FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Meyskens, FL Szabo, E AF Meyskens, FL Szabo, E TI Diet and cancer: The disconnect between epidemiology and randomized clinical trials SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article; Proceedings Paper CT Translational Cancer Prevention Workshop CY MAY 04-06, 2004 CL Haifa, ISRAEL ID BETA-CAROTENE; CALCIUM SUPPLEMENTATION; COLON-CANCER; LUNG-CANCER; VITAMIN-D; PREVENTION; DISEASE; NUTRITION; FOLATE; RISK AB Dietary epidemiology has been highly successful in identifying the responsible agent in many diseases, including scurvy, pellagra, blindness, and spinal bifida. Case-control, cohort, and ecologic observational studies have consistently associated increased consumption of fruits and vegetables with a decreased risk for a wide variety of epithelial cancers and, in many cases, specific dietary components seem to decrease the risk for a wide array of epithelial cancers. Over time, there has been enthusiasm for one or another compounds, such as carotene in the past and folate currently. Despite the success of translating similar epidemiologic observations to clinical benefit in other areas of medicine via the crucible of the randomized clinical trial, this strategy has not been nearly as successful for cancer. We propose that the inability of nutritional epidemiology to identify effective chemopreventive strategies is not just a problem of quantitation, but rather that the discipline is usually qualitatively incapable of identifying a dietary compound(s) that will be efficacious. One needs to consider the following basic questions in trying to understand why nutritional epidemiology has not been translated into progress in cancer prevention: Why do fruits and vegetable show a consistent protective effect against many epithelial cancers in epidemiologic studies? Once a specific dietary compound is identified as protective in observational studies, why do most subsequent observational studies confirm the effect? Why are dietary epidemiology observations frequently not confirmed by the randomized clinical trial? We call the identified problems "fishing with only one bait" and the "four-legged stool problem." The considerations identified in this analysis offer a number of possible solutions to puzzling findings: (a) Fruits and vegetables consistently show a protective effect against cancer in observational studies because they represent the entire "biological action package." (b) Dietary compounds show a protective effect in observational studies, but not in clinical trials, because this is an inevitable consequence of one compound being falsely identified as the active agent in a system in which multiple agents or multiple interacting regulatory molecules underlie the biological effect. The consequences are serious for trying to use epidemiology to identify effective nutritional compounds. The major conclusion has to be as follows: Supplementation with single dietary compounds is rarely going to be as effective as epidemiologic studies suggest; it is the biological action package that determines efficacy. Options for how we should move forward will be discussed. Dietary observational epidemiology is complex and involves many biases and confounders. We need to be more critical in the design of large randomized trials based on observational epidemiology or analysis. Rules of evidence are frequently ignored or misunderstood although the limitations of observational epidemiology are analogous to the problems associated with discovery-based research and biomarker identification. We need to be much more self-critical in the important and critical assessment of dietary compounds and their role in cancer prevention given the very high appeal for this approach both within the lay and scientific communities. C1 Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Dept Med, Orange, CA 92668 USA. Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Dept Biol Chem, Orange, CA 92668 USA. NCI, Div Canc Prevent, NIH, Bethesda, MD 20892 USA. RP Meyskens, FL (reprint author), Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Dept Med, Bldg 44,Route 81,101 City Dr, Orange, CA 92668 USA. EM flmeyske@uci.edu FU NCI NIH HHS [CA-62203] NR 20 TC 73 Z9 73 U1 0 U2 8 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2005 VL 14 IS 6 BP 1366 EP 1369 DI 10.1158/1055-9965.EPI-04-0666 PG 4 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 935GB UT WOS:000229766600008 PM 15941942 ER PT J AU Potischman, N Troisi, R Thadhani, R Hoover, RN Dodd, K Davis, WW Sluss, PM Hsieh, CC Ballard-Barbash, R AF Potischman, N Troisi, R Thadhani, R Hoover, RN Dodd, K Davis, WW Sluss, PM Hsieh, CC Ballard-Barbash, R TI Pregnancy hormone concentrations across ethnic groups: Implications for later cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID BREAST-CANCER; AFRICAN-AMERICAN; ESTROGEN-LEVELS; UNITED-STATES; IN-UTERO; WOMEN; TESTOSTERONE; MEN; ASSOCIATIONS; ENVIRONMENT AB A variety of in utero factors have been associated with risk of adult cancers, particularly birth weight, toxemia, and gestational age. These factors are thought to reflect hormonal exposures during pregnancy. We hypothesized that the prenatal hormonal milieu may explain part of the variation in cancer rates across ethnic groups, for example, the higher incidence of breast cancer in the Caucasian compared with Hispanic women and the higher incidence of prostate and lower incidence of testicular cancers among African-Americans compared with Caucasians. We measured hormones in early pregnancy blood samples from three ethnic groups in a health care plan in Boston, MA. Mean levels of androstenedione, testosterone, estrone, and prolactin were significantly lower in Caucasian women compared with Hispanic women. Although not statistically significant, estradiol levels were lower in Caucasian compared with Hispanic or African-American women. Concentrations of androstenedione, testosterone, and progesterone were notably higher in African-American compared with Caucasian or Hispanic women. These data are consistent with hypotheses that in utero hormonal exposures may explain some of the ethnic group differences in cancer risk. C1 NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Stat Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NCI, Program Epidemiol, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Massachusetts, Sch Med, Worcester, MA USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. RP Potischman, N (reprint author), NCI, Appl Res Program, Div Canc Control & Populat Sci, 4005 EPN,6130 Executive Blvd, Bethesda, MD 20892 USA. EM potischn@mail.nih.gov NR 39 TC 37 Z9 37 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 JUN PY 2005 VL 14 IS 6 BP 1514 EP 1520 DI 10.1158/1055-9965.EPI-04-0869 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 935GB UT WOS:000229766600031 PM 15941965 ER PT J AU Roth, MJ Paltoo, DN Albert, PS Baer, DJ Judd, JT Tangrea, J Taylor, PR AF Roth, MJ Paltoo, DN Albert, PS Baer, DJ Judd, JT Tangrea, J Taylor, PR TI Common leptin receptor polymorphisms do not modify the effect of alcohol ingestion on serum leptin levels in a controlled feeding and alcohol ingestion study SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Editorial Material ID BREAST-CANCER; GROWTH-FACTOR; GENE POLYMORPHISMS; EPITHELIAL-CELLS; PROSTATE-CANCER; OBESITY; WOMEN; ASSOCIATION; INSULIN; DIET AB We explored whether serum leptin response to alcohol ingestion was related to common leptin receptor gene polymorphisms, K109R (Lys(109)Arg), Q223R (Gln(223)Arg), S343S [Ser(T)(343)Ser(C)], and K656N (Lys(656)Asn), of reported physiologic significance during a controlled intervention. Fifty-three participants rotated through three 8-week treatment periods and consumed 0, 15 (equivalent to one drink), or 30 g (equivalent to two drinks) of alcohol (95% ethanol in 12 ounces of orange juice) per day, in random order. During the controlled feeding periods, all food and beverages including alcoholic beverages were prepared and supplied by the staff of the Beltsville Human Nutrition Research Center's Human Study Facility (Beltsville, MD), and energy intake was adjusted to maintain a constant weight. Blood was collected after an overnight fast on 3 separate days during the last week of each controlled feeding period and pooled for hormone analysis. Circulating serum leptin concentration was measured in duplicate by RIA and genotype analysis was done on DNA extracted from WBC using real-time PCR analysis amplification (TaqMan). Linear mixed models with a single random intercept reflecting a participant effect were used to estimate changes in serum leptin levels at 15 and 30 g of alcohol per day relative to 0 g of alcohol per day. No significant effects were found between common leptin receptor polymorphisms and serum leptin levels (P >= 0.26). C1 NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. NCI, Canc Res Ctr, Bethesda, MD 20892 USA. NHLBI, Clin & Mol Med Program, Bethesda, MD 20892 USA. USDA ARS, Beltsville Agr Res Ctr, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. RP Roth, MJ (reprint author), NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Suite 705,MSC 8314, Bethesda, MD 20892 USA. EM mr166i@nih.gov NR 23 TC 2 Z9 3 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 JUN PY 2005 VL 14 IS 6 BP 1576 EP 1578 DI 10.1158/1055-9965.EPI-05-0008 PG 3 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 935GB UT WOS:000229766600043 PM 15941977 ER PT J AU Medin, JA Liang, SB Hou, JWS Kelley, LS Peace, DJ Fowler, DH AF Medin, JA Liang, SB Hou, JWS Kelley, LS Peace, DJ Fowler, DH TI Efficient transfer of PSA and PSMA cDNAs into DCs generates antibody and T cell antitumor responses in vivo SO CANCER GENE THERAPY LA English DT Article DE dendritic cells; immunotherapy; onco-retrovirus ID PROSTATE-SPECIFIC ANTIGEN; PULSED DENDRITIC CELLS; BONE-MARROW-CELLS; FABRY-DISEASE; GENE-TRANSFER; CANCER; LYMPHOCYTES; THERAPY; ADENOCARCINOMA; IMMUNOTHERAPY AB Gene therapy for prostate cancer may be realized through transduction of whole genes, such as PSA or PSMA, into immunotherapeutic dendritic cells (DCs). An oncoretroviral vector encoding human PSMA and a bicistronic oncoretroviral vector encoding human PSA and cell surface CD25 cDNAs were constructed. Remarkably, transfer of PSA/CD25 or PSMA cDNA during murine hematopoietic cell differentiation into DCs occurred with approximately 80% efficiency. In vitro, transduced DCs retained allostimulatory function and primed syngeneic T cells for tumor antigen-specific IFN-γ secretion. In test experiments designed to elucidate mechanisms in vivo, syngeneic recipients of transduced DCs had increased anti-human PSA antibody titers and tumor-specific CD8(+) T cell IFN-γ secretion with no detectable immune response to CD25. Gene-modified DC recipients had increased protection from specific tumor challenge for at least 18 weeks post-vaccination. DC vaccination also protected both male and female recipients. Gene-modified DC vaccination mediated regression of established, specific gene-expressing, TRAMP-C1 prostate cancer cell tumors. These findings indicate that antibody and cellular responses generated through PSA and PSMA gene transfer into DC yielded protective immunity, thereby providing further preclinical support for the implementation of immuno-gene therapy approaches for prostate cancer. C1 Ontario Canc Inst, Div Expt Therapeut, Toronto, ON M5G 2M1, Canada. Univ Toronto, Dept Med Biophys, Toronto, ON M5G 2M1, Canada. NCI, Expt Transplantat & Immunol Branch, Bethesda, MD 20892 USA. Univ Illinois, Dept Med, Hematol Oncol Sect, Chicago, IL 60607 USA. RP Medin, JA (reprint author), Univ Hlth Network, 67 Coll St Room 406, Toronto, ON M5G 2M1, Canada. EM jmedin@uhnres.utoroto.ca NR 40 TC 22 Z9 23 U1 0 U2 0 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 JUN PY 2005 VL 12 IS 6 BP 540 EP 551 DI 10.1038/sj.cgt.7700810 PG 12 WC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Oncology; Genetics & Heredity; Research & Experimental Medicine GA 926RR UT WOS:000229140800004 PM 15678150 ER PT J AU Slebos, RJC Livanos, E Yim, HW Randell, SH Parsons, AM Detterbeck, FC Rivera, MP Taylor, JA AF Slebos, RJC Livanos, E Yim, HW Randell, SH Parsons, AM Detterbeck, FC Rivera, MP Taylor, JA TI Chromosomal abnormalities in bronchial epithelium from smokers, nonsmokers, and lung cancer patients SO CANCER GENETICS AND CYTOGENETICS LA English DT Article ID RISK; INDIVIDUALS; ABERRATIONS; LYMPHOCYTES AB The identification of individuals who are at greatest risk of developing lung cancer would greatly improve diagnosis and possibly lead to early treatment. To study the use of karyotypes for this purpose, we used short-term human bronchial epithelial (hBE) cell cultures from nonsmokers, smokers, and lung cancer patients. Twenty-five metaphases were scored for hBE cell cultures obtained from 32 patients: 8 were nonsmokers, and 24 had a history of smoking (of whom 11 had had lung cancer surgery). The number of abnormal metaphases ranged from 0 to 4 per cell culture. No overall differences in the number of abnormal metaphases were observed between nonsmokers and smokers or between lung cancer patients and non-lung cancer patients. The most commonly observed abnormalities were structural changes in chromosome 1 (six cultures), loss of chromosome 17 (six cultures), and trisomy of chromosome 20 (three cultures). These specific alterations were found almost exclusively in patients with a history of tobacco smoking. The results did not indicate that general chromosomal abnormalities are a useful marker for tobacco smoke exposure or cancer risk. (c) 2005 Elsevier Inc. All rights reserved. C1 NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Pathol, Chapel Hill, NC USA. Univ N Carolina, Dept Cell & Mol Physiol, Chapel Hill, NC USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. Univ N Carolina, Dept Surg, Chapel Hill, NC 27599 USA. NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Taylor, JA (reprint author), NIEHS, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. EM taylor@niehs.nih.gov OI taylor, jack/0000-0001-5303-6398 NR 15 TC 3 Z9 3 U1 0 U2 0 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 JUN PY 2005 VL 159 IS 2 BP 137 EP 142 DI 10.1016/j.cancergencyto.2004.10.008 PG 6 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 933UA UT WOS:000229657200006 PM 15899385 ER PT J AU Matsuoka, M Jeang, KT AF Matsuoka, M Jeang, KT TI Human T-cell leukemia virus type I at age 25: A progress report SO CANCER RESEARCH LA English DT Review ID NF-KAPPA-B; PROTEASOME INHIBITOR PS-341; HTLV-I; TAX ONCOPROTEIN; TERMINAL REPEAT; LYMPHOCYTES; LEUKEMIA/LYMPHOMA; ACTIVATION; TRANSPLANTATION; EXPRESSION AB It has been 25 years since the discovery of human T-cell leukemia virus type I (HTLV-1) and its role in adult T-cell leukemia. Here, in brief, we review the current state of our understanding of HTLV-1 epidemiology, viral biology, pathogenesis, and treatment. We discuss how HTLV-1 may transform cells through destabilization of cellular genomic integrity and induction of cellular tolerance for chromosomal errors. C1 Kyoto Univ, Inst Virus Res, Lab Virus Immunol, Kyoto 606, Japan. NIAID, Mol Microbiol Lab, NIH, Bethesda, MD 20892 USA. RP Jeang, KT (reprint author), Bldg 4,Room 306,9000 Rockville Pike, Bethesda, MD 20892 USA. EM kj7e@nih.gov RI Jeang, Kuan-Teh/A-2424-2008; OI Matsuoka, Masao/0000-0002-0473-754X NR 53 TC 19 Z9 21 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2005 VL 65 IS 11 BP 4467 EP 4470 DI 10.1158/0008-5472.CAN-05-0559 PG 4 WC Oncology SC Oncology GA 930HZ UT WOS:000229407800001 PM 15930259 ER PT J AU Kirschner, LS Kusewitt, DF Matyakhina, L Towns, WH Carney, JA Westphal, H Stratakis, CA AF Kirschner, LS Kusewitt, DF Matyakhina, L Towns, WH Carney, JA Westphal, H Stratakis, CA TI A mouse model for the Carney complex tumor syndrome develops neoplasia in cyclic AMP-responsive tissues SO CANCER RESEARCH LA English DT Article ID PROTEIN-KINASE-A; MCCUNE-ALBRIGHT SYNDROME; SUBUNIT TYPE 1A; REGULATORY SUBUNIT; FIBROUS DYSPLASIA; TRANSCRIPTIONAL ACTIVITY; ACTIVATING MUTATIONS; SCHWANN-CELLS; ALPHA GENE; RI-ALPHA AB Carney complex is an autosomal dominant neoplasia syndrome characterized by spotty skin pigmentation, myxomatosis, endocrine tumors, and schwannomas. This condition may be caused by inactivating mutations in PRKAR1A, the gene encoding the type 1A regulatory subunit of protein kinase A. To better understand the mechanism by which PRKAR1A mutations cause disease, we have developed conventional and conditional null alleles for Prkar1a in the Mouse. Prkar1a(-/-) mice developed nonpigmented schwannomas and fibro-osseous bone lesions beginning at similar to 6 months of age. Although genotype-specific cardiac and adrenal lesions were not seen, benign and malignant thyroid neoplasias were observed in older mice. This spectrum of tumors overlaps that seen in Carney complex patients, confirming the validity of this mouse model. Genetic analysis indicated that allelic loss occurred in a subset of tumor cells, suggesting that complete loss of Prkar1a plays a key role in tumorigenesis. Similarly, tissue-specific ablation of Prkar1a from a subset of facial neural crest cells caused the formation of schwannomas with divergent differentiation. These observations confirm the identity of PRKAR1A as a tumor suppressor gene with specific importance to cyclic AMP-responsive tissues and suggest that these mice may be valuable tools not only for understanding endocrine tumorigenesis but also for understanding inherited predispositions for schwannoma formation. C1 Ohio State Univ, Human Canc Genet Program, Columbus, OH 43210 USA. Ohio State Univ, Dept Internal Med, Div Endocrinol, Columbus, OH 43210 USA. Ohio State Univ, Vet Biosci Program, Columbus, OH 43210 USA. NICHHD, Sect Genet & Endocrinol, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genet & Dev, NIH, Bethesda, MD 20892 USA. Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. RP Kirschner, LS (reprint author), Ohio State Univ, Human Canc Genet Program, TMRF 544,420 W 12th Ave, Columbus, OH 43210 USA. EM Kirschner-1@medctr.osu.edu RI Kirschner, Lawrence/E-3392-2011 FU NCI NIH HHS [CA16058]; NICHD NIH HHS [HD01323] NR 46 TC 120 Z9 120 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2005 VL 65 IS 11 BP 4506 EP 4514 DI 10.1158/0008-5472.CAN-05-0580 PG 9 WC Oncology SC Oncology GA 930HZ UT WOS:000229407800007 PM 15930266 ER PT J AU Milyavsky, M Tabach, Y Shats, I Erez, N Cohen, Y Tang, XH Kalis, M Kogan, I Buganim, Y Goldfinger, N Ginsberg, D Harris, CC Domany, E Rotter, V AF Milyavsky, M Tabach, Y Shats, I Erez, N Cohen, Y Tang, XH Kalis, M Kogan, I Buganim, Y Goldfinger, N Ginsberg, D Harris, CC Domany, E Rotter, V TI Transcriptional programs following genetic alterations in p53, INK4A, and H-Ras genes along defined stages of malignant transformation SO CANCER RESEARCH LA English DT Article ID IMMORTALIZED HUMAN FIBROBLASTS; BREAST-CANCER; COLORECTAL TUMORIGENESIS; MEDIATED TRANSFORMATION; EXPRESSION PATTERNS; MICROARRAY DATA; GROWTH-CONTROL; CELL LYMPHOMA; P16(INK4A); SARCOMA AB The difficulty to dissect a complex phenotype of established malignant cells to several critical transcriptional programs greatly impends our understanding of the malignant transformation. The genetic elements required to transform some primary human cells to a tumorigenic state were described in several recent studies. We took the advantage of the global genomic profiling approach and tried to go one step further in the dissection of the transformation network. We sought to identify the genetic signatures and key target genes, which underlie the genetic alterations in p53, Ras, INK4A locus, and telomerase, introduced in a stepwise manner into primary human fibroblasts. Here, we show that these are the minimally required genetic alterations for sarcomagenesis in vivo. A genome-wide expression profiling identified distinct genetic signatures corresponding to the genetic alterations listed above. Most importantly, unique transformation hallmarks, such as differentiation block, aberrant mitotic progression, increased angiogenesis, and invasiveness, were identified and coupled with genetic signatures assigned for the genetic alterations in the p53, INK4A locus, and H-Ras, respectively. Furthermore, a transcriptional program that defines the cellular response to p53 inactivation was an excellent predictor of metastasis development and bad prognosis in breast cancer patients. Deciphering these transformation fingerprints, which are affected by the most common oncogenic mutations, provides considerable insight into regulatory circuits controlling malignant transformation and will hopefully open new avenues for rational therapeutic decisions. C1 Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. Weizmann Inst Sci, Dept Phys Complex Syst, IL-76100 Rehovot, Israel. Natl Canc Inst, Human Carcinogenesis Lab, NIH, Bethesda, MD USA. RP Rotter, V (reprint author), Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel. EM varda.rotter@weizmann.ac.il RI Milyavsky, Michael/E-8306-2011; DOMANY, EYTAN/K-1560-2012 FU NCI NIH HHS [5 PO1 CA 65930-06] NR 58 TC 44 Z9 44 U1 0 U2 6 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 JUN 1 PY 2005 VL 65 IS 11 BP 4530 EP 4543 DI 10.1158/0008-5472.CAN-04-3880 PG 14 WC Oncology SC Oncology GA 930HZ UT WOS:000229407800011 PM 15930270 ER PT J AU Song, L Zlobin, A Ghoshal, P Zhang, Q Houde, C Weijzen, S Jiang, Q Nacheva, E Yagan, D Davis, E Galiegue-Zouitina, S Catovsky, D Grogan, T Fisher, RI Miele, L Coignet, LJ AF Song, L Zlobin, A Ghoshal, P Zhang, Q Houde, C Weijzen, S Jiang, Q Nacheva, E Yagan, D Davis, E Galiegue-Zouitina, S Catovsky, D Grogan, T Fisher, RI Miele, L Coignet, LJ TI Alteration of SMRT tumor suppressor function in transformed non-Hodgkin lymphomas SO CANCER RESEARCH LA English DT Article ID HISTONE DEACETYLASE COMPLEX; B-CELL LYMPHOMA; TRANSCRIPTIONAL REPRESSION; BURKITT-LYMPHOMA; HORMONE RECEPTORS; COREPRESSOR SMRT; KAPPA-B; N-COR; GENE; EXPRESSION AB Indolent non-Hodgkin lymphomas are characterized by a prolonged phase that is typically followed by a clinical progression associated with an accelerated clinical course and short survival time. Previous studies have not identified a consistent cytogenetic or molecular abnormality associated with transformation. The development of a transformed phenotype, evolving from the original low-grade component, most likely depends on multiple genetic events, including the activation of synergistic dominant oncogenes and a loss of tumor suppressor gene functions. Complex karyotypes and relatively bad chromosome morphology are typical of transformed non-Hodgkin lymphomas, rendering complete cytogenetic analysis difficult. Here, we report the use of transformed non-Hodgkin lymphoma cell lines and primary samples to identify the involvement of the silencing mediator of retinoic acid and thyroid hormone receptor (SMRT) gene that maps at chromosome 12q24 in transformed non-Hodgkin lymphomas. We also show that down-regulation of SMRT in the immortalized "Weinberg's model" cell lines induces transformation of the cells. Assessment of cDNA array profiles should further help us to design a working model for SMRT involvement in non-Hodgkin lymphoma transformation as a novel, nonclassical tumor suppressor. C1 Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. Loyola Univ, Med Ctr, Cardiunal Bernardin Canc Ctr, Dept Med, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Cardiunal Bernardin Canc Ctr, Dept Pathol, Maywood, IL 60153 USA. Royal Free Hosp, Dept Haematol, London NW3 2QG, England. Royal Marsden Hosp, Canc Res Inst, London, England. Illinois Math & Sci Acad, Aurora, IL USA. Natl Canc Inst, Metab Branch, Bethesda, MD USA. INSERM, F-59045 Lille, France. Univ Arizona, Dept Pathol, Tucson, AZ USA. RP Coignet, LJ (reprint author), Roswell Pk Canc Inst, Dept Canc Genet, Cell & Virus Bldg,Room 323 Elm & Carlton St, Buffalo, NY 14263 USA. EM lionel.coignet@roswellpark.org RI Miele, Luca/C-2255-2015 OI Miele, Luca/0000-0003-3464-0068 FU NCI NIH HHS [R01CA95429] NR 58 TC 14 Z9 15 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2005 VL 65 IS 11 BP 4554 EP 4561 DI 10.1158/0008-5472.CAN-04-4108 PG 8 WC Oncology SC Oncology GA 930HZ UT WOS:000229407800013 PM 15930272 ER PT J AU Chen, JG Xu, XN Underhfll, CB Yang, SM Wang, LP Chen, YX Hong, SG Creswell, K Zhang, LR AF Chen, JG Xu, XN Underhfll, CB Yang, SM Wang, LP Chen, YX Hong, SG Creswell, K Zhang, LR TI Tachyplesin activates the classic complement pathway to kill tumor cells SO CANCER RESEARCH LA English DT Article ID KLEBSIELLA-PNEUMONIAE; HYALURONAN SYNTHASE-3; ANTIBIOTIC PEPTIDE; IMMUNE-COMPLEXES; PROSTATE-CANCER; C1Q; MEMBRANE; GROWTH; DEFENSINS; BINDING AB Tachyplesin is a small, cationic peptide that possesses antitumor properties. However, little is known about its action mechanism. We used phage display to identify a protein that interacted with tachyplesin and isolated a sequence corresponding to the collagen-like domain of C1q, a key component in the complement pathway. Their interaction was subsequently confirmed by both ELISA and affinity precipitation. Tachyplesin seemed to activate the classic complement cascade because it triggered several downstream events, including the cleavage and deposition of C4 and C3 and the formation of C5b-9. When TSU tumor cells were treated with tachyplesin in the presence of serum, activated C4b and C3b could be detected on tumor cells by flow cytometry, Western blotting, and confocal microscopy. However, this effect was blocked when the tumor cells were treated with hyaluronidase or a large excess of hyaluronan, indicating that hyaluronan or related glycosaminoglycans were involved in this process. Treatment of cells with tachyplesin and serum increased in membrane permeability as indicated by the ability of FITC-dextran to enter the cytoplasm. Finally, the combination of tachyplesin and human serum markedly inhibited the proliferation and caused death of TSU cells, and these effects were attenuated if the serum was heat-inactivated or if hyaluronidase was added. Taken together, these observations suggest that tachyplesin binds to both hyaluronan on the cell surface and C1q in the serum and activates the classic complement cascade, which damages the integrity of the membranes of the tumor cells resulting in their death. C1 Univ Rochester, Med Ctr, Dept Radiat Oncol, Rochester, NY 14642 USA. Georgetown Univ, Med Ctr, Lombardi Comprehens Canc Ctr, Dept Oncol, Washington, DC 20007 USA. Natl Canc Inst, NIH, Bethesda, MD USA. Beijing Cent Hosp, Dept Pathol, Beijing, Peoples R China. Xiamen Univ, Educ Minist Cell Biol & Tumor Cell Engn, Key Lab China, Fujian, Peoples R China. RP Zhang, LR (reprint author), Univ Rochester, Med Ctr, Dept Radiat Oncol, 601 Elmwood Ave, Rochester, NY 14642 USA. EM Lurong_Zhang@urmc.rochester.edu RI Chen, YX/G-3937-2010 FU NCI NIH HHS [R29 CA71545] NR 38 TC 39 Z9 61 U1 1 U2 5 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2005 VL 65 IS 11 BP 4614 EP 4622 DI 10.1158/0008-5472.CAN-04-2253 PG 9 WC Oncology SC Oncology GA 930HZ UT WOS:000229407800020 PM 15930279 ER PT J AU Hodge, DR Peng, B Cherry, JC Hurt, EM Fox, SD Kelley, JA Munroe, DJ Farrar, WL AF Hodge, DR Peng, B Cherry, JC Hurt, EM Fox, SD Kelley, JA Munroe, DJ Farrar, WL TI Interleukin 6 supports the maintenance of p53 tumor suppressor gene promoter methylation SO CANCER RESEARCH LA English DT Article ID CPG ISLAND METHYLATION; EMBRYONIC STEM-CELLS; DE-NOVO METHYLATION; MULTIPLE-MYELOMA; DNA METHYLATION; CANCER-CELLS; PROSTATE-CANCER; EXPRESSION; BINDING; ZEBULARINE AB A strong association exists between states of chronic inflammation and cancer, and it is believed that mediators of inflammation may be responsible for this phenomenon. Interleukin 6 (IL-6) is an inflammatory cytokine known to play a role in the growth and survival of many types of tumors, yet the mechanisms employed by this pleomorphic cytokine to accomplish this feat are still poorly understood. Another important factor in tumor development seems to be the hypermethylation of CpG islands located within the promoter regions of tumor suppressor genes. This common epigenetic alteration enables tumor cells to reduce or inactivate the expression of important tumor suppressor and cell cycle regulatory genes. Here we show that in the IL-6-responsive human multiple myeloma cell line KAS 6/1, the promoter region of p53 is epigenetically modified by methyltransferases, resulting in decreased levels of expression. Furthermore, cells treated with IL-6 exhibit an increase in the expression of the DNA maintenance methylation enzyme, DNMT-1. The DNA methyltransferase inhibitor zebularine reverses the methylation of the p53 promoter, allowing the resumption of its expression. However, when zebularine is withdrawn from the cells, the reestablishment of the original CpG island methylation within the p53 promoter does not occur in the absence of IL-6, and cells which do not receive IL-6 eventually die, as p53 expression continues unchecked by remethylation. Interestingly, this loss of viability seems to involve not the withdrawal of cytokine, but the inability of the cell to resilence the promoter. Consistent with this model, when cells that express IL-6 in an autocrine fashion are subjected to identical treatment, p53 expression is reduced shortly after withdrawal of zebularine. Therefore, it seems IL-6 is capable of maintaining promoter methylation thus representing one of the possible mechanisms used by inflammatory mediators in the growth and survival of tumors. C1 NCI, Mol Immunoregulat Lab, Cytokine Mol Mech Sect, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Lab Mol Technol, Ctr Canc Res, Frederick, MD 21702 USA. NCI, Med Chem Lab, Ctr Canc Res, Frederick, MD 21702 USA. Sci Applicat Int Corp, Intramural Res Support Program, Basic Res Program, Frederick, MD USA. Sci Applicat Int Corp, Seperat Technol Grp, Frederick, MD USA. RP Hodge, DR (reprint author), NCI, Mol Immunoregulat Lab, Cytokine Mol Mech Sect, Ctr Canc Res, Bldg 560,Room 31-76,1050 Boyles St, Frederick, MD 21702 USA. EM hodge@mail.ncifcrf.gov NR 51 TC 126 Z9 134 U1 0 U2 10 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 JUN 1 PY 2005 VL 65 IS 11 BP 4673 EP 4682 DI 10.1158/0008-5472.CAN-04-3589 PG 10 WC Oncology SC Oncology GA 930HZ UT WOS:000229407800026 PM 15930285 ER PT J AU Jiang, JG Chen, CL Card, JW Yang, SL Chen, JX Fu, XN Ning, YG Xiao, X Zeldin, DC Wang, DW AF Jiang, JG Chen, CL Card, JW Yang, SL Chen, JX Fu, XN Ning, YG Xiao, X Zeldin, DC Wang, DW TI Cytochrome P450 2J2 promotes the neoplastic phenotype of carcinoma cells and is up-regulated in human tumors SO CANCER RESEARCH LA English DT Article ID ARACHIDONIC-ACID METABOLISM; EPIDERMAL-GROWTH-FACTOR; EPOXYEICOSATRIENOIC ACIDS; MOUSE MODEL; EPOXYGENASE; EXPRESSION; PATHWAYS; CYCLOOXYGENASE-2; INHIBITION; ENZYMES AB Cytochrome P450 (CYP) arachidonic acid epoxygenase 2J2 converts arachidonic acid to four regioisomeric epoxyeicosatrienoic acids, which exert diverse biological activities in cardiovascular system and endothelial cells. However, it is unknown whether this enzyme highly expresses and plays any role in cancer. In this study, we found that very strong and selective CYP2J2 expression was detected in human carcinoma tissues in 101 of 130 patients (77%) as well as eight human carcinoma cell lines but undetectable in adjacent normal tissues and nontumoric human cell lines by Western, reverse transcription-PCR, and immunohistochemical staining. In addition, forced overexpression of CYP2J2, and CYP BM3F87V or addition of epoxyeicosatrienoic acids (EET) in cultured carcinoma cell lines in vitro markedly accelerated proliferation by analyses of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte-trazolium bromide, cell accounts, and cell cycle analysis, and protected carcinoma cells from apoptosis induced by tumor necrosis factor alpha (TNF-alpha) in cultures. In contrast, antisense 2J2 transfection or addition of epoxygenase inhibitors 17-ODYA inhibited proliferation and accelerated cell apoptosis induced by TNF-alpha. Examination of signaling pathways on the effects of CYP2J2 and EETs revealed activation of mitogen-activated protein kinases and P13 kinase-AKT systems and elevation of epithelial growth factor receptor phosphorylation level. These results strongly suggest that CYP epoxygenase 2J2 plays a previously unknown role in promotion of the neoplastic cellular phenotype and in the pathogenesis of a variety of human cancers. C1 Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Ctr, Dept Internal Med, Wuhan 430030, Peoples R China. Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Ctr, Gene Therapy Ctr, Wuhan 430030, Peoples R China. NIEHS, Div Intramural Res, NIH, Res Triangle Pk, NC 27709 USA. Univ Pittsburgh, Dept Mol Genet, Pittsburgh, PA USA. Univ Pittsburgh, Dept Biochem, Pittsburgh, PA USA. Univ Pittsburgh, Gene Therapy Ctr, Pittsburgh, PA USA. RP Wang, DW (reprint author), Huazhong Univ Sci & Technol, Tongji Hosp, Tongji Med Ctr, Dept Internal Med, Wuhan 430030, Peoples R China. EM dwwang@tjh.tjmu.edu.cn NR 26 TC 139 Z9 148 U1 4 U2 18 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 JUN 1 PY 2005 VL 65 IS 11 BP 4707 EP 4715 DI 10.1158/0008-5472.CAN-04-4173 PG 9 WC Oncology SC Oncology GA 930HZ UT WOS:000229407800030 PM 15930289 ER PT J AU Beppu, Y Nakamura, K Linehan, WM Rapisarda, A Thiele, CJ AF Beppu, Y Nakamura, K Linehan, WM Rapisarda, A Thiele, CJ TI Topotecan blocks hypoxia-inducible factor-1 alpha, and vascular endothelial growth factor expression induced by insulin-like growth factor-I in neuroblastoma cells SO CANCER RESEARCH LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1; PHOSPHATIDYLINOSITOL 3-KINASE; RECEPTOR; INHIBITION; REGRESSION; TUMORS; GENES; VEGF; LINE AB The extent of angiogenesis and/or vascular endothelial growth factor (VEGF) expression in neuroblastoma tumors correlates with metastases, N-myc amplification, and poor clinical outcome. Understanding the mechanisms regulating VEGF expression in neuroblastoma cells provides additional therapeutic options to control neuroblastoma tumor growth. VEGF mRNA is controlled by growth factors and hypoxia via the transcription factor hypoxia-inducible factor (HIF-1 alpha). HIF-1 alpha protein levels are regulated by the von Hippel Lindau tumor suppressor gene, VHL, which targets HIF-1 alpha degradation. To determine whether the levels of VEGF in neuroblastomas are due to mutations in VHL, we evaluated genomic DNA from 15 neuroblastoma cell lines using PCR. We found no mutations in exons 1, 2, or 3 of the VHL gene. VEGF mRNA levels in neuroblastoma cells cultured in serum-free medium increased after 8 to 16 hours in serum, insulin-like growth factor-I (IGF-I), epidermal growth factor, or platelet-derived growth factor. Serum/IGF-I induced increases in HIF-1 alpha protein that temporally paralleled increases in VEGF mRNA, whereas HIF-1 beta levels were unaffected. VEGF and HIF-1 alpha levels were blocked by inhibitors of phosphatidylinositol 3-kinase and mammalian target of rapamycin. Furthermore, we confirmed that HIF-1 alpha mediates similar to 40% of the growth factor activity stimulating VEGF protein expression. Topotecan blocked the IGF-I-stimulated increase in HIF-1 alpha. but not HIF-1 beta, and this resulted in a decrease in VEGF in four neuroblastoma cell lines tested. These data indicate that growth factors in an autocrine or paracrine manner play a major role in regulating VEGF levels in neuroblastoma cells and that targeted therapies to phosphatidylinositol 3-kinase, mammalian target of rapamycin, and/or HIF-1 alpha have the potential to inhibit VEGF expression and limit neuroblastoma tumor growth. C1 NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Cell & Mol Biol Sect, Urol Oncol Branch, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp Frederick Inc, Frederick, MD 21701 USA. RP Nakamura, K (reprint author), NCI, Cell & Mol Biol Sect, Pediat Oncol Branch, Ctr Canc Res,NIH, 1-3940 MSC-1105, Bethesda, MD 20892 USA. EM ct47a@nih.gov NR 25 TC 3 Z9 3 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2005 VL 65 IS 11 BP 4775 EP 4781 PG 7 WC Oncology SC Oncology GA 930HZ UT WOS:000229407800038 ER PT J AU Liao, ZY Sordet, O Zhang, HL Kohlhagen, G Antony, S Gmeiner, WH Pommier, Y AF Liao, ZY Sordet, O Zhang, HL Kohlhagen, G Antony, S Gmeiner, WH Pommier, Y TI Novel polypyrimidine antitumor agent FdUMP[10] induces thymineless death with topoisomerase I-DNA complexes SO CANCER RESEARCH LA English DT Article ID 5-FLUOROURACIL INCORPORATION; THYMIDYLATE SYNTHASE; CARCINOMA-CELLS; OXYGEN RADICALS; BASE-PAIR; ARA-C; CAMPTOTHECIN; CLEAVAGE; MECHANISM; RNA AB FdUMP[10], a 10mer of 5-fluoro-2'-deoxyuridine 5'-monophosphate (FdUMP), the thymidylate synthase inhibitory metabolite of 5-fluorouracil (FU), is most closely correlated with the DNA topoisomerase 1 (Top1) inhibitor camptothecin in the National Cancer Institute COMPARE analysis, but not with FU. FdUMP[10] exhibits more potent antiproliferative activity than FdUMP or 5-fluoro-2'-deoxyuridine (FdU) and is markedly more active than FU. Camptothecin-resistant P388/CPT45 cells lacking Top1 are cross-resistant to FdUMP[10] as well as to FdUMP, FdU, and the thymidylate synthase inhibitor raltitrexed (Tomudex). FdUMP[10] induces DNA single-strand breaks and cellular Top1-DNA complexes. Such complexes are also observed in response to FdUMP, FdU, raltitrexed, and FU. The FdUMP[10]-induced Top1-DNA complexes are not inhibited by the caspase inhibitor z-VAD-fmk and form independently of apoptotic DNA fragmentation, indicating that they do not correspond to apoptotic Top1-DNA complexes. In biochemical assay, Top1 is directly trapped at uracil and FdU misincorporation sites. We propose that FdUMP[10] damages DNA by trapping Top1 at uracil and FdU misincorporation sites resulting from thymidylate synthase inhibition and thymine depletion. C1 NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Wake Forest Univ, Sch Med, Dept Canc Biol, Winston Salem, NC 27109 USA. RP Pommier, Y (reprint author), NCI, Mol Pharmacol Lab, Canc Res Ctr, NIH,Dept Hlth & Human Serv, Bldg 37,Room 5066,37 Convent Dr, Bethesda, MD 20892 USA. EM pommier@nih.gov RI Sordet, Olivier/M-3271-2014 FU NCI NIH HHS [U01 CA102532] NR 49 TC 23 Z9 25 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUN 1 PY 2005 VL 65 IS 11 BP 4844 EP 4851 DI 10.1158/0008-5472.CAN-04-1302 PG 8 WC Oncology SC Oncology GA 930HZ UT WOS:000229407800046 PM 15930305 ER PT J AU Ahmed-Belkacem, A Pozza, A Munoz-Martinez, F Bates, SE Castanys, S Gamarro, F Di Pietro, A Perez-Victoria, JM AF Ahmed-Belkacem, A Pozza, A Munoz-Martinez, F Bates, SE Castanys, S Gamarro, F Di Pietro, A Perez-Victoria, JM TI Flavonoid structure-activity studies identify 6-prenyichrysin and tectochrysin as potent and specific inhibitors of breast cancer resistance protein ABCG2 SO CANCER RESEARCH LA English DT Article ID HUMAN P-GLYCOPROTEIN; MULTIDRUG-RESISTANCE; HALF-TRANSPORTER; FUNCTIONAL-CHARACTERIZATION; ATPASE ACTIVITY; BINDING SITES; CELLS; MODULATION; SUBSTRATE; REVERSAL AB overexpression of breast cancer resistance protein ABCG2 confers multidrug resistance in cancer cells. The GF120918-sensitive drug efflux activity of human wild-type (R482) ABCG2-transfected cells was used for rational screening of inhibitory flavonoids and establishment of structure-activity relationships. Flavones were found more efficient than flavonols, isoflavones, and flavanones. Differentially substituted flavone derivatives indicated positive OH effects at position 5, in contrast to positions 3 and 7. A methoxy at position 7 was slightly positive in tectochrysin, whereas a strong positive effect was produced by prenylation at position 6. The potency of 6-prenylchrysin was comparable with that of GF120918 (IC50 = 0.3 mu mol/L). Both 6-prenylchrysin and tectochrysin seemed specific for ABCG2 because no interaction was detected with either P-glycoprotein or MRP1. The ABCG2 resistance profile in vitro is altered by mutation at amino acid 482. The R482T mutation limited the effect of prenylation on ABCG2 inhibition. Whereas GF120918 strongly inhibited the ATPase activity of wild-type ABCG2, neither 6-prenylchrysin nor tectochrysin altered the activity. In contrast, all three inhibitors stimulated the ATPase activity of mutant ABCG2. 6-Prenylchrysin at 0.5 mu mol/L efficiently sensitized the growth of wild-type ABCG2-transfected cells to mitoxantrone, whereas higher concentrations were required for the mutant ones. In contrast, 1 mu mol/L tectochrysin was sufficient to fully sensitize mutant ABCG2-transfected cells, whereas higher concentrations were required for the wild-type ones. Both flavones exhibited a lower intrinsic cytotoxicity than GF120918 and were apparently not transported by ABCG2. 6-Prenylchrysin and tectochrysin therefore constitute new and promising inhibitors for the reversal of ABCG2-mediated drug transport. C1 Univ Lyon 1, CNRS, UMR 5086, Inst Biol & Chim Prot,IFR 128 BioSci Lyon Gerland, F-69367 Lyon, France. CSIC, Inst Parasitol & Biomed Lopez Neyra, Granada, Spain. NCI, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Di Pietro, A (reprint author), Univ Lyon 1, CNRS, UMR 5086, Inst Biol & Chim Prot,IFR 128 BioSci Lyon Gerland, 7 Passage Vercors, F-69367 Lyon, France. EM a.dipietro@ibcp.fr NR 46 TC 123 Z9 126 U1 1 U2 13 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 JUN 1 PY 2005 VL 65 IS 11 BP 4852 EP 4860 DI 10.1158/0008-5472.CAN-04-1817 PG 9 WC Oncology SC Oncology GA 930HZ UT WOS:000229407800047 PM 15930306 ER PT J AU Lee, JS Grisham, JW Thorgeirsson, SS AF Lee, JS Grisham, JW Thorgeirsson, SS TI Comparative functional genomics for identifying models of human cancer SO CARCINOGENESIS LA English DT Editorial Material ID TRANSGENIC MOUSE MODEL; GENE-EXPRESSION PROFILES; ACTIVATED RECEPTOR-ALPHA; ACYL-COA OXIDASE; B-CELL LYMPHOMA; HEPATOCELLULAR-CARCINOMA; C-MYC; PEROXISOME PROLIFERATOR; LIVER CARCINOGENESIS; TUMOR-FORMATION AB Genetically modified mice with overexpressed and/or deleted genes have been used extensively to model human cancer. However, it is uncertain as to what extent the mouse models reproduce the corresponding cancers in humans. We have compared the global gene expression patterns in human and mouse hepatocellular carcinomas (HCCs) in an attempt to identify the mouse models that most extensively reproduce the molecular pathways in the human tumors. The comparative analysis of the gene expression patterns in murine and human HCC indicates that certain genetic mouse models closely reproduce the gene expression patterns of HCC in humans, while others do not. Identification of mouse models that reproduce the molecular features of specific human cancers (or subclasses of specific human cancers) promises to accelerate both the understanding of the molecular pathogenesis of cancer and the discovery of therapeutic targets. We propose that this method, comparative functional genomics, could be effectively applied to the analysis of mouse models for other human cancers. C1 NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 70 TC 37 Z9 39 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2005 VL 26 IS 6 BP 1013 EP 1020 DI 10.1093/carcin/bgi030 PG 8 WC Oncology SC Oncology GA 934HO UT WOS:000229700100001 PM 15677630 ER PT J AU Blankenburg, S Konig, IR Moessner, R Laspe, P Thoms, KM Krueger, U Khan, SG Westphal, G Berking, C Volkenandt, M Reich, K Neumann, C Ziegler, A Kraemer, KH Emmert, S AF Blankenburg, S Konig, IR Moessner, R Laspe, P Thoms, KM Krueger, U Khan, SG Westphal, G Berking, C Volkenandt, M Reich, K Neumann, C Ziegler, A Kraemer, KH Emmert, S TI Assessment of 3 xeroderma pigmentosum group C gene polymorphisms and risk of cutaneous melanoma: a case-control study SO CARCINOGENESIS LA English DT Article ID DNA-REPAIR CAPACITY; NUCLEOTIDE EXCISION-REPAIR; BASAL-CELL CARCINOMA; LUNG-CANCER; MALIGNANT-MELANOMA; NECK-CANCER; DAMAGE; XPD; FAMILIES; SEQUENCE AB Individuals with the rare DNA repair deficiency syndrome xeroderma pigmentosum (XP) are sensitive to the sun and exhibit a 1000-fold increased risk for developing skin cancers, including cutaneous melanoma. Inherited polymorphisms of XP genes may contribute to subtle variations in DNA repair capacity and genetic susceptibility to melanoma. We investigated the role of three polymorphic alleles of the DNA repair gene XPC in a hospital-based case-control study of 294 Caucasian patients from Germany who had cutaneous melanoma and 375 healthy cancer-free sex-matched Caucasian control subjects from the same area. We confirmed that the XPC intron 9 PAT+, intron 11 -6A, and the exon 15 2920C polymorphisms are in a linkage disequilibrium. Only 1.6% of the 669 donors genotyped were discordant for these three polymorphisms. The allele frequencies (cases: controls) were for intron 9 PAT+ 41.7%:36.9%, for intron 11 -6A 41.8%:37.0% and for exon 15 2920C 41.3%:37.3%. Using multivariate logistic regression analyses to control for age, skin type and number of nevi, the three polymorphisms were significantly associated with increased risks of melanoma: OR 1.87 (95% CI: 1.10-3.19; P = 0.022), OR 1.83 (95% CI: 1.07-3.11; P = 0.026), and OR 1.82 (95% CI: 1.07-3.08; P = 0.026), respectively. Exploratory multivariate analyses of distinct subgroups revealed that these polymorphisms were associated with increased risks for the development of multiple primary melanomas (n = 28). The results of our case-control study support the hypothesis that the intron 9 PAT+, intron 11 -6A and exon 15 2920C haplotype may contribute to the risk of developing cutaneous melanoma by increasing the rate of an alternatively spliced XPC mRNA isoform that skips exon 12 and leads to reduced DNA repair. Our results should be validated in independent samples in order to guard against false positive findings. C1 Univ Gottingen, Dept Dermatol, D-37075 Gottingen, Germany. Univ Gottingen, Dept Occupat & Social Med, D-37075 Gottingen, Germany. Univ Hosp Schleswig Holstein, Inst Med Biometry & Stat, Lubeck, Germany. NCI, Basic Res Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Munich, Dept Dermatol, D-8000 Munich, Germany. RP Emmert, S (reprint author), Univ Gottingen, Dept Dermatol, Von Siebold Str 3, D-37075 Gottingen, Germany. EM semmert@gwdg.de RI Konig, Inke/A-4544-2009; OI Ziegler, Andreas/0000-0002-8386-5397 FU Intramural NIH HHS [Z01 BC004517-31] NR 55 TC 75 Z9 82 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2005 VL 26 IS 6 BP 1085 EP 1090 DI 10.1093/carcin/bgi055 PG 6 WC Oncology SC Oncology GA 934HO UT WOS:000229700100008 PM 15731165 ER PT J AU Hou, LF Chatterjee, N Huang, WY Baccarelli, A Yadavalli, S Yeager, M Bresalier, RS Chanock, SJ Caporaso, NE Ji, BT Weissfeld, JL Hayes, RB AF Hou, LF Chatterjee, N Huang, WY Baccarelli, A Yadavalli, S Yeager, M Bresalier, RS Chanock, SJ Caporaso, NE Ji, BT Weissfeld, JL Hayes, RB TI CYP1A1 Val(462) and NQO1 Ser(187) polymorphisms, cigarette use, and risk for colorectal adenoma SO CARCINOGENESIS LA English DT Article ID DT-DIAPHORASE ACTIVITY; CANCER SUSCEPTIBILITY; GENETIC POLYMORPHISMS; CYTOCHROME P4501A1; DNA-DAMAGE; CARCINOMA; SMOKING; LUNG; REDUCTASE; ASSOCIATION AB Cigarette use is a risk factor for colorectal adenoma, a known precursor of colorectal cancer. Polymorphic variants in NQO1 and CYP1A1 influence the activation of carcinogenic substances in tobacco smoke, possibly impacting on tobacco-associated risks for colorectal tumors. We investigated the association of cigarette smoking with risk for advanced colorectal adenoma in relation to the CYP1A1 Val(462) and NQO1 Ser(187) polymorphic variants. Subjects were 725 non-Hispanic Caucasian cases with advanced colorectal adenoma of the distal colon (descending colon, sigmoid and rectum) and 729 gender- and ethnicity-matched controls, randomly selected from participants in the prostate, lung, colorectal and ovarian cancer screening trial. Subjects carrying either CYP1A1 Val(462) or NQO1 Ser(187) alleles were weakly associated with risk of colorectal adenoma; however, subjects carrying both CYP1A1 Val(462) and NQO1 Ser(187) alleles showed increased risks (OR = 2.2, 95% CI = 1.1-4.5), particularly among recent (including current) (OR = 17.4, 95% CI = 3.8-79.8, P for interaction = 0.02) and heavy cigarette smokers (> 20 cigarettes/day) (OR = 21.1, 95% CI = 3.9-114.4, P for interaction = 0.03) compared with non-smokers who did not carry either of these variants. These genotypes were unassociated with risk in non-smokers. In analysis of adenoma subtypes, the combined gene variants were most strongly associated with the presence of multiple adenoma (P = 0.002). In summary, joint carriage of CYP1A1 Val(462) and NQO1 Ser(187) alleles, particularly in smokers, was related to colorectal adenoma risk, with a propensity for formation of multiple lesions. C1 NCI, US Dept HHS, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NCI, Sect Genom Variat, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, SAIC Frederick, Frederick, MD 21701 USA. Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med & Nutr, Houston, TX 77030 USA. Univ Pittsburgh, Inst Canc, Dept Epidemiol, Pittsburgh, PA USA. RP Hou, LF (reprint author), NCI, US Dept HHS, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,EPS 8123, Bethesda, MD 20892 USA. EM lifangh2@mail.nih.gov OI Baccarelli, Andrea/0000-0002-3436-0640; Hayes, Richard/0000-0002-0918-661X NR 46 TC 44 Z9 47 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2005 VL 26 IS 6 BP 1122 EP 1128 DI 10.1093/carcin/bgi054 PG 7 WC Oncology SC Oncology GA 934HO UT WOS:000229700100013 PM 15731166 ER PT J AU Teng, O Rai, T Tanaka, Y Takei, Y Nakata, T Hirasawa, M Kulkarni, AB Hirokawa, N AF Teng, OJunlin Rai, Tatemitsu Tanaka, Yosuke Takei, Yosuke Nakata, Takao Hirasawa, Motoyuki Kulkarni, Ashok B. Hirokawa, Nobutaka TI The KIF3 motor transports N-cadherin and organizes the developing neuroepithelium SO CELL STRUCTURE AND FUNCTION LA English DT Meeting Abstract C1 [Teng, OJunlin; Rai, Tatemitsu; Tanaka, Yosuke; Takei, Yosuke; Nakata, Takao; Hirokawa, Nobutaka] Univ Tokyo, Grad Sch Sci, Dept Cell Biol & Anat, Tokyo 1130033, Japan. [Hirasawa, Motoyuki; Kulkarni, Ashok B.] NIDCR, NIH, Funct Genom Sect, Craniofacial Dev Biol & Regenerat Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JAPAN SOC CELL BIOLOGY PI KYOTO PA C/O NAKANISHI PRINTING SHIMODACHIURI OGAWA HIGASHI, KAMIGYO-KU, KYOTO, 602-8048, JAPAN SN 0386-7196 EI 1347-3700 J9 CELL STRUCT FUNCT JI Cell Struct. Funct. PD JUN PY 2005 VL 30 SU S BP 67 EP 67 PG 1 WC Cell Biology SC Cell Biology GA V44IE UT WOS:000202995600210 ER PT J AU Mitsunari, T Nakatsu, F Shioda, N Love, PE Grinberg, A Bonifacino, JS Ohno, H AF Mitsunari, Takashi Nakatsu, Fubito Shioda, Noriko Love, Paul E. Grinberg, Alexander Bonifacino, Juan S. Ohno, Hiroshi TI Clathrin adaptor AP-2 is essential for cell viability SO CELL STRUCTURE AND FUNCTION LA English DT Meeting Abstract C1 [Mitsunari, Takashi; Nakatsu, Fubito; Ohno, Hiroshi] RIKEN, Res Ctr Allergy & Immunol, Lan Epithelial Immunobiol, Yokohama, Kanagawa 2300045, Japan. [Mitsunari, Takashi; Shioda, Noriko] Kanazawa Univ, Canc Res Inst, Div Mol Membrane Biol, Kanazawa, Ishikawa 9200934, Japan. [Love, Paul E.; Grinberg, Alexander; Bonifacino, Juan S.] NICHHD, NIH, Bethesda, MD 20892 USA. [Ohno, Hiroshi] Yokohama City Univ, Grad Sch Integrated Sci, Yokohama, Kanagawa 2300045, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JAPAN SOC CELL BIOLOGY PI KYOTO PA C/O NAKANISHI PRINTING SHIMODACHIURI OGAWA HIGASHI, KAMIGYO-KU, KYOTO, 602-8048, JAPAN SN 0386-7196 EI 1347-3700 J9 CELL STRUCT FUNCT JI Cell Struct. Funct. PD JUN PY 2005 VL 30 SU S BP 69 EP 69 PG 1 WC Cell Biology SC Cell Biology GA V44IE UT WOS:000202995600219 ER PT J AU Saavedra, JM AF Saavedra, JM TI Brain angiotensin II: New developments, unanswered questions and therapeutic opportunities SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Review DE renin angiotensin system; angiotensin II receptors; AT(1) receptors; AT(2) receptors; stress; ischemia; gastric ulcers; sympathetic system; hormones; brain development; sensory systems; cerebrovascular circulation ID NITRIC-OXIDE SYNTHASE; CEREBRAL-BLOOD-FLOW; SPONTANEOUSLY HYPERTENSIVE-RATS; RECEPTOR ANTAGONIST CV-11974; INDUCED GASTRIC INJURY; CENTRAL-NERVOUS-SYSTEM; SMOOTH-MUSCLE CELLS; BINDING-SITES; GENE-EXPRESSION; AUTORADIOGRAPHIC LOCALIZATION AB 1. There are two Angiotensin II systems in the brain. The discovery of brain Angiotensin II receptors located in neurons inside the blood brain barrier confirmed the existence of an endogenous brain Angiotensin II system, responding to Angiotensin II generated in and/or transported into the brain. In addition, Angiotensin II receptors in circumventricular organs and in cerebrovascular endothelial cells respond to circulating Angiotensin II of peripheral origin. Thus, the brain responds to both circulating and tissue Angiotensin II, and the two systems are integrated. 2. The neuroanatomical location of Angiotensin If receptors and the regulation of the receptor number are most important to determine the level of activation of the brain Angiotensin II systems. 3. Classical, well-defined actions of Angiotensin II in the brain include the regulation of hormone formation and release, the control of the central and peripheral sympathoadrenal systems, and the regulation of water and sodium intake. As a consequence of changes in the hormone, sympathetic and electrolyte systems, feed back mechanisms in turn modulate the activity of the brain Angiotensin II systems. It is reasonable to hypothesize that brain Angiotensin II is involved in the regulation of multiple additional functions in the brain, including brain development, neuronal migration, process of sensory information, cognition, regulation of emotional responses, and cerebral blood flow. 4. Many of the classical and of the hypothetical functions of brain Angiotensin II are mediated by stimulation of Angiotensin It AT, receptors. 5. Brain AT(2) receptors are highly expressed during development. In the adult, AT2 receptors are restricted to areas predominantly involved in the process of sensory information. However, the role of AT(2) receptors remains to be clarified. 6. Subcutaneous or oral administration of a selective and potent non-peptidic AT(1) receptor antagonist with very low affinity for AT(2) receptors and good bioavailability blocked AT(1) receptors not only outside but also inside the blood brain barrier. The blockade of the complete brain Angiotensin II AT(1) system allowed us to further clarify some of the central actions of the peptide and suggested some new potential therapeutic avenues for this class of compounds. 7. Pretreatment with peripherally administered AT(1) antagonists completely prevented the hormonal and sympathoadrenal response to isolation stress. A similar pretreatment prevented the development of stress-induced gastric ulcers. These findings strongly suggest that blockade of brain AT(1) receptors could be considered as a novel therapeutic approach in the treatment of stress-related disorders. 8. Peripheral administration of AT(1) receptor antagonists strongly affected brain circulation and normalized some of the profound alterations in cerebrovascular structure and function characteristic of chronic genetic hypertension. AT(1) receptor antagonists were capable of reversing the pathological cerebrovascular remodeling in hypertension and the shift to the right in the cerebral autoregulation, normalizing cerebrovascular compliance. In addition, AT(1) receptor antagonists normalized the expression of cerebrovascular nitric oxide synthase isoenzymes and reversed the inflammatory reaction characteristic of cerebral vessels in hypertension. As a consequence of the normalization of cerebrovascular compliance and the prevention of inflammation, there was, in genetically hypertensive rats a decreased vulnerability to brain ischemia. After pretreatment with AT(1) antagonists, there was a protection of cerebrovascular flow during experimental stroke, decreased neuronal death, and a substantial reduction in the size of infarct after occlusion of the middle cerebral artery. At least part of the protective effect of AT(1) receptor antagonists was related to the inhibition of the Angiotensin II system, and not to the normalization of blood pressure. These results indicate that treatment with AT(1) receptor antagonists appears to be a major therapeutic avenue for the prevention of ischemia and inflammatory diseases of the brain. 9. Thus, orally administered AT(1) receptor antagonists may be considered as novel therapeutic compounds for the treatment of diseases of the central nervous system when stress, inflammation and ischemia play major roles. 10. Many questions remain. How is brain Angiotensin II formed, metabolized, and distributed? What is the role of brain AT(2) receptors? What are the molecular mechanisms involved in the cerebrovascular remodeling and inflammation which are promoted by AT(1) receptor stimulation? How does Angiotensin II regulate the stress response at higher brain centers? Does the degree of activity of the brain Angiotensin II system predict vulnerability to stress and brain ischemia? We look forward to further studies in this exiting and expanding field. C1 NIMH, Pharmacol Sect, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Saavedra, JM (reprint author), NIMH, Pharmacol Sect, NIH, Dept Hlth & Human Serv, 10 Ctr Dr,Room 2D-57, Bethesda, MD 20892 USA. EM saavedrj@mail.nih.gov NR 111 TC 159 Z9 164 U1 1 U2 9 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD JUN PY 2005 VL 25 IS 3-4 BP 485 EP 512 DI 10.1007/s10571-005-4011-5 PG 28 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 944AF UT WOS:000230396600004 PM 16075377 ER PT J AU Daly, JW AF Daly, JW TI Nicotinic agonists, antagonists, and modulators from natural sources SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Review DE anatoxin; cocaine; cytisine; dihydro-beta-erythroidine; epibatidine; epiquinamide; galanthamine; histrionicotoxin; ibogaine; methyllycaconitine; muscarine; nicotine; noncompetitive antagonists; tubocurarine ID ACETYLCHOLINE-RECEPTOR BINDING; ALPHA-BUNGAROTOXIN BINDING; ION CHANNEL COMPLEX; HALOGENATED CYTISINE DERIVATIVES; POTENT NONCOMPETITIVE BLOCKER; PYRIDINE-MODIFIED ANALOGS; ECUADORIAN POISON FROG; RAT-BRAIN MEMBRANES; RING-E ANALOGS; EPIBATIDINE ANALOGS AB 1. Acetylcholine receptors were initially defined as nicotinic or muscarinic, based on selective activation by two natural products, nicotine and muscarine. Several further nicotinic agonists have been discovered from natural sources, including cytisine, anatoxin, ferruginine, anabaseine, epibatidine, and epiquinamide. These have provided lead structures for the design of a wide range of synthetic agents. 2. Natural sources have also provided competitive nicotinic antagonists, such as the Erythrina alkaloids, the tubocurarines, and methyllycaconitine. Noncompetitive antagonists, such as the histrionicotoxins, various izidines, decahydroquinolines, spiropyrrolizidine oximes, pseudophrynamines, ibogaine, strychnine, cocaine, and sparteine have come from natural sources. Finally, galanthamine, codeine, and ivermectin represent positive modulators of nicotinic function, derived from natural sources. 3. Clearly, research on acetylcholine receptors and functions has been dependent on key natural products and the synthetic agents that they inspired. C1 NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bethesda, MD 20892 USA. RP Daly, JW (reprint author), NIDDKD, Bioorgan Chem Lab, NIH, DHHS, Bldg 8,Rm 1A17, Bethesda, MD 20892 USA. EM jdaly@nih.gov NR 240 TC 126 Z9 128 U1 1 U2 30 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD JUN PY 2005 VL 25 IS 3-4 BP 513 EP 552 DI 10.1007/s10571-005-3968-4 PG 40 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 944AF UT WOS:000230396600005 PM 16075378 ER PT J AU Zhang, BJ Yamashita, M Fields, R Kusano, K Gainer, H AF Zhang, BJ Yamashita, M Fields, R Kusano, K Gainer, H TI EGFP-tagged vasopressin precursor protein sorting into large dense core vesicles and secretion from PC12 cells SO CELLULAR AND MOLECULAR NEUROBIOLOGY LA English DT Article DE green fluorescent protein; vasopressin; neurophysin; regulated secretory pathway; exocytosis ID GREEN FLUORESCENT PROTEIN; NERVE GROWTH-FACTOR; HYPOTHALAMO-NEUROHYPOPHYSEAL SYSTEM; PHEOCHROMOCYTOMA CELLS; ULTRASTRUCTURAL DEMONSTRATION; TANNIC-ACID; MONOCLONAL-ANTIBODIES; CARBOXYPEPTIDASE-E; CRYSTAL-STRUCTURE; ENDOCRINE-CELLS AB 1. Hypothalamic magnocellular neurons synthesize, store, and secrete large quantities of the neuropeptides, vasopressin (VP) and oxytocin (OT), which are synthesized as protein precursors also containing proteins called neurophysins. These protein precursors are sorted through the regulated secretory pathway (RSP), packaged into large dense core vesicles LDCVs, and their peptide products are secreted from nerve terminals in the posterior pituitary. 2. It has been hypothesized that this efficient packaging is dependent oil the interaction of the peptide with neurophysin in a complex that forms the granule core. To test this, PC12 cells were transfected with vasopressin precursor DNA constructs that either contained or deleted the neurophysin moiety and tagged with enhanced green fluorescent protein (EGFP) as reporters. The intracellular routing and secretion of the EGFP-tagged VP precursor proteins were studied by in differentiated PC12 cells by fluorescence microscopy, electron microscopic immunocytochemistry, and fluorescent imaging techniques. 3. The data showed that only when the neurophysin was present in the VP precursor construct did the fluorescent fusion protein become routed to the RSP and get efficiently packaged into LDCVs and secreted. These data ire consistent with the view that routing of the precursor to LDCVs requires the amino acids that encode the intravesicular chaperone, neurophysin. C1 NINDS, Neurochem Lab, NIH, Bethesda, MD 20892 USA. RP Gainer, H (reprint author), NINDS, Neurochem Lab, NIH, Bldg 36,Room 4D04, Bethesda, MD 20892 USA. EM gainerh@ninds.nih.gov NR 64 TC 7 Z9 8 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0272-4340 J9 CELL MOL NEUROBIOL JI Cell. Mol. Neurobiol. PD JUN PY 2005 VL 25 IS 3-4 BP 581 EP 605 DI 10.1007/s10571-005-3970-x PG 25 WC Cell Biology; Neurosciences SC Cell Biology; Neurosciences & Neurology GA 944AF UT WOS:000230396600007 PM 16075380 ER PT J AU Lee, JK Seki, N Sayers, TJ Subleski, J Gruys, EM Murphy, WJ Wiltrout, RH AF Lee, JK Seki, N Sayers, TJ Subleski, J Gruys, EM Murphy, WJ Wiltrout, RH TI Constitutive expression of functional CD40 on mouse renal cancer cells: Induction of Fas and Fas-mediated killing by CD40L SO CELLULAR IMMUNOLOGY LA English DT Article DE CD40; cytotoxicity; tumor immunity; renal cancer ID HUMAN B-LYMPHOCYTES; IN-VIVO; ENDOTHELIAL-CELLS; CD40-CD40 LIGAND; DENDRITIC CELLS; SOLID TUMORS; IFN-GAMMA; NK CELLS; T-CELLS; APOPTOSIS AB CD40, a member of the TNF receptor superfamily, is expressed on B cells, dendritic cells, and some tumor cells, including melanoma and bladder carcinoma. In this study, we report that both mouse and human renal carcinoma cells (RCC) also constitutively express functional CD40. Treatment of mouse RCC with CD40L induced strong expression of genes and proteins for ICAM-1 and Fas, and this expression was further enhanced by combining CD40L with IFN-gamma. Similar effects were demonstrated using an agonist anti-CD40 antibody. The increased levels of Fas expression on RCC after treatment with CD40L plus IFN-gamma resulted in potent killing by either FasL-positive effector cells or agonistic anti-Fas antibody. The combination of CD40L plus IFN-gamma also significantly enhanced killing of RCC by tumor-specific CTL lines. Our results demonstrate that constitutively expressed CD40 is functionally active and may provide a molecular target for the development of new approaches to the treatment of RCC. Published by Elsevier lnc. C1 NCI, Lab Expt Immunol, Canc Res Ctr, Frederick, MD 21701 USA. Natl Genome Res Inst, NIH, Eunpyung Ku, Seoul 122701, South Korea. Kurume Univ, Res Ctr Innovat Canc Therapy, Kurume, Fukuoka 830, Japan. SAIC, Intramural Res Support Program, Frederick, MD 21702 USA. Univ Nevada, Sch Med, Dept Microbiol, Reno, NV 89557 USA. RP Wiltrout, RH (reprint author), NCI, Lab Expt Immunol, Canc Res Ctr, Frederick, MD 21701 USA. EM wiltrour@mail.nih.gov NR 30 TC 15 Z9 22 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 0008-8749 J9 CELL IMMUNOL JI Cell. Immunol. PD JUN PY 2005 VL 235 IS 2 BP 145 EP 152 DI 10.1016/j.cellimm.2005.08.029 PG 8 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 987QT UT WOS:000233533100008 PM 16213477 ER PT J AU Welch, KD Wen, B Goodlett, DR Yi, EC Lee, H Reilly, TP Nelson, SD Pohl, LR AF Welch, KD Wen, B Goodlett, DR Yi, EC Lee, H Reilly, TP Nelson, SD Pohl, LR TI Proteomic identification of potential susceptibility factors in drug-induced liver disease SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID TANDEM MASS-SPECTROMETRY; ACETAMINOPHEN-INDUCED HEPATOTOXICITY; SHOCK-PROTEIN INDUCTION; NITRIC-OXIDE SYNTHASE; HSP70 ATPASE ACTIVITY; CODED AFFINITY TAGS; HEAT-SHOCK; MOUSE-LIVER; KUPFFER CELLS; LIQUID-CHROMATOGRAPHY AB Drug-induced liver disease (DILD) causes significant morbidity and mortality and impairs new drug development. Currently, no known criteria can predict whether a drug will cause DILD or what risk factors make an individual susceptible. Although it has been shown in mouse studies that the disruption of key regulatory factors, such as cyclooxygenase-2 (COX-2), interleukin (IL)-6, and IL-10, increased susceptibility to DILD caused by acetaminophen (APAP), no single factor seems to be absolute. As an approach to better understand the multifactorial basis of DILD, we compared the hepatic proteome of mice that are resistant (SJL) and susceptible (C57Bl/6) to APAP-induced liver disease (AILD), using solution-based isotope-coded affinity tag (ICAT) liquid chromatography mass spectrometry. Several novel factors were identified that were more highly expressed in the livers of SJL mice, including those involved in stress response, cell proliferation and tissue regeneration, and protein modification, implicating these proteins as potential hepatoprotective factors. There was also a selective loss of several mitochondrial proteins from the livers of the susceptible C57Bl/6 mice, suggesting that the loss of functional mitochondria may indeed play a role in AILD. These findings indicate that comparative hepatic proteomic analyses of susceptible and resistant mouse strains may provide a global approach for identifying potential risk factors and mechanistic pathways responsible for DILD. C1 NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Washington, Dept Med Chem, Seattle, WA 98195 USA. Inst Syst Biol, Seattle, WA 98103 USA. RP Welch, KD (reprint author), NHLBI, Mol & Cellular Toxicol Sect, Lab Mol Immunol, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM WelchKD@nhlbi.nih.gov OI Lee, Hookeun/0000-0002-0696-8421 FU NCRR NIH HHS [P51 RR 00166]; NIEHS NIH HHS [P30 ES 07033] NR 89 TC 54 Z9 58 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUN PY 2005 VL 18 IS 6 BP 924 EP 933 DI 10.1021/tx050011b PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 939ME UT WOS:000230076200003 PM 15962927 ER PT J AU Pittman, PR Leitman, SF Oro, JGB Norris, SL Marano, NM Ranadive, MV Sink, BS McKee, KT AF Pittman, PR Leitman, SF Oro, JGB Norris, SL Marano, NM Ranadive, MV Sink, BS McKee, KT TI Protective antigen and toxin neutralization antibody patterns in anthrax vaccinees undergoing serial plasmapheresis SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID MONOCLONAL-ANTIBODIES; BIOLOGICAL WEAPON; IMMUNOGLOBULIN-G; GUINEA-PIGS; SERUM; IMMUNITY; MANAGEMENT; INFECTION; COMPONENT; CORRELATE AB Recipients of licensed anthrax vaccine (AVA; Biothrax) could serve as a source of hyperimmune plasma and immunoglobulin for therapy and prophylaxis. We measured serum antibodies during serial weekly to biweekly plasmapheresis in 38 individuals previously vaccinated with 4 to 27 doses of AVA. Immunoglobulin G (IgG) to protective antigen (PA) and toxin neutralization assay (TNA) antibody levels were highly correlated (r = 0.86930 and P < 0.0001 for anti-PA concentration versus TNA concentration). Significant decreases in antibody titer and concentration were observed over time when compared for the number of days from the last AVA injection (P < 0.0001 for both anti-PA and TNA concentration) and for the number of days from the first plasmapheresis (P = 0.0007 for anti-PA concentration and P = 0.0025 for TNA concentration). The rate of the decrease in total IgG concentration (half-life [t(1/2)] = 198.90 days after first plasmapheresis) was significantly less than the decrease in anti-PA IgG (t(1/2) = 63.53 days) (P < 0.0001), indicating that the reduction in anti-PA IgG was more likely due to natural decay than plasmapheresis. The time since the last injection and the time after initial plasmapheresis are important elements in considering an optimal schedule for collecting anthrax hyperimmune plasma. Good correlation between IgG to PA and TNA antibodies suggests that the anti-PA enzyme-linked immunosorbent assay can be used as a high-throughput screen for functional immune reactivity in donor plasma units. C1 USA, Med Res Inst Infect Dis, Camber Corp, Ft Detrick, MD 21702 USA. NIH, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. RP McKee, KT (reprint author), DynPort Vaccine Co LLC, 64 Thomas Johnson Dr, Frederick, MD 21702 USA. EM phillip.pittman@amedd.army.mil; kelly.mckee@amedd.army.mil NR 44 TC 27 Z9 29 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JUN PY 2005 VL 12 IS 6 BP 713 EP 721 DI 10.1128/CDLI.12.6.713-721.2005 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 955AO UT WOS:000231197200005 PM 15939745 ER PT J AU Maxwell, GL Chandramouli, GVR Dainty, L Litzi, TJ Berchuck, A Barrett, JC Risinger, JI AF Maxwell, GL Chandramouli, GVR Dainty, L Litzi, TJ Berchuck, A Barrett, JC Risinger, JI TI Microarray analysis of endometrial carcinomas and mixed mullerian tumors reveals distinct gene expression profiles associated with different histologic types of uterine cancer SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 35th Annual Meeting of the Society-of-Gynecologic-Oncologists CY FEB 07-11, 2004 CL San Diego, CA SP Soc Gynecol Oncol ID E-CADHERIN; MICROSATELLITE INSTABILITY; METAPLASTIC CARCINOMAS; CARCINOSARCOMAS; P53; OVEREXPRESSION; ADENOCARCINOMA; MUTATIONS; UTERUS; ORIGIN AB Previous studies using cDNA microarray have indicated that distinct gene expression profiles characterize endometrioid and papillary serous carcinomas of the endometrium. Molecular studies have observed that mixed mullerian tumors, characterized by both carcinomatous and sarcomatous components, share features that are characteristic of endometrial carcinomas. The objective of this analysis was to more precisely define gene expression patterns that distinguish endometrioid and papillary serous histologies of endometrial carcinoma and mixed mullerian tumors of the uterus. One hundred nineteen pathologically confirmed uterine cancer samples were studied (66 endometrioid, 24 papillary serous, and 29 mixed mullerian tumors). Gene expressions were analyzed using the Affymetrix Human Genome Arrays U133A and U133B Genechip set. Unsupervised analysis revealed distinct global gene expression patterns of endometrioid, papillary serous, mixed mullerian tumors, and normal tissues as grossly separated clusters. Two-sample t tests comparing endometrioid and papillary serous, endometrioid and mixed mullerian tumor, and papillary serous and mixed mullerian tumor pairs identified 1,055, 5,212, and 1,208 differentially expressed genes at P < 0.001, respectively. These data revealed that distinct patterns of gene expression characterize various histologic types of uterine cancer. Gene expression profiles for select genes were confirmed using quantitative PCR. An understanding of the molecular heterogeneity of various histologic types of endometrial cancer has the potential to lead to better individualization of treatment in the future. C1 Walter Reed Army Med Ctr, Div Gynecol Oncol, Washington, DC 20307 USA. NCI, Lab Biosyst & Canc, Bethesda, MD 20892 USA. Duke Univ, Dept Obstet & Gynecol, Div Gynecol Oncol, Durham, NC USA. RP Maxwell, GL (reprint author), Walter Reed Army Med Ctr, Div Gynecol Oncol, 6900 Georgia Ave, Washington, DC 20307 USA. EM george.maxwell@na.amedd.army.mil NR 35 TC 57 Z9 59 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 JUN 1 PY 2005 VL 11 IS 11 BP 4056 EP 4066 DI 10.1158/1078-0432.CCR-04-2001 PG 11 WC Oncology SC Oncology GA 930YK UT WOS:000229452800010 PM 15930340 ER PT J AU Sparreboom, A Scripture, CD Trieu, V Williams, PJ De, TP Yang, A Beals, B Figg, WD Hawkins, M Desai, N AF Sparreboom, A Scripture, CD Trieu, V Williams, PJ De, TP Yang, A Beals, B Figg, WD Hawkins, M Desai, N TI Comparative preclinical and clinical pharmacokinetics of a cremophor-free, nanoparticle albumin-bound paclitaxel (ABI-007) and paclitaxel formulated in cremophor (Taxol) SO CLINICAL CANCER RESEARCH LA English DT Article; Proceedings Paper CT 16th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY SEP 28-OCT 01, 2004 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR ID SURFACE AREA; PHASE-I; EL; CANCER; METABOLISM; AGENT; BLOOD; RAT AB Purpose: To compare the preclinical and clinical pharmacokinetic properties of paclitaxel formulated as a Cremophor-free, albumin-bound nanoparticle (ABI-007) and formulated in Cremophorethanol (Taxol). Experimental Design: ABI-007 and Taxol were given i.v. to Harlan Sprague-Dawley male rats to determine pharmacokinetic and drug disposition. Paclitaxel pharmacokinetic properties also were assessed in 27 patients with advanced solid tumors who were randomly assigned to treatment with ABI-007 (260 mg/m(2), 30 minutes; n = 14) or Taxol (175 mg/m(2), 3 hours; n = 13), with cycles repeated every 3 weeks. Results: The volume of distribution at steady state and clearance for paclitaxel formulated as Cremophor-free nanoparticle ABI-007 were significantly greater than those for paclitaxel formulated with Cremophor (Taxol) in rats. Fecal excretion was the main elimination pathway with both formulations. Consistent with the preclinical data, paclitaxel clearance and volume of distribution were significantly higher for ABI-007 than for Taxol in humans [21.13 versus 14.76 L/h/m(2) (p 0.048) and 663.8 versus 433.4 L/m(2) (P = 0.040), respectively]. Conclusions: Paclitaxel formulated as ABI-007 differs from paclitaxel formulated as Taxol, with a higher plasma clearance and a larger volume of distribution. This finding is consistent with the absence of paclitaxel -sequestering Cremophor micelles after administration of ABI-007. This unique property of ABI-007 could be important for its therapeutic effectiveness. C1 Amer BioSci Inc, Santa Monica, CA USA. Univ Pacific, Stockton, CA 95211 USA. RP Sparreboom, A (reprint author), NCI, Clin Pharmacol Res Core, 9000 Rockville Pike,Bldg 10,Room 5A01, Bethesda, MD 20892 USA. EM sparreba@mail.nih.gov RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 26 TC 217 Z9 228 U1 2 U2 41 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 JUN 1 PY 2005 VL 11 IS 11 BP 4136 EP 4143 DI 10.1158/1078-0432.CCR-04-2291 PG 8 WC Oncology SC Oncology GA 930YK UT WOS:000229452800019 PM 15930349 ER PT J AU Wright, MA Morrison, G Lin, PX Leonard, GD Nguyen, D Guo, XD Szabo, E Hopkins, JL Leguizamo, JP Harold, N Fioravanti, S Schuler, B Monahan, BP Saif, MW Quinn, MG Pang, J Grem, JL AF Wright, MA Morrison, G Lin, PX Leonard, GD Nguyen, D Guo, XD Szabo, E Hopkins, JL Leguizamo, JP Harold, N Fioravanti, S Schuler, B Monahan, BP Saif, MW Quinn, MG Pang, J Grem, JL TI A phase I pharmacologic and pharmacogenetic trial of sequential 24-hour infusion of irinotecan followed by leucovorin and a 48-hour infusion of fluorouracil in adult patients with solid tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID ADVANCED COLORECTAL-CANCER; UDP-GLUCURONOSYLTRANSFERASE GENE; LOW-DOSE LEUCOVORIN; THYMIDYLATE SYNTHASE; 7-ETHYL-10-HYDROXYCAMPTOTHECIN SN-38; INTRAVENOUS-INFUSION; REPEATED SEQUENCES; ACTIVE METABOLITE; GILBERTS-SYNDROME; ENHANCER REGION AB Purpose: In preclinical studies, sequential exposure to irinotecan (CPT-11) then fluorouracil (5-FU) is superior to concurrent exposure or the reverse sequence; a 24-hour infusion of CPT-11 may be better tolerated than shorter infusions. Experimental Design: CPT-11 was first given at four levels (70-140 mg/m(2)/24 hours), followed by leucovorin 500 mg/m(2)/0.5 hours and 5-FU 2,000 mg/m(2)/48 hours on days 1 and 15 of a 4-week cycle. 5-FU was then increased in three cohorts up to 3,900 mg/m(2)/48 hours. Results: Two patients had dose-limiting toxicity during cycle 1 at 140/3,900 of CPT-11/5-FU (2-week delay for neutrophil recovery; grade 3 nausea despite antiemetics); one of six patients at 140/3,120 had dose-limiting toxicity (grade 3 diarrhea, grade 4 neutropenia). Four of 22 patients with colorectal cancer had partial responses, two of which had prior bolus CPT-11/5-FU. The mean 5-FU plasma concentration was 5.1 mu mol/L at 3,900 mg/m(2)/48 hours. The end of infusion CPT-11 plasma concentration averaged 519 nmol/L at 140 mg/m(2)/24 hours. Patients with UDP-glucuronosyltransferase (UGT1A1;TA)6/6 promoter genotype had a lower ratio of free to glucuronide form of SN-38 than inpatients with >= 1 (TA)7 allele. Thymidylate synthase genotypes for the 28-base promoter repeat were 2/2 (13%), 2/3 (74%), 3/3 (13%); all four responders had a 2/3 genotype. Conclusions: Doses (mg/m(2)) of CPT-11 140/24 hours, leucovorin 500/0.5 hours and 5-FU 3,120/48 hours were well tolerated. C1 Natl Naval Med Res Inst, Gastroinestinal Tumor Sect, Bethesda, MD USA. Natl Naval Med Res Inst, Canc Therapeut Branch, Bethesda, MD USA. Natl Naval Med Res Inst, Med Oncol Clin Res Unit, Bethesda, MD USA. Natl Naval Med Res Inst, Ctr Canc Res, Bethesda, MD USA. Natl Naval Med Res Inst, Canc Prevent Program, Bethesda, MD USA. Natl Naval Med Res Inst, Natl Canc Inst, Bethesda, MD USA. Natl Naval Med Res Inst, Div Hematol & Med Oncol, Bethesda, MD USA. RP Grem, JL (reprint author), Univ Nebraska Med Ctr, Hematol Oncol Sect, 600 S 42nd St, Omaha, NE 68198 USA. EM jgrem@unmc.edu NR 50 TC 4 Z9 4 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 JUN 1 PY 2005 VL 11 IS 11 BP 4144 EP 4150 DI 10.1158/1078-0432.CCR-04-2439 PG 7 WC Oncology SC Oncology GA 930YK UT WOS:000229452800020 PM 15930350 ER PT J AU Papadimitrakopoulou, V Agelaki, S Tran, HT Kies, M Gagel, R Zinner, R Kim, E Ayers, G Wright, J Khuri, F AF Papadimitrakopoulou, V Agelaki, S Tran, HT Kies, M Gagel, R Zinner, R Kim, E Ayers, G Wright, J Khuri, F TI Phase I study of the farnesyltransferase inhibitor BMS-214662 given weekly in patients with solid tumors SO CLINICAL CANCER RESEARCH LA English DT Article ID FARNESYL TRANSFERASE INHIBITOR; PRECLINICAL ANTITUMOR-ACTIVITY; RECEPTOR TYROSINE KINASE; NEOPLASIA TYPE 2B; RAS MUTATIONS; MYELODYSPLASTIC SYNDROME; RET PROTOONCOGENE; MYELOID-LEUKEMIA; ACTIVATION; CANCER AB Purpose: A phase I trial of BMS-214662, a selective farnesyltransferase inhibitor with significant preclinical antitumor activity in which drug was given as a weekly 1-hour infusion for four of six weeks, was conducted to evaluate the tolerability, pharmacokinetics, and pharmacodynamic effect on farnesyltransferase activity in peripheral blood mononuclear cells. Experimental Design: BMS-214662 was given to 27 patients with solid tumors at 10 escalating dose levels (28-220 mg/m(2)) allowing intrapatient dose escalation; pharmacokinetics and pharmacodynamics were done at the first seven dose levels. Results: Grade 4 neutropenia (four patients) was the most common dose-limiting toxicity followed by aminotransferase elevation (grade 3 alanine aminotransferase and grade 4 aspartate aminotransferase) and grade 3 dehydration. Most frequent toxicities were neutropenia in 11 (14%), anemia in 15 (19%), fatigue in 9 (12%), and nausea and diarrhea in 6 (8%) of courses, respectively. One minor response lasting 18 weeks in a patient with non-small cell lung cancer, serum calcitonin level reduction accompanied by disease stabilization in two of four patients with medullary thyroid carcinoma, and stable disease in 16 of 25 evaluable patients was seen. No correlation was observed between dose and C-max, total body clearance (mean, 26.15 +/- 10.88 L per hour per m 2), volume of distribution at steady state (mean, 39.51 +/- 17.91 L/m(2)), or half-life (mean, 2.63 +/- 1.81 hours); a moderate correlation existed between dose given and systemic drug exposure (AUC). Substantial inhibition of peripheral blood mononuclear cell farnesyltransferase activity but near complete recovery by 24 hours was seen. Conclusion: BMS-214667 was well tolerated as a weekly 1-hour i.v. infusion for four of six weeks with evidence of pharmacodynamic effect. The study was terminated before maximum tolerated dose was reached. Alternative schedules of drug administration might result in improved pharmacodynamic profile. C1 Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Unit 432, Houston, TX 77030 USA. NCI, Canc Therapy Evaluat Program, Bethesda, MD 20892 USA. Emory Univ, Sch Med, Winship Canc Ctr, Atlanta, GA 30322 USA. RP Papadimitrakopoulou, V (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Unit 432, 1515 Holcombe Blvd, Houston, TX 77030 USA. EM vpapadim@mdanderson.org FU NCI NIH HHS [2UO1 CA062461-11] NR 52 TC 12 Z9 12 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN 1 PY 2005 VL 11 IS 11 BP 4151 EP 4159 DI 10.1158/1078-0432.CCR-04-1659 PG 9 WC Oncology SC Oncology GA 930YK UT WOS:000229452800021 PM 15930351 ER PT J AU Adams, PC Reboussin, DM Leiendecker-Foster, C Moses, GC McLaren, GD McLaren, CE Dawkins, FW Kasvosve, I Acton, RT Barton, JC Zaccaro, D Harris, EL Press, R Chang, H Eckfeldt, JH AF Adams, PC Reboussin, DM Leiendecker-Foster, C Moses, GC McLaren, GD McLaren, CE Dawkins, FW Kasvosve, I Acton, RT Barton, JC Zaccaro, D Harris, EL Press, R Chang, H Eckfeldt, JH TI Comparison of the unsaturated iron-binding capacity with transferrin saturation as a screening test to detect C282Y homozygotes for hemochromatosis in 101168 participants in the hemochromatosis and iron overload screening (HEIRS) study SO CLINICAL CHEMISTRY LA English DT Article ID HEREDITARY HEMOCHROMATOSIS; POPULATION; CONSEQUENCES; DIAGNOSIS; CURVES; GENE C1 London Hlth Sci Ctr, Dept Med, London, ON, Canada. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Winston Salem, NC 27109 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. MDS Labs, Toronto, ON, Canada. Univ Calif Irvine, Dept Med, Div Hematol Oncol, Irvine, CA 92717 USA. Vet Affiars Long beach Healthcare Syst, Long Beach, CA USA. Univ Calif Irvine, Dept Med, Div Epidemiol, Irvine, CA USA. Howard Univ, Dept Med, Washington, DC 20059 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. Univ Alabama, Dept Int Hlth, Birmingham, AL 35294 USA. So Iron Disorders Ctr, Birmingham, AL USA. Kaiser Permanente Ctr Hlth Res, Portland, OR USA. Oregon Hlth Sci Univ, Dept Pathol, Portland, OR 97201 USA. NHLBI, Div Blood Dis & Resources, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Adams, PC (reprint author), London Hlth Sci Ctr, Dept Med, 339 Windermere Rd, London, ON, Canada. EM padams@uwo.ca NR 23 TC 24 Z9 24 U1 0 U2 0 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 JUN PY 2005 VL 51 IS 6 BP 1048 EP 1052 DI 10.1373/clinchem.2005.048371 PG 5 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 930YI UT WOS:000229452600027 PM 15833784 ER PT J AU Segal, BH Barnhart, LA Anderson, VL Walsh, TJ Malech, HL Holland, SM AF Segal, BH Barnhart, LA Anderson, VL Walsh, TJ Malech, HL Holland, SM TI Posaconazole as salvage therapy in patients with chronic granulomatous disease and invasive filamentous fungal infection SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID IN-VITRO ACTIVITIES; AMPHOTERICIN-B; PULMONARY ASPERGILLOSIS; VORICONAZOLE; ITRACONAZOLE; RESISTANT; SPP.; SUSCEPTIBILITY; PROPHYLAXIS; FLUCONAZOLE AB Chronic granulomatous disease (CGD) is characterized by life-threatening bacterial and fungal infections. Treatment with posaconazole led to a complete response in 7 of 8 patients with CGD with invasive mold infections ( 7 proven cases and 1 possible case) after failure or intolerance of treatment with standard antifungal agents. In this preliminary study, salvage treatment with posaconazole was safe and effective. C1 NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. Roswell Pk Canc Inst, Dept Med, Div Infect Dis, Buffalo, NY 14263 USA. Roswell Pk Canc Inst, Dept Immunol, Div Infect Dis, Buffalo, NY 14263 USA. NIAID, Host Def Lab, NIH, Bethesda, MD 20892 USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Holland, SM (reprint author), NIAID, Lab Clin Infect Dis, NIH, 10 Ctr Dr,CRC B3-4141,MSC 1684, Bethesda, MD 20892 USA. EM smh@nih.gov NR 32 TC 85 Z9 88 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2005 VL 40 IS 11 BP 1684 EP 1688 DI 10.1086/430068 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 923AD UT WOS:000228880100018 PM 15889369 ER PT J AU Walsh, TJ van Burik, JAH AF Walsh, TJ van Burik, JAH TI Choosing a study population for the evaluation of antifungal prophylaxis - Reply SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID FUNGAL-INFECTIONS; MARROW TRANSPLANTATION; FLUCONAZOLE; CANDIDIASIS; MICAFUNGIN C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, Bethesda, MD 20892 USA. Univ Minnesota, Minneapolis, MN 55455 USA. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, CRC 1-5750,10 Ctr Dr, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov RI Young, Jo-Anne/G-2617-2013 OI Young, Jo-Anne/0000-0003-4182-341X NR 8 TC 2 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUN 1 PY 2005 VL 40 IS 11 BP 1699 EP 1701 DI 10.1086/429823 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 923AD UT WOS:000228880100023 ER PT J AU Wheaton, LA Nolte, G Bohlhalter, S Fridman, E Hallett, M AF Wheaton, LA Nolte, G Bohlhalter, S Fridman, E Hallett, M TI Synchronization of parietal and premotor areas during preparation and execution of praxis hand movements SO CLINICAL NEUROPHYSIOLOGY LA English DT Article DE EEG; parietofrontal networks; ideomotor apraxia; coherence ID SUPPLEMENTARY MOTOR AREA; EVENT-RELATED COHERENCE; RHESUS-MONKEY; CORTICOCORTICAL CONNECTIONS; SEQUENTIAL MOVEMENTS; HUMAN BRAIN; CORTEX; APRAXIA; EEG; ORGANIZATION AB Objective: We sought to determine temporal patterns of functional connectivity between the parietal, premotor, and motor cortices during preparation and execution of praxis hand movements. Methods: Normal subjects were instructed to perform six transitive (tool use) and intransitive (communicative gesture) self-paced pantomimes with the right hand while recording 64-channel electroencephalography (EEG) and electromyography (EMG) from right thumb and forearm flexors. Focusing on corticocortical coherence, we explored the time-course of synchronously active parietal and premotor circuits involved in these motor tasks. Trials were marked for EMG onset and averaged across subjects to determine changes in coherence relative to baseline between parietal, premotor, and motor areas. Results: Coherence of homologous electrode pairs was similar when comparing transitive and intransitive movements. During preparation, beta band (18-22 Hz) coherence was maximal between electrodes over the left parietal lobe and left premotor electrodes. Additionally during preparation, the premotor area showed high coherence to the motor hand area and the parietal cortex. Electrodes over the supplementary motor area also showed coherence to the motor and parietal, but not the premotor area. Before and during execution, a second peak of high coherence increase was present in each area that demonstrated coherence increases during preparation. There was no coherence increase between parietal and motor areas. Coherence rapidly diminished 1.5-2.0 s after movement onset. Conclusions: Patterns of increased corticocortical coupling within a parietal, premotor, and motor network are present during preparation and execution of praxis movements. Significance: This study adds to evidence that parietofrontal networks may be critical for integrating preparatory and motor-related activity for praxis movements. (c) 2005 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. C1 NINDS, Human Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. Inst Neurol Res FLENI, Dept Neurol, Neurorehabil Sect, Buenos Aires, DF, Argentina. RP Hallett, M (reprint author), NINDS, Human Control Sect, Med Neurol Branch, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov RI Wheaton, Lewis /B-4482-2009; OI Wheaton, Lewis /0000-0003-0771-0294; Fridman, Esteban/0000-0001-7879-8874 NR 40 TC 47 Z9 47 U1 3 U2 9 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1388-2457 J9 CLIN NEUROPHYSIOL JI Clin. Neurophysiol. PD JUN PY 2005 VL 116 IS 6 BP 1382 EP 1390 DI 10.1016/j.clinph.2005.01.008 PG 9 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 938FC UT WOS:000229984300017 PM 15978500 ER PT J AU Levine, RJ Karumanchi, SA AF Levine, RJ Karumanchi, SA TI Circulating angiogenic factors in preeclampsia SO CLINICAL OBSTETRICS AND GYNECOLOGY LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; RECEPTOR AGONISTIC ANTIBODIES; GESTATIONAL-AGE PREGNANCIES; TYROSINE KINASE-1 SFLT1; MATERNAL SERUM LEVELS; AT(1) RECEPTOR; CYTOTROPHOBLAST DIFFERENTIATION; HYPERTENSIVE PREGNANCY; ENDOVASCULAR INVASION; RANDOMIZED-TRIAL C1 NICHHD, Div Epidemiol Stat & Prevent Res, US Dept HHS, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Dept Med, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Obstet, Boston, MA 02215 USA. Beth Israel Deaconess Med Ctr, Dept Gynecol, Boston, MA 02215 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Levine, RJ (reprint author), NICHD, NIH, Bldg 6100,Rm 7B03, Bethesda, MD 20892 USA. EM LevineRJ@mail.nih.gov FU NIDDK NIH HHS [DK064255, DK065997] NR 83 TC 80 Z9 85 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-9201 J9 CLIN OBSTET GYNECOL JI Clin. Obstet. Gynecol. PD JUN PY 2005 VL 48 IS 2 BP 372 EP 386 DI 10.1097/01.grf.0000160313.82606.d7 PG 15 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 959PZ UT WOS:000231531600012 PM 15805796 ER PT J AU Giacoia, GP Mattison, DR AF Giacoia, GP Mattison, DR TI Newborns and drug studies: The NICHD/FDA newborn drug development initiative SO CLINICAL THERAPEUTICS LA English DT Article; Proceedings Paper CT Newborns Drug Development Initiative Workshop CY SEP 19, 2003-MAR 30, 2004 CL Rockville, MD SP NICHD, FDA DE neonate; Nnational Institute of Child Health and Human Development; US Food and Drug Administration; NDDI ID INTENSIVE-CARE UNIT; PROPYLENE-GLYCOL; TERM INFANTS; PRETERM INFANTS; TOLAZOLINE; PHARMACOKINETICS; CHILDREN; NEONATE; HYPEROSMOLALITY; MATURATION AB Background: Progress has been made in research on the effects of drug therapy on pediatric patients, but neonates are still an understudied population. Those most likely to receive drug therapy (eg, preterm infants) are least likely to be studied. Objectives: The purposes of this article are to summarize an initiative developed jointly by the National Institute of Child Health and Human Development (NICHD) and the US Food and Drug Administration (FDA) and to introduce a series of articles developed as a result of this initiative. Methods: Information for this article was gathered from the proceedings of a workshop cosponsored by the NICHD and the FDA that took place March 29 and 30, 2004, in Rockville, Maryland. Results: Dosing based on use in adults and older children has resulted in adverse events among newborn infants, and may have long-term effects. Moreover, formulations appropriate for use in neonates are often unavailable, and compensatory efforts such as mixing crushed tablets into formula may interfere with accurate dose delivery. Under the Best Pharmaceuticals for Children Act of 2002, government agencies work with experts in pediatrics and pediatric research to develop and prioritize a list of off-patent drugs for which pediatric studies are urgently needed. Four such listings were published in the Federal Register from January 2003 through January 2005. The NICHD and FDA have also initiated the Newborn Drug Development Initiative (NDDI), a multiphase program to determine gaps in knowledge concerning neonatal pharmacology and clinical trial design and to explore novel study designs for use in newborns, with the ultimate goal of increasing our knowledge about the safety and efficacy of drugs used to treat newborns. Conclusions: Most drugs used to treat newborns still lack appropriate dosing, efficacy, and safety studies in this vulnerable population. The NICHD and FDA developed the NDDI as an ongoing process to identify and suggest strategies for addressing obstacles to conducting drug trials in the newborn. Copyright (c) 2005 Excerpta Medica, Inc. C1 NICHHD, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Childrens, NIH,Dept Hlth & Human Serv, Bethesda, MD 20847 USA. RP Giacoia, GP (reprint author), NICHHD, Obstet & Pediat Pharmacol Branch, Ctr Res Mothers & Childrens, NIH,Dept Hlth & Human Serv, 6100 Execut Blvd,MSC 7510, Bethesda, MD 20847 USA. EM gg65m@nih.gov RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 67 TC 16 Z9 16 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PD JUN PY 2005 VL 27 IS 6 BP 796 EP 813 DI 10.1016/j.clinthera.2005.06.008 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 945VS UT WOS:000230531000014 PM 16117987 ER PT J AU Anand, KJS Aranda, JV Berde, CB Buckman, S Capparelli, EV Carlo, WA Hummel, P Lantos, P Johnston, CC Lehr, VT Lynn, AM Maxwell, LG Oberlander, TF Raju, TNK Soriano, SG Taddio, A Walco, GA AF Anand, KJS Aranda, JV Berde, CB Buckman, S Capparelli, EV Carlo, WA Hummel, P Lantos, P Johnston, CC Lehr, VT Lynn, AM Maxwell, LG Oberlander, TF Raju, TNK Soriano, SG Taddio, A Walco, GA TI Analgesia and anesthesia for neonates: Study design and ethical issues SO CLINICAL THERAPEUTICS LA English DT Article; Proceedings Paper CT Newborns Drug Development Initiative Workshop CY SEP 19-MAR 30, 2003-2004 CL Rockville, MD SP NICHD, FDA DE analgesia; anesthesia; pain; stress; neonate; infant ID BIRTH-WEIGHT INFANTS; INTENSIVE-CARE-UNIT; EXTRACORPOREAL MEMBRANE-OXYGENATION; INDIVIDUALIZED DEVELOPMENTAL CARE; RANDOMIZED CONTROLLED-TRIAL; WEEKS POSTCONCEPTIONAL AGE; PLACEBO-CONTROLLED TRIALS; PATENT DUCTUS-ARTERIOSUS; PAIN REGULATORY SYSTEMS; FORMER PRETERM INFANTS AB Objective: The purpose of this article is to summarize the clinical, methodologic, and ethical considerations for researchers interested in designing future trials in neonatal analgesia and anesthesia, hopefully stimulating additional research in this field. Methods: The MEDLINE, PubMed, EMBASE, and Cochrane register databases were searched using subject headings related to infant, newborn, neonate, analgesia, anesthesia, ethics, and study design. Cross-references and personal files were searched manually. Studies reporting original data or review articles related to these topics were assessed and critically evaluated by experts for each topical area. Data on population demographics, study characteristics, and cognitive and behavioral outcomes were abstracted and synthesized in a systematic manner and refined by group members. Data synthesis and results were reviewed by a panel of independent experts and presented to a wider audience including clinicians, scientists, regulatory personnel, and industry representatives at the Newborn Drug Development Initiative workshop. Recommendations were revised after extensive discussions at the workshop and between committee members. Results: Designing clinical trials to investigate novel or currently available approaches for analgesia and anesthesia in neonates requires consideration of salient study designs and ethical issues. Conditions requiring treatment include pain/stress resulting from invasive procedures, surgical operations, inflammatory conditions, and routine neonatal intensive care. Study design considerations must define the inclusion and exclusion criteria, a rationale for stratification, the confounding effects of comorbid conditions, and other clinical factors. Significant ethical issues include the constraints of studying neonates, obtaining informed consent, making risk-benefit assessments, defining compensation or rewards for participation, safety considerations, the use of placebo controls, and the variability among institutional review boards in interpreting federal guidelines on human research. For optimal study design, investigators must formulate well-defined study questions, choose appropriate trial designs, estimate drug efficacy, calculate sample size, determine the duration of the studies, identify pharmacokinetic and pharmacodynamic parameters, and avoid drug-drug interactions. Specific outcome measures may include scoring on pain assessment scales, various biomarkers and their patterns of response, process outcomes (eg, length of stay, time to extubation), intermediate or long-term outcomes, and safety parameters. Conclusions: Much more research is needed in this field to formulate a scientifically sound, evidence-based, and clinically useful framework for management of anesthesia and analgesia in neonates. Newer study designs and additional ethical dilemmas may be defined with accumulating data in this field. Copyright (c) 2005 Excerpta Medica, Inc. C1 Univ Arkansas Med Sci, Coll Med, Dept Pediat, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Med, Dept Anesthesiol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Med, Dept Neurobiol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Med, Dept Pharmacol, Little Rock, AR 72205 USA. Childrens Hosp Michigan, Dept Pediat, Detroit, MI 48201 USA. Childrens Hosp Michigan, Dept Pharmacol, Detroit, MI 48201 USA. Childrens Hosp Michigan, Pharmaceut Sci Network, Detroit, MI 48201 USA. Harvard Univ, Sch Med, Div Pain Med, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Anesthesia, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Pediat, Boston, MA 02115 USA. US FDA, Ctr Drug Evaluat & Res, Off Counter Terrorism & Pediat Drug Dev, Rockville, MD 20857 USA. Univ Calif San Diego, Pediat Pharmacol Res Unit, San Diego, CA 92103 USA. Univ Alabama Birmingham, Div Neonatol, Birmingham, AL USA. Loyola Univ, Med Ctr, Dev Follow Up Program, Maywood, IL 60153 USA. Univ Chicago, Dept Pediat, Chicago, IL 60637 USA. Univ Chicago, Dept Med, Chicago, IL 60637 USA. McGill Univ, Sch Nursing, Montreal, PQ, Canada. Wayne State Univ, Eugene Applebaum Sch Pharm & Hlth Sci, Dept Pharm Practice, Detroit, MI USA. Univ Washington, Sch Med, Childrens Hosp & Reg Med Ctr, Dept Anesthesiol, Seattle, WA 98195 USA. Univ Washington, Sch Med, Childrens Hosp & Reg Med Ctr, Dept Pediat, Seattle, WA 98195 USA. Childrens Hosp Philadelphia, Dept Anesthesiol, Philadelphia, PA 19104 USA. British Columbia Childrens Hosp, Div Dev Pediat, Vancouver, BC V6H 3V4, Canada. NICHHD, Pregnancy & Perinatol Branch, Ctr Dev Biol & Perinatal Med, Rockville, MD USA. Childrens Hosp, Dept Anesthesia, Boston, MA 02115 USA. Hosp Sick Children, Populat Hlth Sci Res Inst, Toronto, ON M5G 1X8, Canada. Hosp Sick Children, Dept Pharm, Toronto, ON M5G 1X8, Canada. Hackensack Univ, Med Ctr, Dept Pediat, Hackensack, NJ USA. RP Anand, KJS (reprint author), Arkansas Childrens Hosp, 800 Marshall St, Little Rock, AR 72202 USA. EM anandsunny@uams.edu OI Anand, Kanwaljeet/0000-0001-6498-1483; Maxwell, Lynne/0000-0002-4406-9232 NR 242 TC 31 Z9 33 U1 1 U2 3 PU ELSEVIER PI BRIDGEWATER PA 685 ROUTE 202-206, BRIDGEWATER, NJ 08807 USA SN 0149-2918 EI 1879-114X J9 CLIN THER JI Clin. Ther. PD JUN PY 2005 VL 27 IS 6 BP 814 EP 843 DI 10.1016/j.clinthera.2005.06.021 PG 30 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 945VS UT WOS:000230531000015 PM 16117988 ER PT J AU Denslow, S Bohning, DE Bohning, PA Lomarev, MP George, MS AF Denslow, S Bohning, DE Bohning, PA Lomarev, MP George, MS TI An increased precision comparison of TMS-induced motor cortex BOLD fMRI response for image-guided versus function-guided coil placement SO COGNITIVE AND BEHAVIORAL NEUROLOGY LA English DT Review DE neuronavigation; functional magnetic resonance imaging; transcranial magnetic stimulation; motor cortex ID TRANSCRANIAL MAGNETIC STIMULATION; CEREBRAL-CORTEX; PREFRONTAL CORTEX; BRAIN-STIMULATION; HAND AREA; LOCALIZATION; MRI; REPRESENTATION; VARIABILITY; PERCEPTION AB Objective: To examine with high precision the differences between function-guided and image-guided transcranial magnetic stimulation (T M S). Method: Using a calibrated TMS coil holder/positioner, interleaved TMS/functional magnetic resonance imaging (fMRI), and individualized anatomy-based regional normalization, we conducted a two-phase study of TMS coil positioning guided by either function (elicited thumb motion) or image-based targeting of the "hand knob," the anatomy associated with fMRI activation during thumb motion. Results: in every case, image-guided TMS coil placement produced a thumb movement response at thresholds similar to those found under function guidance. Unexpectedly, function-guided coil locations clustered bimodally over central and precentral sulci. Image-guided locations clustered as anticipated toward the targeted gyral crown. Despite these differences, blood oxygenation level-dependent (BOLD) activation locations and magnitude for the two methods displayed no consistent differences in mean or variance between or within subjects. Image guidance produced more consistent coil placement from subject to subject relative to targeted anatomy. Surprisingly, BOLD time courses from image-guided experiments showed significantly slower return to baseline after TMS than was observed under function guidance. Conclusions: The results demonstrate the effectiveness and precision of image-guided positioning of TMS coils combined with a precisely adjustable holder/positioner and regional normalization. Image guidance provides an accurate TMS placement relative to individual anatomy when no external sign is available. C1 Med Univ S Carolina, Dept Radiol, Ctr Adv Imaging Res & Brain Stimulat Labs, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Psychiat, Charleston, SC 29425 USA. NINDS, Bethesda, MD 20892 USA. Inst Human Brain, St Petersburg, Russia. Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. Ralph H Johnson Vet Hosp, Charleston, SC USA. RP Denslow, S (reprint author), Med Univ S Carolina, Dept Radiol, Ctr Adv Imaging Res & Brain Stimulat Labs, 169 Ashley Ave, Charleston, SC 29425 USA. EM denslows@musc.edu FU NCRR NIH HHS [R01 RR14080-02] NR 50 TC 21 Z9 21 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1543-3633 J9 COGN BEHAV NEUROL JI Cogn. Behav. Neurol. PD JUN PY 2005 VL 18 IS 2 BP 119 EP 126 DI 10.1097/01.wnn.0000160821.15459.68 PG 8 WC Behavioral Sciences; Clinical Neurology SC Behavioral Sciences; Neurosciences & Neurology GA 941OK UT WOS:000230223900007 PM 15970732 ER PT J AU Grady, C Dickert, N Jawetz, T Gensler, G Emanuel, E AF Grady, C Dickert, N Jawetz, T Gensler, G Emanuel, E TI An analysis of US practices of paying research participants SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE payment; compensation; reimbursement for research AB Background: Despite controversy about paying research subjects, little is known about actual practices in the U.S., including what type of studies offer payment, to what type of subjects, and how amounts are determined. Objective: To document current U.S. practices regarding payment to research subjects. Methods: The protocols and consent forms of 467 studies offering payment to research subjects approved by 11 IRBs across the U.S. were reviewed to analyze how they describe and justify payment to subjects. Results: Money was offered in a wide variety of study types, from short term physiologic studies to large clinical trials of therapeutic interventions, to both patient (61%) and healthy (24.4%) subjects or both (14.6%). Dollar amounts varied widely and were infrequently explicitly described as based on time (19%) or procedures (12%). Unexplained variation in dollar amounts occurred in similar studies or in the same (multi-site) study at different sites, and for similar procedures across studies sometimes even within one site. Although the range was wide ($5-$2000), total amounts were usually modest (overall median $155), and almost always described in the consent form (94.4%) and usually as pro-rated (73%). Conclusions: Both patient and healthy subjects are offered payment in a wide variety of types of research in the U.S. Variation in the dollar amounts offered is largely unexplained. (c) 2005 Elsevier Inc. All rights reserved. C1 NIH, Dept Clin Bioeth, Bethesda, MD 20892 USA. Emmes Corp, Rockville, MD USA. RP Grady, C (reprint author), Magnuson Clin Ctr, NIH, Bldg 10-1C118,WG, Bethesda, MD 20892 USA. EM cgrady@nih.gov NR 9 TC 44 Z9 45 U1 2 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JUN PY 2005 VL 26 IS 3 BP 365 EP 375 DI 10.1016/j.cct.2005.02.003 PG 11 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 937VU UT WOS:000229954900011 PM 15911470 ER PT J AU Raymond, EG Chen, PL Condon, S Luoto, J Barnhart, KT Creinin, MD Poindexter, A Wan, L Martens, M Schenken, R Blackwell, R AF Raymond, EG Chen, PL Condon, S Luoto, J Barnhart, KT Creinin, MD Poindexter, A Wan, L Martens, M Schenken, R Blackwell, R TI Acceptability of five nonoxynol-9 spermicides SO CONTRACEPTION LA English DT Article DE spermicide; randomized trial; acceptability AB Objective: To examine the acceptability of five nonoxynol-9 (N-9) spermicides. Methods: We analyzed data from a randomized trial of five products, including three gels containing different amounts of N-9 per dose, a film and a suppository. In the trial, 1536 participants were asked to use the assigned spermicide for 7 months and to complete questionnaires 4 weeks after admission and at discontinuation. Results: Overall, 43% of participants liked their spermicide "very much." This proportion was higher in the three gel groups than in the suppository and film groups. Difficulty with insertion, messiness and discontent with timing of insertion were common complaints in all groups. After adjustment for selected baseline factors, acceptability on the first questionnaire was not related to duration or consistency of subsequent spermicide use or to subsequent time to pregnancy. Conclusions: In this study, all five spermicides were considered acceptable by most users. Acceptability did not appear to influence spermicide use or pregnancy risk. (c) 2005 Elsevier Inc. All rights reserved. C1 Family Hlth Int, Res Triangle Pk, NC 27709 USA. NICHHD, Rockville, MD 20892 USA. Univ Penn, Med Ctr, Dept Obstet & Gynecol, Philadelphia, PA 19104 USA. Univ Penn, Med Ctr, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. Univ Pittsburgh, Dept Obstet Gynecol & Reprod Sci, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Magee Womens Res Inst, Pittsburgh, PA 15213 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. NYU, Sch Med, Dept Obstet & Gynecol, New York, NY 10016 USA. Hennepin Cty Med Ctr, Minneapolis Med Res Fdn, Dept Obstet & Gynecol, Minneapolis, MN 55415 USA. Univ Texas, Hlth Sci Ctr, Dept Obstet & Gynecol, San Antonio, TX 78229 USA. Univ Alabama, Dept Obstet & Gynecol, Birmingham, AL 35233 USA. RP Raymond, EG (reprint author), Family Hlth Int, POB 13950, Res Triangle Pk, NC 27709 USA. EM eraymond@fhi.org FU NCRR NIH HHS [M01 RR000056]; NICHD NIH HHS [N01-HD-7-3271.] NR 4 TC 18 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD JUN PY 2005 VL 71 IS 6 BP 438 EP 442 DI 10.1016/j.contraception.2004.12.023 PG 5 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 940HC UT WOS:000230133300008 PM 15914133 ER PT J AU Sprague, JE Moze, P Caden, D Rusyniak, DE Holmes, C Goldstein, DS Mills, EM AF Sprague, JE Moze, P Caden, D Rusyniak, DE Holmes, C Goldstein, DS Mills, EM TI Carvedilol reverses hyperthermia and attenuates rhabdomyolysis induced by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) in an animal model SO CRITICAL CARE MEDICINE LA English DT Article DE 3,4-methylenedioxymethamphetamine; norepinephrine; alpha(1)- and beta(3)-adrenergic receptors; creatine kinase; hyperthermia; carvedilol ID EPHEDRINE-INDUCED THERMOGENESIS; INHIBITION; HUMANS; BETA(3)-ADRENOCEPTORS; PROPRANOLOL; STIMULATION; AMPHETAMINE AB Objective. Hyperthermia is a potentially fatal manifestation of severe 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) intoxication. No proven effective drug treatment exists to reverse this potentially life-threatening hyperthermia, likely because mechanisms of peripheral thermogenesis are poorly understood. Using a rat model of MDMA hyperthermia, we evaluated the acute drug-induced changes in plasma catecholamines and used these results as a basis for the selection of drugs that could potentially reverse this hyperthermia. Design: Prospective, controlled, randomized animal study. Setting: A research institute laboratory. Subjects: Male, adult Sprague-Dawley rats. Interventions: Based on MDMA-induced changes in plasma catecholamine levels, rats were subjected to the nonselective (beta(1) + beta(2)) adrenergic receptor antagonists propranolol or nadolol or the alpha(1)- + beta(1,2,3)-adrenergic receptor antagonist carvedilol before or after a thermogenic challenge of MDMA. Measurement and Main Results. Plasma catecholamines levels 30 mins after MDMA (40 mg/kg, subcutaneously) were determined by high-pressure liquid chromatography and electrochemical detection. Core temperature was measured by a rectal probe attached to a thermocouple. Four hours after MDMA treatment, blood was drawn and serum creatine kinase levels were measured as a marker of rhabdomyolysis using a Vitros analyzer. MDMA induced a 35-fold increase in norepinephrine levels, a 20-fold increase in epinephrine, and a 2.4-fold increase in dopamine levels. Propranolol (10 mg/kg, intraperitoneally) or nadolol (10 mg/kg, intraperitoneally) administered 30 mins before MDMA had no effect on the thermogenic response. In contrast, carvedilol (5 mg/kg, intraperitoneally) administered 15 mins before or after MDMA prevented this hyperthermic response. Moreover, when administered 1 hr after MDMA, carvedilol completely reversed established hyperthermia and significantly attenuated subsequent MDMA-induced creatine kinase release. Conclusion: These data show that alpha(1) and beta(3)-adrenergic receptors may contribute to the mediation of MDMA-induced hyperthermia and that drugs targeting these receptors, such as carvedilol, warrant further investigation as novel therapies for the treatment of psychostimulant-induced hyperthermia and its sequelae. C1 NHLBI, Cardiovasc Branch, NIH, Bethesda, MD 20892 USA. NHLBI, Dept Anim Med & Surg, NIH, Bethesda, MD 20892 USA. Ohio No Univ, Dept Pharmaceut & Biomed Sci, Raabe Coll Pharm, Ada, OH 45810 USA. Univ Ljubljana, Fac Pharm, Ljubljana, Slovenia. Indiana Univ, Sch Med, Dept Emergency Med & Pharmacol & Toxicol, Indianapolis, IN 46202 USA. NINDS, Clin Neurosci Branch, NIH, Bethesda, MD 20892 USA. RP Mills, EM (reprint author), NHLBI, Cardiovasc Branch, NIH, Bldg 10, Bethesda, MD 20892 USA. EM ted_mills@mail.utexas.edu NR 34 TC 41 Z9 42 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2005 VL 33 IS 6 BP 1311 EP 1316 DI 10.1097/01.CCM.0000165969.29002 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 939HU UT WOS:000230064100019 PM 15942349 ER PT J AU Eichacker, PQ Natanson, CN AF Eichacker, PQ Natanson, CN TI Forums for expressing concerns - Reply SO CRITICAL CARE MEDICINE LA English DT Letter ID ACTIVATED PROTEIN-C; SEVERE SEPSIS; COST-EFFECTIVENESS; PROWESS TRIAL; ORGAN DYSFUNCTION; COAGULATION; SUBGROUPS; MORTALITY; SURVIVAL C1 NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Warren Grant Magnuson Clin Ctr, Dept Crit Care Med, Bethesda, MD 20892 USA. NR 28 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2005 VL 33 IS 6 BP 1467 EP 1468 DI 10.1097/01.CCM.0000166884.72944.53 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 939HU UT WOS:000230064100071 ER PT J AU Berra, L Panigada, M Kolobow, T AF Berra, L Panigada, M Kolobow, T TI Monitoring intra-cuff pressure in subglottic aspiration - Reply SO CRITICAL CARE MEDICINE LA English DT Letter ID MECHANICALLY VENTILATED PATIENTS; ENDOTRACHEAL-TUBE; BACTERIAL-COLONIZATION; SECRETION; WORK C1 NHLBI, NIH, Pulm & Crit Care Med Branch, Bethesda, MD 20892 USA. Osped Politecn Milan, Ist Anestesia & Rianimaz, I-20133 Milan, Italy. RP Berra, L (reprint author), NHLBI, NIH, Pulm & Crit Care Med Branch, Bldg 10, Bethesda, MD 20892 USA. RI Panigada, Mauro/K-4650-2014 OI Panigada, Mauro/0000-0003-4841-9794 NR 18 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD JUN PY 2005 VL 33 IS 6 BP 1470 EP 1471 DI 10.1097/01.CCM.0000166887.58141.E4 PG 2 WC Critical Care Medicine SC General & Internal Medicine GA 939HU UT WOS:000230064100075 ER PT J AU Woodhouse, EC Liotta, LA AF Woodhouse, EC Liotta, LA TI Drosophila neoplasias: Clues towards the understanding of human cancers SO CURRENT GENOMICS LA English DT Article DE tumor suppressor; Drosophila; neoplasia; lgl; dlg; scrib ID LARGE TUMOR-SUPPRESSOR; BORDER-CELL-MIGRATION; PROTEASOME-MEDIATED DEGRADATION; PAPILLOMAVIRUS E6 PROTEINS; II HEAVY-CHAIN; HUMAN HOMOLOG; DIFFERENTIAL EXPRESSION; CYTOSKELETAL PROTEIN; HUMAN SCRIBBLE; LAP PROTEIN AB A large number of tumor suppressor genes have been identified in Drosophila. Mutations in these genes cause effects in a wide range of tissues resulting in hyperplastic and, in the case of a few specific genes, neoplastic growth. The study of these tumors can provide molecular and cellular information that may shed some light on the possible mechanisms of tumorigenesis and invasiveness of human tumor cells. Recently, several studies have shown links between homologs of Drosophila tumor suppressor genes and human cancer. These recent advances are reviewed. C1 NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. RP Woodhouse, EC (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, Bldg 10,Rm 2A33, Bethesda, MD 20892 USA. EM elisa@mail.nih.gov NR 50 TC 1 Z9 1 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-2029 J9 CURR GENOMICS JI Curr. Genomics PD JUN PY 2005 VL 6 IS 4 BP 251 EP 256 DI 10.2174/1389202054395946 PG 6 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 944JZ UT WOS:000230425100004 ER PT J AU Milner, JD Gergen, PJ AF Milner, JD Gergen, PJ TI Transient environmental exposures on the developing immune system: implications for allergy and asthma SO CURRENT OPINION IN ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Review DE immunomodulation; neonate; vitamins ID COWS MILK-PROTEINS; VITAMIN-D; EARLY-CHILDHOOD; ATOPIC DISEASE; BIRTH-COHORT; NEONATAL EXPOSURE; BRONCHIAL-ASTHMA; CONTROLLED-TRIAL; UMBILICAL-CORD; FISH-OIL AB Purpose of review Early environmental exposures have been extensively studied as potential causes of the observed increase in allergic disease over time. Transient fetal or neonatal exposures in particular are of interest in that they may occur during critical windows of immune system development. Due to the tremendous complexity of variables in early life, as well as the difficulty in randomizing many interventions, it is very difficult to properly study these exposures. Some progress, however, has been made and some more candidates for study may be emerging. Of particular interest are micronutrients, whose ever-changing use and immunomodulatory capabilities make them prime targets for study. Recent findings New risk factors for atopic disease have emerged from the pool of early life interventions, such as caesarian section, prolonged labor and infant multivitamin supplementation. Data are emerging regarding micronutrient status and supplementation and their effects on the developing immune system and risk for allergic disease. Clinical trials have yet to demonstrate much causality but, in some cases, it is too early to make any judgments. Summary The gold standard of randomized clinical trials has not borne out a number of proposed early life allergic risk factors, while other trials are too incomplete to draw any conclusions so far. Properly designed studies for other risk factor interventions may still be achievable, provided that there is a proper understanding of the interventions, populations and outcomes. C1 NIAID, Immunol Lab, NIH, Asthma Allergy & Inflammat Branch, Bethesda, MD 20892 USA. NIAID, Div Allergy Immunol & Transplantat, NIH, Asthma Allergy & Inflammat Branch, Bethesda, MD 20892 USA. RP Milner, JD (reprint author), NIAID, Immunol Lab, NIH, Asthma Allergy & Inflammat Branch, 9000 Rockville Pike,10 Ctr Dr, Bethesda, MD 20892 USA. EM jdmilner@niaid.nih.gov FU NICHD NIH HHS [K12 HD00850] NR 60 TC 4 Z9 4 U1 1 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 1528-4050 J9 CURR OPIN ALLERGY CL JI Curr. Opin. Allergy Clin. Immunol. PD JUN PY 2005 VL 5 IS 3 BP 235 EP 240 DI 10.1097/01.all.0000168787.59335.8a PG 6 WC Allergy; Immunology SC Allergy; Immunology GA 970GO UT WOS:000232293500006 PM 15864081 ER PT J AU Subramaniam, S AF Subramaniam, S TI Bridging the imaging gap: visualizing subcellular architecture with electron tomography SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID FROZEN-HYDRATED SECTIONS; CHEMOTAXIS RECEPTOR TSR; CRYOELECTRON TOMOGRAPHY; ESCHERICHIA-COLI; ANGSTROM RESOLUTION; MICROSCOPY; CELLS; RECONSTRUCTION; MICROGRAPHS; COMPLEX AB Transmission electron microscopy is a powerful tool that is used to explore the internal structure of tissues, c ells, organelles and macromolecular complexes. By integrating data from a series of images in which the orientation of the specimen is progressively varied relative to the incident electron beam it is also possible to extend electron microscopic imaging into the third dimension. This approach, commonly referred to as electron tomography, has been greatly aided in recent years by advances in technology for imaging specimens at cryogenic temperatures, as well as by substantial progress in procedures for automated data collection and image processing. The intense pace of developments in this field is inspired, in a large part, by the hope that the quality of the data will ultimately be good enough to allow interpretation of tomograms of cells, organelles, bacteria and viruses in terms of the three-dimensional spatial arrangements of the constituent molecules. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Subramaniam, S (reprint author), NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM ss1@nih.gov NR 42 TC 55 Z9 58 U1 0 U2 7 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD JUN PY 2005 VL 8 IS 3 BP 316 EP 322 DI 10.1016/j.mib.2005.04.012 PG 7 WC Microbiology SC Microbiology GA 939UN UT WOS:000230098000013 PM 15939356 ER PT J AU Speer, R Wulfkuhle, JD Liotta, LA Petricoin, EF AF Speer, R Wulfkuhle, JD Liotta, LA Petricoin, EF TI Reverse-phase protein microarrays for tissue-based analysis SO CURRENT OPINION IN MOLECULAR THERAPEUTICS LA English DT Article DE microarrays; protein proteomics; reverse phase; tailored therapy ID PHOSPHORYLATED PROTEINS; CLINICAL PROTEOMICS; KINASE INHIBITORS; PROSTATE-CANCER; BREAST-CANCER; ZD1839 IRESSA; SPECIMENS; MICROENVIRONMENT; TRASTUZUMAB; DIAGNOSIS AB The deciphering of the human genome has elucidated our biological structural design and has generated insights into disease development and pathogenesis. At the same time, knowledge of genetic changes during disease processes has demonstrated the need to move beyond genomics towards proteomics and a systems biology approach to science. Analyzing the proteome comprises more than just a numeration of proteins. In fact, it characterizes proteins within cells in the context of their functional status and interactions in their physiological micro- and macro-environments. As dysregulated signaling often underpins most human diseases, an overarching goal of proteomics is to profile the working state of signaling pathways, to develop 'circuit maps' of normal and diseased protein networks and identify hyperactive, defective or inoperable transduction pathways. Reverse-phase protein microarrays represent a new technology that can generate a multiplex readout of dozens of phosphorylated events simultaneously to profile the state of a signaling pathway target even after the cell is lyzed and the contents denatured. C1 NCI, Ctr Canc Res, FDA NCI Clin Proteom Program, Lab Pathol,NIH, Bethesda, MD 20892 USA. George Mason Univ, Ctr Appl Proteom & Mol Med, Dept Mol & Microbiol, Manassas, VA 20110 USA. RP Petricoin, EF (reprint author), NCI, Ctr Canc Res, FDA NCI Clin Proteom Program, Lab Pathol,NIH, Bethesda, MD 20892 USA. EM epetrico@gmu.edu NR 40 TC 22 Z9 25 U1 2 U2 8 PU CURRENT DRUGS LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1P 6LB, ENGLAND SN 1464-8431 J9 CURR OPIN MOL THER JI Curr. Opin. Mol. Ther. PD JUN PY 2005 VL 7 IS 3 BP 240 EP 245 PG 6 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 933HF UT WOS:000229618800007 PM 15977421 ER PT J AU Hall, TMT AF Hall, TMT TI Multiple modes of RNA recognition by zinc finger proteins SO CURRENT OPINION IN STRUCTURAL BIOLOGY LA English DT Review ID TRANSCRIPTION FACTOR IIIA; INTERNAL CONTROL REGION; AU-RICH ELEMENTS; MESSENGER-RNA; 5S RNA; CRYSTAL-STRUCTURE; DNA RECOGNITION; XENOPUS OOCYTES; SEQUENCE; TRISTETRAPROLIN AB Zinc finger proteins are generally thought of as DNA-binding transcription factors; however, certain classes of zinc finger proteins, including the common C2H2 zinc fingers, function as RNA-binding proteins. Recent structural studies of the C2H2 zinc fingers of transcription factor IIIA (TFIIIA) and the CCCH zinc fingers of Tis11d in complex with their RNA targets have revealed new modes of zinc finger interaction with nucleic acid. The three C2H2 zinc fingers of TFIIIA use two modes of RNA recognition that differ from the classical mode of DNA recognition, whereas the CCCH zinc fingers of Tis11d recognize specific AU-rich sequences through backbone atom interaction with the Watson-Crick edges of the adenine and uracil bases. C1 Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. RP Hall, TMT (reprint author), Natl Inst Environm Hlth Sci, Struct Biol Lab, NIH, Res Triangle Pk, NC 27709 USA. EM hall4@niehs.nih.gov NR 31 TC 133 Z9 141 U1 1 U2 23 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0959-440X J9 CURR OPIN STRUC BIOL JI Curr. Opin. Struct. Biol. PD JUN PY 2005 VL 15 IS 3 BP 367 EP 373 DI 10.1016/j.sbi.2005.04.004 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 943VA UT WOS:000230381600017 PM 15963892 ER PT J AU Kishigami, S Mishina, Y AF Kishigami, S Mishina, Y TI BMP signaling and early embryonic patterning SO CYTOKINE & GROWTH FACTOR REVIEWS LA English DT Review DE TGF-beta; BMP; receptor; embryogenesis; gastrulation; embryonic patterning ID LEFT-RIGHT ASYMMETRY; LEFT-RIGHT AXIS; BONE MORPHOGENETIC PROTEIN-4; PRIMORDIAL GERM-CELLS; EARLY MOUSE EMBRYO; GROWTH-FACTOR-BETA; ANTERIOR VISCERAL ENDODERM; CERBERUS-RELATED GENE; NEURAL CREST CELLS; TGF-BETA AB Bone morphogenetic proteins (BMPs) play pleiotropic roles during embryonic development as well as throughout life. Recent genetic approaches especially using the mouse gene knockout system revealed that BMP signaling is greatly involved in early embryonic patterning, which is a dynamic event to establish three-dimensional polarities. The purpose of this review is to describe the diverse function of BMPs through different receptor signaling systems during embryonic patterning including gastrulation and establishment of the left-right asymmetry. (c) 2005 Elsevier Ltd. All rights reserved. C1 NIEHS, Mol Dev Biol Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Mishina, Y (reprint author), NIEHS, Mol Dev Biol Sect, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. EM kishigami@cdb.riken.go.jp; mishina@niehs.nih.gov NR 163 TC 165 Z9 175 U1 1 U2 6 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1359-6101 J9 CYTOKINE GROWTH F R JI Cytokine Growth Factor Rev. PD JUN PY 2005 VL 16 IS 3 BP 265 EP 278 DI 10.1016/j.cytogfr.2005.04.002 PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 950KV UT WOS:000230856900003 PM 15871922 ER PT J AU Nishioka, N Nagano, S Nakayama, R Kiyonari, H Ijiri, T Taniguchi, K Shawlot, W Hayashizaki, Y Westphal, H Behringer, RR Matsuda, Y Sakoda, S Kondoh, H Sasaki, H AF Nishioka, N Nagano, S Nakayama, R Kiyonari, H Ijiri, T Taniguchi, K Shawlot, W Hayashizaki, Y Westphal, H Behringer, RR Matsuda, Y Sakoda, S Kondoh, H Sasaki, H TI Ssdp1 regulates head morphogenesis of mouse embryos by activating the Lim1-Ldb1 complex SO DEVELOPMENT LA English DT Article DE Ssdp1; head organizer; prechordal plate; headshrinker; Lim1; Ldb1; cell proliferation; mouse ID DNA-BINDING PROTEIN; LIM-DOMAIN; MESODERM DIFFERENTIATION; TRANSCRIPTION FACTORS; HOMEODOMAIN PROTEINS; NEURALIZING ACTIVITY; VISCERAL ENDODERM; XENOPUS-EMBRYOS; IN-VIVO; EXPRESSION AB The transcriptional activity of LIM-homeodomain (LIM-HD) proteins is regulated by their interactions with various factors that bind to the LIM domain. We show that reduced expression of single-stranded DNA-binding protein 1 (Ssdp1), which encodes a co-factor of LIM domain interacting protein I (Ldb1), in the mouse mutant headshrinker (hsk) disrupts anterior head development by partially mimicking Lim1 mutants. Although the anterior visceral endoderm and the anterior definitive endoderm, which together comprise the head organizer, were able to form normally in Ssdp1(hsk/hsk) mutants, development of the prechordal plate was compromised. Head development is partially initiated in Ssdp1(hsk/hsk) mutants, but neuroectoderm tissue anterior to the midbrain-hindbrain boundary is lost, without a concomitant increase in apoptosis. Cell proliferation is globally reduced in Ssdp1(hsk/hsk) mutants, and approximately half also exhibit smaller body size, similar to the phenotype observed in Lim1 and Ldb1 mutants. We also show that Ssdp1 contains an activation domain and is able to enhance transcriptional activation through a Lim1-Ldb1 complex in transfected cells, and that Ssdp1 interacts genetically with Lim1 and Ldb1 in both head development and body growth. These results suggest that Ssdp1 regulates the development of late head organizer tissues and body growth by functioning as an essential activator component of a Lim1 complex through interaction with Ldb1. C1 RIKEN, Ctr Dev Biol, Lab Embryon Induct, Chuo Ku, Kobe, Hyogo 6500047, Japan. Osaka Univ, Grad Sch Frontier Biosci, Suita, Osaka 5650871, Japan. Osaka Univ, Grad Sch Med, Dept Neurol, Suita, Osaka 5650871, Japan. RIKEN, Ctr Dev Biol, LARGE, Chuo Ku, Kobe, Hyogo 6500047, Japan. Hokkaido Univ, Grad Sch Environm Earth Sci, Div Biosci, Sapporo, Hokkaido 0600810, Japan. Univ Minnesota, Dept Genet Cell Biol & Dev, Minneapolis, MN 55455 USA. RIKEN, Genom Sci Ctr, Lab Genome Explorat Res Grp, Yokohama, Kanagawa 2300045, Japan. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Genet, Houston, TX 77030 USA. Hokkaido Univ, Ctr Adv Sci & Technol, Sapporo, Hokkaido 0600810, Japan. RP Sasaki, H (reprint author), RIKEN, Ctr Dev Biol, Lab Embryon Induct, Chuo Ku, 2-2-3 Minatojima Minamimachi, Kobe, Hyogo 6500047, Japan. EM sasaki@cdb.riken.jp RI Kiyonari, Hiroshi/N-7936-2015 NR 61 TC 44 Z9 45 U1 0 U2 2 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD JUN PY 2005 VL 132 IS 11 BP 2535 EP 2546 DI 10.1242/dev.018144 PG 12 WC Developmental Biology SC Developmental Biology GA 939HI UT WOS:000230062800004 PM 15857913 ER PT J AU Blair, RJR AF Blair, RJR TI Applying a cognitive neuroscience perspective to the disorder of psychopathy SO DEVELOPMENT AND PSYCHOPATHOLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; ORBITOFRONTAL CORTEX DYSFUNCTION; PRESCHOOL CHILDRENS CONCEPTIONS; STARTLE REFLEX MODULATION; PREFRONTAL CORTEX; ANTISOCIAL-BEHAVIOR; CRIMINAL PSYCHOPATHS; FACIAL EXPRESSIONS; CONDUCT PROBLEMS; PERSONALITY-DISORDERS AB Four models of psychopathy (frontal lobe dysfunction, response set modulation, fear dysfunction, and violence inhibition mechanism hypotheses) are reviewed from the perspective of cognitive neuroscience. Each model is considered both with respect to the psychopathy data and, more importantly, for the present purposes, with respect to the broader cognitive neuroscience fields to which the model refers (e.g., models of attention with respect to the response set modulation account and models of emotion with respect to the fear dysfunction and violence inhibition mechanism models). The paper concludes with an articulation of the more recent integrated emotion systems model, an account inspired both by recent findings in affective cognitive neuroscience as well as in the study of psychopathy. Some directions for future work are considered. C1 NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Blair, RJR (reprint author), NIMH, Unit Affect Cognit Neurosci, Mood & Anxiety Disorders Program, 15K North Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov NR 212 TC 147 Z9 150 U1 12 U2 53 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0954-5794 J9 DEV PSYCHOPATHOL JI Dev. Psychopathol. PD SUM PY 2005 VL 17 IS 3 BP 865 EP 891 DI 10.1017/S0954579405050418 PG 27 WC Psychology, Developmental SC Psychology GA 990VT UT WOS:000233772000015 PM 16262996 ER PT J AU Kim, JW Sitaraman, S Hierro, A Beach, BM Odorizzi, G Hurley, JH AF Kim, JW Sitaraman, S Hierro, A Beach, BM Odorizzi, G Hurley, JH TI Structural basis for endosomal targeting by the Bro1 domain SO DEVELOPMENTAL CELL LA English DT Article ID MULTIVESICULAR BODY PATHWAY; RECEPTOR DOWN-REGULATION; ALG-2-INTERACTING PROTEIN ALIX; ESCRT-I; SACCHAROMYCES-CEREVISIAE; UBIQUITINATED PROTEINS; BINDING PARTNER; SORTING COMPLEX; REPEAT DOMAIN; HUMAN HOMOLOG AB Proteins delivered to the lysosome or the yeast vacuole via late endosomes are sorted by the ESCRT complexes and by associated proteins, including Alix and its yeast homolog Bro1. Alix, Bro1, and several other late endosomal proteins share a conserved 160 residue Bro1 domain whose boundaries, structure, and function have not been characterized. The crystal structure of the Bro1 domain of Bro1 reveals a folded core of 367 residues. The extended Bro1 domain is necessary and sufficient for binding to the ESCRT-III subunit Snf7 and for the recruitment of Brol to late endosomes. The structure resembles a boomerang with its concave face filled in and contains a triple tetratricopeptide repeat domain as a substructure. Snf7 binds to a conserved hydrophobic patch on Bro1 that is required for protein complex formation and for the protein-sorting function of Bro1. These results define a conserved mechanism whereby Brol domain-containing proteins are targeted to endosomes by Snf7 and its orthologs. C1 Univ Colorado, Dept Mol Cellular & Dev Biol, Boulder, CO 80309 USA. RP Hurley, JH (reprint author), NIDDK, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. EM hurley@helix.nih.gov RI Hierro, Aitor/F-9998-2011; OI Hierro, Aitor/0000-0002-7721-1581; Odorizzi, Greg/0000-0002-1143-1098 FU NIGMS NIH HHS [GM065505, R01 GM065505, R01 GM065505-01A1] NR 69 TC 123 Z9 124 U1 0 U2 2 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1534-5807 J9 DEV CELL JI Dev. Cell PD JUN PY 2005 VL 8 IS 6 BP 937 EP 947 DI 10.1016/j.devcel.2005.04.001 PG 11 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 938LZ UT WOS:000230006200017 PM 15935782 ER PT J AU Herold, KC Gitelman, SE Masharani, U Hagopian, W Bisikirska, B Donaldson, D Rother, K Diamond, B Harlan, DM Bluestone, JA AF Herold, KC Gitelman, SE Masharani, U Hagopian, W Bisikirska, B Donaldson, D Rother, K Diamond, B Harlan, DM Bluestone, JA TI A single course of anti-CD3 monoclonal antibody hOKT3 gamma 1(Ala-Ala) results in improvement in C-peptide responses and clinical parameters for at least 2 years after onset of type 1 diabetes SO DIABETES LA English DT Article ID SELF-TOLERANCE; T-CELLS; MELLITUS; CYCLOSPORINE; REMISSION; TRIAL; OKT3; CD3; IMMUNOSUPPRESSION; PREDNISONE AB Despite advances in understanding autoimmune diabetes in animal models, there has been little progress in altering the natural course of the human disease, which involves progression to insulin deficiency. Studies with immunosuppressive agents have shown short-term effectiveness, but they have not induced tolerance, and continuous treatment is needed. We studied the effects of hOKT3 gamma 1(Ala-Ala), a humanized Fc mutated anti-CD3 monoclonal antibody, on the progression of type 1 diabetes in patients with recent-onset disease in a randomized controlled trial. In general, the drug was well tolerated. A single course of treatment, within the first 6 weeks after diagnosis, preserved C-peptide responses to a mixed meal for 1 year after diagnosis (97 9.6% of response at study entry in drug-treated patients vs. 53 +/- 7.6% in control subjects, P < 0.01), with significant improvement in C-peptide responses to a mixed meal even 2 years after treatment (P < 0.02). The improved C-peptide responses were accompanied by reduced HbA(1c), and insulin requirements. Clinical responses to drug treatment were predicted by an increase in the relative number of CD8(+) T-cells in the peripheral blood after the lymphocyte count recovered 2 weeks after the last dose of drug. We conclude that treatment with the anti-CD3 monoclonal antibody hOKT3 gamma 1(Ala-Ala) results in improved C-peptide responses and clinical parameters in type 1 diabetes for at least 2 years in the absence of continued immunosuppressive medications. C1 Columbia Univ, Coll Phys & Surg, Dept Med, Div Endocrinol, New York, NY 10032 USA. Columbia Univ, Coll Phys & Surg, Naomi Berrie Diabet Ctr, New York, NY 10032 USA. Univ Calif San Francisco, Ctr Diabet, San Francisco, CA 94143 USA. Pacific NW Res Inst, Seattle, WA USA. Univ Utah, Dept Pediat, Salt Lake City, UT USA. NIDDKD, Bethesda, MD 20892 USA. RP Herold, KC (reprint author), Columbia Univ, Coll Phys & Surg, Dept Med, Div Endocrinol, PH10-105,630 W 168th St, New York, NY 10032 USA. EM kh318@columbia.edu FU NCRR NIH HHS [M01 RR000645, M01 RR001271, M01-RR-00645, M01-RR-01271]; NIDDK NIH HHS [P30 DK063608, P30-DK-63608, P60 DK020595, P60-DK-20595, R01 DK057846, R01-DK-57846]; PHS HHS [U19A146132] NR 27 TC 401 Z9 412 U1 3 U2 9 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0012-1797 EI 1939-327X J9 DIABETES JI Diabetes PD JUN PY 2005 VL 54 IS 6 BP 1763 EP 1769 DI 10.2337/diabetes.54.6.1763 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 931QI UT WOS:000229499600018 PM 15919798 ER PT J AU Koh, KK Ahn, JY Han, SH Shin, EK Quon, MJ AF Koh, KK Ahn, JY Han, SH Shin, EK Quon, MJ TI Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia SO DIABETES CARE LA English DT Article; Proceedings Paper CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06-09, 2005 CL Orlando, FL SP Amer Coll Cardiol ID DENSITY-LIPOPROTEIN CHOLESTEROL; CORONARY-ARTERY-DISEASE; SENSITIVITY CHECK INDEX; INSULIN SENSITIVITY; HYPERTENSIVE PATIENTS; NITRIC-OXIDE; RESISTANCE; ATHEROSCLEROSIS; ASSOCIATION; EXPRESSION AB OBJECTIVE - improvement in endothelial function is predicted to improve insulin sensitivity, and this may be one mechanism by which fenofibrate decreases the incidence of coronary heart disease. We hypothesize fenofibrate improves endothelial function by enhancing insulin sensitivity. RESEARCH DESIGN AND METHODS - We administered placebo or fenofibrate 200 mg daily for 8 weeks to 46 patients with primary hypertriglyceridemia (24 had metabolic syndrome). This study was randomized, double blind, placebo controlled, and crossover in design. RESULTS - Compared with placebo, fenofibrate decreased total cholesterol, non-HDL cholesterol, apolipoprotein B, and triglycerides and increased HDL cholesterol and apolipoprotein A-I (all P < 0.001) while tending to decrease LDL cholesterol (P = 0.069). Fenofibrate significantly improved percent flow-mediated dilator response to hyperemia by 48 &PLUSMN; 5% (P < 0.001) and lowered plasma levels of high-sensitivity C-reactive protein (hsCRP) relative to baseline measurements from 0.80 to 0.70 mg/l (P = 0.001) and fibrinogen levels by 16 &PLUSMN; 3% (P < 0.001). Compared with placebo, fenofibrate therapy significantly increased plasma levels of adiponectin by 14 &PLUSMN; 5% (P = 0.008) and increased insulin sensitivity (assessed by quantitative insulin sensitivity check index [QUICKI]) by 6 &PLUSMN; 2% (P = 0.048). There were significant correlations between percent changes in adiponectin levels and percent changes in flow-mediated dilation (r = 0.401, P = 0.006), hsCRP (r = -0.443, P = 0.002), or QUICKI (r = 0.292, P = 0.049). Multivariate regression analysis showed that only changes in adiponectin levels persisted as an independent predictor of changes in flow-mediated dilation (r = 0.504, P = 0.013). Overall, we observed similar results in 24 patients with metabolic syndrome. CONCLUSIONS - Fenofibrate therapy significantly improved percent flow-mediated dilator response to hyperemia, reduced inflammation marker levels, increased adiponectin levels, and improved insulin sensitivity in hypertriglyceridemic or metabolic syndrome patients. C1 Gachon Med Sch, Gil Heart Ctr, Div Cardiol, Vasc Med & Atherosclerosis Unit, Inchon 405760, South Korea. Gachon Med Sch, Div Lab Med, Inchon, South Korea. NIH, Diabet Unit, Clin Invest Lab, Natl Ctr Complementary & Alternat Med, Bethesda, MD 20892 USA. RP Koh, KK (reprint author), Gachon Med Sch, Gil Heart Ctr, Div Cardiol, Vasc Med & Atherosclerosis Unit, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@ghil.com RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 21 TC 114 Z9 124 U1 0 U2 2 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD JUN PY 2005 VL 28 IS 6 BP 1419 EP 1424 DI 10.2337/diacare.28.6.1419 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 931QM UT WOS:000229500000024 PM 15920062 ER PT J AU Wang, SS Dasgupta, A Sherman, ME Walker, JL Gold, MA Zuna, R Sakoda, L Wacholder, S Schiffman, M Baker, CC AF Wang, SS Dasgupta, A Sherman, ME Walker, JL Gold, MA Zuna, R Sakoda, L Wacholder, S Schiffman, M Baker, CC TI Towards improved biomarker studies of cervical neoplasia - Effects of precolposcopic procedures on gene expression patterns SO DIAGNOSTIC MOLECULAR PATHOLOGY LA English DT Article DE gene expression; microarray; tissue acquisition ID FALSE DISCOVERY RATE; MICROARRAY DATA; PREDICTION; BIOPSIES AB Among tumor sites. cervical cancer offers an ideal model for investigating differences in gene expression associated with transitions from normal to precancer and invasion to cancer. To evaluate the validity of assessing gene expression in cervical tissues acquired in a clinical setting, we investigated whether standard procedures, namely the application of acetic acid and/or Lugol's iodine, employed for the visualization of colposcopically directed biopsies, altered patterns in oligonucleotide (oligo) arrays. We compared microarray profiles from six women, each with three adjacent tissue samples removed from benign hysterectomy specimens and treated as follows: immediately frozen. acetic acid application only, acetic acid, and Lugol's iodine. Of the 22,464 original spots on the microarray, 4,850 spots were expressed at detectable levels for further evaluation upon data normalization and filtration. For each spot, the difference between topical applications was computed, and P values were calculated using a bivariate T-2 test. Upon adjustment for multiple comparisons using both the Holm's and Hochberg's procedures as well as the False Discovery Rate (Benjamini-Hochberg and Benjamini-Yeuketili [BY]), we failed to identify genes differentially expressed and conclude that standard precolposcopic procedures do not substantially affect the overall gene expression patterns in the normal cervix. C1 Natl Canc Inst, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Canc Inst, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD USA. Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Pathol, Oklahoma City, OK USA. Natl Canc Inst, Cellular Oncol Lab, Ctr Canc Res, Bethesda, MD USA. RP Wang, SS (reprint author), Natl Canc Inst, Hormonal & Reprod Epidemiol Branch, Div Canc Epidemiol & Genet, 6120 Execut Blvd,EPS MSC 7234, Bethesda, MD 20892 USA. EM wangso@mail.nih.gov FU NCI NIH HHS [N02CP31102]; NCRR NIH HHS [M01 RR-14467] NR 20 TC 4 Z9 4 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1052-9551 J9 DIAGN MOL PATHOL JI Diagn. Mol. Pathol. PD JUN PY 2005 VL 14 IS 2 BP 59 EP 64 DI 10.1097/01.pas.0000162754.45908.d4 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pathology GA 930CQ UT WOS:000229393800001 PM 15905687 ER PT J AU Perkins, GL Derfoul, A Ast, A Hall, DJ AF Perkins, GL Derfoul, A Ast, A Hall, DJ TI An inhibitor of the stretch-activated cation receptor exerts a potent effect on chondrocyte phenotype SO DIFFERENTIATION LA English DT Article DE chondrocyte gene expression; gadolinium chloride ID BOVINE ARTICULAR CHONDROCYTES; PRO-ALPHA-1(II) COLLAGEN GENE; CELL-LINE; DEDIFFERENTIATED CHONDROCYTES; INTRACELLULAR CALCIUM; CARTILAGE FORMATION; RAT CHONDROSARCOMA; ION CHANNELS; IN-VITRO; EXPRESSION AB Rat chondrosarcoma (RCS) cells are unusual in that they display a stable chondrocyte phenotype in monolayer culture. This phenotype is reflected by a rounded cellular morphology with few actin-containing stress fibers and production of an extracellular matrix rich in sulfated proteoglycans, with high-level expression of aggrecan, COMP, Sox9, and collagens type II, IX, and XI. Additionally, these cells do not express collagen type I. Here it is shown that in the absence of any mechanical stimulation, treatment of RCS cells with gadolinium chloride (Gd3+), a stretch-activated cation channel blocker, caused the cells to undergo de-differentiation, adopting a flattened fibroblast phenotype with the marked appearance of actin stress fibers and vinculin-containing focal contacts. This change was accompanied by a dramatic reduction in the expression of aggrecan, Sox9, collagen types II, IX, and XI, with a corresponding increase in the expression of collagen type I and fibronectin. These effects were found to be reversible by simple removal of Gd3+ from the medium. Gd3+ also had a similar effect on expression of chondrocyte marker genes in freshly isolated human chondrocytes. These data suggest that mechanoreceptor signaling plays a key role in maintenance of the chondrocyte phenotype, even in the absence of mechanical stimulation. Further, treatment of RCS cells with Gd3+ provides a tractable system for assessing the molecular events underlying the reversible differentiation of chondrocytes. C1 NIAMSD, Cartilage Mol Genet Grp, Cartilage Biol & Orthopaed Branch, US Dept HHS,NIH, Bethesda, MD 20892 USA. RP Hall, DJ (reprint author), NIAMSD, Cartilage Mol Genet Grp, Cartilage Biol & Orthopaed Branch, US Dept HHS,NIH, Bldg 13,Room 3W17,MSC 5755, Bethesda, MD 20892 USA. EM halld@mail.nih.gov NR 60 TC 24 Z9 26 U1 1 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD JUN PY 2005 VL 73 IS 5 BP 199 EP 211 DI 10.1111/j.1432-0436.2005.00024.x PG 13 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 942PH UT WOS:000230293800001 PM 16026542 ER PT J AU Behnan, SM Guo, C Gong, TW Shum, L Gong, SG AF Behnan, SM Guo, C Gong, TW Shum, L Gong, SG TI Gene and protein expression of Transforming growth factor beta 2 gene during murine primary palatogenesis SO DIFFERENTIATION LA English DT Article DE midface; primary palate fusion; clefts of lip and palate; in situ hybridization; craniofacial development ID GROWTH-FACTOR-BETA; PALATE MESENCHYMAL CELLS; MEDIAL EDGE EPITHELIUM; CLEFT-LIP; IMMUNOHISTOCHEMICAL LOCALIZATION; DIFFERENTIAL EXPRESSION; SECONDARY PALATE; KNOCKOUT MICE; FUSION; TGF-BETA-3 AB The molecular mechanisms by which the primordia of the midface grow and fuse to form the primary palate are not well characterized. This is in spite of the fact that failure of growth and/or fusion of these facial primordia leads to the common human craniofacial birth defects, clefts of the lip with or without clefts of the palate. Members of the transforming growth factor beta (Tgf beta) superfamily have been shown to play critical roles during craniofacial development. Specifically, the role of Tgf beta-3 in mediating the fusion of the embryonic secondary palatal shelves is well documented. In a screen for genes expressed during fusion of the murine midfacial processes, Tgf beta 2 was identified as a gene differentially expressed during fusion of the lateral and medial nasal processes. The objective of our study was to analyze the spatial and temporal expression of Tgf beta 2 during critical stages of midfacial morphogenesis at both the transcript and protein levels. We also compared the pattern of expression of Tgf beta 2 with that of Bmp4, a gene shown previously to be involved in mediating the fusion process in the midface. Our results showed Tgf beta 2 expression in a very restrictive area of the epithelial layer along the borders of the midfacial primordia, in a pattern very similar to that of Bmp4. The highly restrictive and spatial and temporal pattern of expression of Tgf beta 2 implicates its role in mediating the fusion of the midfacial processes, possibly through interacting with Bmp4 in the regulation of apoptosis and/or epithelial-mesenchymal transformation. A greater understanding of the role of this gene will clarify how the normal midface grows and the mechanisms behind cleft development. C1 Univ Michigan, Sch Dent, Ann Arbor, MI 48109 USA. Univ Michigan, Kresge Hearing Res Inst, Dept Otolaryngol Head & Neck Surg, Ann Arbor, MI 48109 USA. NIDCR, Physiol Pharmacogenet & Injury Program, Div Basic & Translat Sci, NIH, Bethesda, MD USA. RP Gong, SG (reprint author), Univ Michigan, Sch Dent, 1011 N Univ Ave, Ann Arbor, MI 48109 USA. EM sggong@umich.edu FU NIDCR NIH HHS [DE009101] NR 39 TC 6 Z9 6 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0301-4681 J9 DIFFERENTIATION JI Differentiation PD JUN PY 2005 VL 73 IS 5 BP 233 EP 239 DI 10.1111/j.1432-0436.2005.00022.x PG 7 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 942PH UT WOS:000230293800004 PM 16026545 ER PT J AU Pessoa, L Japee, S Ungerleider, LG AF Pessoa, L Japee, S Ungerleider, LG TI Visual awareness and the detection of fearful faces SO EMOTION LA English DT Editorial Material ID EMOTIONAL FACIAL EXPRESSIONS; SKIN-CONDUCTANCE RESPONSES; BACKWARD-MASKING; ATTENTION; STIMULI; NEUROPHYSIOLOGY; PERCEPTION; AMYGDALA; BRAIN AB A commonly held view is that emotional stimuli are processed independently of awareness. Here, the authors parametrically varied the duration of a fearful face target stimulus that was backward masked by a neutral face. The authors evaluated awareness by characterizing behavioral performance using receiver operating characteristic curves from signal detection theory. Their main finding was that no universal objective awareness threshold exists for fear perception. Although several subjects displayed a behavioral pattern consistent with previous reports (i.e., targets masked at 33 ms), a considerable percentage of their subject, (64%) were capable of reliably detecting 33 ms targets. Their findings suggest that considerable information is available even in briefly presented stimuli (possibly as short as 17 Ins) to support masked fear detection. C1 Brown Univ, Dept Psychol, Providence, RI 02912 USA. NIMH, Lab Brain & Cognit, Bethesda, MD 20892 USA. RP Pessoa, L (reprint author), Brown Univ, Dept Psychol, 89 Waterman St, Providence, RI 02912 USA. EM pessoa@brown.edu FU NIMH NIH HHS [1 R01 MH071589-01] NR 24 TC 113 Z9 119 U1 4 U2 19 PU AMER PSYCHOLOGICAL ASSOC/EDUCATIONAL PUBLISHING FOUNDATION PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1528-3542 J9 EMOTION JI Emotion PD JUN PY 2005 VL 5 IS 2 BP 243 EP 247 DI 10.1037/1528-3542.5.2.243 PG 5 WC Psychology, Experimental SC Psychology GA 944QL UT WOS:000230443800013 PM 15982091 ER PT J AU Doyle, ME Mcconville, P Theodorakis, MJ Goetschkes, MM Bernier, M Spencer, RGS Holloway, HW Greig, NH Egan, JM AF Doyle, ME Mcconville, P Theodorakis, MJ Goetschkes, MM Bernier, M Spencer, RGS Holloway, HW Greig, NH Egan, JM TI In vivo biological activity of exendin (1-30) SO ENDOCRINE LA English DT Article DE rodents; magnetic resonance imaging; diabetes; insulinotropic compounds ID GLUCAGON-LIKE PEPTIDE-1; GLP-1 RECEPTOR; CELL MASS; GLUCOSE; RATS; EXPRESSION; GLUCAGON-LIKE-PEPTIDE-1; STABILITY; PANCREAS; HUMANS AB Activation of the glucagon-like peptide-1 (GLP-1) receptor on pancreatic beta cells by GLP-1 and exendin-4 (a more potent and stable agonist of the GLP-1 receptor than GLP-1) increases insulin secretion. Exendin-4 is 39 amino acids long, unlike GLP-1 which has 30 amino acids. Because of its non-mammalian (lizard) origin and unique C-terminal sequence, exendin-4 may be immunogenic in humans. We showed previously that the C terminally truncated exendin peptide exendin (1-30) has a reduced affinity for the GLP-1 receptor and a diminished ability to increase intracellular cAMP in insulinoma cells. Here we show that daily intraperitoneal injection of exendin (1-30) (1 nmol/kg) for 20 d followed by 31 d twice daily to Lepr(db)/Lepr(db) (db/db) mice significantly reduced the amount of visceral fat relative to saline-treated controls and improved HbA(1C) (control 9.5 +/- 0.2 % vs treated 7.9 +/- 0.2 %, p = 0.001) but was not as effective as exendin-4. To examine the ability of exendin (1-30) to stimulate beta-cell growth, we injected one group of 3-mo-old Fisher rats with exendin (1-30) (1 nmol/kg) and another group with saline for 8 d. We observed no change in beta-cell area, but did see a change in the number of islets with nuclei positive for BrdU [10.7 +/- 1.8% exendin (1-30) vs 6.5 +/- 0.5% control]. C1 Pathol Serv Inc, Cambridge, MA 02139 USA. Natl Inst Aging, Diabet Sect, NIH, Baltimore, MD 21224 USA. Natl Inst Aging, NMR Unit, NIH, Baltimore, MD 21224 USA. Natl Inst Aging, Drug Design & Dev Sect, NIH, Baltimore, MD 21224 USA. RP Doyle, ME (reprint author), Univ Florida, Dept Oral Biol, Dent Sci Bldg,Box 100424,Rm D5-15,1600 SW Archer, Gainesville, FL 32610 USA. EM medoyle@dental.ufl.edu OI Bernier, Michel/0000-0002-5948-368X NR 27 TC 10 Z9 10 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DRIVE SUITE 208, TOTOWA, NJ 07512 USA SN 0969-711X J9 ENDOCRINE JI Endocrine PD JUN PY 2005 VL 27 IS 1 BP 1 EP 9 DI 10.1385/ENDO:27:1:001 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 957AN UT WOS:000231341700001 PM 16077164 ER PT J AU Brouwers, FM Petricoin, EF Ksinantova, L Breza, J Rajapakse, V Ross, S Johann, D Mannelli, M Shulkin, BL Kvetnansky, R Eisenhofer, G Walther, MM Hitt, BA Conrads, TP Veenstra, TD Mannion, DP Wall, MR Wolfe, GM Fusaro, VA Liotta, LA Pacak, K AF Brouwers, FM Petricoin, EF Ksinantova, L Breza, J Rajapakse, V Ross, S Johann, D Mannelli, M Shulkin, BL Kvetnansky, R Eisenhofer, G Walther, MM Hitt, BA Conrads, TP Veenstra, TD Mannion, DP Wall, MR Wolfe, GM Fusaro, VA Liotta, LA Pacak, K TI Low molecular weight proteomic information distinguishes metastatic from benign pheochromocytoma SO ENDOCRINE-RELATED CANCER LA English DT Article ID PROSTATE-CANCER; CHROMOSOMES 1P; OVARIAN-CANCER; BREAST-CANCER; SERUM; IDENTIFICATION; PARAGANGLIOMAS; DIAGNOSIS; PROFILES; PATTERNS AB Metastatic lesions occur in up to 36% of patients with pheochromocytorna. Currently there is no way to reliably detect or predict which patients are at risk for metastatic pheochromocytorna. Thus, the discovery of biomarkers that could distinguish patients with benign disease from those with metastatic disease would be of great clinical value. Using surface-enhanced laser desorption ionization protein chips combined with high-resolution mass spectrometry, we tested the hypothesis that pheochromocytorna pathologic states can be reflected as biomarker information within the low molecular weight (LMW) region of the serum proteome. LMW protein profiles were generated from the serum of 67 pheochromocytorna patients from four institutions and analyzed by two different bioinformatics approaches employing pattern recognition algorithms to determine if the LMW component of the circulatory proteome contains potentially useful discriminatory information. Both approaches were able to identify combinations of LMW molecules which could distinguish all metastatic from all benign pheochromocytomas in a separate blinded validation set. In conclusion, for this study set low molecular mass biomarker information correlated with pheochromocytorna pathologic state using blinded validation. If confirmed in larger validation studies, efforts to identify the underlying diagnostic molecules by sequencing would be warranted. In the future, measurement of these biomarkers could be potentially used to improve the ability to identify patients with metastatic disease. C1 NICHHD, Reprod Biol & Med Branch, Bethesda, MD 20892 USA. NCI, FDA Clin Proteom Program, Offf Cell & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bethesda, MD USA. Slovak Acad Sci, Inst Expt Endocrinol, SK-83306 Bratislava, Slovakia. Komensky Fac Med, Dept Urol, Bratislava, Slovakia. NCI, FDA Clin Proteom Program, Pathol Lab, Ctr Canc Res, Bethesda, MD USA. Univ Florence, Dept Clin Physiopathol, Endocrine Unit, Florence, Italy. St Jude Childrens Res Hosp, Dept Radiol Sci, Memphis, TN 38105 USA. NINDS, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Correl Syst Inc, Bethesda, MD USA. NCI, Natl Canc Inst Biomed Proteom Program, Analyt Chem Lab, Mass Spect Ctr,SAIC Frederick Inc, Frederick, MD 21701 USA. Predict Diagnost Inc, Vacaville, CA USA. RP Pacak, K (reprint author), NICHD, Unit Clin Neuroendocrinol, NIH, RBMB,Bldg 10,CRC,Room 1E-3140,10 Ctr Dr,MSC-1109, Bethesda, MD 20892 USA. EM karel@mail.nih.gov OI Mannelli, Massimo/0000-0002-8001-9857 NR 36 TC 35 Z9 38 U1 1 U2 1 PU BIOSCIENTIFICA LTD PI BRISTOL PA EURO HOUSE, 22 APEX COURT WOODLANDS, BRADLEY STOKE, BRISTOL BS32 4JT, ENGLAND SN 1351-0088 J9 ENDOCR-RELAT CANCER JI Endocr.-Relat. Cancer PD JUN PY 2005 VL 12 IS 2 BP 263 EP 272 DI 10.1677/erc.1.00913 PG 10 WC Oncology; Endocrinology & Metabolism SC Oncology; Endocrinology & Metabolism GA 939OT UT WOS:000230083000005 PM 15947101 ER PT J AU Emmen, JMA Couse, JF Elmore, SA Yates, MM Kissling, GE Korach, KS AF Emmen, JMA Couse, JF Elmore, SA Yates, MM Kissling, GE Korach, KS TI In vitro growth and ovulation of follicles from ovaries of estrogen receptor (ER)alpha and ER beta null mice indicate a role for ER beta in follicular maturation SO ENDOCRINOLOGY LA English DT Article ID RAT GRANULOSA-CELLS; LUTEINIZING-HORMONE RECEPTOR; ALPHA-STIMULATED GENE-6; REPRODUCTIVE PHENOTYPES; ANDROGEN RECEPTOR; KNOCKOUT MOUSE; MESSENGER-RNA; EXPRESSION; DIFFERENTIATION; PROLIFERATION AB Both estrogen receptor (ER) α and β are expressed within the ovary and lack of either of these receptors affects ovarian function. In this study, the role of ERα and ERβ in folliculogenesis and ovulation was further analyzed. Evaluation of ovarian follicle populations in wild-type and ERβ knockout (β ERKO) ovaries revealed reduced late antral growth and ovulatory capacity of β ERKO follicles, indicated by reduced numbers of large antral follicles and corpora lutea and increased atresia of large antral follicles. An in vitro culture system was used to study growth, rupture, and luteinization of wild-type, ERα knockout (α ERKO) and β ERKO ovarian follicles. α ERKO follicles exhibited wild-type-like growth and ovulation rates but an increased capacity to synthesize estradiol. In contrast, β ERKO follicles showed a significant lack of progression from early antral to large antral stage, decreased estradiol production, and reduced ovulation. Expression patterns of several genes involved in follicle maturation and ovulation were analyzed in follicles grown in vitro. Ar, Pgr, and Has2 mRNA expression levels were the same among the three genotypes. However, β ERKO follicles showed reduced expression of Cyp19 mRNA during follicle maturation and reduced Lhcgr and Ptgs2 mRNA expression after human chorionic gonadotropin stimulus. Luteinization occurs normally in α ERKO and β ERKO follicles, shown by increased progesterone secretion and increased cdkn1b mRNA expression after human chorionic gonadotropin. Collectively, these data indicate that ERβ, but not ERα, plays a direct role in folliculogenesis. ERβ appears to facilitate follicle maturation from the early antral to the preovulatory stage. C1 NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Lab Expt Pathol, NIH, Res Triangle Pk, NC 27709 USA. NIEHS, Biostat Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Korach, KS (reprint author), NIEHS, Receptor Biol Sect, Reprod & Dev Toxicol Lab, NIH, MD B3-02,POB 12233, Res Triangle Pk, NC 27709 USA. EM korach@niehs.nih.gov OI Korach, Kenneth/0000-0002-7765-418X NR 46 TC 83 Z9 91 U1 0 U2 5 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 JUN PY 2005 VL 146 IS 6 BP 2817 EP 2826 DI 10.1210/en.2004-1108 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 926QL UT WOS:000229137600041 PM 15731357 ER PT J AU Lindsay, JR Nieman, LK AF Lindsay, JR Nieman, LK TI Differential diagnosis and imaging in Cushing's syndrome SO ENDOCRINOLOGY AND METABOLISM CLINICS OF NORTH AMERICA LA English DT Article ID INFERIOR PETROSAL SINUS; CORTICOTROPIN-RELEASING-HORMONE; DEXAMETHASONE SUPPRESSION TEST; ECTOPIC ADRENOCORTICOTROPIN SYNDROME; SOMATOSTATIN RECEPTOR SCINTIGRAPHY; SECRETING PITUITARY MICROADENOMAS; INAPPARENT ADRENAL MASS; INTERNAL JUGULAR-VEIN; CAVERNOUS SINUS; STIMULATION TEST AB Establishing the cause of Cushing's syndrome (CS) is one of the most challenging processes in clinical endocrinology. Biochemical testing, including measurement of plasma adrenocorticotropin (ACTH), high-dose dexamethasone suppression, and corticotropin-releasing hormone stimulation testing, is integral to the differential diagnosis. No existing test has sufficient diagnostic accuracy when used alone, however. The adjunctive use of focused imaging, including CT, MRI, and nuclear imaging modalities, often can provide a diagnosis. In patients with ACTH-dependent CS, bilateral inferior petrosal sinus sampling can facilitate a diagnosis in those with discrepant clinical features, biochemistry, or imaging. This article focuses on current biochemical and radiologic strategies for the differential diagnosis of CS. C1 NICHHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Nieman, LK (reprint author), NICHHD, Reprod Biol & Med Branch, NIH, 10 Ctr Dr,Bldg 10,CRC 1-3140, Bethesda, MD 20892 USA. EM niemanl@mail.nih.gov NR 88 TC 64 Z9 69 U1 1 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8529 J9 ENDOCRIN METAB CLIN JI Endocrinol. Metabol. Clin. North Amer. PD JUN PY 2005 VL 34 IS 2 BP 403 EP + DI 10.1016/j.ecl.2005.01.009 PG 20 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 927JU UT WOS:000229191000011 PM 15850850 ER PT J AU Arbes, SJ Sever, M Vaughn, B Mehta, J Lynch, JT Mitchell, H Hoppin, JA Spencer, HL Sandler, DP Zeldin, DC AF Arbes, SJ Sever, M Vaughn, B Mehta, J Lynch, JT Mitchell, H Hoppin, JA Spencer, HL Sandler, DP Zeldin, DC TI Feasibility of using subject-collected dust samples in epidemiologic and clinical studies of indoor allergens SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE allergens; environment; epidemiology; sampling ID DER-P-I; MITE; EXPOSURE; ASTHMA; RISK; SENSITIZATION; DESIGN; VARIABILITY; ENDOTOXIN; CAT AB Studies of indoor aflergen exposures are often limited by the cost and logistics of sending technicians to homes to collect dust. In this study we evaluated the feasibility of having subjects collect their own dust samples. The objectives were to compare allergen concentrations between subject- and technician-collected samples and to examine the sample return rate. Using a dust collection device and written instructions provided to them by mail, 102 subjects collected a combined dust sample from a bed and bedroom floor. Later the same day, a technician collected a side-by-side sample. Dust samples were weighed and analyzed for the cat allergen Fel d 1 and the dust mite allergen Der p 1. Fifty additional subjects who were enrolled by telephone were mailed dust collection packages and asked to return a dust sample and questionnaire by mail. A technician did not visit their homes. Correlations between subject- and technician-collected samples were strong for concentrations of Fel d 1 (r = 0.88) and Der p 1 (r = 0.87). With allergen concentrations dichotomized at lower limits of detection and clinically relevant thresholds, agreements between methodologies ranged from 91 to 98%. Although dust weights were correlated (r = 0.48, p < 0.001), subjects collected lighter samples. Among the group of 50 subjects, 46 returned a dust sample and completed questionnaire. The median number of days to receive a sample was 15. With some limitations, subject-collected dust sampling appears to be a valid and practical option for epidemiologic and clinical studies that report allergen concentration as a measure of exposure. C1 NIEHS, Lab Resp Biol, Div Intramural Res, Dept Hlth & Human Serv,NIH, Res Triangle Pk, NC 27709 USA. Rho Inc, Chapel Hill, NC USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Chapel Hill, NC USA. RP Zeldin, DC (reprint author), NIEHS, Lab Resp Biol, Div Intramural Res, Dept Hlth & Human Serv,NIH, Res Triangle Pk, NC 27709 USA. EM zeldin@niehs.nih.gov OI Sandler, Dale/0000-0002-6776-0018 FU Intramural NIH HHS NR 17 TC 22 Z9 22 U1 0 U2 3 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 2005 VL 113 IS 6 BP 665 EP 669 DI 10.1289/ehp.7648 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 931BL UT WOS:000229460700025 PM 15929886 ER PT J AU Forrest, MS Lan, O Hubbard, AE Zhang, LP Vermeulen, R Zhao, X Li, GL Wu, YY Shen, M Yin, SN Chanock, SJ Rothman, N Smith, MT AF Forrest, MS Lan, O Hubbard, AE Zhang, LP Vermeulen, R Zhao, X Li, GL Wu, YY Shen, M Yin, SN Chanock, SJ Rothman, N Smith, MT TI Discovery of novel biomarkers by microarray analysis of peripheral blood mononuclear cell gene expression in benzene-exposed workers SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article ID PLATELET FACTOR-IV; C-JUN; CYCLE PROGRESSION; CHINESE WORKERS; RT-PCR; PROLIFERATION; INHIBITION; EXPOSURES; PROFILES; MICE AB Benzene is an industrial chemical and component of gasoline that is an established cause of leukemia. To better understand the risk benzene poses, we examined the effect of benzene exposure on peripheral blood mononuclear cell (PBMC) gene expression in a population of shoe-factory workers with well-characterized occupational exposures using microarrays and real-time polymerase chain reaction (PCR). PBMC RNA was stabilized in the field and analyzed using a comprehensive human array, the U133A/B Affymetrix GeneChip set. A matched analysis of six exposed-control pairs was performed. A combination of robust multiarray analysis and ordering of genes using paired t-statistics, along with bootstrapping to control for a 5% familywise error rate, was used to identify differentially expressed genes in a global analysis. This resulted in a set of 29 known genes being identified that were highly likely to be differentially expressed. We also repeated these analyses on a smaller subset of 508 cytokine probe sets and found that the expression of 19 known cytokine genes was significantly different between the exposed and the control subjects. Six genes were selected for confirmation by real-time PCR, and of these, CXCL16, ZNF331, JUN, and PF4 were the most significantly affected by benzene exposure, a finding that was confirmed in a larger data set from 28 subjects. The altered expression was not caused by changes in the makeup of the PBMC fraction. Thus, microarray analysis along with real-time PCR confirmation reveals that altered expressions of CXCL16, ZNF331, JUN, and PF4 are potential biomarkers of benzene exposure. C1 Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NCI, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Inst Occupat Hlth & Poison Control, Chinese Ctr Dis Control & Prevent, Beijing, Peoples R China. RP Smith, MT (reprint author), Univ Calif Berkeley, Sch Publ Hlth, 140 Warren Hall, Berkeley, CA 94720 USA. EM martynts@berkeley.edu RI Vermeulen, Roel/F-8037-2011; OI Vermeulen, Roel/0000-0003-4082-8163; Forrest, Matthew/0000-0002-2141-0303 FU NIEHS NIH HHS [R01ES006721, P30ES0011896] NR 36 TC 81 Z9 95 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 JUN PY 2005 VL 113 IS 6 BP 801 EP 807 DI 10.1289/ehp.7635 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 931BL UT WOS:000229460700047 PM 15929907 ER PT J AU De Roos, AJ Svec, MA Blair, A Rusiecki, JA Dosemeci, M Alavanja, MC Hoppin, JA Sandler, DP AF De Roos, AJ Svec, MA Blair, A Rusiecki, JA Dosemeci, M Alavanja, MC Hoppin, JA Sandler, DP TI Glyphosate results revisited: De Roos et al. respond SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Letter ID ROUNDUP C1 Univ Washington, Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. Natl Canc Inst, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, NIH, Dept Hlth & Human Serv, Res Triangle Pk, NC USA. RP De Roos, AJ (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Program Epidemiol, Seattle, WA 98195 USA. EM deroos@u.washington.edu NR 8 TC 1 Z9 1 U1 2 U2 8 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 JUN PY 2005 VL 113 IS 6 BP A366 EP A367 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 931BL UT WOS:000229460700006 ER PT J AU Newton, S Schwartz, DA AF Newton, S Schwartz, DA TI NIEHS priorities: The process of strategic planning SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 NIEHS, Off Sci Policy & Planning, Res Triangle Pk, NC 27709 USA. RP Newton, S (reprint author), NIEHS, Off Sci Policy & Planning, Res Triangle Pk, NC 27709 USA. EM schwarrzd@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 JUN PY 2005 VL 113 IS 6 BP A362 EP A362 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 931BL UT WOS:000229460700002 PM 15929874 ER PT J AU Galperin, MY AF Galperin, MY TI The vibrio that sheds light SO ENVIRONMENTAL MICROBIOLOGY LA English DT Editorial Material ID EXTENSIVE DNA INVERSIONS; GENOME SEQUENCE; ENVIRONMENT; EXPRESSION; FISCHERI; CHOLERAE C1 Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. RP Galperin, MY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM galperin@ncbi.nlm.nih.gov RI Galperin, Michael/B-5859-2013 OI Galperin, Michael/0000-0002-2265-5572 NR 13 TC 3 Z9 3 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1462-2912 J9 ENVIRON MICROBIOL JI Environ. Microbiol. PD JUN PY 2005 VL 7 IS 6 BP 757 EP 760 DI 10.1111/j.1462-2920.2005.00839.x PG 4 WC Microbiology SC Microbiology GA 924EX UT WOS:000228962800001 PM 15892694 ER PT J AU Blanchard, J Grosell, M AF Blanchard, J Grosell, M TI Effects of salinity on copper accumulation in the common killifish (Fundulus heteroclitus) SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article DE inorganic speciation; copper homeostasis; mummichog; seawater; brackish water ID TROUT ONCORHYNCHUS-MYKISS; PLATICHTHYS-FLESUS L; ACID-BASE REGULATION; MARINE TELEOST FISH; RAINBOW-TROUT; METABOLISM; EXPOSURE; BALANCE; SILVER; ION AB Results of laboratory and field studies have demonstrated that salinity influences the accumulation of copper. The present study is, to our knowledge, the first to examine the effect of salinity on copper accumulation in a teleost fish across a comprehensive range of salinity from freshwater to seawater. This was done in an effort to identify potential target tissues and differences in chemical interactions across salinities that will aid in the development of a seawater biotic ligand model (BLM) for copper. Killifish (Fundulus heteroclitus) were acclimated to five salinities (0, 5, 11, 22, and 28 ppt) and exposed to three copper concentrations (0 [nominal], 30, and 150 μ g L-1), yielding 15 treatment groups. Fish from each group were sampled for tissue copper analysis at 0, 4, 12, and 30 d postexposure. Whole-body and liver accumulations were highest at lower salinities. The liver accounted for 57 to 86% of the whole-body copper even though it accounted for less than 4% of the body mass. Similarly, the gill accumulated more copper at lower salinities, whereas the intestine generally accumulated more copper at higher salinities. Speciation calculations indicate that CuCO3 likely accounts for much of the accumulation, possibly with some contributions from CuOH+ and Cu(OH)(2) The free ion, Cull, does not appear to be associated with copper accumulation. However, the differences in physiology and in the concentrations of competing cations across salinities suggest that speciation alone cannot explain accumulation. The present findings may have implications for future development of a BLM for saline environments by identifying potential target tissues. C1 Univ Miami, NIEHS Marine & Freshwater Biomed Sci Ctr, Div Marine Biol & Fisheries, Rosenstiel Sch Marine & Atmospher Sci, Miami, FL 33149 USA. RP Blanchard, J (reprint author), Univ Miami, NIEHS Marine & Freshwater Biomed Sci Ctr, Div Marine Biol & Fisheries, Rosenstiel Sch Marine & Atmospher Sci, 4600 Rickenbacker Causeway, Miami, FL 33149 USA. EM jblanchard@rsmas.miami.edu FU NIEHS NIH HHS [ES05705] NR 29 TC 31 Z9 31 U1 0 U2 8 PU SETAC PI PENSACOLA PA 1010 NORTH 12TH AVE, PENSACOLA, FL 32501-3367 USA SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD JUN PY 2005 VL 24 IS 6 BP 1403 EP 1413 DI 10.1897/04-373R.1 PG 11 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 926RN UT WOS:000229140400013 PM 16117116 ER PT J AU Kaminski, RM Marini, H Kim, WJ Rogawski, MA AF Kaminski, RM Marini, H Kim, WJ Rogawski, MA TI Anticonvulsant activity of androsterone and etiocholanolone SO EPILEPSIA LA English DT Article DE androsterone; etiocholanolone; epiandrosterone; pentylenetetrazol; pilocarpine; 4-aminopyridine; 6-Hz model; seizure; mouse ID GAMMA-AMINOBUTYRIC-ACID; URINARY STEROID METABOLITES; RECEPTOR FUNCTION; 5-ALPHA-REDUCTASE INHIBITOR; REPRODUCTIVE HORMONES; CIRCULATING ANDROGENS; PREMENSTRUAL-SYNDROME; SERUM ANDROGENS; GABAA RECEPTOR; KAINIC ACID AB Purpose: Men with epilepsy often have sexual or reproductive abnormalities that are attributed to alterations in androgen levels, including subnormal free testosterone. Levels of the major metabolites of testosterone-androsterone (5 alpha-androstan-3 alpha-ol-17-one; 5 alpha,3 alpha-A), a neurosteroid that acts as a positive allosteric modulator of GABA(A) receptors, and its 5 epimer etiocholanolone (5 beta-androstan-3 alpha-ol-17-one; 5 beta,3 alpha-A)-also may be reduced in epilepsy. 5 alpha,3 alpha-A has been found in adult brain, and both metabolites, which also can be derived from androstenedione, are present in substantial quantities in serum along with their glucuronide and sulfate conjugates. This study sought to determine whether these endogenous steroid metabolites can protect against seizures. Methods: The anticonvulsant activity of 5 alpha,3 alpha-A and 5 beta,3 alpha-A was investigated in electrical and chemoconvulsant seizure models in mice. The steroids also were examined for activity against extracellularly recorded epileptiform discharges in the CA3 region of the rat hippocampal slice induced by perfusion with 55 mu M 4-aminopyridine (4-AP). Results: Intraperitoneal injection of 5 alpha,3 alpha-A-protected mice in a dose-dependent fashion from seizures in the following models (ED50, dose in mg/kg protecting 50% of animals): 6-Hz electrical stimulation (29.1), pentylenetetrazol (43.5), pilocarpine (105), 4-AP (215), and maximal electroshock (224). 5 beta,3 alpha-A also was active in the 6-Hz and pentylenetetrazol models, but was less potent (ED50 values, 76.9 and 139 mg/kg, respectively), whereas epiandrosterone (5 alpha,3 beta-A) was inactive (ED50, <= 300 mg/kg). 5 alpha,3 beta-A (10-100 mu M) also inhibited epileptiform discharges in a concentration-dependent fashion in the in vitro slice model, whereas 5 beta,3 alpha-A was active but of lower potency, and 5 alpha,3 beta-A was inactive. Conclusions: 5 alpha,3 alpha-A and 5 beta,3 alpha-A have anticonvulsant properties. Although of low potency, the steroids are present in high abundance and could represent endogenous modulators of seizure susceptibility. C1 NINDS, Epilepsy Res Sect, Porter Neurosci Res Ctr, NIH, Bethesda, MD 20892 USA. Univ Messina, Fac Med & Surg, AOU G Martino, Messina, Italy. RP Rogawski, MA (reprint author), NINDS, Epilepsy Res Sect, Porter Neurosci Res Ctr, NIH, Bldg 35,Room 1C-1002,35 Convent Dr MSC 3702, Bethesda, MD 20892 USA. EM michael.rogawski@nih.gov RI Rogawski, Michael/B-6353-2009; OI Rogawski, Michael/0000-0002-3296-8193; MARINI, Herbert Ryan/0000-0002-8254-177X FU NINDS NIH HHS [Z01 NS002877-13, Z01 NS002732-19] NR 57 TC 56 Z9 58 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD JUN PY 2005 VL 46 IS 6 BP 819 EP 827 DI 10.1111/j.1528-1167.2005.00705.x PG 9 WC Clinical Neurology SC Neurosciences & Neurology GA 935RX UT WOS:000229802200003 PM 15946323 ER PT J AU Norris, KC Agodoa, LY AF Norris, KC Agodoa, LY TI The need for health professionals and scientists from underrepresented minority and disadvantaged communities SO ETHNICITY & DISEASE LA English DT Editorial Material DE student research; biomedical programs; minority health research C1 Charles R Drew Univ Med & Sci, Sch Med, Los Angeles, CA 90059 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NIDDK, NIH, Bethesda, MD USA. RP Norris, KC (reprint author), Charles R Drew Univ Med & Sci, Sch Med, 1621 E 120th St, Los Angeles, CA 90059 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU INT SOC HYPERTENSION BLACKS-ISHIB PI ATLANTA PA 100 AUBURN AVE NE STE 401, ATLANTA, GA 30303-2527 USA SN 1049-510X J9 ETHNIC DIS JI Ethn. Dis. PD SUM PY 2005 VL 15 IS 3 SU 4 BP 1 EP 2 PG 2 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 959VE UT WOS:000231546600001 PM 16208943 ER PT J AU Joglekar, AP Hay, JC AF Joglekar, AP Hay, JC TI Evidence for regulation of ER/Golgi SNARE complex formation by hsc70 chaperones SO EUROPEAN JOURNAL OF CELL BIOLOGY LA English DT Article DE SNARE; membrane fusion; vesicle transport; Golgi apparatus; encloplasmic reticulum; molecular chaperone; heat shock protein ID MEMBRANE-FUSION; T-SNARE; PROTEIN; EXOCYTOSIS; PURIFICATION; DYNAMICS; SUBUNIT; ATPASE; MEMBER; ROLES AB SNARE proteins control intracellular membrane fusion through formation of membrane-bridging helix bundles of amplupathic SNARE motifs. Repetitive cycles of membrane fusion likely involve repetitive folding/unfolding of the SNARE motif helical structure. Despite these conformational demands, little is known about conformational regulation of SNAREs by other proteins. Here we demonstrate that hsc70 chaperones stimulate in vitro SNARE complex formation among the ER/Golgi SNAREs syntaxin 5, membrin, rbet1 and sec22b, under conditions in which assembly is normally inhibited. Thus, molecular chaperones can render the SNARE motif more competent for assembly. Partially purified hsc70 fractions from brain cytosol had higher specific activities than fully Purified hsc70, suggesting the involvement of unidentified cofactors. Using chemical crosslinking of cells followed by immunoprecipitation, we found that hsc70 was associated with ER/Golgi SNAREs in vivo. Consistent with a modulatory role for lisc70 in transport, we found that excess hsc70 specifically inhibited ER-to-Golgi transport in permeabilized cells. (c) 2005 Elsevier GmbH. All rights reserved. C1 Univ Montana, COBRE Ctr Struct & Funct Neurosci, Missoula, MT 59812 USA. Univ Michigan, Dept Mol Cellular & Dev Biol, Ann Arbor, MI 48109 USA. RP Hay, JC (reprint author), Univ Montana, Div Biol Sci, 32 Campus Dr HS410, Missoula, MT 59812 USA. EM jesse.hay@umontana.edu FU NIGMS NIH HHS [GM59378] NR 33 TC 14 Z9 15 U1 1 U2 2 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-9335 J9 EUR J CELL BIOL JI Eur. J. Cell Biol. PD JUN PY 2005 VL 84 IS 5 BP 529 EP 542 DI 10.1016/j.ejcb.2004.12.028 PG 14 WC Cell Biology SC Cell Biology GA 941GD UT WOS:000230202400001 PM 16003907 ER PT J AU Khasar, SG Dina, OA Green, PG Levine, JD AF Khasar, SG Dina, OA Green, PG Levine, JD TI Estrogen regulates adrenal medullary function producing sexual dimorphism in nociceptive threshold and beta(2)-adrenergic receptor-mediated hyperalgesia in the rat SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE desensitization; epinephrine; hormone; nociception; pain ID POSTTRAUMATIC-STRESS-DISORDER; SYMPATHETIC-NERVOUS-SYSTEM; CHRONIC-FATIGUE-SYNDROME; FIBROMYALGIA SYNDROME; MECHANICAL HYPERALGESIA; FEMALE RAT; SYMPATHOADRENAL ACTIVITY; CATECHOLAMINE SYNTHESIS; INTERSTITIAL CYSTITIS; PLASMA EXTRAVASATION AB Epinephrine produces sexually dimorphic beta(2)-adrenergic receptor-mediated mechanical hyperalgesia, with male rats exhibiting greater hyperalgesia. Because female rats have higher plasma epinephrine levels, and beta-adrenergic receptor sensitivity is affected by chronic exposure to agonists, we tested the hypothesis that this sexual dimorphism is due to epinephrine-induced desensitization of beta(2)-adrenergic receptors. Following gonadectomy, epinephrine hyperalgesia, as measured by the Randall-Selitto paw-withdrawal test, was unchanged in male rats while in females it was increased. Prepubertal male and female rats do not demonstrate sexual dimorphism in either plasma epinephrine level or epinephrine-induced hyperalgesia. Adrenal medullectomy and adrenal denervation both significantly enhanced epinephrine hyperalgesia, but only in females. In contrast, the sexually dimorphic hyperalgesia induced by prostaglandin E-2, another agent that acts directly to sensitize primary afferent nociceptors, was not enhanced by adrenal medullectomy or denervation. Chronic administration of epinephrine in male rats, to produce plasma levels similar to those of gonad-intact females, significantly attenuated epinephrine-induced hyperalgesia, making it similar to that in females. These results strongly support the suggestion that estrogen regulates plasma epinephrine in female rats and differential sensitivity to beta(2)-adrenergic agonists accounts for the sexual dimorphism in epinephrine-induced hyperalgesia. Unexpectedly, regulation of adrenal medullary function by estrogen was also found to modulate baseline nociceptive threshold such that females had a lower nociceptive threshold. C1 Univ Calif San Francisco, NIH, Pain Ctr, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Oral & Maxillofacial Surg, San Francisco, CA 94143 USA. Univ Calif San Francisco, Div Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH, Pain Ctr, Box 0440,C-522, San Francisco, CA 94143 USA. EM levine@itsa.ucsf.edu RI Green, Paul/C-5943-2011 FU NIAMS NIH HHS [AR 048821] NR 70 TC 22 Z9 24 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUN PY 2005 VL 21 IS 12 BP 3379 EP 3386 DI 10.1111/j.1460-9568.2005.04158.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 939EA UT WOS:000230054000017 PM 16026475 ER PT J AU Malik-Hall, M Dina, OA Levine, JD AF Malik-Hall, M Dina, OA Levine, JD TI Primary afferent nociceptor mechanisms mediating NGF-induced mechanical hyperalgesia SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE integrins; primary afferent nociceptor; rat; signalling pathways; TrkA ID NERVE GROWTH-FACTOR; ACTIVATED PROTEIN-KINASE; PRIMARY SENSORY NEURONS; NEUROTROPHIN RECEPTOR P75(NTR); INFLAMMATORY PAIN; NEUROPATHIC PAIN; NEURITE GROWTH; PC12 CELLS; IN-VITRO; RAT AB The underlying mechanism for nerve growth factor (NGF) evoked pain and long-lasting mechanical hyperalgesia remains poorly understood. Using intrathecal antisense against the NGF receptor, receptor tyrosine kinase (TrkA), we found NGF to act at the primary afferent nociceptor directly in the Sprague-Dawley rat. Inhibitors of the three major pathways for TrkA receptor signalling, extracellular signal-related kinase (ERK)/mitogen-activated protein kinase kinase (MEK) (ERK/MEK), phosphatidylinositol 3-kinase (PI3K), and phospholipase C gamma (PLC gamma) all attenuate NGF-induced hyperalgesia. Although inhibitors of kinases downstream of PI3K and PLC gamma[glycogen synthetase kinase 3 (GSK3), calmodulin-dependent protein kinase II (CAMII-K) or protein kinase C (PKC)] do not reduce mechanical hyperalgesia, hyperalgesia induced by activation of PI3K was blocked by ERK/MEK inhibitors, suggesting cross-talk from the PI3K to the ERK/MEK signalling pathway. As integrins have been shown to modulate epinephrine and prostaglandin E-2-induced hyperalgesia, we also evaluated a role for integrins in NGF-induced mechanical hyperalgesia using beta(1)-integrin-specific antisense or antibodies. C1 Univ Calif San Francisco, NIH, Pain Ctr, Div Neurosci, San Francisco, CA 94143 USA. Univ Calif San Francisco, Program Biomed Sci, San Francisco, CA 94143 USA. RP Levine, JD (reprint author), Univ Calif San Francisco, NIH, Pain Ctr, Div Neurosci, 521 Parnassus Ave, San Francisco, CA 94143 USA. EM levine@itsa.ucsf.edu NR 41 TC 75 Z9 79 U1 0 U2 5 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUN PY 2005 VL 21 IS 12 BP 3387 EP 3394 DI 10.1111/j.1460-9568.2005.04173.x PG 8 WC Neurosciences SC Neurosciences & Neurology GA 939EA UT WOS:000230054000018 PM 16026476 ER PT J AU Xi, ZX Gilbert, JG Pak, AC Ashby, CR Heidbreder, CA Gardner, EL AF Xi, ZX Gilbert, JG Pak, AC Ashby, CR Heidbreder, CA Gardner, EL TI Selective dopamine D-3 receptor antagonism by SB-277011A attenuates cocaine reinforcement as assessed by progressive-ratio and variable-cost-variable-payoff fixed-ratio cocaine self-administration in rats SO EUROPEAN JOURNAL OF NEUROSCIENCE LA English DT Article DE dopamine; D-3 receptor; drug addiction; meso-accumbens; reward ID CONDITIONED PLACE PREFERENCE; BRAIN-STIMULATION REWARD; NUCLEUS-ACCUMBENS; 6-HYDROXYDOPAMINE LESIONS; NEGATIVE REINFORCERS; SEEKING BEHAVIOR; DRUG-ADDICTION; ANIMAL-MODELS; HIGH-AFFINITY; D3 RECEPTOR AB In rats, acute administration of SB-277011A, a highly selective dopamine (DA) D-3 receptor antagonist, blocks cocaine-enhanced brain stimulation reward, cocaine-seeking behaviour and reinstatement of cocaine-seeking behaviour. Here, we investigated whether SB-277011A attenuates cocaine reinforcement as assessed by cocaine self-administration under variable-cost-variable-payoff fixed-ratio (FR) and progressive-ratio (PR) reinforcement schedules. Acute i.p. administration of SB-277011A (3-24 mg/kg) did not significantly alter cocaine (0.75 mg/kg/infusion) self-administration reinforced under FR1 (one lever press for one cocaine infusion) conditions. However, acute administration of SB-277011A (24 mg/kg, i.p.) progressively attenuated cocaine self-administration when: (a) the unit dose of self-administered cocaine was lowered from 0.75 to 0.125-0.5 mg/kg, and (b) the work demand for cocaine reinforcement was increased from FR1 to FR10. Under PR (increasing number of lever presses for each successive cocaine infusion) cocaine reinforcement, acute administration of SB-277011A (6-24 mg/kg i.p.) lowered the PR break point for cocaine self-administration in a dose-dependent manner. The reduction in the cocaine (0.25-1.0 mg/kg) dose-response break-point curve produced by 24 mg/kg SB-277011A is consistent with a reduction in cocaine's reinforcing efficacy. When substituted for cocaine, SB-277011A alone did not sustain self-administration behaviour. In contrast with the mixed DA D-2/D-3 receptor antagonist haloperidol (1 mg/kg), SB-277011A (3, 12 or 24 mg/kg) failed to impede locomotor activity, failed to impair rearing behaviour, failed to produce catalepsy and failed to impair rotarod performance. These results show that SB-277011A significantly inhibits acute cocaine-induced reinforcement except at high cocaine doses and low work requirement for cocaine. If these results extrapolate to humans, SB-277011A or similar selective DA D-3 receptor antagonists may be useful in the treatment of cocaine addiction. C1 NIDA, Neuropsychopharmacol Sect, Intramural Res Program, NIH,DHHS, Baltimore, MD 21224 USA. St Johns Univ, Coll Pharm & Allied Hlth Profess, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. GlaxoSmithKline Pharmaceut, Ctr Excellence Drug Discovery Psychiat, Dept Neuropsychopharmacol, I-37135 Verona, Italy. RP Gardner, EL (reprint author), NIDA, Neuropsychopharmacol Sect, Intramural Res Program, NIH,DHHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM egardner@intra.nida.nih.gov FU Intramural NIH HHS [Z99 DA999999] NR 84 TC 89 Z9 93 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0953-816X J9 EUR J NEUROSCI JI Eur. J. Neurosci. PD JUN PY 2005 VL 21 IS 12 BP 3427 EP 3438 DI 10.1111/j.1460-9568.2005.04159.x PG 12 WC Neurosciences SC Neurosciences & Neurology GA 939EA UT WOS:000230054000022 PM 16026480 ER PT J AU McCrae, RR Lockenhoff, CE Costa, PT AF McCrae, RR Lockenhoff, CE Costa, PT TI A step toward DSM-V: Cataloguing personality-related problems in living SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Article ID 5-FACTOR MODEL; CONSTRUCT-VALIDITY; SELF-REPORTS; AXIS II; TRAITS; DISORDERS; DIMENSIONS; PATHOLOGY; RATINGS; FACETS AB Intractable problems with DSM-IV's Axis II mandate an entirely new approach to the diagnosis of personality-related pathology. The Five-Factor Model of personality provides a scientifically grounded basis for personality assessment, and Five-Factor Theory postulates that personality pathology is to be found in characteristic maladaptations that are shaped by both traits and environment. A four-step process of personality disorder (PD) diagnosis is proposed, in which clinicians assess personality, problems in living, clinical severity, and, optionally PD patterns. We examine item content in five problem checklists to update the list of personality-related problems used in Step 2 of the four-step process. Problems were reliably assigned to relevant factors and facets, and a number of additions were made to an earlier catalogue. The four-step process can be used by clinicians, and may be incorporated in a future DSM. This article is a U.S. government publication and is in the public domain in the United States. C1 NIA, Gerontol Res Ctr, NIH, DHHS, Baltimore, MD 21224 USA. RP McCrae, RR (reprint author), NIA, Gerontol Res Ctr, NIH, DHHS, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mccraej@grc.nia.nih.gov OI Loeckenhoff, Corinna/0000-0003-1605-1323; Costa, Paul/0000-0003-4375-1712 NR 70 TC 43 Z9 43 U1 0 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD JUN PY 2005 VL 19 IS 4 BP 269 EP 286 DI 10.1002/per.564 PG 18 WC Psychology, Social SC Psychology GA 948HA UT WOS:000230705500003 ER PT J AU Bagby, RM Costa, PT Widiger, TA Ryder, AG Marshall, M AF Bagby, RM Costa, PT Widiger, TA Ryder, AG Marshall, M TI DSM-IV personality disorders and the five-factor model of personality: A multi-method examination of domain- and facet-level predictions SO EUROPEAN JOURNAL OF PERSONALITY LA English DT Article ID ASSESSING AXIS II; NEO-PI-R; STRUCTURED INTERVIEW; DIMENSIONS; CLASSIFICATION; QUESTIONNAIRE; VALIDATION; PROTOTYPES; PATHOLOGY; VALIDITY AB The personality disorder classification system (Axis II) in the various versions of the Diagnostic and Statistical Manuals of Mental Disorders (DSM) has been the target of repeated criticism, with conceptual analysis and empirical evidence documenting its flaws. In response, many have proposed alternative approaches for the assessment of personality psychopathology, including the application of the Five-Factor Model of personality (FFM). Many remain sceptical, however, as to whether domain and facet traits from a model of general personality functioning can be successfully applied to clinical patients with personality disorders (PDs). In this study, with a sample of psychiatric patients (n = 115), personality disorder symptoms corresponding to each of the 10 PDs were successfully predicted by the facet and domain traits of the FFM, as measured by a semi-structured interview, the Structured Interview for the Five Factor Model (SIFFM; Trull & Widiger 1997) and a self-report questionnaire, the Revised NEO Personality Inventory (NEO PI-R; Costa and McCrae, 1992). These results provide support for the perspective that personality psychopathology can be captured by general personality dimensions. The FFM has the potential to provide a valid and scientifically sound framework from which to assess personality psychopathology, in a way that covers most of the domains conceptualized in DSM while transcending the limitations of the current categorical approach to these disorders. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Univ Toronto, Ctr Addict & Mental Hlth, Toronto, ON M5T 1R8, Canada. NIA, Baltimore, MD 21224 USA. Univ Kentucky, Lexington, KY 40506 USA. Concordia Univ, Montreal, PQ, Canada. McGill Univ, Montreal, PQ H3A 2T5, Canada. RP Bagby, RM (reprint author), Univ Toronto, Ctr Addict & Mental Hlth, Clark Site,250 Coll St, Toronto, ON M5T 1R8, Canada. EM michael_bagby@camh.net RI Ryder, Andrew/A-1108-2008; OI Ryder, Andrew/0000-0003-3041-7168; Costa, Paul/0000-0003-4375-1712 NR 62 TC 56 Z9 58 U1 16 U2 32 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0890-2070 J9 EUR J PERSONALITY JI Eur. J. Personal. PD JUN PY 2005 VL 19 IS 4 BP 307 EP 324 DI 10.1002/per.563 PG 18 WC Psychology, Social SC Psychology GA 948HA UT WOS:000230705500005 ER PT J AU Eton, DT Lai, JS Cella, D Reeve, BB Talcott, JA Clark, JA McPherson, CP Litwin, MS Moinpour, CM AF Eton, DT Lai, JS Cella, D Reeve, BB Talcott, JA Clark, JA McPherson, CP Litwin, MS Moinpour, CM TI Data pooling and analysis to build a preliminary item bank - An example using bowel function in prostate cancer SO EVALUATION & THE HEALTH PROFESSIONS LA English DT Article DE bowel function; prostate cancer; quality of life; item response theory; self-report ID QUALITY-OF-LIFE; PATIENT-ASSESSED-BOTHER; BEAM RADIATION-THERAPY; RADICAL PROSTATECTOMY; INSTRUMENT-VALIDATION; RANDOMIZED-TRIAL; RADIOTHERAPY; OUTCOMES; MEN; SYMPTOMS AB Assessing bowel function (BF) in prostate cancer can help determine therapeutic trade-offs. We determined the components of BF commonly assessed in prostate cancer studies as an initial step in creating an item bank for clinical and research application. We analyzed six archived data sets representing 4,246 men with prostate cancer. Thirty-one items from validated instruments were available for analysis. Items were classified into domains (diarrhea, rectal urgency, pain, bleeding, bother/distress, and other)then subjected to conventional psychometric and item response theory (IRT) analyses. Items fit the IRT model if the ratio between observed and expected item variance was between 0.60 and 1.40. Four of 31 items had inadequate fit in at least one analysis. Poorly fitting items included bleeding (2), rectal urgency (1), and bother/distress (1). A fifth item assessing hemorrhoids was poorly correlated with other items. Our analyses supported four related components of BF: diarrhea, rectal urgency, pain, and bother/distress. C1 Northwestern Univ, Sch Med, Evanston, IL 60208 USA. NCI, Bethesda, MD 20892 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Boston Univ, Sch Publ Hlth, Boston, MA 02215 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA 90024 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. RP Eton, DT (reprint author), Northwestern Univ, Sch Med, Evanston, IL 60208 USA. EM d-eton@north-western.edu NR 41 TC 2 Z9 2 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0163-2787 J9 EVAL HEALTH PROF JI Eval. Health Prof. PD JUN PY 2005 VL 28 IS 2 BP 142 EP 159 DI 10.1177/0163278705275338 PG 18 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 924YR UT WOS:000229018000003 PM 15851770 ER PT J AU Wheaton, LA Yakota, S Hallett, M AF Wheaton, LA Yakota, S Hallett, M TI Posterior parietal negativity preceding self-paced praxis movements SO EXPERIMENTAL BRAIN RESEARCH LA English DT Article ID RESOLUTION DC-EEG; VOLUNTARY MOVEMENT; FINGER MOVEMENTS; ACTIVATION; CORTEX; PREMOTOR; STROKE; ORGANIZATION; TOPOGRAPHY; PARADIGM AB Studies of movement-related cortical potentials (MRCPs) for simple movements have shown a slowly rising negativity (Bereitschaftspotential, or BP) about 2 s prior to movement onset, centered in the bilateral sensorimotor area. However, complex movements may elicit a different temporal and spatial distribution of this pre-movement activity. In this study, 64-channel electroencephalography (EEG) was recorded while normal volunteers were asked to perform a simple thumb adduction once every 10-15 s for three 10-15 min blocks. Following this, they were asked to make tool-use movements (hammer, scissor, and screwdriver pantomime) in the same manner. Surface electromyography (EMG) was recorded on the thumb adductor and forearm flexor. MRCP was analyzed for the beginning part of the epoch (from 3.5 s to 1.5 s before EMG onset, with 0.5 s time bins) for differences in the amplitude and spatial distribution of the BP. Significant differences were seen from 3.0 s to 2.0 s before EMG onset, where the amplitude was greater for the more complex movements. On average, negativity began at 3.0 s before onset for praxis movements, and only 1.7 s before onset for thumb adduction. Additionally, the negativity seen for the complex movements had a distribution beginning over the left hemisphere posterior parietal area, whereas, thumb adduction movements had a more anterior distribution, over the bilateral sensorimotor area. The posterior parietal negativity (PPN) suggests that early parietal activity is essential for tool-use movements and is not a part of preparing simple movements. C1 NINDS, Human Motor Control Sect, Med Neurol Branch, NIH, Bethesda, MD 20892 USA. Univ Maryland, College Pk, MD 20742 USA. Kyoto Univ, Sch Med, Sakyo Ku, Kyoto 606, Japan. RP Hallett, M (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 hallettm@ninds.nih.gov RI Wheaton, Lewis /B-4482-2009 OI Wheaton, Lewis /0000-0003-0771-0294 NR 27 TC 18 Z9 19 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 JUN PY 2005 VL 163 IS 4 BP 535 EP 539 DI 10.1007/s00221-005-2314-x PG 5 WC Neurosciences SC Neurosciences & Neurology GA 938AO UT WOS:000229972500012 PM 15883800 ER PT J AU Kang, EM Zickler, PP Burns, S Langemeijer, SM Brenner, S Phang, OA Patterson, N Harlan, D Tisdale, JF AF Kang, EM Zickler, PP Burns, S Langemeijer, SM Brenner, S Phang, OA Patterson, N Harlan, D Tisdale, JF TI Hematopoietic stem cell transplantation prevents diabetes in NOD mice but does not contribute to significant islet cell regeneration once disease is established SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID INSULIN-PRODUCING CELLS; PANCREATIC BETA-CELLS; MARROW-DERIVED CELLS; BONE-MARROW; IN-VIVO; MYOCARDIAL INFARCTS; NONHUMAN-PRIMATES; DIFFERENTIATION; TOLERANCE; MUSCLE AB The treatment of type I diabetes by islet cell transplantation, while promising, remains restricted due to the incomplete efficacy and toxicity associated with current immunosuppression, and by limited organ availability. Given reports suggesting bone marrow derived stem cell plasticity, we sought to determine whether such cells could give rise to pancreatic islet cells in vivo. In the context of autoimmune diabetes, we transplanted unfractionated bone marrow from beta-gal trangenic donor mice into NOD mice prior to, at, and two weeks beyond the onset of disease. Successful bone marrow engraftment before diabetes onset prevented disease in all mice and for 1 year after transplant. However, despite obtaining full hematopoietic engraftment in over 50 transplanted mice, only one mouse became insulin independent, and no beta-Gal positive islets were detected in any of the mice. To test whether tolerance to islets was achieved, we injected islets obtained from the same allogeneic donor strain as the hematopoietic cells into 4 transplant recipients, and 2 had a reversion of their diabetes. Thus allogeneic bone marrow transplantation prevents autoimmune diabetes and tolerizes the recipient to donor islet grants, even in diabetic animals, yet the capacity of bone marrow derived cells to differentiate into functional islet cells, at least without additional manipulation, is limited in our model. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NIAID, LHD, Bethesda, MD 20892 USA. NHLBI, HB, Bethesda, MD 20892 USA. NIDDK, IAB, DHHS, NIH, Bethesda, MD USA. Univ Klin Carl Gustav Carus, Klin Kinder & Jugendmed, Dresden, Germany. RP Tisdale, JF (reprint author), NIDDKD, Mol & Clin Hematol Branch, Dept Hlth & Human Serv, NIH, Bldg 10,Room 9N116,9000 Rockville Pike, Bethesda, MD 20895 USA. EM JohnTis@intra.niddk.nih.gov RI Brenner, Sebastian/D-7456-2013 NR 38 TC 38 Z9 44 U1 0 U2 2 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 JUN PY 2005 VL 33 IS 6 BP 699 EP 705 DI 10.1016/j.exphem.2005.03.008 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 935QA UT WOS:000229795600010 PM 15911094 ER PT J AU Bauer, TR Gu, YC Tuschong, LM Burkholder, T Bacher, JD Starost, MF Donahue, RE Sokolic, RA Hickstein, DD AF Bauer, TR Gu, YC Tuschong, LM Burkholder, T Bacher, JD Starost, MF Donahue, RE Sokolic, RA Hickstein, DD TI Nonmyeloablative hematopoietic stem cell transplantation corrects the disease phenotype in the canine model of leukocyte adhesion deficiency SO EXPERIMENTAL HEMATOLOGY LA English DT Article ID BONE-MARROW-TRANSPLANTATION; SEVERE COMBINED IMMUNODEFICIENCY; PERIPHERAL-BLOOD; ADOPTIVE IMMUNOTHERAPY; MONOCLONAL-ANTIBODIES; CHIMERISM; ANEMIA; DONORS; COLONY; LFA-1 AB Objective. The aim of this study was to test a nonmyeloablative hematopoietic stem cell transplant regimen applicable to children with leukocyte adhesion deficiency (LAD) who have a histocompatible sibling donor by using the canine model of LAD, namely canine leukocyte adhesion deficiency or CLAD. Methods. Thirteen CLAD pups received a hematopoietic stem cell transplant from a dog leukocyte antigen (DLA)-matched littermate donor after pretransplant nonmyeloablative conditioning with 200 cGy total-body irradiation and posttransplant immunosuppression with cyclosporine and mycophenolate mofetil. Donor chimerism following transplant was assessed by flow cytometry for the presence of donor CD18 peripheral blood leukocytes and leukocyte subsets. Results. Eleven of the 13 transplanted animals achieved stable mixed donor chimerism and reversal of the severe CLAD phenotype without graft-vs-host disease. The level of donor chimerism ranged from 3.9 to 95.5% at 1 year following transplant. There was one early death 3 weeks after transplant from thrombocytopenia and hemorrhage, and one dog with donor microchimerism (0.5% CD18(+) donor leukocytes) who had attenuation of the CLAD phenotype. Conclusion. These results demonstrate that a nonmyeloablative transplant regimen from a DLA-matched littermate donor leads to mixed chimerism and reversal of the severe disease phenotype in dogs with CLAD, and provides support for the use of this approach in children with LAD who possess a histocompatible sibling donor. (c) 2005 International Society for Experimental Hematology. Published by Elsevier Inc. C1 NCI, Expt Transplantat & Immunol Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NIH, Off Res SErv, Div Vet Resources, Bethesda, MD 20892 USA. NHLBI, Hematol Branch, NIH, Rockville, MD USA. RP Bauer, TR (reprint author), NCI, Expt Transplantat & Immunol Branch, NIH, 10 Ctr Dr,MSC1203,Bldg 10-CRC,Rm 3-3264, Bethesda, MD 20892 USA. EM bauert@mail.nih.gov RI Sokolic, Robert/I-6072-2012 NR 33 TC 22 Z9 23 U1 1 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 JUN PY 2005 VL 33 IS 6 BP 706 EP 712 DI 10.1016/j.exphem.2005.03.010 PG 7 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 935QA UT WOS:000229795600011 PM 15911095 ER PT J AU Isaacs, JS AF Isaacs, JS TI Heat-shock protein 90 inhibitors in antineoplastic therapy: is it all wrapped up? SO EXPERT OPINION ON INVESTIGATIONAL DRUGS LA English DT Review DE 17-(desmethoxy)-17-allylaminogeldanamycin; Akt; angiogenesis; chaperone; combination therapy; ErbB2; geldanamycin; Hsp90; hypoxia inducible factor; renal cancer; solid tumour; VEGF ID HEAT-SHOCK-PROTEIN; HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; ENDOTHELIAL GROWTH-FACTOR; HISTONE DEACETYLASE INHIBITOR; TUMOR-SUPPRESSOR GENE; NITRIC-OXIDE SYNTHASE; FOCAL ADHESION KINASE; HIPPEL-LINDAU PROTEIN; SUBEROYLANILIDE HYDROXAMIC ACID; AKT-DEPENDENT PHOSPHORYLATION AB Heat-shock protein (Hsp)-90 belongs to the class of molecular chaperone proteins that are capable of sensing cellular stress. Although Hsp90 is essential for viability, the pharmacological inhibition of this chaperone has emerged as an attractive means to inhibit tumorigenesis. This phenomenon is due to a unique property of Hsp90; its 'client proteins' are universally involved in signal transduction pathways commonly dysregulated in, and contributing to, cancer. The natural product geldanamycin, a potent ansamycin Hsp90 inhibitor, has served as a lead compound for the development of several derivatives that are currently undergoing clinical trials. Inhibition of Hsp90 with geldanamycin simultaneously depletes Hsp90-associated clients and impairs numerous signalling cascades that depend on chaperone function. importantly, tumour cells are exquisitely sensitive to Hsp90 inhibition, lending credence to the feasibility of selectively targeting cancer tissue via the pharmacological modulation of Hsp90 function. Even more remarkably, Hsp90 inhibitors sensitise tumour cells to the cytotoxic effects of a variety of standard therapeutics, and thus, they are likely to have broad utility in combination therapy. Although these are promising developments, much remains to be discovered about client-chaperone biology and the tumour-specific effects of Hsp90 blockade. This information is required to fully grasp the multifaceted roles of Hsp90 in cancer biology towards the goal of optimising the use of these agents in the clinic. Elucidation of these nuances will undoubtedly lead to better targeting of relevant oncogenic pathways and translate into the development of more effective anticancer regimens. C1 NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Rockville, MD 20857 USA. RP Isaacs, JS (reprint author), NCI, Urol Oncol Branch, Ctr Canc Res, NIH, Rockville, MD 20857 USA. EM isaacsj@mail.nih.gov NR 189 TC 14 Z9 18 U1 0 U2 1 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 JUN PY 2005 VL 14 IS 6 BP 569 EP 589 DI 10.1517/113543784.14.6.569 PG 21 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 955GZ UT WOS:000231215200002 PM 16004589 ER PT J AU Murphy, E Steenbergen, C AF Murphy, E Steenbergen, C TI Inhibition of GSK-3 beta as a target for cardioprotection: the importance of timing, location, duration and degree of inhibition SO EXPERT OPINION ON THERAPEUTIC TARGETS LA English DT Review DE apoptosis; cardiac hypertrophy; cardioprotection; glycogen synthase kinase (GSK); heart; metabolism ID GLYCOGEN-SYNTHASE KINASE-3; RABBIT SKELETAL-MUSCLE; KAPPA-B ACTIVATION; PROTEIN-KINASE; BETA-CATENIN; CARDIAC-HYPERTROPHY; GENE-EXPRESSION; NUCLEAR EXPORT; IN-VIVO; SELECTIVE INHIBITORS AB Cardiovascular disease is the major cause of morbidity and mortality in western countries such as the US. Myocardial infarction leads to loss of myocytes and with extremely limited ability to replenish cardiomyocytes, the heart exhibits depressed contractility. This ultimately results in hypertrophy of the remaining viable myocytes, which is the primary predictor for heart failure. Thus, drug therapies which can reduce myocyte cell death and reduce postischaemic dysfunction would be expected to greatly reduce cardiac hypertrophy and subsequent heart failure and death. Inhibition of glycogen synthase kinase (GSK)-3 beta has been proposed as a strategy to improve postischaemic cardiomyocyte survival, as inhibition of GSK-3 beta has been shown to reduce myocardial cell death following ischaemia and reperfusion. Therapies for inhibiting GSK are feasible as there are a number of newly developed specific inhibitors of GSK available, although most of these drugs have not been tested in long-term animal studies. C1 NIEHS, Lab Signal Transduct, NIH, DHHS, Res Triangle Pk, NC 27709 USA. Duke Univ, Sch Med, Dept Pathol, Durham, NC 27710 USA. RP Murphy, E (reprint author), NIEHS, Lab Signal Transduct, NIH, DHHS, POB 12233, Res Triangle Pk, NC 27709 USA. EM murphyl@niehs.nih.gov FU NHLBI NIH HHS [R01 HL039752] NR 87 TC 45 Z9 46 U1 0 U2 2 PU ASHLEY PUBLICATIONS LTD PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1472-8222 J9 EXPERT OPIN THER TAR JI Expert Opin. Ther. Targets PD JUN PY 2005 VL 9 IS 3 BP 447 EP 456 DI 10.1517/14728222.9.3.447 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 937HU UT WOS:000229916000003 PM 15948666 ER PT J AU Conrads, TP Veenstra, TD AF Conrads, TP Veenstra, TD TI What have we learned from proteomic studies of serum? SO EXPERT REVIEW OF PROTEOMICS LA English DT Editorial Material C1 NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. RP Veenstra, TD (reprint author), NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, POB B,Bldg 469,Room 160, Frederick, MD 21702 USA. EM conrads@ncifcrf.gov; veenstra@ncifcrf.gov NR 3 TC 4 Z9 5 U1 0 U2 0 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD JUN PY 2005 VL 2 IS 3 BP 279 EP 281 DI 10.1586/14789450.2.3.279 PG 3 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 971TB UT WOS:000232406500001 PM 16000073 ER PT J AU Braunschweig, T Chung, JY Hewitt, SM AF Braunschweig, T Chung, JY Hewitt, SM TI Tissue microarrays: bridging the gap between research and the clinic SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE cell line; clinical trials; high throughput; histology methodologies; pathology; proteomics; tissue microarray; TMA; translational medicine; xenograft ID METASTATIC BREAST-CANCER; GROWTH-FACTOR RECEPTOR; IN-SITU HYBRIDIZATION; RENAL-CELL CARCINOMA; PROTEIN EXPRESSION; PROSTATE-CANCER; MOLECULAR CLASSIFICATION; PROGNOSTIC MARKER; TUMOR-TISSUE; LUNG-CANCER AB Tissue microarrays are a high-throughput method for the Investigation of biomarkers in multiple tissue specimens at once. This technique allows for the analysis of up to 500 tissue samples in a single experiment using immunohistochemistry and in situ hybridization. Recently, cell lines and xenografts have been reduced to a tissue microarray format and are being applied to preclinical drug development. In clinical research, tissue microarrays are applied at multiple levels: comprehensive analysis of samples in the context of a clinical trial or across a population. Tissue microarrays play a central role in translational research, facilitating the discovery of molecules that have potential roles in the diagnosis, prognosis and prediction of response to therapy. C1 NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. Inje Univ, Coll Med, PharmacoGenom Res Ctr, Pusan, South Korea. Inje Univ, Coll Med, Mol Cell Physiol Res Grp, Pusan 614735, South Korea. RP Hewitt, SM (reprint author), NCI, Tissue Array Res Program, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. EM braunsct@mail.nih.gov; chungjo@mail.nih.gov; genejock@helix.nih.gov OI Hewitt, Stephen/0000-0001-8283-1788; Chung, Joon-Yong/0000-0001-5041-5982 NR 80 TC 46 Z9 51 U1 0 U2 5 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD JUN PY 2005 VL 2 IS 3 BP 325 EP 336 DI 10.1586/14789450.2.3.325 PG 12 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 971TB UT WOS:000232406500007 PM 16000080 ER PT J AU Manoli, I Le, H Alesci, S McFann, KK Su, YA Kino, T Chrousos, GP Blackman, MR AF Manoli, I Le, H Alesci, S McFann, KK Su, YA Kino, T Chrousos, GP Blackman, MR TI Monoamine oxidase-A is a major target gene for glucocorticoids in human skeletal muscle cells SO FASEB JOURNAL LA English DT Article DE dexamethasone; myopathy; mitochondria; catecholamine; hydrogen peroxide ID TRANSCRIPTION FACTOR SP1; OXIDATIVE STRESS; MAO-A; MITOCHONDRIAL DYSFUNCTION; THERAPEUTIC IMPLICATIONS; PROTEIN-SYNTHESIS; EXPRESSION; DEXAMETHASONE; MYOBLASTS; APOPTOSIS AB Skeletal myopathy is a common complication of endogenous and exogenous glucocorticoid excess, yet its pathogenetic mechanisms remain unclear. There is accumulating evidence that mitochondrial dysfunction and oxidative stress are involved in this process. To explore the glucocorticoid-induced transcriptional adaptations that may affect mitochondrial function in skeletal muscle, we studied gene expression profiles in dexamethasone-treated primary human skeletal myocytes using a cDNA microarray, which contains 501 mitochondria-related genes. We found that monoamine oxidase A (MAO-A) was the most significantly up-regulated gene. MAO-A is the primary enzyme metabolizing catecholamines and dietary amines, and its role in skeletal muscle remains largely unexplored. Dexamethasone induced dose- and time- dependent increases of MAO-A gene and protein expression, while its effects on MAO-B were minimal. Both the glucocorticoid receptor ( GR) and the Sp1 transcription factor were required for dexamethasone-induced MAO-A mRNA expression, as blockade of the GR with RU 486 or ablation of Sp1 binding with mithramycin abrogated MAO-A mRNA induction. The observed dexamethasone effect was biologically functional, as this steroid significantly increased MAO-mediated hydrogen peroxide production. We suggest that MAO-A-mediated oxidative stress can lead to cell damage, representing a novel pathogenetic mechanism for glucocorticoid-induced myopathy and a potential target for therapeutic intervention. C1 Natl Ctr Complementary & Alternat Med, Endocrine Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. UOA, Dept Pediat 1, GR-11527 Athens, Greece. NIMH, Clin Neuroendocrinol Branch, NIH, Bethesda, MD 20892 USA. NCCAM, Off Clin & Regulat Affairs, NIH, Bethesda, MD 20892 USA. LUMC, Dept Pathol, Maywood, IL 60153 USA. NICHD, Reprod Biol & Med Branch, NIH, Bethesda, MD 20892 USA. RP Natl Ctr Complementary & Alternat Med, Endocrine Sect, Clin Invest Lab, NIH, 9 Mem Dr,Bldg 9,Room 1N105, Bethesda, MD 20892 USA. EM manolii@mail.nih.gov OI Manoli, Irini/0000-0003-1543-2941 NR 64 TC 43 Z9 45 U1 2 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 EI 1530-6860 J9 FASEB J JI Faseb J. PD JUN PY 2005 VL 19 IS 8 BP 1359 EP + DI 10.1096/fj.04-3660fje PG 23 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 941IF UT WOS:000230207800021 PM 15946989 ER PT J AU Ren-Patterson, RF Kim, DK Zheng, X Sherrill, S Huang, SJ Tolliver, T Murphy, DL AF Ren-Patterson, RF Kim, DK Zheng, X Sherrill, S Huang, SJ Tolliver, T Murphy, DL TI Serotonergic-like progenitor cells propagated from neural stem cells in vitro: survival with SERT protein expression following implantation into brains of mice lacking SERT SO FASEB JOURNAL LA English DT Article DE precursor; differentiation; serotonin transporter; uptake ID DOPAMINERGIC PHENOTYPE; NEUROTROPHIC FACTOR; NEURONS; DIFFERENTIATION; CNS; MOUSE; TRANSPLANTATION; INDUCTION; MIDBRAIN; THERAPY AB Neural stem cells (NSCs) obtained from the midbrain region of embryonic (E14) mice were initially cultured with basic fibroblast growth factor ( bFGF), Sonic hedgehog, and FGF-8 in a serum-free N-2 culture medium to foster differentiation into a serotonergic-like phenotype. During the initial differentiating phase, these progenitor cells expressed En1, Pax3, and Pax5 mRNA. Subsequently, a single serotonin [5- hydroxytryptamine (5-HT)] and tryptophan hydroxylase-positive clone was isolated, which gave rise to cells that developed serotonergic properties. Sixty percent of these progenitor cells expressed the serotonin transporter (SERT), as indicated by specific ligand binding of [I-125]-RTI-55. To further evaluate SERT functionality, we showed that these progenitor cells possessed specific [H-3]-5-HT uptake activity. Implantation of the serotonergic-like progenitors into the hippocampus of adult mice genetically lacking SERT was followed by migration of these cells into adjacent brain regions, and survival of the cells at 8 weeks was accompanied by a gradual increase in density of SERT protein expression, which was not found in vehicle-injected, control mice. These findings suggest that this serotonergic-like NSC model will be a useful contribution to the development of cell biotechnology in regard to the expression of missing genes such as SERT in the adult brain. C1 NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Ren-Patterson, RF (reprint author), NIMH, Clin Sci Lab, NIH, Bldg 10 Room 3D41, Bethesda, MD 20892 USA. EM renpatr@intra.nimh.nih.gov FU Intramural NIH HHS NR 51 TC 6 Z9 6 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD JUN PY 2005 VL 19 IS 8 BP 1537 EP + DI 10.1096/fj.04-3657fje PG 22 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 941IF UT WOS:000230207800013 PM 15972295 ER PT J AU LaRonde-LeBlanc, N Guszczynski, T Copeland, T Wlodawer, A AF LaRonde-LeBlanc, N Guszczynski, T Copeland, T Wlodawer, A TI Autophosphorylation of Archaeoglobus fulgidus Rio2 and crystal structures of its nucleotide-metal ion complexes SO FEBS JOURNAL LA English DT Article DE autophosphorylation; nucleotide complex; protein kinase; ribosome biogenesis; Rio2 ID DEPENDENT PROTEIN-KINASE; PRE-RIBOSOMAL-RNA; SACCHAROMYCES-CEREVISIAE; CATALYTIC SUBUNIT; PEPTIDE INHIBITOR; IDENTIFICATION; REFINEMENT; GENOME; FAMILY AB The highly conserved, atypical RIO serine protein kinases are found in all organisms, from archaea to man. In yeast, the kinase activity of Rio2 is necessary for the final processing step of maturing the 18S ribosomal rRNA. We have previously shown that the Rio2 protein from Archaeoglobus fulgidus contains both a small kinase domain and an N-terminal winged helix domain. Previously solved structures using crystals soaked in nucleotides and Mg2+ or Mn2+ showed bound nucleotide but no ordered metal ions, leading us to the conclusion that they did not represent an active conformation of the enzyme. To determine the functional form of Rio2, we crystallized it after incubation with ATP or ADP and Mn2+. Co-crystal structures of Rio2-ATP-Mn and Rio2-ADP-Mn were solved at 1.84 and 1.75 angstrom resolution, respectively. The gamma-phosphate of ATP is firmly positioned in a manner clearly distinct from its location in canonical serine kinases. Comparison of the Rio2-ATP-Mn complex with the Rio2 structure with no added nucleotides and with the ADP complex indicates that a flexible portion of the Rio2 molecule becomes ordered through direct interaction between His126 and the gamma-phosphate oxygen of ATP. Phosphopeptide mapping of the autophosphorylation site of Rio2 identified Ser128, within the flexible loop and directly adjacent to the part that becomes ordered in response to ATP, as the target. These results give us further information about the nature of the active site of Rio2 kinase and suggest a mechanism of regulation of its enzymatic activity. C1 NCI, Prot Struct Sect, Macromol Crystallog Lab, Frederick, MD 21702 USA. NCI, Lab Prot Dynam & Signaling, Frederick, MD 21702 USA. RP Wlodawer, A (reprint author), NCI, Prot Struct Sect, Macromol Crystallog Lab, MCL 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 27 TC 30 Z9 34 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 JUN PY 2005 VL 272 IS 11 BP 2800 EP 2810 DI 10.1111/j.1742-4658.2005.04702.x PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 930AY UT WOS:000229389400017 PM 15943813 ER PT J AU Maggio, R Novi, F Scarselli, M Corsini, GU AF Maggio, R Novi, F Scarselli, M Corsini, GU TI The impact of G-protein-coupled receptor hetero-oligomerization on function and pharmacology SO FEBS JOURNAL LA English DT Review DE bivalent ligand; G-protein; mitogen-activated protein kinase (MAPK); oligomerization; beta-arrestin ID BETA-ARRESTIN; OPIOID RECEPTORS; CRYSTAL-STRUCTURE; PAIRED ACTIVATION; 2 COMPONENTS; SUBSTANCE-P; HETERODIMERIZATION; DOPAMINE; DOMAIN; SOMATOSTATIN AB Although highly controversial just a few years ago, the idea that G-protein-coupled receptors (GPCRs) may undergo homo-oligomerization or hetero-oligomerization has recently gained considerable attention. The recognition that GPCRs may exhibit either dimeric or oligomeric structures is based on a number of different biochemical and biophysical approaches. Although much effort has been spent to demonstrate the mechanism(s) by which GPCRs interact with each other, the physiological relevance of this phenomenon remains elusive. An additional source of uncertainty stems from the realization that homo-oligomerization and hetero-oligomerization of GPCRs may affect receptor binding and activity in different ways, depending on the type of interacting receptors. In this brief review, the functional and pharmacological effects of the hetero-oligomerization of GPCR on binding and cell signaling are critically analyzed. C1 Univ Pisa, Dept Neurosci, I-56100 Pisa, Italy. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Maggio, R (reprint author), Univ Pisa, Dept Neurosci, Via Roma 55, I-56100 Pisa, Italy. EM r.maggio@drugs.med.unipi.it OI Scarselli, Marco/0000-0001-5087-3182; Maggio, Roberto/0000-0003-4436-2356 NR 47 TC 63 Z9 68 U1 2 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUN PY 2005 VL 272 IS 12 BP 2939 EP 2946 DI 10.1111/j.1742-4658.2005.04729.x PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 939QR UT WOS:000230088000004 PM 15955054 ER PT J AU Lo, SC Wang, RYH Grandinetti, T Zou, NX Hayes, MM Shih, JWK Wear, DJ AF Lo, SC Wang, RYH Grandinetti, T Zou, NX Hayes, MM Shih, JWK Wear, DJ TI Mycoplasma penetrans infections and seroconversion in patients with AIDS: identification of major mycoplasmal antigens targeted by host antibody response SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE Mycoplasma penetrans; major antigen; seroconversion; AIDS ID HIV; ASSOCIATION; LIPOPROTEIN AB We examined Mycoplasma penetrans-specific antibodies in sera of five male homosexual AIDS patients from whom M penetrans was isolated during the disease process. No consistent immune reaction pattern could be recognized in Western blot using whole cell proteins. Serum samples obtained prior to M. penetrans isolation reacted with a number of M. penetrans proteins, most likely due to non-specific cross-reactions. Further analysis revealed that patients produced prominent antibody reaction to lipid-associated membrane proteins (LAMPs) of M. penetrans at the time of mycoplasma isolation, which could not be observed for serum samples obtained prior to M. Penetrans isolation. The positive antibody reaction was mainly directed against two major LAMPs of M. penetrans with molecular mass of 35 and 38 kDa and produced a distinctive pattern of positive immunoreaction bands. Our observation suggested that, comparing with whole mycoplasmal proteins, LAMPs were more specific target antigens in serological assays for M. penetrans infection. (c) 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 Armed Forces Inst Pathol, Dept Environm & Infect Dis Sci, Washington, DC 20306 USA. Armed Forces Inst Pathol, Dept Infect & Parasit Dis Pathol, Amer Registry Pathol, Dept Environm & Infect Dis Sci, Washington, DC 20306 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Transfus Med, Bethesda, MD 20892 USA. RP Lo, SC (reprint author), Armed Forces Inst Pathol, Dept Environm & Infect Dis Sci, Bldg 54,Room 4091,14th St & Alaska Ave NW, Washington, DC 20306 USA. EM los@afip.osd.mil NR 19 TC 4 Z9 5 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD JUN 1 PY 2005 VL 44 IS 3 BP 277 EP 282 DI 10.1016/j.femsim.2004.12.010 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 933JG UT WOS:000229624100004 PM 15907449 ER PT J AU Groff, AA Covington, SN Halverson, LR Fitzgerald, OR Vanderhoof, V Calis, K Nelson, LM AF Groff, AA Covington, SN Halverson, LR Fitzgerald, OR Vanderhoof, V Calis, K Nelson, LM TI Assessing the emotional needs of women with spontaneous premature ovarian failure SO FERTILITY AND STERILITY LA English DT Article DE premature ovarian failure; psychology; emotional needs; emotional response; coping; support; spirituality ID BREAST-CANCER; BAD-NEWS; COMMUNICATION; ADJUSTMENT; MENOPAUSE AB Objective: To examine women's emotional responses to learning the diagnosis of premature ovarian failure (POF) and identify the sources of support used for coping. Design: Observational study. Setting: National Institutes of Health Clinical Center. Patient(s): One hundred women previously diagnosed with POF of median age 28 years at diagnosis. Intervention(s): Structured telephone interviews based on focus group findings. Main Outcome Measure(s): Manner informed of POF diagnosis, emotional response, and areas of emotional support. Result(s): Overall, 71% were unsatisfied with the manner in which they were informed by their clinician, and 89% reported experiencing moderate to severe emotional distress at the time. The degree of emotional distress was positively correlated with the degree of dissatisfaction with the manner in which the women had been informed of the diagnosis. Thorough and accurate medical information on POF, support of others, and spirituality were perceived as helpful in coping. Conclusion(s): Learning the diagnosis of POF can be emotionally traumatic and difficult for women. The findings suggest that the manner in which patients are informed of this diagnosis can significantly impact their level of distress. Patients perceive a need for clinicians to spend more time with them and provide more information about POF. (c) 2005 by American Society for Reproductive Medicine. C1 NICHHD, Sect Womens Hlth Res, Dev Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA. Shady Grove Fertil Reprod Sci Ctr, Rockville, MD USA. ORC Macro, Calverton, MD USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Covington, SN (reprint author), 15001 Shady Grove Rd,Suite 400, Rockville, MD 20854 USA. EM sharon.covington@integramed.com FU Intramural NIH HHS NR 25 TC 50 Z9 51 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0015-0282 J9 FERTIL STERIL JI Fertil. Steril. PD JUN PY 2005 VL 83 IS 6 BP 1734 EP 1741 DI 10.1016/j.fertnstert.2004.11.067 PG 8 WC Obstetrics & Gynecology; Reproductive Biology SC Obstetrics & Gynecology; Reproductive Biology GA 935FI UT WOS:000229764600020 PM 15950644 ER PT J AU Levine, RL AF Levine, RL TI Commentary on "Downregulation of the human Lon protease impairs mitochondrial structure and function and causes cell death" by D.A. Bota, J.K. Ngo, and K.J.A. Davies SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Editorial Material C1 NHLBI, Biochem Lab, Bethesda, MD 20892 USA. RP Levine, RL (reprint author), NHLBI, Biochem Lab, Bldg 10, Bethesda, MD 20892 USA. EM rlevine@nih.gov RI Levine, Rodney/D-9885-2011 NR 10 TC 2 Z9 2 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD JUN 1 PY 2005 VL 38 IS 11 BP 1445 EP 1446 DI 10.1016/j.freeadbiomed.2005.02.027 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 930EN UT WOS:000229398700005 PM 15890618 ER PT J AU Oleksyk, TK Thio, CL Truelove, AL Goedert, JJ Donfield, SM Kirk, GD Thomas, DL O'Brien, SJ Smith, MW AF Oleksyk, TK Thio, CL Truelove, AL Goedert, JJ Donfield, SM Kirk, GD Thomas, DL O'Brien, SJ Smith, MW TI Single nucleotide polymorphisms and haplotypes in the IL10 region associated with HCV clearance SO GENES AND IMMUNITY LA English DT Article DE hepatitis C clearance; IL10 region; IL19; IL20; haplotypes; genetic association ID HEPATITIS-C VIRUS; NECROSIS-FACTOR-ALPHA; INTERLEUKIN-10 GENE PROMOTER; ENVIRONMENTAL-FACTORS; DISEASE PROGRESSION; SUSTAINED RESPONSE; ANTIVIRAL THERAPY; NATURAL-HISTORY; B-VIRUS; INFECTION AB Hepatitis C virus (HCV) is an infectious blood-borne pathogen that usually persists as a chronic infection. However, approximately 15% of the time, patients can clear the virus, indicating that host differences could be critical in determining the course of HCV infection. The inflammatory response is crucial to resolving or failing to resolve an acute HCV infection. Some previous reports have implicated interleukin 10 (IL10) polymorphisms with successful anti-HCV therapy and natural viral clearance. We tested 54 single nucleotide polymorphisms ( SNPs) in the IL10 region ( 7300 kb and 24 within the IL10 gene itself), which contains 13 genes including the IL10 immunomodulatory paralogs IL19, IL20, and IL24, for association with HCV clearance vs persistence. SNPs from two haplotype block regions, one at IL10 and the other from IL19/IL20, were associated with HCV clearance in African Americans ( 91 clearance cases and 183 chronically infected matched controls; P = 0.05 - 0.002) while with expectation-maximization algorithm-reconstructed haplotypes, these associations remained ( P = 0.05 - 0.002). However, no significant associations were detected in European Americans ( 108 clearance and 245 chronic). Our results indicate that variants of the immunomodulatory IL10 and IL19/ IL20 genes may be involved in natural clearance of HCV in the African-American population. C1 NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. NCI, Lab Genom Divers, Frederick, MD 21702 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Rho Inc, Chapel Hill, NC USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA. RP Smith, MW (reprint author), NCI, Basic Res Program, SAIC Frederick, Bldg 560, Frederick, MD 21702 USA. EM smithm@ncifcrf.gov RI Kirk, Gregory/A-8484-2009; Smith, Michael/B-5341-2012; Taras, Oleksyk/J-8805-2013 OI Taras, Oleksyk/0000-0002-8148-3918 FU NCI NIH HHS [N01-CO-12400]; NIDA NIH HHS [DA00441, DA13324] NR 68 TC 61 Z9 65 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1466-4879 J9 GENES IMMUN JI Genes Immun. PD JUN PY 2005 VL 6 IS 4 BP 347 EP 357 DI 10.1038/sj.gene.6364188 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 931DI UT WOS:000229465600010 PM 15815689 ER PT J AU McNeil, N Kim, JS Ried, T Janz, S AF McNeil, N Kim, JS Ried, T Janz, S TI Extraosseous IL-6 transgenic mouse plasmacytoma sometimes lacks Myc-activating chromosomal translocation SO GENES CHROMOSOMES & CANCER LA English DT Article ID HUMAN MULTIPLE-MYELOMA; TRANSCRIPTION FACTOR XBP-1; LIGHT-CHAIN LOCUS; C-MYC; CELL DIFFERENTIATION; BALB/C PLASMACYTOMAS; ABERRANT REARRANGEMENT; NEOPLASTIC DEVELOPMENT; COMPLEX TRANSLOCATION; MURINE PLASMACYTOMA AB The cellular oncogene MYC and plasma cell growth, differentiation, and survival factor IL-6 play critical roles in the natural history of human plasma cell neoplasms such as multiple myeloma (MM). Myc and IL-6 also are at the center of neoplastic plasma cell transformation in BALIB/c Mice that carry a human IL-6 transgene and, therefore, predictably develop plasmacytomas (PCTs). We showed previously that, much like advanced MM or human myeloma cell lines (HMCLs), in which MYC is frequently deregulated in cis because of complex cytogenetic aberrations juxtaposing MYC to immunoglobulin enhancers, IL-6 transgenic PCTs commonly deregulate Myc in cis by chromosomal translocation, predominantly T(12;15)(Igh-Myc). In this article, we show that, analogous to primary MM in which MYC is mostly deregulated in trans by signaling pathways converging at the MYC promoter, IL-6 transgenic PCTs sometimes develop in the absence of Myc translocations, thus activating Myc in trans. We present cytogenetic and molecular evidence on two IL-6 transgenic PCTs that contained overexpressed Myc protein but lacked T(12; 1 5)(Igh-Myc) and two related Myc-deregulating translocations that juxtapose Myc to immunoglobulin light-chain instead of heavy-chain enhancers: T(6;15)(1gK-PYt1) and T(15;16)(Pvt1-lg lambda). We conclude that Myc translocations are not strictly required for IL-6-driven PCT development in mice. IL-6 transgenic PCTs may provide a valuable model system for elucidating both trans and cis mechanisms of Myc deregulation of great relevance for MYC deregulation in human MM. (c) 2005 Wiley-Liss, Inc. C1 NCI, Genet Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Genet Branch, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. RP Janz, S (reprint author), NCI, Genet Lab, Canc Res Ctr, NIH, Bldg 37,Room 3140A, Bethesda, MD 20892 USA. EM sj4s@nih.gov NR 67 TC 5 Z9 5 U1 1 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUN PY 2005 VL 43 IS 2 BP 137 EP 146 DI 10.1002/gcc.20172 PG 10 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 918HF UT WOS:000228532200003 PM 15751044 ER PT J AU Mummert, SK Lobanenkov, VA Feinberg, AR AF Mummert, SK Lobanenkov, VA Feinberg, AR TI Association of chromosome arm 16q loss with loss of imprinting of insulin-like growth factor-II in Wilms tumor SO GENES CHROMOSOMES & CANCER LA English DT Article ID GENE; CTCF; METHYLATION; HETEROZYGOSITY; H19; CANCER; IGF2; EPIGENETICS; RELAXATION; EXPRESSION AB The most common known molecular defect in Wilms tumor (WT) of the kidney, the most frequent solid tumor of childhood, is loss of imprinting (LOI) of the insulin-like growth factor-II gene (IGF2), which involves activation of the normally silent maternal allele of the gene and hypermethylation of a differentially methylated region upstream of the H 19 gene. Hypermethylation impairs binding of the insulator protein CTCF, allowing activation of IGF2 by an enhancer shared between IGF2 and H19. Loss of heterozygosity (LOH) of 16q22.1 is found in 15% of WTs, and 16q22.1 harbors CTCF, raising the possibility that reduced CTCF could lead to LOI of IGF2 in some cases. We hypothesized that there is an association between LOH of 16q and LOI of IGF2 in WT. In 40 WTs examined, LOH of 16q was found in five, one of which also showed LOH of 11p15. All of the remaining four tumors showed LOI of IGF2, compared to 13 of 32 WTs without LOH of 16q or 11p (P = 0.040). When published data not previously analyzed in this manner were included, 6 of 6 tumors with 16q LOH (and without LOH of 11 p) showed LOI of IGF2, compared to 24 of 52 without LOH (P = 0.015). Thus, a genetic (16q LOH) and an epigenetic (LOI of IGF2) alteration in WT are linked, the first such association described. Finally, haploinsufficiency of CTCF may be the basis of this association, given that CTCF expression in tumors with 16q LOH was 48% that of tumors without LOH. (c) 2005 Wiley-Liss, Inc. C1 Johns Hopkins Univ, Sch Med, Grad Program Biochem Cell & Mol Biol, Baltimore, MD USA. NIAID, Immunopathol Lab, Rockville, MD 20852 USA. Johns Hopkins Univ, Sch Med, Dept Med Oncol, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Mol Biol & Genet, Baltimore, MD 21205 USA. RP Feinberg, AR (reprint author), 1064 Ross,720 Rutland Ave, Baltimore, MD 21205 USA. EM afeinberg@jhtj.edu OI Lobanenkov, Victor/0000-0001-6665-3635 FU NCI NIH HHS [R37 CA054358-15, R37 CA054358, CA54358] NR 21 TC 23 Z9 26 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1045-2257 J9 GENE CHROMOSOME CANC JI Gene Chromosomes Cancer PD JUN PY 2005 VL 43 IS 2 BP 155 EP 161 DI 10.1002/gcc.20176 PG 7 WC Oncology; Genetics & Heredity SC Oncology; Genetics & Heredity GA 918HF UT WOS:000228532200005 PM 15761865 ER PT J AU Rattray, AJ Shafer, BK Neelam, B Strathern, JN AF Rattray, AJ Shafer, BK Neelam, B Strathern, JN TI A mechanism of palindromic gene amplification in Saccharomyces cerevisiae SO GENES & DEVELOPMENT LA English DT Article DE DNA palindrome; gene amplification; MR complex; SAE2; Saccharomyces cerevisiae; BFB ID DOUBLE-STRAND BREAKS; INVERTED REPEATS; FRAGILE SITES; HOMOLOGOUS RECOMBINATION; NUCLEASE ACTIVITY; DRUG-RESISTANCE; DNA PALINDROMES; BUDDING YEAST; MRE11 COMPLEX; CANCER-CELLS AB Selective gene amplification is associated with normal development, neoplasia, and drug resistance. One class of amplification events results in large arrays of inverted repeats that are often complex in structure, thus providing little information about their genesis. We made a recombination substrate in Saccharomyces cerevisiae that frequently generates palindromic duplications to repair a site-specific double-strand break in strains deleted for the SAE2 gene. The resulting palindromes are stable in sae2 Delta cells, but unstable in wild-type cells. We previously proposed that the palindromes are formed by invasion and break-induced replication, followed by an unknown end joining mechanism. Here we demonstrate that palindrome formation can occur in the absence of RAD50, YKU70, and LIG4, indicating that palindrome formation defines a new class of nonhomologous end joining events. Sequence data from 24 independent palindromic duplication junctions suggest that the duplication mechanism utilizes extremely short (4-6 bp), closely spaced (2-9 bp), inverted repeats to prime DNA synthesis via an intramolecular foldback of a 3' end. In view of our data, we present a foldback priming model for how a single copy sequence is duplicated to generate a palindrome. C1 NCI, Frederick Canc Res & Dev Ctr, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. Frederick Inc, Adv Biomed Comp Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. RP Strathern, JN (reprint author), NCI, Frederick Canc Res & Dev Ctr, Gene Regulat & Chromosome Biol Lab, Frederick, MD 21702 USA. EM strather@ncifcrf.gov RI Rattray, Alison/A-4847-2008 NR 63 TC 57 Z9 58 U1 0 U2 1 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 JUN 1 PY 2005 VL 19 IS 11 BP 1390 EP 1399 DI 10.1101/gad.1315805 PG 10 WC Cell Biology; Developmental Biology; Genetics & Heredity SC Cell Biology; Developmental Biology; Genetics & Heredity GA 933JE UT WOS:000229623900012 PM 15937224 ER PT J AU Kastenmayer, JP Lee, MS Hong, AL Spencer, FA Basrai, MA AF Kastenmayer, JP Lee, MS Hong, AL Spencer, FA Basrai, MA TI The C-terminal half of Saccharomyces cerevisiae Mad1p mediates spindle checkpoint function, chromosome transmission fidelity and CEN association SO GENETICS LA English DT Article ID NUCLEAR-PORE COMPLEX; BUDDING YEAST; ASSEMBLY CHECKPOINT; MITOTIC CHECKPOINT; KINETOCHORES; SEGREGATION; PROTEINS; MISSEGREGATION; COMPONENTS; STABILITY AB The evolutionarily conserved spindle checkpoint is a key mechanism ensuring high-fidelity chromosome transmission. The checkpoint monitors attachment between kinetochores and mitotic spindles and the tension between sister kinetochores. In the absence of proper attachment or tension, the spindle checkpoint mediates cell cycle arrest prior to anaphase. Saccharomyces cerevisiae Mad1p is required for the spindle checkpoint and for chromosome transmission fidelity. Moreover, Mad1p associates with the nuclear pore complex (NPC) and is enriched at kinetochores upon checkpoint activation. Using partial mad] deletion alleles we determined that the C-terminal half of Mad1p is necessary and sufficient for checkpoint activation in response to microtubule depolymerizing agents, high-fidelity transmission of a reporter chromosome fragment, and in vivo association with centromeres, but not for robust NPC association. Thus, spindle checkpoint activation and chromosome transmission fidelity correlate and these Mad1p functions likely involve kinetochore association but not robust NPC association. These studies are the basis for elucidating the role of protein complexes containing Mad1p in the spindle checkpoint pathway and in maintaining genome stability in S. cerevisiae and other systems. C1 NCI, Genet Branch, Ctr Canc Res, NIH,Natl Naval Med Ctr, Bethesda, MD 20889 USA. Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21205 USA. RP Basrai, MA (reprint author), NCI, Genet Branch, Ctr Canc Res, NIH,Natl Naval Med Ctr, Bldg 8,Room 5101,8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM basraim@nih.gov FU NHGRI NIH HHS [HG02432, R01 HG002432]; NIGMS NIH HHS [GM50842, GM007445, GM62368, R01 GM062368, T32 GM007445] NR 37 TC 12 Z9 12 U1 0 U2 0 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUN PY 2005 VL 170 IS 2 BP 509 EP 517 DI 10.1534/genetics.105.041426 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 944PT UT WOS:000230441900003 PM 15802513 ER PT J AU Drake, JW Hwang, CBC AF Drake, JW Hwang, CBC TI On the mutation rate of herpes simplex virus type 1 SO GENETICS LA English DT Article ID SEQUENCE; GENE AB All seven DNA-based microbes for which carefully established mutation rates and mutational spectra were previously available displayed a genomic mutation rate in the neighborhood of 0.003 per chromosome replication. The pathogenic mammalian DNA virus herpes simplex type 1 has an estimated genomic mutation rate compatible with that value. C1 NIEHS, Mol Genet Lab, NIH, Res Triangle Pk, NC 27709 USA. SUNY Upstate Med Univ, Coll Med, Dept Microbiol & Immunol, Syracuse, NY 13210 USA. RP Drake, JW (reprint author), NIEHS, Mol Genet Lab, NIH, Room E-344,POB 12233, Res Triangle Pk, NC 27709 USA. EM drake@niehs.nih.gov FU NIAID NIH HHS [R01 AI056359] NR 13 TC 30 Z9 31 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 JUN PY 2005 VL 170 IS 2 BP 969 EP 970 DI 10.1534/genetics.104.040410 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 944PT UT WOS:000230441900043 PM 15802515 ER PT J AU Zainabadi, K Benyamini, P Chakrabarti, R Veena, MS Chandrasekharappa, SC Gatti, RA Srivatsan, ES AF Zainabadi, K Benyamini, P Chakrabarti, R Veena, MS Chandrasekharappa, SC Gatti, RA Srivatsan, ES TI A 700-kb physical and transcription map of the cervical cancer tumor suppressor gene locus on chromosome 11q13 SO GENOMICS LA English DT Article DE cervical cancer; tumor suppressor gene; chromosome 11q13; FRA11A; physical maps; transcription maps; microsatellites ID SPINOCEREBELLAR ATAXIA TYPE-5; SQUAMOUS-CELL CARCINOMAS; FRAGILE SITE FRA16D; HELA-CELLS; BAND 11Q13; HOMOZYGOUS DELETIONS; GENOME INSTABILITY; MULTIPLE-MYELOMA; ENDOCRINE TUMORS; BREAST-CANCER AB Nonrandom deletion of chromosome 11q13 sequences is a significant event in a number of human tumors. We have recently identified a 300-kb minimal area of deletion in primary cervical tumors that overlaps with deletions observed in endocrine and nasopharyngeal tumors. We have also observed a 5.7-kb homozygous deletion within this interval in HeLa cells (a cervical cancer cell line), HeLa cell-derived tumorigenic hybrids, and a primary cervical tumor, suggesting the presence of a tumor suppressor gene in this region. In the present investigation, we have constructed a 700-kb contig map encompassing the 300-kb deletion using the human genome sequence database and confirmed the map using various STS markers from the region. Our map also shows the overlap of a previously published rare, heritable fragile site, FRA11A, with the cervical cancer deletion locus. The mapped region contains highly repetitive GC-poor sequences. We have identified and characterized eight different polymorphic microsatellite markers from the sequences Within and Surrounding the deletion. Further, expression studies performed with 18 different ESTs localized adjacent to the homozygous deletion showed the presence of a transcript for only one of the ESTs, AA282789. This EST mapping within the homozgous deletion is also expressed ill HeLa cells, thereby excluding the EST as the putative tumor suppressor gene. Additionally. analysis of four candidate genes (SF3B2. BRMS1, R1N1, and RAB1B) from the region showed expression of the expected size message in both the nontumorigenic and the tumorigenic HeLa cell hybrids, thereby excluding them as the putative tumor suppressor gene(s). However, Northern blot analysis with a fifth candidate gene, PACS1 (phosphofurin acidic cluster sorting protein), mapped to the deletion/FRA11A overlap region showed the expression of an 8-kb transcript in HeLa and five other tumor cell lines in addition to the expected 4.5-kb transcript. Since the gene shows abundant expression in normal tissues and an altered transcript is observed in tumor cell lines, we hypothesize that this gene Could represent sequences of the putative tumor suppressor gene. Finally, we have observed a perfect 48-bp CAG/CCG repeat 99 kb proximal to D11S913, the marker linked to the neurodegenerative disorder spinocerebellar ataxia 5. The physical and transcription maps and the microsatellite markers of the 700-kb region of chromosome 11q13 should be helpful in the cloning of the cervical cancer tumor Suppressor gene. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Calif Los Angeles, VAGLAHS W Los Angeles, Dept Surg, David Geffen Sch Med, Los Angeles, CA 90073 USA. NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol, Los Angeles, CA 90095 USA. RP Srivatsan, ES (reprint author), Univ Calif Los Angeles, VAGLAHS W Los Angeles, Dept Surg, David Geffen Sch Med, 10H2,Bldg 304,Room E2-218,11301 Wiltshire Blvd, Los Angeles, CA 90073 USA. EM esrivats@ucla.edu NR 56 TC 18 Z9 18 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 0888-7543 J9 GENOMICS JI Genomics PD JUN PY 2005 VL 85 IS 6 BP 704 EP 714 DI 10.1016/j.ygeno.2005.02.014 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 928HY UT WOS:000229263400005 PM 15885497 ER PT J AU Lim, WK Chee, SP Nussenblatt, RB AF Lim, WK Chee, SP Nussenblatt, RB TI Progression of varicella-zoster virus necrotizing retinopathy in an HIV-negative patient with transient immune deviation SO GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY LA English DT Article ID ACUTE RETINAL NECROSIS AB Purpose: To report a case of unilateral varicella-zoster virus (VZV) necrotizing retinopathy that progressed from outer retinitis with features of progressive outer retinal necrosis (PORN) to typical acute retinal necrosis (ARN) in an HIV-negative patient with a transient decrease in CD4 lymphocyte counts and CD4/CD8 ratio. Method: Case report. Results: A 41-year-old Chinese man presenting with blurred vision in the right eye was diagnosed with herpetic necrotizing retinitis without vitritis. Fundus examination revealed retinal arteritis and extensive deep whitish retinal lesions in the mid-periphery with minimal vitritis. Aqueous humor and vitreous PCR were positive for VZV. His CD4 count on presentation was depressed ( 239 cells/ul) and the CD4/CD8 ratio was low ( 0.8). The referring ophthalmologist had treated him with prednisolone 60 mg/day. At our institution, when intravenous acyclovir was started and the steroid therapy discontinued, he developed severe vitritis and the deep retinal lesions progressed to full-thickness retinitis typical of ARN. Repeat CD4 count was 512 cells/ul at day 14. In total, he was treated with 14 days of IV acyclovir ( 12 mg/kg 8-hourly) followed by oral valaciclovir 500 mg three times a day for 3 months. Prednisolone 30 mg once daily was restarted and tapered over 3 months. Despite prophylactic argon retinal photocoagulation to the edge of the retinitis, the patient developed a total retinal detachment at 3 months. Conclusions: VZV retinal infection in an HIV-negative patient with transient immune deviation can manifest initially as outer retinitis with features similar to PORN and progress to typical ARN when CD4 counts return to normal. C1 Singapore Natl Eye Ctr, Singapore 168751, Singapore. NEI, NIH, Bethesda, MD 20892 USA. Natl Univ Singapore, Singapore 117548, Singapore. RP Chee, SP (reprint author), Singapore Natl Eye Ctr, 11 3rd Hosp Ave, Singapore 168751, Singapore. EM weekiak@cyberway.com.sg; chee_soon_phaik@snec.com.sg NR 11 TC 7 Z9 8 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0721-832X J9 GRAEF ARCH CLIN EXP JI Graefes Arch. Clin. Exp. Ophthalmol. PD JUN PY 2005 VL 243 IS 6 BP 607 EP 609 DI 10.1007/s00417-004-0998-4 PG 3 WC Ophthalmology SC Ophthalmology GA 937DA UT WOS:000229903600015 PM 15657772 ER PT J AU Wei, WQ Abnet, CC Lu, N Roth, MJ Wang, GQ Dye, BA Dong, ZW Taylor, PR Albert, P Qiao, YL Dawsey, SM AF Wei, WQ Abnet, CC Lu, N Roth, MJ Wang, GQ Dye, BA Dong, ZW Taylor, PR Albert, P Qiao, YL Dawsey, SM TI Risk factors for oesophageal squamous dysplasia in adult inhabitants of a high risk region of China SO GUT LA English DT Article ID GASTRIC CANCERS; CELL CARCINOMA; INCIDENT ESOPHAGEAL; SHANXI-PROVINCE; LINXIAN; SPECIMENS AB Background: Oesophageal squamous cell carcinoma ( OSCC) is a common cancer worldwide and has a very high mortality rate. Squamous dysplasia is the precursor lesion for OSCC and it can be seen during routine endoscopy with Lugol's iodine staining. We aimed to examine the risk factors for squamous dysplasia and determine if a risk model could be constructed which would be useful in selecting apparently healthy subjects for endoscopic screening in a high risk population in Linzhou, People's Republic of China. Subjects and methods: In this cross sectional study, 724 adult volunteers aged 40 - 65 years were enrolled. All subjects completed a questionnaire regarding potential environmental exposures, received physical and dental examinations, and underwent upper endoscopy with Lugol's iodine staining and biopsy. Subjects were categorised as having or not having histologically proven squamous dysplasia/ early cancer. Risk factors for dysplasia were examined using univariate and multivariate logistic regression. The utility of the final multivariate model as a screening tool was assessed using a receiver operating characteristics curve. Results: We found that 230 of 720 subjects ( 32%) with complete data had prevalent squamous dysplasia. In the final multivariate model, more household members ( odds ratio ( OR) 1.12/ member ( 95% confidence interval ( CI) 0.99, 1.25)), a family history of cancer ( OR 1.57 ( 95% CI 1.13- 2.18)), higher systolic blood pressure OR 1.11/ 10 mm Hg ( 95% CI 1.03- 1.19)), heating the home without a chimney ( OR 2.22 ( 95% CI 1.27 - 3.86)), and having lost more but not all of your teeth ( OR 1.91 for 12 - 31 teeth lost ( 95% CI 1.17 3.15)) were associated with higher odds of having dysplasia. Higher household income ( OR 0.96/ 100 RMB ( 95% CI 0.91 - 1.00)) was associated with a lower odds of having dysplasia. Although we found several statistically significant associations, the final model had little ability to accurately predict dysplasia status, with maximum simultaneous sensitivity and specificity values of 57% and 54%, respectively. Conclusions: We found that risk factors for dysplasia were similar to those previously identified as risk factors for OSCC in this population. The final model did a poor job of identifying subjects who had squamous dysplasia. Other methods will need to be developed to triage individuals to endoscopy in this high risk population. C1 NCI, Canc Prevent Studies Branch, Canc Res Ctr, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Inst Canc, Dept Canc Epidemiol, Beijing 100021, Peoples R China. Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. NCI, Biometr Res Branch, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. RP Abnet, CC (reprint author), NCI, Canc Prevent Studies Branch, Canc Res Ctr, 6116 Execut Blvd,Rm 705, Bethesda, MD 20892 USA. EM abnetc@mail.nih.gov RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 24 TC 46 Z9 49 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JUN PY 2005 VL 54 IS 6 BP 759 EP 763 DI 10.1136/gut.2004.062331 PG 5 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 925FP UT WOS:000229037700009 PM 15888779 ER PT J AU Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL AF Tsai, CJ Leitzmann, MF Willett, WC Giovannucci, EL TI Dietary carbohydrates and glycaemic load and the incidence of symptomatic gall stone disease in men SO GUT LA English DT Article ID CORONARY-HEART-DISEASE; FOOD-FREQUENCY QUESTIONNAIRE; GALLBLADDER-DISEASE; INDEX; GALLSTONES; CHOLESTEROL; INSULIN; WOMEN; LIPEMIA; RISK AB Background: Diets with a high glycaemic response exacerbate the metabolic consequences of the insulin resistance syndrome. Their effects on the incidence of gall stone disease are not clear, particularly in men. Methods: Dietary information was collected as part of the Health Professionals Follow up Study starting in 1986 using a semiquantitative food frequency questionnaire with follow up until 1998. On biennial questionnaires participants reported new symptomatic gall stone disease, diagnosed by radiology, and whether they had undergone cholecystectomy. Results: During 12 years of follow up, we documented 1810 new cases of symptomatic gall stones. After adjusting for age and other known or suspected risk factors in multivariate models, the relative risk ( RR) for the highest compared with the lowest quintile of carbohydrate intake was 1.59 ( 95% confidence interval ( CI) 1.25, 2.02; p for trend = 0.002). The RR for the highest compared with the lowest quintile of dietary glycaemic load was 1.50 ( 95% CI 1.20, 1.88; p for trend = 0.0008), and 1.18 for dietary glycaemic index ( 95% CI 1.01, 1.39; p for trend = 0.04). Independent positive associations were also seen for intakes of starch, sucrose, and fructose. Conclusions: Our findings suggest that a high intake of carbohydrate, glycaemic load, and glycaemic index increases the risk of symptomatic gall stone disease in men. These results add to the concern that low fat high carbohydrate diets may not be an optimal dietary recommendation. C1 Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, Lexington, KY 40536 USA. Harvard Univ, Sch Med, Dept Med, Channing Lab, Boston, MA USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NCI, Div Canc Epidemiol & Genet, DHHS, NIH, Bethesda, MD USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Tsai, CJ (reprint author), Univ Kentucky, Med Ctr, Div Digest Dis & Nutr, 800 Rose St, Lexington, KY 40536 USA. EM hpcjt@channing.harvard.edu FU NCI NIH HHS [CA55075, P01 CA055075]; NIDDK NIH HHS [P30 DK046200, DK46200] NR 39 TC 37 Z9 38 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0017-5749 J9 GUT JI Gut PD JUN PY 2005 VL 54 IS 6 BP 823 EP 828 DI 10.1136/gut.2003.031435 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 925FP UT WOS:000229037700022 PM 15888792 ER PT J AU Young, WB Bloom, MH Hopkins, MM Shaw, JW Gebeline-Myers, C AF Young, WB Bloom, MH Hopkins, MM Shaw, JW Gebeline-Myers, C TI Levetiracetam is effective for episodic migraine: A pilot trial SO HEADACHE LA English DT Meeting Abstract CT 47th Annual Scientific Meeting of the American-Headache-Society CY JUN 23-25, 2005 CL Philadelphia, PA SP Amer Headache Soc C1 Thomas Jefferson Univ, Philadelphia, PA 19107 USA. NCI, Tobacco Control Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0017-8748 J9 HEADACHE JI Headache PD JUN PY 2005 VL 45 IS 6 BP 822 EP 822 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 931OQ UT WOS:000229495000160 ER PT J AU Hashimoto, I Li, XK Bhat, AH Jones, M Sahn, DJ AF Hashimoto, I Li, XK Bhat, AH Jones, M Sahn, DJ TI Quantitative assessment of regional peak myocardial acceleration during isovolumic contraction and relaxation times by tissue Doppler imaging SO HEART LA English DT Article ID VENTRICULAR CONTRACTILITY; STRAIN-RATE; HYPERTROPHIC CARDIOMYOPATHY; DIASTOLIC FUNCTION; INDEX; QUANTIFICATION; ABNORMALITIES; VALIDATION; INFARCTION; CHILDREN AB Objective: To examine regional wall acceleration and its relation to relaxation. Study design: 8 sheep were examined by tissue Doppler ultrasound imaging (VingMed Vivid FiVe) in apical four chamber views to evaluate the left ventricular wall divided into six segments and the mitral annulus in two segments. Peak myocardial acceleration during isovolumic periods (pIVA) derived from tissue Doppler echocardiography was analysed during isovolumic contraction (ICT) and relaxation times (IRT) in each segment. Interventions: After scanning at baseline, haemodynamic status was changed by administration of blood, dobutamine, and metoprolol. Changes of pIVA during IRT and ICT were compared over the four haemodynamic conditions in parallel with their peak positive and negative dP/dt measured with a high frequency manometer tipped catheter. Results: pIVA of the basal lateral segment during ICT correlated most strongly with peak positive dP/dt (r = 0.96, p< 0.0001) and there was good correlation between pIVA of the mitral valve annulus in the septum during IRT and peak negative dP/dt ( r = 0.80, p< 0.0001). pIVA differed significantly between the four haemodynamic conditions during ICT in all segments (p< 0.05); pIVA during IRT did not differ significantly between the four conditions. Conclusions: pIVA of the basal lateral wall during ICT correlated most strongly with peak positive dP/dt, and pIVA of the septal mitral valve annulus during IRT correlated well with peak negative dP/dt. C1 Oregon Hlth Sci Univ, Clin Care Ctr Congenital Heart Dis, Portland, OR 97239 USA. NHLBI, Bethesda, MD 20892 USA. RP Sahn, DJ (reprint author), Oregon Hlth Sci Univ, Clin Care Ctr Congenital Heart Dis, L608,3181 SW Sam Jackson Pk Rd, Portland, OR 97239 USA. EM sahnd@ohsu.edu NR 19 TC 16 Z9 17 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD JUN PY 2005 VL 91 IS 6 BP 811 EP 816 DI 10.1136/hrt.2004.033845 PG 6 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 926LW UT WOS:000229125700023 PM 15894787 ER PT J AU Moak, JP Eldadah, B Holmes, C Pechnik, S Goldstein, DS AF Moak, JP Eldadah, B Holmes, C Pechnik, S Goldstein, DS TI Partial cardiac sympathetic denervation after bilateral thoracic sympathectomy in humans SO HEART RHYTHM LA English DT Article DE sympathetic nervous system; sympathectomy; norepinephrine; positron emission tomography; fluorodopamine ID IDIOPATHIC DILATED CARDIOMYOPATHY; LONG-QT SYNDROME; HEART-FAILURE; METAIODOBENZYLGUANIDINE UPTAKE; VENTRICULAR-TACHYCARDIA; MYOCARDIAL-INFARCTION; PROGNOSTIC VALUE; NERVOUS-SYSTEM; INNERVATION; I-123-MIBG AB BACKGROUND Upper thoracic sympathectomy is used to treat several disorders. Sympathetic nerve fibers emanating from thoracic ganglia innervate the heart. Whether unilateral or bilateral upper thoracic sympathectomy affects cardiac sympathetic innervation in humans in vivo has been unclear. OBJECTIVES The purpose of this study was to assess whether thoracic sympathectomy decreases cardiac sympathetic innervation, as indicated by positron emission tomographic scanning after intravenous injection of the sympathoneural imaging agent 6-[F-18]fluorodopamine. METHODS Nine patients with previous upper thoracic sympathectomies (four right-sided, one left-sided, four bilateral) underwent thoracic 6-[F-18]fluorodopamine scanning between 1 and 2 hours after injection of the imaging agent. In each case, a low rate of entry of norepinephrine into the arm venous drainage (norepinephrine spillover) verified upper limb sympathectomy. Data were compared with those from the interventricular septum of patients with cardiac sympathetic denervation associated with pure autonomic failure and from normal volunteers. RESULTS All four patients with bilateral sympathectomy had low septal myocardial 6-[F-18]fluorodopamine-derived radioactivity (2,673 &PLUSMN; 92 nCi-kg/cc-mCi at an average of 89 minutes after injection) compared with normal volunteers (3,634 &PLUSMN; 311 nCi-kg/cc-mCi at 83 minutes, N = 22, P = .007) and higher radioactivity than in patients with pure autonomic failure (1,320 &PLUSMN; 300 nCi-kg/cc-mCi at 83 minutes, N = 7, P = .003). Patients with unilateral sympathectomy had normal 6-[F-18]fluorodopamine-derived radioactivity (3,971 &PLUSMN; 337 nCi-kg/cc-mCi at 87 minutes). CONCLUSIONS Bilateral upper thoracic sympathectomy partly decreases cardiac sympathetic innervation density. C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. NINDS, NIH, Clin Neurocardiol Sect, Bethesda, MD 20892 USA. RP Moak, JP (reprint author), Bldg 10 Room 6N252,10 Ctr Dr,MSC-1620, Bethesda, MD 20892 USA. EM moakj@ninds.nih.gov NR 39 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD JUN PY 2005 VL 2 IS 6 BP 602 EP 609 DI 10.1016/j.hrthm.2005.03.003 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 932MT UT WOS:000229558500006 PM 15922266 ER PT J AU Adamson, PB Barr, RC Callans, DJ Chen, PS Lathrop, DA Makielski, JC Nerbonne, JM Nuss, HB Olgin, JE Przywara, DA Rosen, MR Rozanski, GJ Spach, MS Yamada, KA AF Adamson, PB Barr, RC Callans, DJ Chen, PS Lathrop, DA Makielski, JC Nerbonne, JM Nuss, HB Olgin, JE Przywara, DA Rosen, MR Rozanski, GJ Spach, MS Yamada, KA TI The perplexing complexity of cardiac arrhythmias: Beyond electrical remodeling SO HEART RHYTHM LA English DT Article DE arrhythmogenesis; cardiac muscle; genetic basis of arrhythmias; ion channels; molecular biology ID LEFT-VENTRICULAR DYSFUNCTION; CONGESTIVE-HEART-FAILURE; ACTION-POTENTIAL DURATION; NITRIC-OXIDE SYNTHASE; ATRIAL-FIBRILLATION; MYOCARDIAL-INFARCTION; POTASSIUM CHANNEL; CALMODULIN KINASE; RANDOMIZED TRIAL; SODIUM-CHANNELS AB Cardiac arrhythmias continue to pose a major medical challenge and significant public health burden. Atrial fibrillation, the most prevalent arrhythmia, affects more than two million Americans annually and is associated with a twofold increase in mortality. In addition, more than 250,000 Americans each year suffer ventricular arrhythmias, often resulting in sudden cardiac death. Despite the high incidence and societal impact of cardiac arrhythmias, presently there are insufficient insights into the molecular mechanisms involved in arrhythmia generation, propagation, and/or maintenance or into the molecular determinants of disease risk, prognosis, and progression. In addition, present therapeutic strategies for arrhythmia abatement often are ineffective or require palliative device therapy after persistent changes in the electrical and conduction characteristics of the heart have occurred, changes that appear to increase the risk for arrhythmia progression. This article reviews our present understanding of the complexity of mechanisms that regulate cardiac membrane excitability and cardiac function and explores the role of derangements in these mechanisms that interact to induce arrhythmogenic substrates. Approaches are recommended for future investigations focused on providing new mechanistic insights and therapeutic interventions. C1 Columbia Univ, Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. Duke Univ, Med Ctr, Durham, NC USA. Univ Penn Hlth Syst, Philadelphia, PA USA. Univ Calif Los Angeles, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. Univ Calif Los Angeles, David Geffen Sch Med, Los Angeles, CA 90048 USA. NHLBI, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI USA. Washington Univ, Sch Med, St Louis, MO USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Nebraska, Med Ctr, Omaha, NE USA. RP Rosen, MR (reprint author), Columbia Univ, Coll Phys & Surg, Dept Pharmacol, 630 W 168 St,PH7W-321, New York, NY 10032 USA. EM mrr1@columbia.edu RI LATHROP, David/A-2758-2008 FU NHLBI NIH HHS [R01 HL066446, R01 HL050537, R01 HL066350, R01 HL066362, R01 HL066378, R01 HL066381, R01 HL066388, R01 HL066389, R01 HL066394, R01 HL066409, R01 HL067449] NR 81 TC 15 Z9 15 U1 0 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1547-5271 J9 HEART RHYTHM JI Heart Rhythm PD JUN PY 2005 VL 2 IS 6 BP 650 EP 659 DI 10.1016/j.hrthm.2005.03.009 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 932MT UT WOS:000229558500017 PM 15922277 ER PT J AU Horvath, KA Berry, GJ AF Horvath, KA Berry, GJ CA ICEM Investigators TI The incidence of emboli during cardiac surgery: A histopathologic analysis of 2297 patients SO HEART SURGERY FORUM LA English DT Article ID ASCENDING AORTA; INTRAAORTIC FILTRATION; PARTICULATE EMBOLI; CAPTURE; ATHEROEMBOLISM; MANAGEMENT; OPERATIONS; OUTCOMES; FILTER; IMPACT AB Objective: Manipulation of the atherosclerotic aorta during cardiac surgery is assumed to cause embolization, which can contribute to adverse outcomes. Recently, as a result of worldwide trials deploying the Embol-X intraaortic filter during cardiac surgery, such emboli were captured and processed for histopathologic analysis. Methods: Filters with a pore size of 120 microns were placed in 2297 patients who underwent the following operations: coronary artery bypass grafting (CABG) (70%), valve (17%), combination CABG/ valve (11%), and other (2%). Results: The filters captured at least one embolus in 98% of the patients. An average of 8.3 particles was captured per filter ( range of 0-74). The surface area of the emboli was on an average 5.8 mm(2) ( range of 0- 188 mm(2)). Histologic analysis of the captured particles indicated that in 79% of the filters fibrous atheromata were noted, in 44% there were platelets and fibrin, 8% had red blood cell thrombus, 3% had fibro-fatty/ adventitial tissue, 2% had other material including cartilage, myocardium, lung, suture, and a teflon pledget. Of the patients enrolled, 1569 were high-risk. The average number of particles captured in the high-risk patients was 8.5 versus 5.8 for the low- to moderate-risk patients ( P <.0001). Concomitantly, there was an increase in the embolic burden between the higher- and lower-risk patients ( surface area 6.6 vs. 4.0 mm(2), P <.0001). Conclusion: These data show the ubiquitous incidence of emboli during cardiac procedures. Intraaortic filtration should reduce adverse outcomes as was demonstrated for the high-risk patients in this study. Aortic manipulation during cardiac surgery can cause embolization and increase morbidity. The use of an intraaortic filter can decrease the embolic burden. We now report the histopathologic analysis of these emboli. C1 NHLBI, CSB, NIH, Bethesda, MD 20892 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. RP Horvath, KA (reprint author), NHLBI, CSB, NIH, Bldg 10,CRC,Rm 6-5140,10 Ctr Dr MSC 1454, Bethesda, MD 20892 USA. EM khorvath@nih.gov NR 17 TC 3 Z9 4 U1 0 U2 0 PU FORUM MULTIMEDIA PUBLISHING, LLC PI CHARLOTTESVILLE PA 375 GREENBRIER DR, CHARLOTTESVILLE, VA 22901 USA SN 1098-3511 J9 HEART SURG FORUM JI Heart Surg. Forum PD JUN PY 2005 VL 8 IS 3 BP E161 EP E166 DI 10.1532/HSF98.20041176 PG 6 WC Cardiac & Cardiovascular Systems; Surgery SC Cardiovascular System & Cardiology; Surgery GA 984WD UT WOS:000233336400009 PM 15870046 ER PT J AU Yahiro, K Shirasaka, D Tagashira, M Wada, A Morinaga, N Kuroda, F Choi, O Inoue, M Aoyama, N Ikeda, M Hirayama, T Moss, J Noda, M AF Yahiro, K Shirasaka, D Tagashira, M Wada, A Morinaga, N Kuroda, F Choi, O Inoue, M Aoyama, N Ikeda, M Hirayama, T Moss, J Noda, M TI Inhibitory effects of polyphenols on gastric injury by Helicobacter pylori VacA toxin SO HELICOBACTER LA English DT Article DE H. pylori; vacuolating cytotoxin; polyphenol ID PROTEIN-TYROSINE-PHOSPHATASE; VACUOLATING CYTOTOXIN; GREEN TEA; KAPPA-B; RECEPTOR; CELLS; ACTIVATION; BETA; PLEIOTROPHIN; EXPRESSION AB Background. Helicobacter pylori induces gastric damage and may be involved in the pathogenesis of gastric cancer. H. pylori-vacuolating cytotoxin, VacA, is one of the important virulence factors, and is responsible for H. pylori-induced gastritis and ulceration. The aim of this study is to assess whether several naturally occurring polyphenols inhibit VacA activities in vitro and in vivo. Materials and methods. Effects of polyphenols on VacA were quantified by the inhibition of: 1, vacuolation; 2, VacA binding to AZ-521 or G401 cells or its receptors; 3, VacA internalization. Effects of hop bract extract (HBT) containing high molecular weight polymerized catechin on VacA in vivo were investigated by quantifying gastric damage after oral administration of toxins to mice. Results. HBT had the strongest inhibitory activity among the polyphenols investigated. HBT inhibited, in a concentration-dependent manner: 1, VacA binding to its receptors, RPTP alpha and RPTP beta; 2, VacA uptake; 3, VacA-induced vacuolation in susceptible cells. In addition, oral administration of HBT with VacA to mice reduced VacA-induced gastric damage at 48 hours. In vitro, VacA formed a complex with HBT. Conclusions. HBT may suppress the development of inflammation and ulceration caused by H. pylori VacA, suggesting that HBT may be useful as a new type of therapeutic agent for the prevention of gastric ulcer and inflammation caused by VacA. C1 Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chiba 2608670, Japan. Kobe Univ, Sch Med, Dept Clin Mol Med, Div Diabet Digest & Kidney Dis, Kobe, Hyogo 650, Japan. Kobe Univ, Sch Med, Dept Endoscopy, Kobe, Hyogo 650, Japan. Asahi Brewery Co Ltd, Fundamental Res Lab, Midori Ku, Ibaraki, Japan. Nagasaki Univ, Inst Trop Med, Dept Bacteriol, Nagasaki 852, Japan. Japan Sci & Technol Corp, PRESTO, Saitama, Japan. NHLBI, Pulm & Crit Care Med Branch, NIH, Bethesda, MD 20892 USA. RP Noda, M (reprint author), Chiba Univ, Grad Sch Med, Dept Mol Infectiol, Chiba 2608670, Japan. EM noda@faculty.chiba-u.jp NR 38 TC 31 Z9 34 U1 0 U2 4 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 1083-4389 J9 HELICOBACTER JI Helicobacter PD JUN PY 2005 VL 10 IS 3 BP 231 EP 239 DI 10.1111/j.1523-5378.2005.00315.x PG 9 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA 927EM UT WOS:000229175200009 PM 15904481 ER PT J AU Cronin, DP Harlan, LC Clegg, LX Stevens, JL Yuan, GG Davis, TA AF Cronin, DP Harlan, LC Clegg, LX Stevens, JL Yuan, GG Davis, TA TI Patterns of care in a population-based random sample of patients diagnosed with non-Hodgkin's lymphoma SO HEMATOLOGICAL ONCOLOGY LA English DT Article DE non-Hodgkin's lymphoma; patterns of care; SEER program; chemotherapy; radiation ID BONE-MARROW-TRANSPLANTATION; HIGH-DOSE THERAPY; B-CELL LYMPHOMA; INTERMEDIATE-GRADE; ELDERLY-PATIENTS; FOLLICULAR LYMPHOMA; TREATMENT OUTCOMES; PHASE-II; CHEMOTHERAPY; SURVIVAL AB New therapies have enhanced treatment of non-Hodgkin's lymphoma (NHL), but extent of treatment use in community practice is unknown. We conducted a population-based study of NHL patients diagnosed in 1999 with histologically confirmed NHL (n = 947) residing in areas covered by the Surveillance, Epidemiology, and End Results program. We performed analyses to study factors associated with receipt of chemotherapy, radiation, and rituximab, and examine factors associated with mortality. Most patients presented with B-cell lymphoma (n = 828). Approximately 20% of patients received no therapy, over 60% received chemotherapy, and 12% received rituximab, alone or in combination. Patients aged 75 +, and males were less likely to have received chemotherapy (p = 0.01). There were no significant associations between receipt of rituximab and the factors analyzed. Patients who presented with B-symptoms or unknown B-symptom. status were less likely to receive radiation (OR = 0.32 and 0.47, respectively, p = 0.0002) than asymptomatic patients. Cause-specific and all-cause mortality were significantly associated with patient age, race/ethnicity, gender, marital status, co-morbid conditions, and histological subgroup. Hispanic and African-Americans, patients age 75 +, males, unmarried patients, or patients with B-symptoms had higher risk of death from NHL and all-cause (p < 0.01). This is the first population-based study examining therapy received for many histological subtypes of NHL. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Canc Registry Ireland, Cork, Ireland. NCI, Appl Res Program, DCCPS, Bethesda, MD 20892 USA. NCI, Surveillance Res Program, DCCPS, Bethesda, MD 20892 USA. NCI, CTEP, DCTD, Bethesda, MD 20892 USA. Informat Management Syst, Silver Spring, MD USA. RP Cronin, DP (reprint author), Canc Registry Ireland, Elm Court,Boreenmanna Rd, Cork, Ireland. EM d.cronin@ncri.ie FU NCI NIH HHS [N01-PC-35141, N01-PC-35136, N01-PC-35145, N01-PC-35139, N01-PC-35142, N01-PC-35138, N01-PC-35133, N01-PC-35137, N01-PC-35135, N01-PC-35143] NR 40 TC 24 Z9 24 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0278-0232 J9 HEMATOL ONCOL JI Hematol. Oncol. PD JUN PY 2005 VL 23 IS 2 BP 73 EP 81 DI 10.1002/hon.747 PG 9 WC Oncology; Hematology SC Oncology; Hematology GA 994PV UT WOS:000234044600006 PM 16170828 ER PT J AU Kleiner, DE Brunt, EM Van Natta, M Behling, C Contos, MJ Cummings, OW Ferrell, LD Liu, YC Torbenson, MS Unalp-Arida, A Yeh, M McCullough, AJ Sanyal, AJ AF Kleiner, DE Brunt, EM Van Natta, M Behling, C Contos, MJ Cummings, OW Ferrell, LD Liu, YC Torbenson, MS Unalp-Arida, A Yeh, M McCullough, AJ Sanyal, AJ CA Nonalcoholic Steatohepatitis Clin TI Design and validation of a histological scoring system for nonalcoholic fatty liver disease SO HEPATOLOGY LA English DT Article ID METABOLIC SYNDROME; UNITED-STATES; STEATOHEPATITIS; CHILDREN; LESIONS AB Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic steatosis in the absence of a history of significant alcohol use or other known liver disease. Nonalcoholic steatohepatitis (NASH) is the progressive form of NAFLD. The Pathology Committee of the NASH Clinical Research Network designed and validated a histological feature scoring system that addresses the full spectrum of lesions of NAFLD and proposed a NAFLD activity score (NAS) for use in clinical trials. The scoring system comprised 14 histological features, 4 of which were evaluated semi-quantitatively: steatosis (0-3), lobular inflammation (0-2), hepatocellular ballooning (0-2), and fibrosis (0-4). Another nine features were recorded as present or absent. An anonymized study set of 50 cases (32 from adult hepatology services, 18 from pediatric hepatology services) was assembled, coded, and circulated. For the validation study, agreement on scoring and a diagnostic categorization ("NASH," "borderline," or "not NASH") were evaluated by using weighted kappa statistics. Inter-rater agreement on adult cases was: 0.84 for fibrosis, 0.79 for steatosis, 0.56 for injury, and 0.45 for lobular inflammation. Agreement on diagnostic category was 0.61. Using multiple logistic regression, five features were independently associated with the diagnosis of NASH in adult biopsies: steatosis (P =.009), hepatocellular ballooning (P =.0001), lobular inflammation (P =.0001), fibrosis (P =.0001), and the absence of lipogranulomas (P =.001). The proposed NAS is the unweighted sum of steatosis, lobular inflammation, and hepatocellular ballooning scores. In conclusion, we present a strong scoring system and NAS for NAFLD and NASH with reasonable inter-rater reproducibility that should be useful for studies of both adults and children with any degree of NAFLD. NAS of >= 5 correlated with a diagnosis of NASH, and biopsies with scores of less than 3 were diagnosed as "not NASH." C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. St Louis Univ, Sch Med, Dept Pathol, Ctr Liver, St Louis, MO 63104 USA. Johns Hopkins Ctr Clin Trials, Baltimore, MD USA. Univ Calif San Diego, Dept Pathol, San Diego, CA 92103 USA. Virginia Commonwealth Univ, Dept Pathol, Richmond, VA USA. Univ Hosp, Dept Pathol, Indianapolis, IN USA. Univ Calif San Francisco, Dept Pathol, San Francisco, CA USA. Metrohlth Med Ctr, Dept Pathol, Cleveland, OH USA. Metrohlth Med Ctr, Div Gastroenterol, Cleveland, OH USA. Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. Univ Washington, Med Ctr, Dept Pathol, Seattle, WA 98195 USA. Virginia Commonwealth Univ, Med Ctr, Dept Internal Med, Div Internal Med,Div Gastroenterol, Richmond, VA USA. RP Kleiner, DE (reprint author), NCI, Pathol Lab, Bldg 10,Room 2N212,MSC 1516, Bethesda, MD 20892 USA. EM KleinerD@mail.nih.gov OI Kleiner, David/0000-0003-3442-4453 FU NHLBI NIH HHS [N01HR761019]; NIDDK NIH HHS [7U01DK061713, 1U01DK061718, 1U01DK061728, 1U01DK061731, 1U01DK061732, 1U01DK061734, 1U01DK061737, 1U01DK061738, 5U01DK061730, U01 DK061730] NR 27 TC 2933 Z9 3015 U1 38 U2 218 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2005 VL 41 IS 6 BP 1313 EP 1321 DI 10.1002/hep.20701 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931WX UT WOS:000229517300014 PM 15915461 ER PT J AU Stratakis, CA Marx, SJ AF Stratakis, CA Marx, SJ TI Multiple endocrine neoplasias in the era of translational medicine SO HORMONE AND METABOLIC RESEARCH LA English DT Editorial Material DE pituitary tumors; adrenal medulla; paraganglioma; hyperparathyroidism and jaw tumor syndrome; multiple endocrine neoplasia-type 1 ID MEDULLARY-THYROID CANCER; GERM-LINE MUTATIONS; PARATHYROID TUMORS; GENE-EXPRESSION; TYPE-1; GROWTH; HYPERPARATHYROIDISM; PHEOCHROMOCYTOMA; PARAGANGLIOMA; METHYLATION AB Medicine is an ever changing art, continuously adjusting to the shifting principles of philosophy and constant discoveries of science; it was beautifully said by Hippocrates: "... medicine does not do the same thing at this moment and the next..." Unabated dissemination of information is the only way that patients are assured that physicians will continue to practice medicine that reflects contemporary science. In the field of Multiple Endocrine Neoplasias (MENs), this is at least in part accomplished by biennially held International Workshops. The articles led by this editorial are the second and last installment of a collection of stateof-the-art presentations given in the course of the ninth such workshop that was held in Bethesda, MD, June 19-22, 2004. In addition to serving as an introduction to the articles that were written by some of the leaders in the field, the text of the editorial review that follows also supports the notion that MENs are poised to lead translational research in endocrinology: these disorders have benefited remarkably from the discoveries of the human genome project and are at a unique position to take advantage of new modalities in basic and clinical science. C1 NICHD, Sect Endocrinol & Genet, DEB, NIH, Bethesda, MD 20892 USA. NIDDK, Metab Dis Branch, NIH, Bethesda, MD USA. RP Stratakis, CA (reprint author), NICHD, Sect Endocrinol & Genet, DEB, NIH, Bldg 10,CRC,Room 1-1330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov NR 41 TC 9 Z9 9 U1 0 U2 1 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUN PY 2005 VL 37 IS 6 BP 343 EP 346 DI 10.1055/s-870183 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 948AH UT WOS:000230687900001 PM 16001325 ER PT J AU Agarwal, SK Kennedy, PA Scacheri, PC Novotny, EA Hickman, AB Cerrato, A Rice, TS Moore, JB Rao, S Ji, Y Mateo, C Libutti, SK Oliver, B Chandrasekharappa, SC Burns, AL Collins, FS Spiegel, AM Marx, SJ AF Agarwal, SK Kennedy, PA Scacheri, PC Novotny, EA Hickman, AB Cerrato, A Rice, TS Moore, JB Rao, S Ji, Y Mateo, C Libutti, SK Oliver, B Chandrasekharappa, SC Burns, AL Collins, FS Spiegel, AM Marx, SJ TI Menin molecular interactions: Insights into normal functions and tumorigenesis SO HORMONE AND METABOLIC RESEARCH LA English DT Review DE MEN1; JunD; MLL; Hox genes; tumor suppressor; oncogene; multiple endocrine neoplasia; transcription; partners ID MULTIPLE ENDOCRINE NEOPLASIA; HISTONE METHYLTRANSFERASE COMPLEX; JUND-ACTIVATED TRANSCRIPTION; METASTASIS SUPPRESSOR NM23; TYPE-1 GENE-PRODUCT; TUMOR-SUPPRESSOR; AP-1 TRANSACTIVATION; MISSENSE MUTANTS; PAF1 COMPLEX; CELL-GROWTH AB Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant disease predisposed by heterozygous germline mutations in the MEN1 tumor suppressor gene. Biallelic loss of MEN1 resulting from small mutation and/or loss of heterozygosity occurs in a large tissue spectrum of MEN1 tumors or non-hereditary tumors. Mouse models of MEN1 underexpression or overexpression have also supported the tumor-suppressor effect of the MEN1 gene. Menin, the 610-amino-acid protein encoded by MEN1, is expressed ubiquitously and found predominantly in the nucleus. Sequence analyses do not reveal motifs of known function other than two nuclear localization sequences. Menin has been found to partner in vitro with a variety of proteins that comprise transcription factors, DNA processing factors, DNA repair proteins, and cytoskeletal proteins. The diverse functions of menin interactors suggest roles for menin in multiple biological pathways. Inactivation of menin switches its JunD partner from a downstream action of growth suppression to growth promotion. This is a plausible mechanism for menin tumorigenesis. C1 NIDDKD, NIH, Bethesda, MD 20892 USA. NHGRI, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NIDCD, NIH, Bethesda, MD USA. RP Agarwal, SK (reprint author), NIDDKD, NIH, Bldg 10,Room 9C-101,9000 Rockville Pike, Bethesda, MD 20892 USA. EM SunitaA@intra.niddk.nih.gov RI Moore, J Bernadette/D-5258-2012; Agarwal, Sunita/D-1428-2016; OI Agarwal, Sunita/0000-0002-7557-3191; Moore, J Bernadette/0000-0003-4750-1550 NR 57 TC 74 Z9 76 U1 1 U2 8 PU GEORG THIEME VERLAG KG PI STUTTGART PA RUDIGERSTR 14, D-70469 STUTTGART, GERMANY SN 0018-5043 J9 HORM METAB RES JI Horm. Metab. Res. PD JUN PY 2005 VL 37 IS 6 BP 369 EP 374 DI 10.1055/s-870139 PG 6 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 948AH UT WOS:000230687900005 PM 16001329 ER PT J AU Scordalakes, EM Yue, CM Mutsuga, N Gainer, H AF Scordalakes, EM Yue, CM Mutsuga, N Gainer, H TI In situ hybridization analysis of changes in heteronuclear oxytocin and vasopressm RNA during lactation and the estrous cycle in the rat hypothalamus SO HORMONES AND BEHAVIOR LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Behavioral-Neuroendocrinology CY JUN 22-25, 2005 CL Univ Texas Austin, Austin, TX SP Soc Behav Neuroendocrinol HO Univ Texas Austin C1 NINDS, Mol Neurosci Sect, 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 0018-506X J9 HORM BEHAV JI Horm. Behav. PD JUN PY 2005 VL 48 IS 1 MA 216 BP 127 EP 127 PG 1 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA 934KR UT WOS:000229708200224 ER PT J AU Temple, JL Laing, ED Wray, S AF Temple, JL Laing, ED Wray, S TI Estrogen acts directly on GnRH-1 neurons to increase activity and synchronization SO HORMONES AND BEHAVIOR LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Behavioral-Neuroendocrinology CY JUN 22-25, 2005 CL Univ Texas Austin, Austin, TX SP Soc Behav Neuroendocrinol HO Univ Texas Austin C1 NINDS, Cellular & Dev Neurobiol Sect, 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 0018-506X J9 HORM BEHAV JI Horm. Behav. PD JUN PY 2005 VL 48 IS 1 MA 230 BP 130 EP 131 PG 2 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA 934KR UT WOS:000229708200238 ER PT J AU Wersinger, SR Young, WS Hu, SB Caldwell, H AF Wersinger, SR Young, WS Hu, SB Caldwell, H TI The vasopressin 1b receptor gene, but not the vasopressin 1a receptor gene, is essential for social aggression in mice SO HORMONES AND BEHAVIOR LA English DT Meeting Abstract CT 9th Annual Meeting of the Society-for-Behavioral-Neuroendocrinology CY JUN 22-25, 2005 CL Univ Texas Austin, Austin, TX SP Soc Behav Neuroendocrinol HO Univ Texas Austin C1 SUNY Buffalo, Buffalo, NY 14260 USA. NIMH, Sect Neural Gent Express, NIH, DHHS, Bethesda, MD 20892 USA. NIMH, Clin Neuroendocrinol Branch, NIH, DHHS, Bethesda, MD 20892 USA. RI Young, W Scott/A-9333-2009 OI Young, W Scott/0000-0001-6614-5112 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 0018-506X J9 HORM BEHAV JI Horm. Behav. PD JUN PY 2005 VL 48 IS 1 MA 245 BP 134 EP 134 PG 1 WC Behavioral Sciences; Endocrinology & Metabolism SC Behavioral Sciences; Endocrinology & Metabolism GA 934KR UT WOS:000229708200253 ER PT J AU Koh, KK Quon, MJ Han, SH Ahn, JY Jin, DK Kim, HS Kim, DS Shin, EK AF Koh, KK Quon, MJ Han, SH Ahn, JY Jin, DK Kim, HS Kim, DS Shin, EK TI Vascular and metabolic effects of combined therapy with ramipril and simvastatin in patients with type 2 diabetes SO HYPERTENSION LA English DT Article; Proceedings Paper CT 77th Scientific Meeting of the American-Heart-Association CY NOV 07-10, 2004 CL New Orleans, LA SP Amer Heart Assoc DE angiotensin-converting enzyme; diabetes mellitus; endothelium; insulin resistance; statins ID SMOOTH-MUSCLE-CELLS; RANDOMIZED CONTROLLED-TRIAL; CORONARY-ARTERY-DISEASE; ANGIOTENSIN-II; INSULIN SENSITIVITY; HYPERTENSIVE PATIENTS; HYPERCHOLESTEROLEMIC PATIENTS; ADIPONECTIN; EXPRESSION; RESISTANCE AB Mechanisms underlying biological effects of statin and angiotensin-converting enzyme inhibitor therapies differ. Therefore, we compared vascular and metabolic responses to these therapies either alone or in combination in patients with type 2 diabetes. This was a randomized, double-blind, placebo-controlled crossover trial with 3 treatment arms ( each 2 months) and 2 washout periods ( each 2 months). Fifty patients with type 2 diabetes were given simvastatin 20 mg and placebo, simvastatin 20 mg and ramipril 10 mg, or ramipril 10 mg and placebo daily during each 2-month treatment period. Ramipril alone or combined therapy significantly reduced blood pressure when compared with simvastatin alone. When compared with ramipril alone, simvastatin alone or combined therapy significantly improved the lipoprotein profile. All 3 treatment arms significantly improved flow-mediated dilator response to hyperemia and reduced plasma levels of malondialdehyde relative to baseline measurements. However, these parameters were changed to a greater extent with combined therapy when compared with simvastatin or ramipril alone ( P < 0.001 by ANOVA). When compared with simvastatin or ramipril alone, combined therapy significantly reduced high-sensitivity C-reactive protein levels ( P = 0.004 by ANOVA). Interestingly, combined therapy or ramipril alone significantly increased plasma adiponectin levels and insulin sensitivity relative to baseline measurements. These changes were significantly greater than in the group treated with simvastatin alone ( P < 0.015 by ANOVA). Ramipril combined with simvastatin had beneficial vascular and metabolic effects when compared with monotherapy in patients with type 2 diabetes. C1 Gachon Med Sch, Dept Cardiol, Inchon 405760, South Korea. Gachon Med Sch, Dept Lab Med, Inchon 405760, South Korea. Gachon Med Sch, Dept Radiol, Inchon 405760, South Korea. Gachon Med Sch, Dept Prevent Med Biostat, Inchon 405760, South Korea. NIH, Clin Invest Lab, Natl Ctr Complimentary & Alternat Med, Bethesda, MD 20892 USA. RP Koh, KK (reprint author), Gachon Med Sch, Gil Heart Ctr, Vasc Med & Atherosclerosis Unit, 1198 Kuwol Dong, Inchon 405760, South Korea. EM kwangk@ghil.com RI Quon, Michael/B-1970-2008; OI Quon, Michael/0000-0002-9601-9915; Quon , Michael /0000-0002-5289-3707 NR 34 TC 105 Z9 109 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 JUN PY 2005 VL 45 IS 6 BP 1088 EP 1093 DI 10.1161/01.HYP.0000166722.91714.ba PG 6 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 930DS UT WOS:000229396600012 PM 15883229 ER PT J AU Kawada, N Solis, G Ivey, N Connors, S Dennehy, K Modlinger, P Hamel, R Kawada, JT Imai, E Langenbach, R Welch, WJ Wilcox, CS AF Kawada, N Solis, G Ivey, N Connors, S Dennehy, K Modlinger, P Hamel, R Kawada, JT Imai, E Langenbach, R Welch, WJ Wilcox, CS TI Cyclooxygenase-1-deficient mice have high sleep-to-wake blood pressure ratios and renal vasoconstriction SO HYPERTENSION LA English DT Article DE hypertension; nitric oxide; prostaglandins; renal circulation; sympathetic nervous activity ID NITRIC-OXIDE SYNTHESIS; ENDOTHELIAL-CELLS; ANGIOTENSIN-II; HYPERTENSION; ACTIVATION; EXPRESSION; KIDNEY; GENE; PROSTAGLANDINS; RESTRICTION AB We used cyclooxygenase-1 (COX-1)-deficient mice to test the hypothesis that COX-1 regulates blood pressure (BP) and renal hemodynamics. The awake time (AT) mean arterial pressures (MAPs) measured by telemetry were not different between COX-1(+/+) and COX-1(-/-) (131+/-2 versus 126+/-3 mm Hg; NS). However, COX-1(-/-) had higher sleep time (ST) MAP (93+/-1 versus 97+/-2 mm Hg; P<0.05) and sleep-to-awake BP ratio (+8.6%; P<0.05). Under anesthesia with moderate sodium loading, COX-1(-/-) had higher MAP (109+/-5 versus 124+/-4 mm Hg; P<0.05), renal vascular resistance (23.5+/-1.6 versus 30.7+/-1.7 mm Hg . mL(-1) . min(-1) . g(-1); P<0.05) and filtration fraction (33.7+/-2.1 versus 40.2+/-2.0%; P<0.05). COX-1(-/-) had a 89% reduction (P<0.0001) in the excretion of TxB(2), a 76% reduction (P<0.01) in PGE(2), a 40% reduction (P<0.0002) in 6-ketoPGF(1 alpha) (6keto), a 27% reduction (P<0.02) in 11-beta PGF(2 alpha) (11 beta), a 35% reduction (P<0.01) in nitrate plus nitrite (NOx), and a 52% increase in metanephrine (P<0.02). The excretion of normetanephrine, a marker for sympathetic nervous activity, was reduced during ST in COX-1(+/+) (6.9+/-0.9 versus 3.2+/-0.6 g . g(-1) creatinine . 10(-3); P<0.01). This was blunted in COX-1(-/-) (5.1+/-0.9 versus 4.9+/-0.7 g . g(-1) creatinine . 10(-3); NS). Urine collection during ST showed lower excretion of 6keto, 11 beta, NOx, aldosterone, sodium, and potassium than during AT in both COX-1(+/+) and COX-1(-/-), and there were positive correlations among these parameters (6keto versus NOx; P<0.005; 11 beta versus NOx; P<0.005; and NOx versus sodium; P<0.005). In conclusion, COX-1 mediates a suppressed sympathetic nervous activity and enhanced NO, which may contribute to renal vasodilatation and a reduced MAP while asleep or under anesthesia. COX-1 contributes to the normal nocturnal BP dipping phenomenon. C1 Georgetown Univ, Med Ctr, Div Nephrol & Hypertens, Washington, DC 20007 USA. Georgetown Univ, Cardiovasc Kidney Inst, Washington, DC USA. Osaka Univ, Grad Sch Med, Div Nephrol, Osaka, Japan. NIEHS, Comparat Med Branch, NIH, Res Triangle Pk, NC 27709 USA. RP Wilcox, CS (reprint author), Georgetown Univ, Med Ctr, Div Nephrol & Hypertens, 3800 Reservoir Rd NW,PHCF6003, Washington, DC 20007 USA. EM wilcoxch@georgetown.edu FU NHLBI NIH HHS [HL-68686]; NIDDK NIH HHS [DK-49870, DK-36079] NR 37 TC 20 Z9 20 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0194-911X J9 HYPERTENSION JI Hypertension PD JUN PY 2005 VL 45 IS 6 BP 1131 EP 1138 DI 10.1161/01.HYP.0000166141.69081.80 PG 8 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 930DS UT WOS:000229396600019 PM 15883230 ER PT J AU Amyot, F Camphausen, K Siavosh, A Sackett, D Gandjbakhche, A AF Amyot, F Camphausen, K Siavosh, A Sackett, D Gandjbakhche, A TI Quantitative method to study the network formation of endothelial cells in response to tumor angiogenic factors SO IEE PROCEEDINGS SYSTEMS BIOLOGY LA English DT Article ID DIFFUSION-LIMITED AGGREGATION; CAPILLARY-LIKE STRUCTURES; SHEAR-STRESS; BASEMENT-MEMBRANE; IN-VITRO; DIFFERENTIATION; CLUSTERS; MATRICES; LAMININ; INVITRO AB To study the network formation of endothelial cells (ECs) in an extracellular matrix (ECM) environment, we have devised an EC aggregation-type model based on a diffusion limited cluster aggregation model (DLCA), where clusters of particles diffuse and stick together upon contact. We use this model to quantify EC differentiation into cord-like structures by comparing experimental and simulation data. Approximations made with the DLCA model, when combined with experimental kinetics and cell concentration results, not only allow us to quantify cell differentiation by a pseudo diffusion coefficient, but also measure the effects of tumor angiogenic factors (TAFs) on the formation of cord-like structures by ECs. We have tested Our model by using an in vitro assay, where we record EC aggregation by analysing time-lapse images that provide us with the evolution of the fractal dimension measure through time. We performed these experiments for various cell concentrations and TAFs (e.g. EVG, FGF-b, and VEGF). During the first six hours of an experiment, ECs aggregate quickly. The value of the measured fractal dimension decreases with time until reaching an asymptotic value that depends solely on the EC concentration. In contrast, the kinetics depend on the nature of TAFs. The experimental and simulation results correlate with each other in regards to the fractal dimension and kinetics, allowing us to quantify the influence of each TAF by a pseudo diffusion coefficient. We have shown that the shape, kinetic aggregation, and fractal dimension of the EC aggregates fit into an in vitro model capable of reproducing the first stage of angiogenesis. We conclude that the DLCA model, combined with experimental results, is a highly effective assay for the quantification of the kinetics and network characteristics of ECs embedded in ECM proteins. Finally, we present a new method that can be used for studying the effect of angiogenic drugs in in vitro assays. C1 NICHHD, Sect Biomed Stochast Phys, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. NCI, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Amyot, F (reprint author), NICHHD, Sect Biomed Stochast Phys, Lab Integrat & Med Biophys, NIH, 9 South Dr, Bethesda, MD 20892 USA. EM amyotf@mail.nih.gov NR 25 TC 6 Z9 6 U1 1 U2 2 PU INST ENGINEERING TECHNOLOGY-IET PI HERTFORD PA MICHAEL FARADAY HOUSE SIX HILLS WAY STEVENAGE, HERTFORD SG1 2AY, ENGLAND SN 1741-2471 J9 IEE P SYST BIOL JI IEE Proc. Syst. Biol. PD JUN PY 2005 VL 152 IS 2 BP 61 EP 66 DI 10.1049/ip-sb:20045036 PG 6 WC Cell Biology; Mathematical & Computational Biology SC Cell Biology; Mathematical & Computational Biology GA 972VV UT WOS:000232482200003 ER PT J AU Yao, RT Seidel, J Liow, JS Green, MV AF Yao, RT Seidel, J Liow, JS Green, MV TI Attenuation correction for the NIH ATLAS small animal PET scanner SO IEEE TRANSACTIONS ON NUCLEAR SCIENCE LA English DT Article DE attenuation correction; computed tomography (CT); dual modality; imaging; positron emission tomography (PET); small animal imaging AB We evaluated an analytic attenuation correction method for the National Institutes of Health (NIH) Advanced Technology Laboratory Animal Scanner (ATLAS) small animal positron emission tomography (PET) scanner. This method is based on the body outline of emission images and an average empirical p (linear attenuation coefficient) value. We evaluated this method using a computed tomography (CT)-based attenuation correction (ACs) as the "gold standard." A specially fabricated attenuation calibration phantom with cylindrical inserts that mimic different body tissues was used to derive the relationship to convert CT values to mu for PET. The methods were applied to three test data sets: 1) a uniform cylinder phantom, 2) the attenuation calibration phantom, and 3) a mouse injected with [F-18]FDG. CT-based correction achieved activity restorations expected for all three data sets. The analytic method showed similar correction factors for the cylinder phantom and the mouse for which the attenuation medium volume matches the detectable emission source distribution. The correction factor for the attenuation calibration phantom was smaller because the emission image outline underestimated the attenuation medium volume. C1 SUNY Buffalo, Dept Nucl Med, Buffalo, NY 14214 USA. NIH, Dept Nucl Med, Ctr Clin, Rockville, MD 20852 USA. NIMH, Mol Imaging Branch, NIH, Rockville, MD 20852 USA. RP Yao, RT (reprint author), SUNY Buffalo, Dept Nucl Med, Buffalo, NY 14214 USA. EM rutaoyao@buffalo.edu; jurgen_seidel@nih.gov; liowj@intra.nimh.nih.gov; mgreen@cc.nih.gov NR 7 TC 11 Z9 11 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9499 J9 IEEE T NUCL SCI JI IEEE Trans. Nucl. Sci. PD JUN PY 2005 VL 52 IS 3 BP 664 EP 668 DI 10.1109/TNS.2005.851467 PN 1 PG 5 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA 949DX UT WOS:000230766200015 ER PT J AU Egawa, T Eberl, G Taniuchi, I Benlagha, K Geissmann, F Hennighausen, L Bendelac, A Littman, DR AF Egawa, T Eberl, G Taniuchi, I Benlagha, K Geissmann, F Hennighausen, L Bendelac, A Littman, DR TI Genetic evidence supporting selection of the V alpha 14i NKT cell lineage from double-positive thymocyte precursors SO IMMUNITY LA English DT Article ID NF-KAPPA-B; T-LYMPHOCYTE DEVELOPMENT; NATURAL-KILLER; CUTTING EDGE; ROR-GAMMA; MEMBRANE LYMPHOTOXIN; MICE; EXPRESSION; THYMUS; REQUIREMENT AB Invariant V alpha 14i NKT (iNKT) cells are a specialized subset of T lymphocytes with regulatory functions. They coexpress TCR alpha beta and natural killer cell markers. They differentiate through interaction of their V alpha 14-J alpha 18 invariant TCR alpha chains with CD1d expressed on double-positive (DP) thymocytes. Although their development has been shown to be thymus dependent, their developmental pathway has not been definitively established. By using genetic analyses, we show here that all iNKT cells are selected from a pool of DP thymocytes. Their development is absolutely dependent on Runx1 and ROR gamma t, transcription factors that influence, but are not required for, development of conventional T cells. Our results indicate that even though CD1d binding DP thymocytes have yet to be observed, V alpha 14-J alpha 18 rearrangement in these cells is required for development of iNKT cells. C1 NYU, Sch Med, Skirball Inst Biomol Med, Mol Pathogenesis Program, New York, NY 10016 USA. NYU, Sch Med, Skirball Inst Biomol Med, Howard Hughes Med Inst, New York, NY 10016 USA. Univ Chicago, Dept Pathol, Chicago, IL 60637 USA. NIDDKD, Lab Genet & Physiol, NIH, Bethesda, MD 20892 USA. RP Littman, DR (reprint author), NYU, Sch Med, Skirball Inst Biomol Med, Mol Pathogenesis Program, 540 1st Ave, New York, NY 10016 USA. EM littman@saturn.med.nyu.edu RI Taniuchi, Ichiro/N-6399-2015; Benlagha, Kamel/I-5035-2016 OI Taniuchi, Ichiro/0000-0002-9853-9068; NR 52 TC 151 Z9 156 U1 0 U2 5 PU CELL PRESS PI CAMBRIDGE PA 1100 MASSACHUSETTS AVE, CAMBRIDGE, MA 02138 USA SN 1074-7613 J9 IMMUNITY JI Immunity PD JUN PY 2005 VL 22 IS 6 BP 705 EP 716 DI 10.1016/j.immuni.2005.03.011 PG 12 WC Immunology SC Immunology GA 940XX UT WOS:000230180300008 PM 15963785 ER PT J AU Taub, DD Longo, DL AF Taub, DD Longo, DL TI Insights into thymic aging and regeneration SO IMMUNOLOGICAL REVIEWS LA English DT Review ID T-CELL-RECEPTOR; AGE-RELATED-CHANGES; GONADOTROPIN-RELEASING-HORMONE; HUMAN GROWTH-HORMONE; BONE-MARROW-TRANSPLANTATION; LEUKEMIA INHIBITORY FACTOR; II-TRANSGENIC MICE; OUTBRED NMRI MICE; IMMUNE-SYSTEM; CALORIC RESTRICTION AB The deterioration of the immune system with progressive aging is believed to contribute to morbidity and mortality in elderly humans due to the increased incidence of infection, autoimmunity, and cancer. Dysregulation of T-cell function is thought to play a critical part in these processes. One of the consequences of an aging immune system is the process termed thymic involution, where the thymus undergoes a progressive reduction in size due to profound changes in its anatomy associated with loss of thymic epithelial cells and a decrease in thymopoiesis. This decline in the output of newly developed T cells results in diminished numbers of circulating naive T cells and impaired cell-mediated immunity. A number of theories have been forwarded to explain this 'thymic menopause' including the possible loss of thymic progenitors or epithelial cells, a diminished capacity to rearrange T-cell receptor genes and alterations in the production of growth factors and hormones. Although to date no interventions fully restore thymic function in the aging host, systemic administration of various cytokines and hormones or bone marrow transplantation have resulted in increased thymic activity and T-cell output with age. In this review, we shall examine the current literature on thymic involution and discuss several interventional strategies currently being explored to restore thymic function in elderly subjects. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. RP Longo, DL (reprint author), NIA, Immunol Lab, NIH, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM longod@grc.nia.nih.gov NR 191 TC 191 Z9 200 U1 0 U2 10 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2005 VL 205 BP 72 EP 93 DI 10.1111/j.0105-2896.2005.00275.x PG 22 WC Immunology SC Immunology GA 924JY UT WOS:000228976300007 PM 15882346 ER PT J AU Hathcock, KS Chiang, YJ Hodes, RJ AF Hathcock, KS Chiang, YJ Hodes, RJ TI In vivo regulation of telomerase activity and telomere length SO IMMUNOLOGICAL REVIEWS LA English DT Review ID T-CELL; REVERSE-TRANSCRIPTASE; MOUSE TELOMERASE; DYSKERATOSIS-CONGENITA; CATALYTIC SUBUNIT; DEFICIENT MICE; RNA COMPONENT; CUTTING EDGE; HUMAN CANCER; ACTIVATION AB Telomeres are specialized DNA-protein structures found at the ends of all linear chromosomes. In mammalian cells, they consist of hexanucleotide (TTAGGG) repeats and multiple associated proteins. Telomeres protect the ends of chromosomes and prevent their recognition as DNA breaks. Loss of functional telomere length below a critical threshold can activate programs leading to cell senescence or death. Telomere length represents a balance between the loss of terminal telomeric repeats, which occurs during cell division with incomplete DNA replication, and the addition of telomeric repeats by the unique RNA-dependent DNA polymerase telomerase. Although most somatic cells do not express telomerase, telomerase is induced in lymphocytes at critical stages of development and activation. Telomerase expression thus may prolong the replicative capacity of lymphocytes and thereby enhance their function in immune responses. We have used murine model systems to address two broadly defined questions about lymphocyte telomere biology: how is telomerase physiologically regulated in T cells responding to antigen challenge, and what is the effect of transcriptionally altered telomerase expression on telomere length and, consequently, on immune function? C1 NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. NIA, Bethesda, MD 20892 USA. RP Hathcock, KS (reprint author), NCI, Expt Immunol Branch, Bldg 10,Room 4B10,10 Ctr Dr, Bethesda, MD 20892 USA. EM hathcock@mail.nih.gov NR 57 TC 38 Z9 40 U1 0 U2 2 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2005 VL 205 BP 104 EP 113 DI 10.1111/j.0105-2896.2005.00267.x PG 10 WC Immunology SC Immunology GA 924JY UT WOS:000228976300009 PM 15882348 ER PT J AU Fann, M Chiu, WK Wood, WH Levine, BL Becker, KG Weng, NP AF Fann, M Chiu, WK Wood, WH Levine, BL Becker, KG Weng, NP TI Gene expression characteristics of CD28(null) memory phenotype CD8(+) T cells and its implication in T-cell aging SO IMMUNOLOGICAL REVIEWS LA English DT Review ID NATURAL-KILLER-CELLS; IN-VIVO; CD28 EXPRESSION; INHIBITORY RECEPTORS; MOLECULAR CHARACTERIZATION; REPLICATIVE SENESCENCE; MEDIATED CYTOTOXICITY; TRANSCRIPTION FACTOR; SIGNAL-TRANSDUCTION; HUMAN-LYMPHOCYTES AB Accumulation of CD28(null)CD8(+) T cells is considered as one of the hallmarks of aging in the human immune system. However, the precise changes of CD28(null)CD8(+) T cells, compared to those of the precursor CD28(+)CD8(+) memory T cells, have not been determined. In this study, we present an analysis of the global gene expression profiles of CD28(+) and CD28(null) memory phenotype CD8(+) T cells. These two CD8(+) T subsets exhibited an overall similar gene expression profile with only a few dozen genes that were differentially expressed. A wide range of functions, including co-stimulation, effector activity, signaling, and transcription, were possessed by these differentially expressed genes, reflecting significant functional changes of CD28(null) memory phenotype CD8(+) T cells from their CD28(+) counterparts. In addition, CD28(null) memory CD8(+) T cells expressed several natural killer cell receptors and high levels of granzymes, perforin, and FasL, indicating an increasing capacity for cytotoxicity during memory CD8(+) T-cell aging. Interestingly, in vitro culture of these two subsets with interleukin-15 showed that similar gene expression changes occurred in both subsets. Our analysis provides the gene expression portraits of CD28(null) memory phenotype CD8(+) T cells and alteration from their CD28(+) counterparts and suggests potential mechanisms of T-cell aging. C1 NIA, Immunol Lab, NIH, Baltimore, MD 21224 USA. NIA, Gene Express & Genom Unit, NIH, Baltimore, MD 21224 USA. Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Weng, NP (reprint author), NIA, Immunol Lab, NIH, 5600 Nathan Shock Dr,Box 21, Baltimore, MD 21224 USA. EM wengn@grc.nia.nih.gov RI Levine, Bruce/D-1688-2009; OI Becker, Kevin/0000-0002-6794-6656 NR 124 TC 45 Z9 45 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 0105-2896 J9 IMMUNOL REV JI Immunol. Rev. PD JUN PY 2005 VL 205 BP 190 EP 206 DI 10.1111/j.0105-2896.2005.00262.x PG 17 WC Immunology SC Immunology GA 924JY UT WOS:000228976300015 PM 15882354 ER PT J AU Butcher, BA Greene, RI Henry, SC Annecharico, KL Weinberg, JB Denkers, EY Sher, A Taylor, GA AF Butcher, BA Greene, RI Henry, SC Annecharico, KL Weinberg, JB Denkers, EY Sher, A Taylor, GA TI p47 GTPases regulate Toxoplasma gondii survival in activated macrophages SO INFECTION AND IMMUNITY LA English DT Article ID INDUCIBLY EXPRESSED GTPASE; IFN-GAMMA; INTERFERON-GAMMA; ENDOPLASMIC-RETICULUM; PERITONEAL-MACROPHAGES; HOST-RESISTANCE; BINDING PROTEIN; 47-KDA GTPASE; GENE; LRG-47 AB The cytokine gamma interferon (IFN-gamma) is critical for resistance to Toxoplasma gondii. IFN-gamma strongly activates macrophages and nonphagocytic host cells to limit intracellular growth of T. gondii; however, the cellular factors that are required for this effect are largely unknown. We have shown previously that IGTP and LRG-47, members of the IFN-gamma-regulated family of p47 GTPases, are required for resistance to acute T. gondii infections in vivo. In contrast, IRG-47, another member of this family, is not required. In the present work, we addressed whether these GTPases are required for IFN-gamma-induced suppression of T. gondii growth in macrophages in vitro. Bone marrow macrophages that lacked IGTP or LRG-47 displayed greatly attenuated IFN-gamma-induced inhibition of T. gondii growth, while macrophages that lacked IRG-47 displayed normal inhibition. Thus, the ability of the p47 GTPases to limit acute infection in vivo correlated with their ability to suppress intracellular growth in macrophages in vitro. Using confocal microscopy and sucrose density fractionation, we demonstrated that IGTP largely colocalizes with endoplasmic reticulum markers, while LRG-47 was mainly restricted to the Golgi. Although both IGTP and LRG-47 localized to vacuoles containing latex beads, neither protein localized to vacuoles containing live T. gondii. These results suggest that IGTP and LRG-47 are able to regulate host resistance to acute T. gondii infections through their ability to inhibit parasite growth within the macrophage. C1 VA Med Ctr, Geriatr Res Educ & Clin Ctr, Durham, NC 27705 USA. Cornell Univ, Coll Vet Med, Dept Microbiol & Immunol, Ithaca, NY 14853 USA. Duke Univ, Ctr Med, Dept Med, Div Geriatr, Durham, NC USA. Duke Univ, Ctr Med, Dept Immunol, Durham, NC USA. Duke Univ, Ctr Med, Ctr Study Aging & Human Dev, Durham, NC USA. Duke Univ, Dept Med, Div Hematol, Durham, NC USA. NIAID, Immunobiol Sect, Lab Parasit Dis, NIH, Bethesda, MD 20892 USA. RP Taylor, GA (reprint author), VA Med Ctr, Geriatr Res Educ & Clin Ctr, 508 Fulton St, Durham, NC 27705 USA. EM gregory.taylor@duke.edu FU NIAID NIH HHS [AI 50617, AI 57831, R01 AI050617, R01 AI057831] NR 30 TC 84 Z9 88 U1 0 U2 5 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 JUN PY 2005 VL 73 IS 6 BP 3278 EP 3286 DI 10.1128/IAI.73.6.3278-3286.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 931LD UT WOS:000229485900009 PM 15908352 ER PT J AU Sasisekhar, B Aparna, M Augustin, DJ Kaliraj, P Kar, SK Nutman, TB Narayanan, RB AF Sasisekhar, B Aparna, M Augustin, DJ Kaliraj, P Kar, SK Nutman, TB Narayanan, RB TI Diminished monocyte function in microfilaremic patients with lymphatic filariasis and its relationship to altered lymphoproliferative responses SO INFECTION AND IMMUNITY LA English DT Article ID INTERLEUKIN-1 RECEPTOR ANTAGONIST; HUMAN DENDRITIC CELLS; CD4(+) T-CELLS; BRUGIA-MALAYI; BANCROFTIAN FILARIASIS; IMMUNE-RESPONSES; CYTOKINE PRODUCTION; IFN-GAMMA; IN-VIVO; ANTIGENS AB Antigen-specific hyporesponsiveness to filarial antigens is a phenomenon observed in patent infection with lymph-dwelling filarial parasites of humans. This phenomenon has been attributed to a multitude of factors, one of which is altered monocyte function. To examine the role played by monocytes in filarial infection, we assessed the responses of monocytes obtained from normal and filarial parasite-infected individuals to both crude filarial antigen and purified recombinant filarial antigen WbSXP-1 and attempted to relate these to the altered lymphoproliferative responses seen in filarial infection. Monocytes from microfilaremic (MF) patients demonstrated an inability to respond to lipopolysaccharide compared to monocytes from endemic normal persons or from lymphedema patients. Indeed, interleukin 1 beta (IL-1 beta) production was severely limited, a finding that did not extend to monocyte responses to filarial antigens. Serum from MF patients reduced adherence and spreading of normal monocytes, a finding not seen with serum from the other clinical groups. Interestingly, there was a significant correlation between the production of IL-1 beta and adherence. Moreover, the levels of spontaneous production of IL-1 beta correlated with high levels of spontaneous secretion of IL-10. The effects observed were not a result of diminished viability or alteration in the expression of the cell surface markers CD14 and HLA-DR. These data suggest that monocyte function is dampened in MF patients, a finding which could alter lymphoproliferative responses during patent infection. C1 Anna Univ, Ctr Biotechnol, Madras 600025, Tamil Nadu, India. Govt Tamil Nadu, Dept Publ Hlth & Prevent Med, Madras, Tamil Nadu, India. Jawaharlal Nehru Univ, Ctr Biotechnol, New Delhi 110067, India. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Narayanan, RB (reprint author), Anna Univ, Ctr Biotechnol, Madras 600025, Tamil Nadu, India. EM rbn@annauniv.edu RI Kar, Santosh/B-8227-2009; Kar, Santosh/J-5334-2012 NR 54 TC 25 Z9 26 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 JUN PY 2005 VL 73 IS 6 BP 3385 EP 3393 DI 10.1128/IAI.73.6.3385-3393.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 931LD UT WOS:000229485900022 PM 15908365 ER PT J AU Babu, S Kumaraswami, V Nutman, TB AF Babu, S Kumaraswami, V Nutman, TB TI Transcriptional control of impaired Th1 responses in patent lymphatic filariasis by T-box expressed in T cells and suppressor of cytokine signaling genes SO INFECTION AND IMMUNITY LA English DT Article ID PARASITE-SPECIFIC ANERGY; IFN-GAMMA PRODUCTION; LINEAGE COMMITMENT; WUCHERERIA-BANCROFTI; IMMUNE-RESPONSE; GATA-3; MAINTENANCE; POLARIZATION; INFECTIONS; INDUCTION AB T-bet (T-box expressed in T cells) and GATA-3 are transcription factors that play a critical role in the development of Th1 and Th2 cells, as do genes of the SOCS (suppressor of cytokine signaling) family, albeit indirectly. Another transcription factor, Foxp3, is a master regulator of natural regulatory T cells (Tregs). To identify the role of these factors in impaired Th1 responses of patent filarial infection, analysis of cytokine, SOCS, and transcription factor mRNA expression was performed on purified T cells of filaria-infected individuals (n = 6) and uninfected controls (n = 6). As expected (and in contrast to cells of uninfected individuals), there was a significant depression of gamma interferon (IFN-gamma) and a concomitant increase in interleukin-4 (IL-4), IL-5, and IL-10 mRNA expression following stimulation with parasite antigen (BmA) but not with a polyclonal T-cell (anti-CD3) stimulus. T-bet (but not GATA-3) was expressed at significantly lower levels in cells of filaria-infected individuals in response to BmA compared with those from the uninfected group, accounting, at least partially, for the diminished IFN-gamma expression. Second, we found no significant differences in expression of Foxp3 between the two groups, although induction of Foxp3 expression correlated with induced expression levels of IL-10, implicating Tregs in the IL-10 expression seen. Finally, parasite-specific T-cell expression of SOCS-1, SOCS-5, and SOCS-7 was significantly diminished among infected patients; in contrast, expression of SOCS-3 increased. Our data therefore indicate that the impaired Th1 responses observed in patent lymphatic filariasis are associated with decreased expression of T-bet, SOCS-1, SOCS-5, and SOCS-7 and increased expression of SOCS-3 in T cells. 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 28 TC 21 Z9 23 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 JUN PY 2005 VL 73 IS 6 BP 3394 EP 3401 DI 10.1128/IAI.73.6.3394-3401.2005 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 931LD UT WOS:000229485900023 PM 15908366 ER PT J AU Mendez, S Valenzuela, JG Wu, WH Hotez, PJ AF Mendez, S Valenzuela, JG Wu, WH Hotez, PJ TI Host cytokine production, lymphoproliferation, and antibody responses during the course of Ancylostoma ceylanicum infection in the Golden Syrian hamster SO INFECTION AND IMMUNITY LA English DT Article ID NECATOR-AMERICANUS INFECTION; MESOCRICETUS-AURATUS; HELMINTH INFECTION; SECRETED PROTEIN; IMMUNE-RESPONSE; MOLECULAR CHARACTERIZATION; HOOKWORM INFECTION; ENDEMIC AREA; CHILDREN; LOOSS AB The Syrian Golden hamster (Mesocricetus auratus) has been used to model infections with the hookworm Ancylostoma ceylanicum. New molecular immunological reagents to measure cellular immune responses in hamsters were developed and used to determine the impact of A. ceylanicum hookworm infection on host cytokine responses and lymphoproliferation. Initial larval infection with 100 third-stage A. ceylanicum larvae resulted in predominant Th1 responses (upregulation of proinflammatory cytokines) that lasted for the duration of larval migration and continued up to 14 days postinfection (prepatency). Subsequently, development of larvae into egg-laying adult hookworms (patency) coincided with a switch to Th2 predominant responses (interleukin-4 [IL-4]) as well as a marked increase in IL-10 production. This switch also concurred with reduced host lymphoproliferative responses to hookworm antigens. The findings demonstrate a similarity in immune responses between hamsters and humans infected with hookworms, suggesting that hamsters will be a useful animal model species for examining host immunity to human hookworm infections. C1 George Washington Univ, Ctr Med, Dept Microbiol & Trop Med, Washington, DC 20037 USA. Sabin Vaccine Inst, Washington, DC 20037 USA. NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD 20852 USA. RP Mendez, S (reprint author), George Washington Univ, Ctr Med, Dept Microbiol & Trop Med, Ross Hall,Rm 726,2300 Eye St NW, Washington, DC 20037 USA. EM mtmsxm@gwumc.edu OI Hotez, Peter/0000-0001-8770-1042 NR 48 TC 26 Z9 27 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 JUN PY 2005 VL 73 IS 6 BP 3402 EP 3407 DI 10.1128/IAI.73.6.3402-3407.2005 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 931LD UT WOS:000229485900024 PM 15908367 ER PT J AU Domenech, P Reed, MB Barry, CE AF Domenech, P Reed, MB Barry, CE TI Contribution of the Mycobacterium tuberculosis MmpL protein family to virulence and drug resistance SO INFECTION AND IMMUNITY LA English DT Article ID MULTIDRUG EFFLUX PUMPS; HUMAN NEUTROPHIL PEPTIDE-1; LARGE PERIPLASMIC LOOPS; PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI; IN-VITRO; TRANSPOSON MUTAGENESIS; SUBSTRATE-SPECIFICITY; IMMUNE-RESPONSE; CELL-DIVISION AB The genome sequence of Mycobacterium tuberculosis revealed the presence of 12 membrane proteins proposed to have a function in the transport of lipids. Insertional inactivation of 11 of these has revealed that only 1 (MmpL3) is apparently essential for viability. Five of these proteins are conserved within the genome of Mycobacterium leprae. The drug susceptibilities of these 11 mutants to a broad spectrum of agents are unaltered, suggesting that unlike their function in other organisms, these proteins do not play a significant role in intrinsic drug resistance. Each of these mutants was assessed for growth kinetics and lethality in a murine low-dose aerosol model of tuberculosis, and four were found to be impaired in one or both measures of virulence. Two of these, with mutations of MmpL4 and the previously characterized MmpL7, which transports phthiocerol dimycocerosate, were found to have both impaired growth kinetics and impaired lethality. Mutants with inactivation of MmpL8, which transports a precursor of the sulfatides, or MmpL11, which transports an unknown substrate, were found to establish infection normally but to be significantly attenuated for lethality in time-to-death studies. These studies support the concept that MmpL-mediated lipid secretion both contributes to the innate ability of the pathogen to survive intracellularly and also contributes directly to the host-pathogen dialogue that determines the ultimate outcome of infection. C1 NIAID, TB Res Sect, Rockville, MD 20852 USA. RP Barry, CE (reprint author), TB Res Sect, Immunogenet Lab, 12441 Parklawn Dr, Rockville, MD 20852 USA. EM cbarry@niaid.nih.gov RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11] NR 53 TC 165 Z9 178 U1 3 U2 16 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 JUN PY 2005 VL 73 IS 6 BP 3492 EP 3501 DI 10.1128/IAI.73.6.3492-3501.2005 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 931LD UT WOS:000229485900035 PM 15908378 ER PT J AU Malkin, EM Diemert, DJ McArthur, JH Perreault, JR Miles, AP Giersing, BK Mullen, GE Orcutt, A Muratova, O Awkal, M Zhou, H Wang, J Stowers, A Long, CA Mahanty, S Miller, LH Saul, A Durbin, AP AF Malkin, EM Diemert, DJ McArthur, JH Perreault, JR Miles, AP Giersing, BK Mullen, GE Orcutt, A Muratova, O Awkal, M Zhou, H Wang, J Stowers, A Long, CA Mahanty, S Miller, LH Saul, A Durbin, AP TI Phase 1 clinical trial of apical membrane antigen 1: an asexual blood-stage vaccine for Plasmodium falciparum malaria SO INFECTION AND IMMUNITY LA English DT Article ID MEROZOITES; INVASION; MONKEYS; AMA1; PROTECTION; ANTIBODIES; CANDIDATE AB Apical membrane antigen 1 (AMA1), a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. A phase I trial was conducted with 30 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1 malaria vaccine. AMA1-C1 contains an equal mixture of recombinant proteins based on sequences from the FVO and 3D7 clones of Plasmodium falciparum. The proteins were expressed in Pichia pastoris and adsorbed on Alhydrogel. Ten volunteers in each of three dose groups (5 mu g, 20 p,g, and 80 mu g) were vaccinated in an open-label study at 0, 28, and 180 days. The vaccine was well tolerated, with pain at the injection site being the most commonly observed reaction. Anti-AMA1 immunoglobulin G (IgG) was detected by enzyme-linked immunosorbent assay (ELISA) in 15/28 (54%) volunteers after the second immunization and in 23/25 (92%) after the third immunization, with equal reactivity to both AMA1FVO and AMA1-3D7 vaccine components. A significant dose-response relationship between antigen dose and antibody response by ELISA was observed, and the antibodies were predominantly of the IgG1 isotype. Confocal microscopic evaluation of sera from vaccinated volunteers demonstrated reactivity with P. falciparum schizonts in a pattern similar to native parasite AMA1 Antigen-specific in vitro inhibition of both FVO and 3D7 parasites was achieved with IgG purified from sera of vaccinees, demonstrating biological activity of the antibodies. To our knowledge, this is the first AMA1 vaccine candidate to elicit functional immune responses in malaria-naive humans, and our results support the further development of this vaccine. C1 NIAID, Malaria Vaccine Dev Branch, NIH, Rockville, MD 20852 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Ctr Immunizat Res, Baltimore, MD USA. RP Malkin, EM (reprint author), NIAID, Malaria Vaccine Dev Branch, NIH, 5640 Fishers Lane,Twinbrook 1, Rockville, MD 20852 USA. EM emalkin@niaid.nih.gov; adurbin@jhsph.edu RI Saul, Allan/I-6968-2013; OI Saul, Allan/0000-0003-0665-4091; Diemert, David/0000-0002-2789-0512; Mahanty, Siddhartha/0000-0003-1068-0524 FU NIAID NIH HHS [N01 AI 15444] NR 23 TC 168 Z9 171 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2005 VL 73 IS 6 BP 3677 EP 3685 DI 10.1128/IAI.73.6.3677-3685.2005 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 931LD UT WOS:000229485900054 PM 15908397 ER PT J AU Kim, HS Choi, EH Khan, J Roilides, E Francesconi, A Kasai, M Sein, T Schaufele, RL Sakurai, K Son, CG Greer, BT Chanock, S Lyman, CA Walsh, TJ AF Kim, HS Choi, EH Khan, J Roilides, E Francesconi, A Kasai, M Sein, T Schaufele, RL Sakurai, K Son, CG Greer, BT Chanock, S Lyman, CA Walsh, TJ TI Expression of genes encoding innate host defense molecules in normal human monocytes in response to Candida albicans SO INFECTION AND IMMUNITY LA English DT Article ID CYTOKINE SIGNALING SOCS; HEAT-SHOCK PROTEINS; ADAPTIVE IMMUNITY; INCREASED SUSCEPTIBILITY; ATTRIBUTABLE MORTALITY; SYSTEMIC CANDIDIASIS; RECEPTOR EXPRESSION; CELL RESPONSES; T-CELLS; INFECTION AB Little is known about the regulation and coordinated expression of genes involved in the innate host response to Candida albicans. We therefore examined the kinetic profile of gene expression of innate host defense molecules in normal human monocytes infected with C albicans using microarray technology. Freshly isolated peripheral blood monocytes from five healthy donors were incubated with C albicans for 0 to 18 h in parallel with time-matched uninfected control cells. RNA from monocytes was extracted and amplified for microarray analysis, using a 42,421-gene cDNA chip. Expression of genes encoding proinflammatory cytokines, including tumor necrosis factor alpha, interleukin 1 (IL-1), IL-6, and leukemia inhibitory factor, was markedly enhanced during the first 6 h and coincided with an increase in phagocytosis. Expression of these genes returned to near baseline by 18 h. Genes encoding chemokines, including IL-8; macrophage inflammatory proteins 1, 3, and 4; and monocyte chemoattractant protein 1, also were strongly up-regulated, with peak expression at 4 to 6 h, as were genes encoding chemokine receptors CCR1, CCR5, CCR7, and CXCR5. Expression of genes whose products may protect monocyte viability, such as BCL2-related protein, metallothioneins, CD71, and SOCS3, was up-regulated at 4 to 6 h and remained elevated throughout the 18-h time course. On the other hand, expression of genes encoding T-cell-regulatory molecules (e.g., IL-12, gamma interferon, and transforming growth factor 0) was not significantly affected during the 18-h incubation. Moreover, genes encoding IL-15, the IL-13 receptor (IL-13Ra1), and CD14 were suppressed during the 18-h exposure to C. albicans. Thus, C. albicans is a potent inducer of a dynamic cascade of expression of genes whose products are related to the recruitment, activation, and protection of neutrophils and monocytes. C1 NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH,CRC, Bethesda, MD 20892 USA. Seoul Natl Univ, Coll Med, Seoul, South Korea. Nihon Univ, Tokyo, Japan. RP Walsh, TJ (reprint author), NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH,CRC, Room 1-5740, Bethesda, MD 20892 USA. EM walsht@mail.nih.gov RI Choi, Eun Hwa/J-5691-2012; Khan, Javed/P-9157-2014 OI Khan, Javed/0000-0002-5858-0488 NR 59 TC 51 Z9 54 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 JUN PY 2005 VL 73 IS 6 BP 3714 EP 3724 DI 10.1128/IAI.73.6.3714-3724.2005 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 931LD UT WOS:000229485900058 PM 15908401 ER PT J AU McKibben, L Horan, TC Tokars, JI Fowler, G Cardo, DM Pearson, ML Brennan, PJ AF McKibben, L Horan, TC Tokars, JI Fowler, G Cardo, DM Pearson, ML Brennan, PJ CA Healthcare Infection Control TI Guidance on public reporting of healthcare-associated infections: Recommendations of the healthcare infection control practices advisory committee SO INFECTION CONTROL AND HOSPITAL EPIDEMIOLOGY LA English DT Article ID BLOOD-STREAM INFECTIONS; NOSOCOMIAL INFECTIONS; SURVEILLANCE SYSTEM; UNITED-STATES; PREVENTION; RATES C1 Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Infect Dis, Atlanta, GA 30330 USA. Ctr Dis Control & Prevent, Healthcare Otucomes Branch, Natl Ctr Infect Dis, Div Healthcare Qual Promot, Atlanta, GA 30330 USA. Ctr Dis Control & Prevent, Prevent & Evaluat Branch, Natl Ctr Infect Dis, Div Healthcare Qual Promot, Atlanta, GA 30330 USA. Univ Penn, Sch Med, Div Infect Dis, Philadelphia, PA 19104 USA. Vanderbilt Univ, Med Ctr, Nashville, TN USA. Sharp Mem Hosp & Rehabil Ctr, San Diego, CA USA. Univ Washington, Sch Med, Seattle, WA 98195 USA. Amer Hosp Assoc, Washington, DC USA. Cleveland Clin Fdn, Cleveland, OH 44195 USA. Duke Univ, Ctr Med, Durham, NC 27706 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Texas Dept Hlth, Austin, TX 78756 USA. Long Beach Mem Med Ctr, Long Beach, CA USA. Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Qualis Hlth Boise, Boise, ID USA. Univ Nebraska, Med Ctr, Omaha, NE 68583 USA. Agcy Healthcare Res & Qual, Rockville, MD USA. Assoc PeriOperat Registered Nurses, Denver, CO USA. Assoc Proffes Infect Control & Epidemiol In, Washington, DC USA. Amer Healthcare, Washington, DC USA. Natl Inst Hlth, Bethesda, MD USA. Hlth Serv Resources Adm, Atlanta, GA USA. Ctr Medicare & Medicaid Serv, Baltimore, MD USA. Food & Drug Adm, Rockville, MD USA. Amer Coll Occupat & Environm Med, Arlington Hts, IL USA. CDC, Advisory Comm Eliminat TB, Atlanta, GA 30333 USA. Soc Healthcare Epidemiol Amer Inc, Alexandria, VA USA. Joint Comm Accreditat Healthcare Org, Oak Brook, IL USA. RP Pearson, ML (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Infect Dis, Mailstop E-68,1600 Clifton Rd,NE, Atlanta, GA 30330 USA. EM mpearson@cdc.gov NR 42 TC 60 Z9 60 U1 0 U2 1 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0899-823X J9 INFECT CONT HOSP EP JI Infect. Control Hosp. Epidemiol. PD JUN PY 2005 VL 26 IS 6 BP 580 EP 587 DI 10.1086/502585 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 973QW UT WOS:000232538700015 PM 16018435 ER PT J AU Reynolds, SJ Quinn, TC AF Reynolds, SJ Quinn, TC TI Developments in STD/HIV interactions: The intertwining epidemics of HIV and HSV-2 SO INFECTIOUS DISEASE CLINICS OF NORTH AMERICA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SEXUALLY-TRANSMITTED-DISEASES; RANDOMIZED CONTROLLED-TRIAL; GENITAL-ULCER-DISEASE; DOUBLE-BLIND; TYPE-2 INFECTION; INTERVENTION TRIALS; HIV-1-INFECTED MEN; RURAL TANZANIA; HERPES AB More than 75 million people worldwide have been infected with HIV over the past 2 decades despite ambitious global prevention programs. Currently 40 million people are living with HIV and over 35 million have died from AIDS. The spread of HIV has been primarily through sexual intercourse with a lesser proportion of cases attributable to intravenous drug use and contaminated blood transfusions. The alarming numbers camouflage the fact that the HIV virus is spread inefficiently through sexual intercourse, perhaps as infrequently as 1 out of 1000 sexual exposures. Sexually transmitted diseases, particularly ulcerative genital diseases, increase infectiousness and susceptibility to HIV infections. Data from international and domestic studies point increasingly to the role of herpes simplex virus type 2 (HSV-2) as a primary cofactor in facilitating the spread of HIV infection. This article reviews the recent developments in this important interaction and the potential impact of different intervention strategies targeting HSV-2. C1 Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Reynolds, SJ (reprint author), Johns Hopkins Univ, Sch Med, Div Infect Dis, Ross 1159,720 Rutland Ave, Baltimore, MD 21205 USA. EM sreynol6@jhmi.edu NR 41 TC 26 Z9 26 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 0891-5520 J9 INFECT DIS CLIN N AM JI Infect. Dis. Clin. North Am. PD JUN PY 2005 VL 19 IS 2 BP 415 EP + DI 10.1016/j.idc.2005.04.005 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 944MS UT WOS:000230433700010 PM 15963880 ER PT J AU Fransman, W Vermeulen, R Kromhout, H AF Fransman, W Vermeulen, R Kromhout, H TI Dermal exposure to cyclophosphamide in hospitals during preparation, nursing and cleaning activities SO INTERNATIONAL ARCHIVES OF OCCUPATIONAL AND ENVIRONMENTAL HEALTH LA English DT Article DE anti-neoplastic drugs; cyclophosphamide; dermal exposure; hospital; nurses; pharmacy technicians ID HANDLING ANTINEOPLASTIC DRUGS; SISTER CHROMATID EXCHANGES; OCCUPATIONAL EXPOSURE; ENVIRONMENTAL CONTAMINATION; CHROMOSOMAL-ABERRATIONS; PHARMACY TECHNICIANS; MASS-SPECTROMETRY; AGENTS; NURSES; WORKERS AB Objectives: To determine levels of potential and actual dermal exposure to cyclophosphamide (CP) during performance of oncology-related tasks in hospitals and to investigate the relationship with potential sources and surface contamination levels of CP. Methods: Dermal exposure to CP was determined for tasks with potential exposure to CP: preparation of CP, decanting of patients' urine, washing of the patient, removal of bed sheets of treated patients and cleaning of patients' toilets on oncology wards. Exposure was assessed by the collection of nitrile and latex protective medical gloves (potential exposure), washing of hands (actual exposure), from cotton pads attached to (un)covered forearms (potential or actual exposure) and a wipe sample of the forehead (actual exposure). Bulk samples (i.e. application fluids and patients' excreta) and possible contact surfaces were monitored to assess the amount of CP available for dermal exposure. Results: Pharmacy technicians, oncology nurses and cleaning personnel showed actual and potential dermal exposure to CP during performance of their daily duties. Exposure occurred predominantly on the hands and sporadically on the forehead and forearms. Although all nurses used gloves during handling of patients' urine and sometimes during the other nursing tasks, skin underneath gloves was repeatedly contaminated. Results of tests on bulk and surface contamination samples confirmed that patients intravenously treated with CP excrete the unmetabolised drug, which could subsequently lead to dermal exposure of hospital personnel. A clear relationship was found between dermal exposure levels and direct sources of exposure for all tasks, except for handling patients' urine. Conclusions: We demonstrated for the first time that actual dermal exposure to CP is common among oncology nurses working with patients treated with this anti-neoplastic drug. Pharmacy technicians and cleaning personnel, on the other hand, are potentially exposed to CP, and protection provided by gloves seemed to be sufficient. C1 Univ Utrecht, IRAS, Environm & Occupat Hlth Div, NL-3508 TD Utrecht, Netherlands. NCI, Div Canc Epidemiol & Genet, Occupat & Environm Epidemiol Branch, Rockville, MD USA. RP Kromhout, H (reprint author), Univ Utrecht, IRAS, Environm & Occupat Hlth Div, POB 80176, NL-3508 TD Utrecht, Netherlands. EM h.kromhout@iras.uu.nl RI Kromhout, Hans/A-9159-2008; Vermeulen, Roel/F-8037-2011 OI Vermeulen, Roel/0000-0003-4082-8163 NR 23 TC 40 Z9 44 U1 1 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0340-0131 J9 INT ARCH OCC ENV HEA JI Int. Arch. Occup. Environ. Health PD JUN PY 2005 VL 78 IS 5 BP 403 EP 412 DI 10.1007/s00420-004-0595-1 PG 10 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 934WK UT WOS:000229739800008 PM 15887018 ER PT J AU Hu, JY Li, GC Tong, YQ Li, YH Zhou, GH He, XJ Xie, PL Wang, JM Sun, QB AF Hu, JY Li, GC Tong, YQ Li, YH Zhou, GH He, XJ Xie, PL Wang, JM Sun, QB TI Transduction of the gene coding for a human G-protein coupled receptor FPRL1 in mouse tumor cells increases host anti-tumor immunity SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Article DE chemoattractant receptors; gene transfer; colorectal cancer; gene therapy ID CYTOLYTIC T-LYMPHOCYTES; HUMAN-MELANOMA; FORMYLPEPTIDE RECEPTOR; ANTIGEN; TUMORIGENICITY; IMMUNIZATION; CANCER; DNA; AUTOIMMUNITY; VACCINE AB Low antigenicity or development of tolerance is believed to be a major contributor to the escape of malignant tumors from immune surveillance of the host. However, anti-tumor responses can be elicited by concomitant immunization of poorly antigenic tumor cells with homologous xenogeneic proteins as 'altered self proteins. In our study, anti-tumor, but not antixenogeneic antigen, immune responses were generated after transduction of the gene coding for a G-protein coupled human formyl peptide receptor like-1 (FPRL1) into a mouse C26 colon cancer cell line. C26 cells transfected with FPRL1 gene exhibited markedly reduced tumorigenicity in syngeneic mice, in association with the appearance of high levels of antibody activity reacting with both FPRL1 containing and wild type C26 cells. The anti-tumor responses required the participation of CD4+ T lymphocytes, since no tumor rejection was observed in nude mice or in syngeneic mice depleted of CD4+ T cells. Furthermore, mice primed with FPRL1 transfected C26 cells were resistant to subsequent challenge by wild type C26 cells. These results indicate that the presence of human FPRL1 is capable of triggering specific anti-tumor host immune responses against poorly antigenic mouse tumor cells. 2005 Elsevier B.V. All rights reserved. C1 NCI, Mol Immunoregulat Lab, Ctr Canc Res, Ft Detrick, MD 21702 USA. EM jinyueh@yahoo.com; libsun@public.cs.hn.cn NR 40 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD JUN PY 2005 VL 5 IS 6 BP 971 EP 980 DI 10.1016/j.intimp.2005.01.011 PG 10 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 922DJ UT WOS:000228815900004 PM 15829413 ER PT J AU Egger, M Boulle, A Schechter, M Miotti, P AF Egger, M Boulle, A Schechter, M Miotti, P TI Antiretroviral therapy in resource-poor settings: scaling up inequalities? SO INTERNATIONAL JOURNAL OF EPIDEMIOLOGY LA English DT Editorial Material ID HIV-INFECTED PATIENTS; SOUTH-AFRICA; HEALTH; KHAYELITSHA; SURVIVAL; HIV/AIDS; ACCESS; HAART; AIDS C1 Univ Bern, Inst Social & Prevent Med, CH-3012 Bern, Switzerland. Univ Cape Town, Sch Publ Hlth & Family Med, ZA-7925 Cape Town, South Africa. Univ Fed Rio de Janeiro, Hosp Univ Clementino Fraga Filho, Rio De Janeiro, Brazil. NIH, Off AIDS Res, Bethesda, MD 20892 USA. RP Egger, M (reprint author), Univ Bern, Inst Social & Prevent Med, Finkenhubelweg 11, CH-3012 Bern, Switzerland. EM egger@ispm.unibe.ch NR 25 TC 21 Z9 21 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0300-5771 J9 INT J EPIDEMIOL JI Int. J. Epidemiol. PD JUN PY 2005 VL 34 IS 3 BP 509 EP 512 DI 10.1093/ije/dyi110 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 937CK UT WOS:000229902000002 PM 15941732 ER PT J AU Gradstein, L Danek, A Grafman, J FitzGibbon, EJ AF Gradstein, L Danek, A Grafman, J FitzGibbon, EJ TI Eye movements in chorea-acanthocytosis SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID SQUARE-WAVE JERKS; GABA-RELATED SUBSTANCES; NEUROACANTHOCYTOSIS SYNDROME; PARKINSONIAN SYNDROMES; SUPERIOR COLLICULUS; HUNTINGTONS-DISEASE; DISORDERS; MONKEY; CARBAMAZEPINE; OSCILLATIONS AB PURPOSE. To describe the eye movement abnormalities in patients with chorea-acanthocytosis (ChAc), a form of neuroacanthocytosis. This autosomal recessive, neurodegenerative disorder with aberrant erythrocyte morphology (acanthocytosis) is caused by mutations in the VPS13A gene. In contrast to Huntington's disease (for which ChAc has occasionally been mistaken), ocular involvement in ChAc has not been systematically studied. METHODS. Three patients aged 26, 30, and 44 years with ChAc and six normal volunteers aged 31 to 48 years were included. Patients had dystonia, chorea, parkinsonism, dysarthria, dysphagia, seizures, cognitive abnormalities, and acanthocytosis. All had heterozygous VPS13A mutations and degeneration of the basal ganglia on magnetic resonance imaging (MRI) typical of ChAc. Patients had an extensive clinical and laboratory work-up. Neuro-ophthalmic examinations and eye movement recordings made with the magnetic search coil technique assessed patients' fixation characteristics, horizontal and vertical saccades, pursuit, and antisaccades. These were compared to the data of control subjects. RESULTS. Patients exhibited more than 30 square-wave jerks (small saccadic intrusions) per minute, versus 0 to 8 in the control subjects, as well as fractionated (multistep) and hypometric horizontal and vertical saccades. Decreased saccadic peak-velocity and reduced saccadic range were more pronounced for vertical saccades. Pursuit testing performed in two patients showed low gain. Results of antisaccade testing done in one patient were abnormal. CONCLUSIONS. The findings suggest brain stem involvement as an additional site of neurodegeneration outside the basal ganglia in ChAc. Patients with this progressive, intractable disease have pronounced ocular motor abnormalities. Eye movement recordings could assist in diagnosing ChAc, monitoring its progression and possible treatment evaluation. C1 NEI, Sensorimotor Res Lab, NIH, Bethesda, MD 20892 USA. Univ Munich, Univ Dept Neurol, Munich, Germany. Natl Inst Neurol Disorders & Stroke, Cognit Neurosci Sect, NIH, Bethesda, MD USA. RP Gradstein, L (reprint author), NEI, Sensorimotor Res Lab, NIH, Bldg 10,Room 10N226, Bethesda, MD 20892 USA. EM libe@nei.nih.gov RI Danek, Adrian/G-7339-2011; OI Danek, Adrian/0000-0001-8857-5383; Grafman, Jordan H./0000-0001-8645-4457 NR 33 TC 15 Z9 18 U1 1 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 JUN PY 2005 VL 46 IS 6 BP 1979 EP 1987 DI 10.1167/iovs.04-0539 PG 9 WC Ophthalmology SC Ophthalmology GA 931SD UT WOS:000229504600015 PM 15914612 ER PT J AU Riazuddin, SA Yasmeen, A Yao, WL Sergeev, YV Zhang, QJ Zulfiqar, F Riaz, A Riazuddin, S Hejtmancik, JF AF Riazuddin, SA Yasmeen, A Yao, WL Sergeev, YV Zhang, QJ Zulfiqar, F Riaz, A Riazuddin, S Hejtmancik, JF TI Mutations in beta B3-crystallin associated with autosomal recessive cataract in two Pakistani families SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID BETA-GAMMA-CRYSTALLINS; EYE LENS; GENETIC-HETEROGENEITY; MYXOCOCCUS-XANTHUS; DOMINANT CATARACT; ALPHA-CRYSTALLIN; LINKAGE ANALYSIS; PROTEIN-S; IDENTIFICATION; TRANSPARENCY AB PURPOSE. To identify the disease locus for autosomal recessive congenital cataracts in consanguineous Pakistani families. METHODS. Two Pakistani families were ascertained, patients were examined, blood samples were collected, and DNA was isolated. A genome-wide scan was performed using >382 polymorphic microsatellite markers on genomic DNA from affected and unaffected family members. Two-point lod scores were calculated, haplotypes were formed by inspection, and candidate genes were sequenced. Real-time quantitative PCR techniques were used to determine the mRNA levels, and molecular modeling was performed to gain a better understanding of the significance of the disease-causing mutation. RESULTS. In the genome-wide scan, maximum lod scores of 2.67 and 2.77 for family 60004 and 2.02 and 2.04 for family 60006 were obtained for markers D22S539 and D22S315, respectively. The linked region, 22.7 cM (10 Mb) flanked by markers D22S420 and D22S1163, contains the beta-crystallin gene cluster including the genes CRYBA4, CRYBB1, CRYBB2, and CRYBB3. Sequencing of these genes showed a G -> C transition in exon 6 of CRYBB3 resulting in a p.G165R change in the beta B3-crystallin protein that cosegregates with the disease in both families. Real-time PCR analysis suggested that beta B3-crystallin mRNA levels approximate those of other beta gamma-crystallins. Molecular modeling predicted changes in electrostatic potential that would be expected to reduce the stability of the fourth Greek-key motif, and hence the entire protein, dramatically. CONCLUSIONS. For the first time, a mutation in CRYBB3 is reported in two consanguineous Pakistani families with autosomal recessive congenital cataracts. C1 NEI, OGVFB, NIH, Bethesda, MD 20892 USA. Univ Punjab, Natl 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 SHEIKH, RIAZUDDIN/L-2406-2015 NR 36 TC 70 Z9 77 U1 0 U2 3 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 JUN PY 2005 VL 46 IS 6 BP 2100 EP 2106 DI 10.1167/iovs.04-1481 PG 7 WC Ophthalmology SC Ophthalmology GA 931SD UT WOS:000229504600032 PM 15914629 ER PT J AU Marchetti, MA Pizarro, GO Sagher, D DeAmicis, C Brot, N Hejtmancik, JF Weissbach, H Kantorow, M AF Marchetti, MA Pizarro, GO Sagher, D DeAmicis, C Brot, N Hejtmancik, JF Weissbach, H Kantorow, M TI Methionine sulfoxide Reductases B1, B2, and B3 are present in the human lens and confer oxidative stress resistance to lens cells SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Article ID HYDROGEN-PEROXIDE; NUCLEAR CATARACT; LIFE-SPAN; CRYSTALLINS; EXPRESSION; GENE; IDENTIFICATION; LOCALIZATION; REDUCTION; MECHANISM AB PURPOSE. Methionine-sulfoxide reductases are unique, in that their ability to repair oxidized proteins and MsrA, which reduces S-methionine sulfoxide, can protect lens cells against oxidative stress damage. To date, the roles of MsrB1, -B2 and -B3 which reduce R-methionine sulfoxide have not been established for any mammalian system. The present study was undertaken to identify those MsrBs expressed by the lens and to evaluate the enzyme activities, expression patterns, and abilities of the identified genes to defend lens cells against oxidative stress damage. METHODS. Enzyme activities were determined with bovine lens extracts. The identities and spatial expression patterns of MsrB1, -B2, and -B3 transcripts were examined by RT-PCR in human lens and 21 other tissues. Oxidative stress resistance was measured using short interfering (si)RNA-mediated gene-silencing in conjunction with exposure to tert-butyl hydroperoxide (tBHP) and MTS viability measurements in SRA04/01 human lens epithelial cells. RESULTS. Forty percent of the Msr enzyme activity present in the lens was MsrB, whereas the remaining enzyme activity was MsrA. MsrB1 (selenoprotein R, localized in the cytosol and nucleus), MsrB2 (CBS-1, localized in the mitochondria), and MsrB3 (localized in the endoplasmic reticulum and mitochondria) were all expressed by the lens. These genes exhibit asymmetric expression patterns between different human tissues and different lens sublocations, including lens fibers. All three genes are required for lens cell viability, and their silencing in lens cells results in increased oxidative-stress-induced cell death. CONCLUSIONS. The present data suggest important roles for both MsrA and -Bs in lens cell viability and oxidative stress protection. The differential tissue distribution and lens expression patterns of these genes, coupled with increased oxidative-stress-induced cell death on their deletion provides evidence that they are important for lens cell function, resistance to oxidative stress, and, potentially, cataractogenesis. C1 Florida Atlantic Univ, Dept Biomed Sci, Boca Raton, FL 33431 USA. Florida Atlantic Univ, Ctr Mol Biol & Biotechnol, Boca Raton, FL 33431 USA. Cornell Univ, Hosp Special Surg, Weill Med Coll, Dept Microbiol & Immunol, New York, NY 10021 USA. NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP Kantorow, M (reprint author), Florida Atlantic Univ, Dept Biomed Sci, 777 Glades Rd,POB 3091, Boca Raton, FL 33431 USA. EM mkantoro@fau.edu FU NEI NIH HHS [EY13022, R01 EY013022] NR 29 TC 48 Z9 53 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 JUN PY 2005 VL 46 IS 6 BP 2107 EP 2112 DI 10.1167/iovs.05-0018 PG 6 WC Ophthalmology SC Ophthalmology GA 931SD UT WOS:000229504600033 PM 15914630 ER PT J AU Mirochnick, M Stek, A Acevedo, M Keller, M Holland, D Capparelli, E Connor, J Huang, S Hughes, M Watts, H Mofenson, L Bryson, Y AF Mirochnick, M Stek, A Acevedo, M Keller, M Holland, D Capparelli, E Connor, J Huang, S Hughes, M Watts, H Mofenson, L Bryson, Y TI Safety and pharmacokinetics of nelfinavir coadministered with zidovudine and lamivudine in infants during the first 6 weeks of life SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE nelfinavir; HIV; pharmacokinetics; neonate ID HUMAN-IMMUNODEFICIENCY-VIRUS; PROTEASE INHIBITOR NELFINAVIR; ANTIRETROVIRAL THERAPY; ACTIVE METABOLITE; HUMAN LIVER; CHILDREN; PLASMA; TYPE-1; TRANSMISSION; PROPHYLAXIS AB The safety and pharmacokinetics of nelfinavir coadministered with zidovudine and lamivudine were studied in 26 infants during the first 6 weeks of life. Cohort 1 infants (n = 7) received 10 mg/kg 3 times a day, and cohort 2 infants (n = 19) received 40 mg/kg twice a day. Two cohort 1 infants at week 1 and none at week 6 exceeded the target 24-hour area under the curve (AUC) of 30 mu g center dot h/mL, equal to the 10th percentile of the AUC for adults receiving standard nelfinavir dosing. In cohort 2, the median 24-hour AUC was 38 mu g center dot h/mL at both time points, with considerable variability among the infants. Three of I I cohort 2 infants at week and 4 of I I at week 6 did not meet the AUC target. Median nelfinavir oral clearance was 2.1 L/h/kg at weeks 1 and 6. The median ratio of the plasma concentrations of the nelfinavir metabolite M8 to unchanged nelfinavir increased from 0.16 (range: 0-0.38) during week 1 to 0.56 (range: 0.4-1.47) during week 6 (P < 0.01). There were no significant differences in any of the other pharmacokinetic parameters when week 1 and week 6 results were compared. Few adverse event, were attributed to nelfinavir. These data suggest that nelfinavir is well tolerated in infants at these doses, but exposure was frequently less than that seen in adults taking standard nelfinavir dosing. Further investigations of larger doses, such as 75 mg/kg twice a day, should be undertaken. C1 Boston Univ, Sch Med, Dept Pediat, Boston, MA 02118 USA. Los Angeles Country Med Ctr, Dept Obstet & Gynecol, Los Angeles, CA USA. San Juan City Hosp, Dept Pediat, San Juan, PR USA. Harbor Univ Calif Los Angeles Sch Med, Dept Pediat, Torrance, CA USA. Univ Calif San Diego, Dept Pediat, San Diego, CA 92103 USA. Ctr Biostat AIDS, Boston, MA USA. NICHHD, Bethesda, MD 20892 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. RP Mirochnick, M (reprint author), Boston Med Ctr, 91 E Concord St,6th Floor, Boston, MA 02118 USA. EM mark.m@bu.edu OI Mofenson, Lynne/0000-0002-2818-9808 FU NCRR NIH HHS [M01RR00425, M01RR0533]; NIAID NIH HHS [2U01AI41089] NR 28 TC 17 Z9 17 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 JUN 1 PY 2005 VL 39 IS 2 BP 189 EP 194 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 930UZ UT WOS:000229443900010 PM 15905735 ER PT J AU Zhou, Y Bian, XW Le, YY Gong, WH Hu, JY Zhang, X Wang, LH Iribarren, P Salcedo, R Howard, OMZ Farrar, W Wang, JM AF Zhou, Y Bian, XW Le, YY Gong, WH Hu, JY Zhang, X Wang, LH Iribarren, P Salcedo, R Howard, OMZ Farrar, W Wang, JM TI Formylpeptide receptor FPR and the rapid growth of malignant human gliomas SO JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID FORMYL PEPTIDE RECEPTOR; NF-KAPPA-B; SERINE PHOSPHORYLATION; CONSTITUTIVE ACTIVATION; CHEMOKINE RECEPTORS; MAXIMAL ACTIVATION; INDUCED APOPTOSIS; STAT3 ACTIVATION; GENE-EXPRESSION; TUMOR-GROWTH AB Background. The formylpeptide receptor (FPR) is a G-protein-coupled receptor (GPCR) that mediates chemotaxis of phagocytic leukocytes induced by bacterial peptide N-formyl-methionyl-leucyl-phenylalanine (fMLF). We previously showed that selected human glioma cell lines also express functional FPR. We therefore investigated the relationship between FPR expression and the biologic behavior of glioma cells. Methods: Expression and function of FPR in the human glioblastoma cell line U-87 were examined by reverse transcription-polymerase chain reaction (RT-PCR) and chemotaxis assays, respectively. FPR protein expression was detected in specimens from 33 human primary gliomas by immunohistochemistry. FPR short interfering (si) RNA was used to block FPR expression in U-87 cells. Cell proliferation was assessed by measuring DNA synthesis. Xenograft tumor formation and growth were measured in nude mice. Endogenous FPR agonist activity released by necrotic tumor cells was assessed by measuring FPR activation in an FPR-transfected basophil leukemia cell line and live U-87 cells. Vascular endothelial growth factor (VEGF) mRNA was assessed by RT-PCR, and VEGF protein was assessed by enzyme-linked immunosorbent assay. All statistical tests were two-sided. Results: FPR was selectively expressed by the highly malignant human glioblastoma cell line U-87 and most primary grade IV glioblastomas multiforme and grade III anaplastic astrocytomas. U-87 cells responded to the FPR agonist fMLF by chemotaxis (i.e., increased motility), increased cell proliferation, and increased production of VEGF protein. FPR siRNA substantially reduced the tumorigenicity of U-87 cells in nude mice (38 days after implantation, mean tumor volume from wild-type U-87 cells = 842 mm(3), 95% confidence interval [CI] = 721 to 963 mm(3); and from FPR-siRNA transfected U-87 cells = 225 mm3, 95% Cl = 194 to 256 mm(3); P =.001). Necrotic glioblastoma cells released a factor(s) that activated FPR in live U-87 cells. Conclusions: FPR is expressed by highly malignant human glioma cells and appears to mediate motility, growth, and angiogenesis of human glioblastoma by interacting with host-derived agonists. Thus, FPR may represent a molecular target for the development of novel antiglioma therapeutics. C1 NCI, Ctr Canc Res, Mol Immunoregulat Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, Ctr Canc Res, Expt Immunol Lab, SAIC Frederick Inc, Frederick, MD 21702 USA. NCI, SAIC Frederick Inc, Basic Res Program, Frederick, MD 21702 USA. Mil Med Univ 3, SW Hosp, Inst Pathol, Chongqing 400038, Peoples R China. RP NCI, Ctr Canc Res, Mol Immunoregulat Lab, SAIC Frederick Inc, Bldg 560,Room 31-40, Frederick, MD 21702 USA. EM wangji@mail.ncifcrf.gov RI Zhang, Xia/B-8152-2008; Bian, Xiuwu/F-1569-2011; Howard, O M Zack/B-6117-2012; Bian, Xiu-wu/D-4736-2017 OI Zhang, Xia/0000-0002-9040-1486; Howard, O M Zack/0000-0002-0505-7052; Bian, Xiu-wu/0000-0003-4383-0197 FU NCI NIH HHS [N01-CO-12400] NR 60 TC 76 Z9 85 U1 3 U2 8 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 JUN 1 PY 2005 VL 97 IS 11 BP 823 EP 835 DI 10.1093/jnci/dji142 PG 13 WC Oncology SC Oncology GA 937PW UT WOS:000229939000010 PM 15928303 ER PT J AU Kocabas, CN Yavuz, AS Lipsky, PE Metcalfe, DD Akin, C AF Kocabas, CN Yavuz, AS Lipsky, PE Metcalfe, DD Akin, C TI Analysis of the lineage relationship between mast cells and basophils using the c-kit D816V mutation as a biologic signature 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 19-23, 2004 CL San Francisco, CA SP Amer Acad Allergy Asthma & Immunol DE mast cells; basophils; c-kit; mastocytosis; hematopoiesis ID BLOOD MONONUCLEAR-CELLS; SYSTEMIC MASTOCYTOSIS; PERIPHERAL-BLOOD; SMOLDERING MASTOCYTOSIS; HEMATOLOGIC DISORDER; PROGENITOR CELLS; STEM-CELLS; INVOLVEMENT; DIFFERENTIATION; EXPRESSION AB Background: Mast cells and basophils share similar morphologic and functional properties; however, it is not known whether they are derived from a bilineage (basophil/mast cell)-restricted progenitor. Objective: To assess whether basophils and mast cells are derived from common committed progenitors using the c-kit D816V mutation as a biologic signature. Methods: The D816V c-kit mutation found in mast cells of patients with systemic mastocytosis is used as a trackable genetic marker to assess the lineage relationship between mast cells and basophils. Blood and bone marrow aspirates were collected from 33 consecutive patients with mastocytosis with different disease severity. Peripheral blood basophils, monocytes and neutrophils were sorted by immunomagnetic beads. Presence of the D816V e-kit mutation was analyzed by restriction fragment length polymorphism in the genomic DNA and mRNA from sorted cells in all patients and in the genomic DNA of individual basophils of 1 patient. Results: The c-kit D816V mutation was detectable in basophils of 5 patients (15%). All 5 patients had the c-kit mutation also detectable in monocytes and thus had multilineage involvement. Single cell analysis of the genomic DNA in I patient showed a similar degree of clonal expansion in basophils, monocytes, and neutrophils. Mutated c-kit was expressed at the mRNA level in all 5 patients. There was no difference in surface Kit expression levels in basophils. Conclusion: Basophils carrying the D816V c-kit mutation in mastocytosis were detected only in the context of a multilineage involvement. These results argue against the presence of a bilineage-restricted committed progenitor for mast cells and basophils. C1 Univ Michigan, Dept Med, Div Allergy & Immunol, Ann Arbor, MI 48109 USA. NIAID, Lab Allerg Dis, Bethesda, MD USA. NIAMSD, Autoimmun Branch, NIH, Bethesda, MD USA. Istanbul Univ, Fac Med, Div Hematol, Istanbul, Turkey. RP Akin, C (reprint author), Univ Michigan, Dept Med, Div Allergy & Immunol, 4220D MSRB-3,Box 0638,1150 W Med Ctr Dr, Ann Arbor, MI 48109 USA. EM cemakin@umich.edu OI Akin, Cem/0000-0001-6301-4520 NR 39 TC 22 Z9 22 U1 1 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2005 VL 115 IS 6 BP 1155 EP 1161 DI 10.1016/j.jaci.2005.02.030 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 935WZ UT WOS:000229815400008 PM 15940128 ER PT J AU Diehl, M Marsiske, M Horgas, AL Rosenberg, A Saczynski, JS Willis, SL AF Diehl, M Marsiske, M Horgas, AL Rosenberg, A Saczynski, JS Willis, SL TI The revised observed tasks of daily living: A performance-based assessment of everyday problem solving in older adults SO JOURNAL OF APPLIED GERONTOLOGY LA English DT Article DE everyday problem solving; everyday competence; performance-based assessment; adulthood; aging ID MINI-MENTAL-STATE; INSTRUMENTAL ACTIVITIES; AFRICAN-AMERICAN; HEALTH-SERVICES; LIFE; SYMPTOMS; TRIAL; RACE AB The Revised Observed Tasks of Daily Living (OTDL-R), a performance-based test of everyday problem solving, was administered to a sample of community-dwelling older adults. The OTDL-R included nine tasks, representing medication use, telephone use, and financial management. The OTDL-R had a desirable range of difficulty and satisfactory internal consistency and showed a relatively invariant pattern of relations between measured tasks and the underlying latent dimensions they represent across White and non-White subsamples. The OTDL-R also correlated significantly with age, education, self-rated health, a paper-and-pencil measure of everyday problem solving, and measures of basic cognitive functioning. Thus, the OTDL-R is a reliable and valid objective measure of everyday problem solving that has great practical utility, for assessing performance in diverse populations. C1 Univ Florida, Dept Psychiat, Gainesville, FL 32611 USA. Hebrew Rehabil Ctr Aged, Boston, MA 02131 USA. NIA, Bethesda, MD 20892 USA. Penn State Univ, University Pk, PA 16802 USA. RP Diehl, M (reprint author), Univ Florida, Dept Psychiat, 508 McCarty Hall,POB 115911, Gainesville, FL 32611 USA. OI Marsiske, Michael/0000-0001-5973-2116 FU NIA NIH HHS [U01 AG014276-05S3, U01 AG014276-05, R37 AG024102, U01 AG014289, U01 AG014276-08, U01 AG014276-07S1, U01 AG014276, U01 AG014276-04, U01 AG014276-05S2, U01 AG014276-06A1, U01 AG014276-07, U01 AG014282, U01 AG014260, U01 AG014263, U01 AG014276-05S1, U01 AG014276-08S1]; NINR NIH HHS [U01 NR004508, U01 NR004507] NR 54 TC 44 Z9 47 U1 5 U2 11 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0733-4648 J9 J APPL GERONTOL JI J. Appl. Gerontol. PD JUN PY 2005 VL 24 IS 3 BP 211 EP 230 DI 10.1177/0733464804273772 PG 20 WC Gerontology SC Geriatrics & Gerontology GA 012JW UT WOS:000235336500003 PM 18160968 ER PT J AU Nguyen, T Rubinstein, NA Vijayasarathy, C Rome, LC Kaiser, LR Shrager, JB Levine, S AF Nguyen, T Rubinstein, NA Vijayasarathy, C Rome, LC Kaiser, LR Shrager, JB Levine, S TI Effect of chronic obstructive pulmonary disease on calcium pump ATPase expression in human diaphragm SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE SERCA1; SERCA2; myosin heavy chain ID SKELETAL-MUSCLE FIBERS; TERM ELECTRICAL-STIMULATION; SARCOPLASMIC-RETICULUM; FAST-TWITCH; RELAXATION RATE; SLOW SKELETAL; SINGLE FIBERS; MYOSIN; FREQUENCY; ISOFORMS AB We have previously demonstrated that human diaphragm remodeling elicited by severe chronic obstructive pulmonary disease ( COPD) is characterized by a fast-to-slow myosin heavy chain isoform transformation. To test the hypothesis that COPD-induced diaphragm remodeling also elicits a fast-to-slow isoform shift in the sarcoendoplasmic reticulum Ca2+ ATPase (SERCA), the other major ATPase in skeletal muscle, we obtained intraoperative biopsies of the costal diaphragm from 10 severe COPD patients and 10 control subjects. We then used isoform-specific monoclonal antibodies to characterize diaphragm fibers with respect to the expression of SERCA isoforms. Compared with control diaphragms, COPD diaphragms exhibited a 63% decrease in fibers expressing only fast SERCA (i.e., SERCA1; P < 0.001), a 190% increase in fibers containing both fast and slow SERCA isoforms ( P < 0.01), and a 19% increase ( P < 0.05) in fibers expressing only the slow SERCA isoform (i.e., SERCA2). Additionally, immunoblot experiments carried out on diaphragm homogenates indicated that COPD diaphragms expressed only one-third the SERCA1 content noted in control diaphragms; in contrast, COPD and control diaphragms did not differ with respect to SERCA2 content. The combination of these histological and immunoblot results is consistent with the hypothesis that diaphragm remodeling elicited by severe COPD is characterized by a fast-to-slow SERCA isoform transformation. Moreover, the combination of these SERCA data and our previously reported myosin heavy chain isoform data ( Levine S, Nguyen T, Kaiser LR, Rubinstein NA, Maislin G, Gregory C, Rome LC, Dudley GA, Sieck GC, and Shrager JB. Am J Respir Crit Care Med 168: 706 - 713, 2003) suggests that diaphragm remodeling elicited by severe COPD should decrease ATP utilization by the diaphragm. C1 Univ Penn, Sch Arts & Sci, Dept Biol, Philadelphia, PA 19104 USA. NEI, NIH, Bethesda, MD 20892 USA. Univ Penn, Sch Med, Dept Surg, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Cell & Dev Biol, Philadelphia, PA 19104 USA. Philadelphia Vet Affairs Med Ctr, Surg Serv, Philadelphia, PA USA. Philadelphia Vet Affairs Med Ctr, Res Serv, Philadelphia, PA USA. RP Levine, S (reprint author), Hosp Univ Penn, Resp Muscle Res Lab, Sect Gen Thorac Surg, 3400 Spruce St,7 Silverstein Pavil, Philadelphia, PA 19104 USA. EM sdlevine@mail.med.upenn.edu FU NIAMS NIH HHS [AR 38404, AR 46125] NR 44 TC 18 Z9 20 U1 0 U2 1 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 JUN PY 2005 VL 98 IS 6 BP 2004 EP 2010 DI 10.1152/japplphysiol.00767.2004 PG 7 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 929SF UT WOS:000229365500006 PM 15718407 ER PT J AU Haley, M Parent, C Cui, XZ Kalil, A Fitz, Y Correa-Araujo, R Natanson, C Danner, RL Banks, SM Eichacker, PQ AF Haley, M Parent, C Cui, XZ Kalil, A Fitz, Y Correa-Araujo, R Natanson, C Danner, RL Banks, SM Eichacker, PQ TI Neutrophil inhibition with L-selectin-directed MAb improves or worsens survival dependent on the route but not severity of infection in a rat sepsis model SO JOURNAL OF APPLIED PHYSIOLOGY LA English DT Article DE shock; adhesion; treatment ID INFLAMMATORY RESPONSE SYNDROME; TUMOR-NECROSIS-FACTOR; MEDIATED LUNG INJURY; SEPTIC SHOCK; MONOCLONAL-ANTIBODY; ADHESION MOLECULES; ENDOTHELIAL-CELLS; DEFICIENT MICE; FACTOR-ALPHA; MECHANISMS AB Both route and severity of infection may influence immunomodulator agents in sepsis. We studied the effect of each variable on HRL- 3, an L-selectin-directed MAb that inhibits neutrophil function, in a rat sepsis model. Animals ( n = 800) were randomized to be treated with either HRL- 3 or placebo and to receive Escherichia coli either intravenously (IV) or intrabronchially (IB) in doses producing low or high mortality rates. Animals received antibiotics and were observed for 168 h. Route but not dose of E. coli altered the effects HRL- 3 on mortality rate ( mean hazards ratio +/- SE). With IV E. coli, compared with control, HRL- 3 was beneficial and reduced the hazards ratio both early ( 0 to 6 h; - 0.75 +/- 0.23) and late ( 6 to 168 h; - 0.72 +/- 0.36) ( P = 0.001 and 0.04, respectively, over all E. coli doses). In contrast, with IB E. coli HRL- 3 reduced the hazards ratio early ( - 1.1 +/- 0.36) but worsened it late ( 0.87 +/- 0.23) ( P = 0.002 for both effects over all E. coli doses) in patterns significantly different from IV E. coli ( P < 0.0001). Compared with control, although HRL- 3 did not alter lung neutrophil numbers or injury score at 6 or 168 h with IV E. coli ( P = ns for all), it reduced both early and increased them late with IB E. coli ( P <= 0.05 for all comparing 6 with 168 h). Thus immunomodulators inhibiting neutrophil function, although potentially beneficial with sepsis due to intravascular infection, may be harmful with extravascular infection regardless of severity. C1 NIH, Dept Crit Care Med, Ctr Clin, Bethesda, MD 20892 USA. RP Eichacker, PQ (reprint author), NIH, Dept Crit Care Med, Ctr Clin, Bldg 10,Rm 7D43, Bethesda, MD 20892 USA. EM peichacker@cc.nih.gov NR 52 TC 14 Z9 14 U1 0 U2 0 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 JUN PY 2005 VL 98 IS 6 BP 2155 EP 2162 DI 10.1152/japplphysiol.01241.2004 PG 8 WC Physiology; Sport Sciences SC Physiology; Sport Sciences GA 929SF UT WOS:000229365500026 PM 15677732 ER PT J AU Rostovtseva, TK Tan, WZ Colombini, M AF Rostovtseva, TK Tan, WZ Colombini, M TI On the role of VDAC in apoptosis: Fact and fiction SO JOURNAL OF BIOENERGETICS AND BIOMEMBRANES LA English DT Review DE apoptosis; VDAC; mitochondria; outer membrane; calcium; arsenic trioxide; permeability transition; Bcl-2 ID DEPENDENT ANION CHANNEL; MITOCHONDRIAL PERMEABILITY TRANSITION; CYTOCHROME-C RELEASE; ADENINE-NUCLEOTIDE TRANSLOCATOR; NEUROSPORA-CRASSA MITOCHONDRIA; PEPTIDE-SPECIFIC ANTIBODIES; OUTER-MEMBRANE CHANNEL; RAT-LIVER MITOCHONDRIA; VOLTAGE-GATED CHANNEL; CELL-DEATH AB Research on VDAC has accelerated as evidence grows of its importance in mitochondrial function and in apoptosis. New investigators entering the field are often confounded by the VDAC literature and its many apparent conflicts and contradictions. This review is an effort to shed light on the situation and identify reliable information from more questionable claims. Our views on the most important controversial issues are as follows: VDAC is only present in the mitochondrial outer membrane. VDAC functions as a monomer. VDAC functions normally with or without Ca2+. It does not form channels that mediate the flux of proteins through membranes (peptides and unfolded proteins are excluded from this statement). Closure of VDAC, not VDAC opening, leads to mitochondria outer membrane permeabilization and apoptosis. C1 NICHD, Lab Phys & Struct Biol, NIH, Bethesda, MD 20892 USA. Univ Maryland, Dept Biol, College Pk, MD 20742 USA. RP Rostovtseva, TK (reprint author), NICHD, Lab Phys & Struct Biol, NIH, Bldg 9,Rm 1E-106, Bethesda, MD 20892 USA. EM rostovtt@mail.nih.gov RI Colombini, Marco/A-1540-2014 FU NINDS NIH HHS [NS 42025] NR 116 TC 148 Z9 162 U1 0 U2 2 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0145-479X J9 J BIOENERG BIOMEMBR JI J. Bioenerg. Biomembr. PD JUN PY 2005 VL 37 IS 3 BP 129 EP 142 DI 10.1007/s10863-005-6566-8 PG 14 WC Biophysics; Cell Biology SC Biophysics; Cell Biology GA 965HB UT WOS:000231940100005 PM 16167170 ER PT J AU Brewer, M Lange, D Baler, R Anzulovich, A AF Brewer, M Lange, D Baler, R Anzulovich, A TI SREBP-1 as a transcriptional integrator of circadian and nutritional cues in the liver SO JOURNAL OF BIOLOGICAL RHYTHMS LA English DT Article DE circadian; liver; sterol response element binding protein; feeding behavior ID ELEMENT-BINDING PROTEINS; FATTY-ACID SYNTHASE; FARNESYL DIPHOSPHATE SYNTHASE; STEROL REGULATION; SUPRACHIASMATIC NUCLEUS; PERIPHERAL-TISSUES; CHOLESTEROL; GENE; PROMOTER; INSULIN AB The act of feeding in mammals can generate such powerful cues for peripheral organs that, under certain conditions, they can override the entraining signals coming from the clock in the brain. Restricting the feeding time to the inactivity period, for example, can completely and quickly reverse the rhythms of gene expression in the liver. This manipulation does not affect the central oscillator in the suprachiasmatic nucleus, which is phase-locked to the light-dark cycle, but does release the peripheral oscillations in the liver from central control. It seems reasonable to predict the existence of one or more immediate response systems designed to sense the need to acutely reverse the sequence of absorptive and postabsorptive phases in the liver. In this study, the authors monitored the posttranslational activation of the sterol response element binding proteins from a circadian point of view to evaluate the role they might play in the circadian organization of the liver transcriptome as well as in the reversal of hepatic physiology that accompanies diurnal restricted feeding. This study highlights a possible direct link between the immediate effects of food consumption on the level of key membrane and humoral factors and the expression status of a set of coordinately regulated target genes in the liver. C1 NIMH, Unit Temporal Gene Express, Lab Cellular & Mol Regulat, NIH, Bethesda, MD 20892 USA. NINDS, Intramural Informat Technol Program, NIH, Bethesda, MD 20892 USA. RP Baler, R (reprint author), NIMH, Unit Temporal Gene Express, Lab Cellular & Mol Regulat, NIH, Neursci Bldg,Room 5248, Bethesda, MD 20892 USA. EM baler@mail.nih.gov RI Jelinek, Milan/C-8515-2011 NR 41 TC 46 Z9 47 U1 0 U2 3 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0748-7304 J9 J BIOL RHYTHM JI J. Biol. Rhythms PD JUN PY 2005 VL 20 IS 3 BP 195 EP 205 DI 10.1177/0748730405275952 PG 11 WC Biology; Physiology SC Life Sciences & Biomedicine - Other Topics; Physiology GA 924RD UT WOS:000228997100001 PM 15851526 ER PT J AU Letocha, AD Cintas, HL Troendle, JF Reynolds, JC Cann, CE Chernoff, EJ Hill, SC Gerber, LH Marini, JC AF Letocha, AD Cintas, HL Troendle, JF Reynolds, JC Cann, CE Chernoff, EJ Hill, SC Gerber, LH Marini, JC TI Controlled trial of pamidronate in children with types III and IV osteogenesis imperfecta confirms vertebral gains but not short-term functional improvement SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Article DE osteogenesis imperfecta; bisphosphonates; pamidronate; BMD; osteoporosis ID BRITTLE BONE-DISEASE; CYCLICAL INTRAVENOUS PAMIDRONATE; BISPHOSPHONATE THERAPY; POSTMENOPAUSAL WOMEN; MINERALIZATION; OSTEOPOROSIS; FORM; ADOLESCENTS; STRENGTH; INFUSION AB Bisphosphonates have been widely administered to children with OI based on observational trials. A randomized controlled trial of q3m intravenous pamidronate in children with types III and IV OI yielded positive vertebral changes in DXA and geometry after 1 year of treatment, but no further significant improvement during extended treatment. The treated group did not experience significantly decreased pain or long bone fractures or have increased motor function or muscle strength. Introduction: Bisphosphonates, antiresorptive drugs for osteoporosis, are widely administered to children with osteogenesis imperfecta (OI). Uncontrolled pamidronate trials in OI reported increased BMD, vertebral coronal area, and mobility, and decreased pain. We conducted a randomized controlled trial of pamidronate in children with types III and IV OI. Materials and Methods: This randomized trial included 18 children (4-13 years of age) with types III and IV OI. The first study year was controlled; 9 children received pamidronate (10 mg/m(2)/day IV for 3 days every 3 months). Four children in each group also received recombinant growth hormone (rGH) injections (0.06 mg/kg/day for 6 days/week). Seven children in the treatment group received pamidronate for an additional 6-21 months. All patients had L-1-L-4 DXA, spine QCT, spine radiographs, and musculoskeletal and functional testing. Results: In the controlled phase, treated patients experienced a significant increase in L-1-L-4 DXA z score (p < 0.001) and increased L-1-L-4 midvertebral height (p = 0.014) and total vertebral area (p = 0.003) compared with controls. During extended treatment, DXA z scores and vertebral heights and areas did not increase significantly beyond the 12-month values. Fracture rate decreased significantly in the upper extremities (p = 0.04) but not the lower extremities (p = 0.09) during the first year of treatment. Gross motor function, muscle strength, and pain did not change significantly during the controlled or extended treatment phases. Conclusions: A controlled trial confirmed the spine benefits of short-term pamidronate treatment in children with types III and IV OI. Pamidronate increased L-1-L-4 vertebral DXA and decreased vertebral compressions and upper extremity fractures. Vertebral measures did not improve during the extended treatment phase. The treatment group did not experience decreased lower extremity long bone fractures, significant improvement in growth, ambulation, muscle strength, or pain. There was substantial variability in individual response to treatment. C1 NICHD, Sect Connect Tissue Disorders, BEMB, NIH, Bethesda, MD 20892 USA. NIH, Dept Rehabil Med, Ctr Clin, Bethesda, MD 20892 USA. NICHD, Biometry & Math Stat Branch, Bethesda, MD USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD 20892 USA. Mindways Software Inc, San Francisco, CA USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. RP Marini, JC (reprint author), NICHD, Sect Connect Tissue Disorders, BEMB, NIH, Bldg 10,Room 9S239,9000 Rockville Pike, Bethesda, MD 20892 USA. EM oidoc@helix.nih.gov NR 44 TC 101 Z9 105 U1 1 U2 3 PU AMER SOC BONE & MINERAL RES PI WASHINGTON PA 2025 M ST, N W, STE 800, WASHINGTON, DC 20036-3309 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD JUN PY 2005 VL 20 IS 6 BP 977 EP 986 DI 10.1359/JBMR.050109 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 928US UT WOS:000229297800012 PM 15883638 ER PT J AU Yim, YI Scarselletta, S Zang, F Wu, XF Lee, DW Kang, YS Eisenberg, E Greeene, LE AF Yim, YI Scarselletta, S Zang, F Wu, XF Lee, DW Kang, YS Eisenberg, E Greeene, LE TI Exchange of clathrin, AP2 and epsin on clathrin-coated pits in permeabilized tissue culture cells SO JOURNAL OF CELL SCIENCE LA English DT Article DE permeabilized cells; clathrin; clathrin adaptors; exchange ID TRANS-GOLGI NETWORK; MEDIATED ENDOCYTOSIS; ACTIN CYTOSKELETON; UNCOATING ATPASE; IN-VIVO; VESICLES; AUXILIN; BINDING; CHOLESTEROL; MEMBRANE AB Clathrin and clathrin adaptors on clathrin-coated pits exchange with cytosolic clathrin and clathrin adaptors in vivo. This exchange might require the molecular chaperone Hsc70 and J-domain-protein auxilin, which, with ATP, uncoat clathrin-coated vesicles both in vivo and in vitro. We find that, although Hsc70 and ATP alone could not uncoat clathrin-coated pits, further addition of auxilin caused rapid uncoating of clathrin but not AP2 and epsin. By contrast, cytosol uncoats clathrin, AP2 and epsin from pits in permeabilized cells, and, concomitantly, these proteins in the cytosol rebind to the same pits, establishing that, like in vivo, these proteins exchange in permeabilized cells. Dissociation and exchange of clathrin in permeabilized cells can be prevented by inhibiting Hsc70 activity. The presence of clathrin-exchange in the permeabilized system substantiates our in vivo observations, and is consistent with the view that Hsc70 and auxilin are involved in the clathrin-exchange that occurs as clathrin-coated pits invaginate in vivo. C1 NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Greeene, LE (reprint author), NHLBI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM greenel@helix.nih.gov NR 38 TC 24 Z9 24 U1 0 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 JUN 1 PY 2005 VL 118 IS 11 BP 2405 EP 2413 DI 10.1242/jcs.02356 PG 9 WC Cell Biology SC Cell Biology GA 939BP UT WOS:000230047500008 PM 15923653 ER PT J AU Elmore, E Siddiqui, S Navidi, M Steele, VE Redpath, JL AF Elmore, E Siddiqui, S Navidi, M Steele, VE Redpath, JL TI Correlation of in vitro chemopreventive efficacy data from the human epidermal cell assay with animal efficacy data and clinical trial plasma levels SO JOURNAL OF CELLULAR BIOCHEMISTRY LA English DT Review DE cancer prevention efficacy; in vitro/in vivo correlation; human keratinocytes; growth inhibition; involucrin expression; in vitro alternatives; clinical correlation ID ABERRANT CRYPT FOCI; INDUCED COLON-CANCER; INDUCED MAMMARY TUMORIGENESIS; INDUCED LUNG-TUMORS; FAMILIAL ADENOMATOUS POLYPOSIS; RAT PROSTATE CARCINOGENESIS; INDUCED SKIN CARCINOGENESIS; AZOXYMETHANE-INDUCED TUMORS; PURIFIED SOY ISOFLAVONES; INDUCED BLADDER-CANCER AB The human epidermal cell (HEC) assay, which uses carcinogen exposed normal skin keratinocytes to screen for cancer prevention efficacy, was used to screen possible preventive agents. The endpoints measured were inhibition of carcinogen-induced growth and induction of involucrin, an early marker of differentiation. Sixteen of twenty agents (apigenin, apomine, budesonide, N-(2-carboxyphenyl)retinamide, ellagic acid, ibuprofen, indomethacin, melatonin, (-)-2-oxo-4-thiazolidine carboxylic acid, polyphenon E, resveratrol, P-sitosterol, sulfasalazine, vitamin E acetate, and zileuton) were positive in at least one of the two assay endpoints. Four agents (4-methoxyphenol, naringenin, palmitoylcarnitine chloride, and silymarin) were negative in the assay. Nine of the sixteen agents were positive for both endpoints. Agents that showed the greatest response included: ellagic acid > budesonide, ibuprofen > apigenin, and quinicrine dihydrochloride. Fifty-eight of sixty-five agents that have been evaluated in the HEC assay have also been evaluated in one or more rodent bioassays for cancer prevention and several are in clinical trials for cancer prevention. The assay has an overall predictive accuracy of similar to 91.4% for efficacy in rodent cancer prevention irrespective of the species used, the tissue model, or the carcinogen used. Comparison of the efficacious concentrations in vitro to plasma levels in clinical trials show that concentrations that produced efficacy in the HEC assay were achieved in clinical studies for 31 of 33 agents for which plasma levels and/or C-max levels were available. For two agents, 9-cis-retinoic acid (RA) and dehydroepiandrosterone (DHEA), the plasma levels greatly exceeded the highest concentration (HC) found to have efficacy in vitro. Thus, the HEC assay hasan excellent predictive potential for animal efficacy and is responsive at clinically achievable concentrations. J. Cell. Biochem. (c) 2005 Wiley-Liss, Inc. C1 Univ Calif Irvine, Dept Radiat Oncol, Irvine, CA 92697 USA. Univ Calif Irvine, Chao Family Comprehens Canc Ctr, Irvine, CA 92697 USA. CCS Associates, Mountain View, CA 94043 USA. NCI, Chemoprevent Agent Dev Res Grp, DCP, NIH, Bethesda, MD 20892 USA. RP Elmore, E (reprint author), Univ Calif Irvine, Dept Radiat Oncol, Med Sci I,B149, Irvine, CA 92697 USA. EM eelmore@uci.edu FU NCI NIH HHS [N01-CN-05104] NR 243 TC 3 Z9 3 U1 1 U2 8 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 JUN 1 PY 2005 VL 95 IS 3 BP 571 EP 588 DI 10.1002/jcb.20426 PG 18 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 929LZ UT WOS:000229348900014 PM 15786488 ER PT J AU Shimazu, K Takeda, K Yu, ZX Jiang, H Liu, XW Nelson, PG Guroff, G AF Shimazu, K Takeda, K Yu, ZX Jiang, H Liu, XW Nelson, PG Guroff, G TI Multiple acute effects on the, membrane potential of PC12 cells produced by nerve growth factor (NGF) SO JOURNAL OF CELLULAR PHYSIOLOGY LA English DT Article ID RAT PHEOCHROMOCYTOMA CELLS; FACTOR-INDUCED INCREASE; SYNAPTIC-TRANSMISSION; HIPPOCAMPAL-NEURONS; NEUROTROPHIC FACTOR; TRK PROTOONCOGENE; LARGE-CONDUCTANCE; CALCIUM-UPTAKE; RECEPTORS; ACTIVATION AB We studied whether nerve growth factor (NGF) can affect the membrane potential and conductance of PC12 cells. We demonstrate that NGF depolarizes the membrane of PC12 cells within a minute and by using transfected NIH 3T3-Trk and -p75 cells we show that both the high affinity NGF receptor p140(trk) and the low affinity NGF receptor or p75(NGF) may be involved in the depolarization. Tyrosine kinase inhibitor, K252a, partially inhibited the depolarization, but two agents affecting intracellular calcium movements, Xestospongin C (XeC) and thapsigargin, did not. The early depolarization was eliminated in Na+ free solutions and under this condition, a 'prolonged' (> 2 min) hyperpolarization was observed in PC12 cells in response to NGF. This hyperpolarization was also induced in PC12 cells by epidermal growth factor (EGF). Voltage clamp experiments showed that NGF produced a late (> 2 min) increase in membrane conductance. The Ca2+-dependent BK-type channel blocker, iberiotoxin, and the general Ca2+-dependent K-channel blocker, TEA, attenuated or eliminated the hyperpolarization produced by NGF in Sodium free media. Under pretreatment with the non-selective cation channel blockers La3+ and Gd3+, NGF hyperpolarized the membrane of PC12 cells. These results suggest that three different Currents are implicated in rapid NGF-induced membrane voltage changes, namely an acutely activated Na+ Current, Ca+-dependent potassium currents and non-selective cation currents. Publislied 2005 Wiley-Liss, Inc. C1 NICHD, Growth Factors Sect, NIH, Bethesda, MD USA. NICHD, Neurobiol Sect, NIH, Bethesda, MD USA. NHLBI, Pathol Sect, NIH, Bethesda, MD USA. RP Nelson, PG (reprint author), NICHHD, Neurobiol Sect, NIH, Bldg 49-Rm 5A38,MSC4480, Bethesda, MD 20892 USA. EM pgnelson@codon.nih.gov NR 31 TC 13 Z9 16 U1 1 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9541 J9 J CELL PHYSIOL JI J. Cell. Physiol. PD JUN PY 2005 VL 203 IS 3 BP 501 EP 509 DI 10.1002/jcp.20309 PG 9 WC Cell Biology; Physiology SC Cell Biology; Physiology GA 922ZE UT WOS:000228877600007 PM 15729735 ER PT J AU Towbin, KE Pradella, A Gorrindo, T Pine, DS Leibenluft, E AF Towbin, KE Pradella, A Gorrindo, T Pine, DS Leibenluft, E TI Autism spectrum traits in children with mood and anxiety disorders SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID PERVASIVE DEVELOPMENTAL DISORDERS; PSYCHIATRICALLY DISTURBED-CHILDREN; UNSUSPECTED LANGUAGE IMPAIRMENTS; DIAGNOSTIC OBSERVATION SCHEDULE; ADAPTIVE-BEHAVIOR SCALES; COMMUNICATION-CHECKLIST; SOCIAL-BEHAVIOR; INTERVIEW; PREVALENCE; INDIVIDUALS AB The autism spectrum disorders (ASDs) can present with symptoms commonly found in mood and anxiety disorders. The Social Communication Questionnaire (SCQ), Children's Communication Checklist (CCC-2), and the Social Reciprocity Scale (SRS) were used to screen children in a mood disorders research clinic setting for symptoms of ASD. Ninety-three patients (mean age, 12.7 +/- 2.8 years; percent male, 63%) completed at least one scale, and 50 children completed all three. The prevalence of those screening positive for a possible ASD on one instrument was 62% and on all three measures was 8%. Fifty-seven percent (n = 21/37; odds ratio, 4.59 [95% confidence interval (CI) = 1.40-15.111) of those scoring in the "ASD-likely" range on the SRS scored in that range on the CCC-2. Only 16% (n = 6/37; odds ratio, not significant (NS)) of those scoring in the ASD-likely range on the SRS, and 14% (n = 5/37; odds ratio, NS) of those scoring in the ASD-likely range on the CCC-2, scored similarly on the SCQ. These results demonstrate a need to develop valid and reliable instruments to screen for ASDs in children presenting outside of ASD clinics. C1 NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Towbin, KE (reprint author), NIMH, Mood & Anxiety Disorders Program, Intramural Res Program, NIH,Dept Hlth & Human Serv, Bldg 10,Rm 3,South 228A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM Kenneth.Towbin@nih.gov NR 48 TC 68 Z9 70 U1 5 U2 17 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD JUN PY 2005 VL 15 IS 3 BP 452 EP 464 DI 10.1089/cap.2005.15.452 PG 13 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 957UN UT WOS:000231398900011 PM 16092910 ER PT J AU Stayer, C Sporn, A Gogtay, N Tossell, JW Lenane, M Gochman, P Greenstein, D Sharp, W Rapoport, JL AF Stayer, C Sporn, A Gogtay, N Tossell, JW Lenane, M Gochman, P Greenstein, D Sharp, W Rapoport, JL TI Multidimensionally impaired: The good news SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID ADOLESCENT-ONSET SCHIZOPHRENIA; PSYCHOTIC DISORDERS; DIAGNOSTIC STABILITY; CHILDHOOD; VALIDITY; RELIABILITY; SCHEDULE; CHILDREN AB Introduction: Long-term outcomes in children with atypical psychosis have been poorly studied. Four to 6 weeks of inpatient observation and up to 11 years (mean, 4.0 +/- 1.3 years) of follow-up have afforded us some experience with this probably heterogeneous group of transiently psychotic patients commonly mislabeled as schizophrenic. Despite severe preadmission morbidity, some patients have successfully remained neuroleptic-free since discharge. Predictors of good versus poor outcome were sought. Methods: Of roughly 150 patients admitted with the presumptive diagnosis of schizophrenia, 32 patients were discharged meeting criteria for psychosis not otherwise specified (NOS), otherwise labeled by the NIMH team as "multidimensionally impaired" (MDI). Admission and biannual follow-up data included a semistructured clinical interview with the Schedule. for Affective Disorders and Schizophrenia for School Age Children (K-SADS), IQ testing, clinical rating scales (e.g., Clinical Global Impression Scale (CGI), Children's Global Assessment Scale (C-GAS), Brief Psychiatric Rating Scale (BPRS), Scales for the Assessment Negative and Positive Symptoms (SANS and SAPS), and Bunney-Hamburg (B-H)). At follow-up (as of February 2005) 38% of patients (12 of 32) met criteria for bipolar 1 disorder, 12% (4 of 23) for major depressive disorder (MDD), and 3% (1 of 32) for schizoaffective disorder. The remaining 47% of patients (15 of 32) were divided into two groups on the basis of whether they were in remission and neuroleptic-free ("good outcome," n = 5) or still severely impaired and/or psychotic regardless of pharmacotherapy ("poor outcome," n = 10) at follow-up. Results: Good-outcome patients had a significantly higher baseline level of functioning (on admission and on medications). This was demonstrated by better scores on CGI (3.5 +/- 0.6 versus 4.8 +/- 0.8; p = 0.03) and C-GAS (66.3 +/- 6.3 versus 38.6 +/- 11.5; p = 0.01). Groups were otherwise comparable in demographic data (gender, race, socioeconomic status, age at onset), months of neuroleptic exposure, severity of psychotic symptoms, and level of premorbid functioning. Conclusion: C-GAS (which correctly classified 85.7% of good-outcome subjects) and CGI at baseline appear to predict outcome. On other variables, MDI subgroups were remarkably similar. C1 NIMH, Child Psychiat Branch, Bethesda, MD 20892 USA. RP Rapoport, JL (reprint author), NIMH, Child Psychiat Branch, Bldg 10,Room 3N 202, Bethesda, MD 20892 USA. EM rapoport@helix.nih.gov RI Gogtay, Nitin/A-3035-2008 NR 31 TC 9 Z9 9 U1 2 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD JUN PY 2005 VL 15 IS 3 BP 510 EP 519 DI 10.1089/cap.2005.15.510 PG 10 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 957UN UT WOS:000231398900015 PM 16092914 ER PT J AU Viding, E Blair, RJR Moffitt, TE Plomin, R AF Viding, E Blair, RJR Moffitt, TE Plomin, R TI Evidence for substantial genetic risk for psychopathy in 7-year-olds SO JOURNAL OF CHILD PSYCHOLOGY AND PSYCHIATRY LA English DT Article DE callous-unemotional traits; genetics; antisocial behaviour ID CHILDREN; MULTIVARIATE; ETIOLOGY; MODELS AB Background: Individuals with early warning signs of life-long psychopathy, callous-unemotional traits (CU) and high levels of antisocial behaviour (AB) can be identified in childhood. We report here the first twin study of high levels of psychopathic tendencies in young children. Methods: At the end of the first school year, teachers provided ratings of CU and AB for 3687 twin pairs from the Twins Early Development Study (TEDS). For the analyses of extreme CU, we selected same-sex twin pairs where at least one twin scored 1.3 or more standard deviations above the mean on the CU scale (612 probands, 459 twin pairs). For the analysis of extreme AB, we selected same-sex twin pairs where at least one twin scored 1.3 or more standard deviations above the mean on AB scale (444 probands, 364 twin pairs). Furthermore, the extreme AB sample was divided into those who were also extreme on CU (children with psychopathic tendencies; 234 probands, 187 twin pairs) and those who did not score in the extreme for CU (children without psychopathic tendencies; 210 probands, 177 twin pairs). Results: DeFries-Fulker extremes analysis indicated that exhibiting high levels of CU is under strong genetic influence. Furthermore, separating children with AB into those with high and low levels of CU showed striking results: AB in children with high levels of CU is under extremely strong genetic influence and no influence of shared environment, whereas AB in children with low levels of CU shows moderate genetic and shared environmental influence. Conclusions: The remarkably high heritability for CU, and for AB children with CU, suggests that molecular genetic research on antisocial behaviour should focus on the CU core of psychopathy. Our findings also raise questions for public policy on interventions for antisocial behaviour. C1 Inst Psychiat, Social Genet & Dev Psychiat Ctr, London SE5 8AF, England. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Viding, E (reprint author), Inst Psychiat, Social Genet & Dev Psychiat Ctr, Box P080,De Crespigny Pk, London SE5 8AF, England. EM spjgemc@iop.kcl.ac.uk RI Moffitt, Terrie/D-5295-2011; Plomin, Robert/B-8911-2008; OI Moffitt, Terrie/0000-0002-8589-6760; Plomin, Robert/0000-0002-0756-3629 FU Medical Research Council [G0601483, G9806489] NR 20 TC 345 Z9 347 U1 13 U2 88 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0021-9630 J9 J CHILD PSYCHOL PSYC JI J. Child Psychol. Psychiatry PD JUN PY 2005 VL 46 IS 6 BP 592 EP 597 DI 10.1111/j.1469-7610.2004.00393.x PG 6 WC Psychology, Developmental; Psychiatry; Psychology SC Psychology; Psychiatry GA 924KZ UT WOS:000228979000005 PM 15877765 ER PT J AU Fox, CS Heard-Costa, NL Vasan, RS Murabito, JM D'Agostino, RB Atwood, LD AF Fox, CS Heard-Costa, NL Vasan, RS Murabito, JM D'Agostino, RB Atwood, LD TI Genomewide linkage analysis of weight change in the Framingham Heart Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID BODY-MASS INDEX; DISEASE RISK-FACTORS; LONG-TERM OVERFEEDING/; QUANTITATIVE-TRAIT; CARDIOVASCULAR-DISEASE; DIABETES-MELLITUS; BLOOD-PRESSURE; VARIANCE-COMPONENTS; GENETIC INFLUENCES; FAT DISTRIBUTION AB Background: Weight gain adversely affects blood pressure, lipids, and glycemia. The genetic contribution to weight change is unknown. Methods: Variance components linkage analysis using microsatellites was performed on 336 families from the Framingham Heart Study offspring cohort, using a 10-cM genome-wide linkage analysis. We evaluated linkage to two traits: short-term (8-yr) weight change and long-term ( up to 24-yr) weight change. Models were adjusted for age, age squared, baseline weight, smoking status, and menopausal status. Results: Mean short-term weight change ranged from 1.4 - 3.8 kg, and mean long-term weight change was 7.7 kg. The heritability of long-term weight change was 0.24; weight change was minimally heritable among younger individuals and over shorter follow-up intervals. We found significant evidence for linkage for long-term weight change, with a peak LOD score of 3.10 on chromosome 20 at 63.7 cM ( nearest marker, D20S481). We also found suggestive evidence for linkage on chromosome 1 at 239.7 cM ( LOD score, 2.28; nearest marker, D1S1644). Conclusion: Long-term weight change is heritable, and evidence for linkage exists on chromosomes 1 and 20. Potential candidate genes include MC3R, ASIP, AGT, and HSD11B1. Additional research is necessary to uncover the genetic underpinnings of weight change that might contribute to associated adverse metabolic profiles. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. NHLBI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Dept Endocrinol Hypertens & Metab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Gen Internal Med, Boston, MA 02118 USA. Boston Univ, Sch Med, Div Cardiol, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Math & Stat, Boston, MA 02118 USA. RP Fox, CS (reprint author), 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM foxca@nhlbi.nih.gov OI Heard-Costa, Nancy/0000-0001-9730-0306; Murabito, Joanne/0000-0002-0192-7516; Ramachandran, Vasan/0000-0001-7357-5970 FU NHLBI NIH HHS [2K24-HL-04334, N01-HC-25195] NR 52 TC 25 Z9 29 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 JUN PY 2005 VL 90 IS 6 BP 3197 EP 3201 DI 10.1210/jc.2004-1752 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 929MU UT WOS:000229351000009 PM 15769990 ER PT J AU Bunt, JC Tataranni, PA Salbe, AD AF Bunt, JC Tataranni, PA Salbe, AD TI Intrauterine exposure to diabetes is a determinant of hemoglobin A(1c) and systolic blood pressure in Pima Indian children SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID INSULIN-RESISTANCE SYNDROME; CARDIOVASCULAR RISK VARIABLES; BIRTH-WEIGHT; METABOLIC SYNDROME; YOUNG ADULTHOOD; OBESITY; ADOLESCENTS; DISEASE; MOTHERS; HYPERTENSION AB Context/Objective: Given the increasing rates of both childhood obesity and type 2 diabetes (T2DM), we investigated whether maternal diabetes status during pregnancy is a determinant of risk factors associated with T2DM or cardiovascular disease in offspring during childhood. Design/Participants: Forty-two Pima Indians, aged 7 - 11 yr, were identified retrospectively from maternal oral glucose tolerance tests as offspring of a diabetic pregnancy ( 22 ODM, eight males, 14 females) or offspring born before the mother developed diabetes ( 20 PRE, 12 males, eight females). Setting/Main Outcome Measures: Weight, height, body mass index, percent body fat, blood pressure, and fasting concentrations of glucose, insulin, hemoglobin A1c (HbA1c), total cholesterol, triglycerides, and high-density lipoprotein-cholesterol were measured while staying in an in-patient clinical research unit and compared in cross-sectional analyses. Results: After adjustment for age and gender, ODM had significantly higher concentrations of HbA1c ( ODM = 5.7 +/- 0.4, PRE = 5.0 +/- 0.4%, P = 0.002), higher systolic (SBP) blood pressure ( ODM = 118 +/- 13, PRE = 107 +/- 10 mm Hg; P = 0.02), and lower concentrations of high-density lipoprotein ( ODM = 41 +/- 9, PRE = 48 +/- 6 mg/dl, P = 0.03) than PRE. Maternal diabetes status during pregnancy persisted as a significant determinant of SBP ( beta = 7.50, P = 0.03) and HbA1c ( beta = 0.43, P = 0.002), independent of age, gender, and percent body fat. Conclusion: Intrauterine exposure to diabetes is a significant determinant of higher SBP and HbA1c during childhood, independent of adiposity and a genetic predisposition to T2DM. These data suggest that in utero exposure to diabetes confers an additional independent risk for the development of T2DM and/or cardiovascular disease later in life. C1 NIDDKD, Obes & Clin Diabet Res Sect, NIH, US Dept HHS, Phoenix, AZ 85016 USA. RP Bunt, JC (reprint author), NIDDKD, Obes & Clin Diabet Res Sect, NIH, US Dept HHS, 4212 N 16th St,Room 541-A, Phoenix, AZ 85016 USA. EM jbunt@mail.nih.gov FU NIDDK NIH HHS [Z01 DK069015-23] NR 49 TC 68 Z9 70 U1 1 U2 3 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 JUN PY 2005 VL 90 IS 6 BP 3225 EP 3229 DI 10.1210/jc.2005-0007 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 929MU UT WOS:000229351000013 PM 15797952 ER PT J AU Adler-Wailes, DC Liu, HG Ahmad, F Feng, NP Londos, C Manganiello, V Yanovski, JA AF Adler-Wailes, DC Liu, HG Ahmad, F Feng, NP Londos, C Manganiello, V Yanovski, JA TI Effects of the human immunodeficiency virus-protease inhibitor, ritonavir, on basal and catecholamine-stimulated lipolysis SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID HORMONE-SENSITIVE LIPASE; NUCLEOTIDE PHOSPHODIESTERASE 3B; ACTIVE ANTIRETROVIRAL THERAPY; ADIPOSE-TISSUE METABOLISM; LIPID STORAGE DROPLETS; HIV-INFECTED MEN; INSULIN-RESISTANCE; 3T3-L1 ADIPOCYTES; PERILIPIN-A; KINASE-A AB Several of the aspartic acid protease inhibitors used to treat HIV infection increase basal lipolysis in adipocytes, but the cellular mechanisms leading to this augmentation are not well understood. We therefore studied the effects of chronic exposure to the HIV protease inhibitor, ritonavir, on the lipolytic cascade in 3T3-L1 adipocytes. Treatment of 3T3-L1 adipocytes with ritonavir for 14 d ( during and after differentiation) enhanced basal, isoproterenol (Iso)-stimulated, and cAMP analog-stimulated lipolysis. Enhancement of lipolysis was observed after Iso at concentrations between 0.1 and 10 mu M. Despite a significant decrease in cyclic nucleotide phosphodiesterase (PDE) 3B activity and protein levels, there were no changes in Iso-stimulated intracellular cAMP, protein kinase A (PKA) expression, or PKA activity. Ritonavir-augmented lipolysis was also observed under conditions that reversed the effect on PDE3B activity via preincubation with 1 mu M (-)- N(6)-(2-phenylisopropyl) adenosine. In ritonavir-treated cells, protein expression of the lipid droplet-protective protein, perilipin, was significantly decreased, whereas there was no change in hormone-sensitive lipase. Activation of ERK1/2 by Iso did not play a role in the augmentation. We conclude that ritonavir decreases PDE3B and perilipin protein expression and affects both basal and catecholamine-stimulated lipolysis in 3T3-L1 adipocytes primarily through actions at sites downstream of PKA. C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, Bethesda, MD 20892 USA. NHLBI, Pulm Crit Care Med Branch, Bethesda, MD 20892 USA. NIDDKD, Membrane Regulat Sect, Cellular & Dev Biol Lab,NIH, US Dept HHS, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NIH, Clin Res Ctr, Room 1-3330,10 Ctr Dr,MSC-1103, Bethesda, MD 20892 USA. EM jy15i@nih.gov OI Yanovski, Jack/0000-0001-8542-1637 FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [Z01 HD000641] NR 78 TC 15 Z9 15 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 JUN PY 2005 VL 90 IS 6 BP 3251 EP 3261 DI 10.1210/jc.2004-2194 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 929MU UT WOS:000229351000017 PM 15741249 ER PT J AU Murabito, JM Yang, Q Fox, C Wilson, PWF Cupples, LA AF Murabito, JM Yang, Q Fox, C Wilson, PWF Cupples, LA TI Heritability of age at natural menopause in the Framingham Heart Study SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID LINKAGE ANALYSIS; COHORT; WOMEN; WINSORIZATION; TRANSITION; SAMPLE; ONSET; POWER; LIFE AB Background: Twin registries and family history studies provide evidence that genetic factors contribute to the onset of menopause, but heritability estimates in population-based samples are limited. We sought to estimate heritability of age at natural menopause in women participating in the multigenerational Framingham Heart Study, a community-based epidemiological study. Methods: A total of 1500 original cohort and 932 offspring cohort women from 1296 extended families reported a natural menopause defined as the natural cessation of menses for 1 yr or more. Correlation coefficients were calculated using family correlations in Statistical Applications for Genetic Epidemiology for mother-daughter, sister-sister, and aunt-niece pairs. Heritability was estimated using variance-components methods in the Sequential Oligogenic Linkage Analysis Routines ( SOLAR) computer package. Covariates in the multivariable models included generation, number of cigarettes smoked, body mass index, and parity. Results: The mean age at natural menopause was 49.1 and 49.4 yr in original cohort and offspring women, respectively. The multivariable-adjusted correlation coefficients for mother-daughter, sister-sister, and aunt-niece pairs were 0.21, 0.22, and 0.12, respectively. The crude and multivariable-adjusted heritability estimates for age at natural menopause were 0.49 (0.37, 0.61) and 0.52 (0.35, 0.69). Conclusions: Our data suggest that at least 50% of the interindividual variability in menopausal age appears to be attributable to genetic effects. C1 NHLBI, Framingham Heart Study, Framingham, MA 01702 USA. Boston Univ, Sch Med, Gen Internal Med Sect, Boston, MA 02118 USA. Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02118 USA. Boston Univ, Sch Med, Dept Neurol, Boston, MA 02118 USA. NHLBI, Bethesda, MD 20892 USA. Brigham & Womens Hosp, Dept Endocrinol Diabet & Hypertens, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Med Univ S Carolina, Dept Endocrinol, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Diabet, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Med Genet, Charleston, SC 29425 USA. RP Murabito, JM (reprint author), NHLBI, Framingham Heart Study, 73 Mt Wayte Ave,Suite 2, Framingham, MA 01702 USA. EM Murabito@bu.edu RI Yang, Qiong/G-5438-2014; OI Cupples, L. Adrienne/0000-0003-0273-7965; Murabito, Joanne/0000-0002-0192-7516 FU NHLBI NIH HHS [N01-HC-25195] NR 24 TC 102 Z9 103 U1 1 U2 5 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2005 VL 90 IS 6 BP 3427 EP 3430 DI 10.1210/jc.2005-0181 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 929MU UT WOS:000229351000042 PM 15769979 ER PT J AU Fruchter, O Kino, T Zoumakis, E Alesci, S De Martino, M Chrousos, G Hochberg, Z AF Fruchter, O Kino, T Zoumakis, E Alesci, S De Martino, M Chrousos, G Hochberg, Z TI The human glucocorticoid receptor (GR) isoform beta differentially suppresses GR alpha-induced transactivation stimulated by synthetic glucocorticoids SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID RHEUMATOID-ARTHRITIS; CORTICOSTEROID RESISTANCE; EXPRESSION; ASTHMA; CELLS; MECHANISMS; SENSITIVITY AB The beta-isoform of human glucocorticoid receptor beta (hGR beta) acts as a natural dominant negative inhibitor of hGR alpha-induced transactivation of glucocorticoid-responsive genes. We determined hGR beta ability to suppress hGR alpha transactivation that was induced by commonly used synthetic glucocorticoids. HepG2/C3A cells were transiently cotransfected with GR cDNA and a glucocorticoid-responsive promoter, luciferase (MMTV-luc). Transfected cells were incubated for 16 h with glucocorticoid and luciferase. For each compound, a dose-response curve was constructed, and half-maximal effective concentrations and maximal transcriptional activities were compared. hGR beta, at a 1: 1 ratio to hGR alpha, differentially suppressed hGR alpha-induced maximal transcriptional activity stimulated by triamcinolone, dexamethasone, hydrocortisone, and betamethasone ( by 96, 68, 62, and 49%, respectively) but not by methylprednisolone. The suppressive effect of hGR beta on hGR alpha-induced transactivation was stronger at lower concentrations of all tested glucocorticoids, whereas it was blunted at higher concentrations. We conclude that the potency of the dominant negative effect of hGR beta on hGR alpha-induced transactivation depends on both the type and the dose of the synthetic glucocorticoids in use. These results may provide helpful information concerning the selection of synthetic glucocorticoids for treatment of pathological conditions in which hGR beta modulates the sensitivity of tissues to glucocorticoids. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Rambam Med Ctr, Meyer Childrens Hosp, IL-31096 Haifa, Israel. RP Fruchter, O (reprint author), NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. EM o_fruchter@rambam.health.gov.il NR 37 TC 26 Z9 28 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 JUN PY 2005 VL 90 IS 6 BP 3505 EP 3509 DI 10.1210/jc.2004-1646 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 929MU UT WOS:000229351000054 PM 15755863 ER PT J AU Charmandari, E Raji, A Kino, T Ichijo, T Tiulpakov, A Zachman, K Chrousos, GP AF Charmandari, E Raji, A Kino, T Ichijo, T Tiulpakov, A Zachman, K Chrousos, GP TI A novel point mutation in the ligand-binding domain (LBD) of the human glucocorticoid receptor (hGR) causing generalized glucocorticoid resistance: The importance of the C terminus of hGR LBD in conferring transactivational activity SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID PRIMARY CORTISOL RESISTANCE; NUCLEAR-LOCALIZATION; HORMONE-BINDING; TRANSCRIPTIONAL COACTIVATOR; ATYPICAL DEPRESSION; CLINICAL PHENOTYPE; GENE; COREGULATORS; MECHANISMS; MULTIPLE AB Glucocorticoid resistance is a rare, familial or sporadic condition characterized by partial end-organ insensitivity to glucocorticoids. The clinical spectrum of the condition is broad, ranging from completely asymptomatic to severe hyperandrogenism and/or mineralocorticoid excess. The molecular basis of glucocorticoid resistance has been ascribed to mutations in the human glucocorticoid receptor-alpha(hGR alpha) gene, which impair one or more of the molecular mechanisms of GR action, thus altering tissue sensitivity to glucocorticoids. We identified a new case of generalized glucocorticoid resistance in a young woman who presented with a long-standing history of fatigue, anxiety, hyperandrogenism, and hypertension. The disease was caused by a novel, heterozygous mutation (T-->C) at nucleotide position 2318 (exon 9) of the hGR alpha gene, which resulted in substitution of leucine by proline at amino acid position 773 in the ligand-binding domain of the receptor. We systematically investigated the molecular mechanisms through which the natural hGR alpha L773P mutant impaired glucocorticoid signal transduction. Compared with the wild-type hGR alpha, hGR alpha L773P demonstrated a 2-fold reduction in the ability to transactivate the glucocorticoid-inducible mouse mammary tumor virus promoter, exerted a dominant negative effect on the wild-type receptor, had a 2.6-fold reduction in the affinity for ligand, showed delayed nuclear translocation ( 30 vs. 12 min), and, although it preserved its ability to bind to DNA, displayed an abnormal interaction with the GR-interacting protein 1 coactivator in vitro. We conclude that the carboxyl terminus of the ligand-binding domain of hGR alpha is extremely important in conferring transactivational activity by altering multiple functions of this composite transcription factor. C1 NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Dept Endocrinol, Boston, MA 02115 USA. RP Charmandari, E (reprint author), Great Ormond St Hosp Children, Dept Pediat Endocrinol, 8th Floor,Southwood Bldg,Great Ormond St, London WC1N 3JH, England. EM charmane@mail.nih.gov RI Charmandari, Evangelia/B-6701-2011 NR 48 TC 55 Z9 58 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2005 VL 90 IS 6 BP 3696 EP 3705 DI 10.1210/jc.2004-1920 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 929MU UT WOS:000229351000079 PM 15769988 ER PT J AU Vogel, TWA Brouwers, FM Lubensky, IA Vortmeyer, AO Weil, RJ Walther, MM Oldfield, EH Linehan, WM Pacak, K Zhuang, ZP AF Vogel, TWA Brouwers, FM Lubensky, IA Vortmeyer, AO Weil, RJ Walther, MM Oldfield, EH Linehan, WM Pacak, K Zhuang, ZP TI Differential expression of erythropoietin and its receptor in von Hippel-Lindau-associated and multiple endocrine neoplasia type 2-associated pheochromocytomas SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID CHROMAFFIN CELLS; DISEASE; GENE; APOPTOSIS; DIAGNOSIS; BCL-X(L); LINEAGE; CANCER; TUMORS; RET AB Pheochromocytoma is a neuroendocrine tumor associated with a variety of genetic disorders, which include von Hippel-Lindau disease (VHL), multiple endocrine neoplasia type 2 ( MEN 2), neurofibromatosis type 1, hereditary paraganglioma, and succinate dehydrogenase gene-related tumors. Previous studies of VHL-associated and MEN 2-associated pheochromocytomas suggest morphological, biochemical, and clinical differences exist among the tumors, but the process by which they develop remains unclear. Studies in other VHL-associated tumors suggest that VHL gene deficiency causes coexpression of erythropoietin (Epo) and its receptor (Epo-R), which facilitates tumor growth. The objective of this study was to understand the different process of tumorigenesis for VHL and MEN 2-associated pheochromocytomas. Ten pheochromocytomas ( VHL patients n = 5, MEN 2 patients n = 5) were examined for the presence or absence of Epo and Epo-R using Western blot, immunohistochemistry, and RT-PCR analyses. Coexpression of Epo and Epo-R was found in all five VHL-associated pheochromocytomas; in contrast, expression of Epo-R, but not Epo, was documented in all five MEN 2-associated pheochromocytomas. Expression of Epo appears to be a result of VHL gene deficiency, possibly through activation of the hypoxia inducible factor-1 pathway, whereas Epo-R is an embryonal marker whose sustained expression in both VHL- and MEN 2-associated pheochromocytomas reflects an arrest or defect in development. These findings suggest an alternative process of tumorigenesis in VHL- and MEN 2-associated pheochromocytomas and implicate Epo as a clinical biomarker to differentiate these tumors. C1 NINDS, Surg Neurol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat & Reprod Endocrinol Branch, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Zhuang, ZP (reprint author), NINDS, Surg Neurol Branch, NIH, Bldg 10,Room 5d-37, Bethesda, MD 20892 USA. EM zhuangp@ninds.nih.gov NR 30 TC 13 Z9 14 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD JUN PY 2005 VL 90 IS 6 BP 3747 EP 3751 DI 10.1210/jc.2004-1899 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 929MU UT WOS:000229351000085 PM 15769989 ER PT J AU Matyakhina, L Freedman, RJ Bourdeau, I Wei, MH Stergiopoulos, SG Chidakel, A Walther, M Abu-Asab, M Tsokos, M Keil, M Toro, J Linehan, WM Stratakis, CA AF Matyakhina, L Freedman, RJ Bourdeau, I Wei, MH Stergiopoulos, SG Chidakel, A Walther, M Abu-Asab, M Tsokos, M Keil, M Toro, J Linehan, WM Stratakis, CA TI Hereditary leiomyomatosis associated with bilateral, massive, macronodular adrenocortical disease and atypical Cushing syndrome: A clinical and molecular genetic investigation SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article ID ENDOCRINE NEOPLASIA TYPE-1; MCCUNE-ALBRIGHT-SYNDROME; RENAL-CELL CANCER; ALPHA REGULATORY SUBUNIT; ADRENAL INCIDENTALOMAS; FUMARATE-HYDRATASE; UTERINE LEIOMYOMAS; CUTANEOUS LEIOMYOMATOSIS; ACTIVATING MUTATIONS; SOMATIC MUTATIONS AB Hereditary leiomyomatosis and renal cell cancer (HLRCC) is an autosomal dominant disorder caused by mutations in the fumarate hydratase (FH) gene on chromosome 1q42.3 - 43. Massive macronodular adrenocortical disease (MMAD) is a heterogeneous condition associated with Cushing syndrome ( CS) and bilateral hyperplasia of the adrenal glands. In MMAD, cortisol secretion is often mediated by ectopic, adrenocortical expression of receptors for a variety of substances; however, to date, no consistent genetic defects have been identified. In a patient with HLRCC caused by a germline-inactivating FH mutation, we diagnosed atypical ( subclinical) CS due to bilateral, ACTH-independent adrenocortical hyperplasia. A clinical protocol for the detection of ectopic expression of various hormone receptors was employed. Histology was consistent with MMAD. The tumor tissue harbored the germline FH mutation and demonstrated allelic losses of the 1q42.3 - 43 FH locus. We then searched the National Institutes of Health (NIH) databases of patients with MMAD or HLRCC and found at least three other cases with MMAD that had a history of tumors that could be part of HLRCC; among patients with HLRCC, there were several with some adrenal nodularity noted on computed tomography but none with imaging findings consistent with MMAD. From two of the three MMAD patients, adrenocortical tumor DNA was available and sequenced for coding FH mutations; there were none. We conclude that in a patient with HLRCC, adrenal hyperplasia and CS were due to MMAD. The latter was likely due to the FH germline mutation because in tumor cells, only the mutant allele was retained. However, other patients with MMAD and HLRCC, or HLRCC patients with adrenal imaging findings consistent with MMAD, or MMAD patients with somatic FH mutations were not found among the NIH series. Although a fortuitous association cannot be excluded, HLRCC may be added to the short list of monogenic disorders that have been reported to be associated with the development of adrenal tumors; FH may be considered a candidate gene for MMAD. C1 NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH,Clin Res Ctr, Bethesda, MD 20892 USA. SAIC Frederick Inc, Div Canc Epidemiol & Genet Program, Frederick, MD USA. NCI, Sect Electron Microscopy, NIH, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Epidemiol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Inter Inst Endocrinol Training Program, NIH, Bethesda, MD 20892 USA. RP Stratakis, CA (reprint author), NICHHD, Sect Endocrinol & Genet, Dev Endocrinol Branch, NIH,Clin Res Ctr, Bldg 10,Room I-3330 E Labs,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM stratakc@mail.nih.gov RI Levesque, Isabelle/A-1899-2012; OI Abu-Asab, Mones/0000-0002-4047-1232; Chidakel, Aaron/0000-0002-0854-7348 NR 43 TC 35 Z9 35 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 JUN PY 2005 VL 90 IS 6 BP 3773 EP 3779 DI 10.1210/jc.2004-2377 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 929MU UT WOS:000229351000090 PM 15741255 ER PT J AU Bafica, A Scanga, CA Serhan, C Machado, F White, S Sher, A Aliberti, J AF Bafica, A Scanga, CA Serhan, C Machado, F White, S Sher, A Aliberti, J TI Host control of Mycobacterium tuberculosis is regulated by 5-lipoxygenase-dependent lipoxin production SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID BACTERICIDAL/PERMEABILITY-INCREASING PROTEIN; RANDOMIZED CONTROLLED-TRIAL; HUMAN MUCOSAL EPITHELIA; RECEPTOR DEFICIENCY; TOXOPLASMA-GONDII; IL-12 PRODUCTION; MODERATE ASTHMA; INFECTION; IMMUNITY; MICE AB Th1 type cytokine responses are critical in the control of Mycobacterium tuberculosis infection. Recent findings indicate that 5-lipoxygenase-dependent(5-LO-dependent) lipoxins regulate host IL-12 production in vivo. Here, we establish lipoxins as key chemical mediators in resistance to M. tuberculosis infection. High levels of lipoxin A(4) (LXA(4)) were detected in sera from infected WT but not infected 5-LO-deficient mice. Moreover, lungs from M. tuberculosis-infected 5-16(-/-) animals showed increased IL-12, IFN-γ, and NO synthase 2 (NOS2) mRNA levels compared with the same tissues in WT mice. Similarly, splenocyte recall responses were enhanced in mycobacteria-infected 5-lo(-/-) versus WT mice. Importantly, bacterial burdens in 5-lo(-/-) lungs were significantly lower than those from WT mice, and this enhancement in the resistance of the 5-lo(-/-) animals to M. tuberculosis was completely prevented by administration of a stable LXA4 analog. Together our results demonstrate that lipoxins negatively regulate protective Th1 responses against mycobacterial infection in vivo and suggest that the inhibition of lipoxin biosynthesis could serve as a strategy for enhancing host resistance to M. tuberculosis. C1 Duke Univ, Med Ctr, Sch Med, Dept Immunol, Durham, NC 27710 USA. NIAID, Immunobiol Sect, Parasit Dis Lab, Bethesda, MD 20892 USA. Fdn Oswaldo Cruz, Lab Imunorregulacao & Microbiol, Ctr Pesquisas Goncalo Moinz, Salvador, BA, Brazil. Harvard Univ, Brigham & Womens Hosp, Ctr Expt Therapeut & Reperfus Injury, Dept Anesthesiol Perioperat & Pain Med,Sch Med, Boston, MA 02115 USA. RP Aliberti, J (reprint author), Duke Univ, Med Ctr, Sch Med, Dept Immunol, 136 Jones Bldg,Box 3010, Durham, NC 27710 USA. EM julio.aliberti@duke.edu RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 30 TC 124 Z9 129 U1 1 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 JUN PY 2005 VL 115 IS 6 BP 1601 EP 1606 DI 10.1172/JCI23949 PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 932ZC UT WOS:000229592300034 PM 15931391 ER PT J AU Gattinoni, L Klebanoff, CA Palmer, DC Wrzesinski, C Kerstann, K Yu, ZY Finkelstein, SE Theoret, MR Rosenberg, SA Restifo, NP AF Gattinoni, L Klebanoff, CA Palmer, DC Wrzesinski, C Kerstann, K Yu, ZY Finkelstein, SE Theoret, MR Rosenberg, SA Restifo, NP TI Acquisition of full effector function in vitro paradoxically impairs the in vivo antitumor efficacy of adoptively transferred CD8(+) T cells SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID METASTATIC MELANOMA; HOMEOSTATIC PROLIFERATION; SELECTIVE EXPRESSION; CANCER REGRESSION; TRANSFER THERAPY; CENTRAL MEMORY; SOLID TUMORS; LYMPH-NODES; BONE-MARROW; IMMUNITY AB T cell differentiation is a progressive process characterized by phenotypic and functional changes. By transferring tumor-specific CD8(+) T cells into tumor-bearing mice at various stages of differentiation, we evaluated their efficacy for adoptive immunotherapy. We found that administration of naive and early effector T cells, in combination with active immunization and IL-2, resulted in the eradication of large, established tumors. Despite enhanced in vitro antitumor properties, more-differentiated effector T cells were less effective for in vivo tumor treatment. Several events may underlie this paradoxical phenomenon: (a) downregulation of lymphoid-homing and costimulatory molecules; (b) inability to produce IL-2 and access homeostatic cytokines; and (c) entry into a proapoptotic and replicative senescent state. While the progressive acquisition of terminal effector properties is characterized by pronounced in vitro tumor killing, in vivo T cell activation, proliferation, and survival are progressively impaired. These findings suggest that the current methodology for selecting T cells for transfer is inadequate and provide new criteria for the generation and the screening of optimal lymphocyte populations for adoptive immunotherapy. C1 NCI, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Scholars Program, Bethesda, MD 20892 USA. RP Restifo, NP (reprint author), NCI, NIH, Mark O Hatfield Clin Res Ctr, Room 3-5762,10 Ctr Dr, Bethesda, MD 20892 USA. EM restifo@nih.gov RI Gattinoni, Luca/A-2281-2008; Wrzesinski, Claudia/A-3077-2008; 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 53 TC 463 Z9 476 U1 2 U2 12 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 JUN PY 2005 VL 115 IS 6 BP 1616 EP 1626 DI 10.1172/JCI24480 PG 11 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 932ZC UT WOS:000229592300036 PM 15931392 ER PT J AU Zelazny, AM Ferraro, MJ Glennen, A Hindler, JF Mann, LM Munro, S Murray, PR Reller, LB Tenover, FC Jorgensen, JH AF Zelazny, AM Ferraro, MJ Glennen, A Hindler, JF Mann, LM Munro, S Murray, PR Reller, LB Tenover, FC Jorgensen, JH TI Selection of strains for quality assessment of the disk induction method for detection of inducible clindamycin resistance in staphylococci: a CLSI collaborative study SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID COAGULASE-NEGATIVE STAPHYLOCOCCI; AUREUS; SUSCEPTIBILITY; MACROLIDES AB A nine-laboratory collaborative study was conducted to select positive and negative quality assessment control strains for the detection of inducible clindamycin resistance in staphylococci. Four strains of Staphylococcus aureus were tested as unknowns on 10 different days in each laboratory using the recently recommended CLSI (formerly NCCLS) disk diffusion method and the inoculum purity control method. Strains contained either macrolide-lincosamide-streptogramin B (MLSB) resistance genes encoded by erm(A) or erm(C) or a macrolide resistance efflux pump encoded by msr(A). Based upon the results of this study, strain UT 32 (now designated ATCC strain BAA-977) containing erm(A) is recommended as the positive control organism for inducible clindamycin resistance. Strain UT 25 (now designated ATCC BAA-976), which harbors the efflux pump encoded by msr(A), is recommended as the negative control organism. C1 Univ Texas, Hlth Sci Ctr, Dept Pathol, San Antonio, TX 78229 USA. NIH, Microbiol Serv, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Massachusetts Gen Hosp, Microbiol Lab,Clin Microbiol Lab, Boston, MA 02114 USA. Minnesota Dept Hlth, Minneapolis, MN 55414 USA. Univ Calif Los Angeles, Dept Pathol & Lab Med, Los Angeles, CA 90025 USA. Baylor Univ, Med Ctr, Clin Microbiol Lab, Dallas, TX 75246 USA. Stanford Univ, Sch Med, Clin Microbiol Lab, Stanford, CA 94305 USA. Duke Univ, Med Ctr, Clin Microbiol Lab, Durham, NC 27710 USA. Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. RP Jorgensen, JH (reprint author), Univ Texas, Hlth Sci Ctr, Dept Pathol, 7703 Floyd Curl Dr, San Antonio, TX 78229 USA. EM jorgensen@uthscsa.edu NR 10 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2005 VL 43 IS 6 BP 2613 EP 2615 DI 10.1128/JCM.43.6.2613-2615.2005 PG 3 WC Microbiology SC Microbiology GA 936SF UT WOS:000229875000012 PM 15956373 ER PT J AU Conville, PS Witebsky, FG AF Conville, PS Witebsky, FG TI Multiple copies of the 16S rRNA gene in Nocardia nova isolates and implications for sequence-based identification procedures SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID RESTRICTION-ENDONUCLEASE ANALYSIS; DNA; MYCOBACTERIA; RHODOCOCCUS; ASTEROIDES AB Molecular investigation of two Nocardia patient isolates showed unusual restriction fragment length polymorphism patterns with restriction endonuclease assays (REA) using an amplified portion of the 16S rRNA gene. Patterns typical of Nocardia nova were obtained with REA of an amplified portion of the 65-kDa heat shock protein gene. Subsequent sequence analysis of the 16S rRNA gene regions of these isolates showed the presence of ambiguous bases within an expected restriction endonuclease recognition site which were not able to be resolved on repeat testing. Cloning of amplified regions of the 16S rRNA genes and subsequent sequencing of the resulting clones from the two patient isolates showed three different 16S rRNA gene sequences which corresponded to sequences found in N. nova, a molecular variant of N. nova, and a previously undescribed sequence. Hybridization studies using a DNA probe corresponding to an 89-bp conserved region of the 16S rRNA gene confirmed the presence of at least two copies of the 16S rRNA gene in the N. nova type strain, in a patient isolate identical to the molecular variant of N. nova, and in the two other patient isolates. All isolates were found to belong to the species N. nova as determined by DNA-DNA hybridization. Because minimal variation has been found in the 16S rRNA gene sequences of different species of Nocardia, those laboratories employing molecular methods for identification of these species must be aware of the potential identification complications that may be caused by the presence of differing 16S rRNA genes in the same isolate. C1 NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Microbiol Serv,US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Conville, PS (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Lab Med, Microbiol Serv,US Dept Hlth & Human Serv, 10 Ctr Dr,MSC 1508, Bethesda, MD 20892 USA. EM pconville@nih.gov NR 17 TC 27 Z9 29 U1 0 U2 2 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 JUN PY 2005 VL 43 IS 6 BP 2881 EP 2885 DI 10.1128/JCM.43.6.2881-2885.2005 PG 5 WC Microbiology SC Microbiology GA 936SF UT WOS:000229875000051 PM 15956412 ER PT J AU Paik, S Shak, S Tang, G Kim, C Baker, J Cronin, M Watson, D Bryant, J Costantino, J Wolmark, N AF Paik, S Shak, S Tang, G Kim, C Baker, J Cronin, M Watson, D Bryant, J Costantino, J Wolmark, N TI Expression of the 21 genes in the Recurrence Score assay and tamoxifen clinical benefit in the NSABP study B-14 of node negative, estrogen receptor positive breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NSABP, Pittsburgh, PA USA. Genom Hlth Inc, Redwood City, CA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. NR 0 TC 13 Z9 13 U1 4 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 6S EP 6S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326600022 ER PT J AU Swain, SM Land, SR Sundry, R Ritter, M Costantino, J Wolmark, N Ganz, PA AF Swain, SM Land, SR Sundry, R Ritter, M Costantino, J Wolmark, N Ganz, PA TI Amenorrhea in premenopausal women on the doxorubicin (A) and cyclophosphamide (C)-> docetaxel (T) arm of NSABP B-30: Preliminary results. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Natl Canc Inst, Bethesda, MD USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. NR 0 TC 6 Z9 6 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 13S EP 13S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326600049 ER PT J AU Doshi, A Wedam, SB Thomasson, DM Garcia-Eulate, RM Wise, BJ Yao, J Steinberg, SM Liewehr, DJ Choyke, P Swain, SM AF Doshi, A Wedam, SB Thomasson, DM Garcia-Eulate, RM Wise, BJ Yao, J Steinberg, SM Liewehr, DJ Choyke, P Swain, SM TI Dynamic contrast enhanced MRI (DCE-MRI) as a potential predictor of clinical response in patients with inflammatory breast cancer (IBC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Canc Therapeut Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, MOCRU, CCR, NIH, Bethesda, MD 20892 USA. NIH, Dept Radiol, Ctr Clin, Bethesda, MD 20892 USA. NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Mol Imaging Program, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 24S EP 24S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326600096 ER PT J AU Denduluri, N Wedam, SB Yang, SX Parr, A Berman, A Steinberg, S Swain, SM AF Denduluri, N Wedam, SB Yang, SX Parr, A Berman, A Steinberg, S Swain, SM TI Effect of bevacizurnab and chemotherapy on serum levels of sVCAM-1 in patient with inflammatory and locally advanced breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Canc Therapeut Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, MOCRU, CCR, NIH, Bethesda, MD 20892 USA. NCI, Data Management Sect, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 31S EP 31S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326600123 ER PT J AU Lee, JJ Low, JA Croarkin, E Parks, R Berman, AW Mannan, N Steinberg, SM Swain, SM AF Lee, JJ Low, JA Croarkin, E Parks, R Berman, AW Mannan, N Steinberg, SM Swain, SM TI Evaluation of neuropathy in breast cancer patients treated with ixabepilone. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Canc Therapeut Branch, CCR, NIH, Bethesda, MD 20892 USA. NCI, Div Canc Treatment, Canc Therapy Evaluat Program, NIH, Bethesda, MD 20892 USA. NIH, Dept Rehabil Med, Bethesda, MD 20892 USA. NCI, MOCRU, CCR, NIH, Bethesda, MD 20892 USA. NCI, Data Management Sect, CCR, NIH, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 42S EP 42S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326600168 ER PT J AU Tanchiu, E Kaufman, PA Paik, S Ulcickas-Yood, M Mayer, M Tripathy, D Rugo, H Brufsky, A AF Tanchiu, E Kaufman, PA Paik, S Ulcickas-Yood, M Mayer, M Tripathy, D Rugo, H Brufsky, A TI registHER: A prospective, longitudinal cohort study of women with HER2 positive metastatic breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Canc Res Network, Plantation, FL USA. Dartmouth Hitchcock Med Ctr, Lebanon, NH 03766 USA. NSABP, Pittsburgh, PA USA. Episource LLC, Hamden, CT USA. Patient Advocate, New York, NY USA. Univ Texas, SW Med Ctr, Dallas, TX 75230 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 46S EP 46S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326600181 ER PT J AU Arun, B Mohsin, S Miller, A Isaacs, C Saxton, K Hilsenbeck, S Lamph, W Johnson, K Brown, P Elledge, R AF Arun, B Mohsin, S Miller, A Isaacs, C Saxton, K Hilsenbeck, S Lamph, W Johnson, K Brown, P Elledge, R TI Acquisition of breast tissue in a biomarker modulation study using bexarotene in women at high risk of breast cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Canc Therapy & Res Ctr2, San Antonio, TX USA. Georgetown Univ, Washington, DC USA. Ligand Pharmaceut, San Diego, CA USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 106S EP 106S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326600419 ER PT J AU Holmberg, C Adams-Campbell, L Costantino, JP Pearson, J Mccaskill-Stevens, W AF Holmberg, C Adams-Campbell, L Costantino, JP Pearson, J Mccaskill-Stevens, W TI Determinants of participation in the study of tamoxifen and raloxifene (STAR): Experience of a minority-based community oncology program. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Howard Univ, Ctr Canc, Washington, DC 20059 USA. Univ Pittsburgh, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 108S EP 108S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326600429 ER PT J AU Fine, HA Kim, L Royce, C Draper, D Haggarty, I Ellinzano, H Albert, P Kinney, P Musib, L Thornton, D AF Fine, HA Kim, L Royce, C Draper, D Haggarty, I Ellinzano, H Albert, P Kinney, P Musib, L Thornton, D TI Results from phase II trial of enzastaurin (LY317615) in patients with recurrent high grade gliomas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Neurooncol Branch, NIH, Bethesda, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. NCI, Biometr Branch, Bethesda, MD 20892 USA. Eli Lilly, Indianapolis, IN USA. NR 0 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 115S EP 115S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326600454 ER PT J AU Lustig, RA Mikkelesen, T Lesser, G Grossman, S Ye, X Desideri, S Fisher, J Wright, J AF Lustig, RA Mikkelesen, T Lesser, G Grossman, S Ye, X Desideri, S Fisher, J Wright, J TI Pre-radiation R115777 in patients with newly diagnosed glioblastoma multiforme and residual enhancing disease SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Penn, Med Ctr, New Approaches Brain Tumor Therapy Consortium, Philadelphia, PA 19104 USA. Henry Ford Hosp, Detroit, MI 48202 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. Johns Hopkins Univ, Baltimore, MD USA. NABTT Cent Off, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 118S EP 118S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326600467 ER PT J AU Rammohan, M Jeevananthinee, J Zhou, QY Tan, EH Sparreboom, A Verweij, J Balram, C AF Rammohan, M Jeevananthinee, J Zhou, QY Tan, EH Sparreboom, A Verweij, J Balram, C TI The influence of functional polymorphisms in UGT1A7 and UGT1A9 on irinotecan pharmacokinetics in Asian cancer patients. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Natl Canc Ctr, Singapore, Singapore. NCI, Bethesda, MD 20892 USA. Erasmus Univ, Med Ctr, Rotterdam, Neth Antilles. RI Sparreboom, Alex/B-3247-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 136S EP 136S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326600540 ER PT J AU Balram, C Li, J Zhou, QY Tan, EH Mathijssen, RH van Schaik, RH Verweij, J Sparreboom, A Baker, SD AF Balram, C Li, J Zhou, QY Tan, EH Mathijssen, RH van Schaik, RH Verweij, J Sparreboom, A Baker, SD TI Molecular mechanisms of interethnic differences in irinotecan disposition: Impact of variants in ABCG2. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Natl Canc Ctr, Singapore, Singapore. Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Erasmus Univ, Med Ctr, Rotterdam, Neth Antilles. NCI, Bethesda, MD 20892 USA. RI Sparreboom, Alex/B-3247-2008 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 139S EP 139S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326600550 ER PT J AU Sparreboom, A Marsh, S Henningsson, A Karlsson, MO Garsa, A Loos, WJ Verweij, J McLeod, HL AF Sparreboom, A Marsh, S Henningsson, A Karlsson, MO Garsa, A Loos, WJ Verweij, J McLeod, HL TI Effect of genetic variants in CYP2C8, CYP3A4, CYP3A5, and ABCB1 on paclitaxel pharmacokinetics. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Washington Univ, Sch Med, St Louis, MO USA. Uppsala Univ, Uppsala, Sweden. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. RI Sparreboom, Alex/B-3247-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 139S EP 139S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326600552 ER PT J AU Lakhani, NJ Sparreboom, A Venitz, J Dahut, W Figg, WD AF Lakhani, NJ Sparreboom, A Venitz, J Dahut, W Figg, WD TI Single oral dose pharmacokinetics (PK) and safety of 2-methoxyestradiol (2ME2) in patients with solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Natl Canc Inst, Bethesda, MD USA. Virginia Commonwealth Univ, Richmond, VA USA. RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 152S EP 152S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601022 ER PT J AU Adamson, PC Balis, FM Boron, M Shalabi, A O'Brien, M Eby, M Jayaprakash, N Cole, DE Ivy, P Widemann, BC AF Adamson, PC Balis, FM Boron, M Shalabi, A O'Brien, M Eby, M Jayaprakash, N Cole, DE Ivy, P Widemann, BC TI Carboxypeptidase-G2 (CPDG2) and leucovorin (Lv) rescue with and without addition of thymidine (Thd) for high-dose methotrexate (HDMTX) induced renal dysfunction. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 153S EP 153S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601028 ER PT J AU Scripture, CD Szebeni, J Figg, WD Sparreboom, A AF Scripture, CD Szebeni, J Figg, WD Sparreboom, A TI Comparative in vitro properties and pharmacokinetics of paclitaxel following the administration of Taxol and Paxene. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Natl Canc Inst, Bethesda, MD USA. Walter Reed Army Inst Res, Silver Spring, MD USA. RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 157S EP 157S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601043 ER PT J AU van Erp, PH Zhao, M Gelderblom, H Guchelaar, HJ Sparreboom, A Baker, SD AF van Erp, PH Zhao, M Gelderblom, H Guchelaar, HJ Sparreboom, A Baker, SD TI Effect of milk thistle (Silybum marianum) on the pharmacokinetics of irinotecan. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Leiden Univ, Med Ctr, Leiden, Netherlands. Johns Hopkins, SKCCCC, Baltimore, MD USA. Natl Canc Inst, Bethesda, MD USA. RI Sparreboom, Alex/B-3247-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 158S EP 158S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601048 ER PT J AU Gulley, JL Todd, N Dahut, W Schlom, J Arlen, P AF Gulley, JL Todd, N Dahut, W Schlom, J Arlen, P TI A phase II study of PROSTVAC-VF vaccine, and the role of GM-CSF, in patients (pts) with metastatic androgen insensitive prostate cancer (AIPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Natl Canc Inst, NIH, Bethesda, MD USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 166S EP 166S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601079 ER PT J AU Yang, JC Beck, KE Blansfield, JA Tran, KQ Lowy, I Rosenberg, SA AF Yang, JC Beck, KE Blansfield, JA Tran, KQ Lowy, I Rosenberg, SA TI Tumor regression in patients with metastatic renal cancer treated with a monoclonal antibody to CTLA4 (MDX-010). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Natl Canc Inst, NIH, Bethesda, MD USA. Medarex Inc, Bloomsbury, NJ USA. NR 0 TC 4 Z9 5 U1 1 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 166S EP 166S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601076 ER PT J AU Ibrahim, RA Achtar, MS Herrin, VE Gause, B Bernstein, S Grollman, F Contoise, D Steinberg, S Berzofsky, JA Khleif, SN AF Ibrahim, RA Achtar, MS Herrin, VE Gause, B Bernstein, S Grollman, F Contoise, D Steinberg, S Berzofsky, JA Khleif, SN TI Autologous PBMCs pulsed with HPV16 E6 as an immunotherapeutic agent for patients with advanced cervical cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 167S EP 167S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601083 ER PT J AU Arlen, PM Gulley, JL Todd, N Tsang, KY Schlom, J Dahut, WL AF Arlen, PM Gulley, JL Todd, N Tsang, KY Schlom, J Dahut, WL TI Antiandrogen (AA), vaccine (V), and combination therapy in DO.5 prostate cancer (CaP) patients (Pts). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016 OI Gulley, James/0000-0002-6569-2912 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 170S EP 170S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601094 ER PT J AU Achtar, MS Ibrahim, R Herrin, VE Gause, B Steinberg, S Grollman, F Rahma, O Bernstein, S Maruffi, C Berzofsky, J Khleif, SN AF Achtar, MS Ibrahim, R Herrin, VE Gause, B Steinberg, S Grollman, F Rahma, O Bernstein, S Maruffi, C Berzofsky, J Khleif, SN TI Pre-immature dendritic cells pulsed with human papillomavirus 16 E7 peptide vaccine in advanced cervical cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 171S EP 171S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601098 ER PT J AU Janik, JE Morris, JC Stetler-Stevenson, M Gao, WW O'Hagan, D Moses, LS Taylor, M McEwen, C Hammershaimb, LD Waldmann, TA AF Janik, JE Morris, JC Stetler-Stevenson, M Gao, WW O'Hagan, D Moses, LS Taylor, M McEwen, C Hammershaimb, LD Waldmann, TA TI Phase I trial of siplizumab in CD2-positive lymphoproliferative disease. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. MedImmune Oncol Inc, Gaithersburg, MD USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 174S EP 174S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601108 ER PT J AU Correale, P Cusi, MG Tsang, KY Del Vecchio, MT Marsili, S Intrivici, C La Placa, M Aquino, A Bonmassar, E Francini, G AF Correale, P Cusi, MG Tsang, KY Del Vecchio, MT Marsili, S Intrivici, C La Placa, M Aquino, A Bonmassar, E Francini, G TI Immunological and anti-tumor activity of a novel a chemo-immunotherapy regimen with gemcitabine, oxaliplatin, levo-folinic acid, and 5-fluorouracil followed by GM-CSF and Interleukin-2 in patients with metastatic colorectal cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Siena, Sch Med, Sect Oncol, I-53100 Siena, Italy. Univ Siena, Sect Virol, I-53100 Siena, Italy. NCI, Tumor Immunol & Biol Lab, Bethesda, MD 20892 USA. Univ Siena, Sect Pathol, I-53100 Siena, Italy. Univ Rome, Oncol & Pharmacol Sect, Rome, Italy. NR 0 TC 6 Z9 6 U1 2 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 175S EP 175S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601114 ER PT J AU Toubaji, A Achtar, MS Herrin, VE Provenzano, M Bernstein, S Brent-Steel, T Marincola, F Khleif, SN AF Toubaji, A Achtar, MS Herrin, VE Provenzano, M Bernstein, S Brent-Steel, T Marincola, F Khleif, SN TI Immunotherapeutic role of mutant ras peptide-based vaccine as an adjuvant in pancreatic and colorectal cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 184S EP 184S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601148 ER PT J AU Morris, JC Vahanian, N Janik, JE Moses, L Tennant, L Pittaluga, S Gao, W Albert, P Seregina, T Link, CJ AF Morris, JC Vahanian, N Janik, JE Moses, L Tennant, L Pittaluga, S Gao, W Albert, P Seregina, T Link, CJ TI Phase I study of an antitumor vaccination using alpha(1,3) galactosyltransferase expressing allogeneic tumor cells in patients (Pts) with refractory or recurrent non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NewLink Genet Corp, Ames, IA USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 187S EP 187S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601162 ER PT J AU Gregorc, V Cusatis, G Spreafico, A Amoroso, MG Gianmarco, A Ingersoll, RG Sparreboom, A Villa, E Hidalgo, M Baker, SD AF Gregorc, V Cusatis, G Spreafico, A Amoroso, MG Gianmarco, A Ingersoll, RG Sparreboom, A Villa, E Hidalgo, M Baker, SD TI Association of germline mutations in EGFR and ABCG2 with gefitinib response in patients with non-small cell lung cancer (NSCLC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Hosp St Rafael, Inst Sci, Milan, Italy. Johns Hopkins Univ, Baltimore, MD USA. Osp Moriggia Pelascini, Gravedona, Italy. NCI, Bethesda, MD 20892 USA. RI Sparreboom, Alex/B-3247-2008; Cusatis, Gianluca/G-2539-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 197S EP 197S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601200 ER PT J AU Lepper, ER van Oosterom, AT de Bruijn, EA Figg, WD Verweij, J Sparreboom, A Nooter, K AF Lepper, ER van Oosterom, AT de Bruijn, EA Figg, WD Verweij, J Sparreboom, A Nooter, K TI Genetic predisposition to oral absorption of imatinib: Correlation of a variant allele in ABCG2 with transport activity. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, SAIC Frederick, Bethesda, MD USA. Catholic Univ Leuven, Louvain, Belgium. NCI, Bethesda, MD USA. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. RI Sparreboom, Alex/B-3247-2008; Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 198S EP 198S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601204 ER PT J AU Synold, TW Morgan, RJ Newman, EM Lenz, HJ Gandara, DR Colevas, AD Lewis, MD Doroshow, JH AF Synold, TW Morgan, RJ Newman, EM Lenz, HJ Gandara, DR Colevas, AD Lewis, MD Doroshow, JH TI A phase I pharmacokinetic and target validation study of the novel anti-tubulin agent E7389: A California Cancer Consortium trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 City Hop Comprehens Canc Ctr, Duarte, CA USA. USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. UC Davis Canc Ctr, Sacramento, CA USA. Canc Therapy Evaluat Program, Rockville, MD USA. Eisai Res Inst, Andover, MA USA. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 14 Z9 14 U1 0 U2 4 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 200S EP 200S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601213 ER PT J AU Ramanathan, RK Belani, CP Friedland, D Ramalingam, S Agarwala, SS Ivy, P Potter, D Chatta, G Zuhowski, E Egorin, MJ AF Ramanathan, RK Belani, CP Friedland, D Ramalingam, S Agarwala, SS Ivy, P Potter, D Chatta, G Zuhowski, E Egorin, MJ TI Phase I study (twice weekly schedule) of 17-allylamino-17 demethoxygeldanamycin (17AAG, NSC-704057) in patients with advanced refractory tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Pittsburgh, Inst Canc, Pittsburgh, PA 15260 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 204S EP 204S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601228 ER PT J AU Piekarz, RL Frye, R Turner, M Wright, J Leonard, J Allen, S Smith, S Kischbaum, M Zain, J Bates, SE AF Piekarz, RL Frye, R Turner, M Wright, J Leonard, J Allen, S Smith, S Kischbaum, M Zain, J Bates, SE TI Responses and molecular markers in patients with peripheral T-cell lymphoma treated on a phase II trial of depsipeptide, FK228. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. Cornell Univ, New York, NY USA. N Shore Univ Hosp, Manhasset, NY USA. Univ Chicago, Chicago, IL 60637 USA. City Hope Canc Ctr, Duarte, CA USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 207S EP 207S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601238 ER PT J AU Donovan, EA Ryan, Q Acharya, M Chung, E Trepel, J Maynard, K Sausville, E Murgo, A Melillo, G Conley, B AF Donovan, EA Ryan, Q Acharya, M Chung, E Trepel, J Maynard, K Sausville, E Murgo, A Melillo, G Conley, B TI Phase I pharmacokinetic-pharmacodynamic trial of weekly MS-275, an oral histone deacetylase inhibitor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 215S EP 215S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601272 ER PT J AU Duran, I Le, L Saltman, D Kortmansky, J Kocha, W Singh, D Pond, GR Peralba, JM Dancey, J Siu, LL AF Duran, I Le, L Saltman, D Kortmansky, J Kocha, W Singh, D Pond, GR Peralba, JM Dancey, J Siu, LL TI A phase II trial of temsirolimus in metastatic neuroendocrine carcinomas (NECs). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ Chicago, Chicago, IL 60637 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 215S EP 215S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601273 ER PT J AU Menefee, ME Fan, C Edgerly, M Draper, D Chen, C Robey, R Balis, F Figg, WD Bates, S Fojo, AT AF Menefee, ME Fan, C Edgerly, M Draper, D Chen, C Robey, R Balis, F Figg, WD Bates, S Fojo, AT TI Tariquidar (XR9576) is a potent and effective P-glycoprotein (Pgp) inhibitor that can be administered safely with chemotherapy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 215S EP 215S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601270 ER PT J AU Mansky, PJ Wallerstedt, DB Monahan, BP Lee, C Swain, SM Evande, R Blackman, MR Grem, J AF Mansky, PJ Wallerstedt, DB Monahan, BP Lee, C Swain, SM Evande, R Blackman, MR Grem, J TI Mistletoe extract/gemcitabine combination treatment: An interim report from the NCCAM/NCI phase I study in patients with advanced solid tumors SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCCAM, NIH, Bethesda, MD 20892 USA. Natl Naval Med Res Inst, Bethesda, MD USA. NCI, NIH, Bethesda, MD USA. Univ Nebraska, Med Ctr, Omaha, NE USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 216S EP 216S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601276 ER PT J AU Saber-Mahloogi, H Timmer, WC Lee, SL Leighton, J Kane, RC Pilaro, A Rahman, A Johnson, G Pazdur, R AF Saber-Mahloogi, H Timmer, WC Lee, SL Leighton, J Kane, RC Pilaro, A Rahman, A Johnson, G Pazdur, R TI The FDA division of oncology initiative with the NCISBIR/STTR programs SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 US FDA, Rockville, MD 20857 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 234S EP 234S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601347 ER PT J AU Varticovski, L Richardson, M Robles, A AF Varticovski, L Richardson, M Robles, A TI Cell cycle control and apoptosis of p53-isogenic cell lines treated with Hsp90 inhibitors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Jackson State Univ, Jackson, MS USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 241S EP 241S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601375 ER PT J AU Wolmark, N Wieand, S Kuebler, JP Colangelo, L Smith, RE AF Wolmark, N Wieand, S Kuebler, JP Colangelo, L Smith, RE TI A phase III trial comparing FULV to FULV plus oxaliplatin in stage II or III carcinoma of the colon: Results of NSABP Protocol C-07. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. NSABP, Pittsburgh, PA USA. NR 0 TC 25 Z9 25 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 246S EP 246S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601393 ER PT J AU Johnston, PG Benson, A Catalano, P Eapen, S Wolmark, N Sargent, D McDermott, U Colangelo, L Wieand, S Goldberg, R Allegra, C AF Johnston, PG Benson, A Catalano, P Eapen, S Wolmark, N Sargent, D McDermott, U Colangelo, L Wieand, S Goldberg, R Allegra, C TI The clinical significance of thymidylate synthase (TS) expression in primary colorectal cancer: An Intergroup combined analysis. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Queens Univ Belfast, Belfast, Antrim, North Ireland. ECOG, Boston, MA USA. NSABP, Pittsburgh, PA USA. NCCTG, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 248S EP 248S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601402 ER PT J AU Saltz, LB Lenz, HJ Hochster, H Wadler, S Hoff, P Kemeny, N Hollywood, E Gonen, M Wetherbee, S Chen, H AF Saltz, LB Lenz, HJ Hochster, H Wadler, S Hoff, P Kemeny, N Hollywood, E Gonen, M Wetherbee, S Chen, H TI Randomized phase II trial of cetuximab/bevacizumab/irinotecan (CBI) versus cetuximab/bevacizumab (CB) in irinotecan-refractory colorectal cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Univ So Calif, Kenneth Norris Jr Comprehens Canc Ctr, Los Angeles, CA 90033 USA. NYU, New York, NY USA. Cornell Univ, Weill Med Coll, New York, NY USA. MD Anderson Canc Ctr, Houston, TX USA. NCI, CTEP, Bethesda, MD 20892 USA. RI Gonen, Mithat/E-4826-2012 NR 0 TC 33 Z9 34 U1 0 U2 2 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 248S EP 248S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601401 ER PT J AU Kemeny, MM Eapen, S Whitehead, RP Bleday, R Smith, RE Benson, AB AF Kemeny, MM Eapen, S Whitehead, RP Bleday, R Smith, RE Benson, AB TI A randomized phase III intergroup study of perioperative fluorouracil (541.1) in patients with resectable colon cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Queens Hosp Ctr, ECOG, SWOG, CALGB,NSABP,ACOS,OG, Jamaica, NY 11432 USA. ECOG Stat Ctr, Boston, MA USA. Univ Texas, Galveston, TX 77555 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Reg Canc Ctr, Erie, PA USA. Northwestern Univ, Chicago, IL 60611 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 259S EP 259S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601445 ER PT J AU Smith, FM Stephens, R Gaffney, E Crotty, P Petricoin, E Liotta, L Kennedy, J Reynolds, J AF Smith, FM Stephens, R Gaffney, E Crotty, P Petricoin, E Liotta, L Kennedy, J Reynolds, J TI Exploring the proteome as a response predictor for rectal cancer undergoing neoadjuvant radiochemotherapy (RCT). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 St James Hosp, Dublin 8, Ireland. Adelaide & Meath Hosp, Dublin, Ireland. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 264S EP 264S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601467 ER PT J AU Anzick, SL Winter, J Wong, S Davis, S McCall, M Meltzer, PS Choti, MA AF Anzick, SL Winter, J Wong, S Davis, S McCall, M Meltzer, PS Choti, MA TI Use of genetic profiling to discover molecular signatures of the pattern of metastatic spread in human colorectal cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NHGRI, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ Hosp, Baltimore, MD 21287 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 290S EP 290S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326601571 ER PT J AU Yao, JC Ng, C Hoff, PM Phan, AT Hess, K Chen, H Wang, X Abbruzzese, JL Ajani, JA AF Yao, JC Ng, C Hoff, PM Phan, AT Hess, K Chen, H Wang, X Abbruzzese, JL Ajani, JA TI Improved progression free survival (PFS), and rapid, sustained decrease in tumor perfusion among patients with advanced carcinoid treated with bevacizumab SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 10 Z9 10 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 309S EP 309S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326602058 ER PT J AU Thomas, MB Dutta, A Brown, T Charnsangavej, C Rashid, A Hoff, PM Dancey, J Abbruzzese, JL AF Thomas, MB Dutta, A Brown, T Charnsangavej, C Rashid, A Hoff, PM Dancey, J Abbruzzese, JL TI A phase II open-label study of OSI-774 (NSC 718781) in unresectable hepatocellular carcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 317S EP 317S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326602089 ER PT J AU Mares, JE Worah, S Mathew, SV Charnsangavej, C Chen, H Ajani, JA Hoff, PM Phan, AT Yao, JC AF Mares, JE Worah, S Mathew, SV Charnsangavej, C Chen, H Ajani, JA Hoff, PM Phan, AT Yao, JC TI Increased rates of hypertension (HTN) among patients with advanced carcinoid treated with bevacizumab. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 329S EP 329S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326602136 ER PT J AU Mackenzie, MJ Moore, MJ Saltman, D Zbuk, KM Vandesompele, E Lovell, S Degendorfer, P Johnson, C Siu, L Low, J AF Mackenzie, MJ Moore, MJ Saltman, D Zbuk, KM Vandesompele, E Lovell, S Degendorfer, P Johnson, C Siu, L Low, J TI A phase II study of triapine in combination with gemcitabine in advanced pancreatic carcinoma: A Princess Margaret Hospital phase II consortium trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 McMaster Univ, Hamilton Reg Canc Ctr, Hamilton, ON, Canada. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 331S EP 331S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326602143 ER PT J AU Shibata, S Yen, Y Doroshow, J Leong, L Wagman, L Marx, H Clarke, K Frankel, P Lenz, H Gandara, D AF Shibata, S Yen, Y Doroshow, J Leong, L Wagman, L Marx, H Clarke, K Frankel, P Lenz, H Gandara, D TI Phase H study of oxaliplatin in patients with unresectable, metastatic or recurrent hepatocellular cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 City Hope Natl Med Ctr, Duarte, CA 91010 USA. NIH, Washington, DC USA. USC, Los Angeles, CA USA. Univ Calif Davis, Sacramento, CA 95817 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 348S EP 348S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326602211 ER PT J AU Hedley, D Moore, MJ Hirte, H Siu, L Vincent, M Jonker, D Mwang, H Nagai, J Dancey, J AF Hedley, D Moore, MJ Hirte, H Siu, L Vincent, M Jonker, D Mwang, H Nagai, J Dancey, J TI A phase II trial of perifosine as second line therapy for advanced pancreatic cancer. A study of the Princess Margaret Hospital [PMH] phase II consortium. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 349S EP 349S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326602217 ER PT J AU Small, EJ Schellhammer, PF Higano, CS Neumanaitis, J Valone, F Hershberg, R AF Small, EJ Schellhammer, PF Higano, CS Neumanaitis, J Valone, F Hershberg, R TI Phase II prime/boost vaccination using poxviruses expressing PSA in hormone dependent prostate cancer: Follow-up clinical results from ECOG 7897. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Columbia Univ, New York, NY USA. Canc Inst New Jersey, New Brunswick, NJ USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Univ Pittsburgh, Pittsburgh, PA USA. NCI, Bethesda, MD 20892 USA. Univ Wisconsin, Madison, WI USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. NR 0 TC 4 Z9 5 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 378S EP 378S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326602332 ER PT J AU Hussain, M Petrylak, D Dunn, R Vaishampayan, U Lara, PN Chatta, G Nanus, D Glode, LM Trump, D Chen, H Smith, DC AF Hussain, M Petrylak, D Dunn, R Vaishampayan, U Lara, PN Chatta, G Nanus, D Glode, LM Trump, D Chen, H Smith, DC TI Trastuzumab (T), paclitaxel (P), carboplatin (C), and gemcitabine (G) in advanced HER2-positive urothelial carcinoma: Results of a multi-center phase IINCI trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Columbia Presbyterian Med Ctr, New York, NY 10032 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Wayne State Univ, Detroit, MI 48202 USA. Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. Univ Pittsburgh, Pittsburgh, PA 15260 USA. New York Presbyterian Hosp, New York, NY USA. Univ Colorado, Hlth Sci Ctr, Boulder, CO 80309 USA. Roswell Pk, Buffalo, NY USA. NCI, Rockville, MD USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 379S EP 379S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326602337 ER PT J AU Fojo, AT Menefee, ME Poruchynsky, M Edgerly, M Mickley, L Tapia, ELN Merino, M Balis, F Bates, S AF Fojo, AT Menefee, ME Poruchynsky, M Edgerly, M Mickley, L Tapia, ELN Merino, M Balis, F Bates, S TI A translational study of ixabepilone (BMS-247550) in renal cell cancer (RCC): Assessment of its activity and demonstration of target engagement in tumor cells. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 388S EP 388S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326602370 ER PT J AU D'Amico, AV Chen, MH Cox, MC Dahut, W Figg, WD AF D'Amico, AV Chen, MH Cox, MC Dahut, W Figg, WD TI Intermediate end point for survival for patients with hormone refractory metastatic prostate cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Connecticut, Storrs, CT USA. NCI, Bethesda, MD 20892 USA. RI Figg Sr, William/M-2411-2016 NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 391S EP 391S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326602382 ER PT J AU Pollera, CF Merendino, N Cianciulli, AM Gallucci, M Ruggeri, EM Giannarelli, D Felici, A Nelli, F Boccardo, F Cognetti, F AF Pollera, CF Merendino, N Cianciulli, AM Gallucci, M Ruggeri, EM Giannarelli, D Felici, A Nelli, F Boccardo, F Cognetti, F TI Preliminary cytogenetic and pharmacogenomic analysis of muscle-invasive transitional-cell carcinoma (TCC) of the bladder in patients (pts) enrolled in the Italian National Research Council (CNR) phase III randomized trial comparing adjuvant cisplatin-gemcitabine (PG) vs observation (OBS) after radical cystectomy SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Belcolle Hosp, Viterbo, Italy. Univ Tuscia, I-01100 Viterbo, Italy. Regina Elena Inst Canc Res, I-00161 Rome, Italy. Natl Canc Inst, Genoa, Italy. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 400S EP 400S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326602418 ER PT J AU Sridhar, SS Stadler, W Le, L Hedley, D Pond, G Wright, J Vokes, E Thomas, S Moore, M AF Sridhar, SS Stadler, W Le, L Hedley, D Pond, G Wright, J Vokes, E Thomas, S Moore, M TI Phase II study of bortezomib in advanced or metastatic urothelial cancer. A trial of the princess margaret hospital [PMH] phase II consortium. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. NCI, Rockville, MD USA. Oncol Hematol Cent Illinois, Chicago, IL USA. NR 0 TC 3 Z9 3 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 422S EP 422S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326602506 ER PT J AU Hudes, GR Celano, P Torti, F Tabatabai, A Murgo, A Hussain, A AF Hudes, GR Celano, P Torti, F Tabatabai, A Murgo, A Hussain, A TI Phase II study of weekly paclitaxel (PAC) and bryostatin-1 (BRYO) in hormone refractory prostate cancer (HRPC) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. GBMC, Ctr Canc, Baltimore, MD USA. Wake Forest Univ, Comp Canc Ctr, Winston Salem, NC 27109 USA. York Canc Ctr, York, PA USA. CTEP, Natl Canc Inst, Rockville, MD USA. Univ Maryland, Ctr Canc, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 431S EP 431S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326602544 ER PT J AU Posadas, EM Gulley, J Arlen, PM Harold, N Fioravanti, S Meltzer, P Scripture, CD Figg, WD Kohn, EC Dahut, WL AF Posadas, EM Gulley, J Arlen, PM Harold, N Fioravanti, S Meltzer, P Scripture, CD Figg, WD Kohn, EC Dahut, WL TI A phase II study of BAY 43-9006 in patients with androgen-independent prostate cancer (AIPC) with proteomic profiling. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NHGRI, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 443S EP 443S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603003 ER PT J AU Retter, AS Arlen, PM Gulley, JL Latham, LL Steinberg, SM Chen, CC Jones, EC Trout, A Figg, WD Dahut, WL AF Retter, AS Arlen, PM Gulley, JL Latham, LL Steinberg, SM Chen, CC Jones, EC Trout, A Figg, WD Dahut, WL TI A phase II trial of docetaxel (D), estramustine (E) and thalidomide (T) in patients with metastatic androgen-independent prostate cancer (AIPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 443S EP 443S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603004 ER PT J AU Bonome, T Park, DC Hao, K Donninger, H Radonovich, M Brady, J Barrett, JC Wong, WH Welch, WR Mok, SC Birrer, MJ AF Bonome, T Park, DC Hao, K Donninger, H Radonovich, M Brady, J Barrett, JC Wong, WH Welch, WR Mok, SC Birrer, MJ TI Identification of a gene signature that can predict lone-term survival in patients with high-grade late stage serous ovarian cancer. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Rockville, MD USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 462S EP 462S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603074 ER PT J AU Donninger, H Bonome, T Li, JY Park, DC Radonovich, M Pise-Masison, C Brady, J Barrett, JC Mok, SC Birrer, MJ AF Donninger, H Bonome, T Li, JY Park, DC Radonovich, M Pise-Masison, C Brady, J Barrett, JC Mok, SC Birrer, MJ TI Expression profiling of microdissected papillary serous ovarian epithelial cancers identifies genes describing the unique phenotypes of borderline and malignant tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Natl Canc Inst, Rockville, MD USA. Brigham & Womens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 462S EP 462S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603073 ER PT J AU Tsuda, H Ito, YM Ito, K Nishimura, S Yaegashi, N Birrer, MJ Ohashi, Y Hashiguchi, Y Berkowitz, RS Mok, SC AF Tsuda, H Ito, YM Ito, K Nishimura, S Yaegashi, N Birrer, MJ Ohashi, Y Hashiguchi, Y Berkowitz, RS Mok, SC TI Prognostic value of ABCF2 in ovarian clear cell adenocarcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Osaka City Gen Hosp, Osaka, Japan. Univ Tokyo, Tokyo, Japan. Tohoku Univ, Grad Sch Med, Sendai, Miyagi 980, Japan. NCI, Rockville, MD USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Ito, Yoichi/E-2042-2012 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 463S EP 463S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603080 ER PT J AU Nishimura, S Tsuda, H Ito, YM Ito, K Yaegashi, N Birrer, MJ Ohashi, Y Hashiguchi, Y Berkowitz, WS Mok, SC AF Nishimura, S Tsuda, H Ito, YM Ito, K Yaegashi, N Birrer, MJ Ohashi, Y Hashiguchi, Y Berkowitz, WS Mok, SC TI ABCF2 is a new biomarker of ovarian clear cell adenocarcinoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Osaka City Gen Hosp, Osaka, Japan. Univ Tokyo, Tokyo, Japan. Tohoku Univ, Grad Sch Med, Sendai, Miyagi 980, Japan. NCI, Rockville, MD USA. Brigham & Womens Hosp, Boston, MA 02115 USA. RI Ito, Yoichi/E-2042-2012 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 466S EP 466S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603092 ER PT J AU Morgan, RJ Doroshow, JH Frankel, P Leong, LA Chow, W Fleming, G Garcia, AA Lenz, HJ Gandara, D AF Morgan, RJ Doroshow, JH Frankel, P Leong, LA Chow, W Fleming, G Garcia, AA Lenz, HJ Gandara, D TI A phase II trial of bryostatin in combination with cisplatin in patients with recurrent or persistent epithelial ovarian cancer: A California cancer consortium (CCC) trial. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Univ Chicago, Chicago, IL 60637 USA. Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA. USC Norris Comprehens Canc Ctr, Los Angeles, CA USA. Univ Calif Davis, Ctr Canc, Sacramento, CA 95817 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 489S EP 489S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603181 ER PT J AU Vokes, EE Cohen, EEW Mauer, AM Karrison, TG Wong, SJ Skoog-Sluman, LJ Kozloff, MF Dancey, J Dekker, A AF Vokes, EE Cohen, EEW Mauer, AM Karrison, TG Wong, SJ Skoog-Sluman, LJ Kozloff, MF Dancey, J Dekker, A TI A phase I study of erlotinib and bevacizumab for recurrent or metastatic squamous cell carcinoma of the head and neck (HNC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Chicago, Chicago, IL 60637 USA. Med Coll Wisconsin, Milwaukee, WI 53226 USA. Ingalls, Harvey, IL USA. Natl Canc Inst, Rockville, MD USA. NR 0 TC 16 Z9 16 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 501S EP 501S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603227 ER PT J AU Conley, BA Donovan, E Muir, C Morris, J Colevas, AD Gius, D Trehu, E Sausville, E Wright, J Vanwaes, C AF Conley, BA Donovan, E Muir, C Morris, J Colevas, AD Gius, D Trehu, E Sausville, E Wright, J Vanwaes, C TI Proteasome inhibitor bortezomib & re-irradiation (rRT) with scheduled treatment break in patients (pts) with head/neck squamous carcinoma (HNSCC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Millenium Pharmaceut Inc, Cambridge, MA USA. NIDCD, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 522S EP 522S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603314 ER PT J AU Thomas, CR Wilson, JW Mamounas, EP Raich, PC Lagrange, A Dignam, JJ Wickerham, DL Nolmark, N AF Thomas, CR Wilson, JW Mamounas, EP Raich, PC Lagrange, A Dignam, JJ Wickerham, DL Nolmark, N TI Impact of ethnic neutropenia disparity analysis in NSABP breast trials of postoperative doxorubicin (A)/cyclophosphamide (C). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Texas, HSC, NSABP Breast Comm, San Antonio, TX 78285 USA. NSABP, Pittsburgh, PA USA. Aultman Canc Ctr, Canton, OH USA. AMC Canc Res Ctr, Denver, CO USA. Ochsner Canc Inst, New Orleans, LA USA. Univ Chicago, Chicago, IL 60637 USA. Allegheny Gen Hosp, Pittsburgh, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 528S EP 528S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603333 ER PT J AU Agrawal, M Grady, C Fairclough, D Emanauel, E AF Agrawal, M Grady, C Fairclough, D Emanauel, E TI Patients' decision-making process of participating in phase I oncology studies. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD 20892 USA. Univ Colorado, Denver, CO 80202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 531S EP 531S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603345 ER PT J AU Bredart, A Bottomley, A Blazeby, J Conroy, T Chie, WC Arraras, J Costantini, M Schraub, S Fleissner, C AF Bredart, A Bottomley, A Blazeby, J Conroy, T Chie, WC Arraras, J Costantini, M Schraub, S Fleissner, C TI An international prospective study of the psychometric properties of the EORTC satisfaction with care measure (EORTC QLQ SAT-32). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Inst Curie, Paris, France. EORTC Data Ctr, Brussels, Belgium. Univ Bristol, Bristol, Avon, England. Ctr Alexis Vautrin, Vandoeuvre Les Nancy, France. Natl Taiwan Univ, Taipei 10764, Taiwan. Sahlgrenska Hosp, Gothenburg, Sweden. Hosp Navarra, Pamplona, Spain. Natl Canc Inst, Genoa, Italy. Ctr Paul Strauss, Strasbourg, France. Univ Hosp Charite Berlin, Berlin, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 535S EP 535S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603361 ER PT J AU Land, SR Kopec, JA Julian, TB Brown, A Krag, DN Harlow, S Ritter, M Costantino, JP Wolmark, N Ganz, PA AF Land, SR Kopec, JA Julian, TB Brown, A Krag, DN Harlow, S Ritter, M Costantino, JP Wolmark, N Ganz, PA TI Comparison of self-reported outcomes with arm functional measurements in early breast cancer patients undergoing nodal biopsy in NSABP protocol B-32. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Pittsburgh, Pittsburgh, PA 15260 USA. Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. NSABP, Pittsburgh, PA USA. Univ Vermont, Burlington, VT USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Univ Calif Los Angeles, Los Angeles, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 537S EP 537S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603371 ER PT J AU Cronin, DP Harlan, LC Clegg, LX Potosky, AL Mooney, MM AF Cronin, DP Harlan, LC Clegg, LX Potosky, AL Mooney, MM TI Patterns of care for adjuvant therapy for colorectal cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 548S EP 548S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603412 ER PT J AU Dores, G Schonfeld, S Chen, J Hodgson, D Fossa, S Storm, H Hall, P Pukkala, E Gilbert, E Travis, L AF Dores, G Schonfeld, S Chen, J Hodgson, D Fossa, S Storm, H Hall, P Pukkala, E Gilbert, E Travis, L CA NCI-Int Hodgkin Lymphoma Grp TI Long-term cause-specific mortality among 41,146 one-year survivors of Hodgkin lymphoma (HL) SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Int Hodgkin Lymphoma Grp, Bethesda, MD USA. Princess Margaret Hosp, Toronto, ON M4X 1K9, Canada. Norwegian Radium Hosp, Oslo, Norway. Danish Canc Soc, Copenhagen, Denmark. Karolinska Inst, Stockholm, Sweden. Finnish Canc Registry, FIN-00170 Helsinki, Finland. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 562S EP 562S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603469 ER PT J AU Schonfeld, SJ Gilbert, ES Dores, GM Lynch, CF Holowaty, E Hall, P Storm, H Pukkala, E Andersen, A Travis, LB AF Schonfeld, SJ Gilbert, ES Dores, GM Lynch, CF Holowaty, E Hall, P Storm, H Pukkala, E Andersen, A Travis, LB TI Acute leukemia (AL) following Hodgkin's lymphoma (HL): A population-based study of over 38,000 patients SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Int Hodgkin Lymphoma Grp, Bethesda, MD USA. NCI, DHHS, NIH, Bethesda, MD 20892 USA. Univ Iowa, Iowa City, IA USA. Canc Care Ontario, Toronto, ON, Canada. Karolinska Inst, Stockholm, Sweden. Danish Canc Soc, Copenhagen, Denmark. Finnish Canc Registry, FIN-00170 Helsinki, Finland. Canc Registry Norway, Oslo, Norway. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 562S EP 562S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603467 ER PT J AU Wilson, WH Porcu, P Hurd, D Martin, SE Czuczman, M Niedzwiecki, D Saint Louis, JD Johnson, JL Cheson, B Canellos, GP Zelenetz, AD AF Wilson, WH Porcu, P Hurd, D Martin, SE Czuczman, M Niedzwiecki, D Saint Louis, JD Johnson, JL Cheson, B Canellos, GP Zelenetz, AD TI Phase II study of dose-adjusted EPOCH-R in untreated de novo CD20+ diffuse large B-cell lymphoma (DLBCL)-CALGB 50103. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Ohio State Univ, Columbus, OH 43210 USA. Wake Forest Univ, Winston Salem, NC 27109 USA. CCHS, Helen F Graham Canc Ctr, Newark, DE USA. Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Duke Univ, Durham, NC USA. Georgetown Univ, Washington, DC USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 567S EP 567S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603487 ER PT J AU Kalmadi, SR Wu, R Plasinova, M Sloand, E Galili, N Raza, A Maciejewski, J AF Kalmadi, SR Wu, R Plasinova, M Sloand, E Galili, N Raza, A Maciejewski, J TI Pilot study of SELDI-TOF (surface enhanced laser desorption/ionization time of flight) in bone marrow failure syndromes. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Cleveland Clin Fdn, Cleveland, OH 44195 USA. NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. Rush Univ, Myeloid Dis & MDS Ctr, Chicago, IL 60612 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 571S EP 571S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603505 ER PT J AU O'Connor, O Straus, D Moskowitz, C Hamlin, P Portlock, C Gerecitano, J Neylon, E Colevas, D Zelenetz, A AF O'Connor, O Straus, D Moskowitz, C Hamlin, P Portlock, C Gerecitano, J Neylon, E Colevas, D Zelenetz, A TI Targeting the microtubule apparatus in indolent and mantle cell lymphoma with the novel epothilone anlog BMS 247550 induces major and durable remissions in very drug resistant disease. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, CTEP, Bethesda, MD 20892 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 577S EP 577S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603528 ER PT J AU Cole, DE Balis, FM Lowe, ES Grant, ND White, T Dunleavy, K Janik, J Xiao, S Goodspeed, WJ Wilson, WH AF Cole, DE Balis, FM Lowe, ES Grant, ND White, T Dunleavy, K Janik, J Xiao, S Goodspeed, WJ Wilson, WH TI Pharmacokinetics (pk) and tolerance of doxorubicin (dox) and etoposide (etop) during treatment of aggressive B-cell lymphomas indicate doses need not be routinely reduced for hepatic dysfunction. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 578S EP 578S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603532 ER PT J AU Dunleavy, K White, T Grant, N Shovlin, M Stetler-Stevenson, M Pittaluga, S Jaffe, ES Marti, G Janik, J Wilson, WH AF Dunleavy, K White, T Grant, N Shovlin, M Stetler-Stevenson, M Pittaluga, S Jaffe, ES Marti, G Janik, J Wilson, WH TI Phase I study of combination rituximab with apolizumab in relapsed/refractory B-cell lymphoma and chronic lymphocytic leukemia. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 586S EP 586S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603565 ER PT J AU Pro, B Smith, MR Leber, B Younes, A Fayad, L Hagemeister, FB McLaughlin, P Rodriguez, AM Caddick, Y Zwiebel, JA AF Pro, B Smith, MR Leber, B Younes, A Fayad, L Hagemeister, FB McLaughlin, P Rodriguez, AM Caddick, Y Zwiebel, JA TI Phase II study of oblimersen sodium and rituximab in patients with recurrent B-cell non-Hodgkin's lymphoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 MD Anderson Canc Ctr, Houston, TX USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. McMaster Univ, Hamilton, ON, Canada. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 587S EP 587S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326603569 ER PT J AU Sudheendra, D Barth, M Hegde, U Wilson, W Libutti, S Wood, B AF Sudheendra, D Barth, M Hegde, U Wilson, W Libutti, S Wood, B TI Radiofrequency ablation of lymphoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NIH, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Connecticut, Ctr Hlth, Farmington, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 611S EP 611S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326604083 ER PT J AU Leighl, NB Laurie, SA Knox, JJ Ellis, PM Shepherd, FA Burkes, RL Vincent, M Pond, GR Zwiebel, JA Moore, MJ AF Leighl, NB Laurie, SA Knox, JJ Ellis, PM Shepherd, FA Burkes, RL Vincent, M Pond, GR Zwiebel, JA Moore, MJ TI Phase I/II study of GTI-2040 plus docetaxel as 2nd-line treatment in non-small cell lung cancer (NSCLC) and other solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Princess Margaret Hosp, Phase Consortium 2, Toronto, ON M4X 1K9, Canada. Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 683S EP 683S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326604367 ER PT J AU Frankel, AE Abi-Habib, RJ Urieto, JO Liu, S Leppla, SH van de Woude, GF Duesbery, NS AF Frankel, AE Abi-Habib, RJ Urieto, JO Liu, S Leppla, SH van de Woude, GF Duesbery, NS TI Anthrax tumor toxin (LeTx) selectively kills B-RAF mutant melanomas. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. NIH, Bethesda, MD 20892 USA. Van Andel Res Inst, Grand Rapids, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 718S EP 718S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326604503 ER PT J AU Fox, E Adamson, PC Hagey, A Widemann, BC Maris, JM Cohn, SL Cai, Y Medina, DM Meek, KA Balis, FM AF Fox, E Adamson, PC Hagey, A Widemann, BC Maris, JM Cohn, SL Cai, Y Medina, DM Meek, KA Balis, FM TI Phase I trial of oral ABT-751 in pediatric patients: Preliminary evidence of activity in neuroblastoma (NBL). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Abbott Labs, Abbott Pk, IL 60064 USA. Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60614 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 806S EP 806S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326605268 ER PT J AU Fouladi, M Furman, WL Chin, T Freeman, B Stewart, CF Krailo, M Houghton, PJ Wright, J Adamson, PC Blaney, SM AF Fouladi, M Furman, WL Chin, T Freeman, B Stewart, CF Krailo, M Houghton, PJ Wright, J Adamson, PC Blaney, SM TI A phase I trial of depsipeptide in children with refractory solid tumors: A Children's Oncology Group Study. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 St Jude Childrens Res Hosp, Memphis, TN 38105 USA. Childrens Oncol Grp, Arcadia, CA USA. NCI, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Texas Childrens Canc Ctr, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 807S EP 807S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326605269 ER PT J AU Widemann, BC Fox, E Goodspeed, WJ Goodwin, A Cohen, M Fojo, T Colevas, AD Balis, FM AF Widemann, BC Fox, E Goodspeed, WJ Goodwin, A Cohen, M Fojo, T Colevas, AD Balis, FM TI Phase I trial of the epothilone B analog BMS-247550 (ixabepilone) in children with refractory solid tumors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Bristol Myers Squibb Co, Princeton, NJ USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 807S EP 807S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326605271 ER PT J AU Merchant, MS Kontny, HU Mackall, CL AF Merchant, MS Kontny, HU Mackall, CL TI Anti-metastatic activity of interferon gamma in a xenograft model of Ewing's sarcoma. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Univ Freiburg, Childrens Hosp, Freiburg, Germany. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 808S EP 808S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326605273 ER PT J AU Jacobs, SS Stork, L Bostrom, BC Hutchinson, R Holcenberg, J Reaman, GH Erdman, GR Franklin, JL Steinberg, SM Adamson, PC AF Jacobs, SS Stork, L Bostrom, BC Hutchinson, R Holcenberg, J Reaman, GH Erdman, GR Franklin, JL Steinberg, SM Adamson, PC TI Treatment of newly diagnosed children with lower-risk leukemia: A collaborative Children's Cancer Group (CCG)/NCI pilot trial incorporating 6-thioguanine. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Childrens Natl Med Ctr, NCI, POB, Washington, DC 20010 USA. OHSU, Doernbecher Childrens Hosp, Portland, OR USA. Childrens Hosp & Clin, Minneapolis, MN USA. Univ Michigan, CS Mott Childrens Hosp, Ann Arbor, MI 48109 USA. Childrens Hosp & Reg Med Ctr, Seattle, WA USA. Childrens Natl Med Ctr, Childrens Oncol Grp, Bethesda, MD USA. N Dakota State Univ, Coll Pharm, Fargo, ND 58105 USA. Univ So Calif, Childrens Hosp Los Angeles, Los Angeles, CA USA. NCI, Bethesda, MD 20892 USA. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 809S EP 809S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326605280 ER PT J AU Vansant, G Oades, K Fogel, G Khan, J Monforte, J AF Vansant, G Oades, K Fogel, G Khan, J Monforte, J TI Application of multiplexed RT-PCR to cancer diagnosis. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Althea Technol, San Diego, CA USA. Nat Select Inc, San Diego, CA USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 811S EP 811S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326605286 ER PT J AU Dileo, P Rankin, CJ Benjamin, RS von Mehren, M Blanke, C Bramwell, V Maki, R Fletcher, C Borden, EC Demetri, GD AF Dileo, P Rankin, CJ Benjamin, RS von Mehren, M Blanke, C Bramwell, V Maki, R Fletcher, C Borden, EC Demetri, GD TI Incidence and reasons for dose modification of standard-dose vs. high-dose imatinib mesylate (IM) in the Phase III Intergroup Study S0033 of patients (pts) with unresectable or metastatic gastrointestinal stromal tumor (GIST). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 Dana Farber Canc Inst, Boston, MA 02115 USA. Sarcoma Grp, Seattle, WA USA. SWOG Stat Ctr, Seattle, WA USA. MD Anderson Canc Ctr, Houston, TX USA. Intergrp, Houston, TX USA. Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NCI, London, ON, Canada. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Brigham & Womens Hosp, Boston, MA 02115 USA. Cleveland Clin, Taussig Canc Ctr, Cleveland, OH 44106 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 824S EP 824S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326605335 ER PT J AU Helman, LJ Yeung, C Espina, V Eichler, G Krishnan, K Tsokos, M Qualman, S Meyer, W Steinberg, S Petricoin, EF Liotta, LA AF Helman, LJ Yeung, C Espina, V Eichler, G Krishnan, K Tsokos, M Qualman, S Meyer, W Steinberg, S Petricoin, EF Liotta, LA TI Proteomic profiling identifies prognostic subsets in Rhabdomyosarcoma (RMS). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, NIH, Bethesda, MD USA. Columbus Childrens Hosp, Columbus, OH USA. Univ Oklahoma, Hlth Sci Ctr, Oklahoma City, OK USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 837S EP 837S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326605386 ER PT J AU Chang, R Beric, A Liebes, LF Wright, J Ivy, P Norwood, B Escalon, J Muggia, FM Hochster, HS AF Chang, R Beric, A Liebes, LF Wright, J Ivy, P Norwood, B Escalon, J Muggia, FM Hochster, HS TI A phase I study of oxaliplatin (OX) in combination with bortezomib (B) in patients with advanced malignancy. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL SP Amer Soc Clin Oncol C1 NCI, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 880S EP 880S PN 1 PG 1 WC Oncology SC Oncology GA 943BK UT WOS:000230326605558 ER PT J AU Wolmark, N Wieand, HS Kuebler, JP Colangelo, L Smith, RE AF Wolmark, N Wieand, HS Kuebler, JP Colangelo, L Smith, RE TI A phase III trial comparing FULV to FULV plus oxaliplatin in stage II or III carcinoma of the colon: Results of NSABP Protocol C-07. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract CT 41st Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 13-17, 2005 CL Orlando, FL C1 NSABP, Pittsburgh, PA USA. CCOP, Columbus, OH USA. NR 0 TC 10 Z9 10 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 SU S BP 1092S EP 1092S PN 2 PG 1 WC Oncology SC Oncology GA 943BP UT WOS:000230327100005 ER PT J AU Mamounas, EP Bryant, J Leinbersky, B Fehrenbacher, L Sedlacek, SM Fisher, B Wickerham, DL Yothers, G Soran, A Wolmark, N AF Mamounas, EP Bryant, J Leinbersky, B Fehrenbacher, L Sedlacek, SM Fisher, B Wickerham, DL Yothers, G Soran, A Wolmark, N TI Paclitaxel after doxorubicin plus cyclophosphamide as adjuvant chemotherapy for node-positive breast cancer: Results from NSABP B-28 SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the American-Society-of-Clinical-Oncology (ASCO) CY MAY 31-JUN 03, 2003 CL Chicago, IL SP Amer Soc Clin Oncol (ASCO) ID PHASE-II TRIAL; COLONY-STIMULATING FACTOR; HIGH-DOSE PACLITAXEL; 3-HOUR INFUSION; RANDOMIZED-TRIAL; TAMOXIFEN; THERAPY; CELLS; ADRIAMYCIN; INTENSIFICATION AB Purpose The primary aim of National Surgical Adjuvant Breast and Bowel Project (NSABP) B-28 was to determine whether four cycles of adjuvant paclitaxel (PTX) after four cycles of adjuvant doxorubicin/cyclophosphamide (AC) will prolong disease-free survival (DFS) and overall survival (OS) compared with four cycles of AC alone in patients with resected operable breast cancer and histologically positive axillary nodes. Patients and Methods Between August 1995 and May 1998, 3,060 patients were randomly assigned (AC, 1,529; AC followed by PTX [AC -> PTX], 1,531). Patients >= 50 years and those younger than 50 years with estrogen receptor (ER) or progesterone receptor (PR) -positive tumors also received tamoxifen for 5 years, starting with the first dose of AC. Postlumpectomy radiotherapy was mandated. Postmastectomy or regional radiotherapy was prohibited, Median follow-up is 64.6 months. Results The addition of PTX to AC significantly reduced the hazard for DFS event by 17% (relative risk [RR], 0.83; 95% CI, 0.72 to 0.95; P =.006). Five-year DFS was 76% +/- 2% for patients randomly assigned to AC -> PTX compared with 72% +/- 2% for those randomly assigned to AC. Improvement in OS was small and not statistically significant (RR, 0.93; 95% CI, 0.78 to 1.12; P = .46). Five-year OS was 85% +/- 2% for both groups. Subset analysis of the effect of paclitaxel according to hormone receptors or tamoxifen administration did not reveal statistically significant interaction (for DFS, P = .30 and P = .44, respectively). Toxicity with the AC -> PTX regimen was acceptable for the adjuvant setting. Conclusion The addition of PTX to AC resulted in significant improvement in DFS but no significant improvement in OS with acceptable toxicity. No significant interaction between treatment effect and receptor status or tamoxifen administration was observed. C1 Aultman Hlth Fdn, Canton, OH 44710 USA. Univ Pittsburgh, Med Ctr, Natl Surg Adjuvant Breast & Bowel Project, Operat Off, Pittsburgh, PA USA. Univ Pittsburgh, Med Ctr, Ctr Biostat, Pittsburgh, PA USA. Allegheny Gen Hosp, Pittsburgh, PA 15212 USA. Kaiser Permanente, Vallejo, CA USA. Rose Med Ctr, Denver, CO USA. RP Mamounas, EP (reprint author), Aultman Hlth Fdn, 2600 6th St SW, Canton, OH 44710 USA. EM tmamounas@aultman.com OI Yothers, Greg/0000-0002-7965-7333 FU NCI NIH HHS [U10CA-37377, U10CA-12027, U10CA-69951, U10CA-69974] NR 46 TC 343 Z9 356 U1 0 U2 6 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 BP 3686 EP 3696 DI 10.1200/JCO.2005.10.517 PG 11 WC Oncology SC Oncology GA 931CA UT WOS:000229462200008 PM 15897552 ER PT J AU Kammula, US Coit, DG AF Kammula, US Coit, DG TI Pitfalls in the use of RT-PCR as a prognostic indicator in melanoma - In reply SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID SENTINEL LYMPH-NODES C1 NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. Mem Sloan Kettering Canc Ctr, Dept Surg, New York, NY 10021 USA. RP Kammula, US (reprint author), NCI, Surg Branch, NIH, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2005 VL 23 IS 16 BP 3864 EP 3865 DI 10.1200/JCO.2005.05.382 PG 2 WC Oncology SC Oncology GA 931CA UT WOS:000229462200041 ER PT J AU Compton, WM Conway, KP Stinson, FS Colliver, JD Grant, BF AF Compton, WM Conway, KP Stinson, FS Colliver, JD Grant, BF TI Prevalence, correlates, and comorbidity of DSM-IV antisocial personality syndromes and alcohol and specific drug use disorders in the United States: Results from the national epidemiologic survey on alcohol and related conditions SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID INTERVIEW SCHEDULE AUDADIS; GENERAL-POPULATION SAMPLE; SUBSTANCE USE DISORDER; III-R; ICD-10 ALCOHOL; HEAVY DRINKERS; PSYCHIATRIC-DIAGNOSIS; DEPENDENCE; RELIABILITY; VALIDITY AB Objective: The purpose of this study was to provide nationally representative data on the prevalence, sociodemographic correlates, and comorbidity of antisocial syndromes across alcohol and 8 specific drug use disorders, including sedative, tranquilizer, opiate, stimulant, hallucinogen, cannabis, cocaine, and inhalant/solvent abuse and dependence. Method: This study is based on a nationally representative sample of adults. Lifetime prevalences of antisocial syndromes were estimated and logistic regression analyses were used to examine associations between antisocial syndromes and sociodemographic characteristics and substance use disorders. Diagnoses were made according to the criteria of the DSM-IV using the National Institute on Alcohol Abuse and Alcoholism Alcohol Use Disorder and Associated Disabilities Interview Schedule-DSM-IV Version. Results: The lifetime prevalences of antisocial personality disorder (APD), conduct disorder, and adult antisocial behavior were 3.6%, 1.1 %, and 12.3%, respectively. Prevalences of alcohol use disorders and drug use disorders were 30.3% and 10.3%, respectively. In general, men and individuals who were younger, widowed/separated/divorced, of lower socioeconomic status, and living in urban areas or in the West were more likely to have antisocial syndromes. Native Americans were more likely and Asians and Hispanics were less likely to have APD and adult antisocial behavior. Virtually all of the associations between APD and adult antisocial behavior and specific substance use disorders were positive and statistically significant (p <.05). Significant associations between conduct disorder and substance use disorders were concentrated among women. Conclusion: Comorbidity of specific substance disorders with antisocial syndromes is very common in the U.S. population. Further work in many directions is indicated by the results of this study, including the factors that give rise to the associations and the treatment and prevention implications of these conditions when comorbid. C1 NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Bethesda, MD 20892 USA. NIAAA, Div Epidemiol Serv & Prevent Res, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Grant, BF (reprint author), NIAAA, Lab Epidemiol & Biometry, Div Intramural Clin & Biol Res, NIH,Dept Hlth & Human Serv, Room 3077,MS 9304,5635 Fishers Ln, Bethesda, MD 20892 USA. EM bgrant@willco.niaaa.nih.gov OI Conway, Kevin/0000-0002-7638-339X NR 57 TC 209 Z9 212 U1 8 U2 34 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD JUN PY 2005 VL 66 IS 6 BP 677 EP 685 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 938GX UT WOS:000229989000002 PM 15960559 ER PT J AU Vitiello, B Shader, RI Parker, CB Ritz, L Harlan, W Greenblatt, DJ Gadde, KM Krishnan, KRR Davidson, JRT AF Vitiello, B Shader, RI Parker, CB Ritz, L Harlan, W Greenblatt, DJ Gadde, KM Krishnan, KRR Davidson, JRT TI Hyperforin plasma level as a marker of treatment adherence in the National Institutes of Health Hypericum Depression Trial SO JOURNAL OF CLINICAL PSYCHOPHARMACOLOGY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ST-JOHNS-WORT; TRICYCLIC ANTIDEPRESSANTS; ULTRAVIOLET DETECTION; EXTRACTS AB Background: A previously reported clinical trial of Hypericum perforatum (St John's wort) in depression did not demonstrate efficacy. We assessed treatment adherence by measuring plasma hyperforin and evaluated the possible impact of adherence on study results. Methods: Outpatients with major depression (N = 340) were randomized to an 8-week trial of H. perforatum (900-1500 mg/d), sertraline (50-100 mg/d) as active comparator, or placebo. Plasma was available from 292 patients (86% of randomized). Samples from the placebo and H. perforatum groups were assayed for hyperforin, and samples from the sertraline group for sertraline/N-desmethyl-sertraline. Results: Of the 104 patients randomized to placebo, 18 (17%) had detectable plasma hyperforin. Of the 97 patients randomized to H. perforatum, 17 (17%) had no detectable plasma hyperforin. All the assayed sertraline patients (N = 91) had plasma sertraline/N-desmethyl-sertraline. The clinical trial conclusions remained unchanged when only patients with plasma assay consistent with random assignment were included in the analyses. Conclusions: One of every 6 patients assigned to placebo had plasma hyperforin, and 1 of every 6 patients assigned to H. perforatum had no detectable plasma hyperforin. The finding underscores the difficulty of enforcing treatment adherence in clinical trials of preparations that are readily available in the community. C1 NIMH, Bethesda, MD 20892 USA. Tufts Univ, Sch Med, Boston, MA 02111 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Duke Univ, Med Ctr, Durham, NC USA. RP Vitiello, B (reprint author), NIMH, Room 7147,6001 Execut Blvd, Bethesda, MD 20892 USA. EM bvitiell@mail.nih.gov OI Shader, Richard/0000-0002-1888-7565 FU NIMH NIH HHS [N01 MH70007] NR 13 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0271-0749 J9 J CLIN PSYCHOPHARM JI J. Clin. Psychopharmacol. PD JUN PY 2005 VL 25 IS 3 BP 243 EP 249 DI 10.1097/01.jcp.0000162801.72002.85 PG 7 WC Pharmacology & Pharmacy; Psychiatry SC Pharmacology & Pharmacy; Psychiatry GA 927VN UT WOS:000229228700008 PM 15876903 ER PT J AU Compton, WM AF Compton, WM TI Applying a public health approach to drug abuse research SO JOURNAL OF DRUG ISSUES LA English DT Article; Proceedings Paper CT 8th Annual Conference on Health Services Research in Substance Abuse CY OCT 22-24, 2003 CL Univ Georgia, Atlanta, GA SP Ctr Res Behav Hlth & Human Serv, Georgia Inst Technol HO Univ Georgia ID NATIONAL-COMORBIDITY-SURVEY; PSYCHIATRIC-DISORDERS; DEPENDENT SUBJECTS; SUBSTANCE-ABUSE; UNITED-STATES; PREVALENCE AB Applying a public health perspective to drug abuse research has far-reaching implications. First, the health of the entire community is of concern, not just the individual patient. Because of the social impact of drug abuse, these problems become the responsibility of all citizens to address. Second, the perspective requires treating drug abuse as a health issue, not as a criminal justice, moral, or social issue. Third, as in other branches of medicine, applying this perspective to drug abuse research will encourage development of the most effective ways to enhance drug abuse prevention and treatment interventions through cross-disciplinary approaches. The public health approach requires studies that (1) determine need for intervention; (2) provide clues about etiology; (3) determine effective approaches, systems, and financing strategies; and (4) measure the impact of interventions and services on the health of a population. Overall, attending to the public health implications of research will help to assure the maximum impact of scientific findings. C1 NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. RP Compton, WM (reprint author), NIDA, Div Epidemiol Serv & Prevent Res, Bethesda, MD 20892 USA. NR 11 TC 1 Z9 1 U1 1 U2 4 PU J DRUG ISSUES INC PI TALLAHASSEE PA FLORIDA STATE UNIV, SCHOOL CRIMINOLOGY CRIMINAL JUSTICE, PO BOX 66696, TALLAHASSEE, FL 32313-6696 USA SN 0022-0426 J9 J DRUG ISSUES JI J. Drug Issues PD SUM PY 2005 VL 35 IS 3 BP 461 EP 467 PG 7 WC Substance Abuse SC Substance Abuse GA 967UB UT WOS:000232115600002 ER PT J AU Guydish, J Manser, ST Jessup, M Tajima, B Sears, C Montini, T AF Guydish, J Manser, ST Jessup, M Tajima, B Sears, C Montini, T TI Multi-level assessment protocol (MAP) for adoption in multisite clinical trials SO JOURNAL OF DRUG ISSUES LA English DT Article; Proceedings Paper CT 8th Annual Conference on Health Services Research in Substance Abuse CY OCT 22-24, 2003 CL Univ Georgia, Atlanta, GA SP Ctr Res Behav Hlth & Human Serv, Georgia Inst Technol HO Univ Georgia ID METHAMPHETAMINE TREATMENT PROJECT; SUBSTANCE-ABUSE TREATMENT; MATRIX MODEL; PERSPECTIVE AB The National Institute on Drug Abuse (NIDA) Clinical Trials Network (CTN) is intended to test promising drug abuse treatment models in multisite clinical trials and to support adoption of new interventions into clinical practice. Using qualitative research methods we asked the following question: how might the technology of multisite clinical trials be modified to better support adoption of tested interventions? A total of 42 participants, representing eight organizational levels ranging from clinic staff to clinical trial leaders, were interviewed about their role in the clinical trial, its interactions with clinics, and intervention adoption. Among eight clinics participating in the clinical trial, we found adoption of the tested intervention in one clinic only. Analysis of interview data revealed four conceptual themes likely to affect adoption and may be informative in future multisite clinical trials. Planning for adoption in the early stages of protocol development will better serve the aim of integrating new interventions into practice. C1 Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Psychiat, San Francisco, CA 94143 USA. Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA. NIH, Bethesda, MD 20892 USA. RP Guydish, J (reprint author), Univ Calif San Francisco, Inst Hlth Policy Studies, San Francisco, CA 94143 USA. OI Guydish, Joseph/0000-0003-2115-3340 FU NIDA NIH HHS [R01 DA014470-03, U10 DA015815, P50 DA009253, R01 DA014470] NR 32 TC 7 Z9 7 U1 1 U2 1 PU J DRUG ISSUES INC PI TALLAHASSEE PA FLORIDA STATE UNIV, SCHOOL CRIMINOLOGY CRIMINAL JUSTICE, PO BOX 66696, TALLAHASSEE, FL 32313-6696 USA SN 0022-0426 J9 J DRUG ISSUES JI J. Drug Issues PD SUM PY 2005 VL 35 IS 3 BP 529 EP 546 PG 18 WC Substance Abuse SC Substance Abuse GA 967UB UT WOS:000232115600006 PM 20890376 ER PT J AU Voutetakis, A Bossis, I Kok, MR Zhang, WT Wang, JH Cotrim, AP Zheng, CY Chiorini, JA Nieman, LK Baum, BJ AF Voutetakis, A Bossis, I Kok, MR Zhang, WT Wang, JH Cotrim, AP Zheng, CY Chiorini, JA Nieman, LK Baum, BJ TI Salivary glands as a potential gene transfer target for gene therapeutics of some monogenetic endocrine disorders SO JOURNAL OF ENDOCRINOLOGY LA English DT Article ID ADENOASSOCIATED VIRUS VECTORS; RAT SUBMANDIBULAR-GLANDS; GROWTH-HORMONE; IN-VIVO; PROTEIN SECRETION; BETA-THALASSEMIA; ADENOVIRUS; ERYTHROPOIETIN; THERAPY; PATHWAY AB Salivary glands (SGs) exhibit several important features which are also common to endocrine glands: self-containment due to a surrounding capsule, highly efficient protein production and the ability to secrete proteins into the bloodstream. We have hypothesized that SGs are potentially- useful as gene transfer targets for the correction of inherited monogenetic endocrine disorders. In the present communication, we extend our studies and attempt to test our hypothesis by comparing the efficacy of two commonly used viral vectors and the resulting serum and salivary distribution of transgene encoded hormones. A low dose (5 x 10(9) particles) of either an adenoviral serotype 5 (Ad5) vector encoding the human erythropoietin (hEPO) cDNA or an adeno-associated virus serotype 2 (AAV2) vector encoding either the hEPO or human growth hormone (hGH) cDNA was administered to individual submandibular SGs of Balb/c mice. Serum and salivary hEPO and hGH levels were determined at defined time points. Two additional recombinant viruses encoding enhanced green fluorescence protein (GFP) were also used (AdGFP and AAVGFP) in order to perform immunohistochemical analyses of transgenic protein localization in SG sections post-administration. AAV2 vectors led to stable gene transfer unlike the results with the Ads vectors. Indeed, in one mouse we observed hEPO production for a period of two years after administration of AAVhEPO to SGs. hEPO, which is a constitutive pathway secretory protein, was readily secreted into the bloodstream from the SGs, yielding therapeutically adequate serum levels. Conversely, hGH, a regulated secretory pathway protein, was preferentially secreted into saliva. SGs may be an attractive candidate target tissue for gene therapeutics of some monogenetic endocrine deficiency disorders. At present, AAV2 vectors seem particularly useful for such applications, and transgenes encoding constitutive secretory pathway hormones are more suitable for this application with SGs than those encoding regulated secretory pathway hormones. C1 NIDCR, Gene Therapy & Therapeut Branch, NIH, DHHS, Bethesda, MD 20892 USA. Univ Amsterdam, Acad Med Ctr, Dept Clin Immunol & Rheumatol, NL-1105 AZ Amsterdam, Netherlands. NICHD, Pediat & Reprod Endocrinol Branch, NIH, DHHS, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), NIDCR, Gene Therapy & Therapeut Branch, NIH, DHHS, Bethesda, MD 20892 USA. EM bbaum@dir.nidcr.nih.gov NR 45 TC 48 Z9 50 U1 0 U2 0 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 JUN PY 2005 VL 185 IS 3 BP 363 EP 372 DI 10.1677/joe.1.06171 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 936LP UT WOS:000229857800002 PM 15930162 ER PT J AU Harris, MJ Le Couteur, DG Arias, IM AF Harris, MJ Le Couteur, DG Arias, IM TI Progressive familial intrahepatic cholestasis: Genetic disorders of biliary transporters SO JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY LA English DT Review DE ABC transporters; biliary secretion; hereditary cholestasis; intrahepatic; PFIC ID SALT EXPORT PUMP; IDIOPATHIC RECURRENT CHOLESTASIS; INTRA-HEPATIC CHOLESTASIS; P-GLYCOPROTEIN GENE; BILE-ACID METABOLISM; BYLER-DISEASE; LIVER-DISEASE; HEREDITARY CHOLESTASIS; FUNCTIONAL EXPRESSION; MDR3 GENE AB Progressive familial intrahepatic cholestasis types 1, 2 and 3 are childhood diseases of the liver. Benign recurrent intrahepatic cholestasis is predominantly an adult form with similar clinical symptoms that spontaneously resolve. These genetic disorders have significantly helped to unravel the basic mechanisms of the canalicular bile transport processes. Progressive familial intrahepatic cholestasis type 1 involves a gene also linked to benign recurrent intrahepatic cholestasis. The gene codes for an aminophospholipid translocase protein that maintains the integrity of the membrane. How a mutation in this protein causes cholestasis is unknown but is thought to involve the enterohepatic recirculation of bile acids. Progressive familial intrahepatic cholestasis types 2 and 3 involve the canalicular bile salt export pump and a phospholipid translocase, respectively, both of which are fundamental to bile secretion. This review covers the clinical manifestations, genetics, treatment and mechanism of each disease. (C) 2005 Blackwell Publishing Asia Pty Ltd. C1 NIH, Bethesda, MD 20892 USA. NICHHD, Cell Biol & Metab Branch, Bethesda, MD 20892 USA. Concord Repatriat Gen Hosp, Ctr Educ & Res Aging, Sydney, NSW, Australia. Univ Sydney, ANZAC Res Inst, Sydney, NSW 2006, Australia. RP Arias, IM (reprint author), NIH, Bethesda, MD 20892 USA. EM iarias@helix.nih.gov NR 79 TC 34 Z9 38 U1 0 U2 5 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0815-9319 J9 J GASTROEN HEPATOL JI J. Gastroenterol. Hepatol. PD JUN PY 2005 VL 20 IS 6 BP 807 EP 817 DI 10.1111/j.1400-1746.2005.03743.x PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 928OW UT WOS:000229282400002 PM 15946126 ER PT J AU Brienza, RS Whitman, L Ladouceur, L Green, ML AF Brienza, RS Whitman, L Ladouceur, L Green, ML TI Evaluation of a women's safe shelter experience to teach internal medicine residents about intimate partner violence SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE intimate partner violence; medical education; curriculum; randomized controlled trial ID PRIMARY-CARE PHYSICIANS; DOMESTIC VIOLENCE; PANDORA BOX; ABUSE; ATTITUDES; PREVALENCE; HEALTH; IDENTIFICATION; EDUCATION; STUDENTS AB Although intimate partner violence (IPV) remains a major public health problem, physicians often fail to screen female patients. Reported IPV training approaches suffer from weak study designs and limited outcome assessments. We hypothesized that an educational experience for residents at a women's safe shelter would have significantly greater impact on IPV competencies, screening, and care for victims than a workshop seminar alone. In a pre-post randomized controlled trial, we compared residents exposed to the workshop seminar alone (controls) to residents exposed to these methods plus an experience at a women's safe shelter (cases). Competencies were assessed by written questionnaire and included knowledge, skills, attitudes, resource awareness, and screening behaviors. Of the 36 residents in the trial, 22 (61%) completed both pre- and postquestionnaires. Compared to controls, cases showed significantly greater pre- post improvement in the knowledge composite subscale. There were no significant differences between cases and controls in the subscales of skills, attitudes, or resource awareness. Cases increased their self-reported screening frequency but this did not differ significantly from the controls. Enhancing traditional IPV curriculum with a women's safe shelter educational experience may result in small improvements in residents' knowledge about IPV. C1 Hosp St Raphael, Dept Med, New Haven, CT USA. Yale Univ, Sch Med, Dept Internal Med, New Haven, CT 06510 USA. NIAID, Div Aids, NIH, Bethesda, MD 20892 USA. RP Brienza, RS (reprint author), 107 Benson Pl, Fairfield, CT 06824 USA. EM Rebecca.brienza@sbcglobal.net NR 51 TC 10 Z9 11 U1 1 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD JUN PY 2005 VL 20 IS 6 BP 536 EP 540 DI 10.1111/j.1525-1497.2005.0100.x PG 5 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 940KG UT WOS:000230142800009 PM 15987330 ER PT J AU Calvisi, DF Conner, EA Ladu, S Lemmer, ER Factor, VM Thorgeirsson, SS AF Calvisi, DF Conner, EA Ladu, S Lemmer, ER Factor, VM Thorgeirsson, SS TI Activation of the canonical Wnt/beta-catenin pathway confers growth advantages in c-Myc/E2F1 transgenic mouse model of liver cancer SO JOURNAL OF HEPATOLOGY LA English DT Article DE c-Myc; E2F1; beta-catenin; hepatic tumors; transgenic mouse models ID TUMOR-SUPPRESSOR PROTEIN; MYC-INDUCED APOPTOSIS; BETA-CATENIN; C-MYC; HEPATOCELLULAR CARCINOMAS; SIGNALING PATHWAY; RB/E2F PATHWAY; FACTOR-ALPHA; CELL FACTOR; S-PHASE AB Background/Aims: Previously, we showed that activation of the beta-catenin/Wnt pathway is a dominant event during c-Myc/E2F1 hepatocarcinogenesis. Majority of c-Myc/E2F1 HCCs displayed nuclear accumulation of beta-catenin in the absence of beta-catenin mutations, suggesting that alterations in other members of the Wnt pathway might be responsible for nuclear localization of beta-catenin. Here, we investigated the mechanisms responsible for nuclear translocation of wild-type beta-catenin and addressed the potential contribution of the Wnt pathway in c-Myc/E2F1 hepatocarcinogenesis. Methods: Status of the members of the Wnt pathway was determined through microsatellite and Western blot analysis. Results: Majority of c-Myc/E2F1 HCCs exhibited multiple abnormalities in the Wnt pathway regardless of the presence of beta-catenin mutations. The observed abnormalities included overexpression of Wnt-1, Frizzled 1 and 2 receptors, Dishevelled-1, downregulation of Secreted frizzled-related protein-1, GSK-3 beta inactivation, microsatellite instability at the Axin locus as well as induction of beta-catenin target genes, such as glutamine synthetase, glutamate transporter-1, and Wisp-1. HCCs with beta-catenin activation displayed significantly higher proliferation rate and larger tumor size when compared with beta-catenin negative tumors. Conclusions: The data demonstrate that multiple abnormalities in the members of the Wnt pathway lead to nuclear accumulation of beta-catenin and suggest that activation of Wnt pathway provides proliferative advantages in c-Myc/E2F1-driven hepatocarcinogenesis. Published by Elsevier B.V. on behalf of European Association for the Study of the Liver. C1 NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Thorgeirsson, SS (reprint author), NCI, Expt Carcinogenesis Lab, Div Basic Sci, NIH, Bldg 37,Room 4146A,37 Convent Dr MSC 4262, Bethesda, MD 20892 USA. EM snorri_thorgeirsson@nih.gov NR 57 TC 55 Z9 55 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-8278 J9 J HEPATOL JI J. Hepatol. PD JUN PY 2005 VL 42 IS 6 BP 842 EP 849 DI 10.1016/j.jhep.2005.01.029 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 931ZG UT WOS:000229523400010 PM 15885355 ER PT J AU Cuesta, N Martinez, A Cuttitta, F Zudaire, E AF Cuesta, N Martinez, A Cuttitta, F Zudaire, E TI Identification of adrenomedullin in avian type II pneumocytes: Increased expression after exposure to air pollutants SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE adrenomedullin; pigeon; air pollution; lung; surfactant; type II pneumocytes; ozone ID PULMONARY SURFACTANT SYSTEM; TERM OZONE EXPOSURE; LUNG SURFACTANT; PLASMA ADRENOMEDULLIN; ELECTRON-MICROSCOPY; OXIDATIVE STRESS; GENE-EXPRESSION; COLUMBA-LIVIA; SECRETION; PEPTIDE AB Adrenomedullin (AM) is a potent vasodilator peptide present in the lung of mammals where it is expressed mainly in the columnar epithelium and alveolar macrophages. AM increases the secretion of phosphatidylcholine by type II pneumocytes, which suggests a role as an autocrine modulator of surfactant secretion. In this study we show the expression of an AM-like protein in the lung of the pigeon, Columba livia. Using an antibody against its human ortholog, AM-like immunoreactivity was found to be associated with membranous structures of the multivesicular bodies of type II pneumocytes. We also studied the differential expression of AM-like peptide in the lung of pigeons exposed to polluted city air vs cleaner countryside conditions and found that AM-like expression was higher in city animals. Similar results were obtained in an experimental study in which pigeons were exposed to increasing concentrations of a single pollutant, ozone. Taken together, our findings support the implication of AM in the response of type II pneumocytes to air pollutants. C1 Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. RP Cuesta, N (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, 660 W Redwood St, Baltimore, MD 21201 USA. EM ncuesta@som.umaryland.edu RI Cuesta, Natalia/C-1358-2012; Martinez, Alfredo/A-3077-2013; Cuesta, Natalia/J-7761-2015; Cuttitta, Frank/B-4758-2016 OI Martinez, Alfredo/0000-0003-4882-4044; Cuesta, Natalia/0000-0003-0809-2934; NR 46 TC 1 Z9 1 U1 1 U2 6 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD JUN PY 2005 VL 53 IS 6 BP 773 EP 780 DI 10.1369/jhc.4A6498.2005 PG 8 WC Cell Biology SC Cell Biology GA 930FW UT WOS:000229402200010 PM 15928326 ER PT J AU Akimova, OA Bagrov, AY Tremblay, J Hamet, P Orlov, SN AF Akimova, OA Bagrov, AY Tremblay, J Hamet, P Orlov, SN TI Endogenous cardiotonic steroids differentially affect intracellular Na plus and [Na plus ]i/[K plus ]i-independent signaling SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 15th European Meeting on Hypertension CY JUN 17-21, 2005 CL Milan, ITALY SP European Soc Hypertens, AstraZeneca, Bristol-Myers Squibb Co, Boehringer Ingelheim, MSD, NOVARTIS, RECORDATI, SANKYO, Sanofi Aventis, Bayer Healthcare AG, Pfizer Inc, Solvay Pharmaceut GmbH C1 CHUM, Res Ctr, Montreal, PQ, Canada. NIA, NIH, Baltimore, MD 21224 USA. RI ORLOV, SERGEI/I-4071-2013; Cossette, Suzanne/I-8008-2016 NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2005 VL 23 SU 2 BP S355 EP S355 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 947JO UT WOS:000230639802283 ER PT J AU Leenen, F Nwachuku, C Cushman, W Black, H Simpson, L Davis, B AF Leenen, F Nwachuku, C Cushman, W Black, H Simpson, L Davis, B CA ALLHAT Collaborative Res Grp TI Outcomes in high risk hypertensives randomized to calcium channel blocker versus angiotensin converting enzyme inhibitor in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 15th European Meeting on Hypertension CY JUN 17-21, 2005 CL Milan, ITALY SP European Soc Hypertens, AstraZeneca, Bristol-Myers Squibb Co, Boehringer Ingelheim, MSD, NOVARTIS, RECORDATI, SANKYO, Sanofi Aventis, Bayer Healthcare AG, Pfizer Inc, Solvay Pharmaceut GmbH C1 ALLHAT Collaborat Res Grp, Ottawa, ON, Canada. Univ Ottawa, Inst Heart, Ottawa, ON, Canada. NHLBI, Bethesda, MD 20892 USA. Memphis VAMC, Memphis, TN USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60612 USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2005 VL 23 SU 2 BP S113 EP S113 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 947JO UT WOS:000230639800399 ER PT J AU Leenen, F Nwachuku, C Cushman, W Black, H Simpson, L Davis, B AF Leenen, F Nwachuku, C Cushman, W Black, H Simpson, L Davis, B CA ALLHAT Collaborative Res Grp TI Cardiovascular outcomes in hypertensives with coronary artery disease randomized to amlodipine versus lisinopril in the antihypertensive and lipid-lowering treatment to prevent heart attack trial (ALLHAT) SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 15th European Meeting on Hypertension CY JUN 17-21, 2005 CL Milan, ITALY SP European Soc Hypertens, AstraZeneca, Bristol-Myers Squibb Co, Boehringer Ingelheim, MSD, NOVARTIS, RECORDATI, SANKYO, Sanofi Aventis, Bayer Healthcare AG, Pfizer Inc, Solvay Pharmaceut GmbH C1 Univ Ottawa, Heart Inst, Ottawa, ON, Canada. Natl Heart Lung & Blood, Bethesda, MD USA. Memphis VAMC, Memphis, TN USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL USA. Univ Texas, Sch Publ Hlth, Houston, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2005 VL 23 SU 2 BP S21 EP S22 PG 2 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 947JO UT WOS:000230639800065 ER PT J AU Nishikawa, T Suematsu, S Saito, J Soyama, A Ito, H Kino, T Chrousos, G AF Nishikawa, T Suematsu, S Saito, J Soyama, A Ito, H Kino, T Chrousos, G TI Local aldosterone production by human renal mesangial cells SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 15th European Meeting on Hypertension CY JUN 17-21, 2005 CL Milan, ITALY SP European Soc Hypertens, AstraZeneca, Bristol-Myers Squibb Co, Boehringer Ingelheim, MSD, NOVARTIS, RECORDATI, SANKYO, Sanofi Aventis, Bayer Healthcare AG, Pfizer Inc, Solvay Pharmaceut GmbH C1 Yokohama Rosai Hosp, Yokohama, Kanagawa, Japan. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2005 VL 23 SU 2 BP S88 EP S88 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 947JO UT WOS:000230639800305 ER PT J AU Zelinka, T Strauch, B Petrak, O Holaj, R Weisserova, H Pacak, K Widimky, J AF Zelinka, T Strauch, B Petrak, O Holaj, R Weisserova, H Pacak, K Widimky, J TI Analysis of long-term blood pressure variability in patients with pheochromocytoma and essential hypertension SO JOURNAL OF HYPERTENSION LA English DT Meeting Abstract CT 15th European Meeting on Hypertension CY JUN 17-21, 2005 CL Milan, ITALY SP European Soc Hypertens, AstraZeneca, Bristol-Myers Squibb Co, Boehringer Ingelheim, MSD, NOVARTIS, RECORDATI, SANKYO, Sanofi Aventis, Bayer Healthcare AG, Pfizer Inc, Solvay Pharmaceut GmbH C1 Gen Fac Hosp, Prague 2, Czech Republic. NIH, Bethesda, MD 20892 USA. RI Petrak, Ondrej/A-5839-2017; Holaj, Robert/D-4241-2017; Strauch, Branislab/D-4274-2017; Zelinka, Tomas/D-4276-2017 OI Petrak, Ondrej/0000-0001-8992-3562; Holaj, Robert/0000-0002-9488-9706; Strauch, Branislab/0000-0001-5137-7017; Zelinka, Tomas/0000-0003-3395-8373 NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0263-6352 J9 J HYPERTENS JI J. Hypertens. PD JUN PY 2005 VL 23 SU 2 BP S284 EP S284 PG 1 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 947JO UT WOS:000230639802026 ER PT J AU Fry, TJ Mackall, CL AF Fry, TJ Mackall, CL TI The many faces of IL-7: From lymphopoiesis to peripheral T cell maintenance SO JOURNAL OF IMMUNOLOGY LA English DT Review ID THYMIC STROMAL LYMPHOPOIETIN; COMMON LYMPHOID PROGENITORS; RECEPTOR-ALPHA EXPRESSION; BONE-MARROW TRANSPLANT; HOMEOSTATIC PROLIFERATION; INTERLEUKIN-7 RECEPTOR; MEMORY CELLS; IN-VIVO; THYMOCYTE DEVELOPMENT; POSITIVE SELECTION AB IL-7 is well known as a lymphopoietic cytokine, but recent studies have also identified a critical role for IL-7 in peripheral T cell homeostasis. IL-7 is well poised to serve as a homeostatic cytokine because it is produced by resting stromal cells, the IL-7R is present on most T cells, and IL-7 down-regulates its own receptor. These features allow IL-7 to signal large numbers of resting T cells and to be efficiently used when supplies are limiting. Consistent with this, in normal hosts, IL-7 is required for survival of naive T cell populations, and IL-7 contributes to homeostatic cycling of naive and memory cells. In addition, lymphopenic hosts accumulate increased levels of IL-7, and the supranormal levels are largely responsible for inducing homeostatic peripheral expansion in response to lymphopenia. Thus, IL-7 plays critical and nonredundant roles in both T cell lymphopoiesis and in maintaining and restoring peripheral T cell homeostasis. C1 NCI, Ctr Canc Res, Immunol Sect, Pediat Oncol Branch,NIH, Bethesda, MD 20892 USA. RP Fry, TJ (reprint author), NCI, Ctr Canc Res, Immunol Sect, Pediat Oncol Branch,NIH, Bldg 10,Room 1-3940,10 Ctr Dr, Bethesda, MD 20892 USA. EM fryt@mail.nih.gov NR 74 TC 324 Z9 332 U1 1 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 1 PY 2005 VL 174 IS 11 BP 6571 EP 6576 PG 6 WC Immunology SC Immunology GA 928UY UT WOS:000229298400007 PM 15905493 ER PT J AU Medvedev, AE Thomas, K Awomoyi, A Kuhns, DB Gallin, JI Li, XX Vogel, SN AF Medvedev, AE Thomas, K Awomoyi, A Kuhns, DB Gallin, JI Li, XX Vogel, SN TI Cutting edge: Expression of IL-1 receptor-associated kinase-4 (IRAK-4) proteins with mutations identified in a patient with recurrent bacterial infections alters normal IRAK-4 interaction with components of the IL-1 receptor complex SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION PATHWAY; TOLL-LIKE RECEPTORS; FACTOR-KAPPA-B; ADAPTER PROTEIN; INTERLEUKIN-1; ACTIVATION; MYD88; LIPOPOLYSACCHARIDE; MEMBER; FAMILY AB In a patient with recurrent bacterial infections and profound hyporesponsiveness to LPS and IL-1, we previously identified two mutations in IL-IR-associated kinase-4 (IRAK-4) that encoded proteins with truncated kinase domains. Overexpression of either of these mutant IRAK-4 variants in HEK293 cells failed to activate endogenous IRAK-1 and suppressed IL-1-induced IRAK-1 kinase activity, in contrast to wild-type (WT) IRAK-4. In this study, interactions of WIT and mutant IRAK-4 species with IL-1R, IRAK-1, and MyD88 in HEK293 transfectants were compared. IL-1 induced a strong interaction among the IL-1R, activated IRAK-1, MyD88, and WIT, but not mutant, IRAK-4. Truncated IRAK-4 proteins constitutively interacted more strongly with MyD88 and blunted IL-1-induced recruitment of IRAK-1 and MyD88 to the IL-1R. Thus, decreased IL-1-induced association of IRAK-1 and MyD88 with the IL-1RI may result from sequestration of cytoplasmic MyD88 by IRAK-4 mutant proteins. Therefore, mimetics of these truncated IRAK-4 proteins may represent a novel approach to mitigating hyperinflammatory states. C1 Univ Maryland, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. Sci Applicat Int Corp Frederick Inc, Clin Serv Program, NCI, Frederick, MD 21702 USA. NIAID, Lab Host Def, NIH, Bethesda, MD 20892 USA. Cleveland Clin Fdn, Dept Immunol, Cleveland, OH 44195 USA. RP Vogel, SN (reprint author), Univ Maryland, Dept Microbiol & Immunol, 655 W Balitimore St,13-009, Baltimore, MD 21201 USA. EM svogel@som.umaryland.edu FU NIAID NIH HHS [R01 AI059524, AI-44936, AI-059524]; NIGMS NIH HHS [GM-600020]; PHS HHS [N01-C0-12400] NR 23 TC 40 Z9 43 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 JUN 1 PY 2005 VL 174 IS 11 BP 6587 EP 6591 PG 5 WC Immunology SC Immunology GA 928UY UT WOS:000229298400010 PM 15905496 ER PT J AU Brehm, MA Daniels, KA Ortaldo, JR Welsh, RM AF Brehm, MA Daniels, KA Ortaldo, JR Welsh, RM TI Rapid conversion of effector mechanisms from NK to T cells during virus-induced lysis of allogeneic implants in vivo SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; BONE-MARROW ALLOGRAFTS; MHC CLASS-I; TRANSPLANTATION TOLERANCE; VIRAL-INFECTIONS; HETEROLOGOUS IMMUNITY; MONOCLONAL-ANTIBODY; MEDIATED REJECTION; GRAFT-REJECTION; CYTOTOXIC CELLS AB Viral infections can strongly stimulate both NK cell and allospecific CD8 T cell responses, and these same effector cells can lyse allogeneic cell lines in vitro. However, the impact of viral infections on the effector systems mediating rejection of allogeneic tissues in vivo has not been fully explored. Using in vivo cytotoxicity assays, we evaluated the effector systems mediating the rejection of CFSE-labeled allogeneic splenocytes after an infection of C57BL/6 (B6) mice with lymphocytic choriomeningitis virus. Naive B6 mice predominantly used a NK cell-effector mechanism to reject allogeneic splenocytes because they rejected BALB/C (H2(d)) splenocytes but not CBA (H2(k)) splenocytes, and the rejection was prevented by immunodepletion of NK1.1(+) or Ly49D(+) NK cells. This rapid and efficient in vivo cytotoxicity assay recapitulated the specificity of NK cell-mediated rejection seen in longer duration in vivo assays. However, as early as 1 day after infection with lymphocytic choriomeningitis virus, a CD8 T cell-dependent mechanism participated in the rejection process and a broader range of tissue haplotypes (e.g., H2(k)) was susceptible. The CD8 T cell-mediated in vivo rejection process was vigorous at a time postinfection (day 3) when NK cell effector functions are peaking, indicating that the effector systems used in vivo differed from those observed with in vitro assays measuring the killing of allogeneic cells. This rapid generation of allospecific CTL activity during a viral infection preceded the peak of viral epitope-specific T cell responses, as detected by in vivo or in vitro cytotoxicity assays. C1 Univ Massachusetts, Sch Med, Dept Pathol, Worcester, MA 01655 USA. NCI, Expt Immunol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Welsh, RM (reprint author), Univ Massachusetts, Sch Med, Dept Pathol, 55 Lake Ave N, Worcester, MA 01655 USA. EM raymond.welsh@umassmed.edu FU NCI NIH HHS [CA-34461]; NIAID NIH HHS [AI-46629]; NIAMS NIH HHS [AR-35506]; NIDDK NIH HHS [DK-52350] NR 62 TC 25 Z9 25 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 JUN 1 PY 2005 VL 174 IS 11 BP 6663 EP 6671 PG 9 WC Immunology SC Immunology GA 928UY UT WOS:000229298400019 PM 15905505 ER PT J AU Leeanansaksiri, W Wang, H Gooya, JM Renn, K Abshari, M Tsai, S Keller, JR AF Leeanansaksiri, W Wang, H Gooya, JM Renn, K Abshari, M Tsai, S Keller, JR TI IL-3 induces inhibitor of DNA-binding protein-1 in hemopoietic progenitor cells and promotes myeloid cell development SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LOOP-HELIX PROTEINS; COLONY-STIMULATING FACTOR; RETINOIC ACID RECEPTOR; ID PROTEINS; STEM-CELLS; TRANSCRIPTION FACTORS; NEGATIVE REGULATION; DIFFERENTIATION; EXPRESSION; GROWTH AB Hemopoiesis depends on the expression and regulation of transcription factors, which control the maturation of specific cell lineages. We found that the helix-loop-helix transcription factor inhibitor of DNA-binding protein 1 (Id1) is not expressed in hemopoietic stem cells (HSC), but is increased in more committed myeloid progenitors. 141 levels decrease during neutrophil differentiation, but remain high in differentiated macrophages. Id1 is expressed at low levels or is absent in developing lymphoid or erythroid cells. Id1 expression can be induced by IL-3 in HSC during myeloid differentiation, but not by growth factors that promote erythroid and B cell development. HSC were transduced with retroviral vectors that express Id1 and were transplanted in vivo to evaluate their developmental potential. Overexpression of Id1 in HSC promotes myeloid but impairs B and erythroid cell development. Enforced expression of 141 in committed myeloid progenitor cells inhibits granulocyte but not macrophage differentiation. Therefore, Id1 may be part of the mechanism regulating myeloid vs lymphoid/erythroid cell fates, and macrophage vs neutrophil maturation. C1 NCI, Basic Res Program, SAIC Frederick, Frederick, MD 20702 USA. NCI, Lab Mol Immunoregulat, Frederick, MD 20702 USA. NCI, Canc Res Ctr, Frederick, MD 20702 USA. Univ Utah, Sch Med, Div Hematol, Salt Lake City, UT 84132 USA. RP Keller, JR (reprint author), NCI, Basic Res Program, SAIC Frederick, Bldg 560,Room 12-03, Frederick, MD 20702 USA. EM kellerj@ncifcrf.gov FU PHS HHS [N01-C0-12400] NR 58 TC 22 Z9 26 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 JUN 1 PY 2005 VL 174 IS 11 BP 7014 EP 7021 PG 8 WC Immunology SC Immunology GA 928UY UT WOS:000229298400058 PM 15905544 ER PT J AU Johnson, TR Mertz, SE Gitiban, N Hammond, S LeGallo, R Durbin, RK Durbin, JE AF Johnson, TR Mertz, SE Gitiban, N Hammond, S LeGallo, R Durbin, RK Durbin, JE TI Role for innate IFNs in determining respiratory syncytial virus immunopathology SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AIRWAY EPITHELIAL-CELLS; CD4(+) T-CELLS; INTERFERON-GAMMA; BALB/C MICE; INFLAMMATORY RESPONSE; TARGETED DISRUPTION; LINEAGE COMMITMENT; ANTIVIRAL DEFENSE; CXC CHEMOKINES; I-TAC AB Respiratory syncytial virus (RSV) is the major cause of severe lower airway disease in infants and young children, but no safe and effective RSV vaccine is yet available. The difficulties involved in RSV vaccine development were recognized in an early vaccine trial, when children immunized with a formalin-inactivated virus preparation experienced enhanced illness after natural infection. Subsequent research in animal models has shown that the vaccine-enhanced disease is mediated at least in part by memory cells producing Th2 cytokines. Previously we had observed enhanced, eosinophilic lung pathology during primary infection of IFN-deficient STAT1(-/-) mice that are incapable of generating Th1 CD4(+) cells. To determine whether these effects depended only on Th2 cytokine secretion or involved other aspects of IFN signaling, we infected a series of 129SvEv knockout mice lacking the IFN-alpha beta R (IFN-alpha beta R-/-), the IFN-gamma R (IFN-gamma R-/-), or both receptors (IFN-alpha beta gamma R-/-). Although both the IFN-gamma R-/- and the IFN-alpha beta gamma R-/- animals generated strong Th2 responses to RSV-F protein epitopes, predominantly eosinophilic lung disease was limited to mice lacking both IFNRs. Although the absolute numbers of eosinophils in BAL fluids were similar between the strains, very few CD8(+) T cells could be detected in lungs of IFN-alpha beta gamma R-/- animals, leaving eosinophils as the predominant leukocyte. Thus, although CD4(+) Th2 cell differentiation is necessary for the development of allergic-type inflammation after infection and appears to be unaffected by type I IFNs, innate IFNs clearly have an important role in determining the nature and severity of RSV disease. C1 Ohio State Univ, Dept Pediat, Coll Med & Publ Hlth, Columbus Childrens Res Inst, Columbus, OH 43205 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. RP Durbin, JE (reprint author), Ohio State Univ, Dept Pediat, Coll Med & Publ Hlth, Columbus Childrens Res Inst, 700 Childrens Dr,Room WA4014, Columbus, OH 43205 USA. EM durbinj@pediatrics.ohio-state.edu FU NIAID NIH HHS [AI47226] NR 50 TC 48 Z9 49 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 JUN 1 PY 2005 VL 174 IS 11 BP 7234 EP 7241 PG 8 WC Immunology SC Immunology GA 928UY UT WOS:000229298400084 PM 15905569 ER PT J AU Herrero, R Castle, PE Schiffman, M Bratti, MC Hildesheim, A Morales, J Alfaro, M Sherman, ME Wacholder, S Chen, S Rodriguez, AC Burk, RD AF Herrero, R Castle, PE Schiffman, M Bratti, MC Hildesheim, A Morales, J Alfaro, M Sherman, ME Wacholder, S Chen, S Rodriguez, AC Burk, RD TI Epidemiologic profile of type-specific human papillomavirus infection and cervical neoplasia in Guanacaste, Costa Rica SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HPV INFECTION; INTRAEPITHELIAL NEOPLASIA; WOMEN; PREVALENCE; POPULATION; CANCER; CYTOLOGY AB Background. Detailed epidemiologic studies of cervical type-specific human papillomavirus (HPV) infection in large populations are scarce. Methods. We recruited a population-based cohort in Guanacaste, Costa Rica. Participants were interviewed, screened for cervical neoplasia, and tested for >40 HPV types by use of MY09/11 L1 consensus primer polymerase chain reaction. We estimated the risk factors for infection and the associations between type-specific HPV infections and cervical intraepithelial neoplasia (CIN) and cancer in 8514 sexually active women who had not undergone a hysterectomy. Results. The overall HPV prevalence was 26.5%. The most common type was HPV-16 (3.6% of the population). HPV prevalence showed a U-shaped age-specific curve. Sexual behaviors were the main determinants of oncogenic and nononcogenic infections; age at first sexual intercourse was not independently associated with infection. Barrier contraceptive use was somewhat protective against infection. Oncogenic infections were strongly associated with risk of all grades of CIN and of cancer. Types 16, 18, and 58 were the most common in women diagnosed with CIN3 and cancer. Except for those that included HPV-16, multiple-type infections were associated with an increased risk ( compared with that for single-type infections) of all grades of CIN and of cancer. Conclusions. We confirmed the bimodal age pattern of HPV infection in Guanacaste and the sexually transmitted nature of both oncogenic and nononcogenic HPV types. C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Informat Management Serv Inc, Silver Spring, MD USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Fdn INCIENSA, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. RP Herrero, R (reprint author), Fdn INCIENSA, Proyecto Epidemiol Guanacaste, POB 125-6151, Santa Ana 2000, Costa Rica. EM rherrero@amnet.co.cr; castlep@mail.nih.gov NR 26 TC 223 Z9 244 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 JUN 1 PY 2005 VL 191 IS 11 BP 1796 EP 1807 DI 10.1086/428850 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 923AN UT WOS:000228881100004 PM 15871111 ER PT J AU Castle, PE Schiffman, M Herrero, R Hildesheim, A Rodriguez, AC Bratti, MC Sherman, ME Wacholder, S Tarone, R Burk, RD AF Castle, PE Schiffman, M Herrero, R Hildesheim, A Rodriguez, AC Bratti, MC Sherman, ME Wacholder, S Tarone, R Burk, RD TI A prospective study of age trends in cervical human papillomavirus acquisition and persistence in Guanacaste, Costa Rica SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID NATURAL-HISTORY; DNA DETECTION; HIGH-RISK; INFECTION; CANCER; WOMEN; NEOPLASIA; POPULATION; EPIDEMIOLOGY; PREVALENCE AB Background. Cross-sectional human papillomavirus (HPV) DNA prevalence peaks at young ages, reflecting sexual acquisition and typically rapid clearance. In some populations, HPV prevalence demonstrates a second peak in older women. Longitudinal data may help to explain this second peak. Methods. We followed a population-based cohort of 7237 women in Guanacaste, Costa Rica, in which we had previously observed a second peak in the baseline HPV prevalence in older women. We tested for >40 HPV types by polymerase chain reaction. We analyzed age-specific patterns of acquisition and persistence 5-7 years after enrollment for individual HPV types. Results. At enrollment and follow-up, cross-sectional data revealed U-shaped age-specific HPV prevalence curves for virtually every type, with higher prevalences in the younger and older women than in the middle-aged women. Prospectively, acquisition of types decreased significantly as women aged (P-Trend < .05, for both), with the highest peak in young women and a secondary minor peak in older women. Type-specific persistence of HPV increased with age (P-Trend < .0001) Overall, HPV acquisition predominated at younger ages, whereas persistent infections gradually became more prominent with age (P-Trend < .0001) Conclusions. Newly apparent infections decreased, whereas persistence increased, with age; this latter tendency supports the utility of HPV screening in older women. C1 NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Fdn Inciensa, Proyecto Epidemiol Guanacaste, San Jose, Costa Rica. RP Castle, PE (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Dept Hlth & Human Serv, 6120 Execut Blvd,Room 7074,EPS MSC 7234, Bethesda, MD 20892 USA. EM castlep@mail.nih.gov NR 30 TC 222 Z9 243 U1 0 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 JUN 1 PY 2005 VL 191 IS 11 BP 1808 EP 1816 DI 10.1086/428779 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 923AN UT WOS:000228881100005 PM 15871112 ER PT J AU Lorange, EA Race, BL Sebbane, F Hinnebusch, BJ AF Lorange, EA Race, BL Sebbane, F Hinnebusch, BJ TI Poor vector competence of fleas and the evolution of hypervirulence in Yersinia pestis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID PASTEURELLA-PESTIS; EXPERIMENTAL PLAGUE; XENOPSYLLA-CHEOPIS; PSEUDOTUBERCULOSIS; TRANSMISSION; SIPHONAPTERA; TEMPERATURE; EFFICIENCY; VIRULENCE; SURVIVAL AB Population genetics and comparative genomics analyses of the pathogenic Yersinia species have indicated that arthropodborne transmission is an evolutionarily recent adaptation in Yersinia pestis, the agent of plague. We show that the infectivity of Y. pestis to its most proficient vector, the rat flea Xenopsylla cheopis, and subsequent transmission efficiency are both low. The poor vector competence of fleas likely imposed selective pressure that favored the emergence and continued maintenance of a hypervirulent Y. pestis clone. In particular, the rapidly fatal gram-negative sepsis that typifies plague is a consequence of the high threshold bacteremia level that must be attained to complete the transmission cycle. Epidemiological modeling predicts that, to compensate for a relatively short period of infectivity of the mammalian host for the arthropod vector, plague epizootics require a high flea burden per host, even when the susceptible host population density is high. C1 NIAID, NIH, Rocky Mt Labs, Lab Human Bacerial Pathogenesis, Hamilton, MT 59840 USA. RP Hinnebusch, BJ (reprint author), NIAID, NIH, Rocky Mt Labs, Lab Human Bacerial Pathogenesis, 903 S 4th St, Hamilton, MT 59840 USA. EM jhinnebusch@niaid.nih.gov RI Sebbane, Florent/D-4213-2009 NR 44 TC 123 Z9 128 U1 9 U2 14 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 JUN 1 PY 2005 VL 191 IS 11 BP 1907 EP 1912 DI 10.1086/429931 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 923AN UT WOS:000228881100018 PM 15871125 ER PT J AU Tadokoro, T Yamaguchi, Y Batzer, J Coelho, SG Zmudzka, BZ Miller, SA Wolber, R Beer, JZ Hearing, VJ AF Tadokoro, T Yamaguchi, Y Batzer, J Coelho, SG Zmudzka, BZ Miller, SA Wolber, R Beer, JZ Hearing, VJ TI Mechanisms of skin tanning in different racial/ethnic groups in response to ultraviolet radiation SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Article DE melanocyte; melanosome; photoprotection; pigmentation; ultraviolet ID MITF; MELANOSOME; TYROSINASE; ERYTHEMA; MODEL; PIGMENTATION; MELANOCYTES; EXPRESSION; PATTERNS; MEDIATOR AB Ultraviolet radiation stimulates pigmentation in human skin, but the mechanism(s) whereby this increase in melanin production (commonly known as tanning) occurs is not well understood. Few studies have examined the molecular consequences of UV on human skin of various racial backgrounds in situ. We investigated the effects of UV on human skin of various races before and at different times after a single 1 minimal erythemal dose UV exposure. We measured the distribution of DNA damage that results, as well as the melanin content/distribution and the expression of various melanocyte-specific genes. The density of melanocytes at the epidermal:dermal junction in different types of human skin are remarkably similar and do not change significantly within 1 wk after UV exposure. The expression of melanocyte-specific proteins (including TYR (tyrosinase), TYRP1 (tyrosinase-related protein 1), DCT (tyrosinase-related protein 2), MART1 (melanoma antigens recognized by T-cells) gp100 (Pmel17/silver), and MITF (micropthalmia transcription factor)) increased from 0 to 7 d after UV exposure, but the melanin content of the skin increased only slightly. The most significant change, however, was a change in the distribution of melanin from the lower layer upwards to the middle layer of the skin, which was more dramatic in the darker skin. These results provide a basis for understanding the origin of different skin colors and responses to UV within different races. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Beiersdorf AG, R&D, Skin Res, Hamburg, Germany. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Room 2132, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008 NR 34 TC 112 Z9 114 U1 2 U2 19 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD JUN PY 2005 VL 124 IS 6 BP 1326 EP 1332 DI 10.1111/j.0022-202X.2005.23760.x PG 7 WC Dermatology SC Dermatology GA 933NC UT WOS:000229636400033 PM 15955111 ER PT J AU Briard, E Shah, J Musachio, JL Zoghbi, SS Fujita, M Imaizumi, M Cropley, V Innis, RB Pike, VW AF Briard, E. Shah, J. Musachio, J. L. Zoghbi, S. S. Fujita, M. Imaizumi, M. Cropley, V. Innis, R. B. Pike, V. W. TI SYNTHESIS AND EVALUATION OF A NEW F-18-LABELED LIGAND FOR PET IMAGING OF BRAIN PERIPHERAL BENZODIAZEPINE RECEPTORS SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE Fluorine-18; Peripheral benzodiazepine receptor; Radioligand C1 [Briard, E.; Shah, J.; Musachio, J. L.; Zoghbi, S. S.; Fujita, M.; Imaizumi, M.; Cropley, V.; Innis, R. B.; Pike, V. W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NR 2 TC 13 Z9 13 U1 1 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S4 EP S4 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100005 ER PT J AU Briard, E Hong, J Musachio, JL Zoghbi, SS Fujita, M Imaizumi, M Cropley, V Innis, RB Pike, VW AF Briard, E. Hong, J. Musachio, J. L. Zoghbi, S. S. Fujita, M. Imaizumi, M. Cropley, V. Innis, R. B. Pike, V. W. TI SYNTHESIS AND EVALUATION OF TWO CANDIDATE C-11-LABELED RADIOLIGANDS FOR BRAIN PERIPHERAL BENZODIAZEPINE RECEPTORS SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE Periphal Benzodiazepine Receptor; Radioligand; Carbon-11 ID BINDING C1 [Briard, E.; Hong, J.; Musachio, J. L.; Zoghbi, S. S.; Fujita, M.; Imaizumi, M.; Cropley, V.; Innis, R. B.; Pike, V. W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NR 4 TC 19 Z9 19 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S71 EP S71 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100068 ER PT J AU Cai, L Nichols, L Cuevas, J Temme, S Herman, MM Innis, RB Pike, VW AF Cai, L. Nichols, L. Cuevas, J. Temme, S. Herman, M. M. Innis, R. B. Pike, V. W. TI STRUCTURE-ACTIVITY RELATIONSHIP STUDY OF IMPY DERIVATIVES AS CANDIDATE RADIOLIGANDS FOR beta-AMYLOID SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE beta-Amyloid; Structure Activity Relationship; IMPY-Derivatives C1 [Cai, L.; Nichols, L.; Cuevas, J.; Temme, S.; Innis, R. B.; Pike, V. W.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Herman, M. M.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 BP S151 EP S151 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100148 ER PT J AU Cai, L Nichols, L Temme, S Park, K Herman, MM Pike, VW Innis, RB AF Cai, L. Nichols, L. Temme, S. Park, K. Herman, M. M. Pike, V. W. Innis, R. B. TI AN IN VITRO ASSAY TO EVALUATE beta-AMYLOID LIGANDS USING ISOLATED HUMAN AMYLOID PLAQUES OF ALZHEIMER'S DISEASE BRAIN SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE In Vitro Assay; beta-Amyloid; Alzheimer's Disease ID PROTEIN C1 [Cai, L.; Nichols, L.; Temme, S.; Park, K.; Pike, V. W.; Innis, R. B.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Herman, M. M.] NIMH, Clin Brain Disorders Branch, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 BP S42 EP S42 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100040 ER PT J AU Chin, FT Morse, CL Pike, VW AF Chin, F. T. Morse, C. L. Pike, V. W. TI PRODUCTION OF [F-18]SPA-RQ AS A PET RADIOLIGAND FOR IMAGING HUMAN BRAIN NK1 RECEPTORS SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE [18F]SPA-RQ; Neurokinin 1 Receptor; Automation C1 [Chin, F. T.; Morse, C. L.; Pike, V. W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S195 EP S195 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100192 ER PT J AU Donohue, S Halldin, C Brown, A Hong, J Musachio, JL Bacher, J Innis, RB Pike, VW AF Donohue, S. Halldin, C. Brown, A. Hong, J. Musachio, J. L. Bacher, J. Innis, R. B. Pike, V. W. TI SYNTHESIS, RADIOSYNTHESIS AND INITIAL BIOLOGICAL EVALUATION OF A NEW CLASS OF CANDIDATE BRAIN CANNABINOID TYPE-1 (CB1) RECEPTOR RADIOLIGAND SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE CB1 Recptor; PET; Diarylpyrazolines C1 [Donohue, S.; Brown, A.; Hong, J.; Musachio, J. L.; Innis, R. B.; Pike, V. W.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Donohue, S.; Halldin, C.] Karolinska Inst, Dept Clin Neurosci, Stockholm, Sweden. [Bacher, J.] NIH, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S185 EP S185 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100182 ER PT J AU Donohue, S Halldin, C Finnema, S Gulyas, B Schou, M Innis, RB Pike, VW AF Donohue, S. Halldin, C. Finnema, S. Gulyas, B. Schou, M. Innis, R. B. Pike, V. W. TI SYNTHESIS AND EVALUATION OF CANDIDATE RADIOLIGANDS FOR THE BRAIN CANNABINOID TYPE-1 (CB1) RECEPTOR BASED ON 1,5-DIARYLPYRAZOLES SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE CB1 Receptor; 1,5-Diarylpyrazoles; PET C1 [Donohue, S.; Schou, M.; Innis, R. B.; Pike, V. W.] NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. [Donohue, S.; Halldin, C.; Finnema, S.; Gulyas, B.; Schou, M.] Karolinska Hosp, Dept Clin Neurosci, S-10401 Stockholm, Sweden. NR 3 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S160 EP S160 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100157 ER PT J AU Ehrhardt, GJ Moustapha, ME Smith, CJ Szajek, L Eckelmann, WC Jurisson, SS AF Ehrhardt, G. J. Moustapha, M. E. Smith, C. J. Szajek, L. Eckelmann, W. C. Jurisson, S. S. TI PREPARATION OF CYCLOTRON Re-186 AND COMPARISON WITH REACTOR Re-186 AND GENERATOR Re-188 FOR THE LABELING OF BOMBESIN SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE Rhenium-186; Bombesin; Radiotherapy C1 [Ehrhardt, G. J.; Moustapha, M. E.; Jurisson, S. S.] Univ Missouri, Columbia, MO USA. [Smith, C. J.] Harry S Truman Mem Vet Hosp, Columbia, MO 65201 USA. [Szajek, L.; Eckelmann, W. C.] NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 BP S16 EP S16 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100016 ER PT J AU Jagoda, EM Lang, L Tokugawa, J Ma, Y Contoreggi, C Eckelman, WC AF Jagoda, E. M. Lang, L. Tokugawa, J. Ma, Y. Contoreggi, C. Eckelman, W. C. TI EVALUATION OF [F-18]FPWAY AND [F-18]FBWAY, 5-HT1A RECEPTOR PET LIGANDS, FOR SENSITIVITY TO ENDOGENOUS 5-HT IN RAT SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE PET Radioligands; 5-HT ' 1A Receptors; Serotonin C1 [Jagoda, E. M.; Lang, L.; Tokugawa, J.; Ma, Y.] NIBIB, PET Radiochem Grp, Bethesda, MD USA. [Contoreggi, C.] NIDA, IRP, Baltimore, MD USA. [Eckelman, W. C.] NIH, PET Dept, Ctr Clin, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S74 EP S74 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100071 ER PT J AU Kopka, K Law, MP Engelhardt, S Riemann, B Pike, VW Schober, O Schaefers, M Wagner, S AF Kopka, K. Law, M. P. Engelhardt, S. Riemann, B. Pike, V. W. Schober, O. Schaefers, M. Wagner, S. TI A CANDIDATE HIGH AFFINITY beta(1)-ADRENOCEPTOR-SELECTIVE PET RADIOLIGAND: (S)-[METHOXY-C-11]-N-[2-[3-(2-CYANO-PHENOXY)-2-HYDROXY-PROPYLAMINO]-ETHY L]-N '-(4-METHOXY-PHENYL)-UREA (S)-[C-11]ICI-OMe) SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE beta 1-Adrenoceptor Radioligand; ICI 89,406 Derivative; Carbon-11 Synthesis C1 [Kopka, K.; Law, M. P.; Riemann, B.; Schober, O.; Schaefers, M.; Wagner, S.] Univ Hosp Muenster, Sect Radiochem, Dept Nucl Med, Munster, Germany. [Engelhardt, S.] Univ Wurzburg, Rudolf Virchow Ctr, DFG Res Ctr Expt Biomed, Mol Cardiobiol Grp, Wurzburg, Germany. [Pike, V. W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S267 EP S267 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100264 ER PT J AU Lu, SY Hong, J Musachio, JL Chin, FT Vermeulen, ES Wikstrom, HV Pike, VW AF Lu, S. Y. Hong, J. Musachio, J. L. Chin, F. T. Vermeulen, E. S. Wikstrom, H. V. Pike, V. W. TI METHODS FOR LABELING THE 5-HT1A RECEPTOR AGONIST, S14506, WITH A POSITRON-EMITTER AT ANY OF THREE ALTERNATIVE POSITIONS SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE Carbon-11; Fluorine-18; Radiosynthesis C1 [Lu, S. Y.; Hong, J.; Musachio, J. L.; Chin, F. T.; Pike, V. W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Vermeulen, E. S.; Wikstrom, H. V.] Univ Groningen, Dept Med Chem, Groningen, Netherlands. NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S146 EP S146 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100143 ER PT J AU Lu, SY Liow, JS Ichise, M Hong, J Musachio, JL Zoghbi, SS Nichols, L Seidel, J Vermeulen, ES Wikstrom, HV Innis, RB Pike, VW AF Lu, S. Y. Liow, J. S. Ichise, M. Hong, J. Musachio, J. L. Zoghbi, S. S. Nichols, L. Seidel, J. Vermeulen, E. S. Wikstrom, H. V. Innis, R. B. Pike, V. W. TI EVALUATION OF [O-METHYL-C-11]S14506 AS AN AGONIST RADIOLIGAND FOR BRAIN 5-HT1A RECEPTORS IN RAT AND MONKEY SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE 5-HT1A Agonist; Pgp Substrate; PET Imaging C1 [Lu, S. Y.; Liow, J. S.; Ichise, M.; Hong, J.; Musachio, J. L.; Zoghbi, S. S.; Nichols, L.; Innis, R. B.; Pike, V. W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Seidel, J.] NIH, Dept Nucl Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD USA. [Vermeulen, E. S.; Wikstrom, H. V.] Univ Groningen, Dept Med Chem, Groningen, Netherlands. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S72 EP S72 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100069 ER PT J AU Ma, Y Lang, L Jagoda, EM Kiesewetter, DO Szajek, LP Kim, BM Greiner, E Rice, KC Eckelman, WC AF Ma, Y. Lang, L. Jagoda, E. M. Kiesewetter, D. O. Szajek, L. P. Kim, B. M. Greiner, E. Rice, K. C. Eckelman, W. C. TI METABOLISM OF CORTICOTROPIN RELEASING HORMONE TYPE 1 RECEPTOR (CRHR1) PET LIGAND - [Br-76]MJL-1-109-2 SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE PET; Corticotropin Releasing Hormone Type 1 Receptor (CRHR1) Ligand; LC/MS C1 [Ma, Y.; Lang, L.; Jagoda, E. M.; Kiesewetter, D. O.] Natl Inst Biomed Imaging & Bioengn, PET Radiochem Grp, NIH, Bethesda, MD USA. [Kim, B. M.; Greiner, E.; Rice, K. C.] NIDDK, Med Chem Lab, NIH, Bethesda, MD 20892 USA. [Szajek, L. P.; Eckelman, W. C.] NIH, PET Dept, CC, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S196 EP S196 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100193 ER PT J AU McCarron, JA Zoghbi, SS Liow, JS Hong, J Lu, SY Vermeulen, ES Wikstrom, HV Seidel, J Innis, RB Pike, VW AF McCarron, J. A. Zoghbi, S. S. Liow, J. S. Hong, J. Lu, S. Y. Vermeulen, E. S. Wikstrom, H. V. Seidel, J. Innis, R. B. Pike, V. W. TI 5-HT1A RECEPTOR IMAGING WITH [C-11](S)-RWAY IN RAT BRAIN SHOWS A STRIKING DIFFERENCE IN PGP EFFECT COMPARED TO IMAGING IN MONKEY SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE [C-11](S)-RWAY; PET; Rat C1 [McCarron, J. A.; Zoghbi, S. S.; Liow, J. S.; Hong, J.; Lu, S. Y.; Innis, R. B.; Pike, V. W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Vermeulen, E. S.; Wikstrom, H. V.] Univ Groningen, Dept Med Chem, Groningen, Netherlands. [Seidel, J.] NIH, Dept Nucl Med, Warren G Magnuson Clin Ctr, Bethesda, MD USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S73 EP S73 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100070 ER PT J AU Musachio, JL Shah, J Pike, VW AF Musachio, J. L. Shah, J. Pike, V. W. TI SYNTHESIS AND REACTIVITY OF NOVEL F-18-LABELED ARYLSULFONATE ESTERS OF 2-FLUOROETHANOL SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE Fluorine-18; Sulfonate Ester; Labeling Agent C1 [Musachio, J. L.; Shah, J.; Pike, V. W.] NIMH, PET Radiopharmaceut Sci, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S147 EP S147 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100144 ER PT J AU Park, SH Jang, BS Lim, E Bur, M Xie, J Le, N Danthi, N Dewanjee, M Li, KC Carrasquillo, JA Paik, CH AF Park, S. H. Jang, B. S. Lim, E. Bur, M. Xie, J. Le, N. Danthi, N. Dewanjee, M. Li, K. C. Carrasquillo, J. A. Paik, C. H. TI SYNTHESIS AND BIODISTRIBUTION OF Tc-99m(CO)(3)-TRIDENTATE-LABELED INTEGRIN ANTAGONIST IN TUMOR BEARING MICE SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE Tumor Detection; Receptor-Binding Radiopharmaceutical; Technetium-99m Tricarbonyl C1 [Park, S. H.; Jang, B. S.; Lim, E.; Bur, M.; Xie, J.; Le, N.; Danthi, N.; Dewanjee, M.; Li, K. C.; Carrasquillo, J. A.; Paik, C. H.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RI Carrasquillo, Jorge/E-7120-2010; Danthi, Simhan/B-7639-2014 NR 0 TC 1 Z9 1 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S290 EP S290 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100287 ER PT J AU Schou, M Halldin, C Pike, VW Mozley, PD Dobson, D Innis, RB Farde, L Hall, H AF Schou, M. Halldin, C. Pike, V. W. Mozley, P. D. Dobson, D. Innis, R. B. Farde, L. Hall, H. TI POST MORTEM AUTORADIOGRAPHY OF THE HUMAN BRAIN NOREPINEPHRINE TRANSPORTER WITH (S,S)-[F-18]FMeNER-D-2 SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE Norepinephrine Transporter; Autoradiography; Human Brain C1 [Schou, M.; Halldin, C.; Farde, L.; Hall, H.] Karolinska Inst, Karolinska Hosp, Psychiat Sect, Dept Clin Neurosci, S-10401 Stockholm, Sweden. [Schou, M.; Pike, V. W.; Innis, R. B.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. [Mozley, P. D.; Dobson, D.] Eli Lilly & Co, Indianapolis, IN 46285 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S272 EP S272 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100269 ER PT J AU Schou, M Pike, VW Andree, B Gulyas, B Shchukin, E Farde, L Halldin, C AF Schou, M. Pike, V. W. Andree, B. Gulyas, B. Shchukin, E. Farde, L. Halldin, C. TI THE NET RADIOLIGAND (S,S)-[C-11]MeNER PRODUCES A LIPOPHILIC LABELED METABOLITE MEASURED IN HUMAN PLASMA SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE Norepinephrine Transporter; MeNER; Metabolism C1 [Schou, M.; Andree, B.; Gulyas, B.; Shchukin, E.; Farde, L.; Halldin, C.] Karolinska Inst, Karolinska Hosp, Psychiat Sect, Dept Clin Neurosci, S-10401 Stockholm, Sweden. [Schou, M.; Pike, V. W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S273 EP S273 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100270 ER PT J AU Shetty, HU Zoghbi, SS McCarron, JA Liow, JS Hong, J Pike, VW AF Shetty, H. U. Zoghbi, S. S. McCarron, J. A. Liow, J. -S. Hong, J. Pike, V. W. TI CHARACTERIZATION OF IN VIVO RAT METABOLITES OF [O-METHYL-C-11]RWAY BY LC-MS SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE Metabolites; LC-MS; Radioligand ID PET C1 [Shetty, H. U.; Zoghbi, S. S.; McCarron, J. A.; Liow, J. -S.; Hong, J.; Pike, V. W.] NIMH, MIB, Bethesda, MD 20892 USA. NR 3 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S278 EP S278 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100275 ER PT J AU Simeon, FG Pike, VW AF Simeon, F. G. Pike, V. W. TI RADIOSYNTHESES OF 2-[F-18]FLUORO-1,3-THIAZOLES SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE Fluorine-18; Nucleophilic Radiofluoridation; 1,3-Thiazole C1 [Simeon, F. G.; Pike, V. W.] NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NR 3 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S158 EP S158 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100155 ER PT J AU Szajek, LP Plascjak, P Eckelman, W AF Szajek, L. P. Plascjak, P. Eckelman, W. TI INTERNAL CYCLOTRON TARGETS FOR CLINICAL PRODUCTION OF BROMINE RADIONUCLIDES SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE Bromine-76 / Bromine-75; Tangential Target; Radioassay C1 [Szajek, L. P.; Plascjak, P.; Eckelman, W.] NIH, PET Dept, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 BP S339 EP S339 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100336 ER PT J AU Willis, PG Pavlova, OA Chefer, SI Vaupel, DB Mukhin, AG Horti, AG AF Willis, P. G. Pavlova, O. A. Chefer, S. I. Vaupel, D. B. Mukhin, A. G. Horti, A. G. TI NOVEL F-18 LABELLED AMINOALKYLINDOLE WITH POTENTIAL FOR IMAGING NEURONAL CANNABINOID RECEPTOR BY POSITRON EMISSION TOMOGRAPHY SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE Cannabinoid; Radiotracer; PET C1 [Willis, P. G.; Pavlova, O. A.; Chefer, S. I.; Vaupel, D. B.; Mukhin, A. G.] Natl Inst Drug Abuse, Neuroimaging Res Branch, Intramural Res Program, Baltimore, MD USA. [Horti, A. G.] Johns Hopkins Univ, Sch Med, Dept Radiol, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 BP S144 EP S144 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100141 ER PT J AU Zoghbi, SS Shetty, UH Liow, JS Ichise, M Hong, J Musachio, JL Seneca, N Halldin, C Seidel, JL Pike, VW Innis, RB AF Zoghbi, S. S. Shetty, U. H. Liow, J. -S. Ichise, M. Hong, J. Musachio, J. L. Seneca, N. Halldin, C. Seidel, J. L. Pike, V. W. Innis, R. B. TI THE DOPAMINE TRANSPORTER PROBE [C-11]PE2I SHOWS ACTIVE AND INACTIVE RADIOACTIVE METABOLITES IN RAT BRAIN SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract DE [C-11]PE2I; Dopamine Transporter; Metabolism C1 [Halldin, C.] Karolinska Univ Hosp, Stockholm, Sweden. [Zoghbi, S. S.; Shetty, U. H.; Liow, J. -S.; Ichise, M.; Hong, J.; Musachio, J. L.; Seneca, N.; Pike, V. W.; Innis, R. B.] NIMH, MIB, Bethesda, MD 20892 USA. [Seidel, J. L.] NIH, Bethesda, MD 20892 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD JUN PY 2005 VL 48 SU 1 BP S98 EP S98 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 460TB UT WOS:000267210100095 ER PT J AU Tsai, MY Hanson, NQ Straka, RJ Hoke, TR Ordovas, JM Peacock, JM Arends, VL Arnett, DK AF Tsai, MY Hanson, NQ Straka, RJ Hoke, TR Ordovas, JM Peacock, JM Arends, VL Arnett, DK TI Effect of influenza vaccine on markers of inflammation and lipid profile SO JOURNAL OF LABORATORY AND CLINICAL MEDICINE LA English DT Article ID C-REACTIVE PROTEIN; YELLOW-FEVER VACCINATION; CARDIOVASCULAR-DISEASE; PPAR-ALPHA; RISK; ACTIVATORS; MODEL; EXPRESSION; HEALTH; CELLS AB Despite wide use of the influenza vaccine, relatively little is known about its effect on the measurement of inflammatory markers. Because inflammatory markers such as C-reactive protein (CRP) are increasingly being used in conjunction with lipids for the clinical assessment of cardiovascular disease and in epidemiologic studies, we evaluated the effect of influenza vaccination on markers of inflammation and plasma lipid concentrations. We drew blood from 22 healthy individuals I to 6 hours before they were given an influenza vaccination and 1, 3, and 7 days after the vaccination. Plasma CRP, interleukin (IL)-6, monocyte chemotactic protein 1, tumor necrosis factor alpha, IL-2 soluble receptor alpha, and serum amyloid A were measured, and differences in mean concentrations of absolute and normalized values on days 1, 3, and 7 were compared with mean baseline values. There was a significant increase in mean IL-6 (P <.01 absolute values, P <.001 normalized values) on day 1 after receiving the influenza vaccine. The mean increases in normalized high sensitivity CRP values were significant on day 1 (P <.01) and day 3 (P =.05), whereas the mean increase in. normalized serum amyloid A was significant only on day 1 (P <.05). No significant changes were seen in mean concentrations of IL-2 soluble receptor a, monocyte chemotactic protein-1, or tumor necrosis factor-alpha. Of the lipids, significant decreases in mean concentrations of normalized triglyceride values were seen on days 1 (P <.05), 3 (P <.001), and 7 (P <.05) after vaccination. Our findings show that the influenza vaccination causes transient changes in select markers of inflammation and lipids. Consequently, clinical and epidemiologic interpretation of the biomarkers affected should take into account the possible effects of influenza vaccination. C1 Univ Minnesota, Lab Med & Pathol, Minneapolis, MN 55455 USA. Univ Minnesota, Coll Pharm, Minneapolis, MN 55455 USA. NHLBI, Div Heart & Vasc Dis, Bethesda, MD 20892 USA. Tufts Univ, HNRCA, USDA, JM, Boston, MA 02111 USA. Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN 55455 USA. Univ Alabama, Dept Epidemiol, Birmingham, AL 35294 USA. RP Tsai, MY (reprint author), 420 Delaware St SE,Mayo Mail Code 609, Minneapolis, MN 55455 USA. EM tsaix001@tc.umn.edu OI Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [U01 HL72524-01, HL72524-02, HL72524-03, HL72524-04] NR 16 TC 37 Z9 37 U1 0 U2 3 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0022-2143 J9 J LAB CLIN MED JI J. Lab. Clin. Med. PD JUN PY 2005 VL 145 IS 6 BP 323 EP 327 DI 10.1016/j.lab.2005.03.009 PG 5 WC Medical Laboratory Technology; Medicine, General & Internal; Medicine, Research & Experimental SC Medical Laboratory Technology; General & Internal Medicine; Research & Experimental Medicine GA 942QG UT WOS:000230296300007 PM 15976761 ER PT J AU Oppenheim, JJ Dong, HF Plotz, P Caspi, RR Dykstra, M Pierce, S Martin, R Carlos, C Finn, O Koul, O Howard, OMZ AF Oppenheim, JJ Dong, HF Plotz, P Caspi, RR Dykstra, M Pierce, S Martin, R Carlos, C Finn, O Koul, O Howard, OMZ TI Autoantigens act as tissue-specific chemoattractants SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Review DE chemokines; tumor antigens; chemotaxis; migrations; dendritic cells ID TRANSFER-RNA SYNTHETASE; CHEMOKINE RECEPTORS; DENDRITIC CELLS; ANTIGENS; REPERTOIRE AB We have investigated the chemoattractant properties of self-antigens associated with autoinumme diseases and solid tumors. Many autoantigens induced leukocyte migration, especially by immature dendritic cells (iDC) by interacting with various chemoattractant Gi-protein-coupled receptors (GiPCR). Our initial observation that myositis-associated autoantigens, histidyl-tRNA synthetase and asparaginyl-tRNA synthetase, were chemotactic for CC chemokine receptor 5 (CCR5)- and CCR3-expressing leukiocytes, while other nonantoantigenic aminoacyl-tRNA synthesases were not, suggested that only self-antigens capable of interacting with receptors on antigen-presenting cells were immunogenic. We next determined that self-antigens associated with antoimmune diseases, e.g., multiple sclerosis or experimental autoinumme, encephalomyellitis, type I diabetes, scleroderma, systemic lupus erythematosus, autoimmune uveitis, or experimental autoiammune uveitis (EAU), were chemotactic for GiPCR expressed by iDC. The majority of autoantigens were DC chemoattractants at 10-100 ng/nd, but did not induce DC maturation until they reached 1000-fold higher concentrations. Interphotoreceptor retinoid-binding protein and retinal arrestin (S-antigen) are targets of autoantibodies in human uveitis and are chemotactic for CXC chemokine receptor 5 (CXCR5)- and/or CXCR3-expressing iDC. However, although S-antigen does not induce EAU in wild-type mice, it is nevertheless a chemoattractant for murine iDC. These unexpected observations suggested that the chemotactic activity of these tissue-specific self-antigens could be involved in promotion of tissue repair and restoration. Thus, the primary role of autoantigens may be to alert the immune system to danger signals from invaded and damaged tissues to facilitate repair, and autoinumme responses subsequently develop only in subjects with impaired immunoregulatory function. C1 NCI, Mol Immunoregulat Lab, Canc Res Ctr, Frederick, MD 21702 USA. Sci Applicat Int Corp, Frederick, MD 21702 USA. NIAMSD, Arthritis & Rheumatism Branch, Bethesda, MD 20892 USA. NINDS, Bethesda, MD 20892 USA. NEI, Immunol Lab, Bethesda, MD 20892 USA. NIAID, Immunogenet Lab, Rockville, MD 20852 USA. Univ Pittsburgh, Sch Med, Dept Immunol, Pittsburgh, PA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Univ Massachusetts, Sch Med, Shriver Ctr, Waltham, MA USA. RP Oppenheim, JJ (reprint author), NCI, Mol Immunoregulat Lab, Canc Res Ctr, Bldg 560,Room 21-89A, Frederick, MD 21702 USA. EM Oppenhei@ncifcrf.gov RI Howard, O M Zack/B-6117-2012; OI Howard, O M Zack/0000-0002-0505-7052; Caspi, Rachel/0000-0002-7140-7671 FU NCI NIH HHS [N01-CO-12400] NR 12 TC 27 Z9 32 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 JUN PY 2005 VL 77 IS 6 BP 854 EP 861 DI 10.1189/jlb.1004623 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 931MK UT WOS:000229489200003 PM 15917448 ER PT J AU Ha, CT Waterhouse, R Wessells, J Wu, JA Dveksler, GS AF Ha, CT Waterhouse, R Wessells, J Wu, JA Dveksler, GS TI Binding of pregnancy-specific glycoprotein 17 to CD9 on macrophages induces secretion of IL-10, IL-6, PGE(2) and TGF-beta(1) SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE reproductive immunology; cytokines ID ACTIVATED PROTEIN-KINASE; HUMAN PLACENTAL-LACTOGEN; NECROSIS-FACTOR-ALPHA; HEPATITIS-C-VIRUS; SPERM-EGG FUSION; PROSTAGLANDIN E-2; GENE-EXPRESSION; CYCLOOXYGENASE-2 EXPRESSION; INTERLEUKIN-10 EXPRESSION; BETA-1-GLYCOPROTEIN SP1 AB Pregnancy-specific glycoproteins (PSGs) are a family of secreted proteins produced by the Placenta, which are believed to have a critical role in pregnancy success. Treatment of monocytes with three members of the human PSGs induces interleukin (IL)-10, IL-6, and transforming growth factor-beta(1) (TGF-beta(1)) secretion. To determine whether human and murine PSGs have similar functions and use the same receptor, we treated wild-type and CD9-deficient macrophages with murine PSG17N and human PSG1 and -11. Our data show that murine PSG17N induced secretion of IL-10, IL-6, prostaglandin E-2, and TGF-beta(1) and that CD9 expression is required for the observed induction of cytokines. Therefore, the ability of PSG17 to induce anti-inflammatory cytokines parallels that of members of the human PSG family, albeit human and murine PSGs use different receptors, as CD9-deficient and wild-type macrophages responded equally to human PSGs. We then proceeded to examine the signaling mechanisms responsible for the CD9-mediated response to PSG17. Inhibition of cyclooxygenase 2 significantly reduced the PSG17N-mediated increase in IL-10 and IL-6. Further characterization of the response to PSG17 indicated that cyclic adenosine monophosphate-dependent protein kinase A (PKA) is involved in the up-regulation of IL-10 and IL-6, and it is not required for the induction of TGF-beta(1). Conversely, treatment of macrophages with a PKC inhibitor reduced the PSG17-mediated induction of TGF-beta(1), IL-6, and IL-10 significantly. The induction of anti-inflammatory cytokines by various PSGs supports the hypothesis that these glycoproteins have an essential role in the regulation of the maternal immune response in species with hemochorial placentation. C1 Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. NCI, Lab Prot Dynam & Signaling, Frederick, MD 21701 USA. RP Dveksler, GS (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM gdveksler@usuhs.mil FU NICHD NIH HHS [HD35832] NR 55 TC 39 Z9 41 U1 0 U2 3 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 JUN PY 2005 VL 77 IS 6 BP 948 EP 957 DI 10.1189/jlb.0804453 PG 10 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 931MK UT WOS:000229489200015 PM 15772125 ER PT J AU Lalanne, F Lambert, G Amar, MJA Chetiveaux, M Zair, Y Jarnoux, AL Ouguerram, K Friburg, J Seidah, NG Brewer, HB Krempf, M Costet, P AF Lalanne, F Lambert, G Amar, MJA Chetiveaux, M Zair, Y Jarnoux, AL Ouguerram, K Friburg, J Seidah, NG Brewer, HB Krempf, M Costet, P TI Wild-type PCSK9 inhibits LDL clearance but does not affect apoB-containing lipoprotein production in mouse and cultured cells SO JOURNAL OF LIPID RESEARCH LA English DT Article DE Proprotein Convertase Subtilisin Kexin 9; low density lipoprotein; apolipoprotein ID HETEROZYGOUS FAMILIAL HYPERCHOLESTEROLEMIA; AUTOSOMAL-DOMINANT HYPERCHOLESTEROLEMIA; APOLIPOPROTEIN-B; RECEPTOR; MICE; CHOLESTEROL; PROPROTEIN; LIPASE; LIVER; OVEREXPRESSION AB Mutations in Proprotein Convertase Subtilisin Kexin 9 (PCSK9) have been associated with autosomal dominant hypercholesterolemia. In vivo kinetic studies indicate that LDL catabolism was impaired and apolipoprotein B (apoB)-containing lipoprotein synthesis was enhanced in two patients presenting with the S127R mutation on PCSK9. To understand the physiological role of PCSK9, we overexpressed human PCSK9 in mouse and cellular models as well as attenuated the endogenous expression of PCSK9 in HuH7 hepatoma cells using RNA interference. Here, we show that PCSK9 dramatically impairs the expression of the low density lipoprotein receptor (LDLr) and, in turn, LDL cellular binding as well as LDL clearance from the plasma compartment in C57BL6/J mice but not in LDLr-deficient mice, establishing a definitive role for PCSK9 in the modulation of the LDLr metabolic pathway. In contrast to data obtained in S127R-PCSK9 patients presenting with increased apoB production, our study indicates that wild-type PCSK9 does not significantly alter the production and/or secretion of VLDL apoB in either cultured cells or mice. Finally, we show that unlike PCSK9 overexpression in mice, the S127R mutation in patients led to increased VLDL apoB levels, suggesting a potential gain of function for S127R-PCSK9 in humans. C1 Hop Hotel Dieu, CHU Nantes, INSERM, U539, Nantes, France. NHLBI, NIH, Bethesda, MD 20892 USA. Clin Res Inst, Lab Biochem Neuroendocrinol, Montreal, PQ, Canada. RP Costet, P (reprint author), Hop Hotel Dieu, CHU Nantes, INSERM, U539, Nantes, France. EM philippe.costet@univ-nantes.fr RI costet, philippe/A-5314-2010; Seidah, Nabil/I-3596-2013; Chetiveaux, Maud/D-3958-2015 OI Seidah, Nabil/0000-0001-6503-9342; NR 33 TC 69 Z9 76 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0022-2275 J9 J LIPID RES JI J. Lipid Res. PD JUN PY 2005 VL 46 IS 6 BP 1312 EP 1319 DI 10.1194/jlr.M400396-JLR200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 925NZ UT WOS:000229061100024 PM 15741654 ER PT J AU Yocum, AK Oe, T Yergey, AL Blair, IA AF Yocum, AK Oe, T Yergey, AL Blair, IA TI Novel lipid hydroperoxide-derived hemoglobin histidine adducts as biomarkers of oxidative stress SO JOURNAL OF MASS SPECTROMETRY LA English DT Article DE protein adducts; electrospray ionization; lipid peroxidation 4-oxo-2-nonenal; biomarker ID ELECTROSPRAY MASS-SPECTROMETRY; OXIDIZED LDL; PEROXIDATION PRODUCTS; DNA-DAMAGE; COVALENT MODIFICATION; PROTEIN MODIFICATION; LINOLEIC-ACID; ALDEHYDES; LYSINE; 4-HYDROXY-2-ALKENALS AB Hemoglobin (Hb) adducts have long been used as dosimeters of exposure to xenobiotics and endogenously formed reactive metabolites. In this study, hemoglobin chains were separated from each other and their prosthetic heme groups and reacted with 4-oxo-2-nonenal, a major breakdown product of lipid hydroperoxides. The adducts were characterized by matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-TOF/MS) analysis of the intact proteins and by a combination of liquid chromatography/electrospray ionization/tandem MS (MS/MS) and MALDI-TOF/MS/MS analysis of the tryptic peptides. Covalent modifications were found on both hemoglobin chains. The location was determined to be on H-20 of the alpha-hemoglobin chain and on H-63 of the beta-hemoglobin chain. Molecular modeling revealed that these two residues were two most solvent accessible H residues present in intact Hb. The proposed reaction mechanism is based on that described for the reaction of 4-hydroxy-2-nonenal with proteins. Initial nucleophilic Michael addition is followed by hydration of the resulting aldehyde, cyclization, and two sequential dehydration reactions to give stable furan derivatives. This results in the addition of 136 Da from 4-oxo-2-nonenal to give adducts corresponding to (17)VGAH* AGEYGAEALER(31) from alpha-hemoglobin and (62)AH* GK(65) from beta-hemoglobin. These hemoglobin modifications can potentially serve as biomarkers of lipid hydroperoxide-mediated macromolecule damage and may reflect an indirect measurement of the potential for DNA damage in vivo. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Univ Penn, Sch Med, Ctr Canc Pharmacol, Philadelphia, PA 19104 USA. NICHD, Sect Metab & Mass Spect, NIH, Bethesda, MD 20892 USA. RP Blair, IA (reprint author), Univ Penn, Sch Med, Ctr Canc Pharmacol, 854 BRB II-III,421 Curie Blvd, Philadelphia, PA 19104 USA. EM ian@spirit.gcrc.upenn.edu RI Blair, Ian/B-3320-2010 FU NCI NIH HHS [R01-CA95586] NR 49 TC 22 Z9 24 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1076-5174 J9 J MASS SPECTROM JI J. Mass Spectrom. PD JUN PY 2005 VL 40 IS 6 BP 754 EP 764 DI 10.1002/jms.847 PG 11 WC Biophysics; Chemistry, Organic; Spectroscopy SC Biophysics; Chemistry; Spectroscopy GA 941AS UT WOS:000230187600006 PM 15827957 ER PT J AU Esplin, MS Romero, R Chaiworapongsa, T Kim, YM Edwin, S Gomez, R Mazor, M Adashi, EY AF Esplin, MS Romero, R Chaiworapongsa, T Kim, YM Edwin, S Gomez, R Mazor, M Adashi, EY TI Monocyte chemotactic protein-1 is increased in the amnioticfluid of women who deliver preterm in the presence or absence of intra-amniotic infection SO JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE LA English DT Article DE MCP-1; intra-amniotic infection; preterm labor; preterm prelabor rupture of membranes; PROM; amniotic fluid ID ACTIVATING PEPTIDE-1 INTERLEUKIN-8; HUMAN FETAL MEMBRANES; LOWER UTERINE SEGMENT; PREMATURE RUPTURE; HUMAN PARTURITION; CHEMOATTRACTANT PROTEIN-1; MICROBIAL INVASION; GENE-EXPRESSION; GRO-ALPHA; TERM AB Objective. Pro-inflammatory chemokines have been associated with preterm parturition. Monocyte chemotactic protein-1 (MCP-1) is a chemokine capable of recruiting monocytes/macrophages into sites of inflammation, as well as stimulating the respiratory burst required for macrophage activation. MCP-1 transcripts and immuno-reactivity are expressed by uterine tissues (i.e., decidual cells and myometrium) and, thus, may participate in the process of labor. This study was conducted to determine if preterm labor leading to preterm delivery and intra-amniotic infection (IAI) are associated with changes in the amniotic fluid concentrations of MCP-1. Study design. A cross-sectional study was designed to examine the amniotic fluid concentrations of MCP-1 in women in two groups: 1) those presenting with preterm labor with intact membranes; and 2) those with preterm prelabor rupture of membranes ( PROM). Amniotic fluid was obtained by transabdominal amniocentesis from 131 women in preterm labor with intact membranes and 105 women with preterm PROM. IAI was defined by a positive amniotic fluid culture for microorganisms. Group 1 included women with preterm labor and intact membranes ( n = 131), and was subdivided into the following groups: a) delivery at term in the absence of IAI ( n= 42); b) preterm delivery ( 537 weeks) in the absence of IAI ( n = 58); and c) preterm delivery in the presence of IAI ( n = 31). Group 2 consisted of women with PROM ( n= 105), and was subdivided into women with ( n = 51) and without ( n = 54) IAI. Non-parametric statistics were used for data analysis. Results. 1) Immuno-reactive MCP-1 was detected in all amniotic fluid samples; 2) IAI, regardless of the membrane status, was associated with a significantly higher median amniotic fluid concentration of immuno-reactive MCP-1 than those without IAI (p<0.001 for both comparisons); 3) women in preterm labor who delivered preterm without IAI had a significantly higher median amniotic fluid concentration of immuno-reactive MCP-1 than those who delivered at term (p<0.001); 4) histological chorioamnionitis was associated with increased amniotic fluid concentrations of immunoreactive MCP-1; and 5) a significant relationship existed between the amniotic fluid concentrations of immuno-reactive MCP-1 and the interval from amniocentesis to delivery. Conclusions. Amniotic fluid concentrations of immuno-reactive MCP-1 were increased in women in preterm labor with IAI, those without IAI who delivered preterm, and those who displayed acute inflammatory lesions in the extra-placental membranes. These findings suggest that MCP-1 may play a role in preterm labor regardless of the presence of IAI. C1 Univ Utah, Hlth Sci Ctr, Dept Obstet & Gynecol, Salt Lake City, UT USA. NICHHD, Perinatol Res Branch, NIH, DHHS, Bethesda, MD 20892 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. Univ Catolica Chile, Sotero del Rio Hosp, CEDIP, Puente Alto, Chile. Ben Gurion Univ Negev, Soroka Med Ctr, Dept Obstet & Gynecol, IL-84105 Beer Sheva, Israel. RP Romero, R (reprint author), Hutzel Womens Hosp, NICHD, Perinatol Res Branch, NIH,DHHS, 3990 John R,4th Floor, Detroit, MI 48201 USA. EM warfiela@mail.mih.gov NR 37 TC 88 Z9 92 U1 1 U2 4 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 JUN PY 2005 VL 17 IS 6 BP 365 EP 373 DI 10.1080/14767050500141329 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 947SU UT WOS:000230667500001 PM 16009638 ER PT J AU Goker-Alpan, O Hruska, KS Orvisky, E Kishnani, PS Stubblefield, BK Schiffmann, R Sidransky, E AF Goker-Alpan, O Hruska, KS Orvisky, E Kishnani, PS Stubblefield, BK Schiffmann, R Sidransky, E TI Divergent phenotypes in Gaucher disease implicate the role of modifiers SO JOURNAL OF MEDICAL GENETICS LA English DT Article ID HUMAN GLUCOCEREBROSIDASE GENE; INTERMEDIATE PHENOTYPE; INTESTINAL NEOPLASIA; MUTANT ALLELES; APC GENE; IDENTIFICATION; MUTATIONS; GENOTYPE; TYPE-2; PHENYLKETONURIA AB Background: Gaucher disease is classified into neuronopathic and non-neuronopathic forms with wide phenotypic variation among patients sharing the same genotype. While homozygosity for the common L444P allele usually correlates with the neuronopathic forms, how a defined genotype leads to a phenotype remains unknown. Methods: The genetic and epigenetic factors causing phenotypic differences were approached by a clinical association study in 32 children homozygous for the point mutation L444P. Direct sequencing and Southern blots were utilised to establish the genotype and exclude recombinant alleles. Glucocerebrosidase activity was measured in lymphoblast and fibroblast cell lines. Results: Residual enzyme activity was highly variable and did not correlate with the observed clinical course. There was also a wide spectrum of phenotypes. Average age at diagnosis was 15 months, and slowed saccadic eye movements were the most prevalent finding. The most severe systemic complications and highest mortality occurred in splenectomised patients before the advent of enzyme replacement therapy (ERT). On ERT, as morbidity and mortality decreased, developmental and language deficits emerged as a major issue. Some trends related to ethnic background were observed. Conclusion: The wide clinical spectrum observed in the L444P homozygotes implicates the contribution of genetic modifiers in defining the phenotype in Gaucher disease. C1 NIMH, Sect Mol Neurogenet, NSB, NIH, Bethesda, MD 20892 USA. NGHRI, MGB, NIH, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Div Med Genet, Durham, NC USA. NINDS, DMNB, NIH, Bethesda, MD 20892 USA. RP Sidransky, E (reprint author), NIMH, Sect Mol Neurogenet, NSB, NIH, 35 Convent Dr 1A100, Bethesda, MD 20892 USA. EM sidranse@irp.nimh.nih.gov NR 44 TC 46 Z9 47 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 JUN PY 2005 VL 42 IS 6 AR e37 DI 10.1136/jmg.2004.028019 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA 932UQ UT WOS:000229579900018 PM 15937077 ER PT J AU Juhaszova, M Wang, S Zorov, DB Sollott, SJ AF Juhaszova, M Wang, S Zorov, DB Sollott, SJ TI Effect of intracellular Ca2+ on MPT induction in cardiac myocytes SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 25th Annual Scientific Session of the European Section of the International-Society-for-Heart-Research CY JUN 21-25, 2005 CL Univ Tromso, Hlth Sci Bldg, Tromso, NORWAY SP Int Soc Heart Res, European Sect HO Univ Tromso, Hlth Sci Bldg C1 NIA, Cardiovasc Sci Lab, Ctr Gerontol Res, NIH, Baltimore, MD 21224 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUN PY 2005 VL 38 IS 6 MA 096 BP 1032 EP 1033 PG 2 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 935TQ UT WOS:000229806700108 ER PT J AU Yitzhaki, S Shneyvays, V Jacobson, KA Shainberg, A AF Yitzhaki, S Shneyvays, V Jacobson, KA Shainberg, A TI Involvement of uracil nucleotides in a protection of cardiomyocytes against hypoxia SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 25th Annual Scientific Session of the European Section of the International-Society-for-Heart-Research CY JUN 21-25, 2005 CL Univ Tromso, Hlth Sci Bldg, Tromso, NORWAY SP Int Soc Heart Res, European Sect HO Univ Tromso, Hlth Sci Bldg C1 Bar Ilan Univ, Fac Life Sci, Ramat Gan, Israel. NIDDK, NIH, Bioorgan Chem Lab, Bethesda, MD USA. RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUN PY 2005 VL 38 IS 6 MA 190 BP 1066 EP 1067 PG 2 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 935TQ UT WOS:000229806700202 ER PT J AU Zungul, M Ngumbela, K Yang, D Sack, MN Essop, MF AF Zungul, M Ngumbela, K Yang, D Sack, MN Essop, MF TI Genomic modulation of nuclear-encoded SO JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY LA English DT Meeting Abstract CT 25th Annual Scientific Session of the European Section of the International-Society-for-Heart-Research CY JUN 21-25, 2005 CL Univ Tromso, Hlth Sci Bldg, Tromso, NORWAY SP Int Soc Heart Res, European Sect HO Univ Tromso, Hlth Sci Bldg C1 Univ Cape Town, Cardiol Res Inst, Fac Hlth Sci, ZA-7925 Cape Town, South Africa. NHLBI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2828 EI 1095-8584 J9 J MOL CELL CARDIOL JI J. Mol. Cell. Cardiol. PD JUN PY 2005 VL 38 IS 6 MA 243 BP 1086 EP 1087 PG 2 WC Cardiac & Cardiovascular Systems; Cell Biology SC Cardiovascular System & Cardiology; Cell Biology GA 935TQ UT WOS:000229806700255 ER PT J AU Hanada, K Yang, JC AF Hanada, K Yang, JC TI Novel biochemistry: post-translational protein splicing and other lessons from the school of antigen processing SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Review DE protein splicing; tumor antigens; antigen presentation ID TUMOR-INFILTRATING LYMPHOCYTES; OPEN READING FRAME; CYTOLYTIC T-LYMPHOCYTES; HUMAN-MELANOMA ANTIGEN; CLASS-I MOLECULES; CANCER ANTIGEN; CONCANAVALIN-A; ADENOSINE-TRIPHOSPHATASE; METASTATIC MELANOMA; HLA-A2 MELANOMAS AB In the past 15 years, the molecular identification of antigens that can mediate the killing of tumor cells by T cells has been vigorously pursued. Molecular identification of tumor-associated antigens not only provided the means to activate or monitor anti-tumor immunity, but also gave insights into new and unexpected biochemical processes that are taking place within cells. Post-translational splicing, a phenomenon previously identified only in lower organisms or plants, has recently been added to the list of atypical processes generating proteins in humans. The proteasome, whose main function is to degrade intracellular proteins, appears to catalyze this splicing reaction. The discovery of post-translational splicing has immediate and important implications for the complexity of the major histocompatibility complex (MHC) class I peptide repertoire and for the immune recognition of self- and foreign peptides. C1 NCI, Surg Branch, NIH, Clin Res Ctr, Bethesda, MD 20892 USA. RP Hanada, K (reprint author), NCI, Surg Branch, NIH, Clin Res Ctr, Rm 3-3840,10 Ctr Dr,MSC 1201, Bethesda, MD 20892 USA. EM khanada@nih.gov RI Hanada, Ken-ichi/A-4642-2008 NR 76 TC 3 Z9 5 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD JUN PY 2005 VL 83 IS 6 BP 420 EP 428 DI 10.1007/s00109-005-0652-6 PG 9 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 944EP UT WOS:000230409400003 PM 15759099 ER PT J AU Szalai, AJ Wu, J Lange, EM McCrory, MA Langefeld, CD Williams, A Zakharkin, SO George, V Allison, DB Cooper, GS Xie, F Fan, Z Edberg, JC Kimberly, RP AF Szalai, AJ Wu, J Lange, EM McCrory, MA Langefeld, CD Williams, A Zakharkin, SO George, V Allison, DB Cooper, GS Xie, F Fan, Z Edberg, JC Kimberly, RP TI Single-nucleotide polymorphisms in the C-reactive protein (CRP) gene promoter that affect transcription factor binding, alter transcriptional activity, and associate with differences in baseline serum CRP level SO JOURNAL OF MOLECULAR MEDICINE-JMM LA English DT Article DE acute-phase reactants; gene regulation; inflammation ID CORONARY-HEART-DISEASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; ACUTE-PHASE RESPONSE; TRANSGENIC MICE; CARDIOVASCULAR-DISEASE; REPEAT POLYMORPHISM; C/EBP-BETA; INFLAMMATION; MARKERS; RISK AB To investigate whether functional polymorphisms exist in the C-reactive protein (CRP) gene, i.e., ones that contribute directly to differences in baseline CRP among individuals, we sequenced a 1,156-nucleotide-long stretch of the CRP gene promoter in 287 ostensibly healthy people. We identified two single-nucleotide polymorphisms (SNPs), a bi-allelic one at nucleotide -409 (G -> A), and a tri-allelic one at -390 (C -> T -> A), both resident within the hexameric core of transcription factor binding E-box elements. Electrophoretic mobility shift assays confirmed that the SNP within the sequence (-412)CACGTG(-407) (E-box 1) modulates transcription factor binding, and that the one within (-394)CACTTG(-389) (E-box 2) supports transcription factor binding only when the -390 T allele is present. The commonest of four E-box I/E-box 2 haplotypes (-409G/-390T) identified in the population supported highest promoter activity in luciferase reporter assays, and the rarest one (-409A/-390T) supported the least. Importantly, serum CRP in people with these haplotypes reproduced this rank order, i.e., people with the -409G/-390T haplotype had the highest baseline serum CRP (mean SEM 10.9 +/- 2.25 mu g/ml) and people with the -409A/-390T haplotype had the lowest (5.01 +/- 1.56 mu g/ml). Furthermore, haplotype-associated differences in baseline CRP were not due to differences in age, sex, or race, and were still apparent in people with no history of smoking. At least two other SNPs in the CRP promoter lie within E-box elements (-198 C -> T, E-box 4, and -861 T -> C, E-box 3), indicating that not only is the quality of E-box sites in CRP a major determinant of baseline CRP level, but also that the number of E-boxes may be important. These data confirm that the CRP promoter does encode functional polymorphisms, which should be considered when baseline CRP is being used as an indicator of clinical outcome. Ultimately, development of genetic tests to screen for CRP expression variants could allow categorization of healthy people into groups at high versus low future risk of inflammatory disease. C1 Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. Wake Forest Univ, Dept Publ Hlth Sci, Winston Salem, NC 27157 USA. Univ Alabama, Dept Biostat, Sect Stat Genet, Birmingham, AL 35294 USA. Natl Inst Environm Hlth Sci, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. RP Szalai, AJ (reprint author), Univ Alabama, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35294 USA. EM Alex.Szalai@ccc.uab.edu OI Allison, David/0000-0003-3566-9399; Kimberly, Robert/0000-0002-5330-3086 NR 35 TC 112 Z9 124 U1 2 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0946-2716 J9 J MOL MED-JMM JI J. Mol. Med. PD JUN PY 2005 VL 83 IS 6 BP 440 EP 447 DI 10.1007/s00109-005-0658-0 PG 8 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA 944EP UT WOS:000230409400005 PM 15778807 ER PT J AU Fields, RD AF Fields, RD TI Purinergic signaling molecules regulating schwann cell development in response to impulse activity in axons SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-for-Neurochemistry CY JUN 25-29, 2005 CL Madison, WI SP Amer Soc Neurochem C1 NICHD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2005 VL 94 SU 1 BP 2 EP 2 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 942XW UT WOS:000230317200005 ER PT J AU Borchelt, DR Jankowsky, JL Savonenko, A Melinkova, T Slunt, HH Younkin, LH Copeland, NG Jenkins, NA Younkin, SG AF Borchelt, DR Jankowsky, JL Savonenko, A Melinkova, T Slunt, HH Younkin, LH Copeland, NG Jenkins, NA Younkin, SG TI Formation and clearance of amyloid pathology in mouse models of Alzheimer's disease SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-for-Neurochemistry CY JUN 25-29, 2005 CL Madison, WI SP Amer Soc Neurochem C1 Univ Florida, Dept Neurosci, Gainesville, FL 32610 USA. CALTECH, Div Biol, Pasadena, CA 91125 USA. Johns Hopkins Univ, Sch Med, Dept Pathol & Neurosci, Baltimore, MD USA. Mayo Clin, Dept Neurosci, Jacksonville, FL 32224 USA. NCI, Frederick, MD 21701 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2005 VL 94 SU 1 BP 4 EP 4 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 942XW UT WOS:000230317200008 ER PT J AU Wu, CY Wei, JJ Polak, PE Sharp, AR Mao, JL Feinstein, DL Gould, RM Nichols, L Park, K Cai, L Innis, RB Pike, VW Wang, YM AF Wu, CY Wei, JJ Polak, PE Sharp, AR Mao, JL Feinstein, DL Gould, RM Nichols, L Park, K Cai, L Innis, RB Pike, VW Wang, YM TI Development of novel amyloid imaging agents based upon thioflavins SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-for-Neurochemistry CY JUN 25-29, 2005 CL Madison, WI SP Amer Soc Neurochem C1 Univ Illinois, Coll Med Cell Biol & Anat, Dept Med Chem & Pharmacognosy, Chicago, IL USA. Univ Illinois, Coll Med Cell Biol & Anat, Dept Neuroanesthesiol, Chicago, IL USA. NIMH, Mol Imaging Branch, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2005 VL 94 SU 1 BP 27 EP 27 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 942XW UT WOS:000230317200068 ER PT J AU Golovko, MY Faergeman, NJ Cole, NB Castagnet, PI Nussbaum, RL Murphy, EJ AF Golovko, MY Faergeman, NJ Cole, NB Castagnet, PI Nussbaum, RL Murphy, EJ TI Alpha-synuclein gene-ablation decreases brain palmitate uptake and alters palmitate metabolism in brain phospholipids SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-for-Neurochemistry CY JUN 25-29, 2005 CL Madison, WI SP Amer Soc Neurochem C1 Univ N Dakota, Dept Pharmacol, Grand Forks, ND 58201 USA. Univ So Denmark, Dept Biochem, Odense, Denmark. NIH, Genet Dis Res Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2005 VL 94 SU 1 BP 40 EP 40 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 942XW UT WOS:000230317200113 ER PT J AU McKay, R AF McKay, R TI The molecular biology of stem cells SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-for-Neurochemistry CY JUN 25-29, 2005 CL Madison, WI SP Amer Soc Neurochem C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2005 VL 94 SU 1 BP 54 EP 54 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 942XW UT WOS:000230317200158 ER PT J AU Pant, HC Grant, P AF Pant, HC Grant, P TI Topographic phosphorylation of axonal cytoskeletal proteins SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-for-Neurochemistry CY JUN 25-29, 2005 CL Madison, WI SP Amer Soc Neurochem C1 NINDS, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2005 VL 94 SU 1 BP 73 EP 73 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 942XW UT WOS:000230317200202 ER PT J AU Mezey, E Shahar, T Leker, R Pastorino, S Key, S Szalayova, I Bratincsak, A Toth, Z AF Mezey, E Shahar, T Leker, R Pastorino, S Key, S Szalayova, I Bratincsak, A Toth, Z TI From blood to brain: can circulating blood cells help repair the brain? SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-for-Neurochemistry CY JUN 25-29, 2005 CL Madison, WI SP Amer Soc Neurochem C1 NINDS, NIH, Bethesda, MD 20892 USA. NIDCR, NIH, Bethesda, MD USA. NIMH, NIH, Bethesda, MD 20892 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2005 VL 94 SU 1 BP 77 EP 77 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 942XW UT WOS:000230317200210 ER PT J AU Schengrund, CL Borges, AOR Puri, A Blumenthal, R Krebs, FC Johnson, BT Rawat, SS AF Schengrund, CL Borges, AOR Puri, A Blumenthal, R Krebs, FC Johnson, BT Rawat, SS TI Glycosphingolipids - portals for infection SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-for-Neurochemistry CY JUN 25-29, 2005 CL Madison, WI SP Amer Soc Neurochem C1 Penn State Univ, Coll Med, Hershey, PA USA. NCI, Ctr Canc Res, Frederick, MD 21701 USA. Drexel Univ, Coll Med, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2005 VL 94 SU 1 BP 100 EP 100 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 942XW UT WOS:000230317200283 ER PT J AU Yamada, M Araya, R Kitamura, N Kishida, H Mishina, Y AF Yamada, M Araya, R Kitamura, N Kishida, H Mishina, Y TI BMP signaling regulates glial scarring SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-Society-for-Neurochemistry CY JUN 25-29, 2005 CL Madison, WI SP Amer Soc Neurochem C1 RIKEN, Brain Sci Inst, Yamada Res Unit, Wako, Saitama 35101, Japan. Natl Inst Environm Hlth Sci, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2005 VL 94 SU 1 BP 126 EP 126 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 942XW UT WOS:000230317200357 ER PT J AU Romm, E Nielsen, JA Kim, JG Hudson, LD AF Romm, E Nielsen, JA Kim, JG Hudson, LD TI Myt1 family recruits histone deacetylase to regulate neural transcription SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE histone deacetylase; mSin3; Myt1; repression; transcription; zinc finger ID CO-REPRESSOR COMPLEXES; CENTRAL-NERVOUS-SYSTEM; ZINC-FINGER; OLIGODENDROCYTE LINEAGE; FACTOR-1 MYT1; DNA-BINDING; FACTOR-I; DIFFERENTIATION; NEURONS; PROTEIN AB The myelin transcription factor 1 (Myt1) gene family is comprised of three zinc finger genes [Myt1, Myt1L (Myt1-Like) and NZF3] of the structurally unique CCHHC class that are expressed predominantly in the developing CNS. To understand the mechanism by which this family regulates neural differentiation, we searched for interaction partners. In both yeast and a mammalian two-hybrid system, Myt1 and Myt1L interacted with Sin3B, a protein that mediates transcriptional repression by binding to histone deacetylases (HDACs). Myt1-Sin3B complexes were co-immunoprecipitated from transfected mammalian cells and included HDAC1 and HDAC2. Myt1 and Myt1L could partner with all three Sin3B isoforms, the long form (Sin3B(LF)) that includes the HDAC-binding domain, and the two short forms (Sin3B(SF293) and Sin3B(SF302)) that lack this domain and may consequently antagonize Sin3B(LF)/HDAC-mediated co-repression. Myt1 or Myt1L interactions with the HDAC-binding form of Sin3B conferred repression on a heterologous promoter. Oligodendrocytes were shown to express transcripts encoding each of the Sin3B isoforms. We present a model in which the Myt1 family of zinc finger proteins, when bound to a neural promoter, can recruit Sin3B. Depending on the relative availability of Sin3B isoforms, the Myt1 gene family may favor the silencing of genes during neural development. C1 NINDS, Sect Dev Genet, NIH, Bethesda, MD 20892 USA. RP Hudson, LD (reprint author), Bldg 49,Room 5A82,49 Convent Dr, Bethesda, MD 20892 USA. EM hudsonl1@od.nih.gov FU NINDS NIH HHS [Z01 NS002528-24] NR 25 TC 67 Z9 69 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 JUN PY 2005 VL 93 IS 6 BP 1444 EP 1453 DI 10.1111/j.1471-4159.2005.03131.x PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 930OM UT WOS:000229425800009 PM 15935060 ER PT J AU Murakami, Y Saito, K Hara, A Zhu, YY Sudo, K Niwa, M Fujii, H Wada, H Ishiguro, H Mori, H Seishima, M AF Murakami, Y Saito, K Hara, A Zhu, YY Sudo, K Niwa, M Fujii, H Wada, H Ishiguro, H Mori, H Seishima, M TI Increases in tumor necrosis factor-alpha following transient global cerebral ischemia do not contribute to neuron death in mouse hippocampus SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE bilateral common carotid artery occlusion; bone marrow transplanted mice; central nerve system; neuronal death; tumor necrosis factor-alpha gene-deficient mice; tumor necrosis factor-alpha-related molecules ID CENTRAL-NERVOUS-SYSTEM; DEFICIENT LIVER-REGENERATION; BONE-MARROW-TRANSPLANTATION; TNF-ALPHA; MICE LACKING; BRAIN-INJURY; FOREBRAIN ISCHEMIA; GENE-EXPRESSION; FACTOR RECEPTOR; RAT-BRAIN AB The actions of tumor necrosis factor-alpha (TNF-alpha) produced by resident brain cells and bone marrow-derived cells in brain following a transient global ischemia were evaluated. In wild-type mice (C57Bl/6J) following 20 min ischemia with bilateral common carotid artery occlusion (BCCAo), TNF-alpha mRNA expression levels in the hippocampus were significantly increased at 3 h and 36 h and exhibited a biphasic expression pattern. There were no hippocampal TNF-alpha mRNA expression levels at early time points in either wild-type mice bone marrow transplanted (BMT)-chimeric-TNF-alpha gene-deficient (T/W) or TNF-alpha gene-deficient mice BMT-TNF-alpha gene-deficient mice (T/T), although TNF-alpha mRNA levels were detectable in T/W BMT mice at 36 h. Histopathological findings showed no intergroup differences between wild-type and TNF-alpha gene-deficient mice at 4 and 7 days after transient ischemia. In addition, nuclear factor-kappa B (NF-kappa B) was activated within 12 h after global cerebral ischemia, but electrophoretic mobility shift assays (EMSA) showed no intergroup differences between wild type and TNF-alpha gene-deficient mice. In summary, early hippocampal TNF-alpha mRNA expression may not be related to bone marrow-derived cells, and secondary TNF-alpha expression as early as 36 h after ischemia probably resulted mainly from endogenous brain cells and possibly a few bone marrow-derived cells. Although we cannot exclude the possibility of the TNF-alpha contribution to the physiologic changes of hippocampus after transient global ischemia, these results indicate that TNF-alpha does not influence the morphological changes of the hippocampal neurons under our study condition. C1 Gifu Univ, Grad Sch Med, Dept Informat Clin Med, Gifu, Japan. Gifu Univ, Grad Sch Med, Dept Pathol, Gifu, Japan. Gifu Univ, Grad Sch Med, Med Educ Dept, Gifu, Japan. NIMH, Dept Neurotoxicol, NIH, Bethesda, MD 20892 USA. Nippon Organon KK, R&D Lab, Osaka, Japan. RP Saito, K (reprint author), 1-1 Yanagido, Gifu 5011194, Japan. EM saito@cc.gifu-u.ac.jp NR 43 TC 35 Z9 39 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2005 VL 93 IS 6 BP 1616 EP 1622 DI 10.1111/j.1471-4159.2005.03163.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 930OM UT WOS:000229425800027 PM 15935078 ER PT J AU Xiromerisiou, G Gourbali, V Aggelakis, K Dardiotis, E Tsimourtou, V Papadimitriou, A Papakonstantinou, I Scarmeas, N Singleton, A Hadjigeorgiou, G AF Xiromerisiou, G Gourbali, V Aggelakis, K Dardiotis, E Tsimourtou, V Papadimitriou, A Papakonstantinou, I Scarmeas, N Singleton, A Hadjigeorgiou, G TI Association of alpha-synuclein Rep1 polymorphism with risk for Parkinson's disease and influence on age at onset of Parkinson's disease SO JOURNAL OF NEUROLOGY LA English DT Meeting Abstract CT 15th Meeting of the European-Neurological-Society CY JUN 18-22, 2005 CL Vienna, AUSTRIA SP European Neurol Soc C1 Univ Thessaly, Larisa, Greece. Gen Hosp, Trikala, Greece. Columbia Univ, New York, NY USA. NIH, Neurogenet Lab, Bethesda, MD 20892 USA. RI Singleton, Andrew/C-3010-2009 NR 0 TC 0 Z9 0 U1 0 U2 1 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 JUN PY 2005 VL 252 SU 2 BP 31 EP 32 PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 937QV UT WOS:000229941500103 ER PT J AU Samuel, M Voon, V AF Samuel, M Voon, V TI Beyond the holy grail of motor symptoms: deep brain stimulation for Parkinson's disease SO JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY LA English DT Editorial Material C1 Kings Coll Hosp London, Dept Neurol, London SE5 9RS, England. Natl Inst Neurol Disorders & Stroke, NIH, Bethesda, MD USA. RP Samuel, M (reprint author), Kings Coll Hosp London, Dept Neurol, Denmark Hill, London SE5 9RS, England. EM mike.samuel@kingsch.nhs.uk NR 3 TC 1 Z9 1 U1 1 U2 1 PU BMJ 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 JUN PY 2005 VL 76 IS 6 BP 759 EP 760 DI 10.1136/jnnp.2004.061911 PG 2 WC Clinical Neurology; Psychiatry; Surgery SC Neurosciences & Neurology; Psychiatry; Surgery GA 926MC UT WOS:000229126300002 PM 15897490 ER PT J AU Parnas, H Slutsky, I Rashkovan, G Silman, I Wess, J Parnas, I AF Parnas, H Slutsky, I Rashkovan, G Silman, I Wess, J Parnas, I TI Depolarization initiates phasic acetylcholine release by relief of a tonic block imposed by presynaptic M-2 muscarinic receptors SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID VOLTAGE-DEPENDENT INTERACTION; FROG NEUROMUSCULAR-JUNCTION; G-PROTEIN MODULATION; K+-CHANNEL PROTEINS; MOTOR-NERVE ENDINGS; TRANSMITTER RELEASE; CALCIUM-CHANNELS; NEUROTRANSMITTER RELEASE; BETA-GAMMA; SYNAPTIC PLASTICITY AB The role of presynaptic muscarinic autoreceptors in the initiation of phasic acetylcholine (ACh) release at frog and mouse neuromuscular junctions was studied by measuring the dependency of the amount (m) of ACh release on the level of presynaptic depolarization. Addition of methoctramine (a blocker of M-2 muscarinic receptors), or of acetylcholinesterase (AChE), increased release in a voltage-dependent manner; enhancement of release declined as the depolarizing pulse amplitude increased. In frogs and wild-type mice the slope of log m/log pulse amplitude (PA) was reduced from about 7 in the control to about 4 in the presence of methoctramine or AChE. In M-2 muscarinic receptor knockout mice, the slope of log m/log PA was much smaller (about 4) and was not further reduced by addition of either methoctramine or AChE. The effect of a brief (0.1 ms), but strong (-1.2 mu A) depolarizing prepulse on the dependency of m on PA was also studied. The depolarizing prepulse had effects similar to those of methoctramine and AChE. In particular, it enhanced release of test pulses in a voltage-dependent manner and reduced the slope of log m/log PA from about 7 to about 4. Methoctramine + AChE occluded the prepulse effects. In knockout mice, the depolarizing prepulse had no effects. The cumulative results suggest that initiation of phasic ACh release is achieved by depolarization-mediated relief of a tonic block imposed by presynaptic M-2 muscarinic receptors. C1 Hebrew Univ Jerusalem, Dept Neurobiol, Otto Loewi Minerva Ctr Cellular & Mol Neurobiol, IL-91904 Jerusalem, Israel. Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. NIDDKD, Bioorgan Chem Lab, Bethesda, MD 20892 USA. RP Parnas, H (reprint author), Hebrew Univ Jerusalem, Dept Neurobiol, Otto Loewi Minerva Ctr Cellular & Mol Neurobiol, IL-91904 Jerusalem, Israel. EM hanna@vms.huji.ac.il NR 61 TC 15 Z9 15 U1 0 U2 0 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 2005 VL 93 IS 6 BP 3257 EP 3269 DI 10.1152/jn.01131.2004 PG 13 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 929AE UT WOS:000229313100029 PM 15703226 ER PT J AU Koyama, S Kanemitsu, Y Weight, FF AF Koyama, S Kanemitsu, Y Weight, FF TI Spontaneous activity and properties of two types of principal neurons from the ventral tegmental area of rat SO JOURNAL OF NEUROPHYSIOLOGY LA English DT Article ID MIDBRAIN DOPAMINERGIC-NEURONS; SUBSTANTIA-NIGRA; I-H; SMALL-CONDUCTANCE; K+ CHANNELS; RECEPTORS; AFTERHYPERPOLARIZATION; SUBPOPULATIONS; TRANSMISSION; MODULATION AB We investigated the spontaneous activity and properties of freshly isolated ventral tegmental area (VTA) principal neurons by whole cell recording and single-cell RT-PCR. The VTA principal neurons, which were tyrosine hydroxylase-positive and glutamic acid decarboxylase (GAD(67))-negative, exhibited low firing frequency and a long action potential (AP) duration. The VTA principal neurons exhibited a calretinin-positive and parvalbumin-negative Ca2+-binding protein mRNA expression pattern. The VTA principal neurons were classified into two subpopulations based on their firing frequency coefficient of variation (CV) at room temperature (21-23 degrees C): irregular-type neurons with a large CV and tonic-type neurons with a small CV. These two firing patterns were also recorded at the temperature of 34 degrees C and in nystatin-perforated patch recording. In VTA principal neurons, the AP afterhyperpolarization (AHP) amplitude contributed to the firing regularity and AHP decay slope contributed to the firing frequency. The AHP amplitude in the irregular-type VTA principal neurons was smaller than that in the tonic-type VTA principal neurons. There was no significant difference in the AHP decay slope between the two-types of VTA principal neurons. Apamin-sensitive small-conductance Ca2+-activated K+ (SK) channels contributed to the AHP and the regular firing of the tonic-type neurons but contributed little to the AHP and firing of the irregular-type neurons. In voltage-clamp tail-current analysis, in both conventional and nystatin-perforated whole cell recording, the apamin-sensitive AHP current density of the tonic-type neurons was significantly larger than that of the irregular-type neurons. We suggest that apamin-sensitive SK current contributes to intrinsic firing differences between the two subpopulations of VTA principal neurons. C1 NIAAA, Mol & Cellular Neurobiol Lab, NIH, Bethesda, MD USA. RP Koyama, S (reprint author), Univ Illinois, Dept Physiol & Biophys, M-C 901,835 S Wolcott Ave, Chicago, IL 60612 USA. EM koyama@uic.edu FU NIAAA NIH HHS [AA-05846] NR 43 TC 14 Z9 14 U1 0 U2 1 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3077 J9 J NEUROPHYSIOL JI J. Neurophysiol. PD JUN PY 2005 VL 93 IS 6 BP 3282 EP 3293 DI 10.1152/jn.00776.2004 PG 12 WC Neurosciences; Physiology SC Neurosciences & Neurology; Physiology GA 929AE UT WOS:000229313100031 PM 15659533 ER PT J AU Thiriet, N Deng, XL Solinas, M Ladenheim, B Curtis, W Goldberg, SR Palmiter, RD Cadet, JL AF Thiriet, N Deng, XL Solinas, M Ladenheim, B Curtis, W Goldberg, SR Palmiter, RD Cadet, JL TI Neuropeptide y protects against methamphetamine-induced neuronal apoptosis in the mouse striatum SO JOURNAL OF NEUROSCIENCE LA English DT Article DE amphetamines; cell death; NPY; neurodegenerative diseases; neuroprotection; Y-2 receptor ID DISMUTASE TRANSGENIC MICE; MANGANESE SUPEROXIDE-DISMUTASE; HUNTINGTONS-DISEASE; NADPH-DIAPHORASE; NERVOUS-SYSTEM; INDUCED NEUROTOXICITY; CEREBRAL-CORTEX; FOOD-INTAKE; CHO-CELLS; MN-SOD AB Methamphetamine ( METH) is an illicit drug that causes neuronal apoptosis in the mouse striatum, in a manner similar to the neuronal loss observed in neurodegenerative diseases. In the present study, injections of METH to mice were found to cause the death of enkephalin-positive projection neurons but not the death of neuropeptide Y(NPY)/nitric oxide synthase-positive striatal interneurons. In addition, these METH injections were associated with increased expression of neuropeptide Y mRNA and changes in the expression of the NPY receptors Y-1 and Y-2. Administration of NPY in the cerebral ventricles blocked METH-induced apoptosis, an effect that was mediated mainly by stimulation of NPY Y-2 receptors and, to a lesser extent, of NPY Y-1 receptors. Finally, we also found that neuropeptide Y knock-out mice were more sensitive than wild-type mice to METH-induced neuronal apoptosis of both enkephalin- and nitric oxide synthase-containing neurons, suggesting that NPY plays a general neuroprotective role within the striatum. Together, our results demonstrate that neuropeptide Y belongs to the class of factors that maintain neuronal integrity during cellular stresses. Given the similarity between the cell death patterns induced by METH and by disorders such as Huntington's disease, our results suggest that NPY analogs might be useful therapeutic agents against some neurodegenerative processes. C1 NIDA, NIH, Dept Hlth & Human Serv, Mol Neuropsychiat Branch,Intramural Res Program, Baltimore, MD 21224 USA. NIDA, NIH, Dept Hlth & Human Serv, Behav Neurosci Branch,Intramural Res Program, Baltimore, MD 21224 USA. Univ Poitiers, CNRS 6187, F-86000 Poitiers, France. Univ Washington, Howard Hughes Med Inst, Dept Biochem, Seattle, WA 98195 USA. RP Cadet, JL (reprint author), NIDA, NIH, Dept Hlth & Human Serv, Mol Neuropsychiat Branch,Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jcadet@intra.nida.nih.gov RI Solinas, Marcello/M-3500-2016 OI Solinas, Marcello/0000-0002-0664-5964 NR 58 TC 57 Z9 59 U1 4 U2 7 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 1 PY 2005 VL 25 IS 22 BP 5273 EP 5279 DI 10.1523/JNEUROSCI.4893-04.2005 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 931OR UT WOS:000229495100003 PM 15930374 ER PT J AU Garraux, G McKinney, C Wu, T Kansaku, K Nolte, G Hallett, M AF Garraux, G McKinney, C Wu, T Kansaku, K Nolte, G Hallett, M TI Shared brain areas but not functional connections controlling movement timing and order SO JOURNAL OF NEUROSCIENCE LA English DT Article DE motor control; fMRI; connectivity; cerebellum; putamen; cognition ID WORKING-MEMORY; PARKINSONS-DISEASE; HUMAN CEREBELLUM; TIME PERCEPTION; BASAL GANGLIA; SERIAL ORDER; SEQUENCES; FMRI; ACTIVATION; MECHANISMS AB Virtually every aspect of the enormous repertoire of human behaviors is embedded in a sequential context, but brain mechanisms underlying the adjustment of two fundamental dimensions defining a motor sequence (order of a series of movements and intervals separating them) as a function of a given goal are poorly understood. Using functional magnetic resonance imaging, we demonstrate that, at the neuronal level, these tasks can only be distinguished by differences in functional interactions between associative areas of common activation, which included bilateral subcortico-parieto-frontal regions, and two subcortical structures. Activity in these shared associative areas was preferentially coupled with that in right putamen during manipulation of timing and with that in right posterior cerebellum during manipulation of serial order. This finding is important because it provides evidence for an efficient organization of the brain during cognitive control of motor sequences and supports a recently proposed principle according to which the role of brain regions involved in different behavioral tasks without differential alterations in their measured activity depends on changes in their interactions with other connected areas as a function of the tasks. C1 NINDS, Human Motor Control Sect, NIH, Bethesda, MD 20892 USA. Univ Liege, Cyclotron Res Ctr, B-4000 Liege, Belgium. Univ Liege, Dept Neurol, B-4000 Liege, Belgium. RP Hallett, M (reprint author), NINDS, Human Motor Control Sect, NIH, Bldg 10,Room 5N226,10 Ctr Dr,MSC 1428, Bethesda, MD 20892 USA. EM hallettm@ninds.nih.gov RI Garraux, Gaetan/G-9050-2011 NR 51 TC 42 Z9 42 U1 2 U2 9 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 1 PY 2005 VL 25 IS 22 BP 5290 EP 5297 DI 10.1523/JNEUROSCI.0340-5.2005 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 931OR UT WOS:000229495100005 PM 15930376 ER PT J AU Wang, B Shaham, Y Zitzman, D Azari, S Wise, RA You, ZB AF Wang, B Shaham, Y Zitzman, D Azari, S Wise, RA You, ZB TI Cocaine experience establishes control of midbrain glutamate and dopamine by corticotropin-releasing factor: A role in stress-induced relapse to drug seeking SO JOURNAL OF NEUROSCIENCE LA English DT Article DE stress; addiction; relapse; ventral tegmental area; corticotropin-releasing factor; cocaine ID VENTRAL TEGMENTAL AREA; INDUCED REINSTATEMENT; PREFRONTAL CORTEX; BEHAVIORAL SENSITIZATION; NUCLEUS-ACCUMBENS; STRIA TERMINALIS; HEROIN-SEEKING; CRF RECEPTORS; BED NUCLEUS; RATS AB Footshock stress can reinstate cocaine-seeking behavior through a central action of the stress-associated neurohormone corticotropin-releasing factor (CRF). Here we report (1) that footshock stress releases CRF in the ventral tegmental area (VTA) of the rat brain, (2) that, in cocaine-experienced but not in cocaine-naive rats, this CRF acquires control over local glutamate release, (3) that CRF-induced glutamate release activates the mesocorticolimbic dopamine system, and (4) that, through this circuitry, footshock stress triggers relapse to drug seeking in cocaine-experienced animals. Thus, a long-lasting cocaine-induced neuroadaptation, presumably at the level of glutamate terminals in the VTA, appears to play an important role in stress-induced relapse to drug use. Similar neuroadaptations may be important for the comorbidity between addiction and other stress-related psychiatric disorders. C1 NIDA, Intramural Res Program, Behav Neurosci Branch, NIH, Baltimore, MD 21224 USA. RP Wise, RA (reprint author), NIDA, Intramural Res Program, Behav Neurosci Branch, NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rwise@intra.nida.nih.gov RI Wise, Roy/A-6465-2012; shaham, yavin/G-1306-2014 NR 46 TC 206 Z9 210 U1 0 U2 5 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD JUN 1 PY 2005 VL 25 IS 22 BP 5389 EP 5396 DI 10.1523/JNEUROSCI.0955-05.2005 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 931OR UT WOS:000229495100017 PM 15930388 ER PT J AU Calvo, CF Amigou, E Tence, M Yoshimura, T Glowinski, J AF Calvo, CF Amigou, E Tence, M Yoshimura, T Glowinski, J TI Albumin stimulates monocyte chemotactic protein-1 expression in rat embryonic mixed brain cells SO JOURNAL OF NEUROSCIENCE RESEARCH LA English DT Article DE brain; cytology; monocyte chemoattractant protein-1; agonist; albumins; pharmacology ID CENTRAL-NERVOUS-SYSTEM; HUMAN SERUM-ALBUMIN; CHEMOATTRACTANT PROTEIN-1; SUPEROXIDE PRODUCTION; CHEMOKINE RECEPTORS; GENE-EXPRESSION; IDENTIFICATION; ASTROCYTES; MICROGLIA; MCP-1 AB Albumin, a blood protein absent from the adult brain in physiological situations, can be brought into contact with brain cells during development or, in adult, following breakdown of the blood-brain barrier occurring as a result of local inflammation. In the present study, we show that ovalbumin and albumin induce the release of monocyte chemotactic protein 1 (MCP-1/CCL2) from rat embryonic mixed brain cells. A short-term exposure to ovalbumin during the cell dissociation procedure is sufficient to generate MCP-1 mRNA. A comparable effect is observed when the cells are incubated for 4 hr with ovalbumin or rat albumin, while MCP-1 messengers are barely detectable following bovine albumin exposure. The amount of MCP-1 protein measured in 4 hr-supernatants of albumin-treated cells followed the same albumin-inducing pattern as that of MCP-1 mRNA, while all albumins tested induced MCP-1 protein after a 17 hr-incubation period. The albumin-induced MCP-1 production is significantly inhibited in calphostin C-treated cells, suggesting the implication of a protein kinase C-dependent signaling pathway. This MCP-1-inducing activity is maintained after a lipid extraction procedure but abolished by proteinase K or trypsin treatments of albumin. The MCD-1 secretion following. albumin contact with nervous cells could thus interfere, by chemotactic gradient formation, with the brain infiltration program of blood-derived cells during development or brain injury. (c) 2005 Wiley-Uss, Inc. C1 Coll France, Chaire Neuropharmacol, INSERM, U114, F-75231 Paris, France. NCI, Immunopathol Sect, Immunobiol Lab, Frederick, MD 21701 USA. RP Calvo, CF (reprint author), Coll France, Chaire Neuropharmacol, INSERM, U114, F-75231 Paris, France. EM charles-felix.calvo@college-de-france.fr NR 31 TC 8 Z9 8 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0360-4012 J9 J NEUROSCI RES JI J. Neurosci. Res. PD JUN 1 PY 2005 VL 80 IS 5 BP 707 EP 714 DI 10.1002/jnr.20511 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 931KS UT WOS:000229484800012 PM 15880558 ER PT J AU Fiala, M Eshleman, AJ Cashman, J Lin, J Lossinsky, AS Suarez, V Yang, W Zhang, J Popik, W Singer, E Chiappelli, F Carro, E Weinand, M Witte, M Arthos, J AF Fiala, M Eshleman, AJ Cashman, J Lin, J Lossinsky, AS Suarez, V Yang, W Zhang, J Popik, W Singer, E Chiappelli, F Carro, E Weinand, M Witte, M Arthos, J TI Cocaine increases human immunodeficiency virus type 1 neuroinvasion through remodeling brain microvascular endothelial cells SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE cocaine; brain microvascular endothelial cells; HIV-1; HIV-1 macropinocytosis ID AIDS DEMENTIA COMPLEX; SEROTONIN TRANSPORTER; HIV; INFECTION; INVASION; BARRIER; ABUSE; PHOSPHORYLATION; LOCALIZATION; PERMEABILITY AB Cocaine is a suspected cofactor in human immunodeficiency virus (HIV)-associated dementia but cocaine's effects are not clear. Herein the authors describe investigations of the mechanisms by which cocaine increases HIV-1 invasion through brain microvascular endothelial cells (BMVECs). Cocaine binds to a site on BMVECs, which is not a biogenic amine transporter, a binding site for estrogen, or a muscarinic receptor and for which benztropine and tamoxifen have the highest affinity. Cocaine treatment of BMVECs disrupts intercellular junctions and induces cell ruffling, which could account for their increased permeability and decreased electrical resistance. HIV-1 enters BMVECs by macropinocytosis and is transported to lysosomes and inactivated. In cocaine-treated BMVECs, the virus enters and persists in large cytoplasmic "lakes." Cocaine exposure of BMVECs up-regulates transcription of genes important in cytoskeleton organization, signal transduction, cell swelling, vesicular trafficking, and cell adhesion. The toxicity of cocaine for the blood-brain barrier may lead to increased virus neuroinvasion and neurovascular complications of cocaine abuse. C1 Univ Calif Los Angeles, Sch Med, Dept Neurol, Los Angeles, CA 90095 USA. W Los Angeles Vet Affairs Med Ctr, Dept Med, Los Angeles, CA 90073 USA. VA Med Ctr, Dept Pharmacol, Portland, OR USA. Human Biomol Res Inst, San Diego, CA USA. Huntington Med Res Inst, Pasadena, CA USA. Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA. CSIC, Inst Cajal, Neuroendocrinol Lab, E-28002 Madrid, Spain. Univ Arizona, Dept Surg, Tucson, AZ USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. RP Fiala, M (reprint author), Univ Calif Los Angeles, Sch Med, Dept Neurol, CHS 63-090,10833 Le Conte, Los Angeles, CA 90095 USA. EM Fiala@ucla.edu FU NHLBI NIH HHS [HL48493, HL63639]; NIAID NIH HHS [AI42557, AI50461]; NIDA NIH HHS [DA10442]; PHITPO CDC HHS [HK63065] NR 34 TC 42 Z9 46 U1 2 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD JUN PY 2005 VL 11 IS 3 BP 281 EP 291 DI 10.1080/13550280590952835 PG 11 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 945LS UT WOS:000230504600006 PM 16036808 ER PT J AU Walsh, MC Morris, BH Wrage, LA Vohr, BR Poole, WK Tyson, JE Wright, LL Ehrenkranz, RA Stoll, BJ Fanaroff, AA AF Walsh, MC Morris, BH Wrage, LA Vohr, BR Poole, WK Tyson, JE Wright, LL Ehrenkranz, RA Stoll, BJ Fanaroff, AA CA Natl Inst Child Hlth Neonatal Res Network Natl Inst Human Dev Neonatal Res Network TI Extremely low birthweight neonates with protracted ventilation: Mortality and 18-month neurodevelopmental outcomes SO JOURNAL OF PEDIATRICS LA English DT Article ID CHRONIC LUNG-DISEASE; POSTNATAL CORTICOSTEROIDS; PROLONGED VENTILATION; NATIONAL INSTITUTE; PREMATURE-INFANT; RESEARCH NETWORK; INTENSIVE-CARE; CHILD HEALTH; RISK; SURVIVAL AB Objective To compare duration of ventilation to mortality and adverse neurodevelopmental outcomes among extremely low birth weight (ELBW; 501-1000 g) infants. Study design Retrospective analysis of prospectively collected data from 5364 infants with a birth weight of 501 to 1000 g born at National Institute of Child Health and Human Development (NICHD) Neonatal Research Network centers from 1995 to 1998. The main outcome measures were: survival, duration of mechanical ventilation, and neurodevelopmental-outcome. Results Overall survival was 71%. The median duration of ventilation for survivors was 23 days; 75% were free of mechanical ventilation by 39 days, and 7% were ventilated for >= 60 days. Of those ventilated for >= 60 days, 24% survived without impairment. Of those ventilated for >= 90 days, only 7% survived without impairment. Of those ventilated >= 120 days, all survivors were impaired. Conclusions The prognosis for ELBW with protracted ventilation remains grim. The cohort who remain intubated have diminished survival and high rates of impairment. Parents of these infants should be informed of changes in prognosis as the time of ventilation increases. C1 Case Western Reserve Univ, Dept Pediat, Cleveland, OH 44106 USA. Univ Texas, Hlth Sci Ctr, Sch Med, Houston, TX USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Brown Univ, Dept Pediat, Providence, RI 02912 USA. NICHHD, Bethesda, MD 20892 USA. Yale Univ, Dept Pediat, Sch Med, New Haven, CT 06520 USA. Emory Univ, Dept Pediat, Atlanta, GA 30322 USA. RP Walsh, MC (reprint author), Rainbow Babies & Childrens Hosp, Mailstop 6010,11100 Euclid Ave, Cleveland, OH 44106 USA. EM mcw3@po.cwru.edu FU NCRR NIH HHS [M01 RR 00997, M01 RR 00070, M01 RR 00750, M01 RR 06022, M01 RR08084]; NICHD NIH HHS [U01 HD36790, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21397, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27856, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD34216] NR 22 TC 113 Z9 115 U1 0 U2 2 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 JUN PY 2005 VL 146 IS 6 BP 798 EP 804 DI 10.1016/j.jpeds.2005.01.047 PG 7 WC Pediatrics SC Pediatrics GA 941BB UT WOS:000230188500021 PM 15973322 ER PT J AU McCrae, RR Costa, PT Martin, TA AF McCrae, RR Costa, PT Martin, TA TI The NEO-PI-3: A more readable revised NEO Personality Inventory SO JOURNAL OF PERSONALITY ASSESSMENT LA English DT Article ID 5-FACTOR MODEL; ACADEMIC-PERFORMANCE; PI-R; TRAITS; VALIDATION; CULTURES AB Use of the Revised NEO Personality Inventory (NEO-PI-R; Costa & McCrae, 1992) in adolescent samples has shown that a few respondents have difficulty with a subset of items. We identified 30 items that were not understood by at least 2% of adolescent respondents and 18 additional items with low item-total correlations, and we wrote 2 trial replacement items for each. We used self-report and observer rating data from 500 respondents aged 14 to 20 to select replacement items. The modified instrument retained the intended factor structure and showed slightly better internal consistency, cross-observer agreement, and readability (Flesch-Kincaid grade level = 5.3). The NEO-PI-3 appears to be useful in high school and college samples and may have wider applicability to adults as well. C1 NIA, Dept Hlth & Human Serv, NIH, Baltimore, MD 21224 USA. Susquehanna Univ, Dept Psychol, Selinsgrove, PA 17870 USA. RP McCrae, RR (reprint author), Gerontol Res Ctr, 5600 Nathan Shock Dr,Box 03, Baltimore, MD 21224 USA. EM mccraej@grc.nia.nih.gov OI Costa, Paul/0000-0003-4375-1712 NR 26 TC 101 Z9 103 U1 10 U2 72 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0022-3891 J9 J PERS ASSESS JI J. Pers. Assess. PD JUN PY 2005 VL 84 IS 3 BP 261 EP 270 DI 10.1207/s15327752jpa8403_05 PG 10 WC Psychology, Clinical; Psychology, Social SC Psychology GA 929JR UT WOS:000229342900005 PM 15907162 ER PT J AU Feinberg, EC Bromer, JG Catherino, WH AF Feinberg, EC Bromer, JG Catherino, WH TI The evolution of in vitro fertilization: Integration of pharmacology, technology, and clinical care SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID FOLLICLE-STIMULATING-HORMONE; GONADOTROPIN-RELEASING-HORMONE; LUTEAL-PHASE SUPPORT; HUMAN MENOPAUSAL GONADOTROPINS; MATERNAL-FETAL INTERFACE; APPARENTLY PURE FSH; INVITRO FERTILIZATION; ASSISTED REPRODUCTION; GNRH-AGONIST; OVARIAN HYPERSTIMULATION AB For the couple having trouble achieving pregnancy, the options and opportunities for assistance have never been brighter. Options such as controlled ovarian hyperstimulation, in vitro fertilization, and intracytoplasmic sperm injection have been developed over the past five decades and provide hope for couples that previously would have been considered infertile. In vitro fertilization and intracytoplasmic sperm injection represent a coalescence of advances in physiology, endocrinology, pharmacology, technology, and clinical care. In vitro fertilization has assisted well over one million couples in their efforts to start or build a family, and the demand for such services continues to increase. The purpose of this manuscript is to review the pharmacological advances that made controlled ovarian hyperstimulation, and therefore in vitro fertilization and intracytoplasmic sperm injection, possible. We will discuss the early stages of gonadotropin use to stimulate ovarian production of multiple mature eggs, the advances in recombinant technology that allowed purified hormone for therapy, and the use of other hormones to regulate the menstrual cycle such that the likelihood of successful oocyte retrieval and embryo implantation is optimized. Finally, we will review current areas that require particular attention if we are to provide more opportunity for infertile couples. C1 Uniformed Serv Univ Hlth Sci, Dept Obstet & Gynecol, Bethesda, MD 20814 USA. NIH, Combined Fed Fellowship Reprod Endocrinol & Ferti, Bethesda, MD 20892 USA. Georgetown Univ, Georgetown Univ Hosp, Pasquerilla Healthcare Ctr, Dept Obstet & Gynecol, Washington, DC USA. RP Catherino, WH (reprint author), Bldg A,Room 3077,4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM catheriw@mail.nih.gov NR 62 TC 1 Z9 1 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 JUN PY 2005 VL 313 IS 3 BP 935 EP 942 DI 10.1124/jpet.104.080051 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 927OM UT WOS:000229203200001 PM 15769869 ER PT J AU Gautam, D Han, SJ Heard, TS Cui, YH Miller, G Bloodworth, L Wess, J AF Gautam, D Han, SJ Heard, TS Cui, YH Miller, G Bloodworth, L Wess, J TI Cholinergic stimulation of amylase secretion from pancreatic acinar cells studied with muscarinic acetylcholine receptor mutant mice SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID KNOCKOUT MICE; EXOCRINE SECRETION; DEFICIENT MICE; SUBTYPES; EXPRESSION; RESPONSES; LACKING; SERUM; M-1; M1 AB Muscarinic acetylcholine receptors (mAChRs) expressed by pancreatic acinar cells play an important role in mediating acetylcholine-dependent stimulation of digestive enzyme secretion. To examine the potential roles of M-1 and M-3 mAChRs in this activity, we used M-1 and M-3 receptor single knockout (KO) and M-1/M-3 receptor double KO mice as novel experimental tools. Specifically, we examined the ability of the muscarinic agonist carbachol to stimulate amylase secretion in vitro, using dispersed pancreatic acini prepared from wild-type and mAChR mutant mice. Quantitative reverse transcription-polymerase chain reaction studies using RNA prepared from mouse pancreatic acini showed that deletion of the M-1 or M-3 mAChR genes did not lead to significantly altered mRNA levels of the remaining mAChR subtypes. Moreover, immunoprecipitation studies with M-1 and M-3 mAChR-selective antisera demonstrated that both mAChR subtypes are expressed by mouse pancreatic acini. Strikingly, carbachol-induced stimulation of amylase secretion was significantly impaired in acinar preparations from both M-1 and M-3 receptor single KO mice and abolished in acinar preparations from M-1/M-3 receptor double KO mice. However, another pancreatic secretagogue, bombesin, retained its ability to fully stimulate amylase secretion in acinar preparations from M-1/M-3 receptor double KO mice. Together, these studies support the concept that cholinergic stimulation of pancreatic amylase secretion is mediated by a mixture of M-1 and M-3 mAChRs and that other mAChR subtypes do not make a significant contribution to this activity. These findings clarify the long-standing question regarding the molecular nature of the mAChR subtypes mediating the secretion of digestive enzymes from the exocrine pancreas. C1 NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. NIH, Div Vet Resources, Off Res Serv, Bethesda, MD 20892 USA. RP Wess, J (reprint author), NIDDKD, Mol Signaling Sect, Bioorgan Chem Lab, NIH, Bldg 8A,Room B1A-05,8 Ctr Dr,MSC 0810, Bethesda, MD 20892 USA. EM jwess@helix.nih.gov RI Han, Sung-Jun/B-9547-2012 NR 44 TC 31 Z9 31 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 2005 VL 313 IS 3 BP 995 EP 1002 DI 10.1124/jpet.105.084855 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 927OM UT WOS:000229203200006 PM 15764735 ER PT J AU Li, SM Newman, AH Katz, JL AF Li, SM Newman, AH Katz, JL TI Place conditioning and locomotor effects of N-substituted, 4 ',4 ''-difluorobenztropine analogs in rats SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID RHESUS-MONKEYS; DOPAMINE TRANSPORTER; COCAINE REINFORCEMENT; BENZTROPINE ANALOGS; UPTAKE INHIBITORS; IN-VITRO; PREFERENCE; INJECTION; LIGANDS; BINDING AB Previous studies demonstrated that analogs of benztropine [3 alpha-(diphenyl-methoxy)tropane (BZT)] bind to the dopamine (DA) transporter with high affinity, inhibit DA uptake, but do not maintain rates of responding in self-administration procedures comparable with those maintained by cocaine. Some BZT analogs have an onset of action that is slower than that for cocaine that may contribute to this decreased effectiveness. In addition, some BZT analogs have affinity for muscarinic-M1 receptors that may interfere with reinforcing effects. The present study assessed effects of BZT analogs in place-conditioning procedures designed to accommodate variations in onset of effect. BZT analogs with variations in relative affinities for the DA transporter over M1 receptors from equal [AHN 1-055 (3 alpha-[bis(4'- fluorophenyl)methoxy]-tropane)] to 16-fold [JHW 007 (N-(n-butyl)-3 alpha-[bis(4'-fluorophenyl) methoxy]-tropane)] were compared with cocaine and the muscarinic antagonist, atropine. Cocaine (10 - 20 mg/kg) but not atropine (1.0 - 5.6 mg/kg) produced dose-related place conditioning. The N-methyl-substituted BZT analog, AHN 1-055, was without significant effects at doses that ranged from 0.3 to 3.0 mg/kg and when administered up to 90 min before conditioning trials. In contrast, effects of AHN 2-005 (N-allyl-3 alpha-[bis(4'-fluorophenyl)methoxy]-tropane; 0.1 - 10.0 mg/ kg) were significant, and those of JHW 007 approached significance when administered 45 min but not immediately or 90 min before trials. Atropine blocked the effect of AHN 2-005 and approached significant antagonism of cocaine. The present study further supports and extends previous results showing minimal preclinical indications of abuse liability of BZT analogs and suggests that these differences from cocaine are not entirely accounted for by a slower onset of action or muscarinic M1 receptor affinity. C1 NIDA, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. NIDA, Med Chem Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH, Baltimore, MD 21224 USA. RP Katz, JL (reprint author), NIDA, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM jkatz@intra.nida.nih.gov OI Katz, Jonathan/0000-0002-1068-1159 NR 37 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 2005 VL 313 IS 3 BP 1223 EP 1230 DI 10.1124/jpet.105.084541 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 927OM UT WOS:000229203200031 PM 15743929 ER PT J AU Oz, M Jackson, SN Woods, AS Morales, M Zhang, L AF Oz, M Jackson, SN Woods, AS Morales, M Zhang, L TI Additive effects of endogenous cannabinoid anandamide and ethanol on alpha(7)-nicotinic acetylcholine receptor-mediated responses in Xenopus oocytes SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID T-TUBULE MEMBRANES; RECTIFYING POTASSIUM CHANNELS; DEPENDENT CALCIUM FLUXES; ACID ETHYL-ESTERS; DIRECT INHIBITION; ARACHIDONIC-ACID; HUMAN BRAIN; ENDOCANNABINOID CONTENTS; SYNTHETIC CANNABINOIDS; CA2+ FLUXES AB The interaction between the effects of the endogenous cannabinoid receptor agonist anandamide and ethanol on the function of homomeric alpha(7)-nicotinic acetylcholine (nACh) receptors expressed in Xenopus oocytes were investigated using the two-electrode voltage-clamp technique. Anandamide and ethanol reversibly inhibited currents evoked with 100 mu M acetylcholine in a concentration-dependent manner. Coapplication of anandamide and ethanol caused a significantly greater inhibition of alpha(7)-nACh receptor function than anandamide or ethanol alone. The IC50 value of 238 +/- 34 nM for anandamide inhibition decreased significantly to 104 +/- 23 nM in the presence of 30 mM ethanol. The inhibition of alpha(7)-mediated currents by co-application of anandamide and ethanol was not altered by phenylmethylsulfonyl fluoride, an inhibitor of anandamide hydrolyzing enzyme, or N-(4-hydroxyphenyl)- arachidonylamide, an anandamide transport inhibitor. Analysis of oocytes by matrix-assisted laser desorption/ionization technique indicated that ethanol treatment did not alter the lipid profile of oocytes, and there is negligible, if any, anandamide present in these cells. Results of studies with chimeric alpha(7)-nACh-5-HT3 receptors comprised of the amino-terminal domain of the alpha(7)-nACh receptor and the transmembrane and carboxyl-terminal domains of 5-HT3 receptors suggest that although ethanol inhibition of the alpha(7)-nACh receptor is likely to involve the N-terminal region of the receptor, the site of action for anandamide is located in the transmembrane and carboxyl-terminal domains of the receptors. These data indicate that endocannabinoids and ethanol potentiate each other's inhibitory effects on alpha(7)-nACh receptor function through distinct regions of the receptor. C1 NIDA, Intramural Res Program, Cellular Neurobiol Branch, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. NIAAA, NIH, Dept Hlth & Human Serv, Mol & Cellular Neurobiol Lab, Bethesda, MD USA. RP Oz, M (reprint author), NIDA, Intramural Res Program, Cellular Neurobiol Branch, NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM moz@intra.nida.nih.gov RI Oz, Murat/E-2148-2012 NR 54 TC 13 Z9 14 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 2005 VL 313 IS 3 BP 1272 EP 1280 DI 10.1124/jpet.104.01315 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 927OM UT WOS:000229203200037 PM 15687372 ER PT J AU Rothman, RB Blough, BE Woolverton, WL Anderson, KG Negus, SS Mello, NK Roth, BL Baumann, MH AF Rothman, RB Blough, BE Woolverton, WL Anderson, KG Negus, SS Mello, NK Roth, BL Baumann, MH TI Development of a rationally designed, low abuse potential, biogenic amine releaser that suppresses cocaine self-administration SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID D-AMPHETAMINE TREATMENT; RHESUS-MONKEYS; 5-HT2B RECEPTORS; D-FENFLURAMINE; RAT-BRAIN; SEROTONIN; PHENTERMINE; DEPENDENCE; ADDICTION; DOPAMINE AB Convergent lines of evidence support a dual deficit model of stimulant withdrawal, where reductions in synaptic dopamine (DA) and 5-hydroxytryptamine (serotonin) (5-HT) contribute to dysphoria, drug craving, and relapse. Thus, we predicted that a nonamphetamine compound with substrate activity at DA and 5-HT transporters (i.e., a dual DA/5-HT releaser) would be an effective medication for treating stimulant addictions. Ideally, this type of medication would alleviate withdrawal symptoms, suppress cocaine self-administration, and lack side effects commonly associated with central nervous system stimulants. In the present work, more than 350 compounds were screened in vitro for activity as substrate-type releasing agents at DA, 5-HT, and norepinephrine transporters. These efforts identified PAL-287 (1-napthyl-2-aminopropane) as a nonamphetamine compound with potent substrate activity at biogenic amine transporters. In vivo microdialysis in rats demonstrated that PAL-287 (1-3 mg/kg i.v.) increased extracellular DA and 5-HT in frontal cortex, but effects on 5-HT were somewhat greater. PAL-287 induced substantially less locomotor stimulation than (+)-amphetamine, a drug that increases only extracellular DA. Administration of high-dose(+)-methamphetamine or (+)-3,4-methylenedioxymethamphetamine to rats produced long-lasting depletion of cortical 5-HT, whereas PAL-287 (18 mg/kg i.p. x 3) did not. PAL-287 displayed little or no reinforcing properties in rhesus monkeys trained to self-administer cocaine, yet PAL-287 produced a dose-dependent decrease in responding for cocaine when infused at a dose of 1.0 mg/kg/h. Collectively, the findings reported here demonstrate that nonamphetamine monoamine releasing agents such as PAL-287 might be promising candidate medications for the treatment of stimulant dependence. C1 Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. Res Triangle Inst Int, Chem & Life Sci Grp, Res Triangle Pk, NC USA. Univ Mississippi, Med Ctr, Dept Pharmacol & Psychiat, Jackson, MS 39216 USA. Harvard Univ, Sch Med, Alcohol & Drug Abuse Res Ctr, McLean Hosp, Belmont, MA 02178 USA. Case Western Reserve Univ, NIMH, Psychoact Drug Screening Program, Sch Med, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Biochem, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Neurosci, Cleveland, OH 44106 USA. Case Western Reserve Univ, Sch Med, Dept Psychiat, Cleveland, OH 44106 USA. RP Rothman, RB (reprint author), Natl Inst Drug Abuse, Clin Psychopharmacol Sect, Intramural Res Program, NIH,Dept Hlth & Human Serv, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM rrothman@intra.nida.nih.gov RI Roth, Bryan/F-3928-2010 FU NIDA NIH HHS [R01 DA-10352, DA02519, K05-DA00101, K05-DA15343, P01-DA14528, R01 DA12970] NR 53 TC 65 Z9 66 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUN PY 2005 VL 313 IS 3 BP 1361 EP 1369 DI 10.1124/jpet.104.082503 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 927OM UT WOS:000229203200048 PM 15761112 ER PT J AU Rudd, RE Horowitz, AM AF Rudd, RE Horowitz, AM TI Health and literacy: Supporting the oral health research agenda SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Editorial Material ID CANCER EDUCATIONAL-MATERIALS C1 NIDCR, NIH, Bethesda, MD 20892 USA. Harvard Sch Publ Hlth, Dept Soc Human Dev & Hlth, Boston, MA USA. RP Horowitz, AM (reprint author), NIDCR, NIH, Bldg 45,Rm 4AS27A, Bethesda, MD 20892 USA. EM Alice.Horowitz@nih.gov NR 12 TC 6 Z9 6 U1 0 U2 4 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD SUM PY 2005 VL 65 IS 3 BP 131 EP 132 DI 10.1111/j.1752-7325.2005.tb02801.x PG 2 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 955GA UT WOS:000231212400003 PM 16171256 ER PT J AU Baur, CE Comings, JP Evans, C Garcia, R Horowitz, AM Ismail, AI Kenyon, DM Kirsch, IS Kleinman, DV Rudd, RE Strucker, J Taylor, GW White, KK AF Baur, CE Comings, JP Evans, C Garcia, R Horowitz, AM Ismail, AI Kenyon, DM Kirsch, IS Kleinman, DV Rudd, RE Strucker, J Taylor, GW White, KK CA Natl Inst Dent Craniofacial Res US Publ Hlth Serv TI The invisible barrier: Literacy and its relationship with oral health SO JOURNAL OF PUBLIC HEALTH DENTISTRY LA English DT Article DE oral health; dental health; literacy; health literacy; health communications AB Although oral health in the United States has improved significantly over time, preventable and treatable oral diseases remain common, especially among the poor and underserved. Limited literacy skills among adults are hypothesized to be one of many barriers to better oral health outcomes. Adults must be able to understand, interpret, and act on health information, whether it is communicated in spoken or in written form, to maintain their oral health and manage disease. While the body of health literacy research has grown in recent years, little is known about oral health literacy. Research is needed to build an understanding of oral health literacy and its impact on a variety of outcomes, including adoption of effective disease prevention regimens and actions, adherence to treatment regimens, effectiveness of caregivers and ultimately, improved oral health status. In addition, the effect of oral health literacy on the validity of clinical research such as response to surveys and adherence to research protocols is another area that is important to investigate. This paper defines oral health literacy and offers a framework for studying relationships between oral health literacy and other points of intervention for improving health outcomes. Findings of existing health literacy research are summarized, and a research plan for oral health literacy is proposed. A broad-based collaborative effort will be required to develop a detailed agenda for research, one that is aimed at reducing literacy barriers to oral health and ensuring that the information and insights emanating from new oral health research are more widely adopted. C1 Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. US PHS, Dept Hlth & Human Serv, Washington, DC USA. RP Baur, CE (reprint author), Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD 20892 USA. NR 22 TC 5 Z9 5 U1 1 U2 5 PU AAPHD NATIONAL OFFICE PI PORTLAND PA 3760 SW LYLE COURT, PORTLAND, OR 97221 USA SN 0022-4006 J9 J PUBLIC HEALTH DENT JI J. Public Health Dent. PD SUM PY 2005 VL 65 IS 3 BP 174 EP 182 PG 9 WC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health SC Dentistry, Oral Surgery & Medicine; Public, Environmental & Occupational Health GA 955GA UT WOS:000231212400010 ER PT J AU Bourdon, KH Goodman, R Rae, DS Simpson, G Koretz, DS AF Bourdon, KH Goodman, R Rae, DS Simpson, G Koretz, DS TI The strengths and difficulties questionnaire: US normative data and psychometric properties SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE questionnaire; psychopathology; normative banding; epidemiology ID COMMUNITY SAMPLE; SWEDISH VERSION; CHILD; SDQ; ADOLESCENTS; VALIDATION AB To evaluate the Strengths and Difficulties Questionnaire in a U.S. national population sample of children and adolescents, develop normative scoring bands, and test the association of high-scoring groups with service contacts or use for mental health reasons. Method: An Americanized version of the Strengths and Difficulties Questionnaire parent report was administered to parents of 10,367 4-to 17-year-olds in the 2001 National Health Interview Survey. Scoring bands were developed to differentiate low, medium, and high levels of emotional or behavioral difficulties. Children at high risk of serious difficulties were identified by three different scoring methods: (1) high symptom scores, (2) parental perception of definite or severe difficulties, and (3) high symptoms plus impairment. These ratings were validated against service contact or use and other well-established demographic and broader risk factors for child emotional and behavioral problems. Results: Results indicated good acceptability and internal consistency. Normative scoring bands were similar, though not identical, to the original British bands. Results of each scoring method had a strong association with service contact/use. Conclusions: This study supports the usefulness of the Strengths and Difficulties Questionnaire as an effective and efficient screener for child and adolescent mental health problems in the United States. C1 NIMH, Div Pediat Translant Res & Treatment Dev, Psychosocial Stress & Related Disorders Branch, Bethesda, MD 20892 USA. Natl Ctr Hlth Stat, Hyattsville, MD USA. Harvard Univ, Off Provast, Boston, MA USA. Kings Coll London, Inst Psychiat, London, England. RP Bourdon, KH (reprint author), NIMH, Div Pediat Translant Res & Treatment Dev, Psychosocial Stress & Related Disorders Branch, 6001 Execut Blvd,Room 6198,MSC 9617, Bethesda, MD 20892 USA. EM kbourdon@mail.nih.gov NR 27 TC 203 Z9 208 U1 5 U2 52 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 JUN PY 2005 VL 44 IS 6 BP 557 EP 564 DI 10.1097/01.chi.0000159157.57075.c8 PG 8 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 928BH UT WOS:000229245600010 PM 15908838 ER PT J AU Pihlstrom, BL Tabak, L AF Pihlstrom, BL Tabak, L TI The National Institute of Dental and Craniofacial Research - Research for the practicing dentist SO JOURNAL OF THE AMERICAN DENTAL ASSOCIATION LA English DT Article DE National Institute of Dental and Craniofacial Research; dental practitioner; oral health research ID LOW-BIRTH-WEIGHT; DEPENDENT DIABETES-MELLITUS; CORONARY-HEART-DISEASE; C-REACTIVE PROTEIN; PERIODONTAL-DISEASE; PRETERM BIRTH; SALIVARY-GLANDS; CARDIOVASCULAR-DISEASE; NOSOCOMIAL INFECTIONS; AFFERENT NEURONS AB Background and Overview Established in 1948 the National Institute of Dental and Craniofacial Research (NIDCR) has helped transform dentistry into a profession that is based firmly in prevention and technological innovation. This article introduces the new NIDCR intiative in general dentistry practice-based research. It also highlights research supported by the NIDCR and its implications for dental practice in restorative dentistry oral and systemic disease, stem cell research, salivary diagnostics, gene transfer, therapy and pain. Clinical Implications. The NIDCR supports research that will help guide the practitioner in the delivery of patient care and have a direct impact on the practice of dentistry. C1 Natl Inst Dent & Cranofacial Res, Div Clin Res & Hlth Promot, Bethesda, MD 20892 USA. RP Pihlstrom, BL (reprint author), Natl Inst Dent & Cranofacial Res, Div Clin Res & Hlth Promot, 4AS43G,45 Ctr Dr, Bethesda, MD 20892 USA. EM bruce.pihlstrom@nih.gov NR 60 TC 14 Z9 16 U1 0 U2 3 PU AMER DENTAL ASSN PI CHICAGO PA 211 E CHICAGO AVE, CHICAGO, IL 60611 USA SN 0002-8177 J9 J AM DENT ASSOC JI J. Am. Dent. Assoc. PD JUN PY 2005 VL 136 IS 6 BP 728 EP 737 PG 10 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 936MQ UT WOS:000229860500009 PM 16022037 ER PT J AU Affenito, SG Thompson, DR Barton, BA Franko, DL Daniels, SR Obarzanek, E Schreiber, GB Striegel-Moore, RH AF Affenito, SG Thompson, DR Barton, BA Franko, DL Daniels, SR Obarzanek, E Schreiber, GB Striegel-Moore, RH TI Breakfast consumption by African-American and white adolescent girls correlates positively with calcium and fiber intake and negatively with body mass index SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID NEW-YORK-STATE; PHYSICAL-ACTIVITY; DIETARY-INTAKE; EATING PATTERNS; MEAL PATTERNS; CHILDREN; STUDENTS; HEALTH; SCHOOLCHILDREN; ASSOCIATIONS AB Objective To describe age- and race-related differences in breakfast consumption and to examine the association of breakfast intake with dietary calcium and fiber and body mass index (BMI). Design Data from the National Heart, Lung, and Blood Institute Growth and Health Study, a 9-year, longitudinal biracial cohort study with annual 3-day food records. Subjects/setting The National Heart, Lung, and Blood Institute Growth and Health Study recruited 2,379 girls (1,166 white and 1,213 African American), aged 9 or 10 years at baseline for an observational study. Retention rates were very high at visits two through four (96%, 94%, and 91%), but declined to a low of 82% at visit seven, and increased to 89% at visit 10. Main outcome measures Frequency of breakfast consumption, dietary calcium and fiber, and BMI. Statistical analyses Generalized estimation equations methodology was used to examine differences in the frequency of breakfast eating by age and race. Generalized estimation equations analyses were also conducted to test whether breakfast consumption was predictive of intake of dietary calcium and fiber, and BMI, adjusting for potentially confounding effects of site, age, race, parental education, physical activity, and total energy intake. Results Frequency of breakfast eating declined with age, white girls reported more frequent breakfast consumption than African-American girls, and the racial difference decreased with increasing age. Days eating breakfast were associated with higher calcium and fiber intake in all models, regardless of adjustment variables. Days eating breakfast were predictive of lower BMI in models that adjusted for basic demographics (ie, site, age, and race), but the independent effect of breakfast was no longer significant after parental education, energy intake, and physical activity were added to the model. Conclusions Dietetics professionals need to promote the importance of consuming breakfast to all children and adolescents, especially African-American girls. C1 Wesleyan Univ, Dept Psychiat, Middletown, CT 06459 USA. St Joseph Coll, Dept Nutr, Hartford, CT USA. Maryland Med Res Inst, Baltimore, MD USA. Northeastern Univ, Dept Counseling & Educ Psychol, Boston, MA 02115 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. NHLBI, Prevent Sci Res Grp, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Westat Corp, Rockville, MD USA. RP Striegel-Moore, RH (reprint author), Wesleyan Univ, Dept Psychiat, 207 High St, Middletown, CT 06459 USA. EM rstriegel@wesleyan.edu OI Barton, Bruce/0000-0001-7878-8895 FU NHLBI NIH HHS [HC55023-26, HL/DK71122, U01-HL-48941-44] NR 29 TC 108 Z9 111 U1 0 U2 5 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUN PY 2005 VL 105 IS 6 BP 938 EP 945 DI 10.1016/j.jada.2005.03.003 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 932PN UT WOS:000229565900013 PM 15942545 ER PT J AU Fenton, RA Flynn, A Shodeinde, A Smith, CP Schnermann, J Knepper, MA AF Fenton, RA Flynn, A Shodeinde, A Smith, CP Schnermann, J Knepper, MA TI Renal phenotype of UT-A urea transporter knockout mice SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID NEPHROGENIC DIABETES-INSIPIDUS; COUNTERCURRENT MULTIPLICATION; GLOMERULAR-FILTRATION; CONCENTRATING DEFECT; PROXIMAL TUBULE; COLLECTING DUCT; RAT; MICROPUNCTURE; SECRETION; EXCRETION AB The urea transporters UT-A1 and UT-A3 mediate rapid transepithelial urea transport across the inner medullary collecting duct (IMCD). In a previous study, using a new mouse model in which both UT-A1 and UT-A3 were genetically deleted from the IMCD (UT-A1/3(-/-) mice), we investigated the role of these transporters in the function of the renal inner medulla. Here the authors report a new series of studies investigating more generally the renal phenotype of UT-A1/3(-/-) mice. Pathologic screening of 33 tissues revealed abnormalities in both the testis (increased size) and kidney (decreased size and vascular congestion) of UT-A1/3(-/-) mice. Total urinary nitrate and nitrite (NOx) excretion rates in UT-A1/3(-/-) mice were more than double those in wild-type mice. Total renal blood flow was not different between UT-A1/3(-/-) and wild-type mice but underwent a greater percentage decrease in response to NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME) infusion. Whole kidney GFR (FITC-inulin clearance) was not different in UT-A1/3(-/-) mice compared with controls and underwent a similar increase in response to a greater dietary protein intake. Fractional urea excretion was markedly elevated in UT-A1/3(-/-) mice on a 40% protein diet, reaching 102.4 +/- 8.8% of the filtered load, suggesting that there may be active urea secretion somewhere along the renal tubule. Although there was a marked urinary concentrating defect in UT-A1/3(-/-) mice, there was no decrease in aquaporin 2 or aquaporin 3 expression. Furthermore, although urea accumulation in the inner medulla was markedly attenuated, there was no decrease in sodium ion concentration in tissue from outer medulla or two levels of the inner medulla. These results support our conclusion that the urinary concentrating defect in UT-A1/3(-/-) mice is caused by a failure of urea transport from the IMCD lumen to the inner medullary interstitium, resulting in osmotic diuresis. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. Univ Manchester, Sch Biol Sci, Manchester, Lancs, England. NIDDKD, NIH, Bethesda, MD 20892 USA. RP Fenton, RA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, 10 Ctr Dr,Bldg 10,Room 6N260, Bethesda, MD 20892 USA. EM fentonr@nhlbi.nih.gov FU Intramural NIH HHS [Z99 HL999999, Z01 HL001285-21] NR 40 TC 69 Z9 71 U1 2 U2 5 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2005 VL 16 IS 6 BP 1583 EP 1592 DI 10.1681/ASN.2005010031 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA 930CR UT WOS:000229393900009 PM 15829709 ER PT J AU Plisov, S Tsang, M Shi, GB Boyle, S Yoshino, K Dunwoodie, SL Dawid, IB Shioda, T Perantoni, AO de Caestecker, MP AF Plisov, S Tsang, M Shi, GB Boyle, S Yoshino, K Dunwoodie, SL Dawid, IB Shioda, T Perantoni, AO de Caestecker, MP TI Cited1 is a bifunctional transcriptional cofactor that regulates early nephronic patterning SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID HYPOXIA-INDUCIBLE FACTOR-1-ALPHA; PAPILLARY THYROID-CARCINOMA; MELANOCYTE-SPECIFIC GENE; BETA-CATENIN; METANEPHRIC MESENCHYME; PROTEIN TRANSDUCTION; EARLY ORGANOGENESIS; SIGNALING PATHWAYS; RENAL DEVELOPMENT; MAMMALIAN-CELLS AB In a screen to identify factors that regulate the conversion of mesenchyme to epithelium during the early stages of nephrogenesis, it was found that the Smad4-interacting transcriptional cofactor, Cited1, is expressed in the condensed cap mesenchyme surrounding the tip of the ureteric bud (UB), is downregulated after differentiation into epithelia, and has the capacity to block UB branching and epithelial morphogenesis in cultured metanephroi. Cited1 represses Wnt/beta-catenin but activates Smad4-dependent transcription involved in TGF-beta and Bmp signaling. By modifying these pathways, Cited1 may coordinate cellular differentiation and survival signals that regulate nephronic patterning in the metanephros. C1 Vanderbilt Univ, Div Nephrol, Sch Med, Nashville, TN 37232 USA. NCI, Comparat Carcinogenesis Lab, Frederick, MD 21701 USA. NICHD, Genet Mol Lab, Bethesda, MD USA. St Vincents Hosp, Victor Chang Cardiac Res Inst, Dev Biol Program, Darlinghurst, NSW 2010, Australia. Univ New S Wales, Dept Biotechnol & Biomol Sci, Kensington, NSW 2033, Australia. Univ New S Wales, St Vincents Clin Sch, Kensington, NSW 2033, Australia. Massachusetts Gen Hosp, Ctr Canc, Dept Tumor Biol, Charlestown, MA USA. RP de Caestecker, MP (reprint author), Vanderbilt Univ, Div Nephrol, Sch Med, S3223 Med Ctr,N 21st St S, Nashville, TN 37232 USA. EM mark.de.caestecker@vanderbilt.edu RI TSANG, Michael/E-2758-2013; Tsang, Michael/I-9305-2014; OI TSANG, Michael/0000-0001-6384-2422; Tsang, Michael/0000-0001-7123-0063; Dunwoodie, Sally/0000-0002-2069-7349 FU NCI NIH HHS [1P30 CA68485]; NIDDK NIH HHS [R01-DK061558] NR 54 TC 34 Z9 35 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2005 VL 16 IS 6 BP 1632 EP 1644 DI 10.1681/ASN.2004060476 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA 930CR UT WOS:000229393900014 PM 15843474 ER PT J AU Zhang, YT Choyke, PL Lu, HY Takahashi, H Mannon, RB Zhang, XJ Marcos, H Li, KCP Kopp, JB AF Zhang, YT Choyke, PL Lu, HY Takahashi, H Mannon, RB Zhang, XJ Marcos, H Li, KCP Kopp, JB TI Detection and localization of proteinuria by dynamic contrast-enhanced magnetic resonance imaging using MS325 SO JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY LA English DT Article ID FOCAL SEGMENTAL GLOMERULOSCLEROSIS; BLOOD-POOL AGENT; MS-325; TRANSPLANTATION; MODEL AB After renal transplantation, persistent glomerular disease affecting the native kidneys typically causes albuminuria, at least for a period of time, making it difficult to determine in a noninvasive fashion whether proteinuria originates in the native kidneys or the renal allograft. To address this problem, dynamic contrast-enhanced magnetic resonance imaging (MRI) using gadolinium (Gd)-based albumin-bound blood pool contrast agent (MS325) to localize proteinuria was investigated. Glomerular proteinuria was induced in Sprague-Dawley rats by intravenous injection of puromycin aminonucleoside (PAN), whereas control rats received physiologic saline vehicle. Both groups of animals underwent a 40-min dynamic contrast-enhanced MRI using radio frequency spoiled gradient echo imaging sequence after injection of Gd-labeled MS325. Contrast uptake and clearance curves for cortex and medulla were determined from acquired MR images. Compared with controls, proteinuric rats exhibited significantly lower elimination rate constants. The use of gadopentetate dimeglumine (Gd-DTPA) as a contrast agent showed smaller and less specific differences between proteinuric and control groups. In rats with one proteinuric kidney (PAN-treated) and one normal kidney (transplanted from a normal rat), MRI using MS325 was able to differentiate between the two kidneys. The results suggest that MRI with an albumin-bound blood pool contrast agent may be a useful noninvasive way to localize proteinuria. If this technique can be successfully applied in human patients, it may allow for the localization of proteinuria after kidney transplant and thereby provide a noninvasive way to detect disease affecting the renal allograft. C1 NIDDKD, Kidney Dis Sect, US Dept HHS, NIH, Bethesda, MD 20892 USA. NIH, Warren Grant Magnuson Clin Ctr, Dept Radiol, Bethesda, MD 20892 USA. RP Kopp, JB (reprint author), NIDDKD, Kidney Dis Sect, US Dept HHS, NIH, MSC 1268, Bethesda, MD 20892 USA. EM jbkopp@nih.gov OI Kopp, Jeffrey/0000-0001-9052-186X NR 21 TC 8 Z9 8 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1046-6673 J9 J AM SOC NEPHROL JI J. Am. Soc. Nephrol. PD JUN PY 2005 VL 16 IS 6 BP 1752 EP 1757 DI 10.1681/ASN.2004110981 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 930CR UT WOS:000229393900026 PM 15872075 ER PT J AU Dunson, DB AF Dunson, DB TI Bayesian semiparametric isotonic regression for count data SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article DE Dirichlet process mixture; generalized additive model; log linear; mixture prior; multiple testing; nonparametric regression; smoothing; variable selection ID NONPARAMETRIC PROBLEMS; MODELS; MONOTONICITY; BIOASSAY; POINTS; PRIORS AB This article proposes a semiparametric Bayesian approach for inference on an unknown isotonic regression function, f(x), characterizing the relationship between a continuous predictor, X, and a count response variable, Y, adjusting for covariates, Z. A Dirichlet process mixture of Poisson distributions is used to avoid parametric assumptions on the conditional distribution of Y given X and Z. Then, to also avoid parametric assumptions on f(x), a novel prior formulation is proposed that enforces the nondecreasing constraint and assigns positive prior probability to the null hypothesis of no association. Through the use of carefully tailored hyperprior distributions, we allow for borrowing of information across different regions of X in estimating f(x) and in assessing hypotheses about local increases in the function. Due to conjugacy properties, posterior computation is straightforward using a Markov chain Monte Carlo algorithm. The methods are illustrated using data from an epidemiologic study of sleep problems and obesity. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. EM dunson1@niehs.nih.gov NR 37 TC 30 Z9 30 U1 1 U2 7 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD JUN PY 2005 VL 100 IS 470 BP 618 EP 627 DI 10.1198/016214504000001457 PG 10 WC Statistics & Probability SC Mathematics GA 984NJ UT WOS:000233311300023 ER PT J AU Mayes, R Horwitz, AV AF Mayes, R Horwitz, AV TI DSM-III and the revolution in the classification of mental illness SO JOURNAL OF THE HISTORY OF THE BEHAVIORAL SCIENCES LA English DT Article ID AMERICAN PSYCHIATRY; HEALTH POLICY; DEINSTITUTIONALIZATION; PSYCHOTHERAPY; ADVANTAGES; DISORDERS; NOSOLOGY; HISTORY; TRENDS; DECADE AB A revolution occurred within the psychiatric profession in the early 1980s that rapidly transformed the theory and practice of mental health in the United States. In a very short period of time, mental illnesses were transformed from broad, etiologically defined entities that were continuous with normality to symptom-based, categorical diseases. The third edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-III) was responsible for this change. The paradigm shift in mental health diagnosis in the DSM-III was neither a product of growing scientific knowledge nor of increasing medicalization. Instead, its symptom-based diagnoses reflect a growing standardization of psychiatric diagnoses. This standardization was the product of many factors, including: (1) professional politics within the mental health community, (2) increased government involvement in mental health research and policymaking, (3) mounting pressure on psychiatrists from health insurers to demonstrate the effectiveness of their practices, and (4) the necessity of pharmaceutical companies to market their products to treat specific diseases. This article endeavors to explain the origins of DSM-III, the political struggles that generated it, and its long-term consequences for clinical diagnosis and treatment of mental disorders in the United States. (c) 2005 Wiley Periodicals, Inc. C1 Univ Richmond, Dept Polit Sci, Richmond, VA 23173 USA. Rutgers State Univ, Dept Sociol, Piscataway, NJ 08855 USA. Rutgers State Univ, Inst Hlth Hlth Care Policy & Aging Res, NIMH Postdoctoral Program Mental Hlth Serv & Syst, Piscataway, NJ 08855 USA. RP Mayes, R (reprint author), Univ Richmond, Dept Polit Sci, Richmond, VA 23173 USA. NR 62 TC 138 Z9 148 U1 3 U2 30 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-5061 J9 J HIST BEHAV SCI JI J. Hist. Behav. Sci. PD SUM PY 2005 VL 41 IS 3 BP 249 EP 267 DI 10.1002/jhbs.20103 PG 19 WC History Of Social Sciences SC Social Sciences - Other Topics GA 947PL UT WOS:000230658400003 PM 15981242 ER PT J AU Lee, W Deter, RL McNie, B Goncalves, LF Espinoza, J Chaiworapongsa, T Balasubramaniam, M Romero, R AF Lee, W Deter, RL McNie, B Goncalves, LF Espinoza, J Chaiworapongsa, T Balasubramaniam, M Romero, R TI The fetal arm - Individualized growth assessment in normal pregnancies SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE fetal growth; intrauterine growth restriction; Rossavik growth model; 3-dimensional sonography ID LOW-BIRTH-WEIGHT; MENSTRUAL AGE; HEAD CIRCUMFERENCE; 3-DIMENSIONAL ULTRASOUND; CURVE STANDARDS; LIMB CIRCUMFERENCES; NUTRITIONAL-STATUS; LONGITUDINAL DATA; ASSESSMENT SCORE; FEMUR LENGTH AB Objective. The goals were to introduce fractional arm volume (AVol) as a new soft tissue parameter of fetal growth assessment and to develop individualized growth standards, based on Rossavik models, for AVol, midarm circumference (ArmC), and humeral diaphysis length (HDL). Methods. A prospective longitudinal study of 22 fetuses was conducted using 2- and 3-dimensional sonography. Three new growth parameters (HDL, ArmC, and AVol) were used to establish individualized standards for arm growth with the use of Rossavik functions [P = c(t)(k + s(t)), where P is the anatomic parameter; c, k, and s are model coefficients; and t is the time variable]. Second-trimester models were specified from the linear slopes of growth curves before approximately 28.0 menstrual weeks. For a given fetus, normal third-trimester trajectories were predicted for each parameter. Observed and predicted measurements were compared by percent deviations. Results. Rossavik functions fit all parameter trajectories extremely well (R-2 = 95.7%-99.4%). By fixing coefficients k at their mean values, their respective fits did not change, and the variabilities of both coefficients c and s were reduced. Coefficient c was also significantly related to second-trimester slope, as was s to c, for all 3 parameters (R2 = 97.7%-98.7%; P < .0001). Mean percent deviations between observed and predicted third-trimester HDL, ArmC, and AVol measurements were -0.1% +/- 2.9%, 0.5% +/- 4.6%, and 0.4% +/- 8.5%, respectively Conclusions. Individualized growth assessment, using HDL and ArmC, can accurately predict normal arm growth during the third trimester of pregnancy. AVol may also allow earlier detection and improved monitoring of soft tissue abnormalities that can occur in fetuses with growth disturbances. C1 William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48073 USA. Baylor Coll Med, Dept Obstet & Gynecol, Houston, TX 77030 USA. NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Wayne State Univ, Dept Obstet & Gynecol, Detroit, MI USA. William Beaumont Hosp, Inst Res, Div Biostat, Royal Oak, MI 48072 USA. RP Lee, W (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, 3601 W 13th Mile Rd, Royal Oak, MI 48073 USA. EM wlee@beaumont.edu NR 53 TC 27 Z9 30 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD JUN PY 2005 VL 24 IS 6 BP 817 EP 828 PG 12 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 931BX UT WOS:000229461900010 PM 15914686 ER PT J AU Lee, W Vettraino, IM Comstock, CH Lal, N Kazmierczak, C Shetty, A Raff, G Zakalik, K Romero, R AF Lee, W Vettraino, IM Comstock, CH Lal, N Kazmierczak, C Shetty, A Raff, G Zakalik, K Romero, R TI Prenatal diagnosis of herniated Dandy-Walker cysts SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE Dandy-Walker malformation; fetal magnetic resonance imaging; herniated cyst; heterotopia; 3-dimensional sonography ID ANTENATAL DIAGNOSIS; SUBEPENDYMAL HETEROTOPIA; MALFORMATION; US AB Objective. The purpose of this series is to describe the prenatal diagnosis and pregnancy outcome of fetuses affected with Dandy-Walker malformation in which a posterior cyst herniated through a bony defect of the occipital skull, foramen magnum, or both. Methods. Two- and 3-dimensional sonography were used to examine 2 fetuses with poorly delineated cerebellar structures and a large posterior cystic neck mass. Fetal magnetic resonance imaging (MRI) was added to this evaluation as a complementary diagnostic modality. Results. Three-dimensional sonography helped characterize the precise site of cyst herniation through the occipital skull or foramen magnum. Fetal MRI confirmed the sonographic findings. Neonatal MRI studies identified heterotopic gray matter as evidence of a neuronal migration disorder in both fetuses. The second fetus also had agenesis of the corpus callosum. Retrospective review of the fetal MRI (25.9 weeks' menstrual age) and 3-dimensional sonographic (18.7 weeks' menstrual age) studies confirmed ventricular wall nodularity involving the occipital horns of the second fetus. Conclusions. The antenatal detection of a large posterior cystic neck mass and a poorly defined or nonvisualized cerebellar vermis suggest Dandy-Walker malformation with a herniated cyst. Three-dimensional sonography and fetal MRI are important adjunctive methods that can be used to evaluate the herniation site and a possible neuronal migrational disorder. C1 William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, Royal Oak, MI 48073 USA. William Beaumont Hosp, Dept Diagnost Radiol, Royal Oak, MI 48073 USA. William Beaumont Hosp, Div Cardiol, Dept Internal Med, Royal Oak, MI 48073 USA. William Beaumont Hosp, Div Neurosurg, Royal Oak, MI 48073 USA. William Beaumont Hosp, Dept Pediat, Royal Oak, MI 48073 USA. NICHHD, Perinatol Res Branch, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Lee, W (reprint author), William Beaumont Hosp, Dept Obstet & Gynecol, Div Fetal Imaging, 3601 W 13th Mile Rd, Royal Oak, MI 48073 USA. EM wlee@beaumont.edu NR 19 TC 2 Z9 6 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD JUN PY 2005 VL 24 IS 6 BP 841 EP 848 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 931BX UT WOS:000229461900012 PM 15914688 ER PT J AU Jones, DJ Crump, AD AF Jones, DJ Crump, AD TI Methodological challenges in conducting health disparities research SO JOURNAL OF URBAN HEALTH-BULLETIN OF THE NEW YORK ACADEMY OF MEDICINE LA English DT Editorial Material C1 Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, Serv Res Branch, Bethesda, MD 20892 USA. RP Jones, DJ (reprint author), Natl Inst Drug Abuse, Div Epidemiol Serv & Prevent Res, Serv Res Branch, 6001 Execut Blvd,Room 5185,MSC 9589, Bethesda, MD 20892 USA. EM dj99r@nih.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1099-3460 J9 J URBAN HEALTH JI J. Urban Health PD JUN PY 2005 VL 82 IS 2 SU 3 BP III1 EP III4 DI 10.1093/jurban/jti058 PG 4 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 938BL UT WOS:000229974800001 PM 15933325 ER PT J AU Carter, HB Landis, P Wright, EJ Parsons, JK Metter, EJ AF Carter, HB Landis, P Wright, EJ Parsons, JK Metter, EJ TI Can a baseline prostate specific antigen level identify men who will have lower urinary tract symptoms later in life? SO JOURNAL OF UROLOGY LA English DT Article DE prostate; prostate-specific antigen; prostatic hyperplasia; urinary tract ID HYPERPLASIA; PREDICTOR; FINASTERIDE; THERAPY; VOLUME; RISK AB Purpose: We evaluated the relationship between baseline prostate specific antigen (PSA) and subsequent lower urinary tract symptom development during 3 decades in unselected men in the Baltimore Longitudinal Study of Aging. Materials and Methods: Urinary questionnaires were used to evaluate lower urinary tract symptoms in 704: men during 3 decades. The number of repeat evaluations was I to 18. We divided subjects into age groups of younger than 50 and 50 to 69.9 years at the time of the first PSA evaluation. Subjects were divided into 3 PSA groups based on initial PSA below the 25th, 25th to 75th and above the 75th percentile. A mixed effects Poisson model was used to test whether there was a significant relationship between PSA grouping and symptom score with time. Results: There was no statistically significant difference in symptom score distribution across PSA percentiles in men younger than 50 years (p = 0.87) or 50 to 69.9 years old (p = 0.59). When age was used as an independent variable in the model, there was no statistically significant relationship between baseline PSA and symptom score (p = 0.38). Conclusions: These data suggest that PSA is not a useful predictor of the development of lower urinary tract symptoms in unselected, asymptomatic men. C1 Johns Hopkins Univ, Dept Urol, Johns Hopkins Hosp, Sch Med,James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. NIA, Clin Res Branch, NIH, Harbor Hosp, Baltimore, MD 21224 USA. RP Carter, HB (reprint author), Johns Hopkins Univ, Dept Urol, Johns Hopkins Hosp, Sch Med,James Buchanan Brady Urol Inst, 600 N Wolfe St,403 Marburg, Baltimore, MD 21287 USA. EM hcarter@jhmi.edu NR 15 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD JUN PY 2005 VL 173 IS 6 BP 2040 EP 2043 DI 10.1097/01.ju.0000158372.45211.47 PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 925KJ UT WOS:000229051700037 PM 15879821 ER PT J AU Goldberg, SN Grassi, CJ Cardella, JF Charboneau, JW Dodd, GD Dupuy, DE Gervais, D Gillams, AR Kane, RA Lee, FT Livraghi, T McGahan, J Phillips, DA Rhim, H Silverman, SG AF Goldberg, SN Grassi, CJ Cardella, JF Charboneau, JW Dodd, GD Dupuy, DE Gervais, D Gillams, AR Kane, RA Lee, FT Livraghi, T McGahan, J Phillips, DA Rhim, H Silverman, SG CA Soc Interven Radio Tech Asses Comm Int Work Grp Image Gui Tumor Abla TI Image-guided tumor ablation: Standardization of terminology and reporting criteria SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID PERCUTANEOUS RADIOFREQUENCY ABLATION; SMALL HEPATOCELLULAR-CARCINOMA; LASER-INDUCED THERMOTHERAPY; QUALITY IMPROVEMENT GUIDELINES; MICROWAVE COAGULATION THERAPY; RENAL-CELL CARCINOMA; THERMAL ABLATION; HEPATIC-TUMORS; LIVER METASTASES; TISSUE ABLATION AB The field of interventional oncology with use of image-guided tumor ablation requires standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison between treatments that use different technologies, such as chemical (ethanol or acetic acid) ablation, and thermal therapies, such as radiofrequency (RF), laser, microwave, ultrasound, and cryoablation. This document provides a framework that will hopefully facilitate the clearest communication between investigators and will provide the greatest flexibility in comparison between the many new, exciting, and emerging technologies. An appropriate vehicle for reporting the various aspects of image-guided ablation therapy, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings, are outlined. Methods for standardizing the reporting of follow-up findings and complications and other important aspects that require attention when reporting clinical results are addressed. It is the group's intention that adherence to the recommendations will facilitate achievement of the group's main objective: improved precision and communication in this field that lead to more accurate comparison of technologies and results and, ultimately, to improved patient outcomes. The intent of this standardization of terminology is to provide an appropriate vehicle for reporting the various aspects of image-guided ablation therapy. C1 Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. Lahey Clin Med Ctr, Dept Radiol, Burlington, MA 01803 USA. Univ Colorado, Hlth Sci Ctr, Dept Radiol, Denver, CO 80262 USA. Mayo Clin, Rochester, MN USA. Univ Texas, Hlth Sci Ctr, Dept Radiol, San Antonio, TX 78284 USA. Brown Univ, Rhode Isl Hosp, Div Ultrasound, Providence, RI 02903 USA. Ma Gen Hosp, GI GU Div, Dept Radiol, Boston, MA USA. Middlesex Hosp, London, England. Univ Wisconsin, Ctr Clin Sci, Madison, WI 53706 USA. Osped Civile Vimercate, Dept Radiol, Milan, Italy. Univ Calif Davis, Med Ctr, Sacramento, CA 95817 USA. Univ Massachusetts, Dept Radiol, Worcester, MA 01605 USA. Hanyang Univ Hosp, Seoul, South Korea. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Radiol, Boston, MA USA. Gen Hosp, Dept Radiol, Busto Arsizio, Italy. Univ Frankfurt Hosp, Inst Diagnost Intervent Radiol, Frankfurt, Germany. NIH, Ctr Clin, Dept Radiol, Bethesda, MD 20892 USA. Washington Univ, Sch Med, Mallinckrodt Inst Radiol, St Louis, MO USA. Reading Hosp, Reading, PA USA. Med Ctr, Reading, PA USA. RP Goldberg, SN (reprint author), Beth Israel Deaconess Med Ctr, Dept Radiol, Boston, MA 02215 USA. OI Dupuy, Damian/0000-0003-0524-5982 NR 99 TC 197 Z9 202 U1 2 U2 9 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD JUN PY 2005 VL 16 IS 6 BP 765 EP 778 DI 10.1097/01.RVI.0000170858.46668.65 PG 14 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 936IG UT WOS:000229848100001 PM 15947040 ER PT J AU Steel, JC Cavanagh, HMA Burton, MA Dingwall, DJ Kalle, WHJ AF Steel, JC Cavanagh, HMA Burton, MA Dingwall, DJ Kalle, WHJ TI Modification of liposomal concentration in liposome/adenoviral complexes allows significant protection of adenoviral vectors from neutralising antibody, in vitro SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE adenovirus; liposomes; AL complexes; immuno-protection; neutralising antibodies ID MEDIATED GENE-TRANSFER; CATIONIC LIPOSOMES; EFFICIENCY; LUNG; TOXICITY; CELLS; EXPRESSION; INFECTION; PROSPECTS; INCREASE AB Adenoviral vectors have been commonly used in gene therapy protocols, however the success of their use is often limited by the induction of host immunity to the vector. Following exposure to the adenoviral vector, adenoviral-specific neutralising antibodies are produced which limits further administration. This study examines the efficacy of complexing liposomes to adenovirus for the protection of the adenovirus from neutralising antibodies in an in vitro setting. Dimethyldioctadecylammonium bromide (DDAB)-dioleoyl-(L)-phosphatidylethanol amine (DOPE) liposomes were bound at varying concentrations to adenovirus to form AL complexes and tested these complexes' ability to prevent adenoviral neutralisation. It is shown that by increasing the concentration of liposomes in the adenoviral-liposome (AL) complexes we can increase the level of immuno-shielding afforded the adenovirus. It is also shown that the increase in liposomal concentration may lead to drawbacks such as increased cytotoxicity and reductions in expression levels. © 2005 Elsevier B.V. All rights reserved. C1 NCI, NIH, Ctr Canc Res, Canc Gene Therapy Grp,Metab Branch, Bethesda, MD 20892 USA. Charles Sturt Univ, Sch Biomed Sci, Wagga Wagga, NSW 2678, Australia. RP Steel, JC (reprint author), NCI, NIH, Ctr Canc Res, Canc Gene Therapy Grp,Metab Branch, Bldg 10,Room 4N115,10 Ctr Dr, Bethesda, MD 20892 USA. EM steeljas@mail.nih.gov RI Steel, Jason/D-1805-2013 OI Steel, Jason/0000-0003-3608-7542 NR 27 TC 11 Z9 11 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD JUN PY 2005 VL 126 IS 1-2 BP 31 EP 36 DI 10.1016/j.jviromet.2005.01.017 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 924TJ UT WOS:000229003000004 PM 15847916 ER PT J AU Buchholz, UJ Biacchesi, S Pham, QN Tran, KC Yang, LJ Luongo, CL Skiadopoulos, MH Murphy, BR Collins, PL AF Buchholz, UJ Biacchesi, S Pham, QN Tran, KC Yang, LJ Luongo, CL Skiadopoulos, MH Murphy, BR Collins, PL TI Deletion of M2 gene open reading frames 1 and 2 of human metapneumovirus: Effects on RNA synthesis, attenuation, and immunogenicity SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; TRANSCRIPTION ELONGATION-FACTOR; MESSENGER-RNA; EBOLA-VIRUS; TRACT INFECTIONS; PROTEIN FUNCTION; BINDING PROTEIN; YOUNG-CHILDREN; CLONED CDNA; C PROTEINS AB The M2 gene of human metapneumovirus (HMPV) contains two overlapping open reading frames (ORFs), M2-1 and M2-2. The expression of separate M2-1 and M2-2 proteins from these ORFs was confirmed, and recombinant HMPVs were recovered in which expression of M2-1 and M2-2 was ablated individually or together [r&UDelta; M2-1, r&UDelta; M2-2, and r&UDelta; M2(1+2)]. Each M2 mutant virus directed efficient multicycle growth in Vero cells. The ability to recover HMPV lacking M2-1 contrasts with human respiratory syncytial virus, for which M2-1 is an essential transcription factor. Expression of the downstream HMPV M2-2 ORF was not reduced when translation of the upstream M2-1 ORF was silenced, indicating that it is initiated separately. The r&UDelta; M2-2 mutants exhibited a two- to fivefold increase in the accumulation of mRNA, normalized to the genome template, suggesting that M2-2 has a role in regulating RNA synthesis. Replication and immunogenicity were tested in hamsters. Animals infected intranasally with r&UDelta; M2-1 or r&UDelta; M2(1+2) did not have recoverable virus in the lungs or nasal turbinates on days 3 or 5 postinfection and did not develop HMPV-neutralizing serum antibodies or resistance to HMPV challenge. Thus, M2-1 appears to be essential for significant virus replication in vivo. In animals infected with r&UDelta; M2-2, virus was recovered from only 1 of 12 animals and only in the nasal turbinates on a single day. However, all of the animals developed a high titer of HMPV-neutralizing serum antibodies and were highly protected against challenge with wild-type HMPV. The HMPV r&UDelta; M2-2 virus is a promising and highly attenuated HMPV vaccine candidate. C1 NIAID, NIH, LID, Bethesda, MD 20892 USA. RP Buchholz, UJ (reprint author), NIAID, NIH, LID, Bldg 50,Room 6505,50 S Dr,MSC 8007, Bethesda, MD 20892 USA. EM ubuchholz@niaid.nih.gov RI Biacchesi, Stephane/A-6924-2010 NR 41 TC 50 Z9 56 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 11 BP 6588 EP 6597 DI 10.1128/JVI.79.11.6588-6597.2005 PG 10 WC Virology SC Virology GA 925WY UT WOS:000229085400002 PM 15890897 ER PT J AU Resch, W Weisberg, AS Moss, B AF Resch, W Weisberg, AS Moss, B TI Vaccinia virus nonstructural protein encoded by the A11R gene is required for formation of the virion membrane SO JOURNAL OF VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE MUTANTS; INTERMEDIATE COMPARTMENT; INITIATE MORPHOGENESIS; ENDOPLASMIC-RETICULUM; ESSENTIAL COMPONENT; A14 PHOSPHOPROTEIN; ENVELOPE PROTEIN; VIRAL MEMBRANES; A17L GENE; KINASE AB The vaccinia virus A11R gene has orthologs in all known poxvirus genomes, and the All protein has been previously reported to interact with the putative DNA packaging protein A32 in a yeast two-hybrid screen. Using antisera raised against All peptides, we show that the All protein was (i) expressed at late times with an apparent mass of 40 kDa, (ii) not incorporated into virus particles, (iii) phosphorylated independently of the viral F10 kinase, (iv) coinummoprecipitated with A32, and (v) localized to the viral factory. To determine the role of the All protein and test whether it is indeed involved in DNA packaging, we constructed a recombinant vaccinia virus with an inducible A11R gene. This recombinant was dependent on inducer for single-cycle growth and plaque formation. In the absence of inducer, viral late proteins were produced at normal levels, but proteolytic processing and other posttranslational modifications of some proteins were inhibited, suggesting a block in virus particle assembly. Consistent with this observation, electron microscopy of cells infected in the absence of inducer showed virus factories with abnormal electron-dense viroplasms and intermediate density regions associated with membranes and containing the D13 protein. However, no viral membrane crescents, immature virions, or mature virions were produced. The requirement for nonvirion protein All in order to make normal viral membranes was an unexpected and exciting finding, since neither the origin of these membranes nor their mechanism of formation in the cytoplasm of infected cells is understood. C1 NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIH, 4 Ctr Dr,Bldg 4,Rm 229, Bethesda, MD 20892 USA. EM bmoss@niaid.nih.gov NR 44 TC 46 Z9 50 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 11 BP 6598 EP 6609 DI 10.1128/JVI.79.11.6598-6609.2005 PG 12 WC Virology SC Virology GA 925WY UT WOS:000229085400003 PM 15890898 ER PT J AU Milne, RSB Nicola, AV Whitbeck, JC Eisenberg, RJ Cohen, GH AF Milne, RSB Nicola, AV Whitbeck, JC Eisenberg, RJ Cohen, GH TI Glycoprotein D receptor-dependent, low-pH-Independent Endocytic entry of herpes simplex virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID HEPATITIS-B-VIRUS; COMPLEMENT COMPONENT C3B; HEPARAN-SULFATE; MONOCLONAL-ANTIBODIES; CELL-SURFACE; HUMAN CYTOMEGALOVIRUS; ANTIGENIC ANALYSIS; MEMBRANE-FUSION; LIPID RAFTS; HOST-CELLS AB Two herpes simplex virus type 1 (HSV-1) entry pathways have been described: direct fusion between the virion envelope and the plasma membrane, as seen on Vero cells, and low-pH-dependent endocytosis, as seen on CHO nectin-1 and HeLa cells. In this paper, we studied HSV entry into C10 murine melanoma cells and identified a third entry pathway for this virus. During entry into C10 cells, virion envelope glycoproteins rapidly became protected from the membrane-impermeable chemical cross-linker BS3 and from proteinase K. Protection was gD receptor dependent, and the time taken to detect protected protein was proportional to the rate of virus entry. Ultrastructural examination revealed that virions attached to the surface of C10 cells were localized to membrane invaginations, whereas those on the surface of receptor-negative B78 cells were peripherally attached. Virus entry into C10 cells was energy dependent, and intracellular enveloped virions were seen within membrane-bound vesicles consistent with endocytic entry. Entry was not inhibited by bafilomycin A1 or ammonium chloride, showing that passage of the virion through a low-pH environment was not required for infection. Resistance to similar reagents should therefore not be taken as proof of HSV entry by a nonendosomal pathway. These data define a novel gD receptor-dependent acid-independent endocytic entry pathway for HSV. C1 Univ Penn, Sch Dent Med, Dept Microbiol, Philadelphia, PA 19104 USA. Univ Penn, Ctr Oral Hlth Res, Philadelphia, PA 19104 USA. Univ Penn, Sch Vet Med, Dept Pathobiol, Philadelphia, PA 19104 USA. NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. RP Milne, RSB (reprint author), Univ Penn, Sch Dent Med, Dept Microbiol, 215 Levy Bldg,240 S 40th St, Philadelphia, PA 19104 USA. EM rmilne@biochem.dental.upenn.edu FU NIAID NIH HHS [AI-056045, AI-18289, R01 AI018289, R01 AI056045, R21 AI056045, R37 AI018289]; NINDS NIH HHS [NS-36731, R01 NS036731] NR 51 TC 119 Z9 122 U1 0 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 11 BP 6655 EP 6663 DI 10.1128/JVI.79.11.6655-6663.2005 PG 9 WC Virology SC Virology GA 925WY UT WOS:000229085400008 PM 15890903 ER PT J AU Graff, J Nguyen, H Yu, C Elkins, WR St Claire, MS Purcell, RH Emerson, SU AF Graff, J Nguyen, H Yu, C Elkins, WR St Claire, MS Purcell, RH Emerson, SU TI The open reading frame 3 gene of hepatitis e virus contains a cis-reactive element and encodes a protein required for infection of macaques SO JOURNAL OF VIROLOGY LA English DT Article ID ORF3 PROTEIN; CAPSID PROTEIN; MUTATIONAL ANALYSIS; INSECT CELLS; IN-VITRO; EXPRESSION; GENOMES; REPLICATION; INTERACTS; LIVER AB An infectious cDNA clone of hepatitis E virus was mutated in order to prevent synthesis of either open reading frame 2 (ORF2) protein or ORF3 protein. HuH-7 cells transfected with an 011,172-null mutant produced ORF3, and those transfected with an ORF3-null mutant produced ORF2. Silent mutations introduced into a highly conserved nucleotide sequence in the ORF3 coding region eliminated the synthesis of both ORF2 and ORF3 proteins, suggesting that it comprised a cis-reactive element. A mutant that was not able to produce ORF3 protein did not produce a detectable infection in rhesus macaques. However, a mutant that encoded an ORF3 protein lacking a phosphorylation site reported to be critical for function was able to replicate its genome in cell culture and to induce viremia and seroconversion in rhesus monkeys, suggesting that phosphorylation of ORF3 protein was not necessary for genome replication or for production of infectious virions. C1 NIAID, Mol Hepatitis Sect, NIH, Bethesda, MD 20892 USA. NIAID, Hepatitis Viruses Sect, NIH, Bethesda, MD 20892 USA. NIAID, Primate Virol Sect, NIH, Bethesda, MD 20892 USA. Bioqual Inc, Rockville, MD 20850 USA. RP Emerson, SU (reprint author), NIAID, Mol Hepatitis Sect, NIH, Bldg 50,Rm 6537,50 S Dr,MSC 8009, Bethesda, MD 20892 USA. EM semerson@niaid.nih.gov NR 25 TC 75 Z9 79 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 11 BP 6680 EP 6689 DI 10.1128/JVI.79.11.6680-6689.2005 PG 10 WC Virology SC Virology GA 925WY UT WOS:000229085400011 PM 15890906 ER PT J AU Yang, RC Wheeler, CM Chen, XJ Uematsu, S Takeda, K Akira, S Pastrana, DV Viscidi, RP Roden, RBS AF Yang, RC Wheeler, CM Chen, XJ Uematsu, S Takeda, K Akira, S Pastrana, DV Viscidi, RP Roden, RBS TI Papillomavirus capsid mutation to escape dendritic cell-dependent innate immunity in cervical cancer SO JOURNAL OF VIROLOGY LA English DT Article ID VIRUS-LIKE PARTICLES; TYPE-16 DNA; SEQUENCE VARIATION; PROTEIN GENES; L1; HPV16; CARCINOMA; NEUTRALIZATION; IMMUNIZATION; POPULATIONS AB Infection with oncogenic human papillomaviruses (HPVs), typified by HPV type 16 (HPV16), is a necessary cause of cervical cancer. Prophylactic vaccination with HPV16 L1 virus-like particles (VLPs) provides immunity. HPV16 VLPs activate dendritic cells and a potent neutralizing immunoglobulin G (IgG) response, yet many cervical cancer patients fail to generate detectable VLP-specific IgG. Therefore, we examined the role of the innate recognition of HPV16 L1 in VLP-induced immune responses and its evasion during carcinogenesis. Nonconservative mutations within HPV16 L1 have been described in isolates from cervical cancer and its precursor, high-grade cervical intraepithelial neoplasia (CIN). We determined the effect of mutations in L1 upon in vitro self-assembly into VLPs and their influence upon the induction of innate and adaptive immune responses in mice. Several nonconservative mutations in HPV16 L1 isolated from high-grade CIN or cervical carcinoma prevent self-assembly of L1 VLPs. Intact VLPs, but not assembly-defective L1, activate dendritic cells to produce proinflammatory factors, such as alpha interferon, that play a critical role in inducing adaptive immunity. Indeed, effective induction of L1-specific IgG1 and IgG2a was dependent upon intact VLP structure. Dendritic cell activation and production of virus-specific neutralizing IgG by VLPs requires MyD88-dependent signaling, although the L1 structure that initiates MyD88-mediated signaling is distinct from the neutralizing epitopes. We conclude that innate recognition of the intact L1 VLP structure via MyD88 is critical in the induction of high-titer neutralizing IgG. Tumor progression is associated with genetic instability and L1 mutants. Selection for assembly-deficient L1 mutations suggests the evasion of MyD88-dependent immune control during cervical carcinogenesis. C1 Johns Hopkins Sch Med, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Sch Med, Dept Pediat, Baltimore, MD 21205 USA. Johns Hopkins Sch Med, Dept Gynecol & Obstet, Baltimore, MD 21205 USA. Univ New Mexico, Dept Mol Genet & Microbiol, Albuquerque, NM 87131 USA. Univ Colorado, Hlth Sci Ctr, Sch Med, Dept Biochem & Mol Genet, Denver, CO 80262 USA. Osaka Univ, Dept Host Def, Res Inst Microbial Dis, Suita, Osaka 5650871, Japan. NCI, Cellular Oncol Lab, Bethesda, MD 20892 USA. RP Roden, RBS (reprint author), Johns Hopkins Sch Med, Dept Pathol, Ross Res Bldg,Room 512B,720 Rutland Ave, Baltimore, MD 21205 USA. EM roden@jhmi.edu RI Akira, Shizuo/C-3134-2009; Takeda, Kiyoshi/C-9331-2009 FU NCI NIH HHS [P50 CA098252]; NIAID NIH HHS [P01 AI 48203, P01 AI048203] NR 44 TC 40 Z9 42 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 11 BP 6741 EP 6750 DI 10.1128/JVI.79.11.6741-6750.2005 PG 10 WC Virology SC Virology GA 925WY UT WOS:000229085400017 PM 15890912 ER PT J AU Miles, LR Agresta, BE Khan, MB Tang, SX Levin, JG Powell, MD AF Miles, LR Agresta, BE Khan, MB Tang, SX Levin, JG Powell, MD TI Effect of polypurine tract (PPT) mutations on human immunodeficiency virus type 1 replication: A virus with a completely randomized PPT retains low infectivity SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; PLUS-STRAND DNA; HIV-1 REVERSE-TRANSCRIPTASE; PRIMER-BINDING-SITE; SEQUENCE FEATURES IMPORTANT; LONG TERMINAL REPEAT; RNASE-H; CLEAVAGE SPECIFICITY; ENDOGENOUS RETROVIRUSES; INTEGRATION SITE AB We introduced polypurine tract (PPT) mutations, which we had previously tested in an in vitro assay, into the viral clone NL4-3KFS&UDelta; nef. Each mutant was tested for single-round infectivity and virion production. All of the PPT mutations had an effect on replication; however, mutation of the 5' end appeared to have less of an effect on infectivity than mutation of the 3' end of the PPT sequence. Curiously, a mutation in which the entire PPT sequence was randomized (PPTSUB) retained 12% of the infectivity of the wild type (WT) in a multinuclear activation of galactosidase indicator assay. Supernatants from these infections contained viral particles, as evidenced by the presence of p24 antigen. Two-long terminal repeat (2-LTR) circle junction analysis following PPTSUB infection revealed that the mutant could form a high percentage of normal junctions. Quantification of the 2-LTR circles using real-time PCR revealed that number of 2-LTR circles from cells infected with the PPTSUB mutant was 3.5 logs greater than 2-LTR circles from cells infected with WT virus. To determine whether the progeny virions from a PPTSUB infection could undergo further rounds of replication, we introduced the PPTSUB mutation into a replication-competent virus. Our results show that the mutant virus is able to replicate and that the infectivity of the progeny virions increases with each passage, quickly reverting to a WT PPT sequence. Together, these experiments confirm that the 3' end of the PPT is important for plus-strand priming and that a virus that completely lacks a PPT can replicate at a low level. C1 Morehouse Sch Med, Dept Microbiol, Atlanta, GA 30310 USA. NICHHD, Mol Genet Lab, Bethesda, MD 20892 USA. RP Powell, MD (reprint author), Morehouse Sch Med, Dept Microbiol, 720 Westview Dr S W, Atlanta, GA 30310 USA. EM powellm@msm.edu FU NCRR NIH HHS [G12 RR003034, G12-RR03034]; NIGMS NIH HHS [1F31GM65793, S06 GM008248, S06-GM08248, F31 GM065793] NR 77 TC 19 Z9 19 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 11 BP 6859 EP 6867 DI 10.1128/JVI.79.11.6859-6867.2005 PG 9 WC Virology SC Virology GA 925WY UT WOS:000229085400030 PM 15890925 ER PT J AU Lusso, P Earl, PL Sironi, F Santoro, F Ripamonti, C Scarlatti, G Longhi, R Berger, EA Burastero, SE AF Lusso, P Earl, PL Sironi, F Santoro, F Ripamonti, C Scarlatti, G Longhi, R Berger, EA Burastero, SE TI Cryptic nature of a conserved, CD4-inducible V3 loop neutralization epitope in the native envelope glycoprotein oligomer of CCR5-restricted, but not CXCR4-using, primary human immunodeficiency virus type 1 strains SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; CORECEPTOR USAGE; RECEPTOR-BINDING; SOLUBLE CD4; CONFORMATIONAL-CHANGES; GP120 GLYCOPROTEIN; PRIMARY ISOLATE; HIV TYPE-1; MEDIATED NEUTRALIZATION; V3-SPECIFIC ANTIBODIES AB The external subunit of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein (Env), gp120, contains conserved regions that mediate sequential interactions with two cellular receptor molecules, CD4 and a chemokine receptor, most commonly CCR5 or CXCR4. However, antibody accessibility to such regions is hindered by diverse protective mechanisms, including shielding by variable loops, conformational flexibility and extensive glycosylation. For the conserved neutralization epitopes hitherto described, antibody accessibility is reportedly unrelated to the viral coreceptor usage phenotype. Here, we characterize a novel, conserved gp120 neutralization epitope, recognized by a murine monoclonal antibody (MAb), D19, which is differentially accessible in the native HIV-1 Env according to its coreceptor specificity. The D19 epitope is contained within the third variable (W) domain of gp120 and is distinct from those recognized by other W-specific MAbs. To study the reactivity of MAb D19 with the native oligomeric Env, we generated a panel of PM1 cells persistently infected with diverse primary HIV-1 strains. The D19 epitope was conserved in the majority (23/29; 79.3%) of the subtype-B strains tested, as well as in selected strains from other genetic subtypes. Strikingly, in CCR5-restricted (R5) isolates, the D19 epitope was invariably cryptic, although it could be exposed by addition of soluble CD4 (sCD4); epitope masking was dependent on the native oligomeric structure of Env, since it was not observed with the corresponding monomeric gp120 molecules. By contrast, in CXCR4-using strains (X4 and R5X4), the epitope was constitutively accessible. In accordance with these results, R5 isolates were resistant to neutralization by MAb D19, becoming sensitive only upon addition of sCD4, whereas CXCR4-using isolates were neutralized regardless of the presence of sCD4. Other V3 epitopes examined did not display a similar divergence in accessibility based on coreceptor usage phenotype. These results provide the first evidence of a correlation between HIV-1 biological phenotype and neutralization sensitivity, raising the possibility that the in vivo evolution of HIV-1 coreceptor usage may be influenced by the selective pressure of specific host antibodies. C1 San Raffaele Sci Inst, Dept Biol & Technol Res, Unit Human Virol, I-20132 Milan, Italy. San Raffaele Sci Inst, Unit HIV Mol Epidemiol, I-20132 Milan, Italy. San Raffaele Sci Inst, Unit Leukocyte Biol, I-20132 Milan, Italy. San Raffaele Sci Inst, Dept Biol & Technol Res, I-20132 Milan, Italy. Univ Cagliari, Dept Med Sci, Cagliari, Italy. CNR, I-20133 Milan, Italy. NIAID, Viral Dis Lab, Bethesda, MD 20892 USA. RP Lusso, P (reprint author), San Raffaele Sci Inst, Dept Biol & Technol Res, Unit Human Virol, Via Olgettina 58, I-20132 Milan, Italy. EM paolo.lusso@hsr.it NR 68 TC 63 Z9 67 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 11 BP 6957 EP 6968 DI 10.1128/JVI.79.11.6957-6968.2005 PG 12 WC Virology SC Virology GA 925WY UT WOS:000229085400040 PM 15890935 ER PT J AU Cohen, JI Krogmann, T Ross, JP Pesnicak, L Prikhod'ko, EA AF Cohen, JI Krogmann, T Ross, JP Pesnicak, L Prikhod'ko, EA TI Varicella-zoster virus ORF4 latency-associated protein is important for establishment of latency SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN TRIGEMINAL GANGLIA; READING FRAME-4 PROTEIN; REGULATORY PROTEINS; GENE-EXPRESSION; FUNCTIONALLY DISTINCT; TYPE-1 ICP27; REPLICATION; MUTANTS; ENCODES; TRANSCRIPTION AB Varicella-zoster virus (VZV) encodes at least six genes that are expressed during latency. One of the genes, ORF4, encodes an immediate-early protein that is present in the virion tegument. ORF4 RNA and protein have been detected in latently infected human ganglia. We have constructed a VZV mutant deleted for ORF4 and have shown that the gene is essential for replication in vitro. The ORF4 mutant virus could be propagated when grown in cells infected with baculovirus expressing the ORF4 protein under the human cytomegalovirus immediate-early promoter. In contrast, the VZV ORF4 deletion mutant could not be complemented in cells expressing herpes simplex virus type 1 (HSV-1) ICP27, the homolog of ORF4. Cells infected with baculovirus expressing ORF4 did not complement an HSV-1 ICP27 deletion mutant. VZV-infected cotton rats have been used as a model for latency; viral DNA and latency-associated transcripts are expressed in dorsal root ganglia 1 month or more after experimental infection. Cotton rats inoculated with VZV lacking ORF4 showed reduced frequency of latency compared to animals infected with the parental or ORF4-rescued virus. Thus, in addition to VZV ORF63, which was previously shown to be critical for efficient establishment of latency, ORF4 is also important for latent infection. C1 NIH, Med Virol Sect, Lab Clin Infect Dis, Bethesda, MD 20892 USA. RP Cohen, JI (reprint author), NIH, Med Virol Sect, Lab Clin Infect Dis, Bl;dg 10,Room 11N228,10 Ctr Dr, Bethesda, MD 20892 USA. EM jcohen@niaid.nih.gov NR 37 TC 30 Z9 33 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 11 BP 6969 EP 6975 DI 10.1128/JVI.79.11.6969-6975.2005 PG 7 WC Virology SC Virology GA 925WY UT WOS:000229085400041 PM 15890936 ER PT J AU Sugimoto, K Kaplan, DE Ikeda, F Ding, J Schwartz, J Nunes, FA Alter, HJ Chang, KM AF Sugimoto, K Kaplan, DE Ikeda, F Ding, J Schwartz, J Nunes, FA Alter, HJ Chang, KM TI Strain-specific T-cell suppression and protective immunity in patients with chronic hepatitis C virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID ORIGINAL ANTIGENIC SIN; NONSTRUCTURAL PROTEIN-3; LYMPHOCYTE RESPONSES; VIRAL CLEARANCE; EPITOPES; CD4(+); HCV; INTERFERON; PERSISTENT; VARIANTS AB Hepatitis C virus (HCV) frequently persists with an apparently ineffective antiviral T-cell response. We hypothesized that some patients may be exposed to multiple HCV subtypes and that strain-specific T cells could contribute to the viral dynamics in this setting. To test this hypothesis, CD4 T-cell responses to three genotype la-derived HCV antigens and HCV antibody serotype were examined in chronically HCV infected (genotypes 1a, 1b, 2, 3, and 4) and spontaneously HCV recovered subjects. Consistent with multiple HCV exposure, 63% of patients infected with genotypes 2 to 4 (genotypes 2-4) and 36% of those infected with genotype 1b displayed CD4 T-cell responses to la-derived HCV antigens, while 29% of genotype 2-4-infected patients showed serotype responses to genotype 1. Detection of 1a-specific T cells in patients without active la infection suggested prior self-limited 1a infection with T-cell-mediated protection from 1a but not from non-1a viruses. Remarkably, CD4 T-cell responses to 1a-derived HCV antigens were weakest in patients with homologous 1a infection and greater in non-1a-infected patients: proportions of patients responding were 19% (1a), 36% (1b), and 63% (2-4) (P = 0.0006). Increased 1a-specific CD4 T-cell responsiveness in non-1a-infected patients was not due to increased immunogenicity or cross-reactivity of non-1a viruses but directly related to sequence divergence. We conclude that the T-cell response to the circulating virus is either suppressed or not induced in a strain-specific manner in chronically HCV infected patients and that, despite their ability to clear one HCV strain, patients may be reinfected with a heterologous strain that can then persist. These findings provide new insights into host-virus interactions in HCV infection that have implications for vaccine development. C1 Univ Penn, Div Gastroenterol, Philadelphia, PA 19104 USA. PVAMC, Philadelphia, PA 19104 USA. Penn Hosp, Philadelphia, PA 19107 USA. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. RP Chang, KM (reprint author), Univ Penn, Dept Med, G1 Div, Univ & Woodland Ave, Philadelphia, PA 19104 USA. EM kmchang@mail.med.upenn.edu OI Kaplan, David E./0000-0002-3839-336X FU NCRR NIH HHS [M01 RR000040, M01-RR00040]; NIAAA NIH HHS [R01 AA012849, AA12849]; NIAID NIH HHS [AI47519, R01 AI047519]; NIDDK NIH HHS [P30 DK050306, P30DK50306]; PHS HHS [T32 07066] NR 47 TC 32 Z9 34 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 11 BP 6976 EP 6983 DI 10.1128/JVI.79.11.6976-6983.2005 PG 8 WC Virology SC Virology GA 925WY UT WOS:000229085400042 PM 15890937 ER PT J AU Belov, GA Fogg, MH Ehrenfeld, E AF Belov, GA Fogg, MH Ehrenfeld, E TI Poliovirus proteins induce membrane association of GTPase ADP-ribosylation factor SO JOURNAL OF VIROLOGY LA English DT Article ID BREFELDIN-A; PHOSPHOLIPASE-D; GOLGI MEMBRANES; ENDOPLASMIC-RETICULUM; RNA REPLICATION; CELL-FREE; VESICLE FORMATION; BINDING-PROTEIN; COATED VESICLES; IN-VITRO AB Poliovirus infection results in the disintegration of intracellular membrane structures and formation of specific vesicles that serve as sites for replication of viral RNA. The mechanism of membrane rearrangement has not been clearly defined. Replication of poliovirus is sensitive to brefeldin A (BFA), a fungal metabolite known to prevent normal function of the ADP-ribosylation factor (ARF) family of small GTPases. During normal membrane trafficking in uninfected cells, ARFs are involved in vesicle formation from different intracellular sites through interaction with numerous regulatory and coat proteins as well as in regulation of phospholipase D activity and cytoskeleton modifications. We demonstrate here that ARFs 3 and 5, but not ARF6, are translocated to membranes in HeLa cell extracts that are engaged in translation of poliovirus RNA. The accumulation of ARFs on membranes correlates with active replication of poliovirus RNA in vitro, whereas ARF translocation to membranes does not occur in the presence of BFA. ARF translocation can be induced independently by synthesis of poliovirus 3A or 3CD proteins, and we describe mutations that abolished this activity. In infected HeLa cells, an ARF1-enhanced green fluorescent protein fusion redistributes from Golgi stacks to the perinuclear region, where poliovirus RNA replication occurs. Taken together, the data suggest an involvement of ARF in poliovirus RNA replication. C1 NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Ehrenfeld, E (reprint author), NIAID, Infect Dis Lab, NIH, Bldg 50,Room 6120, Bethesda, MD 20892 USA. EM eehrenfeld@niaid.nih.gov RI Belov, George/B-4625-2008 OI Belov, George/0000-0002-0892-1731 NR 83 TC 63 Z9 65 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 11 BP 7207 EP 7216 DI 10.1128/JVI.79.11.7207.7216.2005 PG 10 WC Virology SC Virology GA 925WY UT WOS:000229085400064 PM 15890959 ER PT J AU Nicola, AV Hou, J Major, EO Straus, SE AF Nicola, AV Hou, J Major, EO Straus, SE TI Herpes simplex virus type 1 enters human epidermal keratinocytes, but not neurons, via a pH-dependent endocytic pathway SO JOURNAL OF VIROLOGY LA English DT Article ID POLARIZED EPITHELIAL-CELLS; EPSTEIN-BARR-VIRUS; GLYCOPROTEINS GB; MDCK CELLS; HUMAN CYTOMEGALOVIRUS; MEMBRANE-FUSION; GH-GL; ENTRY; INFECTION; GD AB Herpes simplex virus (HSV) enters some laboratory cell lines via a pH-dependent, endocytic mechanism. We investigated whether this entry pathway is used in human cell types relevant to pathogenesis. Three different classes of lysosomotropic agents, which raise endosomal pH, blocked HSV entry into primary and transformed human keratinocytes, but not into human neurons or neuroblastoma lines. In keratinocytes, incoming HSV particles colocalized with markers of endocytic uptake. Treatment with the isoflavone genistein, an inhibitor of protein tyrosine kinases, reduced the delivery of incoming viral particles to the nuclear periphery and virus-induced gene expression in keratinocytes but not neurons. Moreover, in keratinocyte monolayer islets, HSV infected both the inner and outer cells in a genistein-sensitive manner, suggesting viral endocytosis from both basolateral and apical plasma membrane surfaces. Together, the results indicate that HSV enters human epidermal keratinocytes, but not neurons, by a low-pH, endocytic pathway that is dependent on host tyrosine phosphorylation. Thus, HSV utilizes fundamentally different cellular entry pathways to infect important target cell populations. C1 NIAID, Med Virol Sect, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NINDS, Lab Mol Med & Neurosci, NIH, Bethesda, MD 20892 USA. RP Nicola, AV (reprint author), 10 Ctr Dr,Room 11N228, Bethesda, MD 20892 USA. EM anicola@niaid.nih.gov NR 57 TC 129 Z9 131 U1 1 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 12 BP 7609 EP 7616 DI 10.1128/JVI.79.12.7609-7616.2005 PG 8 WC Virology SC Virology GA 930LA UT WOS:000229416100032 PM 15919913 ER PT J AU Evans, DT Bricker, JE Sanford, HB Lang, S Carville, A Richardson, BA Piatak, M Lifson, JD Mansfield, KG Desrosiers, RC AF Evans, DT Bricker, JE Sanford, HB Lang, S Carville, A Richardson, BA Piatak, M Lifson, JD Mansfield, KG Desrosiers, RC TI Immunization of macaques with single-cycle simian immunodeficiency virus (SIV) stimulates diverse virus-specific immune responses and reduces viral loads after challenge with SIV(mac)239 SO JOURNAL OF VIROLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY COMPLEX; T-CELL RESPONSES; I MOLECULE MAMU-A-ASTERISK-01; INFECTED RHESUS-MONKEYS; HIV-1 NEF PROTEIN; AIDS VACCINE; ATTENUATED SIV; LYMPHOCYTE RESPONSES; REPLICATIVE CAPACITY; RAPID TURNOVER AB Genetically engineered simian immunodeficiency viruses (SIV) that is limited to a single cycle of infection was evaluated as a nonreplicating AIDS vaccine approach for rhesus macaques. Four Mamu-A*01(+) macaques were inoculated intravenously with three concentrated doses of single-cycle SIV (scSM. Each dose consisted of a mixture of approximately equivalent amounts of scSIV strains expressing the SIV(mac)239 and SIV(mac)316 envelope glycoproteins with mutations in nef that prevent major histocompatibility complex (MHC) class I downregulation. Viral loads in plasma peaked between 10(4) and 10(5) RNA copies/ml on day 4 after the first inoculation and then steadily declined to undetectable levels over the next 4 weeks. SIN Gag-specific T-cell responses were detected in peripheral blood by MHC class I tetramer staining (peak, 0.07 to 0.2% CD8(+) T cells at week 2) and gamma interferon (IFN-gamma) enzyme-linked immunospot (ELISPOT) assays (peak, 50 to 250 spot forming celIS/10(6) peripheral blood mononuclear cell at week 3). Following the second and third inoculations at weeks 8 and 33, respectively, viral loads in plasma peaked between 10(2) and 10(4) RNA copies/ml on day 2 and were cleared over a 1-week period. T-cell-proliferative responses and antibodies to SIV were also observed after the second inoculation. Six weeks after the third dose, each animal was challenged intravenously with SIV(mac)239. All four animals became infected. However, three of the four scSIV-immunized animals exhibited 1 to 3 log reductions in acute-phase plasma viral loads relative to two Mamu-A*01(+) control animals. Additionally, two of these animals were able to contain their viral loads below 2,000 RNA copies/ml as late as 35 weeks into the chronic phase of infection. Given the extraordinary difficulty in protecting against SIV(mac)239, these results are encouraging and support further evaluation of lentiviruses that are limited to a single cycle of infection as a preclinical AIDS vaccine approach. C1 Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, New England Reg Primate Res Ctr, Southborough, MA 01772 USA. Univ Washington, Dept Biostat, Seattle, WA 98104 USA. NCI, Pathogenesis Lab, AIDS Vaccine Program, SAIC Frederick, Frederick, MD 21702 USA. RP Evans, DT (reprint author), Harvard Univ, Sch Med, Dept Microbiol & Mol Genet, New England Reg Primate Res Ctr, 1 Pine Hill Dr, Southborough, MA 01772 USA. EM devans@hms.harvard.edu FU NCRR NIH HHS [K26 RR000168, P51 RR000168, RR00168]; NIAID NIH HHS [AI10464, AI35365, AI52751, F32 AI010464, K22 AI052751, P01 AI035365, U01 AI035365] NR 67 TC 47 Z9 48 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 12 BP 7707 EP 7720 DI 10.1128/JVI.79.12.7707-7720.2005 PG 14 WC Virology SC Virology GA 930LA UT WOS:000229416100042 PM 15919923 ER PT J AU Bubeck, D Filman, DJ Cheng, NQ Steven, AC Hogle, JM Belnap, DM AF Bubeck, D Filman, DJ Cheng, NQ Steven, AC Hogle, JM Belnap, DM TI The structure of the poliovirus 135S cell entry intermediate at 10-Angstrom resolution reveals the location of an externalized polypeptide that binds to membranes SO JOURNAL OF VIROLOGY LA English DT Article ID CRYOELECTRON MICROSCOPY; 3-DIMENSIONAL STRUCTURE; ELECTRON-MICROSCOPY; RECEPTOR; VIRUS; TRANSITIONS; MICROGRAPHS; MUTANTS; MODEL; IMAGE AB Poliovirus provides a well-characterized system for understanding how nonenveloped viruses enter and infect cells. Upon binding its receptor, poliovirus undergoes an irreversible conformational change to the 135S cell entry intermediate. This transition involves shifts of the capsid protein 0 barrels, accompanied by the externalization of VP4 and the N terminus of V-P1. Both polypeptides associate with membranes and are postulated to facilitate entry by forming a translocation pore for the viral RNA. We have calculated cryoelectron microscopic reconstructions of 135S particles that permit accurate placement of the 0 barrels, loops, and terminal extensions of the capsid proteins. The reconstructions and resulting models indicate that each N terminus of VP1 exits the capsid though an opening in the interface between VP1 and VP3 at the base of the canyon that surrounds the fivefold axis. Comparison with reconstructions of 135S particles in which the first 31 residues of VP1 were proteolytically removed revealed that the externalized N terminus is located near the tips of propeller-like features surrounding the threefold axes rather than at the fivefold axes, as had been proposed in previous models. These observations have forced a reexamination of current models for the role of the 135S particle in transmembrane pore formation and suggest testable alternatives. C1 Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA. NIAMSD, Lab Struct Biol Res, NIH, Bethesda, MD 20892 USA. RP Hogle, JM (reprint author), Brigham Young Univ, Dept Chem & Biochem, Provo, UT 84602 USA. EM james_hogle@hms.harvard.edu FU NIAID NIH HHS [R01 AI020566-22, R21 AI020566, R01 AI020566-20A1, AI20566, R37 AI020566, R01 AI020566-24, R01 AI020566-23, R01 AI020566-21, R01 AI020566]; NIGMS NIH HHS [P01-GM62580, P01 GM062580] NR 36 TC 92 Z9 95 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 12 BP 7745 EP 7755 DI 10.1128/JVI.79.12.7745.7755 PG 11 WC Virology SC Virology GA 930LA UT WOS:000229416100046 PM 15919927 ER PT J AU Witvrouw, M Fikkert, V Hantson, A Pannecouque, C O'Keefe, BR McMahon, J Stamatatos, L de Clercq, E Bolmstedt, A AF Witvrouw, M Fikkert, V Hantson, A Pannecouque, C O'Keefe, BR McMahon, J Stamatatos, L de Clercq, E Bolmstedt, A TI Resistance of human immunodeficiency virus type 1 to the high-mannose binding agents cyanovirin N and concanavalin A SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN GP120; INACTIVATING PROTEIN; LINKED GLYCANS; PLANT-LECTINS; STRUCTURAL BASIS; ANTIBODY 2G12; CD4 BINDING; HIV TYPE-1; POTENT; GLYCOSYLATION AB Due to the biological significance of the carbohydrate component of the human immunodeficiency virus type 1 (HIV-1) glycoproteins in viral pathogenesis, the glycosylation step constitutes an attractive target for anti-HIV therapy. Cyanovirin N (CV-N), which specifically targets the high-mannose (HM) glycans on gp120, has been identified as a potent HIV-1 entry inhibitor. Concanavalin A (ConA) represents another mannose-binding lectin, although it has a lower specificity for HNI glycans than that of CV-N. For the present study, we selected CV-N- and ConA-resistant HIV-1 strains in the presence of CV-N and ConA, respectively. Both resistant strains exhibited a variety of mutations eliminating N-linked glycans within gp120. Strains resistant to CV-N or ConA displayed high levels of cross-resistance towards one another. The N-glycan at position 302 was eliminated in both of the lectin-resistant strains. However, the elimination of this glycan alone by site-directed mutagenesis was not sufficient to render HIV-1 resistant to CV-N or ConA, suggesting that HIV-1 needs to mutate several N-glycans to become resistant to these lectins. Both strains also demonstrated clear cross-resistance towards the carbohydrate-dependent monoclonal antibody 2G12. In contrast, the selected strains did not show a reduced susceptibility towards the nonlectin entry inhibitors AMD3100 and enfuvirtide or towards reverse transcriptase or protease inhibitors. Recombination of the mutated gp160 genes of the strains resistant to CV-N or ConA into a wild-type background fully reproduced the (cross-) resistance profiles of the originally selected strains, pointing to the impact of the N-glycan mutations on the phenotypic resistance profiles of both selected strains. C1 Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium. NCI, Mol Targets Dev Program, Canc Res Ctr, Frederick, MD USA. Univ Washington, Seattle Biomed Res Inst, Seattle, WA 98109 USA. Univ Washington, Dept Pathobiol, Seattle, WA 98109 USA. Swedish Inst Infect Dis Control, Ctr Microbiol Preparedness, Solna, Sweden. Gothenburg Univ, Dept Clin Virol, Gothenburg, Sweden. RP Bolmstedt, A (reprint author), Gothenburg Univ, Dept Clin Virol, Guldhedsgatan 10B, S-41346 Gothenburg, Sweden. EM anders.bolmstedt@vgregion.se NR 53 TC 65 Z9 68 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 12 BP 7777 EP 7784 DI 10.1128/JVI.79.12.7777-7784.2005 PG 8 WC Virology SC Virology GA 930LA UT WOS:000229416100049 PM 15919930 ER PT J AU Wang, SX Arthos, J Lawrence, JA Van Ryk, D Mboudjeka, I Shen, SY Chou, THW Montefiori, DC Lu, S AF Wang, SX Arthos, J Lawrence, JA Van Ryk, D Mboudjeka, I Shen, SY Chou, THW Montefiori, DC Lu, S TI Enhanced immunogenicity of gp120 protein when combined with recombinant DNA priming to generate antibodies that neutralize the JR-FL primary isolate of human immunodeficiency virus type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID ENVELOPE GLYCOPROTEIN; IMMUNE-RESPONSES; HIV-1; VACCINES; IMMUNIZATION; VACCINATION; VOLUNTEERS; INFECTION; SUBUNIT; AIDS AB Strategies are needed for human immunodeficiency virus type 1 vaccine development that improves the neutralizing antibody response against primary isolates of the virus. Here we examined recombinant DNA priming followed by subunit protein boosting as a strategy to generate neutralizing antibodies. Both plasmid-based and recombinant protein envelope (Env) glycoprotein immunogens were derived from a primary viral isolate, JR-FL. Serum from rabbits immunized with either gp120 or gp140 DNA vaccines delivered by gene gun inoculation followed by recombinant gp120 protein boosting was capable of neutralizing JR-FL. Neither the DNA vaccines alone nor the gp120 protein alone generated a detectable neutralizing antibody response against this virus. Neutralizing antibody responses using gp120 DNA and gp140 DNA for priming were similar. The results suggest that Env DNA priming followed by gp120 protein boosting provides an advantage over either approach alone for generating a detectable neutralizing antibody response against primary isolates that are not easily neutralized. C1 Univ Massachusetts, Sch Med, Dept Med, Worcester, MA 01605 USA. NIAID, Immunoregulat Lab, Bethesda, MD 20892 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. RP Lu, S (reprint author), Univ Massachusetts, Sch Med, Dept Med, 364 Plantat St,Lazare Res Bldg, Worcester, MA 01605 USA. EM shan.lu@umassmed.edu FU NIAID NIH HHS [R21 AI046294, AI46294, N01AI30034, AI40337] NR 24 TC 58 Z9 58 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2005 VL 79 IS 12 BP 7933 EP 7937 DI 10.1128/JVI.79.12.7933-7937.2005 PG 5 WC Virology SC Virology GA 930LA UT WOS:000229416100070 PM 15919951 ER PT J AU Longo, DL AF Longo, DL TI Closing in on a killer: Anemia in elderly people SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Editorial Material ID QUALITY-OF-LIFE; HEMOGLOBIN CONCENTRATION; CARDIOVASCULAR-DISEASE; OLDER-PEOPLE; PREVALENCE; MORTALITY; SURVIVAL; CANCER; MUSCLE; WOMEN C1 NIA, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Longo, DL (reprint author), NIA, Intramural Res Program, NIH, Rm 1-E-07,5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM longod@grc.nia.nih.gov NR 18 TC 5 Z9 5 U1 0 U2 0 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUN PY 2005 VL 60 IS 6 BP 727 EP 728 PG 2 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 939VL UT WOS:000230100500008 PM 15983174 ER PT J AU Chaves, PHM Semba, RD Leng, SX Woodman, RC Ferrucci, L Guralnik, JM Fried, LP AF Chaves, PHM Semba, RD Leng, SX Woodman, RC Ferrucci, L Guralnik, JM Fried, LP TI Impact of anemia and cardiovascular disease on frailty status of community-dwelling older women: The Women's Health and Aging Studies I and II SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID PHYSICAL PERFORMANCE; ELDERLY-PEOPLE; DISABILITY; HEMOGLOBIN; INTERLEUKIN-6; DECLINE; MUSCLE AB Background. The physiological basis of the geriatric syndrome of frailty, a clinical state of increased vulnerability to adverse outcomes such as disability and mortality, remains to be better characterized. We examined the cross-sectional relationship between hemoglobin (Hb) and a recently-validated measure of frailty in community-dwelling older women, and whether this relationship was modified by cardiovascular disease (CVD) status. Methods. Data were pooled from women 70-80 years old participating in the Women's Health and Aging Studies I and II (Baltimore, MD, 1992-1996) with known frailty status and Hb >= 10 g/dL (n = 670). Logistic regression was used to model the relationship between frailty and Hb, adjusting for demographics, major chronic diseases, and physiologic and functional impairments. Results. Prevalence of frailty was 14%. Frailty risk was highest at the lowest Hb levels, and lowest at mid-normal Hb levels (e.g., 13-14 g/dL). Mildly low and low-normal lib concentrations were independently associated with frailty. Compared to an Hb concentration equal to 13.5 g/dL, the adjusted odds of being frail were 1.9 (95% confidence interval: 1.1-3.4) and 1.5 (95% confidence interval: 1.0-2.1) times higher for Hb concentrations equal to 11.5 g/dL and 12 g/dL, respectively. A statistically significant (p < .05) multiplicative interaction between Hb level and CVD status with respect to frailty risk was observed. Conclusion. In community-dwelling older women, mildly low and low-normal Hb levels were independently associated with increased frailty risk. This risk was synergistically modified by the presence of CVD. These results suggest that mild anemia, and even low-normal Hb levels are independent, potentially modifiable risk factors for frailty in community-dwelling older adults. C1 Johns Hopkins Univ, Ctr Aging & Hlth, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD 21205 USA. Univ Estado Rio De Janeiro, Program Studies Debates Res & Care Elderly, UNATI, UERJ, Rio De Janeiro, Brazil. Ortho Biotech Clin Affairs, Bridgewater, NJ USA. NIA, Lab Clin Invest, Gerontol Res Ctr, Baltimore, MD 21224 USA. NIA, Lab Epidemiol Demog & Biometry, Baltimore, MD 21224 USA. RP Chaves, PHM (reprint author), Johns Hopkins Univ, Ctr Aging & Hlth, 2024 E Monument St,Suitee 2-700, Baltimore, MD 21205 USA. EM pchaves@jhsph.edu FU NCRR NIH HHS [RR00722]; NIA NIH HHS [N01 AG12112, P30 AG021334, R01 AG11703-01] NR 37 TC 117 Z9 120 U1 0 U2 4 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUN PY 2005 VL 60 IS 6 BP 729 EP 735 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 939VL UT WOS:000230100500009 PM 15983175 ER PT J AU Elosua, R Bartali, B Ordovas, JM Corsi, AM Lauretani, F Ferrucci, L AF Elosua, R Bartali, B Ordovas, JM Corsi, AM Lauretani, F Ferrucci, L CA InChianti Investigators TI Association between physical activity, physical performance, and inflammatory biomarkers in an elderly population: The InCHIANTI study SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID C-REACTIVE PROTEIN; CORONARY-HEART-DISEASE; CARDIOVASCULAR-DISEASE; CARDIORESPIRATORY FITNESS; ATHEROSCLEROSIS RISK; HORMONE REPLACEMENT; CLINICAL CARDIOLOGY; US ADULTS; EXERCISE; MARKERS AB Background. Our aim was to determine the association between physical activity and physical performance, and inflammatory biomarkers in elderly persons. Methods. One thousand four persons aged 65 years or more, participants in a cross-sectional population-based study, were included. Interviewers collected information on self-reported physical activity during the previous year, Moreover. 841 participants performed a 400-meter walking test to assess physical performance. plasma concentrations of inflammatory biomarkers were determined. Results. Compared to sedentary men, men practicing light and moderate-high physical activity had a significantly lower erythrocyte sedimentation rate (-0.33 and -0.40 mm/h, p = .023 and p = .006, respectively), fibrinogen level (-43 and -39 mg/dL p = .001 and p = .004, respectively), and logarithm of C-reactive protein (CRP) (-0.43 and -0.73 mg/L; p = .025 and p < .001, respectively), whereas only those men practicing moderate-high physical activity had a significantly lower uric acid level (-0.57 mg/dL; p = .023), log(interleukin 6) levels (-0.33 pg/mL; p = .014), and log(tumor necrosis factor-alpha) (-0.31 pg/mL; p = .030). In women, those practicing tight and moderate-high physical activity had significantly lower uric acid (-0.45 and -0.34 mg/dL; p = .001 and p = .039, respectively) and log(interleukin 6) levels (-0.18 and -0.30 pg/mL; p = .043 and p = .004, respectively); only those women practicing moderate-high physical activity had significantly lower log(CRP) (-0.31 mg/L; p = .020). In women, when the analysis was adjusted for body mass index. the association between physical activity and CRP was no longer significant. Similar findings were observed when we carried these analyses according to physical performance. Conclusions. Current physical activity practice and performance are associated with inflammatory biomarkers. A significant beneficial association is already observed with light physical activity practice and intermediate performance. C1 Inst Municipal Invest Med, Lipids & Cardiovasc Epidemiol Unit, Barcelona 08003, Spain. Tufts Univ, Nutr & Genom Lab, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. Natl Inst Res & Care Aging, Lab Clin Epidemiol, Dept Geriatr, Florence, Italy. Harbor Hosp, Longitudinal Studies Sect, Clin Res Branch, NIA,NIH,ASTRA Unit, Baltimore, MD 21224 USA. RP Elosua, R (reprint author), Inst Municipal Invest Med, Lipids & Cardiovasc Epidemiol Unit, Dr Aiguader 80, Barcelona 08003, Spain. EM relosua@imim.es RI Lauretani, Fulvio/K-5115-2016; OI ELOSUA, ROBERTO/0000-0001-8235-0095; Lauretani, Fulvio/0000-0002-5287-9972; Ordovas, Jose/0000-0002-7581-5680 FU NHLBI NIH HHS [HL54776] NR 41 TC 76 Z9 77 U1 0 U2 3 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD JUN PY 2005 VL 60 IS 6 BP 760 EP 767 PG 8 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 939VL UT WOS:000230100500014 PM 15983180 ER PT J AU Buchanan, D Miller, FG AF Buchanan, D Miller, FG TI Principles of early stopping of randomized trials for efficacy: A critique of equipoise and an alternative nonexploitation ethical framework SO KENNEDY INSTITUTE OF ETHICS JOURNAL LA English DT Article ID EARLY BREAST-CANCER; CLINICAL-TRIALS; POSTMENOPAUSAL WOMEN; THERAPEUTIC MISCONCEPTION; TAMOXIFEN THERAPY; STATISTICS; OBLIGATION; LETROZOLE AB Recent controversial decisions to terminate several large clinical trials have called attention to the need for developing a sound ethical framework to determine when trials should be stopped in light of emerging efficacy data. Currently, the fundamental rationale for stopping trials early is based on the principle that equipoise has been disturbed. We present an analysis of the ethical and practical problems with the "equipoise disturbed" position and describe an alternative ethical framework based on the principle of nonexploitation. This framework acknowledges the need for balancing the dual ethical obligations of clinical research, the protection of human subjects and the generation of new medical knowledge. Based on this framework, we put forward a proposal to make early stopping guidelines more stringent under specified conditions. The temporary withholding of apparent benefits in certain circumstances is justified by achieving a fair contract with the research participants, one that protects them from undue harm and exploitation while reducing the many uncertainties surrounding new investigational treatments that arise when trials are stopped prematurely. C1 NIH, Unit Clin Res, Dept Clin Bioeth, Bethesda, MD 20892 USA. NR 35 TC 21 Z9 21 U1 1 U2 3 PU JOHNS HOPKINS UNIV PRESS PI BALTIMORE PA JOURNALS PUBLISHING DIVISION, 2715 NORTH CHARLES ST, BALTIMORE, MD 21218-4363 USA SN 1054-6863 J9 KENNEDY INST ETHIC J JI Kennedy Inst. Ethics J. PD JUN PY 2005 VL 15 IS 2 BP 161 EP 178 DI 10.1353/ken.2005.0010 PG 18 WC Ethics; Philosophy; Social Issues SC Social Sciences - Other Topics; Philosophy; Social Issues GA 944XK UT WOS:000230464200003 PM 16149206 ER PT J AU Levey, AS Eckardt, KU Tsukamoto, Y Levin, A Coresh, J Rossert, J de Zeeuw, D Hostetter, TH Lameire, N Eknoyan, G AF Levey, AS Eckardt, KU Tsukamoto, Y Levin, A Coresh, J Rossert, J de Zeeuw, D Hostetter, TH Lameire, N Eknoyan, G TI Definition and classification of chronic kidney disease: A position statement from Kidney Disease: Improving Global Outcomes (KDIGO) SO KIDNEY INTERNATIONAL LA English DT Article DE chronic kidney disease; glomerular filtration rate; proteinuria; albuminuria; KDIGO ID GLOMERULAR-FILTRATION-RATE; HIGH BLOOD-PRESSURE; ALBUMIN/CREATININE RATIO; CARDIOVASCULAR-DISEASE; PRACTICE GUIDELINES; K/DOQI DEFINITION; SERUM CREATININE; STRATIFICATION; PREVENTION; EQUATIONS AB Chronic kidney disease (CKD) is a worldwide public health problem, with adverse outcomes of kidney failure, cardiovascular disease (CVD), and premature death. A simple definition and classification of kidney disease is necessary for international development and implementation of clinical practice guidelines. Kidney Disease: Improving Global Outcomes (KDIGO) conducted a survey and sponsored a controversies conference to (1) provide a clear understanding to both the nephrology and nonnephrology communities of the evidence base for the definition and classification recommended by Kidney Disease Quality Outcome Initiative (K/DOQI), (2) develop global consensus for the adoption of a simple definition and classification system, and (3) identify a collaborative research agenda and plan that would improve the evidence base and facilitate implementation of the definition and classification of CKD. The K/DOQI definition and classification were accepted, with clarifications. CKD is defined as kidney damage or glomerular filtration rate (GFR) <60 mL/min/1.73 m(2) for 3 months or more, irrespective of cause. Kidney damage in many kidney diseases can be ascertained by the presence of albuminuria, defined as albumin-to-creatinine ratio >30 mg/g in two of three spot urine specimens. GFR can be estimated from calibrated serum creatinine and estimating equations, such as the Modification of Diet in Renal Disease (MDRD) Study equation or the Cockcroft-Gault formula. Kidney disease severity is classified into five stages according to the level of GFR. Kidney disease treatment by dialysis and transplantation should be noted. Simple, uniform classifications of CKD by cause and by risks for kidney disease progression and CVD should be developed. C1 Tufts Univ New England Med Ctr, Boston, MA 02111 USA. Baylor Coll Med, Houston, TX 77030 USA. Ghent Univ Hosp, B-9000 Ghent, Belgium. NIH, Bethesda, MD 20892 USA. Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands. Hop Tenon, F-75970 Paris, France. Johns Hopkins Med Inst, Baltimore, MD 21205 USA. St Pauls Hosp, Vancouver, BC V6Z 1Y6, Canada. Kasukabe Shuwa Hosp, Saitama, Japan. Univ Hosp Erlangen, Erlangen, Germany. RP Levey, AS (reprint author), Tufts Univ New England Med Ctr, 750 Washington St,Box 391, Boston, MA 02111 USA. EM alevey@tufts-nemc.org RI de Zeeuw, Dick/E-9080-2014 OI de Zeeuw, Dick/0000-0003-3434-7777 NR 30 TC 1247 Z9 1387 U1 9 U2 70 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2005 VL 67 IS 6 BP 2089 EP 2100 DI 10.1111/j.1523-1755.2005.00365.x PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 929ZC UT WOS:000229384300001 PM 15882252 ER PT J AU Dear, JW Kobayashi, H Jo, SK Holly, MK Hu, XZ Yuen, PST Brechbiel, MW Star, RA AF Dear, JW Kobayashi, H Jo, SK Holly, MK Hu, XZ Yuen, PST Brechbiel, MW Star, RA TI Dendrimer-enhanced MRI as a diagnostic and prognostic biomarker of sepsis-induced acute renal failure in aged mice SO KIDNEY INTERNATIONAL LA English DT Article DE sepsis; MRI; gadolinium; dendrimer; acute renal failure; noninvasive; ethyl pyruvate ID CRITICALLY-ILL PATIENTS; TUBULE INJURY; MORTALITY; MULTICENTER; PROTEIN; DAMAGE; ICU AB Background. Acute renal failure (ARF) induced by sepsis has a high mortality. In an aged mouse model of sepsis-induced ARF we have previously shown that renal injury occurs before serum creatinine is elevated. Development of a noninvasive biomarker that could diagnose renal dysfunction early in sepsis and monitor the response to therapy would be very valuable. Methods. We performed magnetic resonance imaging (MRI) with gadolinium-based G4 dendrimer intravenous contrast in a fluid- and antibiotic-treated cecal ligation and puncture (CLP) sepsis model in aged mice. Imaging was also performed in a mouse volume depletion model and in models of ARF induced by ischemia/reperfusion (I/R) and cisplatin. Results. Twenty hours post-CLP, aged mice had a distinct pattern of renal injury using dendrimer-enhanced MRI. This pattern was different from renal injury induced by either cisplatin or I/R. Prerenal azotemia induced by volume depletion was distinguished from sepsis by dendrimer-enhanced MRI. Dendrimer-enhanced MRI detected renal dysfunction 6 hours post-CLP, a time when serum creatinine was still normal. Ethyl pyruvate reversed the renal dysfunction detected by dendrimer-enhanced MRI at 20 hours, but not at 6 hours post-CLP. The appearance of renal dysfunction on dendrimer-enhanced MRI at 6 hours post-CLP predicted the length of survival. Conclusion. Dendrimer-enhanced MRI is a novel biomarker that provides information for the early diagnosis, drug responsiveness, and prognosis of sepsis-induced ARF. C1 NIDDK, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD 20892 USA. NCI, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, Radioimmune & Inorgan Chem Sect, Radiat Oncol Branch, NIH, Bethesda, MD 20892 USA. RP Star, RA (reprint author), NIDDK, Renal Diagnost & Therapeut Unit, NIH, 10 Ctr Dr,Bldg 10,Room 3N108, Bethesda, MD 20892 USA. EM Robert_Star@nih.gov RI Yuen, Peter/B-1954-2008 OI Yuen, Peter/0000-0001-9557-3909 NR 25 TC 45 Z9 46 U1 0 U2 3 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0085-2538 J9 KIDNEY INT JI Kidney Int. PD JUN PY 2005 VL 67 IS 6 BP 2159 EP 2167 DI 10.1111/j.1523-1755.2005.00321.x PG 9 WC Urology & Nephrology SC Urology & Nephrology GA 929ZC UT WOS:000229384300008 PM 15882259 ER PT J AU Feldman, AL Berthold, F Arceci, R Abramowsky, C Shehata, BM Mann, KP Lauer, S Pritchard, J Raffeld, M Sjaffe, ES AF Feldman, AL Berthold, F Arceci, R Abramowsky, C Shehata, BM Mann, KP Lauer, S Pritchard, J Raffeld, M Sjaffe, ES TI Clonal relationship between precursor T-lymphoblastic leukaemia/lymphoma and Langerhans-cell histiocytosis SO LANCET ONCOLOGY LA English DT Article ID LEUKEMIA; LYMPHOMAS; TUMORS C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. Univ Clin Koln, Ctr Paediat Oncol & Haematol, Cologne, Germany. Sidney Kimmel Comprehens Canc Ctr John Hopkins, Baltimore, MD USA. Emory Univ, Med Ctr, Dept Pathol, Atlanta, GA USA. Emory Univ, Med Ctr, Dept Pediat, Atlanta, GA USA. Royal Hosp Sick Children, Dept Haematol & Oncol, Edinburgh EH9 1LF, Midlothian, Scotland. RP Feldman, AL (reprint author), NCI, Pathol Lab, Bldg 10,Room 2N202,10 Ctr Dr, Bethesda, MD 20892 USA. EM feldmana@mail.nih.gov RI Feldman, Andrew/D-5028-2012 NR 11 TC 57 Z9 60 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1470-2045 J9 LANCET ONCOL JI Lancet Oncol. PD JUN PY 2005 VL 6 IS 6 BP 435 EP 437 DI 10.1016/S1470-2045(05)70211-4 PG 3 WC Oncology SC Oncology GA 933HR UT WOS:000229620000031 PM 15925822 ER PT J AU Mestre, C Rubio-Moscardo, F Rosenwald, A Climent, J Dyer, MJS Staudt, L Pinkel, D Siebert, R Martinez-Climent, JA AF Mestre, C Rubio-Moscardo, F Rosenwald, A Climent, J Dyer, MJS Staudt, L Pinkel, D Siebert, R Martinez-Climent, JA TI Homozygous deletion of SOCS1 in primary mediastinal B-cell lymphoma detected by CGH to BAC microarrays SO LEUKEMIA LA English DT Letter ID HODGKIN LYMPHOMA; EXPRESSION; GENE C1 Univ Navarra, Ctr Appl Med Res CIMA, Oncol Mol Lab, Div Oncol, Pamplona, Spain. Univ Valencia, Hosp Clin, Dept Hematol & Med Oncol, E-46003 Valencia, Spain. Univ Wurzburg, Dept Pathol, D-97070 Wurzburg, Germany. Univ Leicester, MRC, Toxicol Unit, Leicester LE1 7RH, Leics, England. NCI, Ctr Canc Res, Bethesda, MD 20892 USA. Univ Calif San Francisco, Canc Res Inst, San Francisco, CA 94143 USA. Univ Hosp Schleswig Holstein, Inst Human Genet, Kiel, Germany. RP Martinez-Climent, JA (reprint author), Univ Navarra, Ctr Appl Med Res CIMA, Oncol Mol Lab, Div Oncol, Avda Pio XII,55, Pamplona, Spain. EM jamcliment@unav.es RI Siebert, Reiner/A-8049-2010; Rubio Moscardo, Francisca/L-6247-2014; Martinez-Climent, Jose/I-9199-2012 OI Rubio Moscardo, Francisca/0000-0002-3609-9992; Martinez-Climent, Jose/0000-0002-7938-3950 NR 10 TC 17 Z9 18 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0887-6924 J9 LEUKEMIA JI Leukemia PD JUN PY 2005 VL 19 IS 6 BP 1082 EP 1084 DI 10.1038/sj.leu.2403741 PG 4 WC Oncology; Hematology SC Oncology; Hematology GA 929EC UT WOS:000229323900032 PM 15815722 ER PT J AU Dunson, DB Herring, AH AF Dunson, DB Herring, AH TI Bayesian model selection and averaging in additive and proportional hazards models SO LIFETIME DATA ANALYSIS LA English DT Article DE additive hazards; Cox model; Gibbs sampler; order restricted inference; posterior probability; proportional hazards; survival analysis; variable selection ID CENSORED SURVIVAL-DATA; VARIABLE SELECTION; SEMIPARAMETRIC ANALYSIS; RISK MODEL; CRITERION AB Although Cox proportional hazards regression is the default analysis for time to event data, there is typically uncertainty about whether the effects of a predictor are more appropriately characterized by a multiplicative or additive model. To accommodate this uncertainty, we place a model selection prior on the coefficients in an additive-multiplicative hazards model. This prior assigns positive probability, not only to the model that has both additive and multiplicative effects for each predictor, but also to sub-models corresponding to no association, to only additive effects, and to only proportional effects. The additive component of the model is constrained to ensure non-negative hazards, a condition often violated by current methods. After augmenting the data with Poisson latent variables, the prior is conditionally conjugate, and posterior computation can proceed via an efficient Gibbs sampling algorithm. Simulation study results are presented, and the methodology is illustrated using data from the Framingham heart study. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. RP Dunson, DB (reprint author), NIEHS, Biostat Branch, MD A3-03,POB 12233, Res Triangle Pk, NC 27709 USA. EM dunson1@niehs.nih.gov NR 23 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1380-7870 J9 LIFETIME DATA ANAL JI Lifetime Data Anal. PD JUN PY 2005 VL 11 IS 2 BP 213 EP 232 DI 10.1007/s10985-004-0384-x PG 20 WC Mathematics, Interdisciplinary Applications; Statistics & Probability SC Mathematics GA 915DJ UT WOS:000228277600004 PM 15938547 ER PT J AU Yang, JH Li, CQ Shen, J AF Yang, JH Li, CQ Shen, J TI In vivo detection of cortical GABA turnover from intravenously infused [1-C-13]D-glucose SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE GABA turnover; cerebral metabolism; carbon-13; high-field in vivo spectroscopy; inhibition ID GAMMA-VINYL GABA; RAT-BRAIN; NMR-SPECTROSCOPY; C-13 NMR; METABOLISM; GLUTAMINE; GLUCOSE; PULSES; QUANTIFICATION; INHIBITION AB In this study [2-C-13] gamma-aminobutyric acid (GABA) was spectrally resolved in vivo and detected simultaneously with [4-C-13]glutamate (Glu) and [4-C-13]glutamine (Gln) in the proton spectra obtained from a localized 40 mu L voxel in rat neocortex with the use of an adiabatic H-1-observed, C-13-edited (POCE) spectroscopy method and an 89-mm-bore vertical 11.7 Tesla microimager. The time-resolved kinetics of C-13 label incorporation from intravenously infused [1-C-13]glucose into [4-C-13]Glu, [4-C-13]Gln, and [2-C-13]GABA were measured after acute administration of gabaculine, a potent and specific inhibitor of GABA-transaminase. In contrast to previous observations of a rapid turnover of [2-C-13]GABA from [1-C-13] glucose in intact rat brain, the rate of C-13 incorporation from [1-C-13]glucose into [2-C-13]GABA in the gabaculine-treated rats was found to be significantly reduced as a result of the blockade of the GABA shunt. Published 2005 Wiley-Liss, Inc.dagger C1 NIMH, Mol Imaging Branch, Bethesda, MD 20892 USA. RP Shen, J (reprint author), NIMH, Mol Imaging Branch, Bldg 10,Rm 2D51A,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shenj@intra.nimh.nih.gov NR 38 TC 18 Z9 18 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JUN PY 2005 VL 53 IS 6 BP 1258 EP 1267 DI 10.1002/mrm.20473 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 931EI UT WOS:000229468200004 PM 15906278 ER PT J AU Jones, DK Travis, AR Eden, G Pierpaoli, C Basser, PJ AF Jones, DK Travis, AR Eden, G Pierpaoli, C Basser, PJ TI PASTA: Pointwise assessment of streamline tractography attributes SO MAGNETIC RESONANCE IN MEDICINE LA English DT Article DE DT-MRI; artifacts; distribution; visualization; hyperstreamline ID DT-MRI DATA; DIFFUSION-TENSOR MRI; HUMAN BRAIN; TRACKING; UNCERTAINTY; ORIENTATION; FEATURES; TISSUES AB Diffusion tensor MRI tractography aims to reconstruct noninvasively the 3D trajectories of white matter fasciculi within the brain, providing neuroscientists and clinicians with a potentially useful tool for mapping brain architecture. While this technique is widely used to visualize white matter pathways, the associated uncertainty in fiber orientation and artifacts have, to date, not been visualized in conjunction with the trajectory data. In this work, the bootstrap method was used to determine the distributions of diffusion indices such as trace and anisotropy, together with the uncertainty in fiber orientation. A novel visualization scheme was developed to encode this information at each point along reconstructed trajectories. By integrating these schemes into a graphical user interface, a new tool which we call PASTA (Pointwise Assessment of Streamline Tractography Attributes) was created to facilitate identification of artifacts in tractography that would otherwise go undetected. Published 2005 Wiley-Liss, Inc. C1 Inst Psychiat, Ctr Neuroimaging Sci, London SE5 8AF, England. NICHHD, Sect Tissue Biophys & Biomimet, Lab Integrat Med & Biophys, NIH, Bethesda, MD 20892 USA. Vanderbilt Univ, Sch Engn, Dept Biomed Engn, Nashville, TN USA. RP Jones, DK (reprint author), Inst Psychiat, Ctr Neuroimaging Sci, De Crespigny Pk,P089, London SE5 8AF, England. EM d.jones@iop.kcl.ac.uk RI Pierpaoli, Carlo/E-1672-2011; Jones, Derek/D-1460-2009; Basser, Peter/H-5477-2011; OI Jones, Derek/0000-0003-4409-8049 FU Wellcome Trust NR 24 TC 58 Z9 58 U1 0 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0740-3194 J9 MAGNET RESON MED JI Magn. Reson. Med. PD JUN PY 2005 VL 53 IS 6 BP 1462 EP 1467 DI 10.1002/mrm.20484 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 931EI UT WOS:000229468200030 PM 15906294 ER PT J AU Egger, JR Cutter, GR Carney, PA Taplin, SH Barlow, WE Hendrick, RE D'Orsi, CJ Fosse, JS Abraham, L Elmore, JG AF Egger, JR Cutter, GR Carney, PA Taplin, SH Barlow, WE Hendrick, RE D'Orsi, CJ Fosse, JS Abraham, L Elmore, JG TI Mammographers' perception of women's breast cancer risk SO MEDICAL DECISION MAKING LA English DT Article DE perception; risk; pretest probability ID SCREENING MAMMOGRAPHY; POPULATION; DECISIONS; JUDGMENTS; OUTCOMES; IMPACT AB Objective. To understand mammographers' perception of individual women's breast cancer risk. Materials and Methods. Radiologists interpreting screening mammography examinations completed a mailed survey consisting of questions pertaining to demographic and clinical practice characteristics, as well as 2 vignettes describing different risk profiles of women. Respondents were asked to estimate the probability of a breast cancer diagnosis in the next 5 years for each vignette. Vignette responses were plotted against mean recall rates in actual clinical practice. Results. The survey was returned by 77% of eligible radiologists. Ninety-three percent of radiologists overestimated risk in the vignette involving a 70-year-old woman; 96% overestimated risk in the vignette involving a 41-year-old woman. Radiologists who more accurately estimated breast cancer risk were younger, worked full-time, were affiliated with an academic medical center, had fellowship training, had fewer than 10 years experience interpreting mammograms, and worked more than 40% of the time in breast imaging. However, only age was statistically significant. No association was found between radiologists' risk estimate and their recall rate. Conclusion. U.S. radiologists have a heightened perception of breast cancer risk. C1 Univ Washington, Harborview Med Ctr, Sch Med, Div Gen Internal Med, Seattle, WA 98104 USA. Univ Nevada, Sch Med, Ctr Res Design & Stat Methods, Reno, NV 89557 USA. Dartmouth Coll Sch Med, Dept Community & Family Med, Lebanon, NH USA. NCI, Appl Res Program, Bethesda, MD 20892 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Northwestern Univ, Sch Med, Lynn Sage Comprehens Breast Ctr, Chicago, IL USA. Emory Hlth Care Serv, Breast Imaging Ctr, Atlanta, GA USA. RP Elmore, JG (reprint author), Univ Washington, Harborview Med Ctr, Sch Med, Div Gen Internal Med, 325 9th Ave,Box 359780, Seattle, WA 98104 USA. EM jelmore@u.washington.edu FU AHRQ HHS [HS10591, R01 HS010591]; NCI NIH HHS [U01 CA063731, U01 CA086082, U01 CA63731, 5 U01 CA 63736-09, R01 CA107623, 1 U01 CA86082-01, CA1040699, K05 CA104699, R01 CA107623-04, U01 CA063736] NR 24 TC 12 Z9 13 U1 2 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0272-989X J9 MED DECIS MAKING JI Med. Decis. Mak. PD JUN PY 2005 VL 25 IS 3 BP 283 EP 289 DI 10.1177/0272989X05276857 PG 7 WC Health Care Sciences & Services; Medical Informatics SC Health Care Sciences & Services; Medical Informatics GA 928WA UT WOS:000229301200005 PM 15951455 ER PT J AU Choi, EH Taylor, JG Foster, CB Walsh, TJ Anttila, VJ Ruutu, T Palotie, A Chanock, SJ AF Choi, EH Taylor, JG Foster, CB Walsh, TJ Anttila, VJ Ruutu, T Palotie, A Chanock, SJ TI Common polymorphisms in critical genes of innate immunity do not contribute to the risk for chronic disseminated candidiasis in adult leukemia patients SO MEDICAL MYCOLOGY LA English DT Article DE chronic disseminated candidiasis; innate immunity; polymorphisms ID HEPATOSPLENIC CANDIDIASIS; HUMAN-DISEASE; HOST-DEFENSE; ALBICANS; INTERLEUKIN-4; SUSCEPTIBILITY; ASSOCIATION; INFECTION; THERAPY; CANCER AB Chronic disseminated candidiasis is a serious fungal infection in immunocompromised patients, particularly those undergoing therapy for acute leukemia. Coordination between innate and adaptive immune system is critical to resistance or susceptibility to Candida infection. In order to investigate possible genetic contribution to chronic disseminated candidiasis of key molecules in the innate immune pathway, we performed a case control study using the candidate gene approach. Forty subjects with chronic disseminated candidiasis and 50 controls without chronic disseminated candidiasis but an underlying diagnosis of leukemia were enrolled in the Helsinki University Central Hospital during the period 1980-1998. Candidate genes were selected for analysis based upon the following criteria: a common polymorphism ( > 5% frequency) and existence a priori of clinical and biological data suggesting a role for the variant in the pathogenesis of chronic disseminated candidiasis. Six genes were selected from critical microbicidal and innate immune pathways, including three low-affinity Fc gamma receptors (FCGR2A, FCGR3A and FCGR3B), chitotriosidase (CHIT1), p22-phox NADPH oxidase (CYBA), and mannose binding lectin (MBL2). There was no statistically significant association of susceptibility to chronic disseminated candidiasis with the polymorphisms in this study. Common variants in the six studied genes most likely do not contribute to the risk for chronic disseminated candidiasis in patients with acute leukemia. C1 NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol,NIH, Bethesda, MD 20892 USA. NCI, Immunocompromised Host Sect, Pediat Oncol Branch, NIH, Bethesda, MD 20892 USA. Univ Helsinki, Cent Hosp, Dept Med, Div Hematol, Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Med, Div Infect Dis, Helsinki, Finland. Univ Helsinki, Cent Hosp, Dept Clin Chem, Helsinki, Finland. RP Chanock, SJ (reprint author), NCI, Sect Genom Variat, Pediat Oncol Branch, Ctr Adv Technol,NIH, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM sc83a@nih.gov OI Taylor, James/0000-0002-4421-1809 NR 23 TC 15 Z9 16 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD JUN PY 2005 VL 43 IS 4 BP 349 EP 353 DI 10.1080/13693780412331282322 PG 5 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 949WP UT WOS:000230819900006 PM 16110781 ER PT J AU Ma, D Parikh, P Lu, W Nystrom, M Hubenschmidt, J Wahab, S Singh, A AF Ma, D Parikh, P Lu, W Nystrom, M Hubenschmidt, J Wahab, S Singh, A TI Patterns of intraabdominal organ motion as measured by quantitative 4D CT SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 24-28, 2005 CL Seattle, WA SP Amer Assoc Physicists Med C1 Washington Univ, St Louis, MO USA. NIH, Washington, DC USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2005 VL 32 IS 6 BP 1948 EP 1948 DI 10.1118/1.1997667 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937EY UT WOS:000229908600296 ER PT J AU Yadava, G Rudin, S Bednarek, D Hoffmann, K Kyprianou, I AF Yadava, G Rudin, S Bednarek, D Hoffmann, K Kyprianou, I TI A total-imaging-systern generalized performance comparison of an x-ray image intensifier and a microangiographic system in neurovascular angiography: Effect of focal spot and scatter SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 24-28, 2005 CL Seattle, WA SP Amer Assoc Physicists Med C1 SUNY Buffalo, Toshiba Stroke Res Ctr, Dept Phys, Buffalo, NY 14260 USA. US FDA, NIBIB, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2005 VL 32 IS 6 BP 2080 EP 2081 DI 10.1118/1.1998339 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937EY UT WOS:000229908601248 ER PT J AU Deye, J AF Deye, J TI NCI talk on funding SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 24-28, 2005 CL Seattle, WA SP Amer Assoc Physicists Med C1 Natl Canc Inst, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2005 VL 32 IS 6 BP 2117 EP 2118 DI 10.1118/1.1998483 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937EY UT WOS:000229908601393 ER PT J AU Zhang, M AF Zhang, M TI Superparamagnetic nanoparticles for brain tumor diagnosis and therapeutics SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 24-28, 2005 CL Seattle, WA SP Amer Assoc Physicists Med C1 Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NCI, Bethesda, MD 20892 USA. Univ Washington, Seattle, WA 98195 USA. RI Zhang, Miqin/F-5537-2010 OI Zhang, Miqin/0000-0001-8974-1494 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2005 VL 32 IS 6 BP 2130 EP 2130 DI 10.1118/1.1998534 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937EY UT WOS:000229908601441 ER PT J AU Clarke, L AF Clarke, L TI Role of imaging in drug response: Challenges and opportunities SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 47th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 24-28, 2005 CL Seattle, WA SP Amer Assoc Physicists Med C1 Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. NCI, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2005 VL 32 IS 6 BP 2135 EP 2136 DI 10.1118/1.1999736 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 937EY UT WOS:000229908601463 ER PT J AU Yang, QE Fong, SE Li, KG Gonda, MA Tobin, GJ AF Yang, QE Fong, SE Li, KG Gonda, MA Tobin, GJ TI Ex vivo expanded murine bone marrow cells with a multiple cytokine cocktail retain long-term hematopoietic reconstitution potentials SO MEDICAL SCIENCE MONITOR LA English DT Article DE stem cell; bone marrow transplantation; ex vivo expansion; cytokine; hematopoietic stimulation factor; hematopoiesis ID UMBILICAL-CORD BLOOD; COLONY-STIMULATING FACTOR; MEDIATED GENE-TRANSFER; PROGENITOR CELLS; STEM-CELLS; TRANSPLANTATION; EXPANSION; ENGRAFTMENT; INTERLEUKIN-3; CULTURE AB Background: Although ex vivo expansion of bone marrow (BM) cells has been proposed as an effective method for the early recovery from pancytopenia in patients with bone marrow stem cell transplantation (BMT), the expansion potential and the long-term reconstitution capability of such BM cells is still controversial. We. describe here a multiple cytokine medium (MCM) containing major hematopoietic stimulation factors and conditioned medium from PHA-stimulated murine spleen cells that permits the expansion of BM cells with long-term hematopoietic reconstitution capacity. Material/Methods: Male murine BM cells were expanded in MCM for 4 to 14 days and injected into lethally irradiated syngeneic female mice. The mice were maintained for 18 months after transplantation for evaluation of hematopoietic reconstitution. Results: The expanded cells contained pluripotent hematopoietic stem cells and lineage committed progenitors as well as terminally differentiated cells. They permitted full recovery of lethally irradiated mice in both early and late stages in same numbers equivalent to that of unexpanded cells. More than 80% of the progenitor cells were donor originated after 18 months. Expanded cells were able to be transduced with a retroviral vector expressing beta-galactosidase, and continued to express the marker following BMT. Conclusions: With the use of MCM, the quantity of donor cells from BM and other sources might be greatly reduced. Ex vivo expanded BM cells might also facilitate gene manipulation in vitro by retroviral vectors. C1 NCI, SAIC Frederick Inc, Lab Cell & Mol Struct, Frederick, MD 21702 USA. Mudanjiang Med Coll, Dept Med, Mudanjiang, Heilongjiang, Peoples R China. TransMolecular Inc, Birmingham, AL USA. Biol Mimet Inc, Frederick, MD USA. RP Yang, QE (reprint author), NCI, SAIC Frederick Inc, Lab Pharmacodynam & Toxicol, Dev Therapeut Program, Bldg 439,POB B, Frederick, MD 21702 USA. EM yangq@dtpax2.ncifcrf.gov FU PHS HHS [N01-C0-56000] NR 43 TC 2 Z9 2 U1 0 U2 0 PU INT SCIENTIFIC LITERATURE, INC PI ALBERTSON PA 1125 WILLIS AVE, ALBERTSON, NY 11507 USA SN 1234-1010 J9 MED SCI MONITOR JI Med. Sci. Monitor PD JUN PY 2005 VL 11 IS 6 BP BR154 EP BR161 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 939YN UT WOS:000230108900003 PM 15917709 ER PT J AU Suwannarat, P O'Brien, K Perry, MB Sebring, N Bernardini, I Kaiser-Kupfer, MI Rubin, BI Tsilou, E Gerber, LH Gahl, WA AF Suwannarat, P O'Brien, K Perry, MB Sebring, N Bernardini, I Kaiser-Kupfer, MI Rubin, BI Tsilou, E Gerber, LH Gahl, WA TI Use of nitisinone in patients with alkaptonuria SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID TYROSINEMIA TYPE-I; 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE; NTBC; GENE; ACID AB Alkaptonuria, a rare autosomal recessive disorder caused by mutations in the HGD gene and deficiency of homogentisate 1,2 dioxygenase, is characterized by ochronosis, arthritis, and daily excretion of gram quantities of homogentisic acid (HGA). Nitisinone, an inhibitor of the enzyme 4-hydroxyphenylpyruvate dioxygenase, can drastically reduce urinary excretion of HGA in individuals with alkaptonuria. We investigated the safety and the HGA-depleting efficacy of nitisinone in an open-label, single-center study of 9 alkaptonuria patients (5 women, 4 men; 35-69 years of age) over the course of 3 to 4 months. Each patient received nitisinone in incremental doses, 0.35 mg bid followed by 1.05 mg bid, and remained on this dosage and a regular diet for 3 months. Nitisinone reduced urinary HGA levels from an average of 4.0 +/- 1.8 (SD) g/day to 0.2 +/- 0.2 g/day (P < .001). The average plasma tyrosine concentration, initially 68 +/- 18 mu mol/L, rose to 760 +/- 181 mu mol/L (P < .001). During the final week of the study, 5 patients adhered to a protein-restricted diet (40 g/day), and their mean plasma tyrosine level fell from 755 +/- 167 to 603 +/- 114 mu mol/L. Six of the 7 patients who received nitisinone for more than I week reported decreased pain in their affected joints. Weekly ophthalmologic examinations showed no signs of corneal toxicity. Adverse events included the passing of kidney stones, the recognition of symptoms related to aortic stenosis, and elevation of liver transaminase levels. We conclude that low-dose nitisinone effectively reduced urinary HGA levels in patients with alkaptonuria. Future long-term clinical trials are planned to determine the benefits of nitisinone in preventing joint deterioration and providing pain relief, and its long-term side effects. (c) 2005 Elsevier Inc. All rights reserved. C1 NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. NIH, Intramural Off Rare Dis, Off Director, Bethesda, MD 20892 USA. NIH, Dept Rehabil Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Dept Nutr, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NEI, Ophthalm Genet & Visual Funct Branch, NIH, Bethesda, MD 20892 USA. RP Gahl, WA (reprint author), NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM bgahl@helix.nih.gov NR 26 TC 59 Z9 63 U1 0 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUN PY 2005 VL 54 IS 6 BP 719 EP 728 DI 10.1016/j.metabol.2004.12.017 PG 10 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 934UI UT WOS:000229733700004 PM 15931605 ER PT J AU Hinton, DM Pande, S Wais, N Johnson, XB Vuthoori, M Makela, A Hook-Barnard, I AF Hinton, DM Pande, S Wais, N Johnson, XB Vuthoori, M Makela, A Hook-Barnard, I TI Transcriptional takeover by sigma appropriation: remodelling of the sigma(70) subunit of Escherichia coli RNA polymerase by the bacteriophage T4 activator MotA and co-activator AsiA SO MICROBIOLOGY-SGM LA English DT Review ID PROTEIN-PROTEIN INTERACTIONS; PROMOTERS IN-VIVO; MIDDLE PROMOTERS; T4 ASIA; REGION 4; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURE; MUTATION ANALYSIS; STRUCTURAL BASIS; BINDING-PROTEIN AB Activation of bacteriophage T4 middle promoters, which occurs about 1 min after infection, uses two phage-encoded factors that change the promoter specificity of the host RNA polymerase. These phage factors, the MotA activator and the AsiA co-activator, interact with the sigma(70) specificity subunit of Escherichia coli RNA polymerase, which normally contacts the -10 and -35 regions of host promoter DNA. Like host promoters, T4 middle promoters have a good match to the canonical 670 DNA element located in the -10 region. However, instead of the sigma(70) DNA recognition element in the promoter's -35 region, they have a 9 bp sequence (a MotA box) centred at -30, which is bound by MotA. Recent work has begun to provide information about the MotA/AsiA system at a detailed molecular level. Accumulated evidence suggests that the presence of MotA and AsiA reconfigures protein-DNA contacts in the upstream promoter sequences, without significantly affecting the contacts of sigma(70) with the -10 region. This type of activation, which is called 'sigma appropriation', is fundamentally different from other well-characterized models of prokaryotic activation in which an activator frequently serves to force sigma(70) to contact a less than ideal - 35 DNA element. This review summarizes the interactions of AsiA and MotA with sigma(70), and discusses how these interactions accomplish the switch to T4 middle promoters by inhibiting the typical contacts of the C-terminal region of sigma(70), region 4, with the host -35 DNA element and with other subunits of polymerase. C1 NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hinton, DM (reprint author), NIDDKD, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. EM dhinton@helix.nih.gov NR 91 TC 35 Z9 35 U1 1 U2 8 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD JUN PY 2005 VL 151 BP 1729 EP 1740 DI 10.1099/mic.0.27972-0 PN 6 PG 12 WC Microbiology SC Microbiology GA 938ZF UT WOS:000230041200002 PM 15941982 ER PT J AU Gao, ZG Kim, SK IJzerman, AP Jacobson, KA AF Gao, ZG Kim, SK IJzerman, AP Jacobson, KA TI Allosteric modulation of the adenosine family of receptors SO MINI-REVIEWS IN MEDICINAL CHEMISTRY LA English DT Review ID SITE-DIRECTED MUTAGENESIS; PROTEIN-COUPLED RECEPTORS; ENHANCER PD 81,723; A(1) RECEPTOR; AMILORIDE ANALOGS; ANTAGONIST BINDING; AGONIST BINDING; ADENOSINE-A1-RECEPTOR BINDING; ALPHA-2-ADRENERGIC RECEPTORS; ENDOGENOUS ADENOSINE AB Allosteric modulators for adenosine receptors (ARs) are of an increasing interest and may have potential therapeutic advantage over orthosteric ligands. Benzoylthiophene derivatives (including PD 81,723), 2-aminothiazolium salts, and related allosteric modulators of the A(1) AR have been studied. The benzoylthiophene derivatives were demonstrated to be selective enhancers for the A(1) AR, with little or no effect on other subtypes of ARs. Allosteric modulation of the A(2A) AR has also been reported. A(3) allosteric enhancers may be predicted to be useful against ischemic conditions. We have recently characterized two classes of A(3) AR allosteric modulators: 3-(2-pyridinyl)isoquinolines (e.g. VUF5455) and 1H-imidazo-[4,5-c]quinolin-4-amines (e.g. DU124183), which selectively decreased the agonist dissociation rate at the human A(3)AR but not at A(1) and A(2)A ARs. DU124183 left-shifted the agonist conc.-response curve for inhibition of forskolin-stimulated cAMP accumulation in intact cells expressing the human A(3)AR with up to 30% potentiation of the maximal efficacy. The increased potency of A(3) agonists was evident only in the presence of an A(3) antagonist, since VUF5455 and DU124183 also antagonized, i.e. displaced binding at the orthosteric site, with K-i values of 1.68 and 0.82 μ M, respectively. A(3)AR mutagenesis studies implicated F182(5.43) and N274(7.45) in the action of the enhancers and was interpreted using a rhodopsin-based A(3)AR molecular model, suggesting multiple binding modes. Amiloride analogues, SCH-202676 (N-(2,3-diphenyl-1,2,4-thiadiazol-5(2H)-ylidene)methanamine), and sodium ions were demonstrated to be common allosteric modulators for at least three subtypes (A(1), A(2)A, and A(3)) of ARs. C1 NIDDK, Mol Recognit Sect, LBC,Dept Hlth & Human Serv, NIH, Bethesda, MD 20892 USA. Leiden Univ, Div Med Chem, Lieden Amsterdam Ctr Drug Res, NL-2300 RA Leiden, Netherlands. RP Jacobson, KA (reprint author), NIDDK, Mol Recognit Sect, LBC,Dept Hlth & Human Serv, NIH, Bldg 8A,Rm B1A-19, Bethesda, MD 20892 USA. EM kajacobs@helix.nih.gov RI Jacobson, Kenneth/A-1530-2009 OI Jacobson, Kenneth/0000-0001-8104-1493 FU Intramural NIH HHS [Z01 DK031117-20, Z99 DK999999] NR 48 TC 46 Z9 48 U1 1 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1389-5575 J9 MINI-REV MED CHEM JI Mini-Rev. Med. Chem. PD JUN PY 2005 VL 5 IS 6 BP 545 EP 553 DI 10.2174/1389557054023242 PG 9 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 932DJ UT WOS:000229534100003 PM 15974932 ER PT J AU Proietti, C Salatino, M Rosemblit, C Carnevale, R Pecci, A Kornblihtt, AR Molinolo, AA Frahm, I Charreau, EH Schillaci, R Elizalde, PV AF Proietti, C Salatino, M Rosemblit, C Carnevale, R Pecci, A Kornblihtt, AR Molinolo, AA Frahm, I Charreau, EH Schillaci, R Elizalde, PV TI Progestins induce transcriptional activation of signal transducer and activator of transcription 3 (Stat3) via a Jak- and Src-dependent mechanism in breast cancer cells SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID GROWTH-FACTOR RECEPTOR; MAMMARY-TUMOR CELLS; PROGESTERONE-RECEPTOR; SUPPRESSES GROWTH; CONSTITUTIVE ACTIVATION; ESTROGEN-RECEPTOR; TYROSINE KINASES; CARCINOMA CELLS; CYCLE ARREST; IN-VIVO AB Interactions between steroid hormone receptors and signal transducer and activator of transcription (Stat)-mediated signaling pathways have already been described. In the present study, we explored the capacity of progestins to modulate Stat3 transcriptional activation in an experimental model of hormonal carcinogenesis in which the synthetic progestin medroxyprogesterone acetate (MPA) induced mammary adenocarcinomas in BALB/c mice and in the human breast cancer cell line T47D. We found that C4HD epithelial cells, from the MPA-induced mammary tumor model, expressed Stat3 and that MPA treatment of C4HD cells up-regulated Stat3 protein expression. In addition, MPA induced rapid, nongenomic Stat3, Jak1, and Jak2 tyrosine phosphorylation in C4HD and T47D cells. MPA treatment of C4HD cells also resulted in rapid c-Src tyrosine phosphorylation. These effects were completely abolished by the progestin antagonist RU486. Abrogation of Jak1 and Jak2 activity by transient transfection of C4HD cells with dominant negative (DN) Jak1 or DN Jak2 vectors, or inhibition of Src activity by preincubation of cells with the Src family kinase inhibitor PP2, blocked the capacity of MPA to induce Stat3 phosphorylation. Treatment of C4HD cells with NIPA induced Stat3 binding to DNA. In addition, MPA promoted strong Stat3 transcriptional activation in C4HD and T47D cells that was inhibited by RU486 and by blockage of Jak1, Jak2, and Src activities. To investigate the correlation between MPA-induced Stat3 activation and cell growth, C4HD cells were transiently transfected with a DN Stat3 expression vector, Stat3Y705-F, or with a constitutively activated Stat3 mutant, Stat3-C. While expression of Stat3Y705-F mutant had an inhibitory effect on MPA-induced growth of C4HD cells, transfection with the constitutively activated Stat3-C vector resulted in MPA-independent proliferation. Finally, we addressed the effect of targeting Stat3 in in vivo growth of C4HD breast tumors. Blockage of Stat3 activation by transfection of C4HD cells with the DN Stat3Y705-F expression vector significantly inhibited these cells' ability to form tumors in syngeneic mice. Our results have for the first time demonstrated that progestins are able to induce Stat3 transcriptional activation, which is in turn an obligatory requirement for progestin stimulation of both in vitro and in vivo breast cancer growth. C1 Consejo Nacl Invest Cient & Tecn, IBYME, RA-2490 Obligado, Argentina. Univ Buenos Aires, Fac Ciencias Exactas & Nat, RA-1053 Buenos Aires, DF, Argentina. Serv Patol, Buenos Aires, DF, Argentina. NCI, Oral & Pharyngeal Canc Branch, Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. RP Elizalde, PV (reprint author), IBYME, Lab Mol Mech Carcinogenesis, Obligado 2490, RA-1428 Buenos Aires, DF, Argentina. EM Elizalde@dna.uba.ar OI Kornblihtt, Alberto/0000-0003-4322-0831 NR 59 TC 77 Z9 84 U1 2 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2005 VL 25 IS 12 BP 4826 EP 4840 DI 10.1128/MCB.25.12.4826-4840.2005 PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 933DZ UT WOS:000229605900002 PM 15923602 ER PT J AU Yamaguchi, T Sharma, P Athanasiou, M Kumar, A Yamada, S Kuehn, MR AF Yamaguchi, T Sharma, P Athanasiou, M Kumar, A Yamada, S Kuehn, MR TI Mutation of SENP1/SuPr-2 reveals an essential role for desumoylation in mouse development SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEAR-PORE COMPLEX; AXIN-BINDING PROTEIN; COVALENT MODIFICATION; DEFICIENT MICE; BETA-CATENIN; IN-VIVO; UBIQUITIN; SUMO; GENE; EXPRESSION AB The covalent modification of proteins by the small ubiquitin-like protein SUMO has been implicated in the regulation of numerous biological processes, including nucleocytoplasmic transport, genomic stability, and gene transcription. Sumoylation occurs by a multienzyme process similar to ubiquitination and, in Saccharomyces cerevisiae, is reversed by desumoylating enzymes encoded by the Ulp1 and Smt4/Ulp2 genes. The physiological importance of desumoylation has been revealed by mutations in either gene, which lead to nonoverlapping defects in cell cycle transition and meiosis. Several mammalian Ulp homologues have been identified, but, to date, nothing is known of the phenotypic effects of their loss of function. Here, we describe a random retroviral insertional mutation of one homolog, mouse SENP1/SuPr-2. The mutation causes increased steady-state levels of the sumoylated forms of a number of proteins and results in placental abnormalities incompatible with embryonic development. Our findings provide the first insight into the critical importance of regulating sumoylation in mammals. C1 NCI, Lab Prot Dynam & Signaling, SAIC Frederick, Frederick, MD 21702 USA. NCI, Basic Res Program, SAIC Frederick, Frederick, MD 21702 USA. RP Kuehn, MR (reprint author), NCI, Lab Prot Dynam & Signaling, SAIC Frederick, Bldg 560,Rm 12-90, Frederick, MD 21702 USA. EM mkuehn@mail.nih.gov RI Kuehn, Michael/A-4573-2014 OI Kuehn, Michael/0000-0002-7703-9160 FU NCI NIH HHS [N01-CO-12400, N01CO12400] NR 50 TC 71 Z9 75 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2005 VL 25 IS 12 BP 5171 EP 5182 DI 10.1128/MCB.25.12.5171-5182.2005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 933DZ UT WOS:000229605900032 PM 15923632 ER PT J AU Fukuda, T Mishina, Y Walker, MP DiAugustine, RP AF Fukuda, T Mishina, Y Walker, MP DiAugustine, RP TI Conditional transgenic system for mouse aurora a kinase: Degradation by the ubiquitin proteasome pathway controls the level of the transgenic protein SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID YEAST CHROMOSOME SEGREGATION; INVASIVE DUCTAL CARCINOMA; CENTROSOME AMPLIFICATION; OVEREXPRESSION; IDENTIFICATION; EXPRESSION; CANCERS; BREAST; PHOSPHORYLATION; PHOSPHATASE AB Aurora A is a mitotic kinase that localizes to centrosomes. Expression of this protein is normally limited to the mitotic stage (G(2)-M) of the cell cycle, whereas human cancer cells frequently exhibit overexpression of Aurora A protein regardless of the cell cycle stage. In the present study, Aurora A transgenic mouse lines were generated with a new conditional expression system (cytomegalovirus immediate early enhancer-chicken beta-actin hybrid promoter-Z-enhanced green fluorescent protein) in order to analyze the function of this protein. Although transcripts for Aurora A were elevated in multiple organs of the transgenic mice, the corresponding protein was not detected in extracts analyzed by immunoblotting. The treatment of transgenic-derived embryonic fibroblasts (MEF) with proteasome inhibitors markedly increased the protein level of transgenic Aurora A, indicating that the transgenic Aurora A protein is readily degraded in normal mouse tissues. Under the exponential growth conditions of MEF cells, transgenic Aurora A was detected within the mitotic stage of the cell cycle and localized to centrosomes. In contrast, the marker of the transgenic promoter (enhanced green fluorescent protein) was continuously expressed throughout the cell cycle, indicating the constitutive transcription of transgenic mRNA. These results indicate that transgenic Aurora A is protected from degradation within G(2)-M but is immediately degraded after translation in the G(1)-S stage of the cell cycle. The findings obtained with this transgenic model and derived cells support that the transition from protection to degradation by the ubiquitin proteasome system at the end of mitosis is an important step in controlling the level of Aurora A protein during the cell cycle. C1 NIEHS, Hormones & Canc Grp, Mol Carcinogenesis Lab, Res Triangle Pk, NC 27709 USA. NIEHS, Reprod & Dev Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP DiAugustine, RP (reprint author), NIEHS, Hormones & Canc Grp, Mol Carcinogenesis Lab, Mail Drop D4-04, Res Triangle Pk, NC 27709 USA. EM diaugus2@niehs.nih.gov NR 39 TC 28 Z9 28 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD JUN PY 2005 VL 25 IS 12 BP 5270 EP 5281 DI 10.1128/MCB.25.12.5270-5281.2005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 933DZ UT WOS:000229605900040 PM 15923640 ER PT J AU Serebriiskii, IG Fang, R Latypova, E Hopkins, R Vinson, C Joung, JK Golemis, EA AF Serebriiskii, IG Fang, R Latypova, E Hopkins, R Vinson, C Joung, JK Golemis, EA TI A combined yeast/bacteria two-hybrid system - Development and evaluation SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID PROTEIN-PROTEIN INTERACTIONS; SACCHAROMYCES-CEREVISIAE; INTERACTION MAP; RAS; SPECIFICITY; INTERACT; GENES; YEAST AB Two-hybrid screening is a standard method used to identify and characterize protein-protein interactions and has become an integral component of many proteomic investigations. The two-hybrid system was initially developed using yeast as a host organism. However, bacterial two-hybrid systems have also become common laboratory tools and are preferred in some circumstances, although yeast and bacterial two-hybrid systems have never been directly compared. We describe here the development of a unified yeast and bacterial two-hybrid system in which a single bait expression plasmid is used in both organismal milieus. We use a series of leucine zipper fusion proteins of known affinities to compare interaction detection using both systems. Although both two-hybrid systems detected interactions within a comparable range of interaction affinities, each demonstrated unique advantages. The yeast system produced quantitative readout over a greater dynamic range than that observed with bacteria. However, the phenomenon of "autoactivation" by baits was less of a problem in the bacterial system than in the yeast. Both systems identified physiological interactors for a library screen with a cI-Ras test bait; however, nonidentical interactors were obtained in yeast and bacterial screens. The ability to rapidly shift between yeast and bacterial systems provided by these new reagents should provide a marked advantage for two-hybrid investigations. In addition, the modified expression vectors we describe in this report should be useful for any application requiring facile expression of a protein of interest in both yeast and bacteria. C1 Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA. Massachusetts Gen Hosp, Dept Pathol, Mol Pathol Unit, Charlestown, MA 02129 USA. Telethon Inst Child Hlth Res, Perth, WA 6872, Australia. Phylogica Ltd, Perth, WA 6872, Australia. NCI, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP Serebriiskii, IG (reprint author), 333 Cottman Ave, Philadelphia, PA 19111 USA. EM ig_serebriiskii@fccc.edu FU NCI NIH HHS [P30 CA006927, R01-CA63366, P30 CA006927-37S2, CA06927, R01 CA063366, R01 CA063366-07]; NIDDK NIH HHS [K08 DK002883-04, K08-DK02883, K08 DK002883]; NIGMS NIH HHS [R01-GM069906]; NIH HHS [DP1 OD006862] NR 24 TC 14 Z9 17 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD JUN PY 2005 VL 4 IS 6 BP 819 EP 826 DI 10.1074/mcp.T500005-MCP200 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 933KW UT WOS:000229628300010 PM 15781424 ER PT J AU Wang, DQ Simons, SS AF Wang, DQ Simons, SS TI Corepressor binding to progesterone and glucocorticoid receptors involves the activation function-1 domain and is inhibited by molybdate SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID NUCLEAR HORMONE-RECEPTORS; PARTIAL AGONIST ACTIVITY; INDUCTION PROPERTIES; N-COR; ANTAGONIST COMPLEXES; GENE-EXPRESSION; DNA-BINDING; IN-VITRO; TRANSCRIPTIONAL ACTIVITY; ESTROGEN-RECEPTORS AB Corepressors are known to interact via their receptor interaction domains (RIDs) with the ligand binding domain in the carboxyl terminal half of steroid/nuclear receptors. We now report that a portion of the activation function-1 domain of glucocorticoid receptors (GRs) and progesterone receptors (PRs), which is the major transactivation sequence, is necessary but not sufficient for corepressor [ nuclear receptor corepressor ( NCoR) and silencing mediator of retinoid and thyroid hormone receptor ( SMRT)] RID binding to GRs and PRs in both mammalian two-hybrid and coimmunoprecipitation assays. Importantly, these two receptor sequences are functionally interchangeable in the context of GR for transactivation, corepressor binding, and corepressor modulatory activity assays. This suggests that corepressors may act in part by physically blocking portions of receptor activation function-1 domains. However, differences exist in corepressor binding to GRs and PRs. The C-terminal domain of PRs has a higher affinity for corepressor than that of GRs. The ability of some segments of the coactivator TIF2 to competitively inhibit corepressor binding to receptors is different for GRs and PRs. With each receptor, the cell-free binding of corepressors to ligand-free receptor is prevented by sodium molybdate, which is a well-known inhibitor of receptor activation to the DNA-binding state. This suggests that receptor activation precedes binding to corepressors. Collectively, these results indicate that corepressor binding to GRs and PRs involve both N- and C-terminal sequences of activated receptors but differ in ways that may contribute to the unique biological responses of each receptor in intact cells. C1 NIDDKD, Steroid Hormones Sect, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. RP Simons, SS (reprint author), NIDDKD, Steroid Hormones Sect, Mol & Cellular Biol Lab, NIH, Bldg 8,Room B2A-07, Bethesda, MD 20892 USA. EM steroids@helix.nih.gov NR 62 TC 28 Z9 28 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 2005 VL 19 IS 6 BP 1483 EP 1500 DI 10.1210/me.2005-0012 PG 18 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 929EH UT WOS:000229324400011 PM 15774497 ER PT J AU Schaaf, MJM Lewis-Tuffin, LJ Cidlowski, JA AF Schaaf, MJM Lewis-Tuffin, LJ Cidlowski, JA TI Ligand-selective targeting of the glucocorticoid receptor to nuclear subdomains is associated with decreased receptor mobility SO MOLECULAR ENDOCRINOLOGY LA English DT Article ID STEROID-HORMONE RECEPTORS; FACTOR-KAPPA-B; LIVING CELLS; ANDROGEN RECEPTOR; DNA-BINDING; SUBCELLULAR-LOCALIZATION; SUBNUCLEAR TRAFFICKING; CROSS-TALK; C-JUN; PROTEIN AB The association between nuclear distribution and mobility of the human glucocorticoid receptor was examined in living COS-1 cells using yellow fluorescent protein- and cyan fluorescent protein-tagged receptors. Quantitation of the nuclear distribution induced by an array of glucocorticoid ligands revealed a continuum from a random (cortisone) to a nonrandom (triamcinolone acetonide) receptor distribution. Structure-function analysis revealed that the 9-fluoro and 17-hydroxy groups on the steroid significantly impact nuclear receptor distribution. Using time-lapse microsopy, the triamcinolone acetonide-induced receptor distribution did not change significantly over a period of 15 sec. However, using fluorescence recovery after photobleaching, the individual receptors moved at a much faster rate, indicating rapid exchange of receptors on immobile nuclear subdomains. Receptor mobilities for 13 different steroids, measured by fluorescence recovery after photobleaching, appeared to correlate with receptor distribution. Ligands that induced a nonrandom distribution induced slower receptor mobility and vice versa. Finally, application of 2-photon confocal microscopy revealed differences in receptor mobility between nuclear subdomains. Areas of high receptor concentration showed slower mobility than areas of low receptor concentration. Thus, glucocorticoid receptors can be targeted ( depending on the ligand) to relatively immobile nuclear subdomains. The transient association of receptor with these domains decreases the mobility of the receptor. C1 NIEHS, Lab Signal Transduct, NIH, US Dept HHS, Res Triangle Pk, NC 27709 USA. RP Schaaf, MJM (reprint author), NIEHS, Lab Signal Transduct, NIH, US Dept HHS, 111 Alexander Dr,POB 12233, Res Triangle Pk, NC 27709 USA. EM schaaf@rulbim.leidenuniv.nl NR 53 TC 32 Z9 34 U1 0 U2 1 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0888-8809 J9 MOL ENDOCRINOL JI Mol. Endocrinol. PD JUN PY 2005 VL 19 IS 6 BP 1501 EP 1515 DI 10.1210/me.2005-0050 PG 15 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 929EH UT WOS:000229324400012 PM 15705660 ER PT J AU Suwannarat, P AF Suwannarat, P TI IEM digest SO MOLECULAR GENETICS AND METABOLISM LA English DT Editorial Material ID ACID STORAGE DISEASE; SALLA-DISEASE; MUTATIONS; SPECTRUM; DISORDER; SIALURIA C1 NHGRI, Clin Genet & Biochem Genet Med Genet Branch, NIH, Bethesda, MD 20892 USA. RP Suwannarat, P (reprint author), NHGRI, Clin Genet & Biochem Genet Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM suwannar@nhgri.nih.gov NR 14 TC 2 Z9 2 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JUN PY 2005 VL 85 IS 2 BP 85 EP 87 DI 10.1016/j.ymgme.2005.04.005 PG 3 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 932DD UT WOS:000229533500001 PM 15973781 ER PT J AU Wassif, CA Krakowiak, PA Wright, BS Gewandter, JS Sterner, AL Javitt, N Yergey, AL Porter, FD AF Wassif, CA Krakowiak, PA Wright, BS Gewandter, JS Sterner, AL Javitt, N Yergey, AL Porter, FD TI Residual cholesterol synthesis and simvastatin induction of cholesterol synthesis in Smith-Lemli-Opitz syndrome fibroblasts SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Smith-Lemli-Opitz syndrome; SLOS; 7-dehydrocholesterol reductase; DHCR7; cholesterol synthesis; simvastatin ID 7-DEHYDROCHOLESTEROL REDUCTASE GENE; MASS ISOTOPOMER ANALYSIS; BLOOD-BRAIN-BARRIER; BILE-ACID SYNTHESIS; IN-VIVO MEASUREMENT; 3-BETA-HYDROXYSTEROL DELTA(7)-REDUCTASE; DELTA-7-STEROL REDUCTASE; STEROL BIOSYNTHESIS; DEUTERATED WATER; RAT-LIVER AB Smith-Lemli-Opitz syndrome (RSH/SLOS) is an autosomal recessive, malformation syndrome caused by mutations in the 3 beta-hydroxysterol Delta(7)- reductase gene (DHCR7). DHCR7 catalyzes the reduction of 7-dehydrocholesterol (7DHC) to cholesterol. We report the mutation analysis and determination of residual cholesterol synthesis in 47 SLOS patients, and the effects of treatment of SLOS skin fibroblasts with simvastatin. Using deuterium labeling we have quantified the amount of synthesized cholesterol and 7DHC in homozygote, heterozygote, and control fibroblast cell lines. In SLOS fibroblasts, the fraction of synthesized cholesterol to total sterol synthesis ranged from undetectable to over 50%. This establishes that different mutant alleles encode enzymes with varying degrees of residual activity. There was a correlation between increased phenotypic severity and decreased residual cholesterol synthesis (r(2) = 0.45, p < 0.0001). Simvastatin treatment of SLOS fibroblasts with residual DHCR7 enzymatic activity decreased 7DHC levels and increased cholesterol synthesis. This increase in cholesterol synthesis is due to increased expression of a mutant allele with residual function. Determination of residual enzymatic activity for specific DHCR7 mutant alleles will help in understanding the processes underlying the broad phenotypic spectrum found in this disorder and will be useful in identifying patients who may benefit from simvastatin therapy. Published by Elsevier Inc. C1 NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. NYU Med Ctr, New York, NY 10016 USA. NICHHD, Lab Cellular & Mol Biophys, NIH, Bethesda, MD 20892 USA. RP Porter, FD (reprint author), NICHHD, Heritable Disorders Branch, NIH, Bethesda, MD 20892 USA. EM fdporter@mail.nih.gov OI Wassif, Christopher/0000-0002-2524-1420 NR 54 TC 32 Z9 33 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JUN PY 2005 VL 85 IS 2 BP 96 EP 107 DI 10.1016/j.ymgme.2004.12.009 PG 12 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 932DD UT WOS:000229533500003 PM 15896653 ER PT J AU Zarzour, W Kleta, R Frangoul, H Suwannarat, P Jeong, A Kim, SY Wayne, AS Gunay-Aygun, M White, J Filipovich, AH Gahl, WA AF Zarzour, W Kleta, R Frangoul, H Suwannarat, P Jeong, A Kim, SY Wayne, AS Gunay-Aygun, M White, J Filipovich, AH Gahl, WA TI Two novel CHS1 (LYST) mutations: Clinical correlations in an infant with Chediak-Higashi syndrome SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Chediak-Higashi syndrome; CHS1; LYST; BEACH; mutation analysis ID BONE-MARROW-TRANSPLANTATION; HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS; SYNDROME GENE; IDENTIFICATION; LYSOSOMES; GRANULES; BEIGE AB Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disease characterized by variable degrees of oculocutaneous albinism, recurrent infections, and a mild bleeding tendency, with late neurologic dysfunction. Most patients also undergo an accelerated phase of lymphohistiocytosis and die at an early age unless they receive an allogeneic hematopoietic stem cell transplant (SCT). Mutations in the CHS1 (LYST) gene result in CHS. Here, we describe an adopted infant who is compound heterozygous for two novel CHS1 gene mutations, both of which are predicted to result in truncated proteins. The two mutations are a nonsense mutation (c.1 540 C > T, CGA > TGA, R514X) in exon 5 and a one base pair deletion (del c.9893T, F3298fsX3304) in exon 43, coding for part of the CHS1 protein's BEACH domain. These two newly described mutations are expected to give rise to a severe phenotype and, indeed, the patient had absolutely no cytotoxicity by natural killer cells or cytotoxic lymphocytes prior to his allogeneic SCT. Published by Elsevier Inc. C1 NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. Damascus Univ, Fac Pharm, Dept Biochem, Damascus, Syria. Off Rare Dis, Intramural Program, Off Director, Bethesda, MD 20892 USA. Vanderbilt Childrens Hosp, Nashville, TN 37232 USA. NCI, Pediat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Univ Minnesota, Dept Lab Med, Minneapolis, MN 55455 USA. Cincinnati Childrens Hosp, Med Ctr, Div Hematol Oncol, Cincinnati, OH 45229 USA. RP Gahl, WA (reprint author), NHGRI, Sect Human Biochem Genet, Med Genet Branch, NIH, Bethesda, MD 20892 USA. EM bgahl@helix.nih.gov NR 36 TC 20 Z9 24 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JUN PY 2005 VL 85 IS 2 BP 125 EP 132 DI 10.1016/j.ymgme.2005.02.011 PG 8 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 932DD UT WOS:000229533500007 PM 15896657 ER PT J AU Guo, J Ikeda, SR AF Guo, J Ikeda, SR TI Coupling of metabotropic glutamate receptor 8 to n-type Ca2+ channels in rat sympathetic neurons SO MOLECULAR PHARMACOLOGY LA English DT Article ID GLUTAMATE-RECEPTOR SUBTYPES; PRESYNAPTIC LOCALIZATION; FUNCTIONAL EXPRESSION; CALCIUM-CHANNELS; MODULATION; CLONING; SUBUNITS; HIPPOCAMPUS; CALMODULIN; VARIANTS AB Group III metabotropic glutamate receptors (mGluRs; mGluR4, 6, 7, and 8) couple to the G alpha(i/o)-containing G protein heterotrimers and act as autoreceptors to regulate glutamate release, probably by inhibiting voltage-gated Ca2+ channels. Although most mGluRs have been functionally expressed in a variety of systems, few studies have demonstrated robust coupling of mGluR8 to downstream effectors. We therefore tested whether activation of mGluR8 inhibited Ca2+ channels. Both L-glutamate (L-Glu) and L-2-amino-4-phosphonobutyric acid (L-AP4), a selective agonist for group III mGluRs, inhibited N-type Ca2+ current in rat superior cervical ganglion neurons previously injected with a cDNA encoding mGluR8a/b. L-AP4 was similar to 100-fold more potent (IC50 = 0.1 mu M) than L-Glu (similar to 10 mu M), but it had efficacy similar to that of L-Glu (similar to 50% maximal inhibition). The potency and efficacy of L-AP4 and L-Glu were similar for both splice variants. Agonist-induced inhibition was abolished by pretreatment with (R,S)-alpha-cyclopropyl-4-phosphonophenylglycine, a selective group III mGluR antagonist, and pertussis toxin. Deletion of either a calmodulin (CaM) binding motif in the C terminus or the entire C terminus of mGluR8 did not affect mGluR8-mediated response. Our studies indicate that both mGluR8a and 8b are capable of inhibiting N-type Ca2+ channel, suggesting a role as presynaptic autoreceptors to regulate neuronal excitability. The studies also imply that the potential CaM binding domain is not required for the mGluR8-mediated Ca2+ channel inhibition and the C terminus of mGluR8a is dispensable for receptor coupling to N-type Ca2+ channels. C1 NIAAA, Lab Mol Physiol, NIH, Bethesda, MD 20892 USA. RP Ikeda, SR (reprint author), NIAAA, Lab Mol Physiol, NIH, Room TS-06,5625 Fisheres Lane, Bethesda, MD 20892 USA. EM sikeda@mail.nih.gov OI Ikeda, Stephen/0000-0002-4088-9508 NR 31 TC 19 Z9 21 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD JUN PY 2005 VL 67 IS 6 BP 1840 EP 1851 DI 10.1124/mol.105.010975 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 926RV UT WOS:000229141200005 PM 15755905 ER PT J AU Addington, AM Gornick, M Duckworth, J Sporn, A Gogtay, N Bobb, A Greenstein, D Lenane, M Gochman, P Baker, N Balkissoon, R Vakkalanka, RK Weinberger, DR Rapoport, JL Straub, RE AF Addington, AM Gornick, M Duckworth, J Sporn, A Gogtay, N Bobb, A Greenstein, D Lenane, M Gochman, P Baker, N Balkissoon, R Vakkalanka, RK Weinberger, DR Rapoport, JL Straub, RE TI GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss SO MOLECULAR PSYCHIATRY LA English DT Article DE GAD1; linkage disequilibrium; transmission disequilibrium test; quantitative transmission disequilibrium test; candidate gene; brain development; child psychosis ID GAMMA-AMINOBUTYRIC-ACID; LINKAGE DISEQUILIBRIUM; AFFECTIVE-DISORDERS; GENE-TRANSCRIPTION; MICE LACKING; K-SADS; EXPRESSION; CHILDREN; GAD(67); GABA AB Postmortem brain studies have shown deficits in the cortical gamma-aminobutyric acid ( GABA) system in schizophrenic individuals. Expression studies have shown a decrease in the major GABA-synthesizing enzyme ( glutamic acid decarboxylase (GAD(67)) mRNA levels in neurons in dorsolateral prefrontal cortex in schizophrenics relative to controls. In the present study, SNPs in and around the GAD1 gene, which encodes the protein GAD67, were tested on a rare, severely ill group of children and adolescents with childhood-onset schizophrenia ( COS) ( n = 72), in a family-based association analysis. Compared to adult-onset samples, the COS sample has evidence for more salient familial, and perhaps genetic, risk factors for schizophrenia, as well as evidence for frontal cortical hypofunction, and greater decline in cortical gray matter volume on anatomic brain MRI scans during adolescence. We performed family-based TDT and haplotype association analyses of the clinical phenotype, as well as association analyses with endophenotypes using the QTDT program. Three adjacent SNPs in the 50 upstream region of GAD1 showed a positive pairwise association with illness in these families ( P = 0.022 - 0.057). Significant transmission distortion of 4-SNP haplotypes was also observed ( P = 0.003 - 0.008). Quantitative trait TDT analyses showed an intriguing association between several SNPs and increased rate of frontal gray matter loss. These observations, when taken together with the positive results reported recently in two independent adult-onset schizophrenia pedigree samples, suggest that the gene encoding GAD67 may be a common risk factor for schizophrenia. C1 NIMH, Child Psychiat Branch, NIH, Bethesda, MD 20892 USA. NIA, Neurogenet Lab, NIH, Bethesda, MD 20892 USA. NIMH, Clin Brain Disorders Branch, NIH, Bethesda, MD 20892 USA. RP Addington, AM (reprint author), NIMH, Child Psychiat Branch, NIH, 10 Ctr Dr,Bldg 10,Rm 3N-202, Bethesda, MD 20892 USA. EM addingta@intra.nimh.nih.gov RI Gogtay, Nitin/A-3035-2008; Addington, Anjene/C-3460-2008 NR 43 TC 110 Z9 117 U1 2 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1359-4184 J9 MOL PSYCHIATR JI Mol. Psychiatr. PD JUN PY 2005 VL 10 IS 6 BP 581 EP 588 DI 10.1038/sj.mp.4001599 PG 8 WC Biochemistry & Molecular Biology; Neurosciences; Psychiatry SC Biochemistry & Molecular Biology; Neurosciences & Neurology; Psychiatry GA 929ZO UT WOS:000229385600011 PM 15505639 ER PT J AU Stone, IM Lurie, DI Kelley, MW Poulsen, DJ AF Stone, IM Lurie, DI Kelley, MW Poulsen, DJ TI Adeno-associated virus-mediated gene transfer to hair cells and support cells of the murine cochlea SO MOLECULAR THERAPY LA English DT Article DE adeno-associated virus; cochlea; hair cells; support cells ID GREEN FLUORESCENT PROTEIN; CENTRAL-NERVOUS-SYSTEM; GUINEA-PIG COCHLEA; IN-VIVO; TRANSGENE EXPRESSION; VIRAL VECTORS; INNER-EAR; SIALIC-ACID; THERAPY; ADENOVIRUS AB More than 28 million Americans suffer from various forms of hearing loss. The lack of effective treatments for many forms of hearing disorders has prompted interest in the potential application of gene delivery techniques to treat both inherited and pathological hearing disorders. However, to develop a gene therapy strategy that will successfully treat hearing disorders, appropriate vectors that are capable of transducing cochlear hair cells and support cells must be identified. In the present study, we examined the efficiency with which AAV vectors (serotypes 1, 2, and 5) transduce hair cells and support cells in cochlear explants from P0 and E13 mice. We further examined the ability of the CBA and GFAP promoters to drive expression of a GFP marker gene in hair cells and support cells. Robust GFP expression was observed in hair cells and support cells following transduction of primary murine cochlear explants with AAV serotypes 1 and 2, but not serotype 5. The CBA promoter predominantly drove GFP expression in hair cells. In contrast, strong expression from the GFAP promoter was observed primarily in support cells. Thus, using AAV vectors and specific promoters, cell-type-specific expression of transgenes can be established within the cochlea. C1 Univ Montana, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA. NIDCD, NIH, Bethesda, MD 20892 USA. RP Poulsen, DJ (reprint author), Univ Montana, Dept Biomed & Pharmaceut Sci, 32 Campus Dr,1552, Missoula, MT 59812 USA. EM David.poulsen@umontana.edu FU NIDCD NIH HHS [DC005462] NR 37 TC 42 Z9 53 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2005 VL 11 IS 6 BP 843 EP 848 DI 10.1016/j.ymthe.2005.02.005 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934TY UT WOS:000229732700007 PM 15922954 ER PT J AU Di Pasquale, G Rzadzinska, A Schneider, ME Bossis, I Chiorini, JA Kachar, B AF Di Pasquale, G Rzadzinska, A Schneider, ME Bossis, I Chiorini, JA Kachar, B TI A novel bovine virus efficiently transduces inner ear neuroepithelial cells SO MOLECULAR THERAPY LA English DT Article DE BAAV; AAV; adeno-associated virus; hair cells; inner ear; stereocilia ID RECOMBINANT ADENOASSOCIATED VIRUS; HEPARAN-SULFATE PROTEOGLYCAN; COCHLEAR HAIR-CELLS; GENE-TRANSFER; IN-VIVO; TRANSGENE EXPRESSION; GUINEA-PIG; MOLECULAR TREADMILL; TYPE-2; VECTORS AB Disruption of the cellular composition or arrangement of the sensory epithelia due to hair cell or supporting cell damage leads to hearing loss and vestibular dysfunctions. These peripheral hearing disorders make good targets for gene therapy; however, development requires efficient gene transfer methods for the inner ear. Here we characterized the cellular tropism of a novel adeno-associated bovine virus vector (BAAV) in cultured rat inner ear epithelia. To help identify transduced cells, we used beta-actin-GFP as a reporter gene. We found that BAAV efficiently transduced auditory and vestibular hair cells as well as all types of supporting cells with no apparent pathological effects. The number of transduced hair cells significantly increased in both a dose- and a time-dependent manner. Transduction was independent of the cells' maturation state and was observed in both P2 and P10 cultures. Interestingly, even after several days of incubation with BAAV, hair cells demonstrated varying progression of beta-actin-GFP incorporation into the stereocilia. This suggests that the onset of viral transduction can occur throughout the course of the experiment. Of the other tested AAVs, AAV2 and AAV5 transduced only a small percentage of inner and vestibular hair cells, respectively, whereas no transduction was detected with AAV4. C1 Natl Inst Dental & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. Natl Inst Deafness & Other Commun Disorders, Sect Struct Cell Biol, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Chiorini, JA (reprint author), Natl Inst Dental & Craniofacial Res, Gene Therapy & Therapeut Branch, NIH, US Dept Hlth & Human Serv, 10-1N133,10 Ctr Dr,MSC1190, Bethesda, MD 20892 USA. EM jchiorini@dir.nidcr.nih.gov NR 39 TC 23 Z9 25 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 1525-0016 J9 MOL THER JI Mol. Ther. PD JUN PY 2005 VL 11 IS 6 BP 849 EP 855 DI 10.1016/j.ymthe.2005.02.004 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 934TY UT WOS:000229732700008 PM 15922955 ER PT J AU Kawasaki, ES Player, A AF Kawasaki, Ernest S. Player, Audrey TI Nanotechnology, nanomedicine, and the development of new, effective therapies for cancer SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Review DE Nanotechnology; Nanomedicine; Nanoparticles; Quantum dots; Drug delivery; Cancer therapy AB Cancer is the leading cause of death in the United States among people younger than 85 years, and for the first time has surpassed heart disease as the number one killer. This worrisome statistic has resulted not from an increase in the incidence of cancer, but because deaths from heart disease have dropped nearly in half while the number of cancer-related deaths has remained about the same. This fact accentuates the need for a new generation of more effective therapies for cancer. In this review, the development of new therapies will be discussed in the context of advances in nanotechnologies related to cancer detection, analysis, diagnosis, and therapeutic intervention. First, several nanoanalytical methods, such as the use of quantum dots in detection and imaging of cancer, will be described. These techniques will be essential to the process of precisely describing cancer at the level of the cell and whole organism. Second, examples of how nanotechnologies can be used in the development of new therapies will be given, including methods that might allow for more efficient and accurate drug delivery and rationally designed, targeted drugs. Finally, a new initiative - the National Cancer Institute Alliance for Nanotechnology in Cancer - will be described and discussed with respect to the scientific issues, policies, and funding. (C) 2005 Elsevier Inc. All rights reserved. C1 [Kawasaki, Ernest S.; Player, Audrey] NCI, Gaithersburg, MD USA. RP Kawasaki, ES (reprint author), NCI, Microarray Facil, Adv Technol Ctr, 8717 Grovemont Circle, Bethesda, MD 20892 USA. EM ke@mail.nih.gov NR 90 TC 141 Z9 147 U1 2 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD JUN PY 2005 VL 1 IS 2 BP 101 EP 109 DI 10.1016/j.nano.2005.03.002 PG 9 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA V45LL UT WOS:000209818000001 PM 17292064 ER PT J AU Lim, EH Danthi, N Bednarski, M Li, KCP AF Lim, Esther H. Danthi, Narasimhan Bednarski, Mark Li, King C. P. TI A review: Integrin alpha(v)beta(3)-targeted molecular imaging and therapy in angiogenesis SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Review C1 [Lim, Esther H.; Danthi, Narasimhan; Bednarski, Mark; Li, King C. P.] NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Lim, EH (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM ElimH@cc.nih.gov RI Danthi, Simhan/B-7639-2014 NR 24 TC 32 Z9 34 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 EI 1549-9642 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD JUN PY 2005 VL 1 IS 2 BP 110 EP 114 DI 10.1016/j.nano.2005.03.008 PG 5 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA V45LL UT WOS:000209818000002 PM 17292065 ER PT J AU Liu, SH Redeye, V Kuremsky, JG Kuhnen, M Molinolo, A Bugge, TH Leppla, SH AF Liu, SH Redeye, V Kuremsky, JG Kuhnen, M Molinolo, A Bugge, TH Leppla, SH TI Intermolecular complementation achieves high-specificity tumor targeting by anthrax toxin SO NATURE BIOTECHNOLOGY LA English DT Article ID PROTECTIVE ANTIGEN; LETHAL FACTOR; CELLULAR RECEPTOR; EDEMA FACTOR; BINDING; METASTASIS; INVASION; IDENTIFICATION; SEQUENCE; PROTEASE AB Anthrax toxin protective antigen (PrAg) forms a heptamer in which the binding site for lethal factor (LF) spans two adjacent monomers(1,2). This suggested that high cell-type specificity in tumor targeting could be obtained using monomers that generate functional LF-binding sites only through intermolecular complementation. We created PrAg mutants with mutations affecting different LF-binding subsites and containing either urokinase plasminogen activator (uPA) or matrix metalloproteinase (MMP) cleavage sites. Individually, these PrAg mutants had low toxicity as a result of impaired LF binding, but when administered together to uPA- and MMP-expressing tumor cells, they assembled into functional LF-binding heteroheptamers. The mixture of two complementing PrAg variants had greatly reduced toxicity in mice and was highly effective in the treatment of aggressive transplanted tumors of diverse origin. These results show that anthrax toxin, and by implication other multimeric toxins, offer excellent opportunities to introduce multiple-specificity determinants and thereby achieve high therapeutic indices. C1 Natl Inst Dent & Craniofacial Res, Oral Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. NIAID, Microbial Pathogenesis Sect, NIH, Bethesda, MD 20892 USA. RP Bugge, TH (reprint author), Natl Inst Dent & Craniofacial Res, Oral Pharyngeal Canc Branch, NIH, Bethesda, MD 20892 USA. EM thomas.bugge@nih.gov; sleppla@niaid.nih.gov FU Intramural NIH HHS [Z01 AI000929-05, Z01 DE000699-08] NR 30 TC 37 Z9 37 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JUN PY 2005 VL 23 IS 6 BP 725 EP 730 DI 10.1038/nbt1091 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 933LA UT WOS:000229628700033 PM 15895075 ER PT J AU Arnaoutov, A Azuma, Y Ribbeck, K Joseph, J Boyarchuk, Y Karpova, T McNally, J Dasso, M AF Arnaoutov, A Azuma, Y Ribbeck, K Joseph, J Boyarchuk, Y Karpova, T McNally, J Dasso, M TI Crm1 is a mitotic effector of Ran-GTP in somatic cells SO NATURE CELL BIOLOGY LA English DT Article ID KINETOCHORE FIBERS; BINDING PROTEIN-2; MICROTUBULE; SPINDLE; ATTACHMENT; NUCLEOPORIN; DOMAIN; SITES; ASSOCIATION; CHECKPOINT AB The Ran GTPase controls multiple cellular processes, including nuclear transport, mitotic checkpoints, spindle assembly and post-mitotic nuclear envelope reassembly(1,2). Here we examine the mitotic function of Crm1, the Ran-GTP-binding nuclear export receptor for leucine-rich cargo ( bearing nuclear export sequence) and Snurportin-1 (ref. 3). We find that Crm1 localizes to kinetochores, and that Crm1 ternary complex assembly is essential for Ran-GTP-dependent recruitment of Ran GTPase-activating protein 1 (Ran-GAP1) and Ran-binding protein 2 (Ran-BP2) to kinetochores. We further show that Crm1 inhibition by leptomycin B disrupts mitotic progression and chromosome segregation. Analysis of spindles within leptomycin B-treated cells shows that their centromeres were under increased tension. In leptomycin B-treated cells, centromeres frequently associated with continuous microtubule bundles that spanned the centromeres, indicating that their kinetochores do not maintain discrete end-on attachments to single kinetochore fibres. Similar spindle defects were observed in temperature-sensitive Ran pathway mutants (tsBN2 cells). Taken together, our findings demonstrate that Crm1 and Ran-GTP are essential for Ran-BP2/Ran-GAP1 recruitment to kinetochores, for definition of kinetochore fibres and for chromosome segregation at anaphase. Thus, Crm1 is a critical Ran-GTP effector for mitotic spindle assembly and function in somatic cells. C1 NICHD, Lab Gene Regulat & Dev, NIH, Bethesda, MD 20892 USA. European Mol Biol Lab, Gene Express Programme, D-69117 Heidelberg, Germany. NCI Core Fluorescence Imaging Facil, Bethesda, MD 20892 USA. RP Dasso, M (reprint author), NICHD, Lab Gene Regulat & Dev, NIH, Bldg 18,Room 16, Bethesda, MD 20892 USA. EM mdasso@helix.nih.gov FU Intramural NIH HHS [Z01 HD008740-06] NR 30 TC 125 Z9 125 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1465-7392 J9 NAT CELL BIOL JI Nat. Cell Biol. PD JUN PY 2005 VL 7 IS 6 BP 626 EP U27 DI 10.1038/ncb1263 PG 10 WC Cell Biology SC Cell Biology GA 932OD UT WOS:000229562100017 PM 15908946 ER PT J AU Carrington, M AF Carrington, M TI Antiviral synergism SO NATURE GENETICS LA English DT Editorial Material ID CYTOMEGALOVIRUS; RECOGNITION; RESISTANCE; RECEPTORS; BINDING; MOUSE AB The restriction of herpesvirus by natural killer cells, initiated before the acquired immune response, illustrates the value of innate immune mechanisms for viral containment. Now, a new study shows that the activating natural killer cell receptor Ly49P and the major histocompatibility complex class I H-2D(k) molecule act in concert to restrict mouse cytomegalovirus infection, identifying a new mechanism of host resistance. C1 NCI, Frederick, MD 21702 USA. RP Carrington, M (reprint author), NCI, Frederick, MD 21702 USA. EM carringt@ncifcrf.gov NR 15 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1061-4036 J9 NAT GENET JI Nature Genet. PD JUN PY 2005 VL 37 IS 6 BP 565 EP 566 DI 10.1038/ng0605-565 PG 2 WC Genetics & Heredity SC Genetics & Heredity GA 931OT UT WOS:000229495300005 PM 15920514 ER PT J AU Boshoff, HI Barry, CE AF Boshoff, HI Barry, CE TI A low-carb diet for a high-octane pathogen SO NATURE MEDICINE LA English DT Editorial Material ID MYCOBACTERIUM-TUBERCULOSIS; GLYOXYLATE CYCLE; MACROPHAGES; VIRULENCE; MICE AB Mycobacterium tuberculosis adapts to the low-glucose conditions in its host by using lipids as a fuel source. This adaptation reveals a weak flank that might be exploited in drug development, as shown in work on mice and human cells ( pages 638 - 644). C1 NIAID, TB Res Sect, NIH, Rockville, MD 20852 USA. RP Barry, CE (reprint author), NIAID, TB Res Sect, NIH, Rockville, MD 20852 USA. EM cbarry@niaid.nih.gov RI Barry, III, Clifton/H-3839-2012 FU Intramural NIH HHS [Z01 AI000783-11] NR 10 TC 13 Z9 13 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUN PY 2005 VL 11 IS 6 BP 599 EP 600 DI 10.1038/nm0605-599 PG 3 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 932YD UT WOS:000229589800018 PM 15937469 ER PT J AU Ravel, S Richmond, BJ AF Ravel, S Richmond, BJ TI Where did the time go? SO NATURE NEUROSCIENCE LA English DT Editorial Material ID DORSOLATERAL PREFRONTAL CORTEX; BASAL-GANGLIA; REWARD; PARALLEL C1 NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Ravel, S (reprint author), NIMH, Neuropsychol Lab, NIH, Dept Hlth & Human Serv, Bldg 49,Room 1B80, Bethesda, MD 20892 USA. EM bjr@ln.nimh.nih.gov NR 10 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUN PY 2005 VL 8 IS 6 BP 705 EP 707 DI 10.1038/nn0605-705 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 929KP UT WOS:000229345300006 PM 15917833 ER PT J AU Pezawas, L Meyer-Lindenberg, A Drabant, EM Verchinski, BA Munoz, KE Kolachana, BS Egan, MF Mattay, VS Hariri, AR Weinberger, DR AF Pezawas, L Meyer-Lindenberg, A Drabant, EM Verchinski, BA Munoz, KE Kolachana, BS Egan, MF Mattay, VS Hariri, AR Weinberger, DR TI 5-HTTLPR polymorphism impacts human cingulate-amygdala interactions: a genetic susceptibility mechanism for depression SO NATURE NEUROSCIENCE LA English DT Article ID SEROTONIN TRANSPORTER; MAJOR DEPRESSION; FUNCTIONAL CONNECTIVITY; PREFRONTAL CORTEX; PROMOTER POLYMORPHISM; AFFECTIVE-DISORDERS; ANTERIOR CINGULATE; GLUCOSE-METABOLISM; MOOD DISORDERS; HUMAN BRAIN AB Carriers of the short allele of a functional 5' promoter polymorphism of the serotonin transporter gene have increased anxiety-related temperamental traits, increased amygdala reactivity and elevated risk of depression. Here, we used multimodal neuroimaging in a large sample of healthy human subjects to elucidate neural mechanisms underlying this complex genetic association. Morphometrical analyses showed reduced gray matter volume in short-allele carriers in limbic regions critical for processing of negative emotion, particularly perigenual cingulate and amygdala. Functional analysis of those regions during perceptual processing of fearful stimuli demonstrated tight coupling as a feedback circuit implicated in the extinction of negative affect. Short-allele carriers showed relative uncoupling of this circuit. Furthermore, the magnitude of coupling inversely predicted almost 30% of variation in temperamental anxiety. These genotype-related alterations in anatomy and function of an amygdala-cingulate feedback circuit critical for emotion regulation implicate a developmental, systems- level mechanism underlying normal emotional reactivity and genetic susceptibility for depression. C1 NIMH, Genes Cognit & Psychosis Program, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Western Psychiat Inst & Clin, Dept Psychiat, Pittsburgh, PA 15213 USA. RP Weinberger, DR (reprint author), NIMH, Genes Cognit & Psychosis Program, NIH, 10 Ctr Dr 4S235, Bethesda, MD 20892 USA. EM weinberd@intra.nimh.nih.gov RI Hariri, Ahmad/D-5761-2011; OI Pezawas, Lukas/0000-0002-1329-6352; Meyer-Lindenberg, Andreas/0000-0001-5619-1123 FU Intramural NIH HHS NR 50 TC 1189 Z9 1224 U1 14 U2 172 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA SN 1097-6256 J9 NAT NEUROSCI JI Nat. Neurosci. PD JUN PY 2005 VL 8 IS 6 BP 828 EP 834 DI 10.1038/nn1463 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 929KP UT WOS:000229345300025 PM 15880108 ER PT J AU Siebenlist, U Brown, K Claudio, E AF Siebenlist, U Brown, K Claudio, E TI Control of lymphocyte development by nuclear factor-kappa B SO NATURE REVIEWS IMMUNOLOGY LA English DT Review ID BRUTONS TYROSINE KINASE; T-CELL DEVELOPMENT; TRANSCRIPTION FACTORS; SIGNALING PATHWAY; TRANSGENIC MICE; MARGINAL ZONE; INCONTINENTIA PIGMENTI; AUTOIMMUNE-DISEASE; GENE-EXPRESSION; IKK-BETA AB The evolutionarily conserved nuclear factor-kappa B family of transcription factors is known to have a crucial role in rapid responses to stress and pathogens, inducing transcription of many genes that are essential for host defence. Now, studies of mice that are deficient in nuclear factor-kappa B-family members (or deficient in the activation of these factors) reveal that nuclear factor-kappa B is extensively involved in the development of T cells and B cells. And, as we review here, although these factors have several roles, their primary cell-autonomous function is to ensure lymphocyte survival at various developmental stages. This function is subverted in numerous diseases and can lead, for example, to survival of self-reactive lymphocytes or tumour cells. C1 NIAID, Lab Immune Regulat, Immune Activat Sect, NIH, Bethesda, MD 20892 USA. RP Siebenlist, U (reprint author), NIAID, Lab Immune Regulat, Immune Activat Sect, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM us3n@nih.gov NR 89 TC 208 Z9 220 U1 1 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1733 J9 NAT REV IMMUNOL JI Nat. Rev. Immunol. PD JUN PY 2005 VL 5 IS 6 BP 435 EP 445 DI 10.1038/nri1629 PG 11 WC Immunology SC Immunology GA 934EG UT WOS:000229689100008 PM 15905862 ER PT J AU Yuste, R MacLean, JN Smith, J Lansner, A AF Yuste, R MacLean, JN Smith, J Lansner, A TI The cortex as a central pattern generator SO NATURE REVIEWS NEUROSCIENCE LA English DT Review ID PRE-BOTZINGER COMPLEX; CAT VISUAL-CORTEX; RESPIRATORY RHYTHM GENERATION; SPONTANEOUS FIRING PATTERNS; MAMMALIAN SPINAL-CORD; IN-VITRO; NEURAL-NETWORKS; PACEMAKER NEURONS; CORTICAL ACTIVITY; NEOCORTEX AB Vertebrate spinal cord and brainstem central pattern generator (CPG) circuits share profound similarities with neocortical circuits. CPGs can produce meaningful functional output in the absence of sensory inputs. Neocortical circuits could be considered analogous to CPGs as they have rich spontaneous dynamics that, similar to CPGs, are powerfully modulated or engaged by sensory inputs, but can also generate output in their absence. We find compelling evidence for this argument at the anatomical, biophysical, developmental, dynamic and pathological levels of analysis. Although it is possible that cortical circuits are particularly plastic types of CPG ('learning CPGs'), we argue that present knowledge about CPGs is likely to foretell the basic principles of the organization and dynamic function of cortical circuits. C1 Columbia Univ, Dept Biol Sci, New York, NY 10027 USA. NINDS, Cellular & Syst Neurobiol Sect, Neural Control Lab, Porter Neurosci Res Ctr,NIH, Bethesda, MD 20892 USA. Stockholm Univ, Dept Comp Sci & Commun, SE-10044 Stockholm, Sweden. Royal Inst Technol KTH, SE-10044 Stockholm, Sweden. RP Yuste, R (reprint author), Columbia Univ, Dept Biol Sci, 1212 Amsterdam Ave,Box 2435, New York, NY 10027 USA. EM rmy5@columbia.edu OI Lansner, Anders/0000-0002-2358-7815 NR 100 TC 150 Z9 152 U1 1 U2 18 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0048 J9 NAT REV NEUROSCI JI Nat. Rev. Neurosci. PD JUN PY 2005 VL 6 IS 6 BP 477 EP 483 DI 10.1038/nrn1686 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 931RM UT WOS:000229502800015 PM 15928717 ER PT J AU Hoorn, EJ Pisitkun, T Zietse, R Gross, P Frokiaer, J Wang, NS Gonzales, PA Star, RA Knepper, MA AF Hoorn, EJ Pisitkun, T Zietse, R Gross, P Frokiaer, J Wang, NS Gonzales, PA Star, RA Knepper, MA TI Prospects for urinary proteomics: Exosomes as a source of urinary biomarkers SO NEPHROLOGY LA English DT Article; Proceedings Paper CT 1st Australasian Home Haemodialysis Workshop CY JUL, 2004 CL Christchurch, NEW ZEALAND DE aquaporin-2; biomarkers; hypertension; kidney disease; urinary proteomics ID MASS-SPECTROMETRY; TUBULE INJURY; STORAGE TIME; PROTEINS; EXCRETION; KIDNEY; AQUAPORIN-2; VASOPRESSIN; TEMPERATURE; CREATININE AB Recent progress in biotechnology offers the promise of better medical care at lower costs. Among the techniques that show the greatest promise is mass spectrometry of proteins, which can identify proteins present in body fluids and tissue specimens at a large scale. Because urine can be collected in large amounts in a non-invasive fashion, the potential exists to use mass spectrometry to discover urinary biomarkers that are early predictors of renal disease, or useful in making therapeutic choices. Recently, the authors demonstrated that both membrane proteins and cytosolic proteins from renal epithelia are highly enriched in low-density urinary structures identified as exosomes. Exosomes were found to contain many disease-associated proteins including aquaporin-2, polycystin-1, podocin, non-muscle myosin II, angiotensin-converting enzyme, Na(+)K(+)2Cl(-) cotransporter (NKCC2), thiazide-sensitive Na-Cl cotransporter (NCC), and epithelial sodium channel (ENaC). Potentially, other disease biomarkers could be discovered by mass spectrometry-based proteomic studies in well-defined patient populations. Herein is described the advantages of using urinary exosomes as a starting material for biomarker discovery. In addition, the purpose of this review is to present an overall strategy for biomarker discovery in urine using exosomes and for developing cost-effective clinical assays for these biomarkers, which can potentially be used for early detection of disease, as a means of differential diagnosis, or as a means of guiding therapy. Finally, potential barriers that need to be overcome before urinary proteomics can be applied clinically, are emphasized. C1 NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bethesda, MD 20892 USA. NIDDKD, Renal Diagnost & Therapeut Unit, NIH, Bethesda, MD USA. Univ Maryland, Dept Chem Engn, College Pk, MD 20742 USA. Univ Maryland, Dept Chem Engn, Bethesda, MD USA. Erasmus Med Ctr, Dept Internal Med, Rotterdam, Netherlands. Univ Hosp Dresden, Dept Med, Dresden, Germany. Univ Aarhus, Water & Salt Res Ctr, Aarhus, Denmark. RP Knepper, MA (reprint author), NHLBI, Kidney & Electrolyte Metab Lab, NIH, Bldg 10,Room 6N260,10 Ctr Dr,MSC 1603, Bethesda, MD 20892 USA. EM knep@helix.nih.gov RI Wang, Nam Sun/E-4253-2016; OI Pisitkun, Trairak/0000-0001-6677-2271 FU Intramural NIH HHS [Z01 HL001285-21, Z99 HL999999] NR 33 TC 98 Z9 103 U1 1 U2 14 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD JUN PY 2005 VL 10 IS 3 BP 283 EP 290 DI 10.1111/j.1440-1797.2005.00387.x PG 8 WC Urology & Nephrology SC Urology & Nephrology GA 932VI UT WOS:000229581900014 PM 15958043 ER PT J AU Abidi, SM Negrete, HO Zahid, I Bennett, PH Nelson, RG AF Abidi, SM Negrete, HO Zahid, I Bennett, PH Nelson, RG TI Diabetic end-stage renal disease in the indigenous population of the Commonwealth of the Northern Mariana Islands SO NEPHROLOGY LA English DT Article; Proceedings Paper CT 1st Australasian Home Haemodialysis Workshop CY JUL, 2004 CL Christchurch, NEW ZEALAND DE Carolinians; Chamorros; end-stage renal disease; survival; type 2 diabetes ID FOLLOW-UP; SURVIVAL; NAURU AB The number of cases of treated end-stage renal disease (ESRD) attributable to type 2 diabetes and survival after the onset of renal replacement therapy was examined in the Commonwealth of the Northern Mariana Islands (CNMI). All Chamorros and Carolinians to receive renal replacement therapy for ESRD between January 1982 and December 2002 were identified. Changes in survival over time were examined by dividing the study into three equal periods. Of 180 new cases of ESRD, 137 (76%; 101 Chamorros, 36 Carolinians) were attributed to diabetes. Ninety-nine subjects, 80% of whom had diabetic ESRD, began renal replacement therapy in the last 7 years of the study compared with 81 (72% with diabetic ESRD) in the previous 14 years. All 137 of the diabetic subjects received haemodialysis. During the 21-year study period, 79 of the diabetic subjects receiving dialysis died. The median survival after the onset of haemodialysis was 37 months in the first time period (1982-1988), 47 months in the second period (1989-1995) and 67 months in the third period (1996-2002). The death rate in the first period was 4.3 times (95% CI, 2.1-8.9) as high and the second period was 2.9 times (95% CI, 1.5-5.8) as high as the most recent period, after adjustment for age, sex and ethnicity in a proportional-hazards analysis. The number of diabetic patients in CNMI who are receiving renal replacement therapy is rising rapidly. Considerable improvement in survival after the onset of haemodialysis has occurred over the past 21 years. C1 NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, Phoenix, AZ 85014 USA. RP Nelson, RG (reprint author), NIDDKD, Phoenix Epidemiol & Clin Res Branch, NIH, 1550 E Indian Sch Rd, Phoenix, AZ 85014 USA. EM rnelson@phx.niddk.nih.gov RI Nelson, Robert/B-1470-2012 NR 20 TC 3 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD JUN PY 2005 VL 10 IS 3 BP 291 EP 295 DI 10.1111/j.1440-1797.2005.00415.x PG 5 WC Urology & Nephrology SC Urology & Nephrology GA 932VI UT WOS:000229581900015 PM 15958044 ER PT J AU Castrop, H Oppermann, M Huang, YN Mizel, D Deng, CX Briggs, JP Schnermann, J AF Castrop, Hayo Oppermann, Mona Huang, Yuning Mizel, Diane Deng, Chuxia Briggs, Josie P. Schnermann, Jurgen TI MACULA DENSA REGULATION OF RENIN SECRETION AND PREGLOMERULAR RESISTANCE IN MICE LACKING THE B-ISOFORM OF THE NA/K/2CL COTRANSPORTER NKCC2 SO NEPHROLOGY LA English DT Meeting Abstract C1 [Castrop, Hayo; Oppermann, Mona; Huang, Yuning; Mizel, Diane; Deng, Chuxia; Briggs, Josie P.; Schnermann, Jurgen] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD JUN PY 2005 VL 10 SU 1 BP A237 EP A237 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA V27SS UT WOS:000208633501015 ER PT J AU Dharnidharka, V Abbott, K Agodoa, L AF Dharnidharka, Vikas Abbott, Kevin Agodoa, Lawrence TI URINARY TRACT INFECTION AFTER KIDNEY TRANSPLANTATION IN CHILDREN: INCIDENCE AND OUTCOMES SO NEPHROLOGY LA English DT Meeting Abstract C1 [Dharnidharka, Vikas] Univ Florida, Gainesville, FL 32611 USA. [Agodoa, Lawrence] NIDDK, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD JUN PY 2005 VL 10 SU 1 BP A333 EP A333 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA V27SS UT WOS:000208633501374 ER PT J AU Hiramatsu, N Shigehara, T Kuroiwa, T Ikeuchi, H Hiromura, K Ueki, K Nojima, Y Kopp, JB AF Hiramatsu, Noriyuki Shigehara, Tetsuya Kuroiwa, Takashi Ikeuchi, Hidekazu Hiromura, Keiju Ueki, Kazue Nojima, Yoshihisa Kopp, Jeffrey B. TI HEMINEPHRECTOMY ACCELERATES THE PROGRESSION OF GLOMERULOSCLEROSIS IN THE CONDITIONAL TRANSGENIC MICE EXPRESSING HIV VPR GENE IN PODOCYTES: IMPLICATION OF INTRAGLOMERULAR PRESSURE FOR THE PROGRESSION OF COLLAPSING FSGS SO NEPHROLOGY LA English DT Meeting Abstract C1 [Hiramatsu, Noriyuki; Shigehara, Tetsuya; Kuroiwa, Takashi; Ikeuchi, Hidekazu; Hiromura, Keiju; Ueki, Kazue] Gunma Univ, Dept Med & Clin Sci, Grad Sch Med, Maebashi, Gumma 371, Japan. [Nojima, Yoshihisa; Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD JUN PY 2005 VL 10 SU 1 BP A40 EP A40 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA V27SS UT WOS:000208633500149 ER PT J AU Hiramatsu, N Shigehara, T Kuroiwa, T Ikeuchi, H Ueki, K Nojima, Y Kopp, JB AF Hiramatsu, Noriyuki Shigehara, Tetsuya Kuroiwa, Takashi Ikeuchi, Hidekazu Ueki, Kazue Nojima, Yoshihisa Kopp, Jeffrey B. TI MESANGIAL CELL-SPECIFIC ENHANCER ACTIVITY IS REGULATED BY OCT-1 IN MOUSE MEGSIN GENE SO NEPHROLOGY LA English DT Meeting Abstract C1 [Hiramatsu, Noriyuki] Gunma Univ, Dept Med & Clin Sci, Grad Sch Med, Gunma, Japan. [Shigehara, Tetsuya; Kuroiwa, Takashi; Ikeuchi, Hidekazu; Ueki, Kazue; Nojima, Yoshihisa] Gunma Univ, Dept Med & Clin Sci, Grad Sch Med, Maebashi, Gumma 371, Japan. [Kopp, Jeffrey B.] NIDDK, Kidney Dis Sect, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD JUN PY 2005 VL 10 SU 1 BP A10 EP A10 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA V27SS UT WOS:000208633500034 ER PT J AU Kim, SM Chen, LM Huang, YN Chen, M Lopez, MLS Gomez, RA Weinstein, SL Briggs, JP Schnermann, J AF Kim, Soo Mi Chen, Limeng Huang, Yuning Chen, Min Lopez, Maria Luisa Sequeira Gomez, R. Ariel Weinstein, S. Lee Briggs, Josie P. Schnermann, Jurgen TI REGULATION OF RENIN SECRETION IN MICE WITH CRE-RECOMBINASE-MEDIATED DELETION OF JUXTAGLOMERULAR GSALPHA SO NEPHROLOGY LA English DT Meeting Abstract C1 [Kim, Soo Mi; Chen, Limeng; Chen, Min; Weinstein, S. Lee; Briggs, Josie P.; Schnermann, Jurgen] NIDDK, NIH, Bethesda, MD 20892 USA. [Lopez, Maria Luisa Sequeira; Gomez, R. Ariel] Univ Virginia, Charlottesville, VA 22903 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD JUN PY 2005 VL 10 SU 1 BP A237 EP A237 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA V27SS UT WOS:000208633501014 ER PT J AU Lotan, D Eisenkraft, A Jacobsson, J Bar-Yosef, O Kleta, R Gal, N Gore, H Anikster, Y AF Lotan, Danny Eisenkraft, Aric Jacobsson, Josef Bar-Yosef, Omer Kleta, Robert Gal, Nurit Gore, Hagar Anikster, Yair TI OSTEOPETROSIS, RENAL TUBULAR ACIDOSIS, AND CEREBRAL CALCIFICATIONS WITH PRIMARY PULMONARY HYPERTENSION - A UNIQUE GENOTYPE AND PHENOTYPE OF CARBONIC ANHYDRASE II DEFICIENCY SO NEPHROLOGY LA English DT Meeting Abstract C1 [Lotan, Danny] Safra Childrens Hosp, Sheba Med Ctr, Dept Pediat Nephrol, Tel Hashomer, Israel. [Eisenkraft, Aric; Bar-Yosef, Omer] Chaim Sheba Med Ctr, Dept Pediat, IL-52621 Tel Hashomer, Israel. [Jacobsson, Josef] Chaim Sheba Med Ctr, Dept Pediat Radiol, IL-52621 Tel Hashomer, Israel. [Kleta, Robert] NHGRI, MGB, NIH, Bethesda, MD 20892 USA. [Gore, Hagar] Chaim Sheba Med Ctr, Metab Dis Unit, IL-52621 Tel Hashomer, Israel. [Anikster, Yair] Safra Childrens Hosp, Metab Dis Unit, Tel Hashomer, Israel. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD JUN PY 2005 VL 10 SU 1 BP A228 EP A228 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA V27SS UT WOS:000208633500856 ER PT J AU Pavkov, ME Bennett, PH Sievers, ML Krakoff, J Williams, DE Knowler, WC Nelson, RG AF Pavkov, Meda E. Bennett, Peter H. Sievers, Maurice L. Krakoff, Jonathan Williams, Desmond E. Knowler, William C. Nelson, Robert G. TI PREDOMINANT EFFECTS OF KIDNEY DISEASE (KD) ON EXCESS MORTALITY IN PIMA INDIANS WITH OR WITHOUT TYPE 2 DIABETES SO NEPHROLOGY LA English DT Meeting Abstract C1 [Pavkov, Meda E.; Bennett, Peter H.; Sievers, Maurice L.; Krakoff, Jonathan; Knowler, William C.; Nelson, Robert G.] NIDDK, Bethesda, MD 20892 USA. [Williams, Desmond E.] CDC, Atlanta, GA 30333 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD JUN PY 2005 VL 10 SU 1 BP A234 EP A235 PG 2 WC Urology & Nephrology SC Urology & Nephrology GA V27SS UT WOS:000208633501007 ER PT J AU Williams, DE Cadwell, B Nelson, RG Cheng, YJ Gregg, EW Engelgau, M Imperatore, G Narayan, KMV Geiss, LS AF Williams, Desmond E. Cadwell, Betsy Nelson, Robert G. Cheng, Yiling J. Gregg, Edward W. Engelgau, Michael Imperatore, Giuseppina Narayan, K. M. Venkat Geiss, Linda S. TI CHANGES IN THE PREVALENCE OF ALBUMINURIA IN THE US POPULATION 1991-1994 TO 1999-2002 SO NEPHROLOGY LA English DT Meeting Abstract C1 [Williams, Desmond E.; Cadwell, Betsy; Cheng, Yiling J.; Gregg, Edward W.; Engelgau, Michael; Imperatore, Giuseppina; Narayan, K. M. Venkat; Geiss, Linda S.] Ctr Dis Control & Prevent, Div Diabet Translat, Atlanta, GA USA. [Nelson, Robert G.] NIDDK, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD JUN PY 2005 VL 10 SU 1 BP A154 EP A154 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA V27SS UT WOS:000208633500587 ER PT J AU Yang, TX Zhang, AH Nelson, RD Gonzalez, FJ Kohan, DE Zhang, H AF Yang, Tianxin Zhang, Aihua Nelson, Raoul D. Gonzalez, Frank J. Kohan, Donald E. Zhang, Hui TI COLLECTING-DUCT-SPECIFIC DELETION OF PPAR gamma BLOCKS THIAZOLIDINEDIONE-INDUCED FLUID RETENTION SO NEPHROLOGY LA English DT Meeting Abstract C1 [Yang, Tianxin; Zhang, Aihua; Nelson, Raoul D.; Kohan, Donald E.; Zhang, Hui] Univ Utah, Salt Lake City, UT 84112 USA. [Gonzalez, Frank J.] NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1320-5358 J9 NEPHROLOGY JI Nephrology PD JUN PY 2005 VL 10 SU 1 BP A237 EP A237 PG 1 WC Urology & Nephrology SC Urology & Nephrology GA V27SS UT WOS:000208633501013 ER PT J AU Esteva-Font, C Ars, E Campistol, JM Jimenez, W Knepper, MA Ballarin, JA Barcelo, P Fernandez-Llama, P AF Esteva-Font, C Ars, E Campistol, JM Jimenez, W Knepper, MA Ballarin, JA Barcelo, P Fernandez-Llama, P TI Cyclosporine-induced hypertension is associated with increased sodium transporter of the loop of Henle (NKCC2/BSC1) SO NEPHROLOGY DIALYSIS TRANSPLANTATION LA English DT Meeting Abstract CT 42nd Annual Meeting of the European-Renal-Association/European-Dialysis-and-Transplant-Association (ERA-EDTA) CY JUN 04-07, 2005 CL Istanbul, TURKEY SP European Renal Assoc, European Diaysis &Transplant Assoc C1 Fdn Puigvert, Mol Biol Lab, Barcelona, Spain. Hosp Clin Barcelona, Renal Transplant Unit, Barcelona, Spain. Hosp Clin Barcelona, Hormonal Lab, Barcelona, Spain. NIH, Kidney & Electrolyte Metab Lab, Bethesda, MD 20892 USA. Fdn Puigvert, Renal Unit, Barcelona, Spain. Fdn Puigvert, Hypertens Unit, Barcelona, Spain. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0931-0509 J9 NEPHROL DIAL TRANSPL JI Nephrol. Dial. Transplant. PD JUN PY 2005 VL 20 SU 5 BP V37 EP V37 PG 1 WC Transplantation; Urology & Nephrology SC Transplantation; Urology & Nephrology GA 999GM UT WOS:000234376900099 ER PT J AU Ravi, LB Poosala, S Ahn, D Chrest, FJ Spangler, EL Jayakumar, R Nagababu, E Mohanty, JG Talan, M Ingram, DK Rifkind, JM AF Ravi, LB Poosala, S Ahn, D Chrest, FJ Spangler, EL Jayakumar, R Nagababu, E Mohanty, JG Talan, M Ingram, DK Rifkind, JM TI Red cell interactions with amyloid-beta(1-40) fibrils in a murine model SO NEUROBIOLOGY OF DISEASE LA English DT Article DE erythrocytes; beta-amyloid; Alzheimer's disease; murine in vivo study; spleen; liver; immunohistochemistry ID ALZHEIMERS AMYLOID-BETA; HIGH-DENSITY-LIPOPROTEIN; NORMAL HUMAN PLASMA; BLOOD-CELLS; BIOTINYLATED ERYTHROCYTES; IMMUNE-COMPLEXES; APOLIPOPROTEIN-J; KUPFFER CELLS; SOLUBLE FORM; DISEASE AB Vascular amyloidosis in Alzheimer's disease (AD) results in the exposure of red blood cells to 3-amyloid fibrils (AD). The potential in vivo ramifications of this exposure have been investigated by injecting A beta(1-40) alone or AD-bound mouse red blood cells into the circulation of C57BL/6 mice. Results indicate that when A beta(1-40) is injected alone, a transient uptake of the fibrils by red blood cells occurs in vivo. When A beta-bound red blood cells were injected, 3-amyloid is rapidly removed from these cells in vivo. Double-labeling experiments indicate that while some of the red blood cells bound to A beta(1-40) are removed from circulation, a major fraction of these cells remain in circulation even after AD is removed. Immunohistochemistry of murine tissue samples obtained after sacrificing the animals suggests that within 1 h after injection of A beta(1-40) or A beta-bound red blood cells, A beta is found in spleen phagocytes and liver Kupffer cells. Heme staining further indicates that the binding of A beta(1-40) to red blood cells enhances red cell phagocytosis by the spleen. (c) 2004 Elsevier Inc. All rights reserved. C1 NIA, Gerontol Res Ctr, Mol Dynam Sect, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Res Resources Branch, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Cardiovasc Sci Lab, Baltimore, MD 21224 USA. NIA, Gerontol Res Ctr, Lab Expt Gerontol, Baltimore, MD 21224 USA. Cent Leather Res Inst, Madras 600020, Tamil Nadu, India. RP Rifkind, JM (reprint author), NIA, Gerontol Res Ctr, Mol Dynam Sect, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM ritkindj@grc.nia.nih.gov NR 31 TC 11 Z9 11 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 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUN-JUL PY 2005 VL 19 IS 1-2 BP 28 EP 37 DI 10.1016/j.nbd.2004.11.004 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 920ET UT WOS:000228672900004 PM 15837558 ER PT J AU Criado, JR Sanchez-Alavez, M Conti, B Giacchino, JL Wills, DN Henriksen, SJ Race, R Manson, JC Chesebro, B Oldstone, MBA AF Criado, JR Sanchez-Alavez, M Conti, B Giacchino, JL Wills, DN Henriksen, SJ Race, R Manson, JC Chesebro, B Oldstone, MBA TI Mice devoid of prion protein have cognitive deficits that are rescued by reconstitution of PrP in neurons SO NEUROBIOLOGY OF DISEASE LA English DT Article DE prion protein; mice; knockout; Transgenic; hippocampus; spatial learning; circular maze; paired-pulse facilitation; LTP ID LONG-TERM POTENTIATION; CELLULAR PRION; NULL MICE; OXIDATIVE STRESS; TRANSGENIC MICE; HIPPOCAMPUS; MEMORY; EXPRESSION; BEHAVIOR; DOPPEL AB Prion protein (PrPC) is a constituent of most normal mammalian cells and plays an essential role in the pathogenesis of transmissible spongiform encephalopathies (TSE). However, the normal cellular function of PrPC remains unclear. Here, we document that mice with a selective deletion of PrPC exhibited deficits in hippocampal-dependent spatial learning, but non-spatial learning remained intact. mPrP(-/-) mice also showed reduction in paired-pulse facilitation and long-term potentiation in the dentate gyros in vivo. These deficits were rescued in transgenic mPrP(-/-) mice expressing PrPC in neurons under control of the neuron-specific enolase (NSE) promoter indicating that they were due to lack of PrPC function in neurons. The deficits were seen in mPrP(-/-) mice with a homogeneous 129/Ola background and in mPrP(-/-) mice in the mixed (129/Ola x C57BL/10) background indicating that these abnormalities were unlikely due to variability of background genes or alteration of the nearby Prnd (doppel) gene. Published by Elsevier Inc. C1 Scripps Res Inst, Dept Neuropharmacol, La Jolla, CA 92037 USA. Scripps Res Inst, Harold L Dorris Neurol Res Ctr, La Jolla, CA 92037 USA. Elan Pharmaceut, San Diego, CA 92121 USA. NIH, Rocky Mt Labs, Persistent Viral Dis Lab, Hamilton, MT 59840 USA. Inst Anim Hlth, Neuropathogenesis Unit, Edinburgh EH9 3JF, Midlothian, Scotland. RP Criado, JR (reprint author), Scripps Res Inst, Dept Neuropharmacol, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM jcriado@scripps.edu FU NIA NIH HHS [AG04342]; NIDA NIH HHS [DA12444, DA12669] NR 39 TC 102 Z9 108 U1 1 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0969-9961 J9 NEUROBIOL DIS JI Neurobiol. Dis. PD JUN-JUL PY 2005 VL 19 IS 1-2 BP 255 EP 265 DI 10.1016/j.nbd.2004.01.001 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 920ET UT WOS:000228672900027 PM 15837581 ER PT J AU Mattson, MP AF Mattson, MP TI NF-kappa B in the survival and plasticity of neurons SO NEUROCHEMICAL RESEARCH LA English DT Review DE antioxidant; apoptosis; bcl-2; calcium; learning and memory; mitochondria; transcription ID TRAUMATIC BRAIN-INJURY; NECROSIS-FACTOR-ALPHA; AMYLOID PRECURSOR PROTEIN; NITRIC-OXIDE SYNTHASE; NERVE GROWTH-FACTOR; HIPPOCAMPAL SYNAPTIC PLASTICITY; CEREBELLAR GRANULE NEURONS; CYANIDE-INDUCED APOPTOSIS; DNA-BINDING ACTIVITY; CELL-DEATH AB The transcription factor nuclear factor kappa-B (NF-kappa B) is involved in regulating responses of neurons to activation of several different signaling pathways in a variety of physiological and pathological settings. During development of the nervous system NF-kappa B is activated in growing neurons by neurotrophic factors and can induce the expression of genes involved in cell differentiation and survival. In the mature nervous system NF-kappa B is activated in synapses in response to excitatory synaptic transmission and may play a pivotal role in processes such as learning and memory. NF-kappa B is activated in neurons and glial cells in acute neurodegenerative conditions such as stroke and traumatic injury, as well as in chronic neurodegenerative conditions such as Alzheimer's disease. Activation of NF-kappa B in neurons can promote their survival by inducing the expression of genes encoding anti-apoptotic proteins such as Bcl-2 and the antioxidant enzyme Mn-superoxide dismutase. On the other hand, by inducing the production and release of inflammatory cytokines, reactive oxygen molecules and excitotoxins, activation of NF-kappa B in microglia and astrocytes may contribute to neuronal degeneration. Emerging findings suggest roles for NF-kappa B as a mediator of effects of behavioral and dietary factors on neuronal plasticity. NF-kappa B provides an attractive target for the development of novel therapeutic approaches for a range of neurological disorders. C1 NIA, Neurosci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Mattson, MP (reprint author), NIA, Neurosci Lab, Gerontol Res Ctr, 5600 Nathan Shock Dr, Baltimore, MD 21224 USA. EM mattsonm@grc.nia.nih.gov RI Mattson, Mark/F-6038-2012 NR 110 TC 148 Z9 158 U1 0 U2 14 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0364-3190 J9 NEUROCHEM RES JI Neurochem. Res. PD JUN PY 2005 VL 30 IS 6-7 BP 883 EP 893 DI 10.1007/s11064-005-6961-x PG 11 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 968LG UT WOS:000232163400019 PM 16187223 ER PT J AU Roper, P AF Roper, P TI Frequency-dependent depletion of secretory vesicle pools modulates bursting in vasopressin neurones of the rat supraoptic nucleus SO NEUROCOMPUTING LA English DT Article; Proceedings Paper CT 13th Annual Computational Neuroscience Meeting (CNS 04) CY JUL 18-20, 2004 CL Baltimore, MD DE bursting; dense-core granule exocytosis; vasopressin; dehydration; dynorphin; endocrine ID CELLS AB When stimulated, vasopressin neurones discharge lengthy, repeating bursts of action potentials. An increase in the stimulus strength causes both a lengthening of the bursts' active phase and an increase in the intra-burst firing frequency. Here we extend our earlier model (P. Roper, J. Callaway, W. Armstrong. J. Neurosci. 24(20) (2004) 4831.) for phasic bursting at a constant stimulus. We show that an increase in burst length could be due to a reduction of the co-secretion of an inhibitory factor, dynorphin, and we propose this to be caused by a frequency-dependent depletion of the pool of secretory vesicles. (c) 2004 Published by Elsevier B.V. C1 NIDDK, Math Res Branch, NIH, Bethesda, MD 20892 USA. RP Roper, P (reprint author), NIDDK, Math Res Branch, NIH, Room 4007,12A S DR,MSC 5621, Bethesda, MD 20892 USA. EM pete.roper@nih.gov NR 10 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-2312 J9 NEUROCOMPUTING JI Neurocomputing PD JUN PY 2005 VL 65 BP 485 EP 491 DI 10.1016/j.neucom.2004.11.005 PG 7 WC Computer Science, Artificial Intelligence SC Computer Science GA 933WM UT WOS:000229663600063 ER PT J AU Kotaleski, JH Plenz, D Blackwell, KT AF Kotaleski, JH Plenz, D Blackwell, KT TI The role of background synaptic noise in striatal fast spiking interneurons SO NEUROCOMPUTING LA English DT Article; Proceedings Paper CT 13th Annual Computational Neuroscience Meeting (CNS 04) CY JUL 18-20, 2004 CL Baltimore, MD DE striatum; fast spiking interneurons; Stochastic resonance; transient A current; up-states ID MEMBRANE-POTENTIAL FLUCTUATIONS; SPINY NEURONS; NEOSTRIATAL NEURONS; RAT NEOSTRIATUM; IN-VIVO; STATES AB Striatal fast spiking (FS) interneurons provide inhibition to each other as well as to medium spiny projection (SP) neurons. They exhibit up-states synchronously with SP neurons, and receive GABAergic and AMPA synaptic input during both up- and down-states. The synaptic input during down-states can be considered noise and might affect detection of up-states. We investigate what role this background noise might play for up-state firing in a 127 compartment FS model neuron. The model has Na, KDr and KA conductances, and is activated through AMPA and GABA synapses. The model's response to current injection and synaptic inputs resembled experimental data. We show that intermediate levels of noise neither facilitates nor degrades the ability of the FS neuron model to detect up-states. (c) 2004 Elsevier B.V. All rights reserved. C1 Royal Inst Technol, Dept Numer Anal & Comp Sci, Kungliga Tekniska Hogskolan, S-10044 Stockholm, Sweden. NIMH, Unit Neural Network Physiol, Lab Syst Neurosci, Bethesda, MD 20892 USA. George Mason Univ, Krasnow Inst, Fairfax, VA 22030 USA. RP Kotaleski, JH (reprint author), Royal Inst Technol, Dept Numer Anal & Comp Sci, Kungliga Tekniska Hogskolan, S-10044 Stockholm, Sweden. EM jeanette@nada.kth.se; plenzd@intra.nimh.nih.gov; avrama@gmu.edu OI Blackwell, Kim/0000-0003-4711-2344 NR 16 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-2312 J9 NEUROCOMPUTING JI Neurocomputing PD JUN PY 2005 VL 65 BP 727 EP 732 DI 10.1016/j.neucom.2004.10.068 PG 6 WC Computer Science, Artificial Intelligence SC Computer Science GA 933WM UT WOS:000229663600094 ER PT J AU Liang, HL Bressler, SL Desimone, R Fries, P AF Liang, HL Bressler, SL Desimone, R Fries, P TI Empirical mode decomposition: a method for analyzing neural data SO NEUROCOMPUTING LA English DT Article; Proceedings Paper CT 13th Annual Computational Neuroscience Meeting (CNS 04) CY JUL 18-20, 2004 CL Baltimore, MD DE selective visual attention; empirical mode decomposition; gamma synchronization; Hilbert transform; nonstationary AB Almost all processes that are quantified in neurobiology are stochastic and nonstationary. Conventional methods that characterize these processes to provide a meaningful and precise description of complex neurobiological phenomenon may be insufficient. Here, we report on the use of the data-driven empirical mode decomposition (EMD) method to study neuronal activity in visual cortical area V4 of macaque monkeys performing a visual spatial attention task. We found that local field potentials were resolved by the EMD into the sum of a set of intrinsic components with different degrees of oscillatory content. High-frequency components were identified as gamma band (35-90Hz) oscillations, whereas low-frequency components in single-trial recordings contributed to the average visual evoked potential (AVEP). Comparison with Fourier analysis showed that EMD may offer better temporal and frequency resolution. The EMD, coupled with instantaneous frequency analysis, may prove to be a vital technique for the analysis of neural data. (c) 2004 Elsevier B.V. All rights reserved. C1 Univ Texas, Hlth Sci Ctr, Sch Hlth Informat Sci, Ctr Computat Biomed, Houston, TX 77030 USA. Florida Atlantic Univ, Ctr Complex Syst & Brain Sci, Boca Raton, FL 33431 USA. NIMH, Neuropsychol Lab, NIH, Bethesda, MD 20892 USA. Univ Nijmegen, FC Donders Ctr Cognit Neuroimaging, NL-6525 EK Nijmegen, Netherlands. RP Liang, HL (reprint author), Univ Texas, Hlth Sci Ctr, Sch Hlth Informat Sci, Ctr Computat Biomed, Houston, TX 77030 USA. EM Hualou.liang@uth.tme.edu RI Fries, Pascal/E-3196-2010 OI Fries, Pascal/0000-0002-4270-1468 NR 5 TC 47 Z9 54 U1 0 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-2312 J9 NEUROCOMPUTING JI Neurocomputing PD JUN PY 2005 VL 65 BP 801 EP 807 DI 10.1016/j.neucom.2004.10.077 PG 7 WC Computer Science, Artificial Intelligence SC Computer Science GA 933WM UT WOS:000229663600103 ER PT J AU Greenwood-van Meerveld, B Johnson, AC Cochrane, S Schulkin, J Myers, DA AF Greenwood-van Meerveld, B Johnson, AC Cochrane, S Schulkin, J Myers, DA TI Corticotropin-releasing factor 1 receptor-mediated mechanisms inhibit colonic hypersensitivity in rats SO NEUROGASTROENTEROLOGY AND MOTILITY LA English DT Article DE antalarmin; colon; corticotropin releasing factor ID CORTICOTROPIN-RELEASING-FACTOR; IRRITABLE-BOWEL-SYNDROME; STRESS-RELATED ALTERATIONS; ANXIETY-LIKE BEHAVIOR; VISCERAL HYPERSENSITIVITY; CRF1 RECEPTOR; COLORECTAL DISTENSION; ANTAGONIST ANTALARMIN; SIGNALING PATHWAYS; STRAIN DIFFERENCES AB The potential relationship between stress and irritable bowel syndrome (IBS) symptomatology suggests a possible role for stress-mediating hormones, such as corticotropin-releasing factor (CRF), in the altered perception of stimuli in IBS patients. In previous studies, Wistar-Kyoto (WKY) rats with genetic indices of high anxiety demonstrated colonic hypersensitivity coupled with a high basal level of CRF within the central nervous system. In the current study we tested the hypothesis that a selective, non-peptide CRF, receptor antagonist, antalarmin, would inhibit hypersensitivity in the WKY rat colon. Colonic sensitivity was determined by monitoring a visceromotor behavioural response during innocuous levels of colorectal distention (30 mmHg). In high anxiety WKY rats we found that antalarmin (20 mg kg(-1), i.p.) significantly decreased the visceromotor response induced by colorectal distention. In a second study central administration (i.c.v.) of CRF was used to induce colonic hypersensitivity in lower anxiety Fischer 344 (F-344) rats, and in this model, antalarmin significantly inhibited the CRF-induced colonic hypersensitivity. In summary, a selective CRF, receptor antagonist, antalarmin, inhibits colonic hypersensitivity apparent in WKY rats or in F-344 rats given a central administration of CRF. Our findings suggest that CRF, receptor antagonism may represent a novel therapeutic approach for the treatment of IBS. C1 Univ Oklahoma, Hlth Sci Ctr, Oklahoma Ctr Neurosci, Oklahoma City, OK USA. Georgetown Univ, Dept Physiol & Biophys, Washington, DC USA. NIMH, Clin Neuroendocrinol Branch, Bethesda, MD 20892 USA. Univ Oklahoma, Hlth Sci Ctr, Dept Obstet & Gynecol, Oklahoma City, OK 73190 USA. RP Greenwood-van Meerveld, B (reprint author), VA Med Ctr Res Adm, Room 151,921 NE 13th St, Oklahoma City, OK 73104 USA. EM beverley-greenwood@ouhsc.edu NR 52 TC 69 Z9 70 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1350-1925 J9 NEUROGASTROENT MOTIL JI Neurogastroenterol. Motil. PD JUN PY 2005 VL 17 IS 3 BP 415 EP 422 DI 10.1111/j.1365-2982.2005.00648.x PG 8 WC Gastroenterology & Hepatology; Clinical Neurology; Neurosciences SC Gastroenterology & Hepatology; Neurosciences & Neurology GA 932FM UT WOS:000229539600013 PM 15916629 ER PT J AU Bolla, KI Eldreth, DA Matochik, JA Cadet, JL AF Bolla, KI Eldreth, DA Matochik, JA Cadet, JL TI Neural substrates of faulty decision-making in abstinent marijuana users SO NEUROIMAGE LA English DT Article DE psychoactive substance use disorder; brain imaging techniques; neuropathology; cognitive neuroscience ID VENTROMEDIAL PREFRONTAL CORTEX; POSITRON-EMISSION-TOMOGRAPHY; CEREBRAL-BLOOD-FLOW; CANNABINOID RECEPTOR; COCAINE ABUSERS; ORBITOFRONTAL CORTEX; FUTURE CONSEQUENCES; MAGNETIC-RESONANCE; TISSUE COMPOSITION; GAMBLING TASK AB Persistent dose-related cognitive decrements have been reported in 28-day abstinent heavy marijuana (MJ) users. However, the neural substrates of these decrements in cognitive performance are not known. This study aimed to determine if 25-day abstinent MJ users show persistent dose-related alterations in performance and brain activity using PET (H2O)-O-15 during the Iowa Gambling Task-IGT (a decision-making task). Eleven heavy MJ users and 11 non-drug users participated. The MJ group resided in an inpatient research unit at the NIH/NIDA-IRP for 25 days prior to testing to ensure abstinence. A dose-related association was found between increased MJ use and lower IGT performance and alterations in brain activity. The MJ group showed greater activation in the left cerebellum and less activation in the right lateral orbitofrontal cortex (OFC) and the right dorsolateral prefrontal cortex (DLPFC) than the Control group. When the MJ group was divided into Moderate (8-35 joints/week) and Heavy users (53-84 joints/week), the Heavy MJ group showed less activation in the left medial OFC and greater activation in the left cerebellum than the Moderate group. However, brain activity and task performance were similar between the Moderate MJ users and the Control group, suggesting a "threshold effect". These preliminary findings indicate that very heavy users of MJ have persistent decision-making deficits and alterations in brain activity. Specifically the Heavy MJ users may focus on only the immediate reinforcing aspects of a situation (i.e., getting high) while ignoring the negative consequences. Thus, faulty decision-making could make an individual more prone to addictive behavior and more resistant to treatment. Finally, it is unclear if these neurologic findings will become progressively worse with continued heavy MJ use or if they will resolve with abstinence from MJ use. (c) 2005 Elsevier Inc. All rights reserved. C1 Johns Hopkins Univ, Dept Neurol, Bayview Med Ctr, Sch Med, Baltimore, MD 21224 USA. Johns Hopkins Univ, Dept Psychiat & Behav Sci, Bayview Med Ctr, Sch Med, Baltimore, MD 21224 USA. Rutgers State Univ, Dept Psychol, Newark, NJ 07102 USA. NIDA, Neuroimaging Res Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD 21224 USA. NIDA, Mol Neuropsychiat Branch, DHHS, NIH,Intramural Res Program, Baltimore, MD 21224 USA. RP Bolla, KI (reprint author), Johns Hopkins Univ, Dept Neurol, Bayview Med Ctr, Sch Med, 4940 Eastern Ave, Baltimore, MD 21224 USA. EM kbolla@jhmi.edu FU NCRR NIH HHS [M01 RR02719]; NIDA NIH HHS [DA 11426] NR 60 TC 201 Z9 207 U1 5 U2 14 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 JUN PY 2005 VL 26 IS 2 BP 480 EP 492 DI 10.1016/j.neuroimage.2005.02.012 PG 13 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 931FV UT WOS:000229472100013 PM 15907305 ER PT J AU Jones, DK Symms, MR Cercignani, M Howard, RJ AF Jones, DK Symms, MR Cercignani, M Howard, RJ TI The effect of filter size on VBM analyses of DT-MRI data SO NEUROIMAGE LA English DT Article DE voxel-based morphometry; DT-MRI; filter size; SPM; fractional anisotropy ID DIFFUSION-TENSOR MRI; VOXEL-BASED MORPHOMETRY; WHITE-MATTER; STATISTICAL-ANALYSIS; HUMAN BRAIN; SCHIZOPHRENIA; ACTIVATION; IMAGES; ANISOTROPY; SCALE AB Voxel-based morphometry (VBM) has been used to analyze diffusion tensor MRI (DT-MRI) data in a number of studies. In VBM, following spatial normalization, data are smoothed to improve the validity of statistical inferences and to reduce inter-individual variation. However, the size of the smoothing filter used for VBM of DT-MRI data is highly variable across studies. For example, a literature review revealed that Gaussian smoothing kernels ranging in size (full width at half maximum) from zero to 16 mm have been used in DT-MRI VBM type studies. To investigate the effect of varying filter size in such analyses, whole brain DT-MRI data from 14 schizophrenic patients were compared with those of 14 matched control subjects using VBM, when the filter size was varied from zero to 16 mm. Within this range of smoothing, four different conclusions regarding apparent patient control differences could be made: (i) no significant patient-control differences; (ii) reduced FA in right superior temporal gyrus (STG) in patients; (iii) reduced FA in both right STG and left cerebellum in patients; and (iv) reduced FA only in left cerebellum in patients. These findings stress the importance of recognizing the effect of the matched filter theorem on VBM analyses of DT-MRI data. Finally, we investigated whether one of the underlying assumptions of parametric VBM, i.e., the normality of the residuals, is met. Our results suggest that, even with moderate smoothing, a large number of voxels within central white matter regions may have non-normally distributed residuals thus making valid statistical inferences with a parametric approach problematic in these areas. Published by Elsevier Inc. C1 Inst Psychiat, Neuroimaging Res Grp, Ctr Neuroimaging Sci, London SE5 8AF, England. NICHD, Lab Integrat Med & Biophys, Sect Tissue Biophys & Biomimet, Bethesda, MD 20892 USA. UCL, Inst Neurol, Dept Clin & Expt Epilepsy, London WC1N 3BG, England. UCL, Inst Neurol, Dept Neuroinflammat, London WC1N 3BG, England. Inst Psychiat, Old Age Psychiat Sect, London SE5 8AF, England. RP Jones, DK (reprint author), Inst Psychiat, Neuroimaging Res Grp, Ctr Neuroimaging Sci, De Crespigny Pk, London SE5 8AF, England. EM djones@iop.kcl.ac.uk RI Jones, Derek/D-1460-2009; Howard, Robert/E-4890-2010; OI Jones, Derek/0000-0003-4409-8049 FU Wellcome Trust NR 48 TC 403 Z9 406 U1 1 U2 17 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 JUN PY 2005 VL 26 IS 2 BP 546 EP 554 DI 10.1016/j.neuroimage.2005.02.013 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 931FV UT WOS:000229472100019 PM 15907311 ER PT J AU Rohl, JE Lunemann, JD Zimmer, C Zschenderlein, R Valdueza, JM AF Rohl, JE Lunemann, JD Zimmer, C Zschenderlein, R Valdueza, JM TI Multiple sclerosis coinciding with Machado-Joseph disease SO NEUROLOGICAL SCIENCES LA English DT Article DE multiple sclerosis (MS); Machado-Joseph disease (MJD); neurodegeneration; chronic inflammatory CNS disease AB Although inflammatory demyelination is considered to be the key feature in multiple sclerosis (MS) pathogenesis, histopathological investigations and MRI studies recently highlighted the extent of neuronal damage that occurs even in the early stages of the disease. We report the unusual case of a patient with Machado-Joseph disease (MJD; spinocerebellar ataxia (SCA) III) and discuss this coincidence in light current pathogenetic paradigms of CNS autoimmunity. C1 Humboldt Univ, Charite, Univ Hosp, Dept Neurol, D-10098 Berlin, Germany. NINDS, NIH, Cellular Immunol Sect, Bethesda, MD 20892 USA. Univ Leipzig, Univ Hosp, Dept Radiol, Neuroradiol Sect, D-7010 Leipzig, Germany. Bad Segeberger Kliniken, Dept Neurol, Bad Segeberg, Germany. RP Rohl, JE (reprint author), Humboldt Univ, Charite, Univ Hosp, Dept Neurol, Schumannstr 20-21, D-10098 Berlin, Germany. EM jens.roehl@charite.de RI Lunemann, Jan/G-8729-2011 OI Lunemann, Jan/0000-0002-3007-708X NR 5 TC 1 Z9 1 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1590-1874 J9 NEUROL SCI JI Neurol. Sci. PD JUN PY 2005 VL 26 IS 2 BP 135 EP 136 DI 10.1007/s10072-005-0447-0 PG 2 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 940TM UT WOS:000230167900011 PM 15995831 ER PT J AU Wiesenfeld-Hallin, Z Xu, XJ Crawley, JN Hokfelt, T AF Wiesenfeld-Hallin, Z Xu, XJ Crawley, JN Hokfelt, T TI Galanin and spinal nociceptive mechanisms: Recent results from transgenic and knock-out models SO NEUROPEPTIDES LA English DT Article; Proceedings Paper CT 3rd International Symposium on Galanin and its Receptors CY OCT 21-22, 2004 CL San Diego, CA DE galanin overexpression; heat; nerve injury; nociception; pain ID C-FIBER STIMULATION; REFLEX EXCITABILITY; INTRATHECAL GALANIN; PERIPHERAL AXOTOMY; SENSORY NEURONS; FLEXOR REFLEX; MICE; RAT; MORPHINE; CORD AB Genetically modified mice with transgenic overexpression of galanin or depletion of genes for galanin or galanin receptors have become available, providing a new approach for analyzing the role of galanin in nociception. Mice overexpressing galanin had a moderate heat hypoalgesia, reduced spinal sensitization after repetitive C-fiber stimulation and reduced development of neuropathic pain-like behavior after sciatic nerve injury. On the other hand, mice lacking the GALR1 receptor (Galr1(-/-)) exhibited only slight increase in heat nociception in the hot plate, but not tail flick, test and showed no increase in spinal sensitization. The duration, but not magnitude, of neuropathic pain-like behaviors, was increased in Galr1(-/-) mice after nerve injury. These results support an inhibitory effect of galanin on nociception, but the physiological role played by galanin via GALR1 receptors needs to be further studied. (c) 2004 Elsevier Ltd. All rights reserved. C1 Karolinska Inst, Dept Neurotec, Div Clin Neurophysiol, S-14186 Huddinge, Sweden. NIMH, Sect Behav Neuropharmacol, Bethesda, MD 20892 USA. Karolinska Inst, Dept Neurosci, Div Chem Neurotransmiss, Stockholm, Sweden. RP Wiesenfeld-Hallin, Z (reprint author), Karolinska Inst, Dept Med Lab Sci & Technol, Div Clin, S-14186 Huddinge, Sweden. EM zsuzsanna.wiesenfeld-hallin@labmed.ki.se NR 14 TC 37 Z9 40 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD JUN PY 2005 VL 39 IS 3 BP 207 EP 210 DI 10.1016/j.npep.2004.12.017 PG 4 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 939MD UT WOS:000230076000014 PM 15944013 ER PT J AU Rustay, NR Wrenn, CC Kinney, JW Holmes, A Bailey, KR Sullivan, TL Harris, AP Long, KC Saavedra, MC Starosta, G Innerfield, CE Yang, RJ Dreiling, JL Crawley, JN AF Rustay, NR Wrenn, CC Kinney, JW Holmes, A Bailey, KR Sullivan, TL Harris, AP Long, KC Saavedra, MC Starosta, G Innerfield, CE Yang, RJ Dreiling, JL Crawley, JN TI Galanin impairs performance on learning and memory tasks: Findings from galanin transgenic and GAL-R1 knockout mice SO NEUROPEPTIDES LA English DT Article; Proceedings Paper CT 3rd International Symposium on Galanin and its Receptors CY OCT 21-22, 2004 CL San Diego, CA DE galanin; learning; memory; peptide overexpression; receptor subtypes; fear conditioning; Alzheimers disease; transgenic mice ID ALZHEIMERS-DISEASE; ACETYLCHOLINE-RELEASE; RAT HIPPOCAMPUS; CHOICE ACCURACY; NUCLEUS BASALIS; ANTAGONIST M40; TREATED RATS; RECEPTOR; DEFICITS; OVEREXPRESSION AB Galanin (GAL) impairs performance on cognitive tasks when administered centrally to rats. GAL transgenic (GAL-tg) mice overexpressing endogenous GAL show deficits on the probe trial of the Morris water maze spatial learning task, on the social transmission of food preference olfactory memory task, and on the trace cued fear conditioning emotional learning and memory task. Knockout mice deficient in the GAL-R1 receptor subtype were normal on most memory tasks, while showing a small deficit in trace cued fear conditioning, suggesting a selective role for the GAL-R1 in aversive memories, and implicating other GAL receptor subtypes in spatial learning and olfactory social memory. The growing body of rodent literature implicating excess GAL in cognitive impairment is relevant to the overexpression of GAL in the basal forebrain during the progression of Alzheimer's disease. Published by Elsevier Ltd. C1 NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. RP Rustay, NR (reprint author), NIMH, Lab Behav Neurosci, Bethesda, MD 20892 USA. EM rustayn@mail.nih.gov NR 40 TC 31 Z9 33 U1 0 U2 1 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0143-4179 J9 NEUROPEPTIDES JI Neuropeptides PD JUN PY 2005 VL 39 IS 3 BP 239 EP 243 DI 10.1016/j.npep.2004.12.026 PG 5 WC Endocrinology & Metabolism; Neurosciences SC Endocrinology & Metabolism; Neurosciences & Neurology GA 939MD UT WOS:000230076000019 PM 15944016 ER PT J AU Lim, WN Isaac, JTR AF Lim, WN Isaac, JTR TI ATP hydrolysis is required for the rapid regulation of AMPA receptors during basal synaptic transmission and long-term synaptic plasticity SO NEUROPHARMACOLOGY LA English DT Article DE AMPA receptor; N-ethylmalcimide-sensitive factor; AMP-PCP; long-term potentiation; long-term depression ID HIPPOCAMPAL-NEURONS; GLUR1 SUBUNIT; PHOSPHORYLATION; DEPRESSION; NSF; POTENTIATION; EXPRESSION; BINDING; ALPHA; PICK1 AB ATP hydrolysis is critical for many cellular processes; however, the acute requirement for ATP hydrolysis in synaptic transmission and plasticity in neurons is unknown. Here we studied the effects of postsynaptically applying the non-hydrolyzable ATP analogue adenosine 5&PRIME;-[β,γ-methylene]triphosphate (AMP-PCP) into hippocarnpal CAl pyramidal cells in hippocampal slices. The effects of this manipulation were investigated on basal transmission and on two forms of long-term synaptic plasticity, long-term potentiation (LTP) and long-term depression (LTD). AMP-PCP caused an increase in basal AMPA receptor (AMPAR)mediated transmission, which occurred rapidly within minutes of infusing the drug. This effect was selective for ANIPARs, since pharmacologically isolated NMDAR-mediated synaptic currents did not exhibit this run up. In two-pathway experiments infusion of ANIP-PCP blocked the induction of both LTD and LTP. These findings show an acute and selective role for ATP hydrolysis in regulating AMPAR function both during basal transmission and long-term synaptic plasticity. Recent evidence indicates that AMPARs are selectively and acutely regulated by the ATPase N-ethylmaleimide-sensitive factor (NSF), which forms part of a multiprotein complex with AMPARs. Our data are consistent with the idea that such a mechanism that can acutely bi-directionally regulate AMPAR function at synapses and requires ATP hydrolysis is necessary for rapid activity-dependent changes in synaptic strength. © 2005 Elsevier Ltd. All rights reserved. C1 Univ Bristol, MRC, Ctr Synapt Plastic, Dept Anat, Bristol BS8 1TD, Avon, England. NINDS, NIH, Bethesda, MD 20892 USA. RP Isaac, JTR (reprint author), Univ Bristol, MRC, Ctr Synapt Plastic, Dept Anat, Bristol BS8 1TD, Avon, England. EM isaacj@ninds.nih.gov FU Wellcome Trust NR 37 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 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUN PY 2005 VL 48 IS 7 BP 949 EP 955 DI 10.1016/j.neuropharm.2005.02.001 PG 7 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 926YT UT WOS:000229160300003 PM 15857621 ER PT J AU Lupica, CR Riegel, AC AF Lupica, CR Riegel, AC TI Endocannabinoid release from midbrain dopamine neurons: A potential substrate for cannabinoid receptor antagonist treatment of addiction SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 2nd Workshop on Future Directionsl in Cannabinoid Therapeutics CY JUN 27, 2004 CL San Diego, CA DE drug abuse; nucleus accumbens; ventral tegmental area; SR141716A; Rimonabant; Marijuana; glutamate; GABA ID VENTRAL TEGMENTAL AREA; GABA-CONTAINING NEURONS; LONG-TERM DEPRESSION; FREELY-MOVING RATS; NUCLEUS-ACCUMBENS; CB1 RECEPTORS; ENDOGENOUS CANNABINOIDS; SYNAPTIC-TRANSMISSION; SUBSTANTIA-NIGRA; PREFRONTAL CORTEX AB Substantial evidence suggests that all commonly abused drugs act upon the brain reward circuitry to ultimately increase extracellular concentrations of the neurotransmitter dopamine in the nucleus accumbens and other forebrain areas. Many drugs of abuse appear to increase dopamine levels by dramatically increase the firing and bursting rates of dopamine neurons located in the ventral mesencephalon. Recent clinical evidence in humans and behavioral evidence in animals indicate that cannabinoid receptor antagonists such as SR141716A (Rimonabant) can reduce the self-administration of, and craving for, several commonly addictive drugs. However, the mechanism of this potentially beneficial effect has not yet been identified. We propose, on the basis of recent studies in our laboratory and others, that these antagonists may act by blocking the effects of endogenously released cannabinoid molecules (endocannabinoids) that are released in an activity- and calcium-dependent manner from mesencephalic dopamine neurons. It is hypothesized that, through the antagonism of cannabinoid CBI receptors located on inhibitory and excitatory axon terminals targeting the midbrain dopamine neurons, the effects of the endocannabinoids are occluded. The data from these studies therefore suggest that the endocannabinoid system and the CBI receptors located in the ventral mesencephalon may play an important role in regulating drug reward processes, and that this substrate is recruited whenever dopamine neuron activity is increased. Published by Elsevier Ltd. C1 NIDA, Neurophysiol Sect, Cellular Neurobiol Branch, Intramural Res Program,NIH,US Dept Hlth & Human S, Baltimore, MD 21224 USA. RP Lupica, CR (reprint author), NIDA, Neurophysiol Sect, Cellular Neurobiol Branch, Intramural Res Program,NIH,US Dept Hlth & Human S, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM clupica@intra.nida.nih.gov NR 96 TC 113 Z9 117 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUN PY 2005 VL 48 IS 8 BP 1105 EP 1116 DI 10.1016/j.neuropharm.2005.03.016 PG 12 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 935XL UT WOS:000229816600007 PM 15878779 ER PT J AU Pacher, P Batkai, S Kunos, G AF Pacher, P Batkai, S Kunos, G TI Blood pressure regulation by endocannabinoids and their receptors SO NEUROPHARMACOLOGY LA English DT Article; Proceedings Paper CT 2nd Workshop on Future Directionsl in Cannabinoid Therapeutics CY JUN 27, 2004 CL San Diego, CA DE hypertension; cannabinoids; hemodynamics; cardiac contractility ID CANNABINOID CB1 RECEPTOR; ENDOGENOUS CANNABINOIDS; HYPERTENSIVE-RATS; CARDIOVASCULAR FUNCTION; VANILLOID RECEPTORS; INDUCED HYPOTENSION; ANANDAMIDE; ARTERIAL; MEDIATE; DELTA-9-TETRAHYDROCANNABINOL AB Cannabinoids and their endogenous and synthetic analogs exert powerful hypotensive and carchodepressor effects by complex mechanisms involving direct and indirect effects on myocardium and vasculature. On the one hand, endocannabinoids and cannabinoid receptors have been implicated in the hypotensive state associated with hemorrhagic, endotoxic and cardiogenic shock, and advanced liver cirrhosis. On the other hand, there is emerging evidence suggesting that the endocannabinergic system plays an important role in the cardiovascular regulation in hypertension. This review is aimed to discuss the in vivo hypotensive and cardiodepressant effects of cannabinoids mediated by cannabinoid and TRPV1 receptors, and focuses on the novel therapeutical strategies offered by targeting the endocannabinoid system in the treatment of hypertension. Published by Elsevier Ltd. C1 NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. RP Pacher, P (reprint author), NIAAA, Lab Physiol Studies, NIH, Bethesda, MD 20892 USA. EM pacher@mail.nih.gov; gkunos@mail.nih.gov RI Batkai, Sandor/G-3889-2010; Pacher, Pal/B-6378-2008; Batkai, Sandor/H-7983-2014 OI Pacher, Pal/0000-0001-7036-8108; FU Intramural NIH HHS [Z01 AA000375-02] NR 56 TC 43 Z9 48 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0028-3908 J9 NEUROPHARMACOLOGY JI Neuropharmacology PD JUN PY 2005 VL 48 IS 8 BP 1130 EP 1138 DI 10.1016/j.neuropharm.2004.12.005 PG 9 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 935XL UT WOS:000229816600009 PM 15910888 ER PT J AU Basselin, M Chang, L Bell, JM Rapoport, SI AF Basselin, M Chang, L Bell, JM Rapoport, SI TI Chronic lithium chloride administration to unanesthetized rats attenuates brain dopamine D-2-like receptor-initiated signaling via arachidonic acid SO NEUROPSYCHOPHARMACOLOGY LA English DT Review DE lithium; phospholipase A(2); dopamine; quinpirole; arachidonic acid; bipolar disorder ID POSITRON-EMISSION-TOMOGRAPHY; CYTOSOLIC PHOSPHOLIPASE A(2); CEREBRAL GLUCOSE-UTILIZATION; INDUCED SUPER-SENSITIVITY; H-3 QUINPIROLE BINDING; D-2 AGONIST QUINPIROLE; DRUG-INDUCED MANIA; LONG-TERM LITHIUM; BIPOLAR DISORDER; G-PROTEINS AB We studied the effect of lithium chloride on dopaminergic neurotransmission via D-2-like receptors coupled to phospholipase A(2) (PLA(2)). In unanesthetized rats injected i.v. with radiolabeled arachidonic acid ( AA, 20: 4 n-6), regional PLA(2) activation was imaged by measuring regional incorporation coefficients k* of AA ( brain radioactivity divided by integrated plasma radioactivity) using quantitative autoradiography, following administration of the D-2-like receptor agonist, quinpirole. In rats fed a control diet, quinpirole at 1 mg/kg i.v. increased k* for AA significantly in 17 regions with high densities of D-2-like receptors, of 61 regions examined. Increases in k* were found in the prefrontal cortex, frontal cortex, accumbens nucleus, caudate - putamen, substantia nigra, and ventral tegmental area. Quinpirole, 0.25 mg/kg i.v. enhanced k* significantly only in the caudate - putamen. In rats fed LiCl for 6 weeks to produce a therapeutically relevant brain lithium concentration, neither 0.25 mg/kg nor 1 mg/kg quinpirole increased k* significantly in any region. Orofacial movements following quinpirole were modified but not abolished by LiCl feeding. The results suggest that downregulation by lithium of D-2-like receptor signaling involving PLA(2) and AA may contribute to lithium's therapeutic efficacy in bipolar disorder. C1 NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. RP Basselin, M (reprint author), NIA, Brain Physiol & Metab Sect, NIH, Bldg 9,Room 15128, Bethesda, MD 20892 USA. EM mirvasln@mail.nih.gov NR 145 TC 42 Z9 42 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 2005 VL 30 IS 6 BP 1064 EP 1075 DI 10.1038/sj.npp.1300671 PG 12 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 928UQ UT WOS:000229297600004 PM 15812572 ER PT J AU Ikemoto, S AF Ikemoto, S TI The supramammillary nucleus mediates primary reinforcement via GABA(A) receptors SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE reward; ventral tegmental area; posterior hypothalamic nucleus; picrotoxin; bicuculline; dopamine antagonist SCH 23390 ID VENTRAL TEGMENTAL AREA; ADJACENT REGIONS; BRAIN; RAT; CARBACHOL; ACCUMBENS; DOPAMINE; REWARD AB The supramammillary nucleus (SUM), a dorsal layer of the mammillary body, has recently been implicated in positive reinforcement. The present study examined whether GABA(A) receptors in the SUM or adjacent regions are involved in primary reinforcement using intracranial self-administration procedures. Rats learned quickly to lever-press for infusions of the GABA(A) antagonist picrotoxin into the SUM. Although picrotoxin was also self-administered into the posterior hypothalamic nuclei and anterior ventral tegmental area, these regions were less responsive to lower doses of picrotoxin than the SUM. The finding that rats learned to respond selectively on the lever triggering drug infusions is consistent with picrotoxin's reinforcing effect. Coadministration of the GABA(A) agonist muscimol disrupted picrotoxin self-administration, and another GABA(A) antagonist, bicuculline, was also self-administered into the SUM; thus, the reinforcing effect of picrotoxin is mediated by GABA(A) receptors. Since rats did not self-administer the GABA(B) antagonist 2-hydroxysaclofen into the SUM, the role of GABA(B) receptors may be distinct from that of GABA(A) receptors. Pretreatment with the dopamine receptor antagonist SCH 23390 (0.05 mg/kg, i.p.) extinguished picrotoxin self-administration into the SUM, suggesting that the reinforcing effects of GABA(A) receptor blockade depend on normal dopamine transmission. In conclusion, the blockade of GABA(A) receptors in the SUM is reinforcing, and the brain 'reward' circuitry appears to be tonically inhibited via supramammillary GABA(A) receptors and more extensive than the meso-limbic dopamine system. C1 NIDA, Behav Neurosci Branch, US Dept HHS, Baltimore, MD 21224 USA. RP Ikemoto, S (reprint author), NIDA, Behav Neurosci Branch, US Dept HHS, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM sikemoto@intra.nida.nih.gov OI Ikemoto, Satoshi/0000-0002-0732-7386 FU Intramural NIH HHS; NIDA NIH HHS [Z01 DA000439-06] NR 16 TC 19 Z9 20 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD JUN PY 2005 VL 30 IS 6 BP 1088 EP 1095 DI 10.1038/sj.npp.1300660 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 928UQ UT WOS:000229297600006 PM 15689963 ER PT J AU Weinrich, M Stuart, M Hoyer, T AF Weinrich, M Stuart, M Hoyer, T TI Rules for rehabilitation: An agenda for research SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE rehabilitation; medicare; chronic illness; hip fracture; stroke ID RANDOMIZED CONTROLLED-TRIAL; COST MINIMIZATION ANALYSIS; CONSTRAINT-INDUCED THERAPY; INPATIENT HOSPITAL-CARE; TOTAL KNEE ARTHROPLASTY; LENGTH-OF-STAY; HIP FRACTURE; STROKE REHABILITATION; HEALTH OUTCOMES; OUTPATIENT REHABILITATION AB Rehabilitation services have grown tremendously in the United States over the past 2 decades. Rules originally designed to guide Medicare reimbursement policies have had substantial effects in shaping the design clinical services. This article traces the development of the most significant federal rules regarding rehabilitation, outlines The existing empirical evidence to support these rules, and discusses an agenda for research to improve the evidence for future policy development. C1 NICHHD, Natl Ctr Med Rehabil Res, NIH, Rockville, MD 20852 USA. Univ Maryland Baltimore Cty, Dept Sociol & Anthropol, Baltimore, MD 21228 USA. RP Weinrich, M (reprint author), NICHHD, Natl Ctr Med Rehabil Res, NIH, 6100 Execut Blvd,Room 2A-01, Rockville, MD 20852 USA. EM mw287k@NIH.GOV NR 94 TC 6 Z9 6 U1 1 U2 5 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD JUN PY 2005 VL 19 IS 2 BP 72 EP 83 DI 10.1177/1545968305275718 PG 12 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 926HP UT WOS:000229114600001 PM 15883352 ER PT J AU Stuart, M Ryser, C Levitt, A Beer, S Kesselring, J Chard, S Weinrich, M AF Stuart, M Ryser, C Levitt, A Beer, S Kesselring, J Chard, S Weinrich, M TI Stroke rehabilitation in Switzerland versus the United States: A preliminary comparison SO NEUROREHABILITATION AND NEURAL REPAIR LA English DT Article DE rehabilitation; stroke; comparative study ID FUNCTIONAL INDEPENDENCE MEASURE; RANDOMIZED-TRIAL; DISABILITY; PHYSIOTHERAPY; INTENSITY; SERVICES; OUTCOMES; BOBATH; ADULTS; IMPACT AB This article compares the structure and process of rehabilitation for stroke patients at 2 internationally recognized rehabilitation hospitals, Klinik Valens ("Valens") in Switzerland and the William Donald Schaeffer Rehabilitation Hospital at Kernan ("Kernan") in the United States. Although the patient mix, structure, and process of rehabilitation were similar in many regards, there were some important differences. Most notably, on average, patients at the U.S. hospital were discharged from rehabilitation at approximately the same day poststroke that rehabilitation began in Switzerland. Patients remained in an inpatient setting an average of 40 days longer in Switzerland (for the combination of acute care and rehabilitation) and bad significantly higher levels of functioning at discharge when compared to their U.S. counterparts. The authors' findings suggest that Europe may offer opportunities for rehabilitation research that would be difficult to duplicate in the United States and highlight policy-relevant questions for future studies aimed at developing efficient managed care systems for stroke survivors. C1 Univ Maryland, Hlth Adm & Policy Program, Dept Sociol & Anthropol, Baltimore, MD 21228 USA. Klin Valens, Valens, Switzerland. Kernan Hosp, Baltimore, MD USA. NIH, Natl Ctr Med Rehabil Res, Bethesda, MD 20892 USA. RP Stuart, M (reprint author), Univ Maryland, Hlth Adm & Policy Program, Dept Sociol & Anthropol, 1000 Hilltop Circle,Baltimore Cty, Baltimore, MD 21228 USA. EM stuart@umbc.edu NR 29 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1545-9683 J9 NEUROREHAB NEURAL RE JI Neurorehabil. Neural Repair PD JUN PY 2005 VL 19 IS 2 BP 139 EP 147 DI 10.1177/1545968305277088 PG 9 WC Clinical Neurology; Rehabilitation SC Neurosciences & Neurology; Rehabilitation GA 926HP UT WOS:000229114600007 PM 15883358 ER PT J AU Berndt, SI Carter, HB Landis, PK Hallfrisch, J Rohrmann, S Metter, EJ Platz, EA AF Berndt, SI Carter, HB Landis, PK Hallfrisch, J Rohrmann, S Metter, EJ Platz, EA TI Prediagnostic plasma vitamin C levels and the subsequent risk of prostate cancer SO NUTRITION LA English DT Article DE antioxidants; vitamin C; plasma; prostate cancer; cohort study ID BETA-CAROTENE; RETINOL; CARCINOMA; BLOOD; CELLS; DIET AB Objective: Antioxidants, such as vitamin C, are hypothesized to prevent prostate carcinogenesis by protecting the DNA from oxidative damage. We assessed whether higher prediagnostic plasma concentrations of vitamin C were associated with a lower risk of prostate cancer in a well-nourished cohort of men. Methods: Plasma concentrations of ascorbic acid (vitamin Q were previously determined in blood specimens collected between 1984 and 1990 in men participating in the Baltimore Longitudinal Study of Aging. Total plasma ascorbic acid (L-ascorbic acid plus dehydro-L-ascorbic acid) levels were measured by using a modification of the 2,4-dinitrophenylhydrazine method. Among the 498 male participants with measured plasma vitamin C levels, 62 men were subsequently diagnosed with prostate cancer during their lifetime. Cox proportional hazards regression models were used to estimate relative risks and 95% confidence intervals for prostate cancer. Results: The median plasma concentration of vitamin C for the cohort was 1.17 mg/dL, which is in the normal to high range for older men. The age-adjusted relative risk of prostate cancer for the highest quartile (median = 1.47 mg/dL, range = 1.36-2.58) compared with the lowest quartile (median = 0.83 mg/dL, range = 0.15-0.98) of plasma vitamin C concentration was 1.31 (95% confidence interval 0.63 to 2.70, P for trend = 0.29). Adjustment for cigarette smoking status, body mass index, or plasma cholesterol concentration did not attenuate the results. Conclusions: This small but prospective study suggests that higher plasma vitamin C concentrations within the normal physiologic range are not associated with a lower risk of prostate cancer in well-nourished men. © 2005 Elsevier Inc. All rights reserved. C1 Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Johns Hopkins Univ Hosp, James Buchanan Brady Urol Inst, Baltimore, MD 21287 USA. USDA, Beltsville Human Nutr Res Ctr, Beltsville, MD 20705 USA. NIA, Lab Clin Invest, Baltimore, MD 21224 USA. RP Platz, EA (reprint author), Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. EM eplatz@jhsph.edu RI Rohrmann, Sabine/D-2113-2012 FU NCI NIH HHS [5 T32-CA09312, CA-58236] NR 26 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0899-9007 J9 NUTRITION JI Nutrition PD JUN PY 2005 VL 21 IS 6 BP 686 EP 690 DI 10.1016/j.nut.2004.11.012 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 932DL UT WOS:000229534300007 PM 15925292 ER PT J AU Rigden, DJ Galperin, MY AF Rigden, DJ Galperin, MY TI OMICS-related research in Latin America SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Editorial Material C1 Univ Liverpool, Liverpool L69 3BX, Merseyside, England. NIH, Bethesda, MD 20892 USA. RP Rigden, DJ (reprint author), Univ Liverpool, Liverpool L69 3BX, Merseyside, England. RI Galperin, Michael/B-5859-2013; OI Galperin, Michael/0000-0002-2265-5572; Rigden, Daniel/0000-0002-7565-8937 NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD SUM PY 2005 VL 9 IS 2 BP 129 EP 129 DI 10.1089/omi.2005.9.129 PG 1 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 942TW UT WOS:000230306800001 ER PT J AU Ismail, ASA Quinn, MG Wright, MA Ernst, A Kao, V Grogan, L Parr, A Grollman, F Kirsch, IR Grem, JL AF Ismail, ASA Quinn, MG Wright, MA Ernst, A Kao, V Grogan, L Parr, A Grollman, F Kirsch, IR Grem, JL TI A phase II and pharmacologic study of fluorouracil given by a 1-hour infusion daily for 5 days with leucovorin and interferon alpha-2a in adenocarcinoma of the large bowel SO ONCOLOGY REPORTS LA English DT Article DE fluorouracil; leucovorin; interferon alpha-2a; large bowel; adenocarcinoma ID METASTATIC COLORECTAL-CANCER; SURGICAL ADJUVANT BREAST; MICROSATELLITE INSTABILITY; COLON-CANCER; THYMIDYLATE SYNTHASE; REPLICATION ERROR; ORAL CAPECITABINE; PREDICTIVE VALUE; DOSE LEUCOVORIN; PLUS LEUCOVORIN AB We have reported that increasing the length of infusion from 5 min to 1 h appeared to substantially reduce the toxicity associated with fluorouracil (5-FU) modulated by leucovorin (LV) and interferon α-2a (IFN-α.). This phase II study assessed the antitumor efficacy of this regimen. Patients (n=38) with colorectal cancer received IFN-α 5 MU/m(2) SC on days 1-6; on days 2-6, LV 200 mg/m(2) IV was given with 5-FU at initial doses of 370-425 mg/m(2)/h. The regimen was well-tolerated with no grade 4 toxicity. At 425 mg/m(2) 5-FU, grade 3 toxicities included diarrhea (8.6%), anorexia, fever and fatigue (5.7% each), neutropenia and nausea/vomiting (2.9% each). Individuals tolerated 5-FU doses up to 644 mg/m(2). Objective responses occurred in 27% of 37 patients; median time to progression and survival were 6.1 and 12.9 months. Only 1 of 25 informative tumor samples had high-frequency microsatellite instability (MSI), while 7 of 23 assessable patients (30%) with MSI-negative tumors had an objective response. With 425 mg/m(2), the average 5-FU Cp and AUC(0-1 h) were 37.4 μ M and 1161 μ M/h. Some 6 patients had extended sampling, and the half-lives of 5-FU and FBAL (apparent) were 8.6 and 100.0 min, respectively. A 1-h infusion of 5-FU is well tolerated; individual dose escalation of 5-FU allows each patient to receive the maximum tolerable dose. C1 USN, Med Ctr, Natl Canc Inst, Canc Therapeut Branch, Bethesda, MD 20889 USA. USN, Med Ctr, Natl Canc Inst, Med Oncol Clin Res Unit, Bethesda, MD 20889 USA. USN, Med Ctr, Natl Canc Inst, Canc Genet Branch,Ctr Canc Res, Bethesda, MD 20889 USA. RP Grem, JL (reprint author), Univ Nebraska, Med Ctr, Hematol Oncol Sect, 600 S 42nd St, Omaha, NE 68198 USA. EM jgrem@unmc.edu NR 34 TC 1 Z9 1 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD JUN PY 2005 VL 13 IS 6 BP 1145 EP 1152 PG 8 WC Oncology SC Oncology GA 925MN UT WOS:000229057300022 PM 15870935 ER PT J AU Cesari, M Pahor, M Lauretani, F Penninx, BWHJ Bartali, B Russo, R Cherubini, A Woodman, R Bandinelli, S Guralnik, JM Ferrucci, L AF Cesari, M Pahor, M Lauretani, F Penninx, BWHJ Bartali, B Russo, R Cherubini, A Woodman, R Bandinelli, S Guralnik, JM Ferrucci, L TI Bone density and hemoglobin levels in older persons: results from the InCHIANTI study SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE anemia; bone density; cortical bone density; hemoglobin ID RISK-FACTORS; PHYSICAL PERFORMANCE; PERNICIOUS-ANEMIA; THALASSEMIA MAJOR; MUSCLE STRENGTH; MINERAL DENSITY; AGING BONE; OSTEOPOROSIS; WOMEN; MEN AB Hypoxemia has been recognized as a risk factor for bone loss. The aim of the present study is to investigate the relationship of bone mass and density measures with anemia and hemoglobin levels in a large sample of older community-dwelling persons. The study is based on data from 950 participants enrolled in the "Invecchiare in Chianti'' ( Aging in the Chianti area, InCHIANTI) study. All the analyses were performed considering continuous hemoglobin levels as well as the dichotomous anemia variable ( defined according to WHO criteria as hemoglobin < 12 g/dl in women and < 13 g/dl in men). A peripheral quantitative computerized tomography (pQCT) scan of the right calf was performed in all participants to evaluate total bone density, trabecular bone density, cortical bone density, and the ratio between cortical and total bone area. Linear regression analyses were used to assess the multivariate relationship of pQCT bone measures with anemia and hemoglobin levels after adjustment for demographics, chronic conditions, muscle strength and biological variables. Participants were 75.0 (SD 6.9) years old. In our sample, 101 participants (10.6%) were anemic. In women, coefficients from adjusted linear regression analyses evaluating the association between pQCT bone measures ( per SD increase) and hemoglobin levels/anemia showed significant associations of anemia with total bone density ( beta=) 0.335, SE= 0.163; P= 0.04) and cortical bone density (beta=) 0.428, SE= 0.160; P= 0.008). Relationships with borderline significance were found for the associations of anemia with trabecular bone density and the ratio between cortical and total bone area. Significant associations were found between hemoglobin levels and trabecular bone density (beta= 0.112, SE= 0.049; P= 0.02), total bone density (beta= 0.101, SE= 0.046; P= 0.03), cortical bone density (beta= 0.100, SE= 0.046; P= 0.03) and the ratio between cortical bone and total area (beta= 0.092, SE= 0.045; P= 0.04). In men, significant associations were found for hemoglobin levels with total bone density (beta= 0.076, SE= 0.036; P= 0.03) and cortical bone density (beta = 0.095, SE= 0.41; P= 0.02). A borderline significance was reported for the association between anemia and cortical bone density. We concluded that anemia and low hemoglobin levels are negatively and independently associated with bone mass and density. The bone loss associated with hemoglobin levels mainly occurs in the cortical bone. Women with lower hemoglobin levels demonstrate a higher bone loss than male counterparts. C1 Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Winston Salem, NC 27157 USA. INRCA, Dept Geriatr, Lab Clin Epidemiol, Florence, Italy. Vrije Univ Amsterdam, Dept Psychiat, Amsterdam, Netherlands. Univ Perugia, Dept Gerontol & Geriatr, I-06100 Perugia, Italy. Ortho Biotech Prod LP, Bridgewater, NJ USA. NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. NIA, Longitudinal Studies Sect, Clin Res Branch, Bethesda, MD 20892 USA. RP Cesari, M (reprint author), Wake Forest Univ, Bowman Gray Sch Med, Sticht Ctr Aging, Med Ctr Blvd, Winston Salem, NC 27157 USA. EM mcesari@wfubmc.edu RI Cesari, Matteo/A-4649-2008; Lauretani, Fulvio/K-5115-2016; OI Cesari, Matteo/0000-0002-0348-3664; Lauretani, Fulvio/0000-0002-5287-9972; Cherubini, Antonio/0000-0003-0261-9897 FU NIA NIH HHS [P30-AG-021332-01] NR 44 TC 28 Z9 29 U1 0 U2 2 PU SPRINGER LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PD JUN PY 2005 VL 16 IS 6 BP 691 EP 699 DI 10.1007/s00198-004-1739-6 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 931TO UT WOS:000229508600015 PM 15455197 ER PT J AU Gallego, SG Loukas, A Slade, RW Neva, FA Varatharajalu, R Nutman, TB Brindley, PJ AF Gallego, SG Loukas, A Slade, RW Neva, FA Varatharajalu, R Nutman, TB Brindley, PJ TI Identification of an astacin-like metallo-proteinase transcript from the infective larvae of Strongyloides stercoralis SO PARASITOLOGY INTERNATIONAL LA English DT Article DE metallo-proteinase; astacin; Strongyloides stercoralis; filariform larva; metzincin; strongylastacin; tolloid; CUB; gene clusters ID GENE FAMILY; CAENORHABDITIS-ELEGANS; ZINC-ENDOPEPTIDASE; MOLECULAR-CLONING; CRYSTAL-STRUCTURE; C-ELEGANS; METALLOENDOPEPTIDASE; PROTEASE; MEMBER; BMP-1 AB Strongyloides stercoralis, an important nematode pathogen of humans, is transmitted by contact with soil contaminated with the microscopic larvae of the parasite. We determined the cDNA sequence and deduced amino acid structure of a metallo-proteinase that is abundantly transcribed expressed by infective stage larvae of S. stercoralis. This deduced structure of the enzyme revealed a multi-domain protein that included an NH2-terminal peptidase. This peptidase consisted of a signal peptide, a pro-enzyme region, and a mature peptidase domain that included the metal ion co-ordinating motifs, HETSHALGVIH and SIMHY ("Met-turn"), characteristic of the catalytic active site of members of the metzincin superfamily of zinc metallo-endopeptidases. It was phylogenetically and structurally similar to astacin from the digestive gland of the crayfish Astacus astacus, to the HCH-1 peptidase of Caenorhabditis elegans required for hatching and migration of a post-embryonic neuroblast, and to the morphogenetically important peptidases, bone morphogenetic protein-1 (BMP-1) and Drosophila tolloid. In addition, the Strongyloides enzyme, designated strongylastacin, includes a central epidermal growth factor (EGF) domain followed by a carboxyl CUB (complement sub component C1r/C1s/embryonic sea urchin protein Uegf/bone morphogenetic protein) domain. Inspection of the dbEST database revealed the presence of at least 9 transcript clusters that are related to greater or lesser extent to strongylastacin; based on these expressed sequence tags, strongylastacin was expressed only in the infective third stage larvae, whereas other transcript clusters were expressed both in filariform and rhabditiform stages or only in the rhabditiform stage. Based on the deduced sequence, structure, and expression profile, strongylastacin is the probable candidate for the zinc-dependent metalloprotease, Ss40, known to be deployed by larvae of S. stercoralis to penetrate human skin to initiate infection. (c) 2005 Elsevier Ireland Ltd. All rights reserved. C1 Tulane Univ, Hlth Sci Ctr, Dept Trop Med, Sch Publ Hlth & Trop Med, New Orleans, LA 70112 USA. Queensland Inst Med Res, Div Infect Dis & Immunol, Brisbane, Qld 4029, Australia. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. RP Brindley, PJ (reprint author), Tulane Univ, Hlth Sci Ctr, Dept Trop Med, Sch Publ Hlth & Trop Med, SL17,1430 Tulane Ave, New Orleans, LA 70112 USA. EM paul.brindley@tulane.edu RI Loukas, Alex/B-7355-2014 OI Loukas, Alex/0000-0002-0896-8441 NR 51 TC 32 Z9 33 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 1383-5769 J9 PARASITOL INT JI Parasitol. Int. PD JUN PY 2005 VL 54 IS 2 BP 123 EP 133 DI 10.1016/j.parint.2005.02.002 PG 11 WC Parasitology SC Parasitology GA 929LK UT WOS:000229347400004 PM 15866474 ER PT J AU Rutten, LJF Arora, NK Bakos, AD Aziz, N Rowland, J AF Rutten, LJF Arora, NK Bakos, AD Aziz, N Rowland, J TI Information needs and sources of information among cancer patients: a systematic review of research (1980-2003) SO PATIENT EDUCATION AND COUNSELING LA English DT Review DE cancer; information needs; information sources ID SUPPORTIVE CARE NEEDS; BREAST-CANCER; PROSTATE-CANCER; RADIATION-THERAPY; GYNECOLOGICAL CANCER; PSYCHOSOCIAL NEEDS; DECISIONAL PREFERENCES; COLORECTAL-CANCER; EMOTIONAL SUPPORT; SEEKING BEHAVIOR AB Understanding what cancer patients need to know and from whom they receive information during the course of care is essential to ensuring quality care. We reviewed 112 articles published from 1980 to 2003 and developed a typology summarizing cancer patients' information needs and the sources from which they receive information. The majority of articles focused on information needs and sources during the diagnosis and treatment phase. Thus, the most frequent information need was treatment-related (38.1%). The most frequent information source was health professionals (27.3%). We examined patients' information needs and sources along the continuum of care and found that during diagnosis and treatment, information needs about the stage of disease, treatment options, and side-effects of treatment were prominent; during post- treatment, patients continued to need information about treatment, and information about recovery was also important. Future research should examine cancer patients' information needs and sources throughout their cancer journey. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. NINR, Bethesda, MD 20892 USA. EM finneyl@mail.nih.gov NR 127 TC 349 Z9 355 U1 6 U2 34 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0738-3991 J9 PATIENT EDUC COUNS JI Patient Educ. Couns. PD JUN PY 2005 VL 57 IS 3 BP 250 EP 261 DI 10.1016/j.pec.2004.06.006 PG 12 WC Public, Environmental & Occupational Health; Social Sciences, Interdisciplinary SC Public, Environmental & Occupational Health; Social Sciences - Other Topics GA 938CT UT WOS:000229978200002 PM 15893206 ER PT J AU Raval, AN Lederman, RJ AF Raval, AN Lederman, RJ TI Real-time magnetic resonance imaging to guide pediatric endovascular procedures SO PEDIATRIC CARDIOLOGY LA English DT Article; Proceedings Paper CT 8th Pediatric Interventional Cardiac Symposium (PICS-VIII)/2nd Conference on Emerging New Technologies in Congenital Heart Surgery (ENTICHS-II) CY 2004 CL Chicago, IL DE magnetic resonance imaging; interventional; pediatric; congenital ID ENHANCED MR-ANGIOGRAPHY; VENA-CAVA FILTER; CARDIAC-CATHETERIZATION; RADIATION-EXPOSURE; UTERINE FIBROIDS; ANIMAL-MODEL; SWINE MODEL; PROJECTION RECONSTRUCTION; CORONARY CATHETERIZATION; PROSTATE BRACHYTHERAPY AB Although x-ray fluoroscopy ( XRF) has guided diagnostic and therapeutic transcatheter procedures for decades, certain limitations still exist. XRF still visualizes tissue poorly and relies on projection of shadows that do not convey depth information. Adjunctive echocardiography overcomes some of these limitations but still suffers suboptimal or unreliable imaging windows. Furthermore, ionizing radiation exposure in children imparts a cancer risk. An interventional platform using real-time magnetic resonance imaging ( MRI) may offer superior image guidance without radiation. Although there are many remaining challenges, but real-time MRI has the potential to revolutionize transcatheter therapeutics. C1 NHLBI, Cardiovasc Branch, Div Intramural Res, NIH, Bethesda, MD 20892 USA. RP Lederman, RJ (reprint author), NHLBI, Cardiovasc Branch, Div Intramural Res, NIH, Bldg 10,Room 2c713,MSC 1538, Bethesda, MD 20892 USA. EM lederman@nih.gov NR 86 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0172-0643 J9 PEDIATR CARDIOL JI Pediatr. Cardiol. PD JUN PY 2005 VL 26 IS 3 BP 251 EP 259 DI 10.1007/s00246-005-1008-2 PG 9 WC Cardiac & Cardiovascular Systems; Pediatrics SC Cardiovascular System & Cardiology; Pediatrics GA 966XU UT WOS:000232056900010 PM 16132301 ER PT J AU Kovacs, A Cowles, MK Britto, P Capparelli, E Fowler, MG Moye, J McIntosh, K Rathore, MH Pitt, J Husson, RN AF Kovacs, A Cowles, MK Britto, P Capparelli, E Fowler, MG Moye, J McIntosh, K Rathore, MH Pitt, J Husson, RN TI Pharmacokinetics of didanosine and drug resistance mutations in infants exposed to zidovudine during gestation or postnatally and treated with didanosine or zidovudine in the first three months of life SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 25-28, 2001 CL SAN FRANCISCO, CA SP Infect Dis Soc Amer DE human immunodeficiency vir-us; infant; resistance; mutations; early treatment; didanosine; zidovudine; pharmacokinetics ID HUMAN-IMMUNODEFICIENCY-VIRUS; GROUP PROTOCOL 076; VERTICAL TRANSMISSION; REVERSE-TRANSCRIPTASE; GENOTYPIC RESISTANCE; HIV-INFECTION; LAMIVUDINE; THERAPY; TYPE-1; CHILDREN AB Background: There are limited numbers of drugs that are available in formulations that are appropriate for neonates and few studies assessing resistance among infants born to human immunodeficiency virus (HIV)-infected women. Methods: Pharmacokinetics and tolerance of didanosine (ddI) were determined for infants <= 120 days of age. Infants received at least 24 hours of zidovudine (ZDV) treatment, followed by a single ddI dose and pharmacokinetic sampling. The target area under the concentration-time curve (AUC) was between 2.5 and 5.0 mu M . hour. Toxicity and drug resistance mutations were assessed at baseline and follow-up times. Results: The initial ddI pharmacokinetic dosing of 50 mg/m(2) for infants > 28 days of age achieved a median AUC(0-infinity) of 2.8 mu M hour . For infants <= 28 days of age, the target AUC was achieved after dose escalation from 25 mg/m(2) (median AUC(0-infinity) 1.4 mu M . hour) to 50 mg/m(2) (median AUC(0-infinity), 5.40 mu M . hour). At baseline, 25% of infected infants had drug resistance mutations (9 of 44 to ZDV and 2 of 44 to ddI). Resistance mutations were present for 29% of infants (5 of 17 infants) with in utero ZDV exposure and 25% (8 of 32 infants) with prior ZDV treatment. The most common ZDV mutation noted at baseline was the T215Y/F (n = 7) mutation; 2 of these infants also had the M41L mutation, which is associated with high level ZDV resistance. No prior exposure was noted for the 2 infants with ddI resistance, which indicates possible perinatal transmission of ddI-resistant virus to these infants. Conclusions: A dose of 50 mg/m(2) is the appropriate ddI dose for infants < 120 days of age and is a safe treatment for newborns when used in combination with ZDV. Genotypic resistance occurs frequently among infected infants exposed to ZDV during gestation or postnatally, which suggests that resistance testing should be considered for infants with newly diagnosed HIV infection. C1 Univ So Calif, Keck Sch Med, Maternal Child & Adolescent Ctr Infect Dis & Viro, Los Angeles, CA 90033 USA. Univ Iowa, Dept Stat & Actuarial Sci, Iowa City, IA 52242 USA. Harvard Univ, Sch Publ Hlth, Ctr Biostat AIDS Res, Boston, MA 02115 USA. Univ Calif San Diego, Pediat Pharmacol Res Unit, San Diego, CA 92103 USA. NIAID, Div Aids, Bethesda, MD 20892 USA. NICHHD, Bethesda, MD 20892 USA. Harvard Univ, Childrens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. Univ Florida, Hlth Sci Ctr, Jacksonville, FL 32209 USA. Columbia Univ, Sch Med, Div Infect Dis, New York, NY USA. RP Kovacs, A (reprint author), Univ So Calif, Keck Sch Med, Maternal Child & Adolescent Ctr Infect Dis & Viro, 1640 Marengo St,Hlth Res Assoc Bldg,3rd Floor, Los Angeles, CA 90033 USA. EM akovacs@usc.edu OI moye, john/0000-0001-9976-8586 NR 30 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUN PY 2005 VL 24 IS 6 BP 503 EP 509 DI 10.1097/01.inf.0000164787.63237.0b PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 938ZW UT WOS:000230042900005 PM 15933559 ER PT J AU Sow, SO Diallo, S Campbell, JD Tapia, MD Keita, T Keita, MM Murray, P Kotloff, KL Levine, MM AF Sow, SO Diallo, S Campbell, JD Tapia, MD Keita, T Keita, MM Murray, P Kotloff, KL Levine, MM TI Burden of invasive disease caused by Haemophilus influenzae type b in Bamako, Mali - Impetus for routine infant immunization with conjugate vaccine SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE Haemophilus influenzae type b; Mali; infant immunization; disease burden ID MENINGOCOCCAL MENINGITIS; BACTERIAL-MENINGITIS; CHILDREN; INFECTIONS; COUNTRIES; EFFICACY; GAMBIA; SURVEILLANCE; PREVENTION; PNEUMONIA AB Background: Population-based, bacteriologically confirmed disease burden data aid decision makers in African countries pondering whether to introduce Haemophilus influenzae type b (Hib) immunization for infants. Methods: A bacteriology laboratory was established in Hopital Gabriel Toure, serving Bamako, Mali. Children age 0-15 years with fever >= 39 degrees C or syndromes compatible with invasive bacterial disease (meningitis, etc.) were eligible. From 2 to 5 mL of blood or relevant body fluid were inoculated into Bactec Ped Plus/F medium for automated culture; body fluids were also inoculated directly onto solid media. Hib was confirmed by standard microbiologic techniques and antibiograms generated by disk diffusion. Results: From June 1, 2002 to May 31, 2004, 3 592 (87.8%) of 4092 children admitted to Hopital Gabriel Tour with high fever or suspected invasive bacterial disease were cultured, including 1745 who were 0-11 months old, 1132 who were 1-4 years old and 715 who were 5-15 years old. Hib was isolated from 207 Bamako children, 81 from blood alone and 124 from cerebrospinal fluid (with or without positive blood culture). Of 207 cases 204 (98.5%) occurred in children younger than age 5 years (annual incidence, 45.2/10(5)) and 159 (77%) in infants age 0-11 months (annual incidence, 158.4/10(5)). Peak incidence (370.0 cases/10(5)) and 12 of 21 Hib deaths occurred in 6- to 7-month-olds. Of the Hib isolates, 11.1% were resistant to ampicillin, 32% to chloramphenicol and 0.5% to ceftriaxone. Conclusions: The substantial burden of invasive Hib disease documented in Bamako has prompted the Malian government to introduce routine infant immunization with Hib conjugate. C1 Gabriel Toure Hosp, CVD Mali, Bamako, Mali. Gabriel Toure Hosp, Serv Pediat, Bamako, Mali. Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. NIH, Clin Microbiol Labs, Bethesda, MD 20892 USA. RP Sow, SO (reprint author), Gabriel Toure Hosp, CVD Mali, Bamako, Mali. RI kotloff, karen/E-7768-2012 OI kotloff, karen/0000-0003-1808-6431 NR 29 TC 23 Z9 23 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD JUN PY 2005 VL 24 IS 6 BP 533 EP 537 DI 10.1097/01.inf.0000164768.28135.0d PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 938ZW UT WOS:000230042900010 PM 15933564 ER PT J AU Bleyer, AJ Hart, TC Willingham, MC Iskandar, SS Gorry, MC Trachtman, H AF Bleyer, AJ Hart, TC Willingham, MC Iskandar, SS Gorry, MC Trachtman, H TI Clinico-pathologic findings in medullary cystic kidney disease type 2 SO PEDIATRIC NEPHROLOGY LA English DT Article DE uromodulin-associated kidney disease; familial juvenile hyperuricemic nephropathy; Tamm Horsfall protein; uromodulin ID JUVENILE HYPERURICEMIC NEPHROPATHY; TAMM-HORSFALL GLYCOPROTEIN; UMOD GENE; UROMODULIN; MUTATIONS; CLUSTER; MCKD AB Medullary cystic kidney disease type 2 is an uncommon autosomal dominant condition characterized by juvenile onset hyperuricemia, precocious gout and chronic renal failure progressing to end-stage renal disease in the 4th through 7th decades of life. A family suffering from this condition is described. The patient in the index case presented with renal insufficiency as a child. A renal biopsy revealed tubular atrophy, and immunohistochemical staining of the tissue for uromodulin (Tamm Horsfall protein) revealed dense deposits in renal tubular cells. Genetic testing revealed a single nucleotide mutation (c.899G>A) resulting in an exchange of a cysteine residue for tyrosine (C300Y). Medullary cystic kidney disease type 2 (also known as uromodulin-associated kidney disease) likely represents a form of endoplasmic reticulum storage disease, with deposition of the abnormal uromodulin protein in the endoplasmic reticulum, leading to tubular cell atrophy and death. C1 Wake Forest Univ, Sch Med, Nephrol Sect, Winston Salem, NC 27109 USA. Natl Inst Dent & Craniofacial Res, NIH, Bethesda, MD USA. Wake Forest Univ, Sch Med, Dept Pathol, Winston Salem, NC 27109 USA. Univ Pittsburgh, Sch Dent Med, Div Oral Biol, Pittsburgh, PA USA. Schneider Childrens Hosp, Div Nephrol, New Hyde Pk, NY USA. RP Bleyer, AJ (reprint author), Wake Forest Univ, Sch Med, Nephrol Sect, Med Ctr Blvd, Winston Salem, NC 27109 USA. EM ableyer@wfubmc.edu OI Trachtman, Howard/0000-0001-7447-9489 FU NIDDK NIH HHS [DK62252] NR 13 TC 13 Z9 14 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0931-041X J9 PEDIATR NEPHROL JI Pediatr. Nephrol. PD JUN PY 2005 VL 20 IS 6 BP 824 EP 827 DI 10.1007/s00467-004-1719-2 PG 4 WC Pediatrics; Urology & Nephrology SC Pediatrics; Urology & Nephrology GA 935MR UT WOS:000229786900025 PM 15844001 ER PT J AU Benfield, MR Tejani, A Harmon, WE McDonald, R Stablein, DM McIntosh, M Rose, S AF Benfield, MR Tejani, A Harmon, WE McDonald, R Stablein, DM McIntosh, M Rose, S CA CCTPT study grp TI A randomized multicenter trial of OKT3 mAbs induction compared with intravenous cyclosporine in pediatric renal transplantation SO PEDIATRIC TRANSPLANTATION LA English DT Article DE renal transplant; immunosuppression; induction; monoclonal antibody; pediatric transplantation; rejection; renal function ID KIDNEY-TRANSPLANTATION; MYCOPHENOLATE-MOFETIL; ACUTE REJECTION; ALLOGRAFT RECIPIENTS; CLINICAL-TRIAL; PREVENTION; GLOMERULONEPHRITIS; IMMUNOSUPPRESSION; THERAPY AB Acute rejection leading to renal graft failure is more frequent among children. In patients treated with T cell antibody induction, retrospective data from the pediatric registry show a 22% reduction in the risk of graft failure. We conducted a randomized trial (n = 287) using OKT3 mAbs in one (OKT3) arm and intravenous cyclosporine in the other arm (CYS). Maintenance therapy consisted of randomized, double blind Sandimmune((R)) or Neoral((R)) together with prednisone and either azathioprine (AZA) or mycophenolate mofetil (MMF). Morbidity, mortality, rejection rates and adverse reactions in the two study arms were similar. Through 4 yr, graft failure was 27% in OKT3 and 19% in CYS (p = 0.15). One-year graft survival was 89.1% in OKT3 and 89.2% in CYS (p = .19). In multivariate analysis, OKT3 had a numerically inferior graft survival (RR = 1.4, CI 0.8-2.2, p = 0.22). In OKT3 graft survival was inferior for children aged 6 yr or younger. Our trial demonstrates that the incidence of acute rejection or graft failure in pediatric patients is not improved by OKT3 induction therapy relative to cyclosporine induction. C1 Univ Alabama, Birmingham, AL USA. New York Med Coll, Valhalla, NY 10595 USA. Harvard Univ, Childrens Hosp, Boston, MA 02115 USA. Childrens Hosp & Reg Med Ctr, Seattle, WA USA. EMMES Corp, Rockville, MD USA. NIH, Off Biotechnol Act, Recombinant DNA Program, Bethesda, MD 20892 USA. RP Harmon, WE (reprint author), NAPRTCS, Span Bldg,Suite 220,330 Brookline Ave, Boston, MA 02215 USA. EM william.harmon@childrens.harvard.edu FU NIAID NIH HHS [5U01AI37206] NR 19 TC 16 Z9 17 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PD JUN PY 2005 VL 9 IS 3 BP 282 EP 292 DI 10.1111/j.1399-3046.2005.00296.x PG 11 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 927GP UT WOS:000229180800004 PM 15910382 ER PT J AU Dhanireddy, KK Maniscalco, J Kirk, AD AF Dhanireddy, KK Maniscalco, J Kirk, AD TI Is tolerance induction the answer to adolescent non-adherence? SO PEDIATRIC TRANSPLANTATION LA English DT Article; Proceedings Paper CT Pediatric Symposium 2004 CY MAY 15, 2004 CL Boston, MD SP ATC DE transplantation tolerance; organ transplantation; adolescent; patient non-adherence; chimerism; costimulation blockade; lymphocyte depletion ID RENAL-TRANSPLANT RECIPIENTS; PEDIATRIC LIVER-TRANSPLANTATION; DOSE CYCLOSPORINE MONOTHERAPY; RECENT THYMIC EMIGRANTS; LARGE-ANIMAL-MODEL; ALLOGRAFT REJECTION; MIXED CHIMERISM; MONOCLONAL-ANTIBODY; LYMPHOCYTE SUBSETS; NONHUMAN-PRIMATES AB By definition, tolerance will eliminate the problem of adolescent medication non-adherence. Although adolescents' propensity toward non-adherence makes them at first glance to be particularly attractive candidates for tolerance trials, there are also immunologic, psychosocial and ethical barriers that temper enthusiasm for their inclusion at present. Limits in emotional and cognitive maturity are combined during the teenage years with adult-like immunologic maturity to lessen the potential for successful implementation of tolerance and near tolerance strategies. Alternatively, an interval step to tolerance in adolescents is to eliminate the medications most likely contributing to non-adherence through harsh side effects such as steroids and calcineurin inhibitors. This manuscript will review the general topic of transplantation tolerance with specific attention given to the application of pro-tolerant therapies in adolescent recipients. C1 NIDDK, Transplantat Branch, NIH, US Dept Hlth & Human Serv, Bethesda, MD USA. Georgetown Univ, Med Ctr, Dept Surg, Washington, DC 20007 USA. George Washington Univ, Sch Med, Childrens Natl Med Ctr, Dept Pediat, Washington, DC USA. RP Kirk, AD (reprint author), Room 11S-219,Bldg 10,Ctr Dr, Bethesda, MD 20892 USA. EM allank@intra.niddk.nih.gov RI Kirk, Allan/B-6905-2012 NR 61 TC 15 Z9 15 U1 0 U2 0 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 1397-3142 J9 PEDIATR TRANSPLANT JI Pediatr. Transplant. PD JUN PY 2005 VL 9 IS 3 BP 357 EP 363 DI 10.1111/j.1399-3046.2005.00285.x PG 7 WC Pediatrics; Transplantation SC Pediatrics; Transplantation GA 927GP UT WOS:000229180800016 PM 15910394 ER PT J AU Hintz, SR Kendrick, DE Vohr, BR Poole, WK Higgins, RD AF Hintz, SR Kendrick, DE Vohr, BR Poole, WK Higgins, RD CA Natl Inst Child Hlth Human Dev Neo TI Changes in neurodevelopmental outcomes at 18 to 22 months' corrected age among infants of less than 25 weeks' gestational age born in 1993-1999 SO PEDIATRICS LA English DT Article DE extremely low birth weight; extremely premature; surfactant; neurodevelopmental; cerebral palsy; Bayley Scales of Infant Development II ID LOW-BIRTH-WEIGHT; NEONATAL RESEARCH NETWORK; EXTREMELY PRETERM BIRTH; CHRONIC LUNG-DISEASE; GROSS MOTOR FUNCTION; DEVELOPMENTAL-DISABILITY; NATIONAL-INSTITUTE; CHILD-HEALTH; FUNCTIONAL OUTCOMES; 401-500 GRAMS AB Background. Increased survival rates for extremely preterm, extremely low birth weight infants during the postsurfactant era have been reported, but data on changes in neurosensory and developmental impairments are sparse. Objective. To compare neuromotor and neurodevelopmental outcomes at 18 to 22 months' corrected age for infants of <25 weeks' estimated gestational age (EGA) who were born in the 1990s. Methods. This was a multicenter, retrospective, comparative analysis of infants of <25 weeks' EGA, with birth weights of 501 to 1000 g, born between January 1993 and June 1996 (epoch I) or between July 1996 and December 1999 (epoch II), in the National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental assessments were performed at 18 to 22 months' corrected age. Logistic-regression models were constructed to evaluate the independent risk of cerebral palsy, Mental Development Index of <70, Psychomotor Development Index of <70, and neurodevelopmental impairment. Results. A total of 366 patients in epoch I and 473 patients in epoch II were evaluated. Prenatal steroid use, cesarean section, surfactant treatment, bronchopulmonary dysplasia, and severe retinopathy of prematurity were more likely in epoch II, whereas Apgar scores of <5 at 5 minutes, patent ductus arteriosus, and severe intraventricular hemorrhage were more likely in epoch I. The prevalences of cerebral palsy, Psychomotor Development Index of <70, and neurodevelopmental impairment were similar between epochs. The prevalences of Mental Development Index of <70 were 40% for epoch I and 47% for epoch II. Regression analysis revealed that epoch II was an independent risk factor for Mental Developmental Index of <70 (epoch I versus II: odds ratio: 0.63; 95% confidence interval: 0.45-0.87) but not for other outcomes. Conclusions. Early childhood neurodevelopmental outcomes among infants of <25 weeks' EGA are not improving in the postsurfactant era, despite more aggressive perinatal and neonatal treatment. Later childhood follow-up assessment is needed to delineate trends in severe cognitive impairment in this extremely high-risk group. C1 Stanford Univ, Sch Med, Dept Pediat, Div Neonatol & Dev Med, Palo Alto, CA 94304 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. Women & Infants Hosp Rhode Isl, Providence, RI USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Hintz, SR (reprint author), Stanford Univ, Sch Med, Dept Pediat, Div Neonatol & Dev Med, 750 Welch Rd,Suite 315, Palo Alto, CA 94304 USA. EM srhintz@stanford.edu FU NICHD NIH HHS [U10 HD27856, U01 HD36790, U10 HD21364, U10 HD21373, U10 HD21385, U10 HD21415, U10 HD27851, U10 HD27853, U10 HD27871, U10 HD27880, U10 HD27881, U10 HD27904, U10 HD34167, U10 HD34216] NR 31 TC 153 Z9 158 U1 0 U2 13 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 2005 VL 115 IS 6 BP 1645 EP 1651 DI 10.1542/peds.2004-2215 PG 7 WC Pediatrics SC Pediatrics GA 931SF UT WOS:000229504800025 PM 15930228 ER PT J AU Van Horn, L Obarzanek, E Friedman, LA Gernhofer, N Barton, B AF Van Horn, L Obarzanek, E Friedman, LA Gernhofer, N Barton, B TI Children's adaptations to a fat-reduced diet: The dietary intervention study in children (DISC) SO PEDIATRICS LA English DT Article DE diet and lipids; food-group analyses; dietary adherence in children ID DENSITY-LIPOPROTEIN CHOLESTEROL; NUTRITION EXAMINATION SURVEYS; NATIONAL-HEALTH; CARDIOVASCULAR-DISEASE; METABOLIC SYNDROME; YOUNG-ADULTS; RISK-FACTORS; US CHILDREN; OBESITY; ADOLESCENTS AB Background. Prevention of cardiovascular disease through diet and lifestyle change is strongly advocated in adults and is initiated preferably during childhood. The Dietary Intervention Study in Children (DISC) was a multicenter, collaborative, randomized trial in 663 preadolescent children (363 boys and 301 girls) with elevated low-density lipoprotein cholesterol, designed to test the efficacy and safety of a dietary intervention to lower saturated-fat and cholesterol intake while also advocating a healthy eating pattern. DISC results have been published extensively. This ancillary study reports new data regarding changes in eating patterns among this cohort. Objective. We set out to compare children's self-selected eating patterns and approaches to achieving adherence to the DISC fat-reduced diet intervention with children in the usual-care group. Methods. An ancillary study was conducted to develop a detailed food-grouping system and report new analyses on dietary adherence to the recommended eating pattern. Every food in the nutrient database was ranked by its saturated-fat and cholesterol content and classified within its relevant food group as a "go" (less atherogenic) or "whoa" (more atherogenic) food. Results. At baseline, go foods contributed similar to 57% of total energy intake and 12.4% to 13.1% total fat energy intake in both groups. At 3 years, go foods contributed 67.4% and 13.7% of total and fat energy intake, respectively, in the intervention group versus 56.8% and 12.8% in the usual-care group. Differences between the 2 treatment groups were significant for changes in consumption of dairy foods, desserts, and fats/oils, with the intervention group reporting a 0.2- to 0.3- serving-per-day greater increase in go foods than the usual-care group. The intervention group also reported a 0.2- to 0.8-serving-per-day greater decrease in whoa foods than the usual-care group for breads/grains, dairy, fats/oils, meat/fish/poultry, snacks, and vegetables. Overall, snack foods, desserts, and pizza contributed approximately one third of total daily energy intake in both groups at 3 years. Conclusions. Children in the intervention group reported consuming more servings per day of go grains, dairy, meats, and vegetable foods compared with children in the usual-care group, but intake of fruits and vegetables was low in both groups. Discovering that snacks, desserts, and pizza actively contribute so heavily to the diets of this age group, even among children who were part of this intervention, offers valuable insights regarding the need for more aggressive, innovative, and realistic approaches for additional dietary counseling. C1 Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, Chicago, IL 60611 USA. NHLBI, Div Epidemiol & Clin Applicat, Bethesda, MD 20892 USA. Maryland Med Res Inst, DISC Coordinating Ctr, Baltimore, MD USA. RP Van Horn, L (reprint author), Northwestern Univ, Feinberg Sch Med, Dept Prevent Med, 680 N Lake Shore Dr,1102, Chicago, IL 60611 USA. EM lvanhorn@northwetern.edu OI Barton, Bruce/0000-0001-7878-8895 FU NHLBI NIH HHS [5R03HL64990-2] NR 35 TC 43 Z9 44 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 2005 VL 115 IS 6 BP 1723 EP 1733 DI 10.1542/peds.2004-2392 PG 11 WC Pediatrics SC Pediatrics GA 931SF UT WOS:000229504800034 PM 15930237 ER PT J AU Norman, AC Drinkard, B McDuffie, JR Ghorbani, S Yanoff, LB Yanovski, JA AF Norman, AC Drinkard, B McDuffie, JR Ghorbani, S Yanoff, LB Yanovski, JA TI Influence of excess adiposity on exercise fitness and performance in overweight children and adolescents SO PEDIATRICS LA English DT Article DE obesity; anaerobic threshold; exercise test; body composition; oxygen uptake; physical fitness; running; walking ID AIR-DISPLACEMENT PLETHYSMOGRAPHY; BODY-FAT; PHYSICAL-ACTIVITY; AEROBIC FITNESS; UNITED-STATES; OBESE WOMEN; CHILDHOOD; CAPACITY; WEIGHT; YOUNG AB Objective. Relatively little is known about how excess body mass affects adolescents' capacity to perform sustained exercise. We hypothesized that most of the difficulty that severely overweight adolescents have with sustained exercise occurs because the metabolic costs of moving excess mass result in use of a high proportion of their total oxygen reserve. Methods. We compared results from a maximal cycle ergometry fitness test in 129 severely overweight adolescents who had BMIs of 41.5 +/- 9.7 kg/m(2) and ages of 14.5 +/- 1.8 years (range: 12.1-17.8 years) and 34 nonoverweight adolescents who had BMIs of 20.1 +/- 2.9 kg/m(2) and ages of 14.5 +/- 1.5 years (range: 12.0-18.1 years). Oxygen uptake (Vo(2)) was compared at 3 times: during a 4-minute period of unloaded cycling (ULVo(2)), at the lactate threshold estimated by gas exchange (LTVo(2)), and at maximal exertion (Vo(2) max). Heart rate was obtained at rest and at Vo(2) max. Participants also completed a 12-minute walk/run performance test to obtain distance traveled (D12) and heart rate. Results. Absolute LTVo(2) and Vo(2) max and LTVo(2) as a percentage of Vo(2) max were not different in overweight and nonoverweight adolescents during the cycle test. However, absolute ULVo(2) was significantly greater in overweight adolescents: ULVo(2) accounted for 35 +/- 8% of Vo(2) max (and 63 +/- 15% of LTVo(2)) in overweight adolescents but only 20 +/- 5% of Vo(2) max (and 39 +/- 12% of LTVo(2)) in nonoverweight adolescents. Resting heart rate before initiating the cycle test was significantly greater in overweight than nonoverweight adolescents (94 +/- 14 vs 82 +/- 15 beats per minute). However, maximal heart rate during the cycle test was significantly lower in overweight adolescents (186 +/- 13 vs 196 +/- 11 beats per minute). During the walk/run test, mean D12 was significantly shorter for overweight than for nonoverweight adolescents (1983 +/- 323 vs 1159 +/- 194 m). D12 was negatively related to BMI SDS (r = -0.81) and to ULVo(2) (r = -0.98). Discussion. Overweight and nonoverweight adolescents had similar absolute Vo(2) at the lactate threshold and at maximal exertion, suggesting that overweight adolescents are more limited by the increased cardiorespiratory effort required to move their larger body mass through space than by cardiorespiratory deconditioning. The higher percentage of oxygen consumed during submaximal exercise indicates that overweight adolescents are burdened by the metabolic cost of their excess mass. Their greater oxygen demand during an unloaded task predicted poorer performance during sustained exercise. Exercise prescriptions for overweight adolescents should account for the limited exercise tolerance imposed by excess body mass, focusing on activities that keep demands below lactate threshold so that exercise can be sustained. C1 NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH,Dept Hlth & Human Serv,Hatfield CRC, Bethesda, MD 20892 USA. Duke Univ, Sch Med, Durham, NC USA. NIH, Dept Rehabil Med, Ctr Clin, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. RP Yanovski, JA (reprint author), NICHHD, Unit Growth & Obes, Dev Endocrinol Branch, NIH,Dept Hlth & Human Serv,Hatfield CRC, Room 1-3330,10 Ctr Dr,MSC 1103, Bethesda, MD 20892 USA. EM jy15i@nih.gov FU Intramural NIH HHS [Z01 HD000641-12, Z99 HD999999]; NICHD NIH HHS [Z01 HD000641, ZO1-HD-00641] NR 41 TC 57 Z9 59 U1 0 U2 6 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 2005 VL 115 IS 6 BP E690 EP E696 DI 10.1542/peds.2004-1543 PG 7 WC Pediatrics SC Pediatrics GA 931SF UT WOS:000229504800067 PM 15930197 ER PT J AU Duda, T Venkataraman, V Ravichandran, S Sharma, RK AF Duda, T Venkataraman, V Ravichandran, S Sharma, RK TI ATP-regulated module (ARM) of the atrial natriuretic factor receptor guanylate cyclase SO PEPTIDES LA English DT Review DE ATP-regulated module; atrial natriuretic factor; guanylate cyclase ID PROTEIN-KINASE-C; HEAT-STABLE ENTEROTOXIN; SIGNAL-TRANSDUCTION ACTIVITIES; SMOOTH-MUSCLE CELLS; ROD OUTER SEGMENTS; PEPTIDE RECEPTOR; LIGAND-BINDING; DIFFERENTIAL ACTIVATION; FUNCTIONAL EXPRESSION; ENDOGENOUS ACTIVATOR AB ATP is an obligatory agent for the atrial natriuretic factor (ANF) and the type C natriuretic peptide (CNP) signaling of their respective receptor guanylate cyclases, ANF-RGC and CNP-RGC. Through a common mechanism, it binds to a defined ARM domain of the cyclase, activates the cyclase and transduces the signal into generation of the second messenger cyclic GMP. In this presentation, the authors review the ATP-regulated transduction mechanism and refine the previously simulated three-dimensional ARM model (Duda T, Yadav P, Jankowska A, Venkataraman V, Sharma RK. Three dimensional atomic model and experimental validation for the ATP-regulated module (ARM) of the atrial natriuretic factor receptor guanylate cyclase. Mol Cell Biochem 2000;214:7-14; reviewed in: Sharma RK, Yadav P, Duda T. Allosteric regulatory step and configuration of the ATP-binding pocket in atrial natriuretic factor receptor guanylate cyclase transduction mechanism. Can J Physiol Pharmacol 200 1;79: 682-9 1; Sharma RK. Evolution of the membrane guanylate cyclase transduction system. Mot Cell Biochem 2002;230:3-30). The model depicts the ATP-binding dependent configurational changes in the ARM and supports the concept that in the first step, ATP partially activates the cyclase and primes it for the subsequent transduction steps, resulting in full activation of the cyclase. (c) 2005 Elsevier Inc. All rights reserved. C1 Univ Med & Dent New Jersey, Sch Osteopath Med, Unit Regulatory & Mol Biol, Dept Cell Biol, Stratford, NJ 08084 USA. Univ Med & Dent New Jersey, Sch Osteopath Med, Unit Regulatory & Mol Biol, Dept Ophthalmol, Stratford, NJ 08084 USA. NCI, Adv Biomed Comp Ctr, Frederick SAIC, Frederick, MD 21702 USA. RP Univ Med & Dent New Jersey, Sch Osteopath Med, Unit Regulatory & Mol Biol, Dept Cell Biol, Stratford, NJ 08084 USA. EM dudatm@umdnj.edu; sharmark@umdnj.edu FU NEI NIH HHS [EY 10828]; NHLBI NIH HHS [HL070015]; NIA NIH HHS [AG00925]; NIDCD NIH HHS [DC005349] NR 125 TC 21 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0196-9781 EI 1873-5169 J9 PEPTIDES JI Peptides PD JUN PY 2005 VL 26 IS 6 BP 969 EP 984 DI 10.1016/j.peptides.2004.08.032 PG 16 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 933IN UT WOS:000229622200006 PM 15911066 ER PT J AU Richell, RA Mitchell, DGV Peschardt, KS Winston, JS Leonard, A Dolan, RJ Blair, RJR AF Richell, RA Mitchell, DGV Peschardt, KS Winston, JS Leonard, A Dolan, RJ Blair, RJR TI Trust and distrust: the perception of trustworthiness of faces in psychopathic and non-psychopathic offenders SO PERSONALITY AND INDIVIDUAL DIFFERENCES LA English DT Article DE social cognition; trustworthiness; psychopathy; amygdala ID ANTISOCIAL PERSONALITY; IMPAIRED RECOGNITION; FEARFUL EXPRESSIONS; SOCIAL INFORMATION; ASPERGER-SYNDROME; HUMAN AMYGDALA; DISTRESS CUES; NORMAL ADULTS; AUTISM; CHILDREN AB Psychopathy is a disorder linked to impairments in social cognition. Individuals with psychopathy and comparison individuals, as defined by the Hare Psychopathy Checklist Revised (Hare, 1991), completed a task requiring complex social judgments. Participants viewed a series of male faces, and made judgments concerning how trustworthy they considered the person pictured to be and the degree to which each face was displaying specific emotions. Judgments of trustworthiness did not differ between the individuals with psychopathy and the comparison individuals. Trustworthiness judgments of the faces negatively correlated with, in particular, ratings of anger in the faces for both groups of participants. The data are discussed with reference to the neural systems, including the amygdala, considered to be involved in the mediation of task performance and also neuro-cognitive models of psychopathy. Published by Elsevier Ltd. C1 NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. UCL, Inst Cognit Neurosci, London, England. UCL, Dept Psychol, London, England. Wellcome Dept Imaging Neurosci, London WC1N 3BG, England. HMP Wormwood Scrubs, London W12 0AE, England. RP Blair, RJR (reprint author), NIMH, Mood & Anxiety Disorders Program, NIH, Dept Hlth & Human Serv, 15K N Dr,Room 206,MSC 2670, Bethesda, MD 20892 USA. EM blairj@intra.nimh.nih.gov RI Winston, Joel/F-6180-2010; OI Winston, Joel/0000-0002-3957-0612; Dolan, Ray/0000-0001-9356-761X NR 50 TC 14 Z9 14 U1 4 U2 15 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0191-8869 J9 PERS INDIV DIFFER JI Pers. Individ. Differ. PD JUN PY 2005 VL 38 IS 8 BP 1735 EP 1744 DI 10.1016/j.paid.2004.11.017 PG 10 WC Psychology, Social SC Psychology GA 923WN UT WOS:000228940300001 ER PT J AU Srimaroeng, C Jutabha, P Pritchard, JB Endou, H Chatsudthipong, V AF Srimaroeng, C Jutabha, P Pritchard, JB Endou, H Chatsudthipong, V TI Interactions of stevioside and steviol with renal organic anion transporters in S2 cells and mouse renal cortical slices SO PHARMACEUTICAL RESEARCH LA English DT Article DE organic anion; organic anion transporter; renal cortical slices; steviol; stevioside ID PARA-AMINOHIPPURATE TRANSPORT; NATURAL SWEETENER; HUMAN KIDNEY; GLYCOSIDIC SWEETENERS; MOLECULAR-CLONING; PROXIMAL TUBULE; APICAL MEMBRANE; BLOOD-PRESSURE; IN-VITRO; RAT AB Purpose. Our previous studies have shown that both stevioside and steviol inhibited transepithelial transport of para-aminohippurate (PAH) in isolated rabbit renal proximal tubules by interfering with organic anion transport system. The current study examined the direct interactions of stevioside and steviol with specific organic anion transporters. Methods. S2 cells expressing human organic anion transporters (hOAT1, hOAT2, hOAT3, and hOAT4) and an intact renal epithelium were used to determine the inhibitory effect of stevioside and steviol on organic anion transport. Results. Stevioside at 0.5-1 mM showed no interaction with any OAT. In contrast, steviol markedly inhibited substrate uptake in all S2hOAT cells. Steviol had low IC50 values for hOAT1 (11.4 mu M) and hOAT3 (36.5 mu M) similar to that of probenecid, whereas IC50 values for hOAT2 ( 1000 mu M) and hOAT4 ( 285 mu M) were much higher. Results obtained in mouse renal cortical slices were very similar; that is, stevioside was without inhibitory effect and steviol was a potent inhibitor of PAH and estrone sulfate (ES) transport. Conclusions. Stevioside has no interaction with human or mouse OATs. In contrast, steviol interacts directly with human OATs, in particular, hOAT1 and hOAT3, with a potency approximating probenecid, suggesting that the inhibition of OAT-mediated transport by steviol could alter renal drug clearance. C1 Mahidol Univ, Fac Sci, Dept Physiol, Bangkok 10400, Thailand. NIEHS, Lab Pharmacol & Chem, NIH, Res Triangle Pk, NC 27709 USA. Kyorin Univ, Sch Med, Dept Pharmacol & Toxicol, Tokyo, Japan. RP Chatsudthipong, V (reprint author), Mahidol Univ, Fac Sci, Dept Physiol, Bangkok 10400, Thailand. EM scvcs@mahidol.ac.th OI Srimaroeng, Chutima/0000-0002-5537-1023 NR 42 TC 12 Z9 13 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD JUN PY 2005 VL 22 IS 6 BP 858 EP 866 DI 10.1007/s11095-005-4580-5 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 934TH UT WOS:000229730800004 PM 15948029 ER PT J AU Lee, SJ Goldstein, JA AF Lee, SJ Goldstein, JA TI Functionally defective or altered CYP3A4 and CYP3A5 single nucleotide polymorphisms and their detection with genotyping tests SO PHARMACOGENOMICS LA English DT Review DE CYP3A4; CYP3A5; genotyping; metabolism; pharmacogenetics; pharmacogenomics; polymorphisms; single nucleotide polymorphisms ID PREGNANE-X-RECEPTOR; CYTOCHROME-P-450 NIFEDIPINE OXIDASE; RENAL-TRANSPLANT PATIENTS; HUMAN LIVER-MICROSOMES; ADULT HUMAN-LIVER; GENETIC VARIANT; CLINICAL PRESENTATION; DRUG-METABOLISM; PROSTATE-CANCER; AFRICAN-AMERICAN AB Among the four cytochrome P450 (CYP)3A genes, CYP3A4 and CYP3A5 are the most abundantly expressed in the human liver. Eighty single nucleotide polymorphisms (SNPs) of CYP3A4/5 have been reported to the Human P450 Allele Nomenclature Committee. CYP3A4 alleles with minimal function compared with wild type include the CYP3A4*6 and CYP3A4*17. Alleles with moderately decreased or altered activity include: CYP3A4*2, *8 *11, *1Z *13, *16, and *18. CYP3A5 alleles with minimal function include the splice variants CYP3A5*3, *5, *6 and CYP3A5* 10, as well as the null allele CYP3A5*7. Alleles with moderately decreased catalytic activity include CYP3A5*8 and CYP3A5*9. This report reviews the current progress in the functional characterization of CYP3A4 and CYP3A5 SNPs and provides genotyping tests for possible defective variants. A combination of genotyping tests for defective CYP3A4/CYP3A5 haplotypes will be necessary to understand the variations in the metabolism and clinical toxicity of a wide variety of clinical drugs, since these two CYP proteins have overlapping substrate specificities. C1 Natl Inst Environm Hlth Sci Ctr, NIH, Human Metab Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. RP Lee, SJ (reprint author), Natl Inst Environm Hlth Sci Ctr, NIH, Human Metab Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. EM lee13@niehs.nih.gov NR 113 TC 48 Z9 51 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JUN PY 2005 VL 6 IS 4 BP 357 EP 371 DI 10.1517/14622416.6.4.357 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 944FI UT WOS:000230411500004 PM 16004554 ER PT J AU Mocellin, S Marincola, FM AF Mocellin, S Marincola, FM TI The challenge of implementing high-throughput technologies in clinical trials SO PHARMACOGENOMICS LA English DT Editorial Material DE clinical trials; functional genomics; high-throughput technology; microarray; pharmacogenomics; proteomics ID CANCER; PROTEOMICS C1 Univ Padua, Dept Oncol & Surg Sci, I-35128 Padua, Italy. NIH, Ctr Clin, Immunogenet Sect, Dept Transfus Med, Bethesda, MD 20892 USA. RP Mocellin, S (reprint author), Univ Padua, Dept Oncol & Surg Sci, Via Giustiniani 2, I-35128 Padua, Italy. EM mocellins@hotmail.com; FMarincola@cc.nih.gov NR 19 TC 2 Z9 2 U1 1 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JUN PY 2005 VL 6 IS 4 BP 435 EP 438 DI 10.1517/14622416.6.4.435 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 944FI UT WOS:000230411500012 PM 16004562 ER PT J AU Foord, SM Bonner, TI Neubig, RR Rosser, EM Pin, JP Davenport, AP Spedding, M Harmar, AJ AF Foord, SM Bonner, TI Neubig, RR Rosser, EM Pin, JP Davenport, AP Spedding, M Harmar, AJ TI International Union of Pharmacology. XLVI. G protein-coupled receptor list SO PHARMACOLOGICAL REVIEWS LA English DT Review ID HUMAN GENOME; PSEUDOGENES; EVOLUTION; FAMILIES; GENE AB NC-IUPHAR (International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification) and its subcommittees provide authoritative reports on the nomenclature and pharmacology of G protein-coupled receptors (GPCRs) that summarize their structure, pharmacology, and roles in physiology and pathology. These reports are published in Pharmacological Reviews (http://www.iuphar.org/nciuphar_arti.html) and through the International Union of Pharmacology (IUPHAR) Receptor Database web site (http://www.iuphar-db.org/iuphar-rd). The essentially complete sequencing of the human genome has allowed the cataloging of all of the human gene sequences potentially encoding GPCRs. The IUPHAR Receptor List (http://www.iuphar-db.org/iuphar-rd/list/index.htm) presents this catalog giving IUPHAR-approved nomenclature (where available), known ligands, and gene names for all of these potential receptors (excluding sensory receptors and pseudogenes) together with links to curated sequence, descriptive information, and additional links in the Entrez Gene database (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene). This list is a major new initiative of NC-IUPHAR that, through continuing curation, defines the target of our ongoing receptor classification and invites further input from the scientific community. C1 GlaxoSmithKline Res & Dev, Stevenage, Herts, England. NIMH, Genet Lab, Bethesda, MD 20892 USA. Univ Michigan, Dept Pharmacol, Ann Arbor, MI 48109 USA. Univ Edinburgh, Div Neurosci, Edinburgh, Midlothian, Scotland. Univ Edinburgh, Ctr Res Neurosci, Edinburgh, Midlothian, Scotland. CNRS, Montpellier, France. Univ Cambridge, Clin Pharmacol Unit, Cambridge, England. Inst Rech Servier, F-92150 Suresnes, France. RP Foord, SM (reprint author), GlaxoSmithKline Res & Dev, Stevenage, Herts, England. EM smf3746@ggr.co.uk RI Davenport, Anthony/A-5773-2008; OI Davenport, Anthony/0000-0002-2096-3117; Spedding, Michael/0000-0002-1248-8221; Harmar, Anthony/0000-0002-3838-9264 NR 19 TC 294 Z9 303 U1 4 U2 20 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0031-6997 J9 PHARMACOL REV JI Pharmacol. Rev. PD JUN PY 2005 VL 57 IS 2 BP 279 EP 288 DI 10.1124/pr.57.2.5 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 928XR UT WOS:000229305700007 PM 15914470 ER PT J AU Gardner, EL AF Gardner, EL TI Endocannabinoid signaling system and brain reward: Emphasis on dopamine SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article; Proceedings Paper CT Symposium on Cannabinoids: Interactions with other Drugs CY JAN, 2004 CL Morzine, FRANCE DE addiction; cannabinoids; dopamine; endocannabinoids; medial forebrain bundle; nucleus accumbens; reinforcement; reward; self-administration; self-stimulation; ventral tegmental area ID CONDITIONED PLACE PREFERENCE; SELF-ADMINISTRATION BEHAVIOR; VENTRAL TEGMENTAL AREA; RAT NUCLEUS-ACCUMBENS; LONG-TERM DEPRESSION; CANNABINOID CB1 RECEPTORS; COCAINE-SEEKING BEHAVIOR; FREELY-MOVING RATS; SYNAPTIC-TRANSMISSION; DRUG-ADDICTION AB The brain's reward circuitry consists of an "in series" circuit of dopaminergic (DA) neurons in the ventral tegmental area (VTA), nucleus accumbens (Acb), and that portion of the medial forebrain bundle (MFB) which links the VTA and Acb. Drugs which enhance brain reward (and have derivative addictive potential) have common actions on this core DA reward system and on animal behaviors relating to its function. Such drugs enhance electrical brain-stimulation reward in this reward system; enhance neural firing and DA tone within it; produce conditioned place preference (CPP), a behavioral model of incentive motivation; are self-administered; and trigger reinstatement of drug-seeking behavior in animals extinguished from drug self-administration. Cannabinoids were long considered different from other reward-enhancing drugs in reward efficacy and in underlying neurobiological substrates activated. However, it is now clear that cannabinoids activate these brain reward processes and reward-related behaviors in similar fashion to other reward-enhancing drugs. This brief review discusses the roles that endogenous cannabinoids (especially activation of the CB1 receptor) may play within the core reward system, and concludes that while cannabinoids activate the reward pathways in a manner consistent with other reward-enhancing drugs, the neural mechanisms by which this occurs may differ. Published by Elsevier Inc. C1 NIDA, Neuropsychopharmacol Sect, Intramural Res Program, NIH, Baltimore, MD 21224 USA. RP Gardner, EL (reprint author), NIDA, Neuropsychopharmacol Sect, Intramural Res Program, NIH, Bldg C-Room 393,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM egardner@intra.nida.nih.gov FU Intramural NIH HHS NR 277 TC 206 Z9 212 U1 3 U2 20 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUN PY 2005 VL 81 IS 2 BP 263 EP 284 DI 10.1016/j.pbb.2005.01.032 PG 22 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 942KM UT WOS:000230281300005 PM 15936806 ER PT J AU Justinova, Z Goldberg, SR Heishman, SJ Tanda, G AF Justinova, Z Goldberg, SR Heishman, SJ Tanda, G TI Self-administration of cannabinoids by experimental animals and human marijuana smokers SO PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR LA English DT Article; Proceedings Paper CT Symposium on Cannabinoids: Interactions with other Drugs CY JAN, 2004 CL Morzine, FRANCE DE cannabis; cannabinoids; delta-9-tetrahydrocannabinol; humans; marijuana; squirrel monkeys; primates; reinforcement; reward; rodents; self-administration; THC ID CONDITIONED PLACE PREFERENCE; DISCRIMINATIVE STIMULUS PROPERTIES; MESOLIMBIC DOPAMINE TRANSMISSION; RECEPTOR AGONIST CP-55,940; RHESUS-MONKEYS; ABUSE LIABILITY; FIXED-RATIO; FOOD-DEPRIVATION; SQUIRREL-MONKEYS; ORAL DELTA(9)-TETRAHYDROCANNABINOL AB Drug self-administration behavior has been one of the most direct and productive approaches for studying the reinforcing effects of psychoactive drugs, which are critical in determining their abuse potential. Cannabinoids, which are usually abused by humans in the form of marijuana, have become the most frequently abused illicit class of drugs in the United States. The early elucidation of the structure and stereochemistry of delta-9-tetrahydrocannabinol (THC) in 1964, which is now recognized as the principal psychoactive ingredient in marijuana, activated cannabinoid research worldwide. This review examines advances in research on cannabinoid self-administration behavior by humans and laboratory animals. There have been numerous laboratory demonstrations of the reinforcing effects of cannabinoids in human subjects, but reliable self-administration of cannabinoids by laboratory animals has only recently been demonstrated. It has now been shown that strong and persistent self-administration behavior can be maintained in experimentally and drug-naive squirrel monkeys by doses of THC comparable to those in marijuana smoke inhaled by humans. Furthermore, reinforcing effects of some synthetic CB1 cannabinoid agonists have been recently reported using intravenous and intracerebroventricular self-administration procedures in rats and mice. These findings support previous conclusions that THC has a pronounced abuse liability comparable to other drugs of abuse under certain experimental conditions. Self-administration of THC by squirrel monkeys provides the most reliable animal model for human marijuana abuse available to date. This animal model now makes it possible to study the relative abuse liability of other natural and synthetic cannabinoids and to preclinically assess new therapeutic strategies for the treatment or prevention of marijuana abuse in humans. Published by Elsevier Inc. C1 NIDA, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. NIDA, Preclin Pharmacol Sect, Behav Neurosci Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. NIDA, Clin Pharmacol & Therapeut Branch, Intramural Res Program, NIH,Dept Hlth & Human Serv, Baltimore, MD 21224 USA. RP Tanda, G (reprint author), NIDA, Psychobiol Sect, Medicat Discovery Res Branch, Intramural Res Program,NIH,Dept Hlth & Human Serv, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM gtanda@intra.nida.nih.gov RI Tanda, Gianluigi/B-3318-2009; Justinova, Zuzana/A-9109-2011 OI Tanda, Gianluigi/0000-0001-9526-9878; Justinova, Zuzana/0000-0001-5793-7484 FU Intramural NIH HHS [Z99 DA999999, Z01 DA000001-23] NR 164 TC 49 Z9 53 U1 8 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0091-3057 J9 PHARMACOL BIOCHEM BE JI Pharmacol. Biochem. Behav. PD JUN PY 2005 VL 81 IS 2 BP 285 EP 299 DI 10.1016/j.pbb.2005.01.026 PG 15 WC Behavioral Sciences; Neurosciences; Pharmacology & Pharmacy SC Behavioral Sciences; Neurosciences & Neurology; Pharmacology & Pharmacy GA 942KM UT WOS:000230281300006 PM 15932767 ER PT J AU Keskin, O Ma, BY Rogale, K Gunasekaran, K Nussinov, R AF Keskin, O Ma, BY Rogale, K Gunasekaran, K Nussinov, R TI Protein-protein interactions: organization, cooperativity and mapping in a bottom-up Systems Biology approach SO PHYSICAL BIOLOGY LA English DT Review ID STRUCTURALLY CONSERVED RESIDUES; ENERGY HOT-SPOTS; INTERACTION SITES; INTERACTION NETWORK; RECOGNITION SITES; SACCHAROMYCES-CEREVISIAE; BINDING INTERFACES; NEURAL-NETWORKS; YEAST PROTEOME; COMPLEXES AB Understanding and ultimately predicting protein associations is immensely important for functional genomics and drug design. Here, we propose that binding sites have preferred organizations. First, the hot spots cluster within densely packed 'hot regions'. Within these regions, they form networks of interactions. Thus, hot spots located within a hot region contribute cooperatively to the stability of the complex. However, the contributions of separate, independent hot regions are additive. Moreover, hot spots are often already pre-organized in the unbound (free) protein states. Describing a binding site through independent local hot regions has implications for binding site definition, design and parametrization for prediction. The compactness and cooperativity emphasize the similarity between binding and folding. This proposition is grounded in computation and experiment. It explains why summation of the interactions may over-estimate the stability of the complex. Furthermore, statistically, charge-charge coupling of the hot spots is disfavored. However, since within the highly packed regions the solvent is screened, the electrostatic contributions are strengthened. Thus, we propose a new description of protein binding sites: a site consists of (one or a few) self-contained cooperative regions. Since the residue hot spots are those conserved by evolution, proteins binding multiple partners at the same sites are expected to use all or some combination of these regions. C1 Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Istanbul, Turkey. Koc Univ, Coll Engn, TR-34450 Istanbul, Turkey. NCI, Lab Expt & Comp Biol, Basic Res Program, SAIC, Frederick, MD 21702 USA. Princeton Univ, Program Appl & Comp Math, Princeton, NJ 08540 USA. Tel Aviv Univ, Sackler Sch Med, Sackler Inst Mol Med, Dept Human Genet & Mol Med, IL-69978 Tel Aviv, Israel. RP Keskin, O (reprint author), Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Istanbul, Turkey. 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 101 TC 75 Z9 76 U1 1 U2 10 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1478-3975 J9 PHYS BIOL JI Phys. Biol. PD JUN PY 2005 VL 2 IS 2 BP S24 EP S35 DI 10.1088/1478-3975/2/2/S03 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 007TJ UT WOS:000234992400004 PM 16204846 ER PT J AU Ma, BY Pan, YP Gunasekaran, K Keskin, O Venkataraghavan, RB Levine, AJ Nussinov, R AF Ma, BY Pan, YP Gunasekaran, K Keskin, O Venkataraghavan, RB Levine, AJ Nussinov, R TI The contribution of the Trp/Met/Phe residues to physical interactions of p53 with cellular proteins SO PHYSICAL BIOLOGY LA English DT Article ID TUMOR-SUPPRESSOR PROTEIN; TRANSCRIPTIONAL ACTIVATION; DNA-DAMAGE; HOMOLOGOUS RECOMBINATION; TRANSACTIVATION DOMAIN; CRYSTAL-STRUCTURE; TERMINAL DOMAIN; POSTTRANSLATIONAL MODIFICATION; SV40-TRANSFORMED CELLS; FUNCTIONAL INTERACTION AB Dynamic molecular interaction networks underlie biological phenomena. Among the many genes which are involved, p53 plays a central role in networks controlling cellular life and death. It not only operates as a tumor suppressor, but also helps regulate hundreds of genes in response to various types of stress. To accomplish these functions as a guardian of the genome, p53 interacts extensively with both nucleic acids and proteins. This paper examines the physical interfaces of the p53 protein with cellular proteins. Previously, in the analysis of the structures of protein-protein complexes, we have observed that amino acids Trp, Met and Phe are important for protein-protein interactions in general. Here we show that these residues are critical for the many functions of p53. Several clusters of the Trp/Met/Phe residues are involved in the p53 protein-protein interactions. Phe19/Trp23 in the TA1 region extensively binds to the transcriptional factors and the MDM2 protein. Trp53/Phe54 in the TA2 region is crucial for transactivation and DNA replication. Met243 in the core domain interacts with 53BP1, 53BP2 and Rad 51 proteins. Met384/Phe385 in the C-terminal region interacts with the S100B protein and the Bromodomain of the CBP protein. Thus, these residues may assist in elucidating the p53 interactions when structural data are not available. C1 Koc Univ, Ctr Computat Biol & Bioinformat, TR-34450 Istanbul, Turkey. Koc Univ, Coll Engn, TR-34450 Istanbul, Turkey. Inst Adv Study, Princeton, NJ 08540 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Ma, BY (reprint author), NCI, Lab Expt & Comp Biol, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. EM mab@ncifcrf.gov; ruthn@ncifcrf.gov RI Ma, Buyong/F-9491-2011 OI Ma, Buyong/0000-0002-7383-719X FU NCI NIH HHS [N01-CO-12400] NR 93 TC 8 Z9 9 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1478-3967 J9 PHYS BIOL JI Phys. Biol. PD JUN PY 2005 VL 2 IS 2 BP S56 EP S66 DI 10.1088/1478-3975/2/2/S06 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 007TJ UT WOS:000234992400007 PM 16204849 ER PT J AU Nussinov, R Tsai, CJ AF Nussinov, R Tsai, CJ TI Preface - Protein-protein interactions: principles and prediction SO PHYSICAL BIOLOGY LA English DT Editorial Material C1 NCI, Lab Expt & Computat Biol, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. Tel Aviv Univ, Sackler Sch Med, Dept Human Genet & Mol Med, Sackler Inst Mol Med, IL-69978 Tel Aviv, Israel. RP Nussinov, R (reprint author), NCI, Lab Expt & Computat Biol, Basic Res Program, SAIC Frederick Inc, Frederick, MD 21702 USA. NR 0 TC 0 Z9 0 U1 1 U2 2 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1478-3967 J9 PHYS BIOL JI Phys. Biol. PD JUN PY 2005 VL 2 IS 2 PG 1 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 007TJ UT WOS:000234992400001 ER PT J AU Geho, DH Bandle, RW Clair, T Liotta, LA AF Geho, DH Bandle, RW Clair, T Liotta, LA TI Physiological mechanisms of tumor-cell invasion and migration SO PHYSIOLOGY LA English DT Review ID PHASE PROTEIN MICROARRAYS; EXTRACELLULAR-MATRIX; MELANOMA-CELLS; GROWTH-FACTOR; LYSOPHOSPHATIDIC ACID; HAPTOTACTIC MIGRATION; CANCER METASTASIS; FOCAL ADHESIONS; MOTILITY FACTOR; RHO-KINASE AB Recent advances in understanding the complex biology of the microenvironment that underlies tumor invasion and migration have revealed novel and promising therapeutic targets. Pharmacological blockade of intra- and extracellular signaling events that regulate migration and survival of multiple cell types may disrupt the host-tumor conspiracy that allows escape from normal developmental regulation. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Geho, DH (reprint author), NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. EM gehod@mail.nih.gov NR 66 TC 91 Z9 94 U1 2 U2 7 PU AMER PHYSIOLOGICAL SOC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 1548-9213 J9 PHYSIOLOGY JI Physiology PD JUN PY 2005 VL 20 BP 194 EP 200 DI 10.1152/physiol.00009.2005 PG 7 WC Physiology SC Physiology GA 929MT UT WOS:000229350900006 PM 15888576 ER PT J AU Dunn, KJ Brady, M Ochsenbauer-Jambor, C Snyder, S Incao, A Pavan, WJ AF Dunn, KJ Brady, M Ochsenbauer-Jambor, C Snyder, S Incao, A Pavan, WJ TI WNT1 and WNT3a promote expansion of melanocytes through distinct modes of action SO PIGMENT CELL RESEARCH LA English DT Article DE neural crest; melanocyte; development; WNT; differentiation; stem cell; SOX10; MITF; beta-catenin ID CREST-DERIVED MELANOCYTE; ENDOTHELIN RECEPTOR-B; DIRECTED GENE-TRANSFER; NEURAL CREST; TRANSCRIPTION FACTOR; WAARDENBURG-SYNDROME; GROWTH-FACTOR; BETA-CATENIN; KIT-LIGAND; DOPACHROME-TAUTOMERASE AB WNT1 and WNT3a have been described as having redundant roles in promoting the development of neural crest-derived melanocytes (NC-Ms). We used cell lineage restricted retroviral infections to examine the effects of WNT signaling on defined cell types in neural crest cultures. RCAS retroviral infections were targeted to melanoblasts (NC-M precursor cells) derived from transgenic mice that express the virus receptor, TVA, under the control of a melanoblast promoter (DCT). As expected, over 90% of DCT-TVA+ cells expressed early melanoblast markers MITF and KIT. However, by following the fate of infected cells in standard culture conditions, we find that only 5% of descendents were NC-Ms. The majority of the descendents were not NC-Ms, but expressed smooth muscle cell markers, demonstrating that mammalian melanoblasts are not committed to the NC-M lineage. RCAS infection of DCT-TVA+ cells demonstrated that overexpression of canonical WNT signaling genes (β CAT, WNT3a or WNT1) can increase NC-M numbers in an endothelin dependent manner. However, WNT1 and WNT3a have different modes of action with respect to melanoblast fate. Intrinsic over-expression of β CAT or WNT3a can increase NC-M numbers by biasing the fate of DCT-TVA+ cells to NC-Ms. In contrast, the DCT-TVA+ melanoblasts cannot respond to WNT1 signaling and do not alter their fate towards NC-M. Instead, WNT1 only increases NC-M numbers through paracrine signaling on melanoblast precursors to increase the numbers of neural crest cells that become NC-Ms. C1 NHGRI, Mouse Embryol Sect, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. RP Pavan, WJ (reprint author), NHGRI, Mouse Embryol Sect, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. EM bpavan@nhgri.nih.gov NR 83 TC 47 Z9 53 U1 0 U2 4 PU BLACKWELL MUNKSGAARD PI FREDERIKSBERG C PA 1 ROSENORNS ALLE, DK-1970 FREDERIKSBERG C, DENMARK SN 0893-5785 J9 PIGM CELL RES JI Pigm. Cell. Res. PD JUN PY 2005 VL 18 IS 3 BP 167 EP 180 DI 10.1111/j.1600-0749.2005.00226.x PG 14 WC Cell Biology; Dermatology SC Cell Biology; Dermatology GA 925RC UT WOS:000229069600004 PM 15892713 ER PT J AU Chao, Y Shiozaki, EN Srinivasula, SM Rigotti, DJ Fairman, R Shi, YG AF Chao, Y Shiozaki, EN Srinivasula, SM Rigotti, DJ Fairman, R Shi, YG TI Engineering a dimeric caspase-9: A re-evaluation of the induced proximity model for caspase activation SO PLOS BIOLOGY LA English DT Article ID CELL-DEATH; APOPTOSIS; OLIGOMERIZATION; PROCASPASE-9; MECHANISMS; INHIBITION; INSIGHTS AB Caspases are responsible for the execution of programmed cell death ( apoptosis) and must undergo proteolytic activation, in response to apoptotic stimuli, to function. The mechanism of initiator caspase activation has been generalized by the induced proximity model, which is thought to drive dimerization-mediated activation of caspases. The initiator caspase, caspase-9, exists predominantly as a monomer in solution. To examine the induced proximity model, we engineered a constitutively dimeric caspase-9 by relieving steric hindrance at the dimer interface. Crystal structure of the engineered caspase-9 closely resembles that of the wild-type ( WT) caspase-9, including all relevant structural details and the asymmetric nature of two monomers. Compared to the WT caspase-9, this engineered dimer exhibits a higher level of catalytic activity in vitro and induces more efficient cell death when expressed. However, the catalytic activity of the dimeric caspase-9 is only a small fraction of that for the Apaf-1-activated caspase-9. Furthermore, in contrast to the WT caspase-9, the activity of the dimeric caspase-9 can no longer be significantly enhanced in an Apaf-1-dependent manner. These findings suggest that dimerization of caspase-9 may be qualitatively different from its activation by Apaf-1, and in conjunction with other evidence, posit an induced conformation model for the activation of initiator caspases. C1 Princeton Univ, Lewis Thomas Lab, Dept Mol Biol, Princeton, NJ 08544 USA. NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. Haverford Coll, Dept Biol, Haverford, PA 19041 USA. RP Shi, YG (reprint author), Princeton Univ, Lewis Thomas Lab, Dept Mol Biol, Princeton, NJ 08544 USA. EM yshi@molbio.princeton.edu FU NCI NIH HHS [R01 CA090269, CA90269] NR 33 TC 69 Z9 70 U1 0 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD JUN PY 2005 VL 3 IS 6 BP 1079 EP 1087 AR e183 DI 10.1371/journal.pbio.0030183 PG 9 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 938IK UT WOS:000229992900017 PM 15941357 ER PT J AU Thiel, M Chouker, A Ohta, A Jackson, E Caldwell, C Smith, P Lukashev, D Bittmann, I Sitkovsky, MV AF Thiel, M Chouker, A Ohta, A Jackson, E Caldwell, C Smith, P Lukashev, D Bittmann, I Sitkovsky, MV TI Oxygenation inhibits the physiological tissue-protecting mechanism and thereby exacerbates acute inflammatory lung injury SO PLOS BIOLOGY LA English DT Article ID RESPIRATORY-DISTRESS-SYNDROME; ADENOSINE A(2A) RECEPTORS; DEFICIENT MICE REVEALS; NECROSIS-FACTOR-ALPHA; TOLL-LIKE RECEPTOR-4; ENDOTHELIAL-CELLS; DOWN-REGULATION; HYPOXIA; EXPRESSION; LIPOPOLYSACCHARIDE AB Acute respiratory distress syndrome ( ARDS) usually requires symptomatic supportive therapy by intubation and mechanical ventilation with the supplemental use of high oxygen concentrations. Although oxygen therapy represents a life-saving measure, the recent discovery of a critical tissue-protecting mechanism predicts that administration of oxygen to ARDS patients with uncontrolled pulmonary inflammation also may have dangerous side effects. Oxygenation may weaken the local tissue hypoxia-driven and adenosine A(2A) receptor ( A(2A)R)-mediated anti-inflammatory mechanism and thereby further exacerbate lung injury. Here we report experiments with wild-type and adenosine A(2A)R-deficient mice that confirm the predicted effects of oxygen. These results also suggest the possibility of iatrogenic exacerbation of acute lung injury upon oxygen administration due to the oxygenation-associated elimination of A(2A)R-mediated lung tissue-protecting pathway. We show that this potential complication of clinically widely used oxygenation procedures could be completely prevented by intratracheal injection of a selective A(2A)R agonist to compensate for the oxygenation-related loss of the lung tissue-protecting endogenous adenosine. The identification of a major iatrogenic complication of oxygen therapy in conditions of acute lung inflammation attracts attention to the need for clinical and epidemiological studies of ARDS patients who require oxygen therapy. It is proposed that oxygen therapy in patients with ARDS and other causes of lung inflammation should be combined with anti-inflammatory measures, e. g., with inhalative application of A(2A)R agonists. The reported observations may also answer the long-standing question as to why the lungs are the most susceptible to inflammatory injury and why lung failure usually precedes multiple organ failure. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. Univ Munich, Clin Anaesthesiol, D-80539 Munich, Germany. Northeastern Univ, New England Inflammat & Tissue Protect Inst, Boston, MA 02115 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA 15260 USA. Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany. RP Sitkovsky, MV (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM m.sitkovsky@neu.edu RI Lukashev, Dmitriy/F-8133-2010; OI Caldwell, Charles/0000-0003-1692-4550 NR 53 TC 127 Z9 130 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1545-7885 J9 PLOS BIOL JI PLoS. Biol. PD JUN PY 2005 VL 3 IS 6 BP 1088 EP 1100 AR e174 DI 10.1371/journal.pbio.0030174 PG 13 WC Biochemistry & Molecular Biology; Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics GA 938IK UT WOS:000229992900018 PM 15857155 ER PT J AU Miller, F AF Miller, F TI The debate over placebo-controlled trials SO PLOS MEDICINE LA English DT Letter C1 NIH, Bethesda, MD 20892 USA. RP Miller, F (reprint author), NIH, Bldg 10, Bethesda, MD 20892 USA. EM fmiller@nih.gov NR 2 TC 3 Z9 3 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD JUN PY 2005 VL 2 IS 6 BP 565 EP 566 AR e157 DI 10.1371/journal.pmed.0020157 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 946BI UT WOS:000230546500026 PM 15971940 ER PT J AU Das, K Lewi, PJ Hughes, SH Arnold, E AF Das, K Lewi, PJ Hughes, SH Arnold, E TI Crystallography and the design of anti-AIDS drugs: Conformational flexibility and positional adaptability are important in the design of non-nucleoside HIV-1 reverse transcriptase inhibitors SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE TMC120-R147681; drug design; drug resistance; etravirine; TMC125-R165335 ID IMMUNODEFICIENCY-VIRUS TYPE-1; DOUBLE-STRANDED DNA; RESISTANCE MUTATIONS; ANGSTROM RESOLUTION; WILD-TYPE; CRYSTAL-STRUCTURES; ANTIRETROVIRAL DRUGS; EFAVIRENZ DMP-266; STRUCTURAL BASIS; K103N MUTANT AB Drug resistance is a key cause of failure for treatment of HIV infection. The efficacy of non-nucleoside reverse transcriptase inhibiting (NNRTI) drugs is impaired by rapid emergence of drug-resistance mutations. A multidisciplinary effort led to the discovery of the potent NNRTIs dapivirine and etravirine, both of which are diarylpyrimidine (DAPY) derivatives. Systematic structural and molecular modeling studies of HIV-1 reverse transcriptase (RT)/NNRTI complexes revealed different modes of inhibitor binding, and some of the DAPY inhibitors can bind to RT in different conformations. The torsional flexibility ("wiggling") of the inhibitors can generate numerous conformational variants and the compactness of the inhibitors permits significant repositioning and reorientation (translation and rotation) within the pocket ("jiggling"). Such adaptations appear to be critical for the ability of the diarylpyrimidine NNRTIs to retain their potency against a wide range of drug-resistant HIV-1 RTs. Exploitation of inhibitor conformational flexibility (such as torsional flexibility about strategically located chemical bonds) C1 Rutgers State Univ, Ctr Adv Biotechnol & Med, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. Janssen Pharmaceut NV, Ctr Mol Design, Vosselaar, Belgium. NCI, HIV Drug Resistance Program, NIH, Frederick, MD USA. RP Arnold, E (reprint author), Rutgers State Univ, Ctr Adv Biotechnol & Med, Dept Chem & Chem Biol, 679 Hoes Lane W, Piscataway, NJ 08854 USA. EM arnold@cabm.rutgers.edu NR 64 TC 163 Z9 173 U1 0 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD JUN PY 2005 VL 88 IS 2 BP 209 EP 231 DI 10.1016/j.pbiomolbio.2004.07.001 PG 23 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 900GU UT WOS:000227204200003 PM 15572156 ER PT J AU Botos, I Wlodawer, A AF Botos, I Wlodawer, A TI Proteins that bind high-mannose sugars of the HIV envelope SO PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY LA English DT Review DE gp120; gp41; 2G12; mannose-binding protein; cyanovirin-N ID HUMAN-IMMUNODEFICIENCY-VIRUS; URTICA-DIOICA AGGLUTININ; CIRCULAR-PERMUTED VARIANT; HUMAN MONOCLONAL-ANTIBODY; DOMAIN-SWAPPED DIMER; LECTIN-CARBOHYDRATE INTERACTIONS; ALPHA-D-GLUCOPYRANOSIDE; HAMSTER OVARY CELLS; FREE CONCANAVALIN-A; CYANOVIRIN-N AB A broad range of proteins bind high-mannose carbohydrates found on the surface of the envelope protein gp120 of the human immunodeficiency virus and thus interfere with the viral life cycle, providing a potential new way of controlling HIV infection. These proteins interact with the carbohydrate moieties in different ways. A group of them interacts as typical C-type lectins via a Ca2+ ion. Another group interacts with specific single, terminal sugars, without the help of a metal cation. A third group is involved in more intimate interactions, with multiple carbohydrate rings and no metal ion. Finally, there is a group of lectins for which the interaction mode has not yet been elucidated. This review summarizes, principally from a structural point of view, the current state of knowledge about these high-mannose binding proteins and their mode of sugar binding. Published by Elsevier Ltd. C1 NCI, Macromol Crystallog Lab, Frederick, MD 21702 USA. RP Wlodawer, A (reprint author), NCI, Macromol Crystallog Lab, Bldg 536,Room 5, Frederick, MD 21702 USA. EM wtodawer@ncifcrf.gov NR 209 TC 66 Z9 69 U1 2 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0079-6107 J9 PROG BIOPHYS MOL BIO JI Prog. Biophys. Mol. Biol. PD JUN PY 2005 VL 88 IS 2 BP 233 EP 282 DI 10.1016/j.pbiomolbio.2004.05.001 PG 50 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 900GU UT WOS:000227204200004 PM 15572157 ER PT J AU Block, ML Hong, JS AF Block, ML Hong, JS TI Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism SO PROGRESS IN NEUROBIOLOGY LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; AMYLOID-BETA-PROTEIN; HUMAN FETAL MICROGLIA; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; AMYOTROPHIC-LATERAL-SCLEROSIS; IMMUNODEFICIENCY-VIRUS TYPE-1; ROTENONE-INDUCED DEGENERATION; BACTERIAL-ENDOTOXIN EXPOSURE; COLONY-STIMULATING FACTOR AB Inflammation, a common denominator among the diverse list of neurodegenerative diseases, has recently been implicated as a critical mechanism responsible for the progressive nature of neurodegeneration. Microglia are the resident innate immune cells in the central nervous system and produce a barrage of factors (IL-1 TNF alpha, NO, PGE(2), superoxide) that are toxic to neurons. Evidence supports that the unregulated activation of microglia in response to environmental toxins, endogenous proteins, and neuronal death results in the production of toxic factors that propagate neuronal injury. In the following review, we discuss the common thread of microglial activation across numerous neurodegenerative diseases, define current perceptions of how microglia are damaging neurons, and explain how the microglial response to neuronal damage results in a self-propelling cycle of neuron death. circle star 2005 Elsevier Ltd. All rights reserved. C1 NIEHS, Neuropharmacol Sect, Res Triangle Pk, NC 27709 USA. RP Block, ML (reprint author), NIEHS, Neuropharmacol Sect, POB 12233,MD F1-01, Res Triangle Pk, NC 27709 USA. EM block@niehs.nih.gov NR 217 TC 741 Z9 778 U1 5 U2 67 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0301-0082 J9 PROG NEUROBIOL JI Prog. Neurobiol. PD JUN PY 2005 VL 76 IS 2 BP 77 EP 98 DI 10.1016/j.pneurobio.2005.06.004 PG 22 WC Neurosciences SC Neurosciences & Neurology GA 970MC UT WOS:000232313300001 PM 16081203 ER PT J AU Schubot, FD Cherry, S Austin, BP Tropea, JE Waugh, DS AF Schubot, FD Cherry, S Austin, BP Tropea, JE Waugh, DS TI Crystal structure of the protease-resistant core domain of Yersinia pestis virulence factor YopR SO PROTEIN SCIENCE LA English DT Article DE Yersinia pestis; plague; type III secretion; YopR; crystal structure ID REFINEMENT; SECRETION AB Yersinia pestis, the causative agent of the plague, employs a type III secretion system (T3SS) to secrete and translocate virulence factors into to the cytoplasm of mammalian host cells. One of the secreted virulence factors is YopR. Little is known about the function of YopR other than that it is secreted into the extracellular milieu during the early stages of infection and that it contributes to virulence. Hoping to gain some insight into the function of YopR, we determined the crystal structure of its protease-resistant core domain, which consists of residues 38-149 out of 165 amino acids. The core domain is composed of five alpha-helices, that display unexpected structural similarity with one domain of YopN, a central regulator of type III secretion in Y. pestis. This finding raises the possibility that YopR may play a role in the regulation of type III secretion. C1 Natl Canc Inst Frederick, Ctr Canc Res, Macromol Crystallog Lab, Ft Detrick, MD 21702 USA. RP Waugh, DS (reprint author), Natl Canc Inst Frederick, Ctr Canc Res, Macromol Crystallog Lab, POB B, Ft Detrick, MD 21702 USA. EM waughd@ncifcrf.gov NR 23 TC 4 Z9 4 U1 1 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 0961-8368 J9 PROTEIN SCI JI Protein Sci. PD JUN PY 2005 VL 14 IS 6 BP 1679 EP 1683 DI 10.1110/ps.051446405 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 931PS UT WOS:000229497900028 PM 15930010 ER PT J AU Stefanek, M McDonald, PG Hess, SA AF Stefanek, M McDonald, PG Hess, SA TI Religion, spirituality and cancer: Current status and methodological challenges SO PSYCHO-ONCOLOGY LA English DT Review ID QUALITY-OF-LIFE; LONG-TERM ADJUSTMENT; BREAST-CANCER; FUNCTIONAL ASSESSMENT; MALIGNANT-MELANOMA; COLORECTAL-CANCER; COPING STRATEGIES; AMERICAN WOMEN; SOCIAL SUPPORT; HEALTH AB The role of religion and spirituality in health has received increasing attention in the scientific and lay literature. While the scientific attention to this issue has expanded, there continue to be methodological and measurement concerns that often prevent firm conclusions about health and adjustment benefits. Limited attention has been provided to the role of spirituality and religion in cancer. This is true when both disease outcome and adjustment are considered. A recent 'levels of evidence' review examining the link between physical health and religion or spirituality found little overall support for the hypotheses that religion or spirituality impact cancer progression or mortality. Studies examining their impact on quality of life and adjustment are decidedly mixed. In sum, research specifically focusing on the role of religion or spirituality on cancer outcomes has been surprisingly sparse. Such research presents a number of methodological and measurement challenges. Due to these unmet challenges in the literature to date, it is premature to determine what role religion and spirituality play in disease, adjustment, or quality of life outcomes in cancer. A number of suggestions are made for continued research in this area. Copyright (c) 2004 John Wiley & Sons, Ltd. C1 NCI, Basic Biobehav Res Branch, Behav Res Program, Div Canc Control & Populat Sci,HIN,Dept Hlth & Hu, Rockville, MD 20852 USA. RP Stefanek, M (reprint author), NCI, Basic Biobehav Res Branch, Behav Res Program, Div Canc Control & Populat Sci,HIN,Dept Hlth & Hu, 6130 Execut Blvd,MSC 7363, Rockville, MD 20852 USA. EM stefanem@mail.nih.gov OI Green, Paige/0000-0001-7886-8924 NR 114 TC 105 Z9 107 U1 2 U2 12 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1057-9249 J9 PSYCHO-ONCOL JI Psycho-Oncol. PD JUN PY 2005 VL 14 IS 6 BP 450 EP 463 DI 10.1002/pon.861 PG 14 WC Oncology; Psychology; Psychology, Multidisciplinary; Social Sciences, Biomedical SC Oncology; Psychology; Biomedical Social Sciences GA 938CK UT WOS:000229977300003 PM 15376283 ER PT J AU Bremner, JD Vermetten, E Schmahl, C Vaccarino, V Vythilingam, M Afzal, N Grillon, C Charney, DS AF Bremner, JD Vermetten, E Schmahl, C Vaccarino, V Vythilingam, M Afzal, N Grillon, C Charney, DS TI Positron emission tomographic imaging of neural correlates of a fear acquisition and extinction paradigm in women with childhood sexual-abuse-related post-traumatic stress disorder SO PSYCHOLOGICAL MEDICINE LA English DT Article ID VIETNAM COMBAT VETERANS; POTENTIATED STARTLE PARADIGM; MEDIAL PREFRONTAL CORTEX; PSYCHOPHYSIOLOGICAL ASSESSMENT; CONDITIONED FEAR; EFFERENT PATHWAY; DIFFERENTIAL CONTRIBUTION; CINGULATE CORTEX; HUMAN AMYGDALA; BRAIN-STEM AB Background. In the conditioned fear paradigm, repeated pairing of an aversive unconditioned stimulus (US) (e.g. electric shock) with a neutral conditioned stimulus (CS) (e.g. bright light) results in a conditioned fear response to the light alone. Animal studies have shown that the amygdala plays a critical role in acquisition of conditioned fear responses, while the medial prefrontal cortex (including anterior cingulate), through inhibition of amygdala responsiveness, has been hypothesized to play a role in extinction of fear responses. No studies have examined neural correlates of fear conditioning and extinction in patients with post-traumatic stress disorder (PTSD). Method. Women with early childhood sexual-abuse-related PTSD (n = 8) and women without abuse or PTSD (n = 11) underwent measurement of psychophysiological (skin conductance) responding as well as positron emission tomographic (PET) measurement of cerebral blood flow during habituation, acquisition and extinction conditions. During habituation subjects were repeatedly exposed to a blue square on a screen. During acquisition, exposure to the blue square (CS) was paired with an electric shock to the forearm (US). With extinction, subjects were again exposed to the blue squares without shock. On a different day subjects went through the same procedure with electric shocks administered randomly in the absence of the blue square. Results. Skin conductance responding to the CS was consistent with the development of conditioned responses with this paradigm. PTSD patients had increased left amygdala activation with fear acquisition, and decreased anterior cingulate function during extinction, relative to controls. Conclusions. These findings implicate amygdala and anterior cingulate in the acquisition and extinction of fear responses, respectively, in PTSD. C1 Emory Univ, Sch Med, Emory Ctr Positron Emiss Tomog, Emory Clin Neurosci Res Unit, Atlanta, GA 30306 USA. Emory Univ, Sch Med, Dept Psychiat & Behav Sci, Atlanta, GA 30306 USA. Emory Univ, Sch Med, Dept Radiol, Atlanta, GA 30306 USA. Emory Univ, Sch Med, Dept Internal Med Cardiol, Atlanta, GA 30306 USA. VAMC, Decatur, GA USA. NIMH, Mood & Anxiety Disorders Program, Bethesda, MD 20892 USA. RP Bremner, JD (reprint author), Emory Univ, Sch Med, Emory Ctr Positron Emiss Tomog, Emory Clin Neurosci Res Unit, Emory W Campus,1256 Briarcliff Rd, Atlanta, GA 30306 USA. EM jdbremn@emory.edu RI Bremner, James/B-1632-2013; Schmahl, C/E-8760-2012; OI Vermetten, Eric/0000-0003-0579-4404 FU NCRR NIH HHS [S10 RR016917, S10 RR016917-01]; NIMH NIH HHS [T32 MH067547, 1P50 MH58922, 1R01MH56120-01A1, K24 MH076955, K24 MH076955-05, P50 MH058922, R01 MH056120, R01 MH056120-12, T32 MH067547-05] NR 71 TC 166 Z9 172 U1 12 U2 28 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUN PY 2005 VL 35 IS 6 BP 791 EP 806 DI 10.1017/S0033291704003290 PG 16 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 959EM UT WOS:000231499900003 PM 15997600 ER PT J AU Hong, JP Samuels, J Bienvenu, OJ Hsu, FC Eaton, WW Costa, PT Nestadt, G AF Hong, JP Samuels, J Bienvenu, OJ Hsu, FC Eaton, WW Costa, PT Nestadt, G TI The longitudinal relationship between personality disorder dimensions and global functioning in a community-residing population SO PSYCHOLOGICAL MEDICINE LA English DT Article ID DSM-III; FOLLOW-UP; EPIDEMIOLOGIC SURVEY; BORDERLINE AB Background. Little is known about the long-term outcome of personality disorder traits. The purpose of this study was to investigate, in a community-residing population, the longitudinal relationship between psychiatrist-assessed personality disorder scores and global functioning 13-18 years later. Method. A stratified random sample of residents of east Baltimore were examined by psychiatrists in 1981 and asssessed for DSM-III personality disorders using a semi-structured instrument, the Standardized Psychiatric Examination. A total of 292 persons were re-examined by different psychiatrists during 1994-1999 using the Schedules for the Assessment of Neuropsychiatry (SCAN). After completion of the SCAN, the subjects' functional status was evaluated using the Global Assessment of Functioning (GAF). The relationships between personality dimensions and follow-up GAF scores were evaluated using linear regression models. Results. All of the personality disorder scales measured in 1981 were inversely related to functioning 13-18 years later, with the exception of narcissistic and compulsive scales. After controlling for Axis I disorders diagnosed contemporaneously with GAF assessment, schizoid, antisocial, borderline, histrionic, and avoidant personality disorder scores significantly predicted GAF scores. Conclusions. Most dimensions of DSM-III personality disorder traits were significantly associated with global functioning after an interval of 15 years. However, only schizoid, antisocial, borderline, histrionic, and avoidant personality disorder traits had long-term effects on functioning when Axis I disorders at follow-up were controlled. This suggests that the functional effect of the other personality disorder traits may be mediated through their relationship with Axis I disorders. Future research is needed using more specific and sensitive outcome measures. C1 Univ Ulsan, Sch Med, Asian Med Ctr, Dept Psychiat, Seoul, South Korea. Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Wake Forest Univ, Sch Med, Dept Publ Hlth Sci, Biostat Sect, Winston Salem, NC 27109 USA. Johns Hopkins Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD USA. NIA, Gerontol Res Ctr, Baltimore, MD 21224 USA. RP Nestadt, G (reprint author), Johns Hopkins Univ Hosp, Meyer 4-181,600 N Wolfe St, Baltimore, MD 21287 USA. EM gnestadt@jhmi.edu OI Samuels, Jack/0000-0002-6715-7905; Costa, Paul/0000-0003-4375-1712 FU NIMH NIH HHS [MH50616, MH47447] NR 17 TC 11 Z9 11 U1 2 U2 8 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 40 WEST 20TH ST, NEW YORK, NY 10011-4211 USA SN 0033-2917 J9 PSYCHOL MED JI Psychol. Med. PD JUN PY 2005 VL 35 IS 6 BP 891 EP 895 DI 10.1017/S0033291704003174 PG 5 WC Psychology, Clinical; Psychiatry; Psychology SC Psychology; Psychiatry GA 959EM UT WOS:000231499900012 PM 15997609 ER PT J AU Qu, Y Villacreses, N Murphy, DL Rapoport, SI AF Qu, Y Villacreses, N Murphy, DL Rapoport, SI TI 5-HT2A/2C receptor signaling via phospholipase A(2) and arachidonic acid is attenuated in mice lacking the serotonin reuptake transporter SO PSYCHOPHARMACOLOGY LA English DT Article DE serotonin; phospholipase A(2); arachidonic acid; signal transduction; imaging; brain; SERT.; knockout; DOI ID HEAD-TWITCH RESPONSE; PROTEIN-KINASE-C; RAT-BRAIN; UNANESTHETIZED RATS; KNOCKOUT MICE; FATTY-ACIDS; AWAKE RATS; FLUOXETINE; AGONIST; CORTEX AB Subjects: The serotonin reuptake transporter (SERT) helps to regulate brain serotonergic transmission and is the target of some antidepressants. To further understand SERT function, we measured a marker of regional brain phospholipase A(2) (PLA(2)) activation in SERT knockout mice (SERT-/-) and their littermate controls (SERT+/+). Methods: Following administration of 1.5 mg/kg s.c. (&PLUSMN;)- 2, 5-dimethoxy-4-iodophenyl-2-aminopropane (DOI), a 5-HT2A/2C receptor agonist, to unanesthetized mice injected intravenously with radiolabeled arachidonic acid ( AA), PLA2 activation, represented as the regional incorporation coefficient k* of AA, was determined with quantitative autoradiography in each of 71 brain regions. Results: In SERT+/+ mice, DOI significantly increased k* in 27 regions known to have 5-HT2A/2C receptors, including the frontal, motor, somatosensory, pyriform and cingulate cortex, white matter, nucleus accumbens, caudate putamen, septum, CA1 of hippocampus, thalamus, and hypothalamus. In contrast, DOI did not increase k* significantly in any brain region of SERT-/- mice. Head twitches following DOI, which also were measured, were robust in SERT+/+ mice but were markedly attenuated in SERT-/- mice. Conclusions: These results show that a lifelong elevation of the synaptic 5-HT concentration in SERT-/- mice leads to downregulation of 5-HT2A/2C receptor-mediated PLA(2) signaling via AA and of head twitches, in response to DOI. C1 Johnson & Johnson Pharmaceut Res & Dev LLC, Drug Discovery, San Diego, CA 92130 USA. NIA, Brain Physiol & Metab Sect, NIH, Bethesda, MD 20892 USA. NIMH, Clin Sci Lab, NIH, Bethesda, MD 20892 USA. RP Qu, Y (reprint author), Johnson & Johnson Pharmaceut Res & Dev LLC, Drug Discovery, 3210 Merryfield Row, San Diego, CA 92130 USA. EM yqu1@prdus.jnj.com NR 62 TC 55 Z9 58 U1 1 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUN PY 2005 VL 180 IS 1 BP 12 EP 20 DI 10.1007/s00213-005-2231-5 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 931TV UT WOS:000229509300002 PM 15834538 ER PT J AU Solinas, M Goldberg, SR AF Solinas, M Goldberg, SR TI Involvement of mu-, delta- and kappa-opioid receptor subtypes in the discriminative-stimulus effects of delta-9-tetrahydrocannabinol (THC) in rats SO PSYCHOPHARMACOLOGY LA English DT Article DE THC; cannabinoid; drug discrimination; heroin; opioid receptor subtypes; rat ID VENTRAL TEGMENTAL AREA; DRUG DISCRIMINATION; NOR-BINALTORPHIMINE; ADDICTION; CANNABINOIDS; DELTA-9-THC; ANTAGONIST; BINDING; SYSTEMS; HEROIN AB Many behavioral effects of delta-9-tetrahydrocannabinol (THC), including its discriminative-stimulus effects, are modulated by endogenous opioid systems. To investigate opioid receptor subtypes involved in the discriminative effects of THC. Rats trained to discriminate 3mg/kg i.p. of THC from vehicle using a two-lever operant drug-discrimination procedure, were tested with compounds that bind preferentially or selectively to either mu-, delta- or kappa-opioid receptors. The preferential mu-opioid receptor agonist heroin (0.3-1.0 mg/kg, i.p.), the selective delta-opioid receptor agonist SNC-80 (1-10 mg/kg, i.p.) and the selective kappa-opioid receptor agonist U50488 (1-10 mg/kg, i.p.) did not produce generalization to the discriminative effects of THC when given alone. However, heroin, but not SNC-80 or U50488, significantly shifted the dose response curve for THC discrimination to the left. Also, the preferential mu-opioid receptor antagonist naltrexone (0.1-1 mg/kg, i.p.), the selective delta-opioid receptor antagonist, naltrindole (1-10 mg/kg, i.p.) and the kappa-opioid receptor antagonist nor-binaltorphimine (n-BNI, 5 mg/kg, s.c.), did not significantly reduce the discriminative effects of the training dose of THC. However, naltrexone, but not naltrindole or n-BNI, significantly shifted the dose response curve for THC discrimination to the right. Finally, naltrexone, but not naltrindole or n-BNI, blocked the leftward shift in the dose response curve for THC discrimination produced by heroin. Conclusion: mu- but not delta- or kappa-opioid receptors are involved in the discriminative effects of THC. Given the role that mu-opioid receptors play in THC's rewarding effects, the present findings suggest that discriminative-stimulus effects and rewarding effects of THC involve similar neural mechanisms. C1 Natl Inst Drug Abuse, Behav Neurosci Res Branch, Preclin Pharmacol Sect, Div Intramural Res,NIH, Baltimore, MD 21224 USA. Univ Poitiers, CNRS 6187, Lab Biol & Physiol Cellulaire, F-86022 Poitiers, France. RP Solinas, M (reprint author), Natl Inst Drug Abuse, Behav Neurosci Res Branch, Preclin Pharmacol Sect, Div Intramural Res,NIH, Room 318,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. EM msolinas@intra.nida.nih.gov RI Solinas, Marcello/M-3500-2016 OI Solinas, Marcello/0000-0002-0664-5964 NR 44 TC 29 Z9 31 U1 1 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0033-3158 J9 PSYCHOPHARMACOLOGY JI Psychopharmacology PD JUN PY 2005 VL 179 IS 4 BP 804 EP 812 DI 10.1007/s00213-004-2118-x PG 9 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 924ZZ UT WOS:000229022600010 PM 15619107 ER PT J AU Pierce, DA Sharp, GB Mabuchi, K AF Pierce, DA Sharp, GB Mabuchi, K TI Joint effects of radiation and smoking on lung cancer risk among atomic bomb survivors SO RADIATION RESEARCH LA English DT Meeting Abstract CT Conference on Radiation and Health CY JUN 26-30, 2004 CL Beaver Creek, CO SP Amer Statis Assoc C1 Radiat Effects Res Fdn, Dept Stat, Hiroshima 732, Japan. Radiat Effects Res Fdn, Dept Epidemiol, Hiroshima 732, Japan. NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Pierce, DA (reprint author), Radiat Effects Res Fdn, Dept Stat, 5-2 Hijiyama Pk, Hiroshima 732, Japan. NR 2 TC 4 Z9 4 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUN PY 2005 VL 163 IS 6 BP 694 EP 695 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 931NE UT WOS:000229491200013 PM 16044494 ER PT J AU Travis, LB Gilbert, E AF Travis, LB Gilbert, E TI Lung cancer after Hodgkin lymphoma: The roles of chemotherapy, radiotherapy and tobacco use SO RADIATION RESEARCH LA English DT Meeting Abstract CT Conference on Radiation and Health CY JUN 26-30, 2004 CL Beaver Creek, CO SP Amer Statis Assoc ID DISEASE; DNA C1 NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Travis, LB (reprint author), NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. NR 10 TC 16 Z9 16 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUN PY 2005 VL 163 IS 6 BP 695 EP 696 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 931NE UT WOS:000229491200014 PM 16044495 ER PT J AU Kleinerman, RA Stovall, M Tarone, RE Tucker, MA AF Kleinerman, RA Stovall, M Tarone, RE Tucker, MA TI Gene environment interactions in a cohort of irradiated retinoblastoma patients SO RADIATION RESEARCH LA English DT Meeting Abstract CT Conference on Radiation and Health CY JUN 26-30, 2004 CL Beaver Creek, CO SP Amer Statis Assoc ID SURVIVORS; CANCER; RISK C1 NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Int Epidemiol Inst, Rockville, MD 20850 USA. RP Kleinerman, RA (reprint author), NCI, Div Canc Epidemiol & Genet, Rockville, MD 20852 USA. RI Tucker, Margaret/B-4297-2015; OI Kleinerman, Ruth/0000-0001-7415-2478 NR 5 TC 4 Z9 4 U1 0 U2 0 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUN PY 2005 VL 163 IS 6 BP 701 EP 702 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 931NE UT WOS:000229491200021 PM 16044502 ER PT J AU Sigurdson, AJ Jones, IM AF Sigurdson, AJ Jones, IM TI Second cancers after radiotherapy: Any evidence for radiation-induced genomic instability? SO RADIATION RESEARCH LA English DT Meeting Abstract CT Conference on Radiation and Health CY JUN 26-30, 2004 CL Beaver Creek, CO SP Amer Statis Assoc ID IONIZING-RADIATION; EXPOSURE C1 NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA USA. RP Sigurdson, AJ (reprint author), NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH,DHHS, Bethesda, MD 20892 USA. NR 6 TC 1 Z9 2 U1 0 U2 1 PU RADIATION RESEARCH SOC PI OAK BROOK PA 820 JORIE BOULEVARD, OAK BROOK, IL 60523 USA SN 0033-7587 J9 RADIAT RES JI Radiat. Res. PD JUN PY 2005 VL 163 IS 6 BP 702 EP 703 PG 2 WC Biology; Biophysics; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Biophysics; Radiology, Nuclear Medicine & Medical Imaging GA 931NE UT WOS:000229491200022 PM 16044503 ER PT J AU Sickles, EA Miglioretti, DL Ballard-Barbash, R Geller, BM Leung, JWT Rosenberg, RD Smith-Bindman, R Yankaskas, BC AF Sickles, EA Miglioretti, DL Ballard-Barbash, R Geller, BM Leung, JWT Rosenberg, RD Smith-Bindman, R Yankaskas, BC TI Performance benchmarks for diagnostic mammography SO RADIOLOGY LA English DT Article ID POSITIVE PREDICTIVE VALUE; PROBABLY BENIGN LESIONS; SCREENING MAMMOGRAPHY; BREAST-CANCER; FOLLOW-UP; QUALITY ASSURANCE; FAMILY HISTORY; MEDICAL AUDIT; BI-RADS; AGE AB Purpose : to evaluate a range of performance parameters pertinent to the comprehensive auditing of diagnostic mammography examinations, and to derive performance benchmarks there from, by pooling data collected from large numbers of patients and radiologists that are likely to be representative of mammography practice in the United States. Materials and Methods: Institutional review board approval was met, informed consent was not required. and this study was Health Insurance Portability and Accountability Act compliant. Six mammography registries contributed data to the Breast Cancer Surveillance Consortium (BCSC), providing patient demographic and clinical information, mammogram interpretation data, and biopsy results from defined population-based catchment areas. The study involved 151 mammography facilities and 646 interpreting radiologists. The study population included women 18 years of age or older who underwent at least one diagnostic mammography examination between 1996 and 2001. Collected data was used to derive mean performance parameter values, including abnormal interpretation rate, positive predictive value (for abnormal interpretation rate, biopsy recommended, and biopsy performed), cancer diagnosis rate, invasive cancer size, and the percentage of minimal cancers, axillary node- negative invasive cancers, and the stage 0 and 1 cancers. Additional benchmarks were derived for these performance parameters, including 10th, 25th, 50th (median), 75th, and 90th percentile values. Results : The study involved 332 926 diagnostic mammography examinations. Mean performance parameter, values were abnormal interpretation rate, 8.0%; positive predictive value for abnormal interpretation, 31.4%; positive predictive value for biopsy performed, 39.5%; cancer diagnosis rate, 25.3 per 1000 examinations; invasive cancer size, 20.2 mm; percentage of minimal cancers, 42.0%; percentage of axillary node-negative invasive cancers, 73.6% and percentage of stage 0 and 1 cancers 62.4%. Conclusions : The presented BCSC outcomes data and performacne becnhmarks may be used by mammography facilities and individual radiologists to evaluate their own performance for diagnostic mammography as determined by means of periodic comprehensive audits. (c) RSNA, 2005. C1 Univ Calif San Francisco, Sch Med, Dept Radiol, San Francisco, CA 94115 USA. Univ Calif San Francisco, Sch Med, Dept Epidemiol Biostat, San Francisco, CA 94115 USA. Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. NCI, Appl Res Program, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. Univ Vermont, Off Hlth Promot Res, Burlington, VT USA. Univ New Mexico, Dept Radiol, HSC, Albuquerque, NM 87131 USA. Univ N Carolina, Dept Radiol, Chapel Hill, NC USA. RP Sickles, EA (reprint author), Univ Calif San Francisco, Sch Med, Dept Radiol, 1600 Divisadero St,Rm H-2801, San Francisco, CA 94115 USA. EM edward.sickles@ucsfmedctr.org FU NCI NIH HHS [U01CA70013, U01CA63740, K07CA86032, U01CA63731, U01CA86076, U01CA70040, U01CA86082-01]; PHS HHS [U0169976] NR 36 TC 118 Z9 120 U1 0 U2 0 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD JUN PY 2005 VL 235 IS 3 BP 775 EP 790 DI 10.1148/radiol.2353040738 PG 16 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 927RE UT WOS:000229217400008 PM 15914475 ER PT J AU Gorin, MB Costantino, JP Kulacoglu, DN Demirci, FYK Wickerham, DL Fisher, B Wolmark, N AF Gorin, MB Costantino, JP Kulacoglu, DN Demirci, FYK Wickerham, DL Fisher, B Wolmark, N TI Is tamoxifen a risk factor for retinal vaso-occlusive disease? SO RETINA-THE JOURNAL OF RETINAL AND VITREOUS DISEASES LA English DT Article ID VEIN OCCLUSION; BREAST-CANCER; EYE DISEASE; PREVENTION C1 Univ Pittsburgh, Sch Med, Dept Ophthalmol, UPMC Eye Ctr, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Human Genet, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Dept Biostat, Pittsburgh, PA 15213 USA. Natl Surg Adjuvant Breast & Bowel Project, Pittsburgh, PA USA. Drexel Univ, Sch Med, Allegheny Gen Hosp, Dept Human Oncol, Pittsburgh, PA USA. RP Gorin, MB (reprint author), Univ Pittsburgh, Sch Med, Dept Ophthalmol, UPMC Eye Ctr, 203 Lothrop St,EEINS Bldg,Rm 1025, Pittsburgh, PA 15213 USA. EM gorinmb@upmc.edu OI Demirci, F. Yesim/0000-0001-6907-9843 NR 9 TC 6 Z9 6 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3261 USA SN 0275-004X J9 RETINA-J RET VIT DIS JI Retin.-J. Retin. Vitr. Dis. PD JUN PY 2005 VL 25 IS 4 BP 523 EP 526 DI 10.1097/00006982-200506000-00023 PG 4 WC Ophthalmology SC Ophthalmology GA 008AN UT WOS:000235012700023 PM 15933605 ER PT J AU Abnet, CC Kamangar, F Dawsey, SM Stolzenberg-Solomon, RZ Albanes, D Pietinen, P Virtamo, J Taylor, PR AF Abnet, CC Kamangar, F Dawsey, SM Stolzenberg-Solomon, RZ Albanes, D Pietinen, P Virtamo, J Taylor, PR TI Tooth loss is associated with increased risk of gastric non-cardia adenocarcinoma in a cohort of Finnish smokers SO SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY LA English DT Article DE Finland; esophageal cancer; gastric cancer; male smokers; tooth loss ID REPUBLIC-OF-CHINA; HELICOBACTER-PYLORI; FOLLOW-UP; CANCER; ESOPHAGEAL; STOMACH; POLYMORPHISMS; INFECTION; DISEASE; TRIAL AB Objective. Tooth loss has been associated with upper gastrointestinal cancer in several studies, but only one previous study used prospectively collected data. The importance of confounding by Helicobacter pylori has not previously been addressed. The objective was to determine the association between tooth loss and upper gastrointestinal cancer in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study cohort and to determine the importance of potentially confounding dietary factors or H. pylori seropositivity. Material and methods. A prospective cohort study with 29,124 subjects included 49 esophageal squamous cell carcinomas, 66 esophageal/gastric cardia adenocarcinomas, and 179 gastric noncardia adenocarcinomas occurring between 1985 and 1999. Cox proportional hazards models adjusted for age and education were used to estimate hazard ratios (HRs) and 95% CIs. Odds ratios and 95% CIs were calculated with and without adjustment for H. pylori seropositivity in a nested case-control group to determine whether H. pylori confounded the association between tooth loss and gastric cancer. Results. Tooth loss significantly increased the hazard ratio for gastric non-cardia cancer, the HR ( 95% CI) for edentulous subjects versus those with < 10 teeth lost was 1.65 (1.09, 2.49, respectively). No statistically significant associations were found between tooth loss and esophageal squamous cell carcinoma or esophageal/gastric cardia adenocarcinoma. Confounding by dietary factors, tobacco smoking, or H. pylori did not explain these results. Conclusions. Tooth loss was associated with increased risk of gastric non-cardia cancer, but not esophageal squamous cell carcinoma or esophageal/gastric cardia adenocarcinoma in this Finnish cohort. C1 NCI, Canc Prevent Studies Branch, Ctr Canc Res, Bethesda, MD 20892 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Natl Publ Hlth Inst, Dept Epidemiol & Hlth Promot, Helsinki, Finland. RP Abnet, CC (reprint author), NCI, Canc Prevent Studies Branch, Ctr Canc Res, 6116 Execut Blvd,Room 705, Bethesda, MD 20892 USA. EM abnetc@mail.nih.gov RI Albanes, Demetrius/B-9749-2015; Abnet, Christian/C-4111-2015 OI Abnet, Christian/0000-0002-3008-7843 FU NCI NIH HHS [N01CN45035, N01CN45165] NR 27 TC 39 Z9 41 U1 0 U2 2 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0036-5521 J9 SCAND J GASTROENTERO JI Scand. J. Gastroenterol. PD JUN PY 2005 VL 40 IS 6 BP 681 EP 687 DI 10.1080/00365520510015430 PG 7 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 930CS UT WOS:000229394000010 PM 16036528 ER PT J AU Addo, A Le, J Li, W Aksentijevich, I Balow, J Lee, A Gregersen, PK Kastner, DL Remmers, EF AF Addo, A Le, J Li, W Aksentijevich, I Balow, J Lee, A Gregersen, PK Kastner, DL Remmers, EF TI Analysis of CARD15/NOD2 haplotypes fails to identify common variants associated with rheumatoid arthritis susceptibility SO SCANDINAVIAN JOURNAL OF RHEUMATOLOGY LA English DT Article ID INFLAMMATORY-BOWEL-DISEASE; CROHNS-DISEASE; AUTOIMMUNE-DISEASES; POPULATION; GENES; POLYMORPHISMS; LINKAGE; REGION; DISEQUILIBRIUM; MUTATIONS AB Objectives: The CARD15/NOD2 gene product plays an important role in host response to bacterial lipopolysaccharides and bacterial muramyl dipeptide via activation of NF-kappaB in monocytes. Mutations in CARD15 are associated with Crohn's disease ( CD), a chronic inflammatory bowel disease. In this study we sought to determine whether CD-associated mutations or any common variants of this gene might contribute to susceptibility to another chronic inflammatory disease, rheumatoid arthritis (RA). Methods: We genotyped 376 Caucasian RA cases and 376 ethnically matched healthy controls for three CD-associated CARD15 mutations. We also genotyped these 752 individuals for 12 common CARD15 single nucleotide polymorphisms ( SNPs), determined the linkage disequilibrium structure of the gene, and compared the frequencies of the common CARD15 haplotypes in the RA cases and controls. Results: None of the CD-associated mutations or the CARD15 SNPs was associated with susceptibility to RA. We also found no significant difference in the frequencies of any of the common haplotypes of the CARD15 gene in RA patients and controls. Our haplotype analysis was consistent with earlier observations that all three CD-associated variants independently arose on the same ancestral haplotype. Conclusions: These data suggest that CARD15 variants are not associated with RA susceptibility. C1 NIAMSD, Genet & Genom Branch, Bethesda, MD 20892 USA. N Shore LIJ Inst Med Res, Robert S Boas Ctr Genom & Human Genet, Manhasset, NY USA. RP Remmers, EF (reprint author), Bldg 9,Rm 1W108,9 Mem Dr MSC 0908, Bethesda, MD 20892 USA. EM remmerse@mail.nih.gov OI Li, Wentian/0000-0003-1155-110X FU NIAMS NIH HHS [N01-AR-7-2232] NR 31 TC 6 Z9 6 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA PO BOX 12 POSTHUSET, NO-0051 OSLO, NORWAY SN 0300-9742 J9 SCAND J RHEUMATOL JI Scand. J. Rheumatol. PD JUN PY 2005 VL 34 IS 3 BP 198 EP 203 DI 10.1080/03009740510018561 PG 6 WC Rheumatology SC Rheumatology GA 946TZ UT WOS:000230597200004 PM 16134725 ER PT J AU Min, B Paul, WE AF Min, B Paul, WE TI Endogenous proliferation: Burst-like CD4 T cell proliferation in lymphopenic settings SO SEMINARS IN IMMUNOLOGY LA English DT Review DE CD4 T cells; endogenous proliferation; homeostasis; lymphopenia ID HOMEOSTATIC PROLIFERATION; CUTTING EDGE; NEONATAL MICE; MHC COMPLEXES; NAIVE; COMPETITION; RECOGNITION; LYMPHOCYTES; REPERTOIRE; SURVIVAL AB Rapid and slow proliferation is observed when naive CD4 T cells are transferred into lymphopenic hosts. We have recently proposed that the rapid, burst-like proliferation, designated endogenous proliferation, is a peripheral mechanism by which memory T cells of diverse specificity are generated without exogenous antigenic stimulation. In this review, we discuss some of unique features of endogenous proliferation. We argue that it is regulated not by the absolute number of memory cells present but by the range of specificities of those cells. We discuss the physiologic significance of endogenous proliferation and outline goals for future studies. Published by Elsevier Ltd. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. RP Min, B (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM minb@ccf.org; wpaul@niaid.nih.gov NR 31 TC 29 Z9 36 U1 1 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1044-5323 J9 SEMIN IMMUNOL JI Semin. Immunol. PD JUN PY 2005 VL 17 IS 3 BP 201 EP 207 DI 10.1016/j.smim.2005.02.005 PG 7 WC Immunology SC Immunology GA 921UJ UT WOS:000228790400005 PM 15826825 ER PT J AU Vgontzas, AN Bixier, EO Chrousos, GP AF Vgontzas, AN Bixier, EO Chrousos, GP TI Sleep apnea is a manifestation of the metabolic syndrome SO SLEEP MEDICINE REVIEWS LA English DT Review DE sleep apnea; visceral obesity; insulin resistance; interleukin-6; tumor necrosis factor-alpha; daytime sleepiness ID POLYCYSTIC-OVARY-SYNDROME; POSITIVE AIRWAY PRESSURE; NECROSIS-FACTOR-ALPHA; EXCESSIVE DAYTIME SLEEPINESS; SUBCUTANEOUS ADIPOSE-TISSUE; INSULIN-RESISTANCE; RISK-FACTOR; OBESE SUBJECTS; SERUM LEPTIN; RESPIRATORY DEPRESSION AB Obstructive steep apnea (OSA) is a prevalent disorder particularly among middle-aged, obese men, although its existence in women as well as in lean individuals is increasingly recognized. Despite the early recognition of the strong association between OSA and obesity, and OSA and cardiovascular problems, steep apnea has been treated as a 'local abnormality' of the respiratory track rather than as a 'systemic illness.' In 1997, we first reported that the pro-inflammatory cytokines interteukin-6 (IL-6) and tumor necrosis factor-α (TNFα) were elevated in patients with disorders of excessive daytime sleepiness (EDS) and proposed that these cytokines were mediators of daytime sleepiness. Also, we reported a positive correlation between IL-6 or TNFa plasma levels and the body-mass-index (BMI). In subsequent studies, we showed that IL-6, TNFa, and insulin levels were elevated in steep apnea independently of obesity and that visceral fat, was the primary parameter linked with steep apnea. Furthermore, our findings that women with the polycystic ovary syndrome (PCOS) (a condition associated with hyperandrogenism and insulin resistance) were much more likely than controls to have steep disordered breathing (SDB) and daytime sleepiness, suggests a pathogenetic role of insulin resistance in OSA. Other findings that support the view that steep apnea and sleepiness in obese patients may be manifestations of the Metabolic Syndrome, include: obesity without steep apnea is associated with daytime sleepiness; PCOS and diabetes type 2 are independently associated with EDS after controlling for SDB, obesity, and age; increased prevalence of steep apnea in post-menopausal women, with hormonal replacement therapy associated with a significantly reduced risk for OSA; lack of effect of continuous positive airway pressure (CPAP) in obese patients with apnea on hypercytokinemia and insulin resistance indices; and that the prevalence of the metabolic syndrome in the US population from the Third National Health and Nutrition Examination Survey (1988-1994) parallels the prevalence of symptomatic steep apnea in general random samples. Finally, the beneficial effect of a cytokine antagonist on EDS in obese, mate apneics and that of exercise on SDB in a general random sample, supports the hypothesis that cytokines and insulin resistance are mediators of EDS and steep apnea in humans. C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Psychiat H073, Hershey, PA 17033 USA. NIH, Pediat & Reprod Endocrinol Branch, Bethesda, MD 20892 USA. RP Vgontzas, AN (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Psychiat H073, 500 Univ Dr, Hershey, PA 17033 USA. EM axv3@psu.edu FU NHLBI NIH HHS [HL40916, HL51931, HL64415] NR 93 TC 255 Z9 286 U1 1 U2 31 PU W B SAUNDERS CO LTD PI LONDON PA 32 JAMESTOWN RD, LONDON NW1 7BY, ENGLAND SN 1087-0792 J9 SLEEP MED REV JI Sleep Med. Rev. PD JUN PY 2005 VL 9 IS 3 BP 211 EP 224 DI 10.1016/j.smrv.2005.01.006 PG 14 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 932OY UT WOS:000229564300006 PM 15893251 ER PT J AU Sunderland, T AF Sunderland, T TI Alzheimer disease SO SOUTHERN MEDICAL JOURNAL LA English DT Editorial Material ID CONTROLLED-TRIAL C1 NIMH, Geriatr Psychiat Branch, Clin Res Ctr 2, Bethesda, MD 20892 USA. RP Sunderland, T (reprint author), NIMH, Geriatr Psychiat Branch, Clin Res Ctr 2, 5360,9000 Rockville Pike, Bethesda, MD 20892 USA. EM trey@mail.nih.gov NR 5 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0038-4348 J9 SOUTH MED J JI South.Med.J. PD JUN PY 2005 VL 98 IS 6 BP 588 EP 589 DI 10.1097/01.SMJ.0000167699.56872.56 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 936ZC UT WOS:000229893200002 PM 16004163 ER EF