERS; GENE-EXPRESSION; DNA METHYLATION; IN-VIVO; FR901228; CHROMATIN AB Histone acetylation status, an epigenetic determinant of gene transcription, is controlled by histone acetyltransferases ( HATs) and histone deacetylases ( HDACs). The potent HDAC inhibitor FK228 [(E)-(1S, 4S, 10S, 21R)-7-[(Z)-ethylidene]-4,21-diisopropyl2- oxa-12,13-dithia- 5,8,20,23- tetraazabicyclo[ 8,7,6]- tricos-16- ene-3,6,9,22-pentanone] is a substrate for multidrug resistance protein (MDR1) and multidrug resistance-associated protein 1 (MRP1), both of which mediate FK228 resistance. To determine the mechanisms underlying acquired FK228 resistance, we developed four FK228-resistant cell lines from HCT-15, IGROV1, MCF7, and K562 cells by stepwise increases in FK228 exposure. Parent and resistant cells were characterized using a 70-oligomer cDNA microarray, real-time reverse transcription-polymerase chain reaction (RT-PCR), Western blot, and cytotoxicity assays. At both mRNA and protein levels, MDR1, but not MRP1 or other potential resistance genes, was strongly up-regulated in all resistant cell lines. HAT or HDAC activities were unaffected in resistant cells, consistent with a lack of cross-resistance to HDAC inhibitors that are not MDR1 substrates. FK228 was found to reversibly induce MDR1 expression by HDAC inhibition and subsequent histone hyperacetylation at the MDR1 promoter, as shown by real-time RTPCR, Western blot, and chromatin immunoprecipitation. This study reveals a significant role of histone acetylation in MDR1 transcription, which seems to mediate FK228 resistance. C1 Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. Ohio State Univ, Dept Pharmacol, Coll Med & Publ Hlth, Columbus, OH 43210 USA. Ohio State Univ, Div Hematol Oncol, Coll Med & Publ Hlth, Columbus, OH 43210 USA. Natl Canc Inst, Rockville, MD USA. RP Chan, KK (reprint author), Ohio State Univ, Coll Pharm, Room 308,OSU CCC,410 W 12th Ave, Columbus, OH 43210 USA. EM chan.56@osu.edu FU NCI NIH HHS [1R21CA 96323] NR 39 TC 55 Z9 57 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 JUL PY 2005 VL 314 IS 1 BP 467 EP 475 DI 10.1124/jpet.105.083956 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 936GF UT WOS:000229842800053 PM 15833893 ER PT J AU Srivastava, S Srivastava, RG AF Srivastava, S Srivastava, RG TI Proteomics in the forefront of cancer biomarker discovery SO JOURNAL OF PROTEOME RESEARCH LA English DT Article ID MASS-SPECTROMETRY; PROSTATE-CANCER; PROTEIN MICROARRAYS; IMMUNE-RESPONSE; OVARIAN-CANCER; LUNG-CANCER; SERUM; IDENTIFICATION; IONIZATION C1 NCI, Div Canc Prevent, Canc Biomarkers Res Grp, Rockville, MD 20852 USA. NCI, Organ Syst Branch, Rockville, MD 20852 USA. RP Srivastava, S (reprint author), NCI, Div Canc Prevent, Canc Biomarkers Res Grp, EPN 3142,6130 Execut Blvd, Rockville, MD 20852 USA. EM srivasts@mail.nih.gov NR 33 TC 29 Z9 31 U1 0 U2 0 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 JUL-AUG PY 2005 VL 4 IS 4 BP 1098 EP 1103 DI 10.1021/pr050016u PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 954VV UT WOS:000231184200006 PM 16083258 ER PT J AU Sheeley, DM Breen, JJ Old, SE AF Sheeley, DM Breen, JJ Old, SE TI Building integrated approaches for the proteomics of complex, dynamic systems: NIH programs in technology and infrastructure development SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE proteomics; NIH; quantitation; cellular dynamics; biomarkers; differential expression ID PROTEIN-PROTEIN INTERACTIONS; MASS-SPECTROMETRY; SACCHAROMYCES-CEREVISIAE; YEAST; NETWORKS; SCALE; IDENTIFICATION; LOCALIZATION; NEUROSCIENCE; PEPTIDES AB Proteomics technology and methods remain inadequate. Technological constraints contribute to an artificially static view of complex biological systems and a barrier between quantitative and interaction studies. Several NIH programs combine proteomics technology development with research on challenging biological problems to drive progress. A new initiative of the NIH Roadmap focuses on characterization of dynamic systems. The success of these programs will be judged by their impact on relevant biological problems. C1 Natl Ctr Res Resources, Div Biomed Technol, Bethesda, MD 20892 USA. NIH, Natl Inst Allergy & Infect Dis, Natl Ctr Res Resources, Bethesda, MD 20892 USA. NIH, Natl Heart Lung & Blood Inst, Bethesda, MD 20892 USA. RP Sheeley, DM (reprint author), Natl Ctr Res Resources, Div Biomed Technol, 6701 Democracy Blvd,MSC4874, Bethesda, MD 20892 USA. EM sheeleyd@mail.nih.gov NR 46 TC 4 Z9 5 U1 1 U2 1 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 JUL-AUG PY 2005 VL 4 IS 4 BP 1114 EP 1122 DI 10.1021/pr050066z PG 9 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 954VV UT WOS:000231184200009 PM 16083261 ER PT J AU Srivastava, S Verma, M Gopal-Srivastava, R AF Srivastava, S Verma, M Gopal-Srivastava, R TI Proteomic maps of the cancer-associated infectious agents SO JOURNAL OF PROTEOME RESEARCH LA English DT Review DE acetylation; apoptosis; biomarkers; chromatin; early detection; epigenetics; epigenome; gene therapy; infectious agents; matrix-assisted laser capture ionization desorption mass spectrometry (MALDI MS); methylation; post-translational modifications (PTM); prevention; protein array; risk assessment; siRNA; vaccine; viral load ID EPSTEIN-BARR-VIRUS; 2-DIMENSIONAL GEL-ELECTROPHORESIS; SARCOMA-ASSOCIATED HERPESVIRUS; FLIGHT MASS-SPECTROMETRY; HEPATITIS-B-VIRUS; TIME-OF-FLIGHT; KAPOSIS-SARCOMA; PROMOTER METHYLATION; TYPE-1 INFECTION; BREAST-CANCER AB The number of infectious agents associated with cancer is increasing. There is a need to develop approaches for the early detection of the infected host which might lead to tumor development. Recent advances in proteomic approaches provide that opportunity, and it is now possible to generate proteomic maps of cancer-associated infectious agents. Protein arrays, interaction maps, data archives, and biological assays are being developed to enable efficient and reliable protein identification and functional analysis. Herein, we discuss the current technologies and challenges in the field, and application of protein signatures in cancer detection and prevention. C1 NIH, Canc Biomarkers Res Grp, Organ Syst Branch, Analyt Epidemiol Branch, Rockville, MD 20852 USA. RP Srivastava, S (reprint author), NIH, Canc Biomarkers Res Grp, Organ Syst Branch, Analyt Epidemiol Branch, Executive Plaza N,Room 3144,6130 Executive Blvd, Rockville, MD 20852 USA. EM srivasts@mail.nih.gov NR 109 TC 5 Z9 6 U1 0 U2 4 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 JUL-AUG PY 2005 VL 4 IS 4 BP 1171 EP 1180 DI 10.1021/pr050017m PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 954VV UT WOS:000231184200015 PM 16083267 ER PT J AU Woods, AS Ferre, S AF Woods, AS Ferre, S TI Amazing stability of the arginine-phosphate electrostatic interaction SO JOURNAL OF PROTEOME RESEARCH LA English DT Article DE electrostatic interaction; receptor heteromers; phosphorylation; CK1; PKA ID DOPAMINE-D-2 RECEPTORS; ADENOSINE A(2A); MASS-SPECTROMETRY; HETEROMERIZATION; OLIGOMERIZATION; PHOSPHORYLATION AB Electrostatic interactions between a basic epitope containing adjacent arginine residues and an acidic epitope containing a phosphorylated serine are involved in receptor heteromerization. In the present study, we demonstrate that this arginine-phosphate electrostatic interaction possesses a "covalent-like" stability. Hence, these bonds can withstand fragmentation by mass spectrometric collision-induced dissociation at energies similar to those that fragment covalent bonds and they demonstrate an extremely low dissociation constant by plasmon resonance. The present work also highlights the importance of phosphorylation-dephosphorylation events in the modulation of this electrostatic attraction. Phosphorylation of the acidic epitope, a casein kinase one consensus site, makes it available to interact with the basic epitope. On the other hand, phosphorylation of serine and/or threonine residues adjacent to the basic epitope, a protein kinase A consensus site, slows down the attraction between the epitopes. Although analyzed here in the frame of receptor heteromerization, the arginine-phosphate electrostatic interaction most likely represents a general mechanism in protein-protein interactions. C1 NIDA, IRP, NIH, Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Woods, AS (reprint author), NIDA, IRP, NIH, Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM awoods@intra.nida.nih.gov RI Ferre, Sergi/K-6115-2014 OI Ferre, Sergi/0000-0002-1747-1779 FU Intramural NIH HHS [Z99 DA999999] NR 17 TC 132 Z9 132 U1 1 U2 14 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 JUL-AUG PY 2005 VL 4 IS 4 BP 1397 EP 1402 DI 10.1021/pr050077s PG 6 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 954VV UT WOS:000231184200040 PM 16083292 ER PT J AU Hallett, M AF Hallett, M TI Neuroplasticity and rehabilitation SO JOURNAL OF REHABILITATION RESEARCH AND DEVELOPMENT LA English DT Editorial Material ID HUMAN MOTOR CORTEX; INDUCED CORTICAL REORGANIZATION; DEPENDENT PLASTICITY; BEHAVIORAL RECOVERY; CHRONIC STROKE; D-AMPHETAMINE; BRAIN-INJURY; HUMAN HAND; STIMULATION; MODULATION C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 36,Rm 4D04, Bethesda, MD 20892 USA. NR 32 TC 15 Z9 15 U1 0 U2 3 PU JOURNAL REHAB RES & DEV PI BALTIMORE PA DEPT OF VETERANS AFFAIRS REHABIL RES & DEVELOP CTR 103 SOUTH GAY STREET, BALTIMORE, MD 21202-4051 USA SN 0748-7711 J9 J REHABIL RES DEV JI J. Rehabil. Res. Dev. PD JUL-AUG PY 2005 VL 42 IS 4 BP XVII EP XXI DI 10.1682/JRRD.2005.07.0126 PG 5 WC Rehabilitation SC Rehabilitation GA 995NB UT WOS:000234105900004 PM 16320136 ER PT J AU Bernatsky, S Clarke, A Cooper, G Mill, C Ramsey-Goldman, R Pineau, C AF Bernatsky, S Clarke, A Cooper, G Mill, C Ramsey-Goldman, R Pineau, C TI Cancer screening in lupus patients: No evidence of surveillance bias SO JOURNAL OF RHEUMATOLOGY LA English DT Meeting Abstract CT 12th Winter Workshop of the Canadian-Rheumatology-Association CY MAR 02-05, 2005 CL Mt Tremblant, CANADA SP Canadian Rheumatol Assoc C1 Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. NIH, Durham, NC USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2005 VL 32 IS 7 MA 6 BP 1386 EP 1386 PG 1 WC Rheumatology SC Rheumatology GA 945WA UT WOS:000230532000056 ER PT J AU Bernatsky, S Clarke, A Cooper, G Mill, C Ramsey-Goldman, R Pineau, C AF Bernatsky, S Clarke, A Cooper, G Mill, C Ramsey-Goldman, R Pineau, C TI Screening for cervical dysplasia: Preliminary results of a survey in SLE patients SO JOURNAL OF RHEUMATOLOGY LA English DT Meeting Abstract CT 12th Winter Workshop of the Canadian-Rheumatology-Association CY MAR 02-05, 2005 CL Mt Tremblant, CANADA SP Canadian Rheumatol Assoc C1 Montreal Gen Hosp, Montreal, PQ H3G 1A4, Canada. NIH, Durham, NC USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUL PY 2005 VL 32 IS 7 MA 11 BP 1388 EP 1388 PG 1 WC Rheumatology SC Rheumatology GA 945WA UT WOS:000230532000061 ER PT J AU Hui, TP Modarres, R Zheng, G AF Hui, TP Modarres, R Zheng, G TI Bootstrap confidence interval estimation of mean via ranked set sampling linear regression SO JOURNAL OF STATISTICAL COMPUTATION AND SIMULATION LA English DT Article DE ranked set sampling; regression estimator; bootstrap confidence interval; concomitant variable ID BIVARIATE FREQUENCY-DISTRIBUTIONS; LIMITING CONDITIONS; GENERAL FORMS AB It is well-known that when ranked set sampling (RSS) scheme is employed to estimate the mean of a population, it is more efficient than simple random sampling (SRS) with the same sample size. One can use a RSS analog of SRS regression estimator to estimate the population mean of Y using its concomitant variable X when they are linearly related. Unfortunately, the variance of this estimate cannot be evaluated unless the distribution of X is known. We investigate the use of resampling methods to establish confidence intervals for the regression estimation of the population mean. Simulation studies show that the proposed methods perform well in a variety of situations when the assumption of linearity holds, and decently well under mild non-linearity. C1 George Washington Univ, Dept Stat, Washington, DC 20052 USA. NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. RP Hui, TP (reprint author), George Washington Univ, Dept Stat, Washington, DC 20052 USA. EM thui@gwu.edu NR 17 TC 6 Z9 6 U1 2 U2 8 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0094-9655 J9 J STAT COMPUT SIM JI J. Stat. Comput. Simul. PD JUL PY 2005 VL 75 IS 7 BP 543 EP 553 DI 10.1080/00949650412331286124 PG 11 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 947DG UT WOS:000230623000004 ER PT J AU Yang, S Hsu, L Zhao, LP AF Yang, S Hsu, L Zhao, LP TI Combining asymptotically normal tests: case studies in comparison of two groups SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE asymptotically normal tests; asymptotic powers; contiguous alternatives; counting processes; critical values; martingales ID EFFICIENCY ROBUST-TESTS; SURVIVAL AB When several candidate tests are available for a given testing problem, and each has nice properties with respect to different criteria such as efficiency and robustness, it is desirable to combine them. We discuss various combined tests based on asymptotically normal tests. When the means of two standardized tests under contiguous alternatives are close, we show that the maximum of the two tests appears to have an overall best performance compared with other forms of combined tests considered, and that it retains most power compared with the better one of the two tests combined. As an application, for testing zero location shift between two groups, we studied the normal, Wilcoxon, median tests and their combined tests. Because of their structural differences, the joint convergence and the asymptotic correlation of the tests are not easily derived from the usual asymptotic arguments of the tests. We developed a novel application of martingale theory to obtain the asymptotic correlations and their estimators. Simulation studies were also performed to examine the small sample properties of these combined tests. Finally we illustrate the methods by a real data example. (c) 2004 Elsevier B.V. All rights reserved. C1 NHLBI, Off Biostat Res, Bethesda, MD 20892 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98109 USA. RP Yang, S (reprint author), NHLBI, Off Biostat Res, 6701 Rockledge Dr,Msc 7938, Bethesda, MD 20892 USA. EM yangso@nhlbi.nih.gov NR 13 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JUL 1 PY 2005 VL 133 IS 1 BP 139 EP 158 DI 10.1016/j.jspi.2004.03.007 PG 20 WC Statistics & Probability SC Mathematics GA 927UO UT WOS:000229226200008 ER PT J AU Nguyen, TL Schoehn, G Weissenhorn, W Hermone, AR Burnett, JC Panchal, RG McGrath, C Zaharevitz, DW Aman, MJ Gussio, R Bavari, S AF Nguyen, TL Schoehn, G Weissenhorn, W Hermone, AR Burnett, JC Panchal, RG McGrath, C Zaharevitz, DW Aman, MJ Gussio, R Bavari, S TI An all-atom model of the pore-like structure of hexameric VP40 from Ebola: Structural insights into the monomer-hexamer transition SO JOURNAL OF STRUCTURAL BIOLOGY LA English DT Article DE oligomerization; pore-like structure; molecular modeling; conformational changed; beta-sandwich; electron microscopy ID MATRIX PROTEIN VP40; BINDING PROPERTIES; VIRUS; OLIGOMERIZATION; TRAFFICKING; ASSOCIATION; MARBURG; TSG101 AB The matrix protein VP40 is an indispensable component of viral assembly and budding by the Ebola virus, VP40 is a monomer in Solution, but can fold into hexameric and octameric states. two oligomeric conformations that play central roles in the Ebola viral life cycle. While the X-ray structures of monomeric and octameric VP40 have been determined, the structure of hexameric VP40 has only been solved by three-dimensional electron microscopy (EM) to a resolution of' similar to 30 angstrom. In this paper. we present the refinement of the EM reconstruction of truncated hexameric VP40 to similar to 20 angstrom and the Construction of an all-atom model (residues 44 212) using the EM model at similar to 20 angstrom and the X-ray structure of monomeric VP40 as templates. The hexamer model suggests that the monomer hexamer transition involves a conformational change in the N-terminal domain that is not evident during octamerization and therefore. may provide the basis for elucidating the biological function of VP40. Published by Elsevier Inc. C1 NCI, Target Struct Based Drug Discovery Grp, Dev Therapeut Program, SAIC, Frederick, MD 21702 USA. Inst Biol Struct, F-38042 Grenoble, France. Univ Grenoble 1, Lab Virol Mol & Struct, F-38042 Grenoble, France. European Mol Biol Lab, F-38042 Grenoble, France. Clin Res Management Inc, Frederick, MD 21702 USA. USA, Med Res Inst Infect Dis, Ft Detrick, Frederick, MD 21702 USA. RP Gussio, R (reprint author), NCI, Target Struct Based Drug Discovery Grp, Dev Therapeut Program, SAIC, Frederick, MD 21702 USA. EM Gussio@neiferf.gov; Sina.Bavari@amedd.army.mil FU NCI NIH HHS [N01-CO-12400] NR 25 TC 16 Z9 17 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 1047-8477 J9 J STRUCT BIOL JI J. Struct. Biol. PD JUL PY 2005 VL 151 IS 1 BP 30 EP 40 DI 10.1016/j.jsb.2005.02.013 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 944FL UT WOS:000230411800004 PM 15908231 ER PT J AU Mattson, ME AF Mattson, ME TI Section 1: Conceptual and methodological foundations of COMBINE SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Editorial Material C1 NIAAA, Div Treatment & Recovery Res, Bethesda, MD 20892 USA. RP Mattson, ME (reprint author), NIAAA, Div Treatment & Recovery Res, Room 2045,NIH Mail Stop 9304,5635 Fishers Lane, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD JUL PY 2005 SU 15 BP 6 EP 7 PG 2 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 958KS UT WOS:000231445600002 ER PT J AU Mattson, ME Litten, RZ AF Mattson, ME Litten, RZ TI Combining treatments for alcoholism: Why and how? SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; NALTREXONE RESPONSE; RELAPSE PREVENTION; DEPENDENT PATIENTS; CLINICAL-TRIALS; DOUBLE-BLIND; ACAMPROSATE; THERAPY; METAANALYSIS; MODERATORS AB Treatment of alcohol disorders through the use of combinations of pharmacological and behavioral modalities may more effectively address the multicomponent nature of the disorder than single-modality approaches. Interdisciplinary models of the biological, psychological and social components of alcohol disorders are emerging rapidly from basic research, and treatment researchers have begun to test various strategies to combine medications and behavioral treatments. In addition to behavioral and pharmacological combinations, effective treatment pairs can be composed of two medications whose mechanisms of action are believed to be compatible and potentially additive, or even synergistic. Combining Medications and Behavioral Interventions (COMBINE) is a large multisite clinical trial sponsored by the National Institute on Alcohol Abuse and Alcoholism. Its goal is to determine if improvements in treatment outcome for alcohol dependence can be achieved by combining pharmacotherapy and behavioral interventions. Under evaluation is the efficacy of two promising medications (naltrexone and acamprosate), both singly and together, when used in conjunction with two behavioral treatments of differing intensities. This supplement describes in detail the methods and rationale for the approach taken in COMBINE. This first article in the supplement has three objectives: (1) to review strategies for conducting combination treatment studies as illustrated with selected examples from the literature, (2) to summarize the main design features of COMBINE as background for the articles in this supplement and (3) to comment on future directions for combination treatment research as the field moves beyond COMBINE. C1 NIAAA, Div Treatment & Recovery Res, Bethesda, MD 20892 USA. RP Mattson, ME (reprint author), NIAAA, Div Treatment & Recovery Res, 5635 Fishers Lane,NIH Mail Stop 9304, Bethesda, MD 20892 USA. EM mmattson@mail.nih.gov NR 51 TC 4 Z9 5 U1 4 U2 7 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD JUL PY 2005 SU 15 BP 8 EP 16 PG 9 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 958KS UT WOS:000231445600003 PM 16223051 ER PT J AU Goldman, D Oroszi, G O'Malley, S Anton, R AF Goldman, D Oroszi, G O'Malley, S Anton, R TI COMBINE genetics study: The pharmacogenetics of alcoholism treatment response: Genes and mechanisms SO JOURNAL OF STUDIES ON ALCOHOL LA English DT Article ID MU-OPIOID RECEPTOR; SEROTONIN TRANSPORTER GENE; COMPULSIVE DRINKING SCALE; PREFRONTAL CORTEX; USE DISORDERS; POLYMORPHISM; ASSOCIATION; ETHANOL; SENSITIVITY; DEPENDENCE AB Objective: Partial efficacy of treatment and differences in adverse events across individuals are a challenge and an opportunity in the treatment of alcoholism. Individuation of therapy and understanding origins of differential treatment response may require identification of inherited functional variants of genes. The neurobiology of reward, executive cognitive function, anxiety and dysphoria have been identified as critical domains that may have a genetic basis that could predict treatment response. Method: The COMBINE Study presents a unique opportunity to evaluate specific genetic loci (markers) that affect neurobiology central to addiction and extended withdrawal. The study also addresses variation in drug metabolism and action. Candidate genetic markers are selected for study based on functionality and abundance. Results: COMT Val158Met is a common (minor allele frequency 0.42), functional, catecholamine-metabolizing enzyme polymorphism with threefold relevance. Val158Met alters executive cognitive function, stress and anxiety responses and brain endogenous opioid function. OPRM1 Asn40Asp is a common (minor allele frequency 0.10), functional polymorphism of the mu-opioid receptor, which may serve as a gatekeeper molecule in naltrexone's actions and was recently reported to affect naltrexone response. HTTLPR (minor allele frequency 0.40) alters serotonin transporter function to affect anxiety, dysphoria and obsessional behavior, which are assessed in COMBINE and may be related to relapse and addictive behavior. Conclusions: All genetic testing is consented through a separate human research protocol, and the testing is conducted nonclinically, confidentially and apart from the clinical record to protect human research participants who have volunteered for this aspect of COMBINE. C1 NIAAA, Neurogenet Lab, NIH, Rockville, MD 20852 USA. RP Goldman, D (reprint author), NIAAA, Neurogenet Lab, NIH, 5625 Fishers Lane,Room 3S32,MSC9412, Rockville, MD 20852 USA. EM dgneuro@box-d.nih.gov RI Goldman, David/F-9772-2010 OI Goldman, David/0000-0002-1724-5405 NR 61 TC 17 Z9 17 U1 5 U2 10 PU ALCOHOL RES DOCUMENTATION INC CENT ALCOHOL STUD RUTGERS UNIV PI PISCATAWAY PA C/O DEIRDRE ENGLISH, 607 ALLISON RD, PISCATAWAY, NJ 08854-8001 USA SN 0096-882X J9 J STUD ALCOHOL JI J. Stud. Alcohol PD JUL PY 2005 SU 15 BP 56 EP 64 PG 9 WC Substance Abuse; Psychology SC Substance Abuse; Psychology GA 958KS UT WOS:000231445600010 PM 16223057 ER PT J AU Pine, DS Klein, RG Mannuzza, S Moulton, JL Lissek, S Guardino, M Woldehawariat, G AF Pine, DS Klein, RG Mannuzza, S Moulton, JL Lissek, S Guardino, M Woldehawariat, G TI Face-emotion processing in offspring at risk for panic disorder SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE anxiety; memory; panic disorder; genetics ID ANXIETY DISORDERS; NEURAL SYSTEMS; CHILDREN; SENSITIVITY; PARENTS; PSYCHOPATHOLOGY; ENGAGEMENT AB Objective: Panic disorder (PD) has been linked to perturbed processing of threats. This study tested the hypotheses that offspring of parents with PD and offspring with anxiety disorders display relatively greater sensitivity and attention allocation to fear provocation. Method: Offspring of adults with PD, major depressive disorder (MDD), or no disorder (ages 9-19) viewed computer-p resented face photographs depicting angry, fearful, and happy faces. Offspring rated (1) subjectively experienced fear level, (2) how hostile the face appeared, and (3) nose width. Attention allocation was indexed by latency to perform ratings. Results: Compared with offspring of parents without PD (n=79), offspring of PD parents (n=65) reported significantly more fear and had slower reaction times to rate fear, controlling for ongoing anxiety disorder in the offspring. Offspring with an anxiety disorder (n=65) reported significantly more fear than offspring without an anxiety disorder but not when parental PD was controlled. Social phobia but no other anxiety disorder in offspring was associated with slower reaction times for fear ratings (but not greater fear ratings). Parental PD and offspring social phobia independently predicted slower reaction time. Conclusions: Results support an association between parental PD and offspring responses to fear provocation. Social phobia in children may have a specific relationship to allocation of attention to subjective anxiety during face viewing. C1 NIMH, Intramural Res Program, Sect Dev Affect Neurosci, Bethesda, MD 20817 USA. Nathan S Kline Inst Psychiat Res, Orangeburg, NY 10962 USA. NYU, Ctr Child Study, New York, NY USA. RP Pine, DS (reprint author), NIMH, Intramural Res Program, Sect Dev Affect Neurosci, 15-K,Room 110,MSC-2670, Bethesda, MD 20817 USA. EM daniel.pine@nih.gov RI Lissek, Shmuel/B-6577-2008 FU NIMH NIH HHS [MH-59171] NR 29 TC 35 Z9 35 U1 1 U2 3 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 JUL PY 2005 VL 44 IS 7 BP 664 EP 672 DI 10.1097/01.chi.0000162580.92029.f4 PG 9 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 938WY UT WOS:000230035300014 PM 15968235 ER PT J AU Schultz, JC Granados, S Vonderheid, EC Hwang, ST AF Schultz, JC Granados, S Vonderheid, EC Hwang, ST TI T-cell clonality of peripheral blood lymphocytes in patients with lymphomatoid papulosis SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID MYCOSIS-FUNGOIDES; LYMPHOPROLIFERATIVE DISORDERS; SEZARY-SYNDROME; CD30 AB Six patients with lymphomatoid papulosis demonstrated a clonal T-cell population in skin lesions by polymerase chain reaction methods. Two of these patients showed identical T-cell clones in their peripheral blood T cells as well. In one case, the clone persisted in the blood despite clearing of skin lesions with methotrexate. C1 NCI, Dermatol Branch, Ctr Canc Res, Bethesda, MD USA. Johns Hopkins Sch Med, Dept Dermatol, Baltimore, MD USA. RP Hwang, ST (reprint author), Bldg 10,Rm12N238,10 Ctr Dr, Bethesda, MD 20892 USA. EM hwangs@mail.nih.gov NR 16 TC 7 Z9 7 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 JUL PY 2005 VL 53 IS 1 BP 152 EP 155 DI 10.1016/j.jaad.2005.01.014 PG 4 WC Dermatology SC Dermatology GA 943PT UT WOS:000230366900025 PM 15965440 ER PT J AU Windham, BG Griswold, ME Fried, LP Rubin, GS Xue, QL Carlson, MC AF Windham, BG Griswold, ME Fried, LP Rubin, GS Xue, QL Carlson, MC TI Impaired vision and the ability to take medications SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE visual acuity; contrast sensitivity; stereopsis; medications; adherence ID VISUAL IMPAIRMENT; COGNITIVE PERFORMANCE; CONTRAST SENSITIVITY; FUNCTIONAL ABILITY; PATIENT COMPLIANCE; STRONG CONNECTION; OLDER ADULTS; SEE PROJECT; DRUG-USE; POPULATION AB OBJECTIVES: To assess relationships between vision (contrast sensitivity, stereopsis, visual acuity) and a performance-based measure of ability to implement new medications. DESIGN: Cross-sectional analysis; prospective cohort study. SETTING: Community-based. PARTICIPANTS: Three hundred thirty-five participants aged 73 to 82 in Year 3 of the Women's Health and Aging Study 11, a representative sample of the two-thirds least-disabled community-dwelling women. MEASUREMENTS: Hopkins Medication Schedule Pillbox Ratio, a joint measure of accuracy and time, and a performance-based measure of ability to Implement a prescription. Participants received written and verbal instructions for taking two medications and were directed to place pills in a pillbox accordingly. Vision assessments: contrast sensitivity (Pelli-Robson letter sensitivity chart), stereopsis (Randot Circles), and visual acuity (Early Treatment Diabetic Retinopathy Study eye chart). RESULTS: Forty-four percent (148/335) of women incorrectly placed one or both medications. Each vision measure was positively associated with Pillbox Ratio scores and varied with cognition and time to completion. Better visual acuity, contrast sensitivity, and stereopsis were each associated with better performance in women with poor cognition who filled the pillbox quickly. Additionally, better visual acuity was associated with better performance in participants with good cognition who filled the pillbox slowly; better stereopsis was associated with better performance in participants with poor cognition who filled the pillbox slowly and whose stereoacuity was below normal. CONCLUSION: Visual acuity, contrast sensitivity, and stereopsis should be considered potential risk factors for impaired ability to implement a medication regimen in older adults. Future research should investigate the role of vision, including contrast sensitivity and stereopsis, on performance of other instrumental activities of daily living. C1 NIA, NIH, Clin Res Branch, Baltimore, MD 21225 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ, Div Geriatr Med & Gerontol, Baltimore, MD USA. Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD USA. Johns Hopkins Univ, Dept Mental Hlth, Baltimore, MD USA. UCL, Inst Ophthalmol, London, England. RP Windham, BG (reprint author), NIA, NIH, Clin Res Branch, 3001 S Hanover St,Room NM536, Baltimore, MD 21225 USA. EM windhamgw@grc.nia.nih.gov FU NCRR NIH HHS [RR00722]; NIA NIH HHS [R01 AG1170301A1] NR 37 TC 20 Z9 23 U1 4 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2005 VL 53 IS 7 BP 1179 EP 1190 DI 10.1111/j.1532-5415.2005.53376.x PG 12 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 944WB UT WOS:000230460500013 PM 16108936 ER PT J AU Atkinson, HH Cesari, M Kritchevsky, SB Penninx, BWJH Fried, LP Guralnik, JM Williamson, JD AF Atkinson, HH Cesari, M Kritchevsky, SB Penninx, BWJH Fried, LP Guralnik, JM Williamson, JD TI Predictors of combined cognitive and physical decline SO JOURNAL OF THE AMERICAN GERIATRICS SOCIETY LA English DT Article DE cognitive; physical; function; decline; women ID LOWER-EXTREMITY FUNCTION; MINI-MENTAL-STATE; FUNCTIONAL DEPENDENCE; HEMOGLOBIN LEVELS; SKELETAL-MUSCLE; OLDER; PERFORMANCE; DISABILITY; LIMITATIONS; ADULTS AB OBJECTIVES: To determine the incidence and correlates of combined declines in cognitive and physical performance. DESIGN: Cohort study of community-dwelling older women with moderate to severe disability. SETTING: The community surrounding Baltimore, Maryland. PARTICIPANTS: Participants in the Women's Health and Aging Study I with Mini-Mental State Examination (MMSE) score or 24 or greater and walking speed greater than 0.4 m/s at baseline. MEASUREMENTS: Cognitive decline was defined as an MMSE score less than 24 and physical decline as a walking speed of 0.4 m/s or less in at least one of the three annual follow-up visits. Participants were stratified into groups based on cognitive or physical decline or both. Group characteristics were compared, and results were adjusted for age, race, education, and significant covariates. RESULTS: Of 558 women that met the baseline MMSE and walking speed inclusion criteria, 21% developed physical decline, 12% developed cognitive decline, and 11% experienced combined cognitive and physical decline. After adjustment, physical decline was associated with age, non-white race, former smoking, baseline walking speed, and instrumental activities of daily living (IADL) impairment. Cognitive decline was associated with age and baseline MMSE score. Combined decline was associated with age, baseline walking speed, MMSE score, IADL impairment, as well as current smoking (odds ratio (OR) = 5.66, 95% confidence interval (CI) = 1.49-21.54) and hemoglobin level (OR = 0.68, 95% CI = 0.47-0.98). CONCLUSION: Potential predictors of cognitive and physical performance decline were identified. The association between smoking and lower hemoglobin levels and combined cognitive and physical decline may represent potentially modifiable risk factors and should be confirmed in future studies. C1 Wake Forest Univ, Sch Med,Sect Gerontol & Geriatr Med, Roena Kulynych Ctr Memory & Cognist Res, Sticht Ctr Aging,Dept Internal Med, Winston Salem, NC 27157 USA. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. NIA, Bethesda, MD 20892 USA. Vrije Univ Amsterdam, Ctr Med, Inst Res Extramural Med, NL-1081 HV Amsterdam, Netherlands. RP Atkinson, HH (reprint author), Wake Forest Univ, Sch Med,Sect Gerontol & Geriatr Med, Roena Kulynych Ctr Memory & Cognist Res, Sticht Ctr Aging,Dept Internal Med, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM hatkinso@wfubmc.edu RI Cesari, Matteo/A-4649-2008; OI Cesari, Matteo/0000-0002-0348-3664; Kritchevsky, Stephen/0000-0003-3336-6781 FU NIA NIH HHS [AG-09834, N01-AG-1-2112, P30-AG-021332-03] NR 30 TC 71 Z9 75 U1 1 U2 6 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0002-8614 J9 J AM GERIATR SOC JI J. Am. Geriatr. Soc. PD JUL PY 2005 VL 53 IS 7 BP 1197 EP 1202 DI 10.1111/j.1532-5415.2005.53362.x PG 6 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 944WB UT WOS:000230460500015 PM 16108938 ER PT J AU Fung, KW Hole, WT Nelson, SJ Srinivasan, S Powell, T Roth, L AF Fung, KW Hole, WT Nelson, SJ Srinivasan, S Powell, T Roth, L TI Integrating SNOMED CT into the UMLS: An exploration of different views of synonymy and quality of editing SO JOURNAL OF THE AMERICAN MEDICAL INFORMATICS ASSOCIATION LA English DT Article ID REPRESENTATION; KNOWLEDGE AB Objective: The integration of SNOMED CT into the Unified Medical Language System (UMLS) involved the alignment of two views of synonymy that were different because the two vocabulary systems have different intended purposes and editing principles. The UMLS is organized according to one view of synonymy, but its structure also represents all the individual views of synonymy present in its source vocabularies. Despite progress in knowledge-based automation of development and maintenance of vocabularies, manual curation is still the main method of determining synonymy. The aim of this study was to investigate the quality of human judgment of synonymy. Design: Sixty pairs of potentially controversial SNOMED CT synonyms were reviewed by 11 domain vocabulary experts (six UMLS editors and five noneditors), and scores were assigned according to the degree of synonymy. Measurements: The synonymy scores of each subject were compared to the gold standard (the overall mean synonymy score of all subjects) to assess accuracy. Agreement between UMLS editors and noneditors was measured by comparing the mean synonymy scores of editors to noneditors. Results: Average accuracy was 71% for UMLS editors and 75% for noneditors (difference not statistically significant). Mean scores of editors and noneditors showed significant positive correlation (Spearman's rank correlation coefficient 0.654, two-tailed p < 0.01) with a concurrence rate of 75% and an interrater agreement kappa of 0.43. Conclusion: The accuracy in the judgment of synonymy was comparable for UMLS editors and nonediting domain experts. There was reasonable agreement between the two groups. C1 Natl Lib Med, Bethesda, MD 20894 USA. RP Fung, KW (reprint author), Natl Lib Med, Bldg 38A,Room 9N904,MS54,8600 Rockville Pike, Bethesda, MD 20894 USA. EM kwfung@nlm.nih.gov NR 21 TC 27 Z9 27 U1 0 U2 0 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1067-5027 J9 J AM MED INFORM ASSN JI J. Am. Med. Inf. Assoc. PD JUL-AUG PY 2005 VL 12 IS 4 BP 486 EP 494 DI 10.1197/jamia.M1767 PG 9 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Information Science & Library Science; Medical Informatics SC Computer Science; Information Science & Library Science; Medical Informatics GA 950LR UT WOS:000230859200015 PM 15802483 ER EF